Basic Sciences, Miscellaneus : Coloproctology (part III)

Survey on colorectal cancer screening knowledge, attitudes, and practices of general practice physicians in Lazio, Italy.
Federici A, Giorgi Rossi P, Bartolozzi F, Farchi S, Borgia P, Guastcchi G.
Prev Med 2005 Jul;41(1):30-5. Epub 2004 Dec 30.

BACKGROUND: Several international guidelines have recommended the involvement of general practitioners (GPs) in screening programs, but current evidence suggests this is very difficult. We implemented a survey to understand the attitudes, knowledge, and practices regarding colorectal cancer screening of GPs in the Lazio region. METHODS: Survey of all GPs working in 13 of the 50 districts in Lazio using a mail-in questionnaire. RESULTS: Out of 1192 GPs, 699 responded (59%). Ninety-four percent consider CRC a preventable disease. Knowledge about oncological screenings is higher in GPs using the guidelines as source of information. Twenty-five percent properly recommend the available screening tests for colorectal cancer, 22% do not recommend any, 6% under-recommend, and 47% over-recommend. Adequate knowledge of oncological screenings is positively associated with correct recommendation. Thirty-two percent of GPs recommend inappropriate follow-up tests for patients with positive fecal occult blood test. CONCLUSIONS: The low response rate reveals the lack of GP's interest in screening. Knowledge about screening and use of guidelines as sources of scientific information are important factors to improve attitudes about screening, but there is a large percentage of well-informed GPs who do not recommend colorectal cancer screening at all. Currently, many GPs do not properly follow the patients up after a positive FOBT.

Mesalazine improves replication fidelity in cultured colorectal cells.
Gasche C, Goel A, Natarajan L, Boland CR.
Cancer Res 2005 May 15;65(10):3993-7.

Epidemiologic studies indicate that mesalazine has chemopreventive effects in inflammatory bowel disease-associated colorectal cancer. Most of our general understanding of chemoprevention in colorectal cancer is, however, derived from aspirin, which is structurally similar to mesalazine. Herein we determined the influence of aspirin and mesalazine on replication fidelity in cultured colorectal cells. Flow cytometry was used for quantitation of mutation rates at a (CA)13 microsatellite in HCT116 cells (mismatch repair deficient) and HCT116+chr3 cells (mismatch repair proficient) that had been stably transfected with pIREShyg2-EGFP/CA13, an enhanced green fluorescence protein-based plasmid, and cultured in the absence or presence of various concentrations of aspirin or mesalazine. Aspirin at doses above 1.25 mmol/L markedly reduced cell growth. Mesalazine doses up to 5.0 mmol/L had no such effect. The mutation rate in mismatch repair-deficient HCT116 cells was 6.8 x 10(-4) +/- 9.0 x 10(-5). In aspirin-treated cultures the mutation rate was 8.2 x 10(-4) +/- 1.3 x 10(-4) (121% of control). Instead, mesalazine lowered the mutation rate in a dose-dependent fashion (5.5 x 10(-4) +/- 1.1 x 10(-4); 81% of control). The effects of mesalazine were most significant in the M1 fraction (P < 0.0001), which represents a mutant population immediate after the polymerase error and were confirmed in mismatch repair-proficient HCT116+chr3 cells. Our data indicate that mesalazine reduces frameshift mutations at a (CA)13 microsatellite in cultured colorectal cells independent of mismatch repair proficiency. This finding suggests that mesalazine improves replication fidelity, an effect that may be active in reducing mutations independent of its anti-inflammatory properties.

Screening and preventive behaviors one year after predictive genetic testing for hereditary nonpolyposis colorectal carcinoma.
Collins V, Meiser B, Gaff C, St John DJ, Halliday J
Cancer 2005 Jun 9;.

Prevention benefits from predictive genetic testing for cancer will only be fully realized if appropriate screening is adopted after testing. The current study assessed screening and preventive behaviors during 12 months after predictive genetic testing for hereditary nonpolyposis colorectal carcinoma (HNPCC) in an Australian clinical cohort. METHODS: Participants received predictive genetic testing for HNPCC at one of five Australian familial cancer clinics. Data on self-reported screening behaviors (colonoscopy, and endometrial sampling and transvaginal ultrasound for women) and prophylactic surgery (colectomy, and hysterectomy and bilateral oophorectomy for women) were collected using postal questionnaires before (baseline) and 12 months after receipt of genetic test results. Age, gender, perceived risk of cancer, and cancer-specific distress were assessed as predictors of colonoscopic screening. RESULTS: In the current study, 114 participants returned baseline questionnaires (32 carriers and 82 noncarriers of an HNPCC mutation). Ninety-eight participants also returned a 12-month follow-up questionnaire. Of those >/= 25 years, 73% reported having had a colonoscopy before genetic testing. At follow-up, 71% (15 of 25) of carriers and 12% (8 of 65) of noncarriers reported having a colonoscopy in the 12 months after receipt of test results. The reduction in colonoscopy among noncarriers was statistically significant (P < 0.001). High perceived risk was associated with colonoscopy at baseline. At follow-up, mutation status was the only variable significantly associated with colonoscopy. Among female mutation carriers, 47% reported having transvaginal ultrasonography and 53% endometrial sampling during follow-up. There was low uptake of prophylactic surgery for colorectal, endometrial, or ovarian carcinomas. CONCLUSIONS: The majority of individuals reported appropriate screening behaviors after predictive genetic testing for HNPCC. The small group of noncarriers who had screening after genetic testing might benefit from additional counseling.

Epidermal growth factor receptor-targeted treatment for advanced colorectal carcinoma.
Venook AP
Cancer 2005 Jun 15;103(12):2435-46.

Substantial effort has focused on the development of novel targeted agents for treating patients with late-stage colorectal carcinoma. These agents are designed specifically to inhibit biochemical processes associated with pathogenesis. Numerous molecules targeting the epidermal growth factor receptor have been investigated as therapeutic agents and appear to herald a shift in the treatment paradigm for colorectal carcinoma. Cancer 2005. (c) 2005 American Cancer Society.

Transanal Excision vs. Major Surgery for T1 Rectal Cancer.
Endreseth BH, Myrvold HE, Romundstad P, Hestvik UE, Bjerkeset T, Wibe A.
Dis Colon Rectum 2005 May 5;.

PURPOSE: The purpose of this national study was to examine the long-term results of transanal excision compared with major surgery of T1 rectal cancer. METHODS: This prospective study from the Norwegian Rectal Cancer Project included all 291 patients with a T1M0 tumor within 15 cm from the anal verge treated by anterior resection, abdominoperineal resection, Hartmann's procedure, or transanal excision in the period from November 1993 to December 1999. RESULTS: Two hundred fifty-six patients were treated by major surgery and 35 patients by transanal excision. None of the patients had neoadjuvant therapy. Macroscopic tumor remnants (R2) occurred in 17 percent (6/35) of the transanal excisions, while major surgery obtained 100 percent R0 resections. Eleven percent of the patients treated with major surgery had glandular involvement. There were no significant differences according to tumor localization, size, or differentiation between Stage I and Stage III tumors. Patients treated with transanal excision were older than patients having major surgery (mean age, 77 vs. 68 years, P < 0.001). After curative resection (R0, R1, Rx) the five-year rate of local recurrence was 12 percent (95 percent confidence interval, 0-24) in the transanal excision group compared with 6 percent (95 percent confidence interval, 2-10) after major surgery (P = 0.010). The overall five-year survival was 70 percent (95 percent confidence interval, 52-88) in the transanal excision group compared with 80 percent (95 percent confidence interval, 74-85) in the major surgery group (P = 0.04) and the five-year disease-free survival was 64 percent (95 percent confidence interval, 46-82) in the transanal excision group compared with 77 percent (95 percent confidence interval, 71-83) in the major surgery group (P = 0.01). CONCLUSIONS: The main problem of transanal excision for early rectal cancer in the present study was the inability to remove all the malignancy. Patients treated with transanal excision had significantly higher rates of local recurrence compared with patients who underwent major surgery. Patients who had transanal excision had inferior survival, but they were older than those who had major surgery.

Nicorandil and Idiopathic Anal Ulceration.
Katory M, Davies B, Kelty C, Arasaradnam R, Skinner P, Brown S, Bagley J, Shorthouse AJ, Hunt LM, Slater R.
Dis Colon Rectum 2005 May 5;.

PURPOSE: Several reports have implicated nicorandil as a reversible cause of anal ulceration. We have recently commenced a specialist clinic for patients presenting with severe anal ulceration to assess treatment in this difficult group. Recognition of this association may avoid unnecessary surgery. METHODS: Twenty-six patients treated with nicorandil had severe painful anal ulceration. Examination under anesthesia was required to biopsy the lesions to exclude neoplasia or inflammatory bowel disease. In total, three patients had proximal diverting stomas without subsequent ulcer resolution, two had perineal debridement with one requiring subsequent skin grafting, and one had an abdominoperineal excision for unremitting pain. RESULTS: The association of perianal ulceration with nicorandil became apparent only in the latter part of this series. Ten ulcers successfully reepithelialized when nicorandil was stopped. Nine patients reported anal pain relief and partial healing on clinical examination at two months but failed to show subsequent complete resolution. One patient agreed to nicorandil cessation and reported symptomatic anal pain relief at two weeks but subsequently developed unstable angina requiring hospital admission. Nicorandil was recommenced with anal pain relapse. CONCLUSIONS: Failure to recognize nicorandil as an etiologic factor in the development of anal ulceration, when other potential underlying well-recognized inflammatory or neoplastic processes have been excluded, may lead to unnecessary surgical intervention in a group of high-risk patients. One of our patients had a potentially avoidable abdominoperineal resection. Pharmaceutical manipulation with alternative antiangina medication may induce healing. Pharmacologic manipulation should be coordinated with a physician to minimize precipitation of unstable angina.

Prospective Manometric Assessment of Botulinum Toxin and Its Correlation With Healing of Chronic Anal Fissure.
Thornton MJ, Kennedy ML, King DW.
Dis Colon Rectum 2005 May 2;.

INTRODUCTION: The efficacy and pharmacokinetics of botulinum toxin for chronic anal fissure continues to be debated. Addressing both issues we prospectively assessed the manometric impact of botulinum toxin on internal anal sphincter pressure, correlating this impact with chronic anal fissure healing. METHODS: Sixty patients with chronic fissures were assessed. Fifty-seven patients had a total of 20 units of botulinum toxin injected into the intersphincteric groove at four o'clock and eight o'clock. Patients were prospectively assessed with a linear analog pain score, bleeding score, clinical fissure score, modified St. Mark's continence score, and anorectal manometry. Each parameter was reassessed two weeks following treatment and again at three months. RESULTS: Fifty-six patients (30 female), median age 43 (range, 17-80) years, were followed for a median of five (range, 3-15) months with fissure healing assessed 12 weeks after treatment. Physical healing and symptom control were dependent on the baseline maximum anal resting pressure and baseline fissure score (P = 0.003, P = 0.009, respectively). Although maximum anal resting pressure fell by 17 (mean, range, 0-71) percent, pressure reduction did not correlate with clinical outcome (P > 0.2). Seventeen patients reported a mean 17 percent increase in continence score. There was no correlation between deterioration in continence and baseline or subsequent reduction in maximum anal resting pressure. CONCLUSION: Patients with Grade 1 lower-pressure fissures are more likely to heal following treatment with 20 units of botulinum toxin. Healing does not appear to be dependent on a reduction in maximum anal resting pressure.

Staging Intra-Abdominal Desmoid Tumors in Familial Adenomatous Polyposis: A Search for a Uniform Approach to a Troubling Disease.
Church J, Berk T, Boman BM, Guillem J, Lynch C, Lynch P, Rodriguez-Bigas M, Rusin L, Weber T
Cancer. Dis Colon Rectum 2005 May 5;.

INTRODUCTION: Desmoid tumors are a clinical problem in 12 to 15 percent of patients with familial adenomatous polyposis. There is no predictably effective treatment for intra-abdominal desmoid tumors, which sometimes cause significant complications by their effects on the ureters or bowel. The relative rarity and the clinical heterogeneity of intra-abdominal desmoid tumors make randomized studies difficult to do. In this article a staging system is proposed to make multi-institutional studies easier. METHODS: Intra-abdominal desmoid tumors can be staged according to their size, clinical presentation and growth pattern. CONCLUSION: A way of staging intra-abdominal desmoid tumors is proposed to facilitate stratification by disease severity during collaborative studies of various treatments.

Crohn's Colitis Presenting With Node-Negative Colon Cancer and Liver Metastasis After Therapy With Infliximab: Report of Two Cases. Nicholson T, Orangio GR, Brandenburg D, Wolf DC, Pennington EE.
Dis Colon Rectum 2005 May 13;.

Plasma levels of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 correlate with disease stage and survival in colorectal cancer patients. Waas ET, Hendriks T, Lomme RM, Wobbes T. Dis Colon Rectum 2005 Apr;48(4):700-10.
The matrix metalloproteinases and their inhibitors are known to be involved in the process of tumor invasion and progression. Our objective was to investigate the potential diagnostic and prognostic value of plasma matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 in colorectal cancer. METHODS: Gelatinase bioactivity and immunoreactivity of pro-matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinase-1, and carcinoembryonic antigen were determined simultaneously in preoperative plasma and serum of colorectal cancer patients (n = 94) and in healthy controls (n = 51). RESULTS: Plasma pro-matrix metalloproteinase-2 levels were lower in colorectal cancer patients (P < 0.0001) than in controls, and its gelatinolytic activity revealed an inverse correlation with adverse clinicopathologic parameters, such as lymph node involvement (P = 0.017), stage (0, I, II vs. III, IV; P = 0.012), and the carcinoembryonic antigen level (P = 0.016). Pro-matrix metalloproteinase-9 levels did not differ between patients and controls. Pro-matrix metalloproteinase-2 gelatinolytic activity showed potential value in colorectal cancer diagnosis, identifying patients with 70 percent sensitivity at 95 percent specificity. Pro-matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and carcinoembryonic antigen all showed lower sensitivities. Combining pro-matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 measurements increased the sensitivity significantly to 84 percent. With respect to prognosis, tissue inhibitor of metalloproteinase-1 showed value in predicting disease outcome in our patient group, whereas pro-matrix metalloproteinase-2 and -9 did not. The combination of tissue inhibitor of metalloproteinase-1 and carcinoembryonic antigen was better in predicting three-year survival than tissue inhibitor of metalloproteinase-1 alone, but it remains to be determined if the combination would be a better marker for survival than carcinoembryonic antigen alone. CONCLUSIONS: Low pro-matrix metalloproteinase-2 levels and high tissue inhibitor of metalloproteinase-1 levels correlate with parameters of colorectal cancer disease. These correlations may be used in the search for new markers in colorectal cancer diagnosis and prognosis.

Ethical Issues in Innovative Colorectal Surgery.
Marron JM, Siegler M.
Dis Colon Rectum 2005 May 2;.

When physicians and surgeons investigate new drugs or devices, they must adhere to stringent regulatory standards governing human experimentation. Although these standards and regulations are not perfect, they serve to protect the interests of patients and research subjects. By contrast, few standards or regulations exist for innovative procedures, including new surgical techniques. Surgeons apply the term "innovative surgery" to describe practices ranging from minor technical modifications in standard procedures to nonvalidated investigational approaches indistinguishable from human research. By focusing on recent innovations in surgery, including colorectal surgery, this article proposes an ethical model of surgical innovation that protects patients while maintaining professional self-regulation of surgical advances.

Anal Carcinomas in HIV-Positive Patients: High-Dose Chemoradiotherapy Is Feasible in the Era of Highly Active Antiretroviral Therapy.
Blazy A, Hennequin C, Gornet JM, Furco A, Gerard L, Lemann M, Maylin C.
Dis Colon Rectum 2005 Apr 27;.

BACKGROUND: Anal carcinoma, a common disease in HIV-positive patients, is usually treated with chemoradiotherapy. Generally tolerance was poor before the availability of highly active antiretroviral therapies. We report our experience of treating anal carcinoma in the era of new antiviral drugs. PATIENTS AND METHODS: Between 1997 and 2001, nine men on highly active antiretroviral therapies with good immune status before chemoradiotherapy received concomitant chemoradiotherapy consisting of 5-fluorouracil and cisplatinum, and high-dose radiotherapy (60-70 Gy) for anal carcinoma. Six cancers were Stage I, two were Stage II, and one was Stage III. CD4+ cell counts were <200/ml for four patients, between 200/ml and 500/ml for four, and >500/ml for one. RESULTS: All patients received the planned dose of radiation (>/=60 Gy). The chemotherapy dose was reduced 25 percent in six patients. Overall treatment time was 58 days. Grade 3 hematologic or skin toxicity occurred in four patients. No association was observed between high-grade toxicity and CD4+ cell count. None of the patients developed opportunistic infections during follow-up. Eight patients were disease-free after a median follow-up of 33 months. Among them, four had no or minor anal function impairment at the last follow-up visit. One patient with T4N2 disease relapsed locally one year after treatment and underwent salvage abdominoperineal excision. CONCLUSION: High-dose chemoradiotherapy for anal carcinomas is feasible with low toxicity in HIV-positive patients treated with highly active antiretroviral therapies. Local control is similar to that obtained for HIV-negative patients.

Squamous-cell carcinoma developing after an ileoanal pouch procedure: report of a case.
Schaffzin DM, Smith LE.
Dis Colon Rectum 2005 May;48(5):1086-9.

Preoperative colonoscopy decreases the need for laparoscopic management of colonic polyps. Lipof T, Bartus C, Sardella W, Johnson K, Vignati P, Cohen J. Dis Colon Rectum 2005 May;48(5):1076-80. PURPOSE: Patients are commonly referred to surgeons for surgical resection of polyps that cannot be excised colonoscopically. Repeating the colonoscopy may be met with resistance by both the patient and the referring endoscopist. However, there are two distinct benefits. First, if the lesion was not marked, tattooing facilitates laparoscopic resection. Second, and more importantly, many of these polyps can be removed endoscopically by an experienced colorectal surgeon, avoiding unnecessary colon resection. Over a period of five years, we have reviewed preoperative colonoscopy in patients who were referred for surgical treatment of benign polyps. METHODS: From January 1999 through September 2003 all patients referred for surgical resection of a benign polyp were consecutively entered into a database by a single group of colorectal surgeons. All patients underwent preoperative colonoscopy on the day before the planned colon resection. Patient charts were reviewed, and demographics were recorded. The referral and preoperative colonoscopy reports and all pathology results were reviewed to record the polyp size, location, histology, and subsequent treatment. RESULTS: Altogether, 71 patients were included in this study. The average size of the polyps was 24 mm (range, 10-60 mm). The location of the polyp as determined by preoperative colonoscopy differed from the location noted on referral colonoscopy in nine patients (13 percent). Surgery was canceled in 23 patients (32 percent), primarily because of complete polypectomy at preoperative colonoscopy. Of the 48 who underwent surgery, 23 (47 percent) had a colonic tattoo placed, at the discretion of the surgeon. Lesions clearly located in the cecum were not tattooed routinely. Of the 48 patients who underwent surgery, 45 (94 percent) underwent laparoscopic colon resection. CONCLUSIONS: We concluded that patients referred for surgical resection of a polyp should undergo repeat colonoscopy preoperatively, given that in our study one-third of patients were spared unnecessary colectomy. In addition, repeat endoscopy by the operating surgeon offers an opportunity to confirm the location of the lesion and place a colonic tattoo to facilitate laparoscopic resection.

Transanal Endoscopic Microsurgery: A Prospective Evaluation of Functional Results.
Cataldo PA, O'brien S, Osler T.
Dis Colon Rectum 2005 May 17;.

PURPOSE: Local excision is a commonly used technique for many benign and selected malignant rectal lesions. Compared with radical resection, it is associated with decreased morbidity and mortality and improved functional results. Transanal endoscopic microsurgery is gaining popularity because of its ability to access the upper rectum and its precise excision techniques. However, the functional consequences have not been extensively studied. METHODS: All patients subject to transanal endoscopic microsurgery prospectively completed preoperative and postoperative (6 weeks) surveys including Fecal Incontinence Severity Index, Fecal Incontinence Quality of Life, number of bowel movements per 24 hours, and ability to defer defecation. All data were collected by an independent research coordinator. Demographics, operative details, and complications were also collected prospectively. RESULTS: Forty-one patients successfully underwent transanal endoscopic microsurgery. Fourteen patients had malignant lesions and 27 had benign lesions. Two patients required abdominoperineal resection based on postoperative diagnosis. Thirty-nine patients have completed follow-up and were available for review. Mean length of surgery was 64 minutes and length of stay was 0.9 day. Average distance from the anal verge to the proximal tumor margin was 11.4 cm and mean tumor size was 8.75 cm. Twenty-three patients had full-thickness excision with primary closure, ten had full-thickness excision without closure, five had partial-thickness excision, one had an excision of a mass in the anovaginal septum, and one had resection of an anastomotic stricture. Each patient served as his own control. Preoperative and postoperative number of bowel movements per 24 hours were 2.0 and 2.0, respectively. Preoperative vs. postoperative urgency (ability to defer defecation less than ten minutes) was unchanged. Mean preoperative and postoperative Fecal Incontinence Severity Index scores were 2.4 (range, 0-43) and 2.4 (range, 0-17), respectively (higher scores indicate worse function). In addition, the four parameters measured by the Fecal Incontinence Quality of Life survey were unchanged when preoperative and postoperative data were compared. CONCLUSIONS: Transanal endoscopic microsurgery allows precise excision of tumors throughout the rectum. However, it involves inserting a 40-mm-diameter operating proctoscope and significant operating times. Despite this, as measured by ability to defer defecation, number of bowel movements per 24 hours, Fecal Incontinence Severity Index, and Fecal Incontinence Quality of Life survey, transanal endoscopic microsurgery has no detrimental affect on fecal continence.

Histologic Risk Factors and Clinical Outcome in Colorectal Malignant Polyp: A Pooled-Data Analysis.
Hassan C, Zullo A, Risio M, Rossini FP, Morini S.
Dis Colon Rectum 2005 May 26;.

PURPOSE: The malignant polyp carries a significant risk of lymphohematic metastasis and mortality. Clinical usefulness of histologic risk factors is still controversial. The study was designed to compute the association between the main histologic risk factors and the occurrence of unfavorable outcomes in patients with malignant polyps. METHODS: A MEDLINE search regarding malignant polyps was performed. Three histologic risk factors (positive resection margin, poor differentiation of carcinoma, vascular invasion) and five (residual disease, recurrent disease, lymph node metastasis, hematogenous metastasis, mortality) unfavorable clinical outcomes were evaluated. Further analysis was performed by subgrouping polyps in high-risk and low-risk groups. RESULTS: Thirty-one studies enrolling 1,900 patients with malignant polyp were selected. Positivity of resection margin was significantly predictive of the presence of residual disease (odds ratio, 22; P < 0.0001), poorly differentiated carcinoma was associated with an increased mortality (odds ratio, 9.2; P < 0.05), and vascular invasion with a higher lymph node metastasis risk (odds ratio, 7; P < 0.05). Patients with high-risk polyps showed a significantly worse outcome than those with low-risk, especially for mortality (odds ratio, 11; P < 0.05). Surgical-related death was as low as 0.8 percent. CONCLUSIONS: All three histologic risk factors are significantly associated with the clinical outcome. Classification in low-risk and high-risk patients may be regarded as a meaningful staging procedure.

Dorsal Transsacrococcygeal Rectal Approach.
Canessa CE.
Dis Colon Rectum 2005 May 27;.

METHODS: A modification of the dorsal rectal approach is described as an alternative to consider in selected low and middle rectal lesions unsuitable for the transanal approach. The dorsal rectal approach is performed through the sacrococcygeal joint and below the gluteus maximus muscle resulting in an easier, safe, and well-tolerated procedure.

Retrorectal Tumors: A Diagnostic and Therapeutic Challenge.
Glasgow SC, Birnbaum EH, Lowney JK, Fleshman JW, Kodner IJ, Mutch DG, Lewin S, Mutch MG, Dietz DW.
Dis Colon Rectum 2005 May 26;.

PURPOSE: Tumors occurring in the retrorectal space are heterogeneous and uncommon. The utility of newer imaging techniques has not been extensively described, and operative approach is variable. This study examined the diagnosis, treatment, and outcome of retrorectal tumors at a tertiary referral center. METHODS: Patients with primary, extramucosal neoplasms occurring in the retrorectal space were identified using a prospectively maintained, procedural database of all adult colorectal surgical patients (1981-2003). Patients also were incorporated from the gynecologic oncology service. Exclusion criteria included inflammatory processes, locally advanced colorectal cancer, and metastatic malignancy. Medical records, radiology, and pathology reports were reviewed retrospectively. RESULTS: Thirty-four patients with retrorectal tumors were treated. Malignant tumors comprised 21 percent. Older age, male gender, and pain were predictive of malignancy (P < 0.05). Sensitivity of proctoscopy was 53 percent; this increased to 100 percent with the use of transrectal ultrasound. Accuracy of magnetic resonance vs. computed tomographic imaging for specific histologic tumor type was 28 vs. 18 percent, respectively. Surgical approach was anterior (n = 14), posterior (n = 11), and combined abdominoperineal (n = 9). Eleven patients required en bloc proctectomy. Patients undergoing posterior resection had lower blood loss and required fewer transfusions (P < 0.05). All benign tumors were resected with normal histologic margins and none recurred (median follow-up, 22 months). All patients with malignancy had recurrence/recrudescence of their disease. For these patients, median disease-free and overall survivals were 38 and 61 months, respectively. CONCLUSIONS: Retrorectal tumors remain a diagnostic and therapeutic challenge. Pain, male gender, and advanced age increase the likelihood of malignancy. Various imaging modalities are useful for planning resection but cannot establish a definitive diagnosis. Whereas benign retrorectal tumors can be completely resected, curative resection of malignant retrorectal tumors remains difficult.

Sargramostim for active Crohn's disease.
Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ.
N Engl J Med 2005 May 26;352(21):2193-201.

BACKGROUND: Sargramostim, granulocyte-macrophage colony-stimulating factor, a hematopoietic growth factor, stimulates cells of the intestinal innate immune system. Preliminary studies suggest sargramostim may have activity in Crohn's disease. To evaluate this novel therapeutic approach, we conducted a randomized, placebo-controlled trial. METHODS: Using a 2:1 ratio, we randomly assigned 124 patients with moderate-to-severe active Crohn's disease to receive 6 mug of sargramostim per kilogram per day or placebo subcutaneously for 56 days. Antibiotics and aminosalicylates were allowed; immunosuppressants and glucocorticoids were prohibited. The primary end point was a clinical response, defined by a decrease from baseline of at least 70 points in the Crohn's Disease Activity Index (CDAI) at the end of treatment (day 57). Other end points included changes in disease severity and the health-related quality of life and adverse events. RESULTS: There was no significant difference in the rate of the primary end point of a clinical response defined by a decrease of at least 70 points in the CDAI score on day 57 between the sargramostim and placebo groups (54 percent vs. 44 percent, P=0.28). However, significantly more patients in the sargramostim group than in the placebo group reached the secondary end points of a clinical response defined by a decrease from baseline of at least 100 points in the CDAI score on day 57 (48 percent vs. 26 percent, P=0.01) and of remission, defined by a CDAI score of 150 points or less on day 57 (40 percent vs. 19 percent, P=0.01). The rates of either type of clinical response and of remission were significantly higher in the sargramostim group than in the placebo group on day 29 of treatment and 30 days after treatment. The sargramostim group also had significant improvements in the quality of life. Mild-to-moderate injection-site reactions and bone pain were more common in the sargramostim group, and three patients in this group had serious adverse events possibly or probably related to treatment. CONCLUSIONS: This study was negative for the primary end point, but findings for the secondary end points suggest that sargramostim therapy decreased disease severity and improved the quality of life in patients with active Crohn's disease.

Statins and the risk of colorectal cancer.
Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G
N Engl J Med 2005 May 26;352(21):2184-92.

BACKGROUND: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and effective lipid-lowering agents. Statins inhibit the growth of colon-cancer cell lines, and secondary analyses of some, but not all, clinical trials suggest that they reduce the risk of colorectal cancer. METHODS: The Molecular Epidemiology of Colorectal Cancer study is a population-based case-control study of patients who received a diagnosis of colorectal cancer in northern Israel between 1998 and 2004 and controls matched according to age, sex, clinic, and ethnic group. We used a structured interview to determine the use of statins in the two groups and verified self-reported statin use by examining prescription records in a subgroup of patients for whom prescription records were available. RESULTS: In analyses including 1953 patients with colorectal cancer and 2015 controls, the use of statins for at least five years (vs. the nonuse of statins) was associated with a significantly reduced relative risk of colorectal cancer (odds ratio, 0.50; 95 percent confidence interval, 0.40 to 0.63). This association remained significant after adjustment for the use or nonuse of aspirin or other nonsteroidal antiinflammatory drugs; the presence or absence of physical activity, hypercholesterolemia, and a family history of colorectal cancer; ethnic group; and level of vegetable consumption (odds ratio, 0.53; 95 percent confidence interval, 0.38 to 0.74). The use of fibric-acid derivatives was not associated with a significantly reduced risk of colorectal cancer (odds ratio, 1.08; 95 percent confidence interval, 0.59 to 2.01). Self-reported statin use was confirmed for 276 of the 286 participants (96.5 percent) who reported using statins and whose records were available. CONCLUSIONS: The use of statins was associated with a 47 percent relative reduction in the risk of colorectal cancer after adjustment for other known risk factors. Because the absolute risk reduction is likely low, further investigation of the overall benefits of statins in preventing colorectal cancer is warranted.

Colonoscopic screening of average-risk women for colorectal neoplasia.
Schoenfeld P, Cash B, Flood A, Dobhan R, Eastone J, Coyle W, Kikendall JW, Kim HM, Weiss DG, Emory T, Schatzkin A, Lieberman D
N Engl J Med 2005 May 19;352(20):2061-8.

BACKGROUND: Veterans Affairs (VA) Cooperative Study 380 showed that some advanced colorectal neoplasias (i.e., adenomas at least 1 cm in diameter, villous adenomas, adenomas with high-grade dysplasia, or cancer) in men would be missed with the use of flexible sigmoidoscopy but detected by colonoscopy. In a tandem study, we examined the yield of screening colonoscopy in women. METHODS: To determine the prevalence and location of advanced neoplasia, we offered colonoscopy to consecutive asymptomatic women referred for colon-cancer screening. The diagnostic yield of flexible sigmoidoscopy was calculated by estimating the proportion of patients with advanced neoplasia whose lesions would have been identified if they had undergone flexible sigmoidoscopy alone. Lesions were considered detectable by flexible sigmoidoscopy if they were in the distal colon or if they were in the proximal colon in patients who had concurrent small adenomas in the distal colon, a finding that would have led to colonoscopy. The results were compared with the results from VA Cooperative Study 380 for age-matched men and women with negative fecal occult-blood tests and no family history of colon cancer. RESULTS: Colonoscopy was complete in 1463 women, 230 of whom (15.7 percent) had a family history of colon cancer. Colonoscopy revealed advanced neoplasia in 72 women (4.9 percent). If flexible sigmoidoscopy alone had been performed, advanced neoplasia would have been detected in 1.7 percent of these women (25 of 1463) and missed in 3.2 percent (47 of 1463). Only 35.2 percent of women with advanced neoplasia would have had their lesions identified if they had undergone flexible sigmoidoscopy alone, as compared with 66.3 percent of matched men from VA Cooperative Study 380 (P<0.001). CONCLUSIONS: Colonoscopy may be the preferred method of screening for colorectal cancer in women.

Cancer Screening Beliefs and Reactions to an Innovative Colorectal Cancer Screening Kit among Chinese Worksite Population.
Hou S, Chen P.
Methods Inf Med 2005;44(2):315-8.

OBJECTIVES: This study assessed the relationships between cancer screening beliefs (perceived pros, cons, and susceptibility) and reactions (acceptance, selfefficacy, intention to purchase) to an innovative home-administered kit (HAK) for fecal occult blood test (FOBT) among Chinese worksite population. METHODS: A total of 450 Chinese people aged 40 and older were recruited from ten worksites in Taiwan (2002), with response rate of 83% (375/450). RESULTS: All the belief scales of cancer screening in general showed good internal consistency (Cronbach alphas >0.70). Perceived benefits and barriers towards cancer screening were significantly correlated with the acceptance, self-efficacy, and order intention towards the FOBT-HAK (p-values <0.001). Perceived susceptibility of cancer was associated with intention to purchase. After taking gender into consideration, the regression analyses showed similar relationships. CONCLUSIONS: Screening beliefs were significantly associated with reactions toward the innovative FOBT-HAK. Intervention programs addressing these beliefs could potentially promote positive reactions to innovative CRC screening strategies.

Crohn's disease after gastric bypass surgery for morbid obesity: is there an association?
Ahn LB, Huang CS, Forse RA, Hess DT, Andrews C, Farraye FA.
Inflamm Bowel Dis 2005 Jun;11(6):622-4.

Normal homocysteine levels in a population of children with inflammatory bowel disease.
Zholudev A, Rifai N, Zurakowski D, Bousvaros A
Inflamm Bowel Dis 2005 Jun;11(6):620-1.

Progression of diverticular colitis to ulcerative colitis.
Hokama A, Kinjo F, Tomiyama R, Maeda K, Saito A, Matayoshi M
Inflamm Bowel Dis 2005 Jun;11(6):618.

Pneumocystis jiroveci (carinii) pneumonia after initiation of infliximab and azathioprine therapy in a patient with Crohn's disease.
Seddik M, Melliez H, Seguy D, Viget N, Cortot A, Colombel JF
Inflamm Bowel Dis 2005 Jun;11(6):618-20.

Debate: should mesalamine be used in Crohn's disease?: comments and conclusions.
Kamm MA
Inflamm Bowel Dis 2005 Jun;11(6):616-7.

Mesalamine has a well-established role in the management of ulcerative colitis. However, its role in the management of Crohn's disease (CD) is less clear. Studies evaluating its therapeutic value in CD have produced both positive and negative results. Meta-analyses have not clarified the situation, possibly because they have combined studies of different design. This debate critically examines the evidence for and against the use of mesalamine in CD.

The case against using 5-aminosalicyclates in Crohn's disease: con.
Stange EF.
Inflamm Bowel Dis 2005 Jun;11(6):613-5.

The case for using 5-aminosalicyclates in Crohn's disease: pro.
Hanauer SB.
Inflamm Bowel Dis 2005 Jun;11(6):609-12.

Mesalamine has a well-established role in the management of ulcerative colitis. However, its role in the management of Crohn's disease (CD) is less clear. Studies evaluating its therapeutic value in CD have produced both positive and negative results. Meta-analyses have not clarified the situation, possibly because they have combined studies of different design. This debate critically examines the evidence for and against the use of mesalamine in CD.

Crohn's disease and month of birth.
Van Ranst M, Joossens M, Joossens S, Van Steen K, Pierik M, Vermeire S, Rutgeerts P.
Inflamm Bowel Dis 2005 Jun;11(6):597-9.

BACKGROUND: Environmental factors trigger the onset of inflammatory bowel disease (IBD) in genetically predisposed individuals. Exposure to seasonal external factors during the maturation of the immune system is suspected to be an inducing factor for IBD. Some studies suggested an association between the month of birth and the later development of IBD. We studied this putative relationship in a large cohort of Belgian patients with Crohn's disease (CD). METHODS: Data from 1025 patients born between 1935 and 1990 were collected. Diagnosis of CD was based on generally accepted clinical, endoscopic, and histologic criteria. As a control group, a cohort of 5125 non-IBD patients seen at the same hospital and matched for birth year and sex was used. Odds ratios were calculated using multivariate unconditional logistic regression including the matching variables and allowing for cyclic variation in risk with month of birth. RESULTS: A cyclic pattern described by a 4-month periodic function was observed with peaks in April and August. Moreover, being born in June significantly reduced the risk of developing CD later in life (P = 0.012). CONCLUSION: In this Belgian cohort, a significant association was found between the month of birth and later development of IBD; a significant reduced risk to develop CD was observed for people born in June. Moreover, environmental yearly reoccurring factors during pregnancy or postpartum might be associated with the occurrence of CD later in life.

Systemic and local cytokine production in quiescent ulcerative colitis and its relationship to future relapse: a prospective pilot study.
Yamamoto T, Umegae S, Kitagawa T, Matsumoto K.
Inflamm Bowel Dis 2005 Jun;11(6):589-96.

BACKGROUND: The main aim of this prospective study was to examine whether systemic (plasma) and local (mucosal) cytokine production is a predictor of future relapse in patients with quiescent ulcerative colitis (UC). The impact of other clinical and laboratory parameters on relapse was also studied. METHODS: Fifty consecutive patients with quiescent UC were included. At enrollment, blood and mucosal (rectal biopsies) samples were collected. All patients were followed up regularly for 1 year after enrollment. Plasma and mucosal cytokine levels were measured by enzyme-linked immunosorbent assay. To identify independent significant predictive factors for relapse, time-dependent analyses using the Kaplan-Meier method and the Cox proportional hazard model were performed. RESULTS: Thirty-four patients remained in remission, and 16 patients relapsed during the 1-year follow-up. Higher interleukin (IL)-8 levels in the rectal mucosa were significantly associated with relapse. In contrast, IL-1beta, IL-6, and tumor necrosis factor-alpha levels in the rectal mucosa were not associated with relapse. Conventional blood markers and plasma cytokines (IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha) did not correlate with relapse. Among clinical factors, age and number of prior relapses were significantly associated with relapse. In multivariate analysis, a higher rectal mucosal IL-8 level (> or = 160 pg/mg of tissue; hazard ratio, 4.7), younger age (<30 yr; hazard ratio, 7.3), and a greater number of prior relapses (> or = 5; hazard ratio, 4.3) were independent significant risk factors for future relapse. CONCLUSIONS: Rectal mucosal IL-8 measurement might be an additional objective diagnostic tool that can predict relapse in patients with quiescent UC.

Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: cytokine production and endoscopic and histological findings.
Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T, Matsumoto K.
Inflamm Bowel Dis 2005 Jun;11(6):580-8.

BACKGROUND: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements. METHODS: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-alpha in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1beta ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1beta ratio. CONCLUSIONS: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD.

Pediatric inflammatory bowel disease: what children can teach adults.
Hait L, Bousvaros A, Grand R.
Inflamm Bowel Dis 2005 Jun;11(6):519-27.

Prune-Belly Syndrome with anorectal malformation.
Angerpointner TA.
J Pediatr Surg 2005 May;40(5):894.

Laparoscopic ligation of the median sacral artery before excision of type I sacrococcygeal teratomas.
Bax KN, van der Zee DC.
J Pediatr Surg 2005 May;40(5):885.

Long-term outcomes of anorectal malformations.
Schmittenbecher P.
J Pediatr Surg 2005 May;40(5):893-4.

Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial.
Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM, Heath RM, Brown JM.
Lancet 2005 May;365(9472):1718-26.

BACKGROUND: Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale randomised trials to support its use. We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes. METHODS: Between July, 1996, and July, 2002, we undertook a multicentre, randomised clinical trial in 794 patients with colorectal cancer from 27 UK centres. Patients were allocated to receive laparoscopic-assisted (n=526) or open surgery (n=268). Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins, proportion of Dukes' C2 tumours, and in-hospital mortality. Analysis was by intention to treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN74883561. FINDINGS: Six patients (two [open], four [laparoscopic]) had no surgery, and 23 had missing surgical data (nine, 14). 253 and 484 patients actually received open and laparoscopic-assisted treatment, respectively. 143 (29%) patients underwent conversion from laparoscopic to open surgery. Proportion of Dukes' C2 tumours did not differ between treatments (18 [7%] patients, open vs 34 [6%], laparoscopic; difference -0.3%, 95% CI -3.9 to 3.4%, p=0.89), and neither did in-hospital mortality (13 [5%] vs 21 [4%]; -0.9%, -3.9 to 2.2%, p=0.57). Apart from patients undergoing laparoscopic anterior resection for rectal cancer, rates of positive resection margins were similar between treatment groups. Patients with converted treatment had raised complication rates. INTERPRETATION: Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes. However, impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use.

Cardiomyopathy associated with celiac disease.
Goel NK, McBane RD, Kamath PS.
Mayo Clin Proc 2005 May;80(5):674-6.

Celiac disease or celiac sprue is predominantly a disease of the small intestine characterized by chronic malabsorption in genetically susceptible individuals who ingest grains containing gluten, such as wheat, barley, and rye. Although previously believed to be uncommon, celiac disease may be present in up to 1% of the general population. Celiac disease is associated frequently with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus, and various connective tissue disorders but is rarely associated with cardiomyopathy. We describe a patient with celiac disease associated with cardiomyopathy whose cardiac function improved substantially after treatment with a gluten-free diet. Cardiomyopathy associated with celiac disease is a serious and potentially lethal condition. However, with early diagnosis and treatment with a gluten-free diet, cardiomyopathy in patients with celiac disease may be completely reversible.

Comparison of resource utilization and long-term quality-of-life outcomes between laparoscopic and conventional colorectal surgery. Sokolovic E, Buchmann P, Schlomowitsch F, Szucs TD.
Surg Endosc 2004 Oct 13;.

BACKGROUND: The outcomes of laparosopic and conventional colorectal surgery, with special reference to costs of treatment and patients' quality of life, were compared. METHODS: A partly retrospective cohort study was designed to assess the use of resources, and a follow-up interview was undertaken to evaluate patients' quality of life after both to define laparoscopic (LAP) and conventional (CON) surgery. RESULTS: The length of hospital stay was significantly lower in the LAP group (median, 11 days; interquartile range [IQR], 9-15) than in the CON group (median, 16 days; IQR, 13-23; p < 0.0001), which is reflected in lower costs of hospitalization calculated for the three most frequent surgical interventions. Statistically significant improvements were noted between the median scores in the domains of physical functioning (LAP 85 vs CON 68; p < 0.05) and vitality (LAP 85 vs CON 69; p < 0.05). CONCLUSION: Laparoscopy is a promising alternative for the treatment of patients with colorectal diseases, offering lower costs and a better quality of life in the long term.

Early outcomes of 100 patients with laparoscopic resection for rectal neoplasm.
Law WL, Chu KW, Tung HM.
Surg Endosc 2004 Oct 13;.

BACKGROUND: Laparoscopic resection has been shown to be a feasible option in patients with colorectal diseases. However, there have been only a few studies on laparoscopic resection for rectal neoplasm. This report aimed to evaluate the early outcomes of patients treated by laparoscopic rectal resection for neoplasm. METHODS: From May 2000 to April 2003, 100 patients underwent laparoscopic resection for rectal neoplasm with mesorectal excision. Data on the patients' demographics, operative details, and outcomes were collected prospectively. In those with successful laparoscopic resection, comparison was made between patients with predominantly intracorporeal surgery (ICS) and those with anterior resection performed with extracorporeal rectal transection and anastomosis following intracorporeal bowel mobilization and vessel ligation (IECS). RESULTS: Sixty-six men and 34 women (median age, 69 years; range, 40-85) were included. Operations included 91 anterior resections, eight abdominoperineal resections, and one Hartmann's procedure. Conversion was required in 15 patients and no conversion was needed in patients treated by laparoscopic abdominoperineal resection. One patient died 30 days after surgery because of liver failure. Postoperative complications occurred in 31 patients. Among them, three had anastomotic leakage and all of them could be treated conservatively. Reoperation was required in one patient with intestinal obstruction. Patients with conversion were found to have significantly more blood loss, longer time to resume diet, a longer hospital stay, and a higher morbidity rate when compared to those with successful laparoscopic surgery. Among those with successful laparoscopic procedures, no difference was observed between patients with ICS (n = 57) and those with IECS (n = 28), except that a shorter incision and less blood loss were found in patients in the former group. CONCLUSIONS: Laparoscopic rectal resection with mesorectal dissection is feasible. The operating mortality and reoperation rates were low. Conversion was associated with an increased morbidity rate, leading to a longer hospital stay. Laparoscopically assisted anterior resection with rectal transection by a transverse stapler through the abdominal incision produced similar results when compared to a procedure that was predominantly intracorporeally performed.

Sealing effect of fibrin glue on the healing of gastrointestinal anastomoses: implications for the endoscopic treatment of leaks.
Bonanomi G, Prince JM, McSteen F, Schauer PR, Hamad GG.
Surg Endosc 2004 Oct 13;.

BACKGROUND: The adoption of advanced laparoscopic techniques for complex surgical procedures has raised the concern that the leak rate might be higher than for open surgery, particularly in the surgeon's early experience or in difficult cases. In this study, the sealing effect of fibrin glue on leaking gastrointestinal anastomoses was evaluated in an experimental swine model. METHODS: A standardized gastrojejunostomy was performed on 20 female pigs (mean weight, 47.7 +/- 5.7 kg). A leak was created on the anterior surface of the anastomosis. The animals were randomized to either fibrin glue or no treatment of the leak. Clinical conditions and vital signs, including body temperature, heart rate and, respiratory rate, were collected three times a day. Preoperative and postoperative complete and differential blood count and lactate dehydrogenase levels were determined. Postmortem analysis was performed when the animals were killed. RESULTS: Clinical signs of peritonitis developed in the control animals by the second or third postoperative day. Findings that confirmed the presence of an anastomotic leak at the postmortem examination were the presence of food or gastrojejunal juices in the abdominal cavity, a localized abscess, or a positive air leak test. Fibrin glue treatment prevented the development of peritonitis in all the animals. Complete sealing of the leak was observed on postoperative day 7 in all treated animals, except one in which an asymptomatic contained leak developed. The postoperative total white blood count was significantly increased in the untreated group (24.69 +/- 5.5 vs 12.74 +/- 3.7 10(3)/ul p < 0.001, paired t-test), as compared with the treated group (15. 55 +/- 2.4 vs 14.89 +/- 2.7 10(3)/ul; p = 0.24). CONCLUSION: In this study, fibrin glue showed reproducible sealing effects on leaking gastrojejunal anastomoses. Fibrin glue application may be a valuable approach for the treatment of gastrointestinal anastomotic leaks.

Inguinal neurectomy for nerve entrapment after open/laparoscopic hernia repair using retroperitoneal endoscopic approach.
Muto CM, Pedana N, Scarpelli S, Galardo R, Guida G, Schiavone V.
Surg Endosc 2005 May 5;.

BACKGROUND: Inguinal neuralgia after open and laparoscopic hernia, repair occurs in about 0.5% of treated patients. If the pain and the functional inability persist, it is possible that the genitofemoral nerve and ileoinguinal nerve are involved in entrapment, and surgical treatment is a possible option. This paper reports a personal endoscopic retroperitoneal approach for ileoinguinal and genitofemoral branches neurectomy. METHODS: A 12-mm trocar is inserted into the lower retroperitoneum and insufflated to create a work space. Neurectomy is performed under endoscopic guidance. RESULTS: Six patients were treated using this technique. The operating time was 55 min, and all patients were completely pain-free after surgery. All patients were discharged the first day after operation and there were no complications. CONCLUSION: This retroperitoneal endoscopic approach is proposed as a new surgical technique for treating inguinal entrapment neuralgia. It is simple and feasible.

The oncological safety of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma.
Bretagnol F, Lelong B, Laurent C, Moutardier V, Rullier A, Monges G, Delpero JR, Rullier E.
Surg Endosc 2005 May 12;.

BACKGROUND: Although experience of laparoscopic treatment of rectal carcinoma has been reported, there is no evidence of its oncological safety because most procedures included partial mesorectal excision or abdominoperineal excision and quality of surgery is lacking. The aim of this study was to assess the oncological results of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma. METHODS: From 2000 to 2003, 144 patients underwent laparoscopic total mesorectal excision with low colorectal or coloanal anastomosis for mid and low rectal adenocarcinoma. There were 88 men and 56 women, with a median age of 65 years. The tumor was located at 5.5 cm (range 1-12) from the anal verge and was classified uT1T2 in 25 cases and uT3 in 119 cases. One hundred twenty patients received preoperative radiotherapy. RESULTS: Postoperative mortality and morbidity were 1% and 34% respectively. Conversion was 14% (n = 20). Macroscopic assessment of the specimen (n = 92) showed an intact mesorectum in 88% of the cases. The distal margin and the circumferential margin were safe in 98% and 94% of the cases, respectively. A complete microscopic excision, i.e., R0 resection, was achieved in 134 cases (93%). Pathological data were similar to those of an open match group. With a median follow-up of 18 months, there was no port-site recurrence and two patients had local recurrence (1.4%). The 3-year overall and disease- free survival rates were 89% and 77%, respectively. CONCLUSIONS: A high quality of surgical excision can be achieved by the laparoscopic dissection, suggesting that this approach in treatment of rectal carcinoma is oncologically safe.

Improvement in survival following surgery for colorectal cancer.
McArdle CS, McKee RF, Finlay IG, Wotherspoon H, Hole DJ.
Br J Surg 2005 Jun 1;.

BACKGROUND: Recent reports based on registry data have shown that survival after surgery for colorectal cancer is improving in the UK. It is not clear whether these improvements are due to earlier presentation or more effective treatment. METHODS: Outcome for 645 patients with colorectal cancer admitted to Glasgow Royal Infirmary between 1974 and 1979 was compared with that for 354 patients admitted between 1991 and 1994. RESULTS: More patients in the later period had Dukes' A or B tumours and fewer had evidence of metastatic spread (P < 0.001); more underwent potentially curative resection (57.6 versus 49.9 per cent; P < 0.001) and fewer underwent palliative diversion. The overall postoperative mortality rate fell from 14.1 to 8.5 per cent (P = 0.017). Overall and cancer-specific 5-year survival after potentially curative resection increased from 40.1 to 60.5 per cent and from 47.3 to 71.7 per cent respectively (both P < 0.001). Compared with the earlier period, the adjusted hazard ratio for cancer-specific survival following potentially curative resection was 0.452 (95 per cent confidence interval 0.329 to 0.622; P < 0.001). CONCLUSION: The observed improvement in survival was mainly due to improvements in the quality of surgery and in perioperative care rather than earlier presentation. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Quality of life assessment in patients with chronic anal fissure after lateral internal sphincterotomy.
Ortiz H, Marzo J, Armendariz P, De Miguel M.
Br J Surg 2005 May 12;.

BACKGROUND: The aim of this study was to compare quality of life of patients with chronic anal fissure before and after open lateral internal sphincterotomy. METHODS: A prospective study was undertaken of 108 consecutive patients with a history of chronic anal fissure who underwent lateral internal sphincterotomy. Quality of life was measured before and 6 months after operation with the Short-Form 36 (SF-36) Health Survey. RESULTS: Quality of life improved significantly in six of the eight scales of the SF-36 questionnaire: physical functioning, role physical, bodily pain, energy, social functioning and mental health. There were no significant differences between the 70 patients who had no change in continence after operation and the 38 patients with continence disturbances after sphincterotomy. However, there were significant improvements in four scales in patients without changes in continence compared with improvements in only two scales in those with continence disturbances. CONCLUSION: Patients with chronic anal fissure showed an improvement in quality of life 6 months after internal lateral sphincterotomy. Patients with postoperative continence disturbances showed improvement in fewer scales of the SF-36 questionnaire than those without changes in continence. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

A prospective study comparing diathermy and scalpel incisions in tension-free inguinal hernioplasty.
Chrysos E, Athanasakis E, Antonakakis S, Xynos E, Zoras O.
Am Surg 2005 Apr;71(4):326-9.

Although still controversial, the use of diathermy instead of scalpel for skin incision and underlying tissue dissection is gradually gaining wide acceptance. This is due to the observation that no change in wound complication rates or postoperative pain are reported with the use of electrocautery. However, these studies include operations without the use of prosthetic materials during abdominal wall closure. The purpose of this study was to investigate the hypothesis that a) application of extreme heat may result in significant postoperative pain and poor wound healing because of excessive tissue damage and scarring respectively, and b) skin incision with the use of diathermy entails increased risk of wound infection in the presence of an underlying prosthetic material. One hundred twenty-five consecutive patients submitted to inguinal hernioplasty using the tension-free technique and fulfilling the inclusion criteria for the study were allocated alternately to either scalpel (n = 60), or diathermy (n = 57) groups. Eight patients had bilateral hernias. Five of them were allocated to the scalpel group and three to the diathermy group. According to the study protocol, they received both approaches for skin and underlying tissues incision, thus resulting in a total of 68 scalpel and 65 diathermy individual hernioplasties. Parameters measured included blood loss during the skin incision and underlying tissue dissection, postoperative pain and requirements for analgesics, the presence of wound dehiscence in the absence of infection, and postoperative wound infection on the day of discharge, on the day staples were removed, and 1 month after surgery. The two groups of patients were similar in relation to patient demographics, type of hernias, and operation details. Blood loss was minimal, and the amount of blood lost did not differ between the two groups. Diathermy group patients required less parenteral analgesics on the first postoperative day. A higher proportion of patients in the scalpel group continued to need oral analgesics on the second postoperative day compared to patients in the diathermy group. There was no difference between the two groups in terms of wound strength. Infectious complications were totally absent. The use of diathermy for skin incision during inguinal hernioplasty is as safe as the use of scalpel in terms of wound healing and reduces the analgesics requirements in the postoperative period.

Noninvasive testing for colorectal cancer: a review.
Ouyang DL, Chen JJ, Getzenberg RH, Schoen RE.
Am J Gastroenterol 2005 Jun;100(6):1393-403.

OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Endoscopic screening is now in favor and its use is increasing, but overall participation rates are poor. A substantial percentage of the population will likely continue to resist endoscopic screening. As such, a noninvasive biomarker for the early detection of CRC remains a priority. Herein, we (i) review the currently available noninvasive screening markers for the early detection of CRC, (ii) discuss newer markers that have undergone preliminary testing, and (iii) introduce and explain potentially promising markers of the future. METHODS: The published literature on markers for early detection of CRC was identified using a MEDLINE/PubMed search with secondary review of cited publications. RESULTS: Noninvasive testing for CRC is most advanced in testing for stool fecal occult blood, globin, or DNA mutations. Study of abnormal mucins has also been explored. Research for serum-based markers is just beginning and includes serum proteomics, nuclear matrix proteins, and serum DNA testing. CONCLUSIONS: Serial guaiac-based fecal occult blood testing (FOBT) is simple, inexpensive, and proven effective at reducing mortality from CRC. Immunochemical fecal occult blood tests facilitate compliance and offer improved specificity, but at increased cost in comparison to FOBT. Fecal DNA testing may provide enhanced sensitivity for detection of CRC in comparison with FOBT, but its high cost limits its use for generalized screening. Rectal mucin testing requires additional evaluation to determine its sensitivity and specificity in comparison with guaiac-based FOBT. Serum tests, such as proteomics, nuclear matrix proteins, and serum DNA, are still in their infancy, but remain a hope for the future. (Am J Gastroenterol 2005;100:1-11).

Are patients with inflammatory bowel disease receiving optimal care?
Reddy SI, Friedman S, Telford JJ, Strate L, Ookubo R, Banks PA.
Am J Gastroenterol 2005 Jun;100(6):1357-61.

OBJECTIVES: Guidelines have been published as a framework for therapy of patients with inflammatory bowel disease (IBD). The purpose of this study was to determine whether patients referred for a second opinion were receiving therapy in accordance with practice guidelines. METHODS: Patients with luminal IBD under the care of a gastroenterologist who sought a a second opinion at Brigham and Women's Hospital between January 2001 and April 2003 were enrolled in this study. Clinical information was obtained by direct patient interview at the time of initial patient visit and by a review of prior records. Data obtained included the diagnosis, clinical symptoms, prior medical therapy, preventive measures for metabolic bone disease, and colon-cancer screening. RESULTS: The study population consisted of 67 consecutive patients: 21 with ulcerative colitis, 44 with Crohn's disease and 2 in whom the diagnosis of IBD could not be confirmed. Of the 65 patients with confirmed IBD, 56 patients had symptoms of active disease and 9 were asymptomatic. All analyses were carried out on the 56 patients with active disease. Of the 33 patients treated with aminosalicylates, 21 (64%) were not receiving maximal doses. Nine of 12 (75%) patients with distal ulcerative colitis were not receiving rectal aminosalicylate therapy. Within 6 months of their clinic visit, 35 patients had received corticosteroid therapy, and 27 (77%) patients had been treated with corticosteroids for greater than 3 months. In 16 of 27 (59%) there was no attempt to start steroid sparing medications such as 6-mercaptopurine (6MP), azathioprine, or infliximab. Of the 11 patients treated with either 6MP or azathioprine, 9 (82%) were suboptimally dosed without an attempt to increase dosage. Of the 27 patients on prolonged corticosteroid therapy 21 (78%) received inadequate treatment to prevent metabolic bone disease. Three of 9 patients (33%) meeting indications for surveillance colonoscopy for dysplasia had not undergone colonoscopy at the appropriate interval. CONCLUSIONS: Patients with IBD often do not receive optimal medical therapy. In particular, there is suboptimal dosing of 5-ASA and immunomodulatory medications, prolonged use of corticosteroids, failure to use steroid-sparing agents, inadequate measures to prevent metabolic bone disease, and inadequate screening for colorectal cancer. (Am J Gastroenterol 2005;100:1-5).

Sphincter function after surgery for vestibular anus in adults.
Delaini GG.
Tech Coloproctol 2005 Apr;9(1):73-4; author reply 74.

Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.
Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom PM, Magnuson A, Curman B.
Gastroenterology 2005 Jun;128(7):1805-11.

Background & Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. Results: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy ( P = .017; odds ratio, 4.9; 95% confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. Conclusions: Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.

Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape.
Huber V, Fais S, Iero M, Lugini L, Canese P, Squarcina P, Zaccheddu A, Colone M, Arancia G, Gentile M, Seregni E, Valenti R, Ballabio G, Belli F, Leo E, Parmiani G, Rivoltini L
Gastroenterology 2005 Jun;128(7):1796-804.

Background & Aims: Normal and neoplastic cells release microvesicles, whose effects on the immune system still need to be elucidated. Because human colorectal cancer cells are hypothesized to escape immune recognition by expressing proapoptotic molecules, we investigated whether microvesicles bearing Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand and inducing apoptosis of activated T cells are secreted by colorectal cancer cells both in vitro and in affected patients. Methods: Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand expression were analyzed in colorectal cancer cells and purified microvesicles by flow cytometry, Western blotting, and immunoelectron microscopy. Microvesicle tumor origin was assessed through simultaneous detection of lysosomal (CD63) and adenocarcinoma (carcinoembryonic antigen) markers. Proapoptotic activity of microvesicles was evaluated by annexin V/propidium iodide staining and caspase activation in T cells, including CD8 + T lymphocytes from colorectal cancer patients. Results: Colorectal cancer cells showed a granular pattern of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand expression, suggesting a secretory behavior. These proapoptotic molecules were detected on isolated microvesicles, together with class I HLA, CD63, and carcinoembryonic antigen. Microvesicles induced Fas ligand-mediated and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of activated CD8 + T cells generated from colorectal cancer patients. Microvesicles with comparable phenotypes and functions were found in plasma from patients with advanced disease, whereas vesicular structures expressing Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand were also detected in colorectal cancer specimens. Conclusions: These data show that colorectal cancer induces T-cell apoptosis through the release of Fas ligand-bearing and tumor necrosis factor-related apoptosis-inducing ligand-bearing microvesicles both in vitro and in vivo. This mechanism of immune escape has potential implications as a prognostic factor and could be targeted for the development of new antitumor therapies in colorectal cancer patients.

Current status of gastrointestinal carcinoids.
Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD.
Gastroenterology 2005 May;128(6):1717-51.

Gastrointestinal (GI) carcinoids are ill-understood, enigmatic malignancies, which, although slow growing compared with adenocarcinomas, can behave aggressively. Carcinoids are classified based on organ site and cell of origin and occur most frequently in the GI (67%) where they are most common in small intestine (25%), appendix (12%), and rectum (14%). Local manifestations-mass, bleeding, obstruction, or perforation-reflect invasion or tumor-induced fibrosis and often result in incidental detection at emergency surgery. Symptoms are protean (flushing, sweating, diarrhea, bronchospasm), usually misdiagnosed, and reflect secretion of diverse amines and peptides. Biochemical diagnosis is established by elevation of plasma chromogranin A (CgA), serotonin, or urinary 5-hydroxyindoleacetic acid (5-HIAA), while topographic localization is by Octreoscan, computerized axial tomography (CAT) scan, or endoscopy/ultrasound. Histological identification is confirmed by CgA and synaptophysin immunohistochemistry. Primary therapy is surgical excision to avert local manifestations and decrease hormone secretion. Hepatic metastases may be amenable to cytoreduction, radiofrequency ablation, embolization alone, or with cytotoxics. Hepatic transplantation may rarely be beneficial. Chemotherapy and radiotherapy have minimal efficacy and substantially decrease quality of life. Intravenously administered receptor-targeted radiolabeled somatostatin analogs are of use in disseminated disease. Local endoscopic excision for gastric (type I and II) and rectal carcinoids may be adequate. Somatostatin analogues provide the most effective symptomatic therapy, although interferon has some utility. Overall 5-year survival for carcinoids of the appendix is 98%, gastric (types I/II) is 81%, rectum is 87%, small intestinal is 60%, colonic carcinoids is 62%, and gastric type III/IV is 33%.

Genetic testing for inherited colon cancer.
Burt R, Neklason DW.
Gastroenterology 2005 May;128(6):1696-716.

The genes associated with each of the inherited syndromes of colon cancer have now been identified, and genetic testing is available for diagnosis. These syndromes include familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and, possibly, Cowden's syndrome. Clinical genetic testing approaches have been developed for each of these syndromes and are now a part of accepted clinical care. Disease-causing mutations can be found in the majority of families affected with one of the inherited syndromes, and, most importantly, once a mutation is found in an index case of the family, relatives can be tested for the presence or absence of that mutation with near 100% accuracy. Cancer screening and management in syndrome families is then based on the results of genetic testing. For the physician to order and properly interpret genetic tests, a basic understanding of the types of mutations that lead to inherited disease and the methods for detecting them is vital. These issues will be presented. Additional clinical issues somewhat unique to genetic testing include genetic counseling and informed consent for genetic testing, both of which will also be reviewed. Often the most difficult aspect of genetic testing is deciding which patients and families should undergo the testing. Furthermore, this issue is quite specific for each of the syndromes. Thus, following presentation of general principles of selection for genetic testing, a detailed approach for identifying persons who should undergo testing for each of the individual syndromes will be given, together with relevant descriptions of the syndromes. Finally, the ongoing work to discover new and possibly more common but less penetrant colon cancer susceptibility genes that cause common familial colon cancer will be presented.

Enteroendocrine tumors other than carcinoid: a review of clinically significant advances.
Warner RR.
Gastroenterology 2005 May;128(6):1668-84.

Only relatively recently has there been an increased clinical recognition and characterization of the heterogenous group of rare gastroenteropancreatic neuroendocrine neoplasms. Most have endocrine function and exhibit varying degrees of malignancy. This review summarizes the derivation of these tumors and the advances in their diagnosis and treatment over the past decade and a half. They are varied in their biological behavior and clinical courses and, depending on their cell type, can produce different hormones causing distinct clinical endocrine syndromes (insulinoma [hypoglycemia], gastrinoma [Zollinger-Ellison syndrome (ZES)], vasoactive intestinal peptideoma [VIPoma], watery diarrhea, hypokalemia-achlorhydria [WDHA], glucagonoma [glucagonoma syndrome], and so forth). In addition to surgery for cure or palliation (by excision and a variety of other cytoreductive techniques), they each are treated with antihormonal agents or drugs targeted to each tumor's specific product or its effects. The majority have benefited from the gut hormone-inhibiting action of somatostatin analogs. Because of their usual slow rate of growth it is recommended that, even when they are advanced and incurable, unlike in patients with common and more malignant cancers, patients with neuroendocrine tumors often can be palliated and appear to survive longer when managed with an active approach using sequential multimodality treatment. Advances in these various therapies are reviewed and the beneficial emergence of global self-help patient support groups is noted.

The role of prostaglandins and other eicosanoids in the gastrointestinal tract.
Wang D, Mann JR, DuBois RN.
Gastroenterology 2005 May;128(5):1445-61.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally prescribed to ameliorate symptoms associated with acute pain and chronic inflammatory diseases such as arthritis. Recent epidemiologic studies and clinical trials indicate that use of NSAIDs and cyclooxygenase (COX)-2 selective inhibitors are associated with a reduced risk of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase enzymes are the best known targets of NSAIDs; this diverse class of compounds blocks conversion of arachidonic acid to prostanoids. Prostaglandins and other eicosanoids derived from COX-1 and COX-2 are involved in a variety of physiologic and pathologic processes in the gastrointestinal tract. Recent efforts to identify the molecular mechanisms by which COX-2-derived prostanoids exert their proneoplastic effects have provided a rationale for the possible use of NSAIDs alone or in a combination with conventional or experimental anticancer agents for the treatment or prevention of gastrointestinal cancers.

Recombinant probiotics for treatment and prevention of enterotoxigenic Escherichia coli diarrhea.
Paton AW, Jennings MP, Morona R, Wang H, Focareta A, Roddam LF, Paton JC.
Gastroenterology 2005 May;128(5):1219-28.

BACKGROUND & AIMS: We have developed a therapeutic strategy for gastrointestinal infections that is based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. The aim of this study was to apply this to the development of a recombinant probiotic for treatment and prevention of diarrheal disease caused by enterotoxigenic Escherichia coli strains that produce heat-labile enterotoxin. METHODS: This was achieved by expressing glycosyltransferase genes from Neisseria meningitidis or Campylobacter jejuni in a harmless Escherichia coli strain (CWG308), resulting in the production of a chimeric lipopolysaccharide capable of binding heat-labile enterotoxin with high avidity. RESULTS: The strongest heat-labile enterotoxin binding was achieved with a construct (CWG308:pLNT) that expresses a mimic of lacto-N-neotetraose, which neutralized > or = 93.8% of the heat-labile enterotoxin activity in culture lysates of diverse enterotoxigenic Escherichia coli strains of both human and porcine origin. When tested with purified heat-labile enterotoxin, it was capable of adsorbing approximately 5% of its own weight of toxin. Weaker toxin neutralization was achieved with a construct that mimicked the ganglioside GM2. Preabsorption with, or coadministration of, CWG308:pLNT also resulted in significant in vivo protection from heat-labile enterotoxin-induced fluid secretion in rabbit ligated ileal loops. CONCLUSIONS: Toxin-binding probiotics such as those described here have considerable potential for prophylaxis and treatment of enterotoxigenic Escherichia coli-induced travelers' diarrhea.

Comparing results of residents and attending surgeons to determine whether laparoscopic colectomy is safe.
Mehall JR, Shroff S, Fassler SA, Harper SG, Nejman JH, Zebley DM.
Am J Surg 2005 Jun;189(6):738-41.

BACKGROUND: This study was undertaken to compare the technical success and outcomes of laparoscopic colectomy performed by resident surgeons (RS) and attending surgeons (AS). METHODS: A review of 451 consecutive laparoscopic colectomies performed by 2 surgeons either with or without a general surgery resident. Data reviewed included demographics, diagnoses, operative data, and outcomes. Comparison was made between patients operated on by RS under attending surgeon supervision, and patients operated on by AS alone. RESULTS: Of 451 patients, 324 were operated on by RS and 127 by AS. The mean age and preoperative diagnoses were similar between groups. Operative time was significantly longer in the RS group (155 minutes vs. 128 minutes, P < .05). Blood loss was slightly higher in RS groups but was not statistically significant (191 mL vs. 174 mL, P = .31). The incidence of conversion to an open procedure, postoperative complications, and length of stay were similar between groups. CONCLUSIONS: Supervised RS can safely perform laparoscopic colectomy with results similar to AS. RS take longer to perform the procedure than AS.

Laparoscopic restoration of intestinal continuity after Hartmann's procedure.
Rosen MJ, Cobb WS, Kercher KW, Sing RF, Heniford BT.
Am J Surg 2005 Jun;189(6):670-4.

BACKGROUND: Colostomy closure after a Hartmann's procedure typically requires a laparotomy. It also carries the risk of significant morbidity including anastomotic leak, wound infection, and incisional hernia. The aim of this study was to review our experience with laparoscopic restoration of intestinal continuity after Hartmann's procedure. METHODS: After institutional review board approval, we retrospectively reviewed the medical records of patients undergoing laparoscopic colostomy reversal between July 1997 and July 2004. RESULTS: Twenty-two patients were identified; all patients had left colon colostomies. A laparoscopic technique was used in 21 patients, and 1 patient underwent hand-assisted colostomy reversal concurrently with right radical nephrectomy. The laparoscopic approach was successful in 20 cases, and there were 2 conversions to open (9%) secondary to dense adhesions around the rectal stump. The mean time to closure of the colostomy was 168 days (range 69-385 days). The mean operative time was 158 minutes (range 84-356 minutes). The estimated blood loss averaged 114 mL (range 30-250 mL). The average length of hospitalization was 4.2 days (range 2-6 days). Bowel function returned on an average of 3.5 days (range 2-5 days). Three patients (14%) developed postoperative wound infections. There were no anastomotic leaks and no mortality. At a mean follow-up of 14.7 months, the only long-term complication has been a small hernia at a colostomy site. CONCLUSIONS: Laparoscopic colostomy reversal after Hartmann's procedure can be performed with low morbidity and a short hospital stay. The need for conversion to open surgery is uncommon despite patients' previous surgeries. A laparoscopic approach to colostomy takedown is safe and feasible and may result in a reduction in complications and length of stay as has been seen with other minimally invasive procedures.

Outcome of colorectal carcinoma in patients under 40 years of age.
Lin JT, Wang WS, Yen CC, Liu JH, Yang MH, Chao TC, Chen PM, Chiou TJ.
J Gastroenterol Hepatol 2005 Jun;20(6):900-5.

Abstract Aims: Colorectal carcinoma in patients under 40 years of age usually has a poor prognosis. Controversies still exist regarding the features and the prognosis of colorectal cancer in young patients. Methods: The records of 45 patients with histologically confirmed colorectal carcinoma treated between 1992 and 2002 at the Division of Oncology at Taipei Veterans General Hospital were reviewed. The relevance of sex, duration of symptoms, tumor site, histological type, lymph node involvement, Karnofsky performance status (KPS), carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) levels at the diagnosis and tumor stage to overall survival (OS) were determined by univariate analysis, and their independent significance were tested by multivariate analysis. Results: Most patients presented with an advanced tumor stage (24% Dukes' C and 66% Dukes' D). Colon carcinoma constituted 76% of the colorectal tumors. Family history was present in two patients and did not affect the OS. Two patients were found to have colon carcinoma during pregnancy. The 5-year survival rate in patients with Stage B, C, and D were 25, 16 and 0%, respectively. With aggressive treatment, patients with early stage carcinoma achieved longer survival. Eleven patients received resection of metastatic carcinoma of the liver, lung and ovary. Adjuvant chemotherapy with irinotecan/5-fluoroucil-based chemotherapy seemed to improve the OS in such patients, though the OS was still poorer than in patients with early stage tumors. In univariate analysis, KPS (P = 0.0001), lymph node involvement (P = 0.0024), CEA (P = 0.0423) and LDH levels (P = 0.0126) at the diagnosis and tumor stage (P = 0.0122) proved to be significant predictors of overall survival. Multivariate analyses revealed that KPS >/=70% (P = 0.007) and normal LDH levels at diagnosis (P = 0.004) were predictive of overall survival in this population. Conclusions: The present study shows that performance status and preoperative LDH levels were the major determinants for survival in patients with colorectal carcinoma under 40 years of age and the present series also suggests that surgical resection of metastatic colorectal carcinoma followed by adjuvant chemotherapy might be beneficial in certain patients. The data also suggests that current treatment modalities for young patients with advanced colorectal cancer might not be effective and more effective therapeutic regimens might be needed. Thus, it is important for surgeons to recognize the potential for colorectal cancer in young patients and to take an aggressive approach to the diagnosis and early treatment of the disease.

Gastrointestinal stromal tumors: Clinical profile, pathogenesis, treatment strategies and prognosis.
Nowain A, Bhakta H, Pais S, Kanel G, Verma S.
J Gastroenterol Hepatol 2005 Jun;20(6):818-24.

Abstract Gastrointestinal stromal tumors (GIST), although the most common mesenchymal neoplasms of the gastrointestinal (GI) tract, account for <1% of all GI malignancies. Up to 94% of these tumors express the CD117 antigen. Most patients present in the fifth to seventh decade, the commonest symptom being that of an abdominal mass. Surgery is the main modality of therapy, but even after adequate resection the vast majority of GIST reoccur, and in approximately 50% the liver is the main site of the metastasis. Long-term, maybe even lifelong follow up of these patients after initial resection cannot be over-emphasized. Initial tumor size and mitotic rate are the most useful parameters to predict malignant potential. In view of high postoperative recurrence, adjuvant forms of therapy are being explored, and the tyrosine kinase inhibitor imatinib holds the most promise. (c) 2005 Blackwell Publishing Asia Pty Ltd.

Discovery of a new biomarker for gastroenterological cancers.
Aburatani H.
J Gastroenterol 2005 Mar;40 Suppl 16:1-6.

Various genomic technologies have been applied to address crucial problems in cancer biology, because cancer develops through the accumulation of various genetic alterations. Of these, gene expression profiling analysis using microarray technology has been widely applied not only to classify cancers at molecular levels, but also to identify novel molecular targets for therapeutics and/or diagnostics. To gain molecular understanding of gastric carcinogenesis, progression, and diversity, we analyzed primary advanced gastric cancer and noncancerous gastric tissues by high-density oligonucleotide microarray. Genes differentially expressed between cancer and noncancerous tissues were identified. In cancer tissues, genes related to cell cycle, growth factor, cell motility, cell adhesion, and matrix remodeling were highly expressed, whereas those related to gastrointestinal-specific function and immune response were rather downregulated. These results provide not only a new molecular basis for understanding biological properties of gastric cancer but also useful resources for future development of therapeutic and diagnostic biomarkers for gastric cancer. Several microarray studies have been published since and have been compared for validation in meta-analysis. As integration of transcriptome information with other biological data is crucial to interpret gene expression data, we have applied oligonucleotide microarray technology to assess allelic gene dosage at 10000 polymorphic loci, namely with an average interval of 200kb. Using a newly developed algorithm, genome imbalance map, loss of heterozygosity (LOH) status can be determined simultaneously. Besides several loci with genomic amplification, we also identified a homozygously deleted chromosomal region in 7q, where frequent chromosomal instability was observed. Finally, we are currently developing novel biomarkers for gastroenterological cancers. Glypican 3 is detected at high levels in serum of hepatocellular carcinoma patients and could be a potential target for antibody therapy.

Probiotics for the Developing World.
Reid G, Anand S, Bingham MO, Mbugua G, Wadstrom T, Fuller R, Anukam K, Katsivo M.
J Clin Gastroenterol 2005 Jul;39(6):485-488.

Every minute of every day more and more children die of diarrheal diseases and women, and girls become infected by HIV. An estimated 7,000 women become infected each day. While many valiant efforts are being made to address these issues, until now they have proved to be markedly ineffective. The notion that lactic acid bacteria, formulated into food or dietary supplements, could have a role to play in slowing the morbidity and mortality associated with HIV/AIDS and gastroenteritis, is built upon sound clinical findings and scientific investigations, yet no international efforts have been placed in this approach, to date. We hereby summarize the reasons why such efforts should be made, provide an example of one model being set up in sub-Saharan Africa, and challenge the international community to consider the potential benefits of probiotics, especially for communities not reached by governmental and nongovernmental agencies.

Probiotics Used in Human Studies.
Montrose DC, Floch MH.
J Clin Gastroenterol 2005 Jul;39(6):469-484.

GOAL: To investigate the literature from 1980 to 2004 for the types of studies and organisms used as probiotics in human studies and diseases. METHODS: PubMed search for probiotic organisms used in studies from 1980 to August 2004. The data from those papers were evaluated for organisms used, dose, vehicle, frequency, and investigator's report of positive or negative results. RESULTS: A total of 185 manuscripts were identified. Investigators reported results of both single and multiple organisms in the same manuscript. A single organism was used in 125 reports, and multiple organisms, ranging from 2 to 9, were used in 60 reports. Positive results were reported in 239 clinical situations and negative results reported in 49 in a total of 288 clinical conclusions drawn by the respective investigators. The studies are tabulated in this review. CONCLUSION: There is a large literature available in credible journals that report benefit of probiotic administration using a wide range of doses, organisms, and clinical situations. Most of the studies are simple reports of a clinical situation and require additional evaluation.

Herbal remedies in gastroenterology.
Comar KM, Kirby DF.
J Clin Gastroenterol 2005 Jul;39(6):457-68.

Complementary and alternative medicine (CAM) is presently not considered to be part of conventional medicine. Nevertheless, an estimated 51% of patients with gastrointestinal disorders have tried some from of CAM. Indeed, 10% of alternative medicines are being used for digestive symptoms. After prayer or spiritual healing, herbal medicine is the second most common CAM therapy. While herbal products make numerous health-related claims, those that have been systematically evaluated are unfortunately few. The modern gastroenterologist must be up to date with the regulations, side effects, and possible benefits of specific herbal products used in patients with gastrointestinal disorders.

Selective effect of infliximab on the inflammatory component of a colonic stricture in Crohn's disease.
Sorrentino D, Avellini C, Beltrami CA, Pasqual E, Zearo E.
Int J Colorectal Dis 2005 Jun 11;.

Although infliximab has been shown to improve the clinical course of Crohn's disease, its effect on intestinal strictures is controversial. We describe the case of a woman with steroid-resistant colonic Crohn's disease presenting with intermittent obstruction because of a tight stricture in the splenic flexure. Compared with uninvolved areas, biopsies showed intense edema and inflammatory cell infiltration and immunohistochemistry revealed an excess of TNF-alpha. Her symptoms responded promptly (CDAI went from 444 to 168) to an infliximab infusion (10 mg kg(-1) BW), which also had a dramatic effect on the stricture, now presenting radiologically as a moderate residual, apparently fibrotic, narrowing of the lumen. Endoscopy and histology confirmed the resolution of inflammation and TNF-alpha virtually disappeared. The patient refused additional infusions and after a few months the disease recurred with features identical to the pre-treatment phase. She then opted for surgery. Histology of the resected strictured colon revealed edema, inflammation, and fibrosis, with TNF-alpha back to pre-treatment levels. This case indicates that, in the colon, infliximab specifically relieves the TNF-alpha-mediated inflammatory component of the stricture while having no effect on fibrosis and suggests that the response to infliximab treatment may depend on the nature of the, stricture itself.

Clinical spectrum and surgical approach of adult intussusceptions: a multicentric study.
Barussaud M, Regenet N, Briennon X, de Kerviler B, Pessaux P, Kohneh-Sharhi N, Lehur PA, Hamy A, Leborgne J, le Neel JC, Mirallie E.
Int J Colorectal Dis 2005 Jun 11;.

BACKGROUND: The preoperative diagnosis of adult intussusceptions (AIs) remains difficult, and the assessment of the radiological methods has been evaluated very little in the literature. The aim of this study was to evaluate the interest of the different imaging modalities for the preoperative diagnosis of AI and describe causes of AI. PATIENTS AND METHODS: Consecutive patients of 15 years and older with the postoperative diagnosis of intussusception from 1979 to 2004 were reviewed retrospectively for this multicentric study. Data concerning clinical considerations, morphological examinations, surgical procedure, histological conclusions, mortality rate and recurrence were analysed. RESULTS: Forty-four patients with documented intussusception were included. The mean age was 51 years (15-93 years). The preoperative diagnosis of intussusception was made in 52% of the cases. The sensitivities of the different radiological methods were abdominal ultrasounds (35%), upper gastrointestinal barium study (33%), abdominal computed tomography (CT) (58%) and barium enema (73%). An organic lesion was identified in 95% of the cases. There was 29 enteric and 15 colonic (including appendicular) intussusceptions. Thirty-seven percent of the enteric lesions were malignant, and a bit less than 50% of them were metastatic melanomas. The benign enteric lesions were Meckel's diverticulum and Peutz-Jeghers syndrome in half of the cases. Fifty-eight percent of the pure colonic lesions (excluding appendix) were malignant, and 85% of them were primary adenocarcinomas. The benign colonic lesions were lipomas in 80% of the cases. All patients, except one, had a surgical treatment, and 13 of them had a complete reduction of the intussusception before resection. The mortality rate was 16% and recurrence occurred in three patients; two of them had a Peutz-Jeghers syndrome. CONCLUSION: Intussusception rarely occurs in adults, but nearly half of their causes are malignant. The CT scan is a helpful examination for enteric intussusceptions whether barium enema seems to be the most performing method for colonic lesions. Surgery is the recommended treatment, with or without a primary reduction of the intussusception. During the surgical procedure, this reduction can lead to a more limited bowel resection.

Reparative properties of a commercial fish protein hydrolysate preparation.
Fitzgerald AJ, Rai PS, Marchbank T, Taylor GW, Ghosh S, Ritz BW, Playford RJ.
Gut 2005 Jun;54(6):775-81.

BACKGROUND: A partially hydrolysed and dried product of pacific whiting fish is currently marketed as a health food supplement to support "intestinal health". However, there has been only limited scientific study regarding its true biological activity. AIMS: We therefore tested its efficacy in a variety of models of epithelial injury and repair. METHODS: Effects on proliferation were determined using [(3)H] thymidine incorporation into epithelial rat intestinal RIE-1 and human colonic HT29 cells. Effects on restitution (cell migration) were analysed using wounded HT29 monolayers and its ability to influence gastric injury analysed using a rat indomethacin restraint model. Partial characterisation of bioactive agents was performed using mass spectroscopy, high pressure liquid chromatography, and gas chromatography. RESULTS: Both cell proliferation and cell migration were increased by about threefold when added at 1 mg/ml (p<0.01). Gastric injury was reduced by 59% when gavaged at 25 mg/ml (p<0.05), results similar to using the potent cytoprotective agent epidermal growth factor at 12.5 mug/ml. The vast majority of biological activity was soluble in ethanol, with glutamine in its single, di-, and tripeptide forms probably accounting for approximately 40% of the total bioactivity seen. Fatty acid constituents may also have contributed to cell migratory activity. CONCLUSIONS: Fish protein hydrolysate possesses biological activity when analysed in a variety of models of injury and repair and could provide a novel inexpensive approach for the prevention and treatment of the injurious effects of non-steroidal anti-inflammatory drugs and other ulcerative conditions of the bowel. Further studies appear justified.

Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).
Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A
N Engl J Med 2005 May 5;352(18):1851-60.

BACKGROUND: Germ-line mutations in the mismatch-repair genes MLH1, MSH2, MSH6, and PMS2 lead to the development of the Lynch syndrome (hereditary nonpolyposis colorectal cancer), conferring a strong susceptibility to cancer. We assessed the frequency of such mutations in patients with colorectal cancer and examined strategies for molecular screening to identify patients with the syndrome. METHODS: Patients with a new diagnosis of colorectal adenocarcinoma at the major hospitals in metropolitan Columbus, Ohio, were eligible for the study. Genotyping of the tumor for microsatellite instability was the primary screening method. Among patients whose screening results were positive for microsatellite instability, we searched for germ-line mutations in the MLH1, MSH2, MSH6, and PMS2 genes with the use of immunohistochemical staining for mismatch-repair proteins, genomic sequencing, and deletion studies. Family members of carriers of the mutations were counseled, and those found to be at risk were offered mutation testing. RESULTS: Of 1066 patients enrolled in the study, 208 (19.5 percent) had microsatellite instability, and 23 of these patients had a mutation causing the Lynch syndrome (2.2 percent). Among the 23 probands with the Lynch syndrome, 10 were more than 50 years of age and 5 did not meet the Amsterdam criteria or the Bethesda guidelines for the diagnosis of hereditary nonpolyposis colorectal cancer (including the use of age and family history to identify patients at high risk for the Lynch syndrome). Genotyping for microsatellite instability alone and immunohistochemical analysis alone each failed to identify two probands. In the families of 21 of the probands, 117 persons at risk were tested, and of these, 52 had Lynch syndrome mutations and 65 did not. CONCLUSIONS: Routine molecular screening of patients with colorectal adenocarcinoma for the Lynch syndrome identified mutations in patients and their family members that otherwise would not have been detected. These data suggest that the effectiveness of screening with immunohistochemical analysis of the mismatch-repair proteins would be similar to that of the more complex strategy of genotyping for microsatellite instability.

Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels.
Matano Y, Okada T, Suzuki A, Yoneda T, Takeda Y, Mabuchi H
Am J Gastroenterol 2005 May;100(5):1154-60.

Locally recurrent rectal cancer: when should radiofrequency ablation be used?
Ripetti V, Ausania F, Zobel B, Coppola R
Int J Colorectal Dis 2005 Apr 12;.

Prospective, randomised study on antibiotic prophylaxis in colorectal surgery. Is it really necessary to use oral antibiotics?
Espin-Basany E, Sanchez-Garcia JL, Lopez-Cano M, Lozoya-Trujillo R, Medarde-Ferrer M, Armadans-Gil L, Alemany-Vilches L, Armengol-Carrasco M
Int J Colorectal Dis 2005 Apr 21;.

BACKGROUND AND AIMS: The use of prophylactic antibiotics in addition to mechanical cleansing is the current standard of care prior to colonic surgery. The question of whether the antibiotics should be administered intravenously or orally, or by both routes, remains controversial. Our aim was to compare three methods of prophylactic antibiotic administration in elective colorectal surgery. METHODS: Three hundred consecutive elective colorectal resections were studied. All patients had preoperative mechanical colon cleansing with oral sodium phosphate and intravenous antibiotic prophylaxis with cefoxitin (one dose before skin incision and two postoperative doses). Patients were randomised to one of the following three groups: group A: three doses of oral antibiotic (neomycin and metronidazole) at the time of mechanical colon cleansing; group B: one dose of oral antibiotic; group C: no oral antibiotics. All patients were followed during their hospital stay and at 7, 14 and 30 days post-surgery. RESULTS: Vomiting occurred in 31%, 11% and 9% of the studied patients (groups A, B and C, respectively) (p<0.001). Nausea was present in 44%, 18% and 13% of patients (p<0.001). Abdominal pain was recorded in 13%, 10% and 4% of patients (p: 0.077). Wound infection was present in 7%, 8% and 6% and suture dehiscence occurred in 2%, 2% and 3% of the patients in the three groups (no differences among them). Neither were differences found among the three groups in terms of urinary infections, pneumonia, postoperative ileus or intra-abdominal abscess. CONCLUSION: The addition of three doses of oral antibiotics to intravenous antibiotic prophylaxis is associated with lower patient tolerance in terms of increased nausea, vomiting and abdominal pain, and has shown no advantages in the prevention of postoperative septic complications. Therefore, we recommend that oral antibiotics should not be used prior to colorectal surgery.

HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN) Impact of HPV analysis of anal lesions on diagnosis and prognosis.
Varnai AD, Bollmann M, Griefingholt H, Speich N, Schmitt C, Bollmann R, Decker D
Int J Colorectal Dis 2005 Apr 29;.

BACKGROUND AND AIMS: Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN). This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN. Results were clinically correlated. METHODS: The study included biopsy samples from 87 patients who had been diagnosed with the following disease patterns: 47 invasive anal carcinoma, 33 AIN of varying severity and seven condylomatous lesions. In 52 of these cases, a tumour was clinically suspected. All biopsies were retrospectively examined for microscopic indications of HPV infection. After microdissection, additional HPV analysis via PCR was carried out. RESULTS: In 38 of 47 cases of anal carcinoma, HPV DNA could be detected via PCR (80.9%), the majority of which were HPV 16 (33/38=86.8%). In 29 of the 33 cases of AIN, HPV DNA was detected (87.9%), most of these in AIN III (15/16=93.8%). Histological markers of HPV infection were detected in all 87 cases. DISCUSSION: In our series, the clinical diagnosis of the invasive anal carcinoma had a high sensitivity of 93.6%, with a specificity of 80%. The positive predictive value was 84.6%, and the negative predictive value 91.4%. In contrast, AIN had been detected clinically in none of the cases. In this situation, especially with high-risk patients, our findings recommend anal HPV screening in combination with anal cytology and anoscopy. CONCLUSION: Based on our results, we urgently recommend for any histological report on excision of anal lesions to include a statement whether histological markers of HPV infection were detected. In individual cases, validation via HPV PCR must be considered.

Blocking MAdCAM-1 in vivo reduces leukocyte extravasation and reverses chronic inflammation in experimental colitis.
Farkas S, Hornung M, Sattler C, Edtinger K, Steinbauer M, Anthuber M, Schlitt HJ, Herfarth H, Geissler EK
Int J Colorectal Dis 2005 Apr 23;.

BACKGROUND: Leukocyte recruitment to sites of intestinal inflammation is a crucial multi-step process, leading ultimately to the accumulation of cells in the inflamed tissue. These interactions in the gut are critically dependent on the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed on endothelial cells within the mesenteric lymph nodes and the lamina propria of the intestine. Here, we investigate the pathophysiologic role of MAdCAM-1 in the intestinal microcirculation in vivo. METHODS: Using a standard mouse model, chronic colitis was established after four cycles of dextran sodium sulfate (DSS) application. MAdCAM-1 expression was investigated by immunohistochemistry and Western blotting, as well as real-time polymerase chain reaction (PCR). Intravital microscopy was used to study the role of MAdCAM-1 on leukocyte-endothelium interactions and leukocyte extravasation. RESULTS: Significant changes in MAdCAM-1 were observed in mice with chronic DSS-induced colitis. Upregulation of MAdCAM-1 expression in chronic colitis was demonstrated on a protein and messenger ribonucleic acid (mRNA) level. Anti-MAdCAM-1 treatment lead to a marked reduction (>60%) of leukocyte sticking and extravasation in vivo, compared to the controls. This was parallelled by a significant reduction (45%) of intestinal inflammation, as measured by the histologic grading score. CONCLUSION: These in vivo results demonstrate a distinct role of MAdCAM-1 in inflammatory intestinal diseases, and suggest that therapeutic strategies targeting this adhesion molecule could be useful in the treatment of chronic colitis.

Tumour regression grading in the evaluation of tumour response after different preoperative radiotherapy treatments for rectal carcinoma.
Vironen J, Juhola M, Kairaluoma M, Jantunen I, Kellokumpu I
Int J Colorectal Dis 2005 Apr 23;.

BACKGROUND AND AIMS: Preoperative radiotherapy (PRT) for rectal carcinoma has been shown to cause tumour regression and increase local control and patient survival. The aim of this study was to examine the usefulness of tumour regression grading (TRG) in quantifying the effect of PRT. METHODS: Depending on the tumour stage (uT), as defined by preoperative endorectal ultrasound (ERUS), fixity and distance from the anal verge, 126 patients with rectal cancer underwent either surgery alone, or received short-course 25-Gy radiotherapy or long-course 50-Gy radiotherapy combined with 5-fluorouracil (5-FU) before surgery. TRG in each group was assessed and compared with the downstaging, defined as a change in preoperative uT stage and pathologic stage (pT). RESULTS: Complete response (no residual tumour, TRG 1) was seen in 7% of the patients (3/44) and total or major regression (TRG 1-3) in 73% of the patients (32/44) treated with 50-Gy chemoradiation. Of those treated with 25-Gy PRT, 21% (9/42) showed major tumour regression. Of the patients who underwent ERUS and PRT, 32% (26/83) were downstaged when comparing uT with pT, but 53% (14/26) of the downstaged tumours showed no response by TRG. In comparison, 50% (28/57) of the tumours with no downstaging showed a marked response by TRG (p=0.05). CONCLUSIONS: Tumour regression grading offers detailed information of the effect of PRT and shows that tumour regression is more marked after long-term chemoradiation than after short-course radiotherapy (p=0.02). In contrast, T-stage downstaging was similar in both groups and did not correlate with the TRG results (p=0.05).

Different role of the colonic pouch for low anterior resection and coloanal anastomosis.
Tonelli F, Garcea A, Batignani G
Tech Coloproctol 2005 Apr;9(1):15-20.

BACKGROUND : Functional outcome after sphincter-saving operations can be improved by colonic pouch compared to the straight procedure. However, it is not clear whether the colonic pouch has a different behavior in patients treated by low anterior resection with colorectal (LAR) or coloanal anastomosis (CAA). METHODS : We evaluated the 1-year results of 75 patients who underwent a sphincter-saving operation for rectal carcinoma or villous tumor of the middle or lower third of the rectum: 18 patients underwent coloanal anastomosis (CAA), in 13 patients we performed a coloanal anastomosis with a colonic pouch (PCAA), 20 patients had low anterior resection (LAR) and 24 had LAR with pouch construction (PLAR). The two groups of patients were similar in terms of age and gender. Anorectal function was assessed 12 months after the initial operation by an interview and anorectal manometry. RESULTS : One year after surgery, the daily mean number of defecations was significantly higher in the LAR group than in the other groups (2.0+/-1.5 in CAA group, 2.2+/-1.0 in PCAA, 2.3+/-1.8 in PLAR, 4.1+/-0.7 in LAR; p<0.05). Frequent soiling was observed in all the groups except PLAR. A lower degree of incontinence and a lower frequency of urgency were found in PCAA than in CAA. There were no differences in anal resting pressure and squeeze pressure among the various groups. Greater distensibility and compliance of the neorectum were observed in CAA, PCAA and PLAR compared to LAR, respectively 8.5+/-7.0 ml air/mmHg for CAA, 8.7+/-5.0 ml air/mmHg for PCAA, 6.3+/-4.0 ml air/mmHg for PLAR and 3.1+/-2.7 ml air/mmHg for LAR. A significant inverse linear correlation was present between the mean daily number of defecations and compliance. No difference in sense of incomplete evacuation was observed among the groups of patients. CONCLUSIONS : Colonic J-pouch provides an advantage over straight anastomosis in sphincter-saving operations by reducing the daily number of defecations, and the frequencies of fecal soiling and urgency. The role of the pouch seems to be different in LAR compared to CAA. In fact, in LAR the pouch increases compliance and consequently decreases the daily number of defecations. In CAA, the pouch does not reduce the number of defecations or the compliance, but reduces the frequency of fecal soiling and urgency.

Stoma formation for fecal diversion: a plea for the laparoscopic approach.
Liu J, Bruch HP, Farke S, Nolde J, Schwandner O
Tech Coloproctol 2005 Apr;9(1):9-14.

BACKGROUND : The aim of this study was to assess the results of laparoscopic stoma creation for fecal diversion, specifically focussing on feasibility, safety, and efficacy, as well as indications and techniques. METHODS : Within a 10-year-period, all patients requiring laparoscopic stoma creation were evaluated prospectively. Patients' profiles and indications, procedures and results of operation, conversion, morbidity, mortality and short-term complications (stoma-related, laparoscopy-associated) were analyzed. RESULTS : A total of 80 patients (39 males, 41 females) with a mean age of 55.5 years (range, 17-91) underwent laparoscopic stoma creation. Most common indications were unresectable advanced colorectal cancer (n=20), pelvic malignant cancer (e. g. ovarian, cervix and prostate cancer, n=16), and perianal Crohn's disease with complex fistulas (n=16). Only in one female patient with pelvic malignant disease was the procedure converted to laparotomy due to obesity (conversion rate, 1.3%). 79 patients underwent laparoscopic stoma creation (completion rate, 98.7%) including loop ileostomy (n=30), loop sigmoid colostomy (n=40) and end sigmoid colostomy (n=9). Postoperative complications were documented in 9 patients (overall morbidity rate, 11.4%), including 4 minor complications treated conservatively (2 cases of prolonged atonia and 1 case each of pneumonia and urinary tract infection) and 5 major complications requiring reoperation (reoperation rate, 6.3%): one parastomal abscess (drainage), one stoma retraction following rod dislocation (laparoscopic stoma recreation), small bowel obstruction in two patients (small bowel resection), one port-site hernia (fascial closure), and hemorrhage (managed by re-laparoscopy). Mean operation time was 74 min (range, 30-245 min). Mean blood loss volume was 80 ml (range, 30-400 ml). Patients were discharged from hospital after a mean of 10.3 days (range, 3-47). Within a 1-year follow-up, no further stoma complications were documented. CONCLUSIONS : The advantages of laparoscopic stoma creation are low morbidity and reoperation rates, and no procedure-related mortality; our results suggest that laparoscopic stoma creation for fecal diversion is safe, feasible and effective. Therefore, at our institution, laparoscopic stoma creation is the method of choice for fecal diversion.

Good colorectal cancer surgery.
Mahteme H, Pahlman L
Tech Coloproctol 2005 Apr;9(1):1-7.

Adenocarcinoma of the colon and rectum is currently diagnosed in about 783 000 new cases annually and 437 000 patients will die of the disease each year worldwide. Colorectal cancer presents as an emergency situation (obstruction, bleeding or perforation) in approximately 25% of cases and with more or less obvious chronic symptoms in the rest of cases. Rectal cancer patients, with a T1 tumour can be offered local excision whereas patients with more advanced cancer must be offered a more radical abdominal procedure. In large bulky tumours (T3 or definitely T4), MRI should guide the choice of preoperative radiotherapy. Three major indications for radiotherapy are reduction of local recurrences in mobile rectal cancer in order to improve survival, down-staging of the tumour in primary irresectable tumours, and downsizing of low-lying tumours in an attempt to perform a sphincter-saving procedure. The surgical strategy is to remove the tumour-bearing bowel segment with, if possible, a locoregional curative procedure, to restorate bowel continuity, and to ensure an optimal quality of life. In most situations, it is possible to achieve local radical resection. In rectal cancer surgery, the main problem is to stick to the embryological planes during the whole procedure. The whole mesorectum is taken out as a packet down to the level of division. This TME procedure dramatically reduced the local recurrence rate to 3%-7%. Surgeon case volume may be an important factor in cancer surgery success. Laparoscopic surgery for colorectal cancer has stimulated a great deal of interest in recent years, but there are concerns regarding this type of surgery. In conclusion, modern surgery for colorectal cancer is a well-defined technique where the anatomical planes have to be identified. Care must be taken to learn all the essential steps. Data from the literature strongly support that the surgeon is the most important factor for an excellent outcome.

Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats.
Meile T, Glatzle J, Habermann FM, Kreis ME, Zittel TT
Int J Colorectal Dis 2005 May 4;.

BACKGROUND: Nitric oxide (NO) is known to inhibit gastrointestinal motility. However, no detailed analysis of gastric, small intestinal and colonic motor effects, including effects on contraction frequency, has, as yet, been reported after NO inhibition in awake rats. We therefore investigated the effects of NO synthase inhibition on gastric, small intestinal and colonic motility in awake rats under baseline conditions and in a postoperative ileus model. METHODS: In Sprague-Dawley rats, strain gauge transducers were sutured either to the gastric corpus, the small intestine or the colon. After 3 days, L: -NMMA (NO synthase inhibitor), D: -NMMA or vehicle was given i.v., while the motility was recorded continuously. In addition, postoperative gastric, small intestinal or colonic motility was investigated after L: -NMMA or vehicle treatment prior to abdominal surgery. The motility index, the contraction amplitude, the area under the contraction amplitude and the contraction frequency were analysed. RESULTS: L: -NMMA decreased gastric motility to 60+/-8% for about 15 min, but continuously increased small intestinal motility to 221+/-22% and colonic motility to 125+/-7% compared to baseline (baseline=100%; p<0.01 for all comparisons). L: -NMMA increased the contraction frequency throughout the gastrointestinal tract (stomach, 13+/-2%; small intestine, 8+/-1%; colon, 16+/-5%; p<0.01 vs. baseline for all comparisons). L: -NMMA injection prior to surgery did not prohibit intraoperative inhibition of gastrointestinal motility, but did result in immediate recovery of gastric, small intestinal and colonic motility postoperatively (L: -NMMA vs. vehicle, 0-60 min postoperatively; stomach, 90+/-9% vs. 53+/-3%; small intestine, 101+/-5% vs. 57+/-3%; colon, 134+/-6% vs. 60+/-5%; p<0.01 for all comparisons; no significant difference between preoperative baseline motility and L: -NMMA treated rats postoperatively). CONCLUSIONS: Under baseline conditions, endogenous NO inhibits small intestinal and colonic motility and gastric, small intestinal and colonic contraction frequency in awake rats. In the early postoperative period, endogenous NO is a major inhibitory component that seems to constitute the common final pathway of mediators and the neural pathways inhibiting gastrointestinal motility in rats.

Ileal pouch-anal anastomosis (IPAA): functional outcome after postoperative pelvic sepsis A prospective study of 100 patients.
Hallberg H, Stahlberg D, Akerlund JE
Int J Colorectal Dis 2005 Apr 30;.

INTRODUCTION: The ileal pouch-anal anastomosis (IPAA) has become a standard procedure for patients with ulcerative colitis requiring surgical intervention. The technique has greatly improved and, since 1990, all patients at Huddinge University Hospital have been operated on with the double stapled technique. Pelvic sepsis is one of the most serious complications postoperatively, and, according to previous reports, leads to impaired function of the pouch and, in some cases, extirpation of the pouch. AIM: The purpose of this study was to find out if pelvic sepsis postoperatively after IPAA leads to impaired functional outcome at long-term follow-up. PATIENTS AND METHODS: One hundred consecutive patients with ulcerative colitis operated on between 1990 and 1997 with double stapled J-shaped pouches were followed prospectively with a standardised questionnaire, clinical follow-up and endoscopy of the pouch. The function of the pouch has been evaluated at a minimum of 2 years after surgery to compare the functional outcome between patients with and without pelvic sepsis postoperatively. RESULTS: Twelve patients developed pelvic sepsis postoperatively. No significant differences were found in pouch evacuation frequency, incontinence, deferral time, usage of protecting pads, skin irritation, evacuation problems, diet, usage of medication or social handicap. There was one failure in the control group. CONCLUSION: In this study, no evidence was found that suggested pelvic sepsis postoperatively impairs functional outcome after IPAA at long-term follow-up.

Immune responses in advanced colorectal cancer following repeated intradermal vaccination with the anti-CEA murine monoclonal antibody, PR1A3: results of a phase I study.
Zbar AP, Thomas H, Wilkinson RW, Wadhwa M, Syrigos KN, Ross EL, Dilger P, Allen-Mersh TG, Kmiot WA, Epenetos AA, Snary D, Bodmer WF
Int J Colorectal Dis 2005 Apr 30;.

BACKGROUND AND AIMS: The aim was to determine the toxicity, clinical and immune responses to the murine monoclonal anti-carcinoembryonic antigen (CEA) antibody, PR1A3, in patients with advanced colorectal cancer. MATERIALS AND METHODS: Fifteen patients with advanced colorectal cancer received either 0.5-, 1.0- or 5.0-mg doses of PR1A3 mixed with 10% w/v Alum adjuvant (Superfos Biosector, Denmark) intradermally at 4-week intervals for 3 months. Patient serum was assessed for anti-idiotypic (Ab2), anti-anti-idiotypic (Ab3) and human anti-mouse antibody (HAMA) reactivity. Peripheral blood mononuclear cell (PBMC) proliferation with phytohaemagglutinin (PHA), CEA and PR1A3, stimulated IL-2, IL-4 and IFN-gamma levels and PR1A3-stimulated IL-2 receptor expression during immunotherapy were determined. Comparisons were made with 16 age-matched controls without malignant disease. RESULTS: Hyperimmune sera from 12 of the 15 patients showed Ab2 reactivity with no detectable Ab3 responses. Strong HAMA reactivity was recorded in 7 of the 15 cases with no adverse clinical effect. Delayed-type hypersensitivity (DTH) responses developed in 12 of the 15 patients. Pre-treatment PBMC proliferation with PHA was subnormal in each patient compared with controls, becoming normal (or supranormal) in all patients during immunisation (P<0.001). PBMC proliferation with CEA and PR1A3 increased during immunotherapy (P<0.001) along with stimulated production of IL-2, IFN-gamma and IL-2 receptor expression. Progressive disease was observed in 14 of the 15 patients with minimal toxicity. CONCLUSION: PR1A3 generated limited idiotypic responses but robust DTH reactivity in most patients. In vitro PBMC proliferation with mitogens and recall antigens is greatly increased during the course of immunisation, with a shift in stimulated cytokine profile.

The utilization of intraluminal formalin for intractable rectal haemorrhage in advanced rectal cancer: a case report.
Zbar AP, Bernstein S, Greaves N, Iniss M, Shenoy RK
Tech Coloproctol 2005 Apr;9(1):49-51.

A patient with a metastatic fixed low rectal carcinoma presented severe rectal bleeding requiring massive transfusion over with a 36-hour period. Bleeding was controlled with the instillation of a 4% intrarectal formalin solution permitting the completion of a course of neoadjuvant chemoradiotherapy. This technique has been reserved for intractable transfusion-dependent radiation proctitis and is presented as a primary alternative in severe rectal bleeding from inoperable rectal cancer.

Anorectal atresia treated with non-continent pull through and artificial bowel sphincter: a case report.
Bracale U, Nastro P, Beral DL, Romano G, Renda A
Tech Coloproctol 2005 Apr;9(1):45-8.

Anorectal atresia, which is classified as a low anorectal malformation, is characterised by the absence of the anal verge and by variable rectal atresia. In some cases, which have been classified as rectal agenesis, the atresia is associated with the absence of the internal sphincter. The therapeutic options are definitely surgical, aiming to relieve the bowel occlusion and to restore faecal continence by lowering the cul-de-sac to the perineum. We present the case of an adult patient with congenital rectal agenesis, double fistula (cul-de-sac-urethra and cul-de-sac-perineum) and caecostomy since birth. The patient was treated with a resection of sigmoid-rectum for the presence of a 20-cm faecaloma in the cul-de-sac, with a non-continent pull-through, and with implantation of an artificial bowel sphincter. Despite some difficulties in managing the device and a slight symptomatic mucosal prolapse, the results after 30 months have so far satisfied both the patient and the medical staff, especially in consideration of the limited number of alternative therapies.

Long-term Oncologic Outcome Following Preoperative Combined Modality Therapy and Total Mesorectal Excision of Locally Advanced Rectal Cancer.
Guillem JG, Chessin DB, Cohen AM, Shia J, Mazumdar M, Enker W, Paty PB, Weiser MR, Klimstra D, Saltz L, Minsky BD, Wong WD
Ann Surg 2005 May;241(5):829-838.

OBJECTIVE: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. SUMMARY BACKGROUND DATA: Locally advanced (T3-4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. METHODS: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6cm from the anal verge (range 0-15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. RESULTS: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). CONCLUSIONS: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study.

Wide local excision or abdominoperineal resection as the initial treatment for anorectal melanoma?
Droesch JT, Flum DR, Mann GN
Am J Surg 2005 Apr;189(4):446-9.

BACKGROUND: Anorectal melanoma (AM) is a rare tumor with a poor prognosis. Treatment with abdominoperineal resection (APR) over wide local excision (WLE) is still debated. This study aimed to compare median survival of WLE and APR in patients with AM. METHODS: A systematic review of the literature was performed. Only series that allowed calculation of median survival were included. RESULTS: Fourteen studies met inclusion criteria. Average median survival of stage I WLE patients (N=34) and stage I APR patients (N=31) was 44 and 22 months, respectively (P=.001). For stage II patients, 7 underwent WLE, and 10 underwent APR with an average median survival of 36 and 14 months, respectively (P=.19). CONCLUSIONS: This study identified no stage-specific survival advantage to APR in favor of AM. Given that WLE is a more limited intervention associated with at least comparable survival, we propose that it be considered the initial treatment of choice for AM.

Comparison of one-stage resection and anastomosis of acute complete obstruction of left and right colon.
Hsu TC
Am J Surg 2005 Apr;189(4):384-7.

BACKGROUND: Although acute obstruction of the right colon is usually handled by primary anastomosis following resection, many surgeons are reluctant to offer one-stage resection and anastomosis to patients with obstructive lesions of the left colon. The aim of the study is to compare the immediate result of one-stage resection and anastomosis for patients with acute complete obstruction of the right colon versus left colon. METHODS: From January 1986 to December 2003, 214 cases of acute colonic obstruction were managed with one-stage resection and anastomosis by a single surgeon. Eighty patients were operated on for obstructive lesions of the right colon, 71 of them for carcinoma of the colon. Operative mortality was 10% (8/80); all except 2 patients died of respiratory failure. There were 2 cases (2.5%) of anastomotic leakage. One hundred thirty-four patients were operated on for obstructive lesions of the left colon, 127 of them for carcinomas of the colon and rectum. Operative mortality was 1.5% (2/134); both patients died of metastasis from the colorectal cancer following surgery. There were 3 cases (2.3%) of anastomotic leakage. CONCLUSION: This experience suggests that an anastomosis can be performed as safely in patients with acute obstruction of the left colon as in those with acute obstruction of the right colon. Mortality following resection and anastomosis is actually lower in left than right colonic obstruction. Neither intraoperative irrigation nor routine subtotal colectomy was found to be necessary in patients with acute colonic obstruction. Intraoperative decompression should be considered in left and also right colonic obstruction prior to the anastomosis following colonic resection.

A prospective study of outcomes of emergency and elective surgeries for complicated colonic cancer.
Biondo S, Marti-Rague J, Kreisler E, Pares D, Martin A, Navarro M, Pareja L, Jaurrieta E
Am J Surg 2005 Apr;189(4):377-83.

BACKGROUND: Although a significantly decreased long-term survival has been observed in patients undergoing surgery for complicated colorectal tumors compared with uncomplicated ones, the role of radical oncologic surgery on emergency colonic cancer is not defined clearly. The aim of this study was to analyze the efficacy of a curative emergency surgery in terms of tumor recurrence and cancer-related survival compared with elective colonic surgery. METHODS: Between January 1996 and December 1998, all patients with colonic cancer deemed to have undergone a curative resection were considered for inclusion in this prospective study. Patients were classified into 2 groups: group 1, after emergency surgery for complicated colonic cancer, and group 2, patients undergoing elective surgery. The main end points were cancer-related survival and the probability of being free from recurrence at 3 years. RESULTS: Of the 266 patients included in the study, 59 patients (22.2%) were in group 1 and 207 patients (77.8%) were in group 2. Postoperative mortality was higher in group 1 (P=.0004). After patients were stratified by the tumor node metastasis system, differences between the groups with respect to overall survival of stage II tumors (P=.0728), the probability of being free from recurrence (P=.0827), and cancer-related survival (P=.1071) of stage III cancers did not reach statistical significance. Differences were observed for the overall survival in stage III tumors (P=.0007), and for the probability of being free from recurrence (P=.0011) and cancer-related survival (P=.0029) in stage II cancers. When patients with elective stage II tumors presenting 1 or more negative prognostic factor were compared with emergency patients affected by a stage II colonic cancer, no differences were observed. CONCLUSION: Curative surgeries for complicated colonic cancer are acceptable in emergency conditions. Cancer-related survival and recurrence in patients with complicated colonic cancers may approach that of elective surgery if a surgical treatment with radical oncologic criteria is performed.

A novel approach to the treatment of ulcerative colitis: is it kosher?
Mayer L
Gastroenterology 2005 Apr;128(4):1117-9.

Ionizing radiation and rectal cancer: victims of our own success.
Grady WM, Russell K
Gastroenterology 2005 Apr;128(4):1114-7.

Colorectal cancer at a young age.
Terdiman JP
Gastroenterology 2005 Apr;128(4):1067-76.

Clostridium difficile toxin B activates the EGF receptor and the ERK/MAP kinase pathway in human colonocytes.
Na X, Zhao D, Koon HW, Kim H, Husmark J, Moyer MP, Pothoulakis C, LaMont JT
Gastroenterology 2005 Apr;128(4):1002-11.

BACKGROUND & AIMS: Clostridium difficile toxin B (TxB) mediates acute inflammatory diarrhea characterized by neutrophil infiltration and intestinal mucosal injury. In a xenograft animal model, TxB was shown to induce interleukin (IL)-8 gene expression in human colonic epithelium. However, the precise mechanisms of this TxB response are unknown. The aim of this study was to investigate the TxB-mediated proinflammatory pathway in colonocytes. METHODS: The effect of TxB on epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) 1/2 signaling pathway and IL-8 gene expression was assessed in nontransformed human colonic epithelial NCM460 cells. TxB regulation of EGFR-ERK1/2 signaling pathways was determined using immunoblot analysis, confocal microscopy, and enzyme-linked immunosorbent assay, whereas IL-8 gene expression was measured by luciferase promoter assay. RESULTS: TxB activates EGFR and ERK1/2 phosphorylation with subsequent release of IL-8 from human colonocytes. Pretreatment with either the EGFR tyrosine kinase inhibitor, AG1478, or an EGFR-neutralizing antibody blocked both TxB-induced EGFR and ERK activation. By using neutralizing antibodies against known ligands of EGFR, we found that the activation of EGFR and ERK1/2 phosphorylation was mediated by transforming growth factor-alpha (TGF-alpha). Inhibition of matrix metalloproteinase (MMP) decreased TGF-alpha secretion and TxB-induced EGFR and ERK activation. Inhibition of MMP, EGFR, and ERK activation significantly decreased TxB-induced IL-8 expression. CONCLUSIONS: TxB signals acute proinflammatory responses in colonocytes by transactivation of the EGFR and activation of the ERK/MAP kinase pathway.

Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis.
Matsuura M, Okazaki K, Nishio A, Nakase H, Tamaki H, Uchida K, Nishi T, Asada M, Kawasaki K, Fukui T, Yoshizawa H, Ohashi S, Inoue S, Kawanami C, Hiai H, Tabata Y, Chiba T

Gastroenterology 2005 Apr;128(4):975-86.
BACKGROUND & AIMS: Basic fibroblast growth factor (bFGF) is a promising therapeutic agent for various diseases. It remains unclear, however, whether bFGF is effective for the treatment of inflammatory bowel disease. The aim of this study was to examine the efficacy of bFGF on 2 experimental murine colitis models and to investigate its molecular mechanisms. METHODS: We evaluated the effects of human recombinant bFGF (hrbFGF) on mice with dextran sulfate sodium (DSS)-induced colitis and mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis as well as normal mice. Body weight, survival rate, and histologic findings of the colonic tissues were examined. Gene expression of tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2, transforming growth factor (TGF)-beta, mucin 2 (MUC2), intestinal trefoil factor (ITF), and vascular endothelial growth factor (VEGF) in the colonic tissues was determined. The proliferation activity of hrbFGF on the colonic epithelium was evaluated by immunohistochemistry. RESULTS: Rectal administration of hrbFGF ameliorated DSS-induced colitis in a dose-dependent manner. Gene expression of TNF-alpha was significantly reduced in the colonic tissues of mice with DSS-induced colitis treated with hrbFGF, whereas MUC2 and ITF messenger RNA expression was up-regulated. Rectal administration of hrbFGF significantly improved the survival rate of mice with TNBS-induced colitis and partially ameliorated colitis. hrbFGF significantly increased the number of Ki-67-positive cells in the colonic epithelium of normal mice, and up-regulated the gene expression of COX-2, TGF-beta, MUC2, ITF, and VEGF in the colonic tissues. CONCLUSIONS: Rectal administration of bFGF might be a promising option for the treatment of inflammatory bowel disease.

Ornidazole for prophylaxis of postoperative Crohn's disease recurrence: a randomized, double-blind, placebo-controlled trial.
Rutgeerts P, Van Assche G, Vermeire S, D'Haens G, Baert F, Noman M, Aerden I, De Hertogh G, Geboes K, Hiele M, D'Hoore A, Penninckx F

Gastroenterology 2005 Apr;128(4):856-61.
BACKGROUND & AIMS: Crohn's disease almost inevitably recurs after ileocolonic resection, and effective prophylactic therapy has not been identified. We investigated the efficacy and safety of ornidazole, a nitroimidazole antibiotic, for the prevention of clinical recurrence of Crohn's disease after curative ileocolonic resection in a placebo-controlled double-blind clinical trial. METHODS: Eighty patients were randomized to ornidazole 1 g/day or placebo started within 1 week of resection and continued for 1 year. The primary end point was the proportion of patients with clinical recurrence at 1 year. Secondary end points were endoscopic recurrence at 3 months and 12 months after resection. RESULTS: Two patients in the ornidazole group withdrew consent and were not dosed. Ornidazole significantly reduced the clinical recurrence rate at 1 year from 15 of 40 (37.5%) patients in the placebo group to 3 of 38 (7.9%) patients in the ornidazole group (Fisher exact test, 8.03; P = .0046; odds ratio, 0.14; 95% confidence interval, 0.037-0.546). Ornidazole reduced endoscopic recurrence at 12 months from 26 of 33 (79%) in the placebo group to 15 of 28 (53.6%) in the ornidazole group (chi2 , 4.37; P = .037; odds ratio, 0.31; 95% confidence interval, 0.10-0.94). Endoscopic recurrence at 3 and 12 months predicted clinical recurrence. Significantly more patients in the ornidazole group dropped out from the study because of side effects (P = .041). CONCLUSIONS: Ornidazole 1 g/day is effective for the prevention of recurrence of Crohn's disease after ileocolonic resection.

Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial.
Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV
Gastroenterology 2005 Apr;128(4):825-32.

BACKGROUND & AIMS: Ulcerative colitis is most common in Western industrialized countries. Inflammatory bowel disease is uncommon in developing countries where helminths are frequent. People with helminths have an altered immunological response to antigens. In animal models, helminths prevent or improve colitis by the induction of regulatory T cells and modulatory cytokines. This study determined the efficacy and safety of the helminth Trichuris suis in therapy of ulcerative colitis. METHODS: This was a randomized, double blind, placebo-controlled trial conducted at the University of Iowa and select private practices. Trichuris suis ova were obtained from the US Department of Agriculture. The trial included 54 patients with active colitis, defined by an Ulcerative Colitis Disease Activity Index of > or =4. Patients were recruited from physician participants and were randomly assigned to receive placebo or ova treatment. Patients received 2500 Trichuris suis ova or placebo orally at 2-week intervals for 12 weeks. RESULTS: The primary efficacy variable was improvement of the Disease Activity Index to > or =4. After 12 weeks of therapy, improvement according to the intent-to-treat principle occurred in 13 of 30 patients (43.3%) with ova treatment compared with 4 of 24 patients (16.7%) given placebo (P = .04). Improvement was also found with the Simple Index that was significant by week 6. The difference in the proportion of patients who achieved an Ulcerative Colitis Disease Activity Index of 0-1 was not significant. Treatment induced no side effects. CONCLUSIONS: Ova therapy seems safe and effective in patients with active colitis.

Increased risk of rectal cancer after prostate radiation: a population-based study.
Baxter NN, Tepper JE, Durham SB, Rothenberger DA, Virnig BA
Gastroenterology 2005 Apr;128(4):819-24.

BACKGROUND & AIMS: Radiation therapy for prostate cancer has been associated with an increased rate of pelvic malignancies, particularly bladder cancer. The association between radiation therapy and colorectal cancer has not been established. METHODS: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) registry data from 1973 through 1994. We focused on men with prostate cancer, but with no previous history of colorectal cancer, treated with either surgery or radiation who survived at least 5 years. We evaluated the effect of radiation on development of cancer for 3 sites: definitely irradiated sites (rectum), potentially irradiated sites (rectosigmoid, sigmoid, and cecum), and nonirradiated sites (the rest of the colon). Using a proportional hazards model, we evaluated the effect of radiation on development of colorectal cancer over time. RESULTS: A total of 30,552 men received radiation, and 55,263 underwent surgery only. Colorectal cancers developed in 1437 patients: 267 in irradiated sites, 686 in potentially irradiated sites, and 484 in nonirradiated sites. Radiation was independently associated with development of cancer over time in irradiated sites but not in the remainder of the colon. The adjusted hazards ratio for development of rectal cancer was 1.7 for the radiation group, compared with the surgery-only group (95% CI: 1.4-2.2). CONCLUSIONS: We noted a significant increase in development of rectal cancer after radiation for prostate cancer. Radiation had no effect on development of cancer in the remainder of the colon, indicating that the effect is specific to directly irradiated tissue.

Further insights into Crohn's disease.
Lang L
Gastroenterology 2005 Apr;128(4):815.

Impaired capsaicin and neurokinin-evoked colonic motility in inflammatory bowel disease.
Smith AS, Smid SD
J Gastroenterol Hepatol 2005 May;20(5):697-704.

Abstract Background: Inflammatory bowel disease (IBD) is associated with altered sensory and motor function in the human colon. The aim of the present study was to compare neuromuscular function in normal and IBD-affected colon in vitro, with emphasis on inhibitory enteric nerves, sensory neuropeptides and stimulation of axon collaterals. Methods: Strips of longitudinal and circular muscle were prepared following colectomy from six patients with intestinal carcinoma (mean age 64.2 +/- 4.8 years) and six patients with IBD (Crohn's disease, n = 3; ulcerative colitis, n = 3: mean age 35.8 +/- 5.7 years). Responses were measured to electrical field stimulation, potassium chloride, 1,1-dimethyl-4-phenylpiperazinium iodide, isoprenaline, calcitonin gene-related peptide (CGRP), capsaicin and neurokinin (NK)-1 and -2 receptor subtype-specific agonists, alone or after muscle precontraction. Results: The NK-1 and CGRP receptor-mediated relaxation was reduced in the circular (by 44%, P < 0.05) and longitudinal (by 61%, P < 0.05) muscle from IBD-affected colon, respectively. Maximal NK-2 receptor-mediated contraction was also significantly decreased in both longitudinal (71%, P < 0.001) and circular (51%, P < 0.01) muscle. Capsaicin evoked relaxation in precontracted colonic longitudinal and circular muscle; this was significantly diminished in the IBD-affected colon (by 63%, P < 0.001 and 76%, P < 0.01, respectively). Responses evoked by stimulation of enteric inhibitory nerves were not significantly altered. Conclusions: Colonic muscle strips from patients with IBD exhibited impaired CGRP and NK-1 receptor-mediated relaxation and NK-2 receptor-mediated contraction. Capsaicin-activated relaxation of colonic smooth muscle is deficient in IBD-affected colon. These results suggest a discrete effect of IBD on sensory-motor coupling and tachykinin-mediated effects on colonic motility.

ASCA in twins with inflammatory bowel disease.
Halfvarson J, Standaert-Vitse A, Jarnerot G, Sendid B, Jouault T, Bodin L, Duhamel A, Colombel JF, Tysk C, Poulain D
Gut 2005 Apr 29;.

BACKGROUND AND AIMS: An increased occurrence of ASCA (anti-Saccharomyces cerevisiae antibodies) is reported in unaffected members of families with Crohn's disease. Whether ASCA is a familial trait due to genetic factors or due to exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population. PATIENTS AND METHODS: ASCA were analyzed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD15/NOD2 genotype. RESULTS: ASCA were more common in Crohn's disease than in ulcerative colitis, 40/70 (57%) twins versus 5/43 (12%) twins. Associations with ileal Crohn's disease, stricturing/penetrating behavior and young age but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5%) healthy siblings in discordant monozygotic pairs with Crohn's disease, compared to 7/27 (26%) in discordant dizygotic pairs. Using the intra-class correlation coefficient (ICC), no agreement in ASCA titers was observed in discordant twin pairs with Crohn's disease, neither in monozygotic (ICC=-0.02) nor dizygotic pairs (ICC=-0.26). In contrast, a high agreement was seen within concordant monozygotic twin pairs with Crohn's disease (ICC=0.76). CONCLUSIONS: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn's disease. The agreement in ASCA titers within concordant monozygotic twin pairs with Crohn's disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that specific gene(s) other than CARD15/NOD2 determine the level of response and perhaps also specific phenotypic characteristics.

Birth size and colorectal cancer risk: a prospective population-based study.
Nilsen TI, Romundstad PR, Troisi R, Potischman N, Vatten LJ
Gut 2005 Apr 20;.

OBJECTIVE: To study whether birth size influences colorectal cancer risk in adulthood. DESIGN: A cohort of Norwegian men and women identified from midwives' birth records with long-term cancer follow-up through the Norwegian Cancer Registry. SETTING: St Olav's University Hospital in Trondheim, Norway. PARTICIPANTS: 16,016 women and 19,681 men born between 1920 and 1958 and alive in 1960. OUTCOME MEASURES: Incidence rate ratios (RRs) for colorectal cancer with 95% confidence intervals (CIs) and two-sided P values for trend across categories of birth dimensions. RESULTS: Men whose birth length was less than 51 cm had nearly two-fold higher risk of colorectal cancer (RR, 1.9, 95 % CI = 1.0 to 3.7) compared to men who were 53 cm or more, after adjustment for birth cohort, maternal age at childbearing, length of gestation, gestational hypertension or preeclampsia, birth order, maternal height, and indicators of maternal socio- economic status. The association displayed a linear trend across categories of birth length (P trend = .03). Among men, similar associations were found for birth weight and head circumference, but for women, there was no association between any of these birth dimensions and risk of colorectal cancer. CONCLUSION: The results suggest that among men, but not for women, being relatively short at birth is associated with increased risk of colorectal cancer in adulthood, indicating that intrauterine growth could be important for colorectal carcinogenesis.

Biologics in inflammatory disease: infliximab associated risk of lymphoma development.
Bucher C, Degen L, Dirnhofer S, Pless M, Herrmann R, Schraml P, Went P
Gut 2005 May;54(5):732-3.

Inflammatory bowel disease stimulates formation of carcinogenic N-nitroso compounds.
de Kok TM, Engels LG, Moonen EJ, Kleinjans JC
Gut 2005 May;54(5):731.

Coexistent chronic idiopathic intestinal pseudo obstruction and inflammatory bowel disease.
Ohlsson B, Fork FT, Veress B, Toth E
Gut 2005 May;54(5):729-30.

Probiotics in IBD: mucosal and systemic routes of administration may promote similar effects.
Foligne B, Grangette C, Pot B
Gut 2005 May;54(5):727-8.

Placenta growth factor expression is correlated with survival of patients with colorectal cancer.
Wei SC, Tsao PN, Yu SC, Shun CT, Tsai-Wu JJ, Wu CH, Su YN, Hsieh FJ, Wong JM
Gut 2005 May;54(5):666-72.

BACKGROUND: Overexpression of vascular endothelial growth factor (VEGF) correlates with vascularity, metastasis, and proliferation in colorectal cancer but the role of its homologue, placenta growth factor (PlGF), is unknown. The aim of this study was to evaluate expression and clinical implications of PlGF in colorectal cancer. METHODS: We investigated 74 tumour/non-tumour pairs of colorectal cryosections. Clinical staging was based on the UICC-TNM classification. Expression levels of mRNA for PlGF and VEGF were analysed with quantitative real time reverse transcription-polymerase chain reaction. Proteins were analysed by immunohistochemical staining and enzyme linked immunoabsorbant assay. Analysis of the differences in PlGF and VEGF levels between tumour and non-tumour tissues in the same patient were performed by paired t test; differences between localised and advanced disease patients by the Mann-Whitney, chi(2), and Fisher's exact tests and survival curves by the Kaplan-Meier method. RESULTS: Expression levels for both growth factors were significantly higher in tumour than in non-tumour tissues (p</=0.001). The ratio of PlGF expression in tumour to non-tumour in the advanced disease group was significantly higher than for the localised disease group (p = 0.009). Patients with more tumour PlGF mRNA had shorter survival (p = 0.028). The majority of PlGF was expressed in tumour cells. CONCLUSIONS: Our results suggest that PlGF expression correlates with disease progression and patient survival and may be used as a prognostic indicator for colorectal cancer.

Increased microvascular blood content is an early event in colon carcinogenesis.
Wali RK, Roy HK, Kim YL, Liu Y, Koetsier JL, Kunte DP, Goldberg MJ, Turzhitsky V, Backman V
Gut 2005 May;54(5):654-60.

BACKGROUND: Increased premalignant epithelial microvascular blood content is a common theme in neoplastic transformation; however, demonstration of this phenomenon in colon carcinogenesis has been stymied by methodological limitations. Our group has recently developed a novel optics technology, four dimensional elastic light scattering fingerprinting (4D-ELF), which allows examination of the colonic mucosal architecture with unprecedented accuracy. In this study, we utilised 4D-ELF to probe the preneoplastic colonic microvasculature. METHODS: Colonic mucosal blood content was assessed by 4D-ELF at serial preneoplastic time points from azoxymethane (AOM) treated Fisher 344 rats and age matched control animals. We also examined the pretumorigenic intestinal mucosa of the MIN mouse, and compared with wild-type mice. Finally, in a pilot study, we examined superficial blood content from the endoscopically normal mid transverse colon in 37 patients undergoing screening colonoscopy. RESULTS: In the AOM treated rat model, augmentation of superficial mucosal and total mucosal/superficial submucosal blood supply preceded the appearance of aberrant crypt foci (ACF) and temporally and spatially correlated with future ACF occurrence. These findings were replicated in MIN mice. The 4D-ELF based results were corroborated with immunoblot analysis for haemoglobin on mucosal scrapings from AOM treated rats. Moreover, 4D-ELF analysis of normal human colonic mucosa indicated that there was a threefold increase in superficial blood in patients who harboured advanced adenomas. CONCLUSION: We report, for the first time, that blood content is increased in the colonic microvasculature at the earliest stages of colon carcinogenesis. These findings may provide novel insights into early biological events in colorectal carcinogenesis and have potential applicability for screening.

Association between family history and mismatch repair in colorectal cancer.
Coggins RP, Cawkwell L, Bell SM, Crockford GP, Quirke P, Finan PJ, Bishop DT
Gut 2005 May;54(5):636-42.

BACKGROUND AND AIMS: Germline mutations in mismatch repair (MMR) genes cause a greatly increased risk of cancer of the gastrointestinal and female reproductive tracts (hereditary non-polyposis colorectal cancer (HNPCC)). Loss of MMR expression is common in colorectal cancer (CRC) overall. Such loss is assumed to be acquired predominantly, although a population of CRC cases will include individuals with unrecognised MMR mutations. This study examines the association between MMR gene expression and family history of cancer among the CRC population. METHODS: Individuals with CRC were identified from two well characterised populations: (1) consecutive hospital patients (n = 644) and (2) a population based cases series (n = 249). CRC was examined for expression of hMLH1 and hMSH2 using immunohistochemistry, and expression was related to family history using logistic regression. RESULTS: hMLH1 and hMSH2 expression was assessed in 732 CRCs with 8% showing loss of expression. No association was seen overall for hMLH1 or hMSH2 expression and family history of CRC. Loss of hMSH2 was predicted by family history of extracolonic cancer (odds ratio (OR) 5.78 (95% confidence interval (CI) 0.95-35.18)) and family history suggestive of HNPCC (OR 27.84 (95% CI 4.37-177.56)). Loss of hMLH1 was not predicted by family history of extracolonic cancer or a family history suggestive of HNPCC but was for a family history of at least two affected relatives (OR 4.88 (95% CI 1.25-19.03)). CONCLUSIONS: Individuals with hMSH2 deficient CRC in the general population exhibit a family history and other characteristics suggestive of HNPCC, and may carry germline MMR mutations. Loss of hMLH1 is only associated with a strong family history of extracolonic cancer at older ages, suggesting a novel mechanism of susceptibility.

Refractory enterovesical and duodenocolic fistulas in Crohn's disease successfully managed with tacrolimus.
Fukuda A, Nakase H, Seno H, Nabeshima M, Sawada M, Chiba T
J Gastroenterol 2005 Apr;40(4):433-5.

Osteopontin expression in ulcerative colitis is distinctly different from that in Crohn's disease and diverticulitis.
Masuda H, Takahashi Y, Asai S, Hemmi A, Takayama T
J Gastroenterol 2005 Apr;40(4):409-13.

BACKGROUND: The aim of the present work was to assess osteopontin (OPN) expression in the colon tissues of ulcerative colitis (UC), Crohn's disease (CD), and diverticulitis (Div) patients. METHODS: This study included three groups: the UC group, CD group, and Div group. Immunohistochemical staining was performed, using an immunoperoxidase method. RESULTS: Regarding OPN expression in intestinal epithelial cells, no difference was noted among the three groups. However, in the submucosa of the UC group, the ratio of two types of large cells (oval and spindle-shaped) expressing OPN was 61.2 +/- 14.4% (mean +/- SD), which was significantly higher than that in the CD group (14.9 +/- 7.0%; P < 0.05) and that in the Div group (11.2 +/- 6.1%; P < 0.05). In addition, in the UC group, the ratio of these cells in the subserosa (50.1 +/- 15.0%; mean +/- SD) was significantly higher than that in the CD group (16.9 +/- 6.2%; P < 0.05) and that in the Div group (12.6 +/- 5.7%; P < 0.05). In a serial section study, the oval-shaped cells were stained for anti-CD 68, while the spindle-shaped cells were stained for anti-vimentin. CONCLUSIONS: OPN in two types of large colon-infiltrating cells is possibly related to one of the pathogenic factors of UC.

Surgical management of perineal masses in patients with anorectal malformations.
Shaul DB, Monforte HL, Levitt MA, Hong AR, Pena A
J Pediatr Surg 2005 Jan;40(1):188-91.

BACKGROUND: The aim of this study was to review the outcome of surgical management of various types of perineal masses encountered in patients with anorectal malformations (ARM). METHODS: Retrospective review from 2 large pediatric anorectal referral centers. RESULTS: Twenty-two patients with a perineal mass were identified in more than 2000 patients treated for an ARM over a 15-year period. The 22 patients (4 men) represented all levels of severity of ARMs. The lesions were of 3 types: lipomas (n = 10), vascular anomalies (n = 4), and hamartomas/choristomas (n = 8). The lipomas were carefully removed from between the muscle fibers during the posterior sagittal anorectoplasty. The vascular anomalies (3 of 4 were hemangiomas) underwent magnetic resonance imaging preoperatively, but none were found to invade deeply and all were excised at the time of the posterior sagittal anorectoplasty. The hamartomas/choristomas all occurred in women, and 50% arose as a pedunculated mass from the vulva. The lesions contained tissues such as glia, osteoid, nephrogenic rests, and endocervical-type mucosa. One was initially misinterpreted as a teratoma, prompting a wider excision. This and all subsequent patients have been correctly diagnosed pathologically as having either hamartomas or choristomas, which were not widely excised. Follow-up ranges from 5 months to 12 years. Six of the 10 lipoma patients are continent. One vascular anomaly was re-excised and there was minor wound separation in another. None of the hamartoma/choristoma lesions recurred. CONCLUSION: The presence of unusual perineal masses can add to the complexity of ARMs; however, most of these lesions can be carefully excised with preservation of the muscle complex and ultimate continence. Hamartomatous lesions can be mistaken for teratomas but do not require aggressive excision with clear margins.

Progression of collagenous colitis to Crohn's disease.
O'beirne JP, Ireland A
Eur J Gastroenterol Hepatol 2005 May;17(5):573-575.

Collagenous colitis is a condition usually characterized by watery diarrhoea, macroscopically normal colonic mucosa and a typically thickened subepithelial collagen band on histological examination. It is rare in children, and coexistence with other inflammatory bowel diseases has been reported only rarely. We describe a case of diarrhoea presenting in infancy subsequently proved to be collagenous colitis that progressed to the typical features of Crohn's disease.

The changing distribution and survival of colorectal carcinoma: an epidemiological study in an area of northern Italy.
Sarli L, Michiara M, Sgargi P, Iusco D, De Lisi V, Leonardi F, Bella MA, Sgobba G, Roncoroni L
Eur J Gastroenterol Hepatol 2005 May;17(5):567-72.

OBJECTIVE: This study analyses the inter-relations of anatomical tumour location, gender, age and incidence rates for colorectal cancer from 1978 to 1999 in an area of northern Italy: the Parma district. METHODS: Data were obtained from the Parma Cancer Registry. Age-adjusted incidence rates were analysed by gender, age and colorectal cancer subsites. In addition, 5 year observed survival rates were determined. RESULTS: In the Parma area, the incidence of colorectal cancer is rising. We have observed a true increase in the rate of the age standardized incidence of right colon cancer, linked to an increased incidence of left colon cancer, while the incidence of rectal cancer has remained constant. The frequency of right-sided colon cancer was higher in aged patients, and in women. Age-standardized relative survival of patients after diagnosis of colorectal cancer between 1992 and 1996 was found to be significantly higher than age-standardized relative survival after diagnosis between 1978 and 1982. CONCLUSIONS: In the Parma area there has been an increased incidence of right colon cancer, linked to an increased incidence of left colon cancer, while the incidence of rectal cancer has remained constant. We feel that this shift, whatever the reason for it, has important implications for the choice of screening techniques.

Continent Ileostomy: Current Experience.
Castillo E, Thomassie LM, Whitlow CB, Margolin DA, Malcolm J, Beck DE
Dis Colon Rectum 2005 Mar 31;.

PURPOSE: This study was designed to review our recent experience with continent ileostomies and evaluate patient outcomes. METHODS: Retrospective chart reviews and phone interviews of patients who underwent a continent ileostomy operation from 1993 to 2003 at the Ochsner Clinic Foundation were performed. RESULTS: Twenty-four patients (19 females; age range, 22-73 years) had construction of continent ileostomies (modified Kock pouch). There were no intraoperative mortalities or stoma-related deaths. The mean operating room time for primary construction was 3.9 +/- 0.57 hours with a mean length of stay of 7 +/- 2 days. The average follow-up period was 66 (range, 6-134) months. The most common underlying indication for the construction of a continent ileostomy was ulcerative colitis (71 percent). Thirteen patients had a continent ileostomy created for conversion of a Brooke ileostomy and seven for a failed ileoanal pouch. Other indications included colonic inertia and incontinence in three patients and one patient who had failed multiple operations for Hirschsprung's disease. A total of 28 revisions were performed in 14 patients (58 percent). Six patients required multiple procedures. Operative revisions included 12 skin level revision for stenosis, 11 operations for valve repairs, and 1 each for peristomal hernia repair, stomal relocation, and pouch repair for fistulas. Two patients had their pouches removed (Crohn's disease and inability to manage pouch). The need for revision by 12 months was 29 percent, and the average time period before the first revision was 24 months (range, 4 days to 109 months). The overall failure rate (converted to conventional ileostomy) was only 8.3 percent. Ninety percent of the patients have continent pouches and are satisfied with their pouch function. CONCLUSIONS: Continent ileostomies continue to have a high rate of reoperations, reasonable functional results, and are a viable option for failed ileal pouch-anal pouch patients. Surgeons electing to perform continent ileostomies must carefully select their patients and advise them of the high potential for reoperations. Despite a high reoperation rate, patients are pleased with their continent ileostomies.

The Role of Arachidonic Acid Regulatory Enzymes in Colorectal Disease.
Abir F, Alva S, Kaminski DL, Longo WE
Dis Colon Rectum 2005 Apr 14;.

PURPOSE: Nonsteroidal anti-inflammatory drugs have a wide ranging effect on diseases of the colon and rectum. Interestingly, nonsteroidal anti-inflammatory drugs seem to play a beneficial role in colorectal cancer chemoprevention and adenoma regression, but may have a deleterious effect in inflammatory bowel disease. Prostaglandin inhibition is central to both the beneficial and toxic effects of this class of drugs. Arachidonic acid metabolism is essential to prostaglandin synthesis. METHODS: A Medline search using "nonsteroidal anti-inflammatory drugs," "colon cancer," "inflammatory bowel disease," "colitis," "COX inhibitors," "arachidonic acid," and "chemoprevention" as key words was performed for English-language articles. Further references were obtained through cross-referencing the bibliography cited in each work. RESULTS: Based on numerous studies, nonsteroidal anti-inflammatory drugs have a beneficial role in colon cancer and colonic adenomas. However, they have been reported to have a deleterious effect on the colon in inflammatory bowel disease and have been shown to cause colitis. Nonsteroidal anti-inflammatory drugs work via multiple pathways, some well defined, and others unknown. CONCLUSIONS: In the new millennium, nonsteroidal anti-inflammatory drugs may be used for chemoprevention of colorectal and other cancers. In addition, they may be used in combination with surgery and chemotherapy to primarily treat colorectal carcinoma. Undoubtedly, the use of novel cyclooxygenase inhibitors with less of a toxicity profile will allow more widespread use of nonsteroidal anti-inflammatory drugs for a variety of diseases. The future of this class of drugs is promising.

Long-Term Function After Restorative Proctocolectomy.
Wheeler JM, Banerjee A, Ahuja N, Jewell DP, Mortensen NJ
Dis Colon Rectum 2005 Mar 28;.

PURPOSE: Early functional outcome after restorative proctocolectomy and formation of an ileoanal pouch is known to be good, but there are minimal data on the long-term function of the pouch. The aim of this study was to look at the long-term functional outcome in patients who had undergone restorative proctocolectomy and formation of an ileoanal pouch. METHODS: A total of 151 consecutive patients (96 males, 55 females) who underwent ileoanal pouch surgery between April 1983 and May 1993 were identified. Functional outcomes from the previous 12 months were appraised by a standardized questionnaire. RESULTS: The median age at surgery was 31 years (range, 6-63 years), with a median follow-up of 142 months (range, 100-221 months). Eighteen patients have had their pouches excised, with another patient being defunctioned. Therefore 19 patients (13 percent) had suffered pouch failure. Altogether, 115 patients were available for follow-up, and 98 patients (85 percent) returned questionnaires. The median pouch-emptying frequency was five times (range, 1-17) during the day and one time (range, 0-6) at night. A total of 74 percent of patients had perfect continence during the day. Most of the patients had no life-style restrictions related to the pouch, and 98 percent of patients would recommend a pouch to others. CONCLUSIONS: Long-term functional outcome after ileoanal pouch surgery is good in most patients. For patients requiring proctocolectomy, ileoanal pouch surgery can now be recommended as an excellent long-term option.

Infrared Coagulatortrade mark: A Useful Tool for Treating Anal Squamous Intraepithelial Lesions.
Goldstone SE, Kawalek AZ, Huyett JW
Dis Colon Rectum 2005 Mar 28;.

PURPOSE: The incidence of invasive anal squamous carcinoma in men who have sex with men is rising, particularly in those with human immunodeficiency virus. As in the cervix the high-grade squamous intraepithelial lesion is thought to be an invasive squamous cell carcinoma precursor. Cervical high-grade squamous intraepithelial lesions are treated by removing the squamocolumnar transition zone. This is not possible in the anus, where treatment is often surgical and is accompanied by significant pain and morbidity. Better office-based techniques to treat anal high-grade squamous intraepithelial lesions are needed. We employed the infrared coagulatortrade mark in an office setting to ablate high-grade squamous intraepithelial lesions. METHODS: A retrospective review of medical records was performed on 68 human immunodeficiency virus-positive men who have sex with men who underwent infrared coagulatortrade mark ablation of biopsy-proven high-grade dysplasia from the time we began using the procedure in 1999. All patients have had at least six months of follow-up. Procedures were performed with local anesthesia on patients with discrete high-grade squamous intraepithelial lesions. Follow-up consisted of anal cytology with high-resolution anoscopy and biopsy of suspicious areas every three to six months. New or recurrent high-grade dysplasia was retreated. Patients with circumferential or bulky disease were treated in the operating room and were excluded from the study. RESULTS: Altogether, 68 patients met the enrollment criteria. The median patient age was 41 years (range 29-62 years). A total of 165 lesions were treated (mean 1.6 lesions, range 1-5) and only 46 (28 percent) persisted. However, 44 patients (65 percent) developed a new or persistent high-grade squamous intraepithelial lesion within a median time of 217 days (range 27-566 days) after infrared coagulation. The remaining 24 patients (35 percent) were free of high-grade dysplasia for a median of 413 days (range 162-1313 days) after infrared coagulation. When patients were treated a second or third time, the incidence of new or persistent high-grade dysplasia dropped to 58 percent and 40 percent, respectively. The probability of curing a retreated lesion was 72 percent. Using generalized estimating equations, the incidence of high-grade dysplasia decreased with repeated infrared coagulatortrade mark treatments. No patient developed squamous-cell carcinoma, had a serious adverse event, or developed anal stenosis. CONCLUSIONS: The infrared coagulatortrade mark is a safe, office-based modality for treating anal high-grade squamous intraepithelial lesion in human immunodeficiency virus-positive men who have sex with men. Successive treatments led to decreased recurrence rates.

Endorectal Ultrasound in the Management of Patients With Malignant Rectal Polyps.
Garcia-Aguilar J, Hernandez de Anda E, Rothenberger DA, Finne CO, Madoff RD
Dis Colon Rectum 2005 Mar 28;.

PURPOSE: This study was designed to determine the efficacy of endorectal ultrasound in the management of patients with malignant rectal polyps removed by snare excision during colonoscopy. METHODS: A retrospective review of the medical records and endorectal ultrasound images of 63 patients with endoscopically removed rectal polyps containing invasive adenocarcinoma subsequently staged by endorectal ultrasound. Patients underwent surgery or were followed at a single institution. The polyp characteristics and ultrasound images were compared with the presence of residual tumor in the surgical specimen in patients who underwent further surgery or with recurrence in patients who did not. RESULTS: The morphology of the polyps was described in 31 patients (49 percent); they were sessile in 26 (41 percent) and pedunculated in 6 (9 percent). The margins were positive in 22 patients (35 percent), negative in 19 (30 percent), and not specified in 22 (35 percent). Most tumors were well or moderately differentiated; only 3 (5 percent) were poorly differentiated. Thirty-three patients underwent further surgery (3 low anterior resection, and 30 transanal excision); 30 had no further surgery. The accuracy of endorectal ultrasound in assessing the presence of residual cancer in the rectal wall in patients who had surgery was 54 percent, with a 39 percent positive predictive value and 65 percent negative predictive value. Endorectal ultrasound accurately identified metastatic lymph nodes in two of three patients who had radical surgery. Endorectal ultrasound was more useful than polyp morphologic or histologic criteria to determine the presence of residual cancer in the rectal wall. CONCLUSIONS: Endorectal ultrasound does not definitely exclude the possibility of residual tumor in the rectal wall or mesenteric nodes of patients who had a malignant polyp snared endoscopically. Consequently, decisions regarding the definitive management of these patients cannot be based exclusively on the endorectal ultrasound images of the polypectomy site.

Endoscopic Transanal Rectal Mucosal Ablation in the Surgical Treatment of Ulcerative Colitis: Preliminary Results of a Novel Technique.
Forshaw MJ, Buchanan GN, Murali K, Stewart M
Dis Colon Rectum 2005 Apr 14;.

PURPOSE: We describe a new technique that endoscopically eradicates rectal stump mucosa after total colectomy for ulcerative colitis. METHODS: Seven patients (5 males; median age, 56 (range, 36-72) years) underwent attempted endoscopic transanal rectal mucosal ablation using the 28-French-gauge urologic resectoscope, either at the time of total colectomy and ileostomy for failed medical therapy (5 patients) or as an alternative to completion proctectomy (2 patients) with rectal stump discharge. All had declined restorative proctocolectomy. Clinical, endoscopic, and histologic follow-up was undertaken during a mean of 15 (range, 3-28) months. RESULTS: The operative technique evolved during these cases; mucosal ablation was successfully performed leaving a denuded muscular rectal tube in situ in six patients. Mean operative time was 45 minutes. Postoperative endoscopic surveillance has not demonstrated any viable rectal mucosa in these six patients, with only granulation tissue detected histologically. Narrowing of the rectal tube has occurred in two patients. Although all patients report insignificant rectal discharge, urinary and sexual function have remained unchanged. CONCLUSIONS: Diathermy ablation of the rectal mucosa via endoscopic transanal rectal mucosal ablation avoids the complications of pelvic dissection and might offer an effective alternative to proctectomy for ulcerative colitis.

Joseph M. Matthews Oration. Globalization comes to colon and rectal surgery.
Goldberg SM
Dis Colon Rectum 2005 Mar;48(3):424-8.

Practice parameters for the management of rectal cancer (revised).
Tjandra JJ, Kilkenny JW, Buie WD, Hyman N, Simmang C, Anthony T, Orsay C, Church J, Otchy D, Cohen J, Place R, Denstman F, Rakinic J, Moore R, Whiteford M

Dis Colon Rectum 2005 Mar;48(3):411-23.
The American Society of Colon and Rectal Surgeons is dedicated to assuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Standards Committee is composed of Society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This Committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus. This is accompanied by developing Clinical Practice Guidelines based on the best available evidence. These guidelines are inclusive, and not prescriptive. Their purpose is to provide information on which decisions can be made, rather than dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.

Failure of Conservative Management After the Passage of a Distal Colonic "Cast": Report of a Case.
Foley CL, Taylor CJ, Aslam M, Reddy KP, Birch HA, Owen ER
Dis Colon Rectum 2005 Mar 28;.

PURPOSE: The spontaneous passage per rectum of a full-thickness colon "cast" is a rare consequence of acute colonic ischemia. Previous cases have undergone surgery soon afterward because of intractable symptoms. We report a patient who was managed conservatively for 11 months but ultimately required definitive surgery. METHODS: The clinical, radiographic, pathologic, and endoscopic findings were obtained from the case notes and compared with previously reported cases. RESULTS: A 67-year-old obese patient underwent a Hartmann's procedure for a perforated diverticular abscess, which was reversed six months later. On the first postoperative night after the reversal, she had a brief hypotensive episode, and three weeks later passed a 21-cm, full-thickness infarcted piece of colon. She did not develop peritonitis and for 11 months experienced only mild symptoms. Under colonoscopic surveillance, the granulation tissue conduit connecting the remaining viable bowel became increasingly stenosed proximally and difficult to dilate. After three rapidly consecutive episodes of large-bowel obstruction, she required a laparotomy to resect the stricture and restore bowel continuity. From a literature review, this is the eighth case of its kind and the first in which such prolonged conservative management has been possible. CONCLUSIONS: When symptoms permit, it is feasible to manage patients conservatively in the short-term after this unusual event to allow recovery from the initial insult and planning of future surgery. However, definitive treatment is surgical and colonoscopic management should not delay this once the patient is fit for surgery.

Inflammation-related erythrocyte aggregation in patients with inflammatory bowel disease.
Zilberman L, Rogowski O, Rozenblat M, Shapira I, Serov J, Halpern P, Dotan I, Arber N, Berliner S
Dig Dis Sci 2005 Apr;50(4):677-83.

Chronic inflammation is associated with increased erythrocyte adhesiveness/aggregation. This might have deleterious effects on the microcirculatory flow and tissue oxygenation. We aimed to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with inflammatory bowel disease (IBD). Fifty-two patients (24 women and 28 men) with ulcerative colitis (UC) at a mean age of 44.0+/-16.8 years and 96 patients (44 women and 52 men) with Crohn's disease (CD) at a mean age of 38.0+/-15.5 years, with various degrees of disease activity, were matched to normal controls. A simple slide test and image analysis were used to determine the degree of erythrocyte adhesiveness/aggregation. CD activity index (CDAI) was determined in patients with CD, while clinical colitis activity index was applied for patients with UC. A significant (P < 0.0005) increment in the degree of erythrocyte adhesiveness/aggregation was noted in both groups of IBD patients compared with matched control groups. This increment was evident even in individuals with a low index of disease activity and during remission. The highly significant correlation with the concentrations of fibrinogen suggests that the degree of erythrocyte adhesiveness/aggregation is an inflammation-related phenomenon. An enhanced state of erythrocyte adhesiveness/aggregation was noted in the peripheral blood of patients with IBD. This might have a deleterious effect on intestinal microcirculatory flow and tissue oxygenation.

Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer.
Ueno M, Oya M, Azekura K, Yamaguchi T, Muto T
Br J Surg 2005 Apr 18;.

BACKGROUND: Lateral lymph node metastases occur in some patients with low rectal cancer and may cause local recurrence after total mesorectal excision. The aims of this study were to identify risk factors for lateral node metastases in patients with pathological tumour (pT) stage 3 or pT4 low rectal adenocarcinoma, and to evaluate the prognostic significance of lateral node metastases. METHODS: A retrospective analysis was performed of the outcome of 237 patients with pT3 or pT4 low rectal adenocarcinoma who underwent R0 resection with systematic lateral node dissection. RESULTS: Lateral lymph node metastases were found in 41 patients (17.3 per cent). Increased risk of lateral lymph node metastases was associated with a distal tumour margin close to the anal margin, histological type other than well or moderately differentiated adenocarcinoma, and the presence of mesenteric lymph node metastases. Patients with lateral node metastases had a significantly shorter postoperative survival (5-year survival rate 42 versus 71.6 per cent; P < 0.001) and an increased risk of local recurrence (44 versus 11.7 per cent; P < 0.001) compared with those without lateral node metastases. CONCLUSION: Tumour site, histological type and the presence of mesenteric lymph node metastasis are factors predicting the risk of lateral node metastasis. The poor prognosis of patients with lateral lymph node metastases after systematic lateral dissection suggests the need for adjuvant therapy. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Insulin-like growth factor binding protein 3 in inflammatory bowel disease.
Kirman I, Whelan RL, Jain S, Nielsen SE, Seidelin JB, Nielsen OH
Dig Dis Sci 2005 Apr;50(4):780-4.

Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed as values of total protein, which is a sum of bioactive intact 43- to 45-kDa protein and its inactive proteolytic cleavage fragments. We aimed to assess the levels of intact IGFBP-3 and its cleaving protease MMP-9 in IBD. Patients with IBD and controls were included. Total plasma IGFBP-3 concentration was measured in ELISA. Western blot analysis, which distinguishes between intact and cleaved IGFBP-3, was performed in order to determine the ratio of intact to total protein; this ratio was used to calculate the concentration of intact IGFBP-3. The profile of plasma proteases was evaluated in zymography and MMP-9 levels were determined in ELISA. The concentration of intact IGFBP-3 was significantly decreased in patients with moderate to severe IBD activity compared to those in remission or controls. Of note, a dramatic depletion of intact IGFBP-3 was found in 7.4% of patients with IBD. Zymography revealed that the dominant gelatinase was the pro-form of MMP-9. However, no differences in MMP-9 levels were noted between those with active disease and controls. The level of intact IGFBP-3 is decreased in IBD patients with moderate to severe disease activity. This decrease may be linked to altered IGFBP-3 production or to increased cleavage by proteases other than MMP-9.

Discrete-choice experiment to measure patient preferences for the surgical management of colorectal cancer.
Salkeld G, Solomon M, Butow P, Short L
Br J Surg 2005 Apr 18;.

BACKGROUND: Establishing trust between a patient and his or her surgeon is of paramount importance. The aim of this study was to assess the relative importance of the 'attributes of trust' between surgeon and patient with colorectal cancer. METHODS: A discrete-choice questionnaire was conducted with 60 men and 43 women who had completed primary treatment for colorectal cancer in two teaching hospitals in Sydney, Australia. RESULTS: Forty-seven of the 103 patients based their choice of surgical management on a single attribute and the remainder were willing to trade between different attributes. In order of importance, patients based their choice of surgical management on specialty training (beta coefficient = 0.83), surgeon's communication (beta = 0.82), type of hospital (beta = 0.72) and who decides treatment (beta = 0.01). Patients who were vigilant in their decision-making style and those who did not have tertiary education were more likely to change their preferences in the repeat interview. CONCLUSION: Clinicians may have a better chance of meeting a patient's expectations about the process of care if they assess the patient's desire for knowledge and give those who do not have tertiary education more time to assimilate information about their treatment. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Myocutaneous flaps promote perineal healing in inflammatory bowel disease.
Collie MH, Potter MA, Bartolo DC
Br J Surg 2005 Apr 18;.
No Abstract.

Salvage reoperation for complications after ileal pouch-anal anastomosis.
Dehni N, Remacle G, Dozois RR, Banchini F, Tiret E, Parc R
Br J Surg 2005 Apr 26;.

BACKGROUND: Surgical revision may be possible in patients with a poor outcome following ileal pouch-anal anastomosis (IPAA), using either a transanal approach or a combined abdominoperineal approach with pouch revision and reanastomosis. METHODS: Sixty-four patients underwent revisional surgery. The indication for salvage was sepsis in 47 patients, mechanical dysfunction in ten, isolated complications of the residual glandular epithelial cuff in three and previous intraoperative difficulties in four patients. RESULTS: A transanal approach was used in 19 patients and a combined abdominoperineal procedure in 45. Six of the latter had pouch enlargement and 25 received a new pouch. During a mean(s.d.) follow-up of 30(25) months, three patients required pouch excision because of Crohn's disease. Two patients had poor continence after abdominoperineal surgery. At last follow-up 60 (94 per cent) of 64 patients had a functional pouch. Half of the patients experienced some degree of daytime and night-time incontinence, but it was frequent in only 15 per cent. Of 58 patients analysed, 27 of 40 who had an abdominoperineal procedure and 13 of 18 who had transanal surgery rated their satisfaction with the outcome as good to excellent. CONCLUSION: Surgical revision after failure of IPAA was possible in most patients, yielding an acceptable level of bowel function in two-thirds of patients. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Laparoscopic surgery for colorectal cancer.
Motson RW
Br J Surg 2005 May;92(5):519-520.
No Abstract.

Adenomas in Young Patients: What is the Optimal Evaluation?
Stoffel EM, Syngal S
Am J Gastroenterol 2005 May;100(5):1150-3.

Colorectal adenomas are a known risk factor for colorectal cancer. The prevalence of colorectal adenomas among individuals under age 40 and the clinical implications of finding a single adenoma in a young individual have not been defined. Until the most recent revision of the Bethesda Guidelines, having one or more adenomas diagnosed at age <40 was an indication for evaluation for hereditary nonpolyposis colorectal cancer (HNPCC). In an effort to explore the association of young-onset adenomas with HNPCC, Velayos et al. tested adenomas from 34 subjects aged 18-39 for pathologic features of HNPCC. Finding that none of the young-onset adenomas demonstrated features of microsatellite instability (MSI) or loss of mismatch repair protein expression by immunohistochemistry (IHC), the authors conclude that the yield of such testing is low, and support the decision to exclude young-onset adenomas from the Revised Bethesda Guidelines for HNPCC. However, this study also revealed that MSI and IHC failed to detect abnormalities in half of the adenomas from control subjects with identified MLH1 and MSH2 mutations. These findings highlight the limitations of current molecular techniques for examining adenomas as an initial screen for HNPCC and the need for further studies evaluating the optimal genetic and clinical evaluation of patients with young-onset adenomas. (Am J Gastroenterol 2005;100:1150-1153).

The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease.
Cantor MJ, Nickerson P, Bernstein CN
Am J Gastroenterol 2005 May;100(5):1134-42.

BACKGROUND AND AIMS: Emerging data indicate that alterations in cytokine synthesis may play a role in inflammatory bowel disease (IBD) pathogenesis. The differential production of cytokines has been linked to single nucleotide polymorphisms in gene promoter regions, signal sequences, and gene introns. The aim of this study was to assess the relationship between polymorphisms involving five cytokine genes (TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma), and IBD susceptibility and disease phenotype. METHODS: Cytokine genotyping was performed utilizing polymerase chain reaction. The specific gene polymorphisms that were probed for included: -1082(G/A), -819(T/C), and -592(A/C) in the IL-10 promoter, -308(G/A) in the TNF-alpha promoter, codon 10 (T/C), and codon 25 (G/C) of the TGF-beta signal sequence, +874(T/A) of intron 1 of IFN-gamma, and -174(C/G) in the IL-6 promoter. RESULTS: A total of 193 IBD patients (138 Crohn's disease (CD) and 55 ulcerative colitis (UC)) and 92 controls were evaluated. No association between IBD, UC, or CD susceptibility and the cytokine gene polymorphisms were found. Patients with ileocolonic CD were more likely to possess the IL-6 -174 GG genotype compared to those with nonileocolonic disease (p= 0.006). Patients with ileal CD were more likely to possess the IL-6 -174 GC genotype compared to those with nonileal disease (p= 0.0004). An increased number of CD patients with isolated colonic disease possessed the IL-6 -174 CC genotype compared to those with nonisolated colonic disease (p= 0.032). CONCLUSION: The cytokine gene polymorphisms studied here do not appear to influence IBD susceptibility. There does, however, appear to be an influence on disease phenotype, particularly on CD site. (Am J Gastroenterol 2005;100:1134-1142).

Tumor necrosis factor receptor gene polymorphisms in Crohn's disease: association with clinical phenotypes.
Waschke KA, Villani AC, Vermeire S, Dufresne L, Chen TC, Bitton A, Cohen A, Thomson AB, Wild GE
Am J Gastroenterol 2005 May;100(5):1126-33.

OBJECTIVES: Crohn's disease (CD) is a chronic multifactorial disorder with diverse clinical features that are influenced by a heterogeneous set of genetic factors. TNF-alpha/TNF receptor interactions play a pivotal role in the pathogenesis of the inflammatory response. Our purpose was to determine whether single nucleotide polymorphisms (SNPs) in the TNF receptors confer susceptibility to Crohn's disease and whether they are associated with clinical phenotype. METHODS: A cohort of 205 consecutively identified and unrelated patients with CD and 106 controls were recruited. Subjects were genotyped for polymorphisms in TNFRSF1A (position +36, -609), TNFRSF1B (+196, +1466), along with the three common CARD15 variants and phenotyped for disease behavior. Genotypic and allelic frequencies were compared between CD and controls and a logistic regression model was constructed to determine independent associations with specific clinical phenotypes. RESULTS: Only the TNFRSF1A +36 and TNFRSF1B +196 SNPs were associated with CD (p= 0.0019 and 0.034, respectively). The TNFRSF1A +36 mutation was negatively associated with stricturing disease phenotype (OR = 0.384; CI = 0.166-0.887). In contrast, the TNFRSF1B +196 was negatively associated with colitis (OR = 0.410; CI = 0.191-0.880). These associations were independent of CARD15 mutation status. Finally, TNFRSF1B +196 was negatively associated with surgery in CARD15 negative patients. CONCLUSIONS: These data constitute the first report of an association of TNFRSF1A and TNFRSF1B polymorphisms with CD in a Caucasian population and address the role of TNFR mutations in determining clinical heterogeneity in CD. (Am J Gastroenterol 2005;100:1126-1133).

Comparison between Prospective and Retrospective Evaluation of Crohn's Disease Activity Index.
Frenz MB, Dunckley P, Camporota L, Jewell DP, Travis SP
Am J Gastroenterol 2005 May;100(5):1117-20.

The Crohn's disease activity index (CDAI) is the most widely used measure of clinical disease activity in patients entered into clinical trials. The prospective nature of the CDAI calculation precludes its use as a clinical assessment tool. We compared the retrospective evaluation of the CDAI with the prospective evaluation in a heterogenous patient population of 100 patients with Crohn's disease. The correlation between the two assessment methods was good with an r-value of 0.84 (p < 0,0001). There was a tendency of patients with a high retrospective CDAI to have a lower prospective CDAI which is explained by intention to treat. This study shows that a retrospective assisted evaluation of the CDAI is as accurate as the traditional prospective evaluation. (Am J Gastroenterol 2005;100:1117-1120).

Impact of Colloid Response on Survival After Preoperative Radiotherapy in Locally Advanced Rectal Carcinoma.
Rullier A, Laurent C, Vendrely V, Bail BL, Bioulac-Sage P, Rullier E
Am J Surg Pathol 2005 May;29(5):602-606.

Neoadjuvant therapy for rectal carcinoma modifies morphology and natural history of the tumor. Colloid response defined by predominant colloid changes with or without residual tumor cells is a form of tumor response whose impact on survival is unknown. This study evaluated influence of tumor histologic response, especially of colloid response, on survival in patients treated by long-course preoperative radiotherapy for rectal cancer. In 200 patients with uT3-T4 or N1 rectal carcinomas, influence of type of surgery, dose of radiotherapy, residual tumor size, surface tumor aspect, tumor response (downstaging vs. colloid or no response), tumor grade, vascular and neural invasion, circumferential margin, and postoperative chemotherapy on 5-year overall and disease-free survival were studied by univariate and multivariate analyses. A colloid response was observed in 20% of the cases. Tumor response, circumferential margin, and vascular invasion were independently associated with the disease-free survival. Patients with downstaging had a better disease-free survival than patients without response (80% vs. 54%), whereas those with colloid response had an intermediate survival (64%). After colloid response, the rate of recurrence was similar to patients with downstaging for local recurrence (0%-3%) and to those with no response for distant recurrence (28%). After preoperative radiotherapy for rectal cancer, survival and type of recurrence are influenced by the tumor response. The intermediate natural history of patients with colloid response suggests taking colloid response into account in postoperative tumor staging to optimize adjuvant therapy.

Probiotic Therapy in the Prevention of Pouchitis Onset: Decreased Interleukin-1beta, Interleukin-8, and Interferon-gamma Gene Expression.
Lammers KM, Vergopoulos A, Babel N, Gionchetti P, Rizzello F, Morselli C, Caramelli E, Fiorentino M, D'errico A, Volk HD, Campieri M
Inflamm Bowel Dis 2005 May;11(5):447-454.

BACKGROUND: Probiotic therapy has been shown to prevent the onset of pouchitis and to improve the quality of life in ulcerative colitis patients who required ileal pouch anal anastomosis. Pouchitis has been associated with elevated levels of proinflammatory cytokines and chemokines. METHODS: In this retrospective analysis of archived endoscopic samples from responding patients enrolled in the above-mentioned trial, we were interested in studying mucosal gene expression of the pleiotropic proinflammatory cytokines (interleukin-1beta, interleukin-6), TH1 cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-12), regulatory cytokines (interleukin-10, transforming growth factor-beta), and the chemokine interleukin-8. In addition to assessment of cytokine gene expression, the presence of polymorphonuclear cells in the mucosal tissue was evaluated. RESULTS: Data show that patients who were treated with probiotics had significant lower mucosal mRNA expression levels of interleukin-1beta, interleukin-8, and interferon-gamma compared with placebo-treated patients. CONCLUSIONS: In addition, a lower number of polymorphonuclear cells was present in the tissue of patients within the probiotic group compared with the number of polymorphonuclear cells in the tissue of patients receiving placebo and patients having an episode of pouchitis. CONCLUSIONS: These data suggest that probiotic treatment regulates the mucosal immune response by reducing mucosal levels of neutrophil-chemoattractant IL-8 and tissue influx of polymorphonuclear cells, and may further act by inhibition of T-cell activation, by reinforcement of barrier function and by a tight control of the potent pro-inflammatory cytokine IL-1beta.

Is it reasonable to add preoperative serum level of CEA and CA19-9 to staging for colorectal cancer?
Chen CC, Yang SH, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Chang SC
J Surg Res 2005 Apr;124(2):169-74.

BACKGROUND: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers for colorectal cancer. The aim of this study was to evaluate the possibility of adding them into the current staging system by analyzing their prognostic significance. MATERIALS AND METHODS: The study population was patients (n = 574, 67.1 +/- 11.3 years old, 397 males) who received potentially curative resection of colorectal adenocarcinoma (stage I-III) between January 1994 and August 2002, including preoperative measurements of CEA and CA19-9. Clinicopathological characteristics and associated follow-up data were retrospectively collected by reviewing available medical charts. CEA higher or equal to 5 ng/ml was defined as abnormal (CEA+). The CA19-9 level was set at 37 U/ml (CA19-9+). Patients were further divided into four groups (1, 2, 3, 4) according to the results of these two markers (CEA/CA19-9: -/-, -/+, +/-, and +/+). Survival was analyzed for AJCC staging, CEA (+) versus (-), CA19-9 (+) versus (-), and four groups. RESULTS: CEA and CA19-9 survival curves were not significantly different. However, the combined use of the two markers revealed a significant survival benefit (P = 0.035) of group 1 ("-" for both markers) over 4 ("+" for both) in stage II. CONCLUSIONS: Patients with an elevated level of both CEA and CA19-9 in stage II of colorectal cancer have a significantly poorer prognosis than those with normal levels of these markers. We recommend adding both CEA and CA19-9 to the current staging system.

Preoperative staging of rectal cancer by MRI; results of a UK survey.
Taylor A, Sheridan M, McGee S, Halligan S
Clin Radiol 2005 May;60(5):579-86.

AIM: To determine current day-to-day practice of and access to preoperative MRI for patients with rectal cancer in the UK, with the aim of identifying constraining factors. MATERIALS AND METHODS: A questionnaire asking for details of rectal cancer workload, multidisciplinary team (MDT) practice, preoperative MRI, the use of alternative imaging methods where appropriate, and an assessment of local access to MRI, was mailed to 283 UK departments of radiology. Replies were received from 142 departments (50.2% response rate). These were collated and response frequencies were determined. RESULTS: According to their replies, 135 (95%) of respondents always discussed rectal cancer cases within the context of an MDT, usually including a radiologist. Only 49% of respondents attempted to offer preoperative MRI to all rectal cancer patients, and 35% of respondents used MRI in less than 25% of cases. Of the 142 respondents, 73 (51%) felt their practice was currently constrained by lack of MR resources. The most frequently cited constraint was an available but over-subscribed MRI scanner. Limited radiology manpower was the next most frequently cited constraint. A significant minority stated that no MRI scanner was available. CONCLUSIONS: The MDT is a well established forum for the discussion of patients with rectal cancer, and a radiologist is usually involved. However, in the face of current guidelines, less than 50% of the units studied were able to offer preoperative MRI to all of their rectal cancer cases. Improved access to MRI and increased radiological manpower are necessary if current management guidelines are to be observed.

National audit of the sensitivity of double-contrast barium enema for colorectal carcinoma, using control charts.
Bartram C
Clin Radiol 2005 May;60(5):555-7.

Necrotizing Enterocolitis: Assessment of Bowel Viability with Color Doppler US.
Faingold R, Daneman A, Tomlinson G, Babyn PS, Manson DE, Mohanta A, Moore AM, Hellmann J, Smith C, Gerstle T, Kim JH
Radiology 2005 May;235(2):587-94.

PURPOSE: To determine whether absence of bowel wall perfusion at color Doppler ultrasonography (US) is indicative of bowel necrosis in neonates with necrotizing enterocolitis (NEC). MATERIALS AND METHODS: This study was approved by the research ethics board, and informed consent was obtained. Sixty-two neonates enrolled in the prospective study underwent US of the bowel wall. Neonates were divided into two groups. Group A included 30 control subjects with gestational ages (GAs) ranging from 24 to 41 weeks. Group B included 32 neonates with GAs ranging from 24 to 40 weeks who were clinically proved to have or suspected of having NEC. All neonates in group B underwent abdominal radiography. Normative values were calculated in group A. In group B, the sensitivities and specificities of color Doppler US and abdominal radiography for detection of bowel necrosis were computed by using the modified Bell staging criteria for NEC as the reference standard. RESULTS: Two neonates were excluded from group B; thus, a total of 60 neonates were included in the study. In group A, bowel wall thickness ranged from 1.1 to 2.6 mm. Bowel wall perfusion was detected with color Doppler US in all 30 neonates. Color Doppler signals ranged from one to nine dots per square centimeter. Twenty-two of 30 neonates in group B received a diagnosis of NEC. Mild to moderate NEC was diagnosed in 12 neonates. Color Doppler US depicted an isolated segment of bowel-absent blood flow in two neonates; this finding was confirmed with laparotomy. In 10 neonates with severe NEC, color Doppler US depicted isolated or multiple segments of bowel with absent perfusion. Pneumoperitoneum was present in only four neonates. The remaining eight neonates at risk for NEC had no evidence of loops without perfusion at color Doppler US. The sensitivity of free air at abdominal radiography as a positive sign for severe NEC with necrotic bowel was 40% compared with the 100% sensitivity of absence of flow at color Doppler US (P = .03). CONCLUSION: Color Doppler US is more accurate than abdominal radiography in depicting bowel necrosis in NEC. (c) RSNA, 2005.

Does a Second-look Operation Improve Survival in Patients with Peritonitis due to Acute Mesenteric Ischemia? A Five-year Retrospective Experience.
Kaminsky O, Yampolski I, Aranovich D, Gnessin E, Greif F
World J Surg 2005 Apr 14;.

Second-look laparotomy is one of the mainstays of surgical treatment of acute mesenteric ischemia (AMI). The aim of this study was to analyze its role in the survival of patients with infarcted gangrenous bowel resulting from AMI. A retrospective chart review of all patients admitted over the study period was undertaken. The study population consisted of 41 patients with clinical evidence of peritonitis and gangrenous, perforated bowel on surgical exploration. Outcome was compared among patients who underwent second-look laparotomy and those who did not. Fifteen patients with an American Society of Anesthesiologists (ASA) score of less than 4 underwent second-look laparotomy. Six patients had residual necrotic bowel that required additional resection. Only one (17%) of them survived. Of the nine remaining patients, who had no evidence of necrosis, only two survived (22%). Overall survival in this group was 20%. Twenty-six patients were managed without second-look laparotomy. Nine of them, with an ASA score of 4-5, died soon after the operation. The decision not to operate on the remaining 17 patients with an ASA score <4 was made by an experienced surgeon. Eleven of those patients (65%) survived. Overall survival in the non-second-look group was 42%. Excluding the early deaths, the survival in the non re-explored group was significantly higher than in the second-look group (65% vs. 20%, p = 0.011). A selective approach to the surgical treatment of acute mesenteric ischemia based on the sound clinical judgment of an experienced surgeon may be as appropriate as its universal application.

Delivery of radiofrequency energy to the gastroesophageal junction (Stretta procedure) for the treatment of gastroesophageal reflux disease.
Cipolletta L, Rotondano G, Dughera L, Repici A, Bianco MA, De Angelis C, Vingiani AM, Battaglia E
Surg Endosc 2005 May 3;.

BACKGROUND: Radiofrequency (RF) energy treatment is increasingly offered before invasive surgical procedures for selected patients with gastroesophageal reflux disease (GERD). METHODS: Thirty-two patients undergoing the Stretta procedure were prospectively evaluated with upper endoscopy, manometry, 24-hour pH testing, SF-36 surveys, and GERD-specific questionnaires (GERD HRQL). RESULTS: Significant clinical improvement was observed in 91% of patients (29/32). Mean heartburn and GERD HRQL scores decreased (p = 0.001 and p = 0.003, respectively), and physical SF-36 increased (p = 0.05). At a minimum follow-up of 12 months, median esophageal acid exposure decreased (p = 0.79) and was normalized in eight patients. Median lower esophageal sphincter (LES) pressure was unchanged. Esophagitis healed in six of eight patients, but two patients with nonerosive disease developed asymptomatic grade A esophagitis during follow-up. At 12 months, 56% of patients were off proton pump inhibits. Morbidity was minimal. CONCLUSIONS: RF delivery to LES is safe and significantly improves symptoms and quality of life in selected GERD patients.

Transanal endoscopic versus total mesorectal laparoscopic resections of T2-N0 low rectal cancers after neoadjuvant treatment: a prospective randomized trial with a 3-years minimum follow-up period.
Lezoche E, Guerrieri M, Paganini AM, D'Ambrosio G, Baldarelli M, Lezoche G, Feliciotti F, De Sanctis A
Surg Endosc 2005 May 4;.

BACKGROUND: This study aimed to compare the results and the oncologic outcomes of transanal endoscopic microsurgery (TEM) with neoadjuvant radiochemotherapy and laparoscopic resection (LR), also with neoadjuvant radiochemotherapy, in the treatment of T(2)-N(0) low rectal cancer. METHODS: The study enrolled 40 patients with T2-N(0) rectal cancer, randomizing 20 to TEM (arm A) and 20 to LR (arm B). RESULTS: After neoadjuvant radiochemotherapy, tumor downstaging was observed for 13 patients (65%) in arm A (7 pT0 and 6 pT1) and in 11 patients (55%) in arm B (7 pT0 and 4 pT1). More than a 50% reduction of the tumor diameter was observed in four arm A cases and in six arm B cases. At a median follow-up period of 56 months (range, 44-67 months) in both arms, one local failure (5%) occurred after 6 months in arm A and one (5%) after 48 months in arm B. Distant metastases occurred in one arm A patient (5%) after 26 months of follow-up evaluation and in one arm B patient (5%) at 31 months. The probability of local or distant failure was 10% for TEM and 12% for laparoscopic resection, whereas the probability of survival was 95% for TEM and 83% for laparoscopic resection. CONCLUSIONS: The findings show comparative results between the two study arms in terms of probability of failure and survival.

Laparoscopic resection for rectal cancer: Outcomes in 194 patients and review of the literature.
Barlehner E, Benhidjeb T, Anders S, Schicke B
Surg Endosc 2005 May 3;.3

BACKGROUND: There are few reports on laparoscopic rectum resection demonstrating its feasibility and efficacy in patients with rectal cancer. Most patient series are small, and results must be considered preliminary and medium-term. Our large prospective conducted study aimed to assess the effectiveness of a totally laparoscopic resection for rectum carcinoma with emphasis on perioperative and long-term oncological outcomes. METHODS: Between November 1992 and July 2003, 194 unselected patients were resected laparoscopically for rectal carcinoma. Patients with locally advanced rectum carcinoma (uT3/uT4) and no evidence of distant metastases were candidates for neoadjuvant chemoradiation. Adjuvant treatment was administered to patients with UICC stage II/III disease. All patients were followed up prospectively to evaluate complications and late outcomes. Survival probability analysis was performed using the Kaplan-Meier method. Study selection was made by Medline search using the following key words: rectal cancer, rectal neoplasms, laparoscopy, and resection. Single case reports and abstracts were excluded. When surgical series were reported more than once, only the most recent reports were considered and listed. RESULTS: The most common procedures were low anterior resection with total mesorectum excision in 65.5% of patients and high anterior resection in 25.3%. Average operative time was 174 min. Average number of lymph nodes removed was 25.4 and length of specimen resected was 27.6 cm. Resection was curative in 145 patients and palliative in 49 cases. UICC tumor stages were as follows: stage I: 25.2%, stage II: 27.3%, stage III: 30.4%, and stage IV: 17%. Intraoperative complications were <1% for lesions of the ureter, urinary bladder, and deferent duct. Conversion to conventional surgery was necessary in two cases (1%). The most common postoperative complication was anastomotic leakage in 13.5% of patients. There was no postoperative mortality. Follow-up evaluation ranged from 1 to 128 months with a mean of 46.1 months. The most common late complication was incisional hernia in 3.6% of patients. Port-site metastases occurred in one patient (0.5%). Tumor recurrence developed in 23 of the 145 curative resected patients (11.7% distant metastases and 4.1% local recurrence). Overall local recurrence rate was 6.7% (4.1% after curative resection and 14.3% after palliative resection). Overall survival rate was 90.6% at 1 year, 74.5% at 3 years, and 66.3% at 5 years. Overall 5-year survival rate was 76.9% after curative resection and 31.8% after palliative resection. Cancer-related survival rate was 94% at 1 year, 82.4% at 3 years, and 78.9% at 5 years. At 5 years it was 87.7% after curative resection and 48.5% after palliative resection. At 5 years, the survival rate was 100% for stage I, 94.4% for stage II, 66.6% for stage III, and 44.6% for stage IV. CONCLUSIONS: Our results and the literature review clearly demonstrate that laparoscopic resection for rectal cancer is not associated with higher morbidity and mortality. Established oncological and surgical principles are respected and long-term outcomes are at least as good as those after open surgery.

Hospitalization after open colectomy: expectations and practice in general surgery.
Nascimbeni R, Cadoni R, Fabio FD, Casella C, Salerni B
Surg Today 2005;35(5):371-6.

PURPOSE: There is increasing pressure to reduce the length of stay (LOS) in hospital after colectomy. To assess the impact of unintended variations on LOS, actual discharge management was compared with the expectations expressed by general surgeons. METHODS: We retrospectively examined 262 patients who underwent elective open colectomy. The effects of patient demographics, surgical variables, and functional recovery on postoperative LOS were assessed in univariate and multivariate models. We also used a structured questionnaire to assess the expectations of surgeons regarding criteria affecting patient discharge. RESULTS: The median LOS was 11 days, which was univariately correlated with morbidity, bowel movement, oral feeding, mobilization, surgeon, rectal procedures, comorbidity, type of analgesia, blood transfusion, and colorectal cancer. According to the multivariate analysis, morbidity (P < 0.001), colorectal cancer (P = 0.026), rectal procedure (P = 0.037), and analgesia (P = 0.04) were correlated with LOS. The surgeons we interviewed believed that discharge should be based on the return of bowel movement and the absence of morbidity. By discharging our patients on postoperative day 5 or 6, these criteria would have been respected in 84% and 88%, respectively. CONCLUSION: Prolonged hospitalization after colectomy persists when critical pathways are not observed and there is a lack of institutional pressure to reduce to the LOS. Many factors affect the delay in patient discharge, possibly reflecting unwanted variation rather than the surgeons' expectations.

Persistent diarrhea in the returning traveler: think beyond persistent infection.
Landzberg BR, Connor BA
Scand J Gastroenterol 2005 Jan;40(1):112-4.

The report describes a young female United Nations worker, stationed in East Timor for an extended duration, who presented with persistent travelers' diarrhea and who was convinced that she was harboring a persistent infestation. In fact, careful history, laboratory evaluation and endoscopy with duodenal biopsies found all the classical hallmarks of unmasked celiac sprue. The patient then had a dramatic response to a gluten-free diet, with complete resolution of symptoms. Persistent travelers' diarrhea is an entity which carries an interesting and extensive differential diagnosis beyond persistent enteric infections or infestations. Rather, many sufferers have long been cleared of the initial offending pathogen and are left with either a post-infectious disorder of absorption, digestion, motility or visceral sensation or carry a chronic gastrointestinal disorder which has been unmasked by an enteric infection, such as idiopathic inflammatory bowel disease, gastrointestinal malignancy or celiac sprue. Other key issues raised by the case include the vanishing incidence of tropical sprue, an entity to which most clinicians would have mistakenly attributed this malabsorptive syndrome arising in a traveler, and the under-recognition of the protean manifestations of celiac sprue, to which we would add persistent travelers' diarrhea.

Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-anal-anastomosis in ulcerative colitis.
Laake KO, Bjorneklett A, Aamodt G, Aabakken L, Jacobsen M, Bakka A, Vatn MH
Scand J Gastroenterol 2005 Jan;40(1):43-51.

OBJECTIVE: Pouchitis is a common and troublesome condition in patients operated on with ileal-pouch-anal-anastomosis (IPAA). A disturbed microecology in the pouch has been suggested as one possible explanation. In a previous double-blind, randomized, controlled study we demonstrated clinical improvement of symptoms in patients with ulcerative colitis (UC) operated on with IPAA, during intervention with live probiotic microbes Lactobacilli and Bifidobacteriae. The aim of the present study was to confirm our previous results in a much larger material, including clinical symptoms, faecal flora and endoscopic evaluation, and to compare the results in UC/IPAA patients with those of patients with familial adenomatous polyposis (FAP) with IPAA and UC patients with ileorectal anastomosis (IRA). MATERIAL AND METHODS: Five hundred millilitres of a fermented milk product (Cultura) containing live lactobacilli (La-5) and bifidobacteriae (Bb-12) was given daily for 4 weeks to 51 UC patients and 10 patients with FAP, operated on with IPAA, and six UC patients operated on for IRA. Stool samples were cultured for examination of lactobacilli, bifidobacteriae, fungi and pH before, during and after intervention. Before, during and after intervention, endoscopic evaluation was performed. Categorized symptomatology was examined prospectively using diary cards in addition to an interview, before and on the last day of intervention. RESULTS: The number of lactobacilli and bifidobacteriae increased significantly during intervention in the UC patients operated on with IPAA and remained significantly increased one week after intervention. Involuntary defecation, leakage, abdominal cramps and the need for napkins (category I), faecal number and consistency (category II) and mucus and urge to evacuate stools (category III) were significantly decreased during intervention in the UC/IPAA group. In the FAP group there was a significant decrease in faecal leakage, abdominal cramps and use of napkins (category I) during intervention. The median endoscopic score of inflammation was significantly decreased during intervention in the UC/IPAA patients. Blood tests, faecal fungi and faecal pH did not change significantly during intervention. CONCLUSIONS: Results of this extended study, showing an effect of probiotics on symptoms and endoscopic inflammation in UC patients operated on with IPAA confirm our previously reported effect of probiotics on clinical symptoms and endoscopic score in a smaller, double-blind, randomized, controlled study. The significantly higher response to probiotics in families with increased risk of IBD will have to be repeated in future studies.

Clostridium difficile--associated diarrhea.
Schroeder MS
Am Fam Physician 2005 Mar 1;71(5):921-8.

Clostridium difficile infection is responsible for approximately 3 million cases of diarrhea and colitis annually in the United States. The mortality rate is 1 to 2.5 percent. Early diagnosis and prompt aggressive treatment are critical in managing C. difficile-associated diarrhea. Major predisposing factors for symptomatic C. difficile colitis include antibiotic therapy; advanced age; multiple, severe underlying diseases; and a faulty immune response to C. difficile toxins. The most common confirmatory study is an enzyme immunoassay for C. difficile toxins A and B. The test is easy to perform, and results are available in two to four hours. Specificity of the assay is high (93 to 100 percent), but sensitivity ranges from 63 to 99 percent. In severe cases, flexible sigmoidoscopy can provide an immediate diagnosis. Treatment of C. difficile-associated diarrhea includes discontinuation of the precipitating antibiotic (if possible) and the administration of metronidazole or vancomycin. Preventive measures include the judicious use of antibiotics, thorough hand washing between patient contacts, use of precautions when handling an infected patient or items in the patient's immediate environment, proper disinfection of objects, education of staff members, and isolation of the patient.

An unusual cause of rectal bleeding and intestinal obstruction in a child with peripheral vascular malformations.
Aziz A, Kane TD, Meza MP, Vaughan KG, Hackam DJ
Pediatr Surg Int 2005 Apr 2;.

Vascular malformations of the small bowel are rare yet important causes of abdominal pain and rectal bleeding in children. This report describes a 6-year-old girl with a known history of musculoskeletal vascular anomalies who presented with recurrent abdominal pain and rectal bleeding after seemingly minor trauma. A diagnosis of enteric vascular malformation was established, and the patient was treated by a combined laparoscopic and open approach. This case highlights the fact that in the child with known vascular anomalies who presents with sudden gastrointestinal bleeding and intestinal obstruction, the diagnosis of gastrointestinal vascular anomaly should be suspected, and exploratory laparoscopy should be considered. The current management of enteric vascular anomalies is reviewed, and the differences between vascular malformations and hemangiomas are analyzed.

Laparoscopic-assisted approach in rectal cancer patients: lessons learned from >200 patients.
Delgado S, Momblan D, Salvador L, Bravo R, Castells A, Ibarzabal A, Pique JM, Lacy AM
Surg Endosc 2004 Oct;18(10):1457-62. Epub 2004 Aug 26.

BACKGROUND: The applicability of laparoscopic surgery in the treatment of colorectal diseases is still controversial. Early reports on laparoscopic-assisted colectomy in patients with colon cancer suggested that it minimizes surgical trauma, decreases perioperative complications, and leads to a more rapid recovery. To our knowledge, no previous studies have compared the laparoscopic vs the open approach in rectal cancer. The aim of this paper was to assess the results of laparoscopic techniques in patients with rectal cancer. METHODS: From March 1998 to February 2003, all patients admitted to our unit with adenocarcinoma of the rectum were evaluated for surgery by the laparoscopic approach. RESULTS: A total of 220 patients with a mean age of 67.3 years were included in the study. One hundred thirty patients (59%) were treated with neoadjuvant chemoradiotherapy. In >75% of the patients, a surgical procedure with sphincter preservation was performed. The rate of conversion to the open approach was 20%. Ten patients had intraoperative complications. Fifty-eight patients (26.3%) developed postoperative complications. The length of hospital stay was 6.8 days. The distribution of tumor stages was as follows: stage I, 16.81%; stage II, 33.6%; stage III, 26.36%; stage IV, 19.09%. The mean number of lymph nodes was 13.8. The incidence of local relapse was 5.3%, with a follow-up of 18 months. CONCLUSION: Laparoscopic surgery can be safely performed in patients with adenocarcinoma of the rectum with good short-term results. Randomized controlled trials are needed to confirm these results.

Adenocarcinoma within a paracoccygeal teratoma in an adult: report of a case.
Tulchinksy H, Tovar A, Gutman H
Surg Today 2005;35(3):259-62.

We report an unusual case of adenocarcinomatous transformation of a paracoccygeal teratoma (PCT) in a 44-year-old woman. The patient was referred to us for surgical treatment of a growing paracoccygeal mass. The findings of a magnetic resonance imaging scan were compatible with soft tissue malignancy. Using the posterior approach, we performed complete surgical removal with coccygectomy. Histological examination of the cystic mass revealed a mature teratoma containing primary adenocarcinoma. The patient has been followed up for 7 years and is free of disease. Because prognosis depends on complete excision, we emphasize the importance of clear-margin surgery, including en bloc removal of the coccyx.

Anal function during pregnancy and postpartum after ileal pouch anal anastomosis for ulcerative colitis.
Kitayama T, Funayama Y, Fukushima K, Shibata C, Takahashi K, Ogawa H, Ueno T, Hashimoto A, Sasaki I
Surg Today 2005;35(3):211-5.

PURPOSE: Total proctocolectomy and ileal pouch anal anastomosis (IPAA) is now a common procedure for ulcerative colitis (UC). Moreover, it has been reported that fertility is preserved in women who undergo this procedure, many of whom can experience normal delivery. METHODS: We assessed the perinatal outcomes and changes in anal function in four women, aged from 27 to 35 years, who gave birth after undergoing IPAA for UC. Pregnancies were confirmed 15-111 months after IPAA, three women had full-term pregnancies, and one gave birth after 31 weeks' gestation. RESULTS: Cephalic delivery with a vacuum extractor was used for one patient, and another underwent cesarean section. The other two patients experienced normal delivery. None of the patients needed artificial insemination and none had any symptoms of intestinal obstruction during their pregnancy. After delivery, two patients suffered a transient increase in bowel frequency and soiling, which gradually resolved. CONCLUSIONS: Although transient anal dysfunction occurred in the puerperal period, there were no changes in anal function during pregnancy. Therefore, there are no factors directly prohibiting pregnancy and vaginal delivery in women who undergo IPAA for UC.

Lack of association of the CD14 promoter polymorphism--159C/T with Caucasian inflammatory bowel disease.
Peters KE, O'Callaghan NJ, Cavanaugh JA
Scand J Gastroenterol 2005 Feb;40(2):194-7.

OBJECTIVE: The inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial diseases resulting from a complex interaction of genetic and environmental factors. The recently described CARD15 and TNF-alpha risk alleles are believed to be contributors to disease by disrupting inflammatory pathways via impaired response to bacteria. Other bacterial receptors, such as CD14, may also have a role in disease. A promoter polymorphism (-159C/T) in CD14 has been implicated in IBD in a number of studies. MATERIAL AND METHODS: We have analysed this CD14 promoter polymorphism in probands from 206 multiplex IBD families, 110 sporadic IBD individuals and 189 healthy controls from the Australian population, all of whom are Caucasian. RESULTS: We could not replicate the described association between the CD14-159T allele and CD or UC, nor did we find any evidence for an interaction between the CARD15 or TNF-alpha risk alleles and the CD14-159T allele. CONCLUSIONS: It is possible that the association seen in other studies may be due to population stratification or to the CD14 polymorphism being in linkage with the real disease-causing variant(s).

Vascular endothelial growth factor expression and microvessel parameters of colonic mucosa correlate with sensitivity to steroid in patients with ulcerative colitis.
Hanabata N, Sasaki Y, Tanaka M, Tsuji T, Hatada Y, Hada R, Munakata A
Scand J Gastroenterol 2005 Feb;40(2):188-93.

OBJECTIVE: Vascular endothelial growth factor (VEGF) expression and microvessel parameters have not yet been quantified in the colonic mucosa of ulcerative colitis (UC). The aim of this study was to correlate the parameters with clinical responsiveness to steroid therapy. MATERIAL AND METHODS: Colorectal biopsy specimens from 39 UC patients with high sensitivity to steroid (H-UC), 9 UC patients with low sensitivity to steroid (L-UC) and 6 normal controls (NC) were examined. METHODS: Tissue sections were immunostained with anti-VEGF antibody for number of inflammatory cells (/mm(2)), VEGF-positive cell (/mm(2)) and VEGF-positive ratio (%), and with CD34 for microvessel counts (/mm(2)) and the mean microvessel diameter (microm). RESULTS: The H-UC group had a significantly larger total cell count (10,048+/-2751, p<0.0001) or VEGF-positive cells (2363+/-707, p<0.0001) than the NC group (7235+/-2088 or 1537+/-297, respectively) with no difference in VEGF-positive ratio (24.3+/-6.9 for H-UC versus 22.7+/-6.9 for NC). The L-UC group had a significantly lower VEGF-positive cell count (1420+/-701, p<0.0005) or VEGF-positive ratio (11.6+/-5.5, p<0.0005) than the H-UC group, whereas microvessel counts were almost constant regardless of the subject groups (345+/-7 0 for NC versus 346+/-99 for H-UC versus 349+/-114 for L-UC). Significant increases in microvessel diameter were seen when comparing NC (6.68+/-0.60) with H-UC (7.83+/-1.09, p<0.0001) and H-UC with L-UC (9.05+/-1.70, p<0.03). Out of the five parameters, VEGF-positive ratio and microvessel diameter had a predictive value for L-UC with an 88.9% sensitivity and 88.9% specificity. CONCLUSIONS: L-UC was characterized either as VEGF underexpression or enlarged microvessel. The disruption of the healing process or disturbance of microcirculation may be involved in low sensitivity to steroid therapy in UC.

Laparoscopic colorectal surgery in obese and nonobese patients: do differences in body mass indices lead to different outcomes?
Schwandner O, Farke S, Schiedeck TH, Bruch HP
Surg Endosc 2004 Oct;18(10):1452-6. Epub 2004 Aug 26.

BACKGROUND: The aim of this prospective study was to compare the outcome of laparoscopic colorectal surgery in obese and nonobese patients. METHODS: All patients who underwent laparoscopic surgery for both benign and malignant disease within the past 5 years were entered into the prospective database registry. Body mass index (BMI; kg/m(2)) was used as the objective measure to indicate morbid obesity. Patients with a BMI >30 were defined as obese, and patients with a BMI <30 were defined as nonobese. The parameters analyzed included age, gender, comorbid conditions, diagnosis, procedure, duration of surgery, transfusion requirements, conversion rate, overall morbidity rate including major complications (requiring reoperation), minor complications (conservative treatment) and late-onset complications (postdischarge), stay on intensive case unit, hospitalization, and mortality. For objective evaluation, only laparoscopically completed procedures were analyzed. Statistics included Student's t test and chi-square analysis. Statistical significance was assessed at the 5% level (p < 0. 05 statistically significant). RESULTS: A total of 589 patients were evaluated, including 95 patients in the obese group and 494 patients in the nonobese group. There was no significant difference in conversion rate (7.3% in the obese group vs 9.5% in the nonobese group, p > 0.05) so that the laparoscopic completion rate was 90.5% (n = 86) in the obese and 92.7% (n = 458) in the nonobese group. The rate of females was significantly lower among obese patients (55.8% in the obese group vs 74.2% in the nonobese group, p = 0.001). No significant differences were observed with respect to age, diagnosis, procedure, duration of surgery, and transfusion requirements (p > 0.05). In terms of morbidity, there were no significant differences related to overall complication rates with respect to BMI (23.3% in the obese group vs 24.5% in the nonobese group, p > 0.05). Major complications were more common in the obese group without showing statistical significance (12.8% in the obese group vs 6.6% in the nonobese group, p = 0.078). Conversely, minor complications were more frequently documented in the nonobese group (8.1% in the obese group vs 15.5% in the nonobese group, p = 0.080). In the postoperative course, no differences were documented in terms of return of bowel function, duration of analgesics required, oral feeding, and length of hospitalization (p > 0.05). CONCLUSION: These data indicate that laparoscopic colorectal surgery is feasible and effective in both obese and nonobese patients. Obese patients who are thought to be at increased risk of postoperative morbidity have the similar benefit of laparoscopic surgery as nonobese patients with colorectal disease.

A comparison of the complication rates between laparoscopic colectomy and laparoscopic low anterior resection.
Yamamoto S, Fujita S, Akasu T, Moriya Y
Surg Endosc 2004 Oct;18(10):1447-51. Epub 2004 Aug 26.

BACKGROUND: This study compared the short-term outcomes, including the complication rate and minimum surgical invasiveness, between patients with colon and rectal carcinomas, who underwent laparoscopic surgery. METHODS: A review evaluated 151 patients who underwent laparoscopic colectomy (Lap-colectomy; n = 120) and laparoscopic low anterior resection (Lap-LAR; n = 31) between July 2001 and December 2003. The short-term outcomes were compared between the two groups. RESULTS: The mean operative time and blood loss were significantly greater in the Lap-LAR group. However, the complication rates and postoperative course between the two approaches were similar, and no anastomotic leakage was observed. There was no significant difference in the serum C-reactive protein level and white blood cell count between the two groups in the early postoperative period. CONCLUSIONS: Lap-LAR for rectal carcinoma can be performed safely without increased morbidity or mortality, and its short-term benefits are comparable with those conferred by Lap-colectomy.

The effect of delayed visual feedback on telerobotic surgery.
Kim T, Zimmerman PM, Wade MJ, Weiss CA 3rd
Surg Endosc 2005 Mar 23;.

BACKGROUND: Telerobotic surgery is ideally suited for remote applications in which the instrument control console is stationed separately from the end-effectors at the patient's bedside. However, if the distance between the console and the patient is great enough, a lag effect or latency between end-effector manipulation and the depicted image leads to alterations in movement patterns. The purpose of this study was to determine the effect of visual delay on surgical task performance. METHODS: At an endoscopic skill station, an analogue delay device was interposed between the surgical field and monitor to delay the transmission of visual information, thus mimicking the distance effect of data transmission. Three surgeons with similar laparoscopic experience participated in the laparoscopic knot tying portion of the study, and seven residents participated in the accuracy and dexterity tasks. The time to complete a single throw was recorded in seconds after adding consecutively increasingly time delay in 50 ms increments. Similar time delay increments were added for the accuracy and dexterity tasks, which involved passing a needle through two adjacent circles and passing a small cylinder through a larger one to reproduce two-handed coordination and spatial resolution. Data were presented as the median time to complete each task. RESULTS: For all three tasks, an incremental increase in time delay was associated with a significant (p < 0.001) increase in the time to complete the task. For dexterity, a statistically significant (p </= 0.05) delay was identified at 0.25 s of delay from control values without delay. A move-and-wait strategy was gradually adopted up to 0.4 s of visual delay. CONCLUSIONS: Compensation for visually delayed image perception occurs on several levels. Initial adaptations include slower end-effector manipulation; late adaptive changes include a move-and-wait strategy. Increased time to perform surgical maneuvers as well as diminished accuracy, diminished dexterity, and increasing fatigue represent additional performance encumbrances evoked by visual time delay. The nuances of both human and digital compensatory mechanisms for visual time delay must be defined and enhanced to maximize the potential for telerobotic surgical applications.

Evaluation of adhesion formation, mesh fixation strength, and hydroxyproline content after intraabdominal placement of polytetrafluoroethylene mesh secured using titanium spiral tacks, nitinol anchors, and polypropylene suture or polyglactin 910 suture.
Joels CS, Matthews BD, Kercher KW, Austin C, Norton HJ, Williams TC, Heniford BT
Surg Endosc 2005 Mar 23;.

BACKGROUND: The purpose of this study is to evaluate fixation methods for polytetrafluoroethylene (ePTFE) mesh with an in vivo model of laparoscopic ventral hernia repair. METHODS: In 40 New Zealand white rabbits, a 4 x 4-cm ePTFE mesh (n = 80, two per animal) was attached to an intact peritoneum with polyglactin 910 (PG 910) (n = 20) or polypropylene (PP) (n = 20) suture, titanium spiral tacks (TS) (n = 20), or nitinol anchors (NA) (n = 20). Mesh was harvested at 8 and 16 weeks for fixation strength testing, adhesion assessment, and collagen (hydroxyproline) content. Fixation strength on day 0 was determined with mesh attached to harvested abdominal wall. Statistical significance was determined as p < 0.05. RESULTS: There was no difference in fixation strength between PP (39.1 N) and PG 910 (40.0 N) sutures at time zero. At week 8, PP (25.7 N) was significantly stronger (p < 0.05) than PG 910 (11.4 N) suture, but not at week 16. The fixation strength of TS and NA (day 0, 15.4 vs 7.4 N; week 8, 17.5 vs 15.3 N; week 16, 19.1 vs 13.8 N) was not significantly different. Fixation with PP suture was significantly (p < 0.05) stronger than that with TS and NA at day 0 (39.1, 15.4, and 7.4 N, respectively) but not at weeks 8 or 16. The fixation strength of suture decreased significantly (p < 0.05) from day 0 to week 16 (PP: day 0 = 39.1 N, week 8 = 25.7 N, week 16 = 21.4 N; PG 910: day 0 = 40.0 N, week 8 = 11.4 N, week 16 = 12.8 N). The fixation strength of NA and TS did not change significantly (NA: day 0 = 7.4 N, week 8 = 15.3 N, week 16 = 13.8 N; TS: week 0 = 15.4 N, week 8 = 17.5 N, week 16 = 19.1 N). There were no differences in adhesion area based on fixation device used; however, there were more (p < 0.05) mesh samples using NA with adhesions compared to TS and adhesion tenacity was greater (p < 0.05) compared to that of TS, PP, and PG. Hydroxyproline content at weeks 8 and 16 was similar for all fixation devices. CONCLUSIONS: The initial fixation strength for nonabsorbable suture is significantly greater than that of the metallic fixation devices, but after 8 weeks there is no difference. Laparoscopic ventral hernia repair without transabdominal suture fixation may be predisposed to acute failure. The metallic devices have similar fixation strength, although the incidence of adhesions and tenacity of adhesions appear to be greater with the nitinol anchors. Since these devices have similar fixation strengths and most likely provide adequate supplementation to transabdominal sutures for mesh fixation after laparoscopic ventral hernia repair, their use should be based on other factors, such as their propensity for adhesions, ease of application, and cost.

Laparoscopic colorectal resection for endometriosis.
Campagnacci R, Perretta S, Guerrieri M, Paganini AM, De Sanctis A, Ciavattini A, Lezoche E
Surg Endosc 2005 Mar 11;.

BACKGROUND: The rectosigmoid colon is affected by deep pelvic endometriosis in 3-37% of cases. In the past, treatment of the affected gastrointestinal tract generally required conversion to conventional surgery. We describe our experience with complete laparoscopic management of deep pelvic endometriosis with bowel involvement. METHODS: From March 1995 to March 2003, 29 consecutive patients with endometriosis requiring laparoscopic intervention were evaluated. In seven patients (24%) colorectal involvement was identified prior to the operation. A low anterior resection was performed in four patients (57%) and a sigmoid resection in three (43%). In all cases, colonoscopy showed a normal mucosa. In all cases, treatment consisted of resection of the bowel involved together with the excision of all other implants. Data analysis included age, previous abdominal operations, previous history of endometriosis, operative time, conversion rate, complications, length of stay, and pain relief. RESULTS: There were seven patients with colorectal involvement whose median age was 32.8 years (range, 28-40), with a history of previous abdominal operation in two (28%). Preoperative symptoms were as follow: dysmenorrea in four patients (57%), dyspareunia in four (57%), pelvic pain in seven (100%), rectal bleeding in one (14%), and tenesmus in five (71%). Mean operative time was 190 min (range, 165-230). Length of stay was 8.3 days (range, 7-11). There were no anastomotic leak and no major postoperative complication. One patient had temporary urinary retention. At a median follow-up of 38.7 months (range, 1-84), complete relief of pelvic symptoms was achieved in five patients (71%), and there was improvement in one patient. In one patient complaining of persistent pain, a new colonic implant was diagnosed two years after the surgery requiring reoperation. CONCLUSIONS: The results show that provided that the surgeon is highly skilled in laparoscopy, laparoscopic resection of deep pelvic endometriosis with rectosigmoid involvement is feasible and effective in nearly all patients.

Laparoscopic vs open total colectomy: a case-matched comparative study.
Pokala N, Delaney CP, Senagore AJ, Brady KM, Fazio VW
Surg Endosc 2005 Mar 11;.

BACKGROUND: Open total colectomy and ileorectal anastomosis (OTC) is a major colorectal procedure which would preclude laparoscopy in many centers because of technical difficulty and the fact that laparoscopic total colectomy (LTC) takes much longer than standard laparoscopic proctosigmoidectomy (LPS). This study compares OTC with LTC and LPS. METHODS: In this study, 34 LTC patients (May 1999 to August 2003) were matched for age, diagnosis, operative period, and procedure with patients undergoing OTC. Patients with a previous major laparotomy were excluded from the open group. Groups were compared for gender, American Society of Anesthesiology (ASA) classification, operating time, estimated blood loss, length of hospital stay (LOS), complications including readmissions, and costs. The LPS cases were picked randomly from the laparoscopic database (every eighth patient), and the OT and LOS were noted. RESULTS: The LTC and OTC groups were matched for age (mean, 31 vs 34 years; p = 0.2), sex (14 vs 13 females; p = 0.8), ASA (8/23/3/0 vs 8/22/4/0, class 1/2/3/4). The body mass index was higher in the open group (23.8 vs 27.9; p = 0.04). The operating time was significantly longer (187 vs 126 min; p = 0.0001) and the median LOS shorter in the LTC group (3 days [IQR, 2.5-5 days] vs 6 days [IQR 4-8 days]; p = 0.0001). The estimated blood loss was significantly less in the LTC group (168 [50-700] ml) vs 238 [50-800] ml); p = 0.001, but there was no significant difference in the complication (26.5% vs 38.2%; p = 0.4) readmission (11.8% vs 14.7%; p = 1.0), reoperative rates (8.8% vs 11.8%; p = 1.0), or direct costs ($4,578 vs $4,562; p = 0.3). One LTC patient died expired on postoperative day 2 of a cardiac event. Four patients (11.8%) required conversion for obesity (n = 2), adhesions (n = 1), or intraoperative hemorrhage (n = 1). The operating times were 36 min longer in the LTC group than in the LPS group (151 vs 187 min; p = 0.02), but there was no significant difference in the LOS. (3 vs 3 days, p = 0.2). CONCLUSIONS: The findings show that LTC provides a significant decrease in the LOS over OTC, with increased operating time, but without any change in other parameters. A laparoscopic approach to subtotal colectomy is recommended for suitable patients when an experienced team is available.

Does laparoscopic colorectal resection for diverticular disease impair male urinary and sexual function?
Lesurtel M, Fritsch S, Sellam R, Molinier N, Mosnier H
Surg Endosc 2004 Dec;18(12):1774-7. Epub 2004 Oct 13.

BACKGROUND: Laparoscopic colorectal resection may induce bladder and sexual dysfunction secondary to injury to the autonomic nervous system. The aim of this study was to evaluate urinary and sexual function in male patients after laparoscopic colorectal resection for diverticular disease. METHODS: From January 1997 to March 2002, we performed a retrospective analysis of urinary and sexual function in 56 consecutive male patients who had undergone laparoscopic colorectal resection for diverticular disease. Preoperative and 6-month postoperative assessment was carried out using data collected via standardized postal questionnaires. RESULTS: Three patients were excluded (one had a prior prostatectomy, one had Peyronie's disease, and one was treated with neuroleptics). Fifty-three patients with a mean age of 54 A+/- 2 years were included in the study. There were no conversions. The morbidity rate was 9.4%. Mean follow-up was 27 A+/- 2 months. There was no significant difference in preoperative and postoperative urinary function. Fifty-one patients (96%) were sexually active preoperatively and were still sexually active postoperatively. Compared with the preoperative period, postoperative impairment of libido, erection, ejaculation, and orgasm were not significant. Every patient was able to achieve ejaculation after the intervention, and no retrograde ejaculations were reported. One patient was unable to have an erection after the intervention. CONCLUSION: Laparoscopic colorectal resection for diverticular disease does not significantly impair urinary and sexual function.

Ultracision Harmonic Scalpel and multifunctional tem400 instrument complement in transanal endoscopic microsurgery: a prospective study.
Ayodeji ID, Hop WC, Tetteroo GW, Bonjer HJ, de Graaf EJ
Surg Endosc 2004 Dec;18(12):1730-7. Epub 2004 Oct 26.

BACKGROUND: For transanal endoscopic microsurgery, the ultracision Harmonic Scalpel (UC) and the multifunctional TEM400 instrument (T400) seem advantageous. This study investigated their clinical use. METHODS: Prospective analysis of tumor, patient, and operation characteristics was performed for 196 tumor resections per instrument intended for application. RESULTS: The T400 instrument was applied in 162 operations, and the UC in 34 operations. Tumor and patient characteristics were similar except for tumor area (respectively, 7.5 and 17 cm(2); p = 0.003). Operative time was proportionate to the tumor area (p < 0.001) and inversely proportionate to its distance from the dentate line to the lower margin of the tumor of the UC (p = 0.002). Application reduced operative time by 26% (p = 0.02, corrected for area). Whereas, T400 was always singly sufficient for excision, the UC required T400 application in 50% of operations, especially for larger tumors (p = 0.026), with the result that more rectal wall circumference was captured (p = 0.043). Both groups had similar safety parameters. CONCLUSIONS: The UC substantially reduced operative time compared with the T400, but frequently required the T400 for procedure completion. The T400 is always singly sufficient.

Genetic Polymorphism in Cytochrome P450 7A1 and Risk of Colorectal Cancer: The Fukuoka Colorectal Cancer Study.
Hagiwara T, Kono S, Yin G, Toyomura K, Nagano J, Mizoue T, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Imaizumi N
Cancer Res 2005 Apr 1;65(7):2979-82.

Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acids from cholesterol in the liver, and thus may be an important determinant of bile acid production. We examined the association between the CYP7A1 A-203C polymorphism and colorectal cancer. The CYP7A1 A-203C polymorphism was determined by the PCR-RFLP method in 685 incident cases of colorectal cancer and 778 controls randomly selected from a community in the Fukuoka area, Japan. The CC genotype was slightly less frequent in the case group, and the adjusted odds ratio for the CC versus AA genotype was 0.88 (95% confidence interval, 0.65-1.20). In the analysis by subsite of the colorectum, a decreased risk associated with the CYP7A1 CC genotype was observed for proximal colon cancer, but not for either distal colon or rectal cancer. The adjusted odds ratios (95% confidence intervals) of proximal colon cancer for the CC genotype were 0.63 (0.36-1.10) compared with the AA genotype, and 0.59 (0.37-0.96) compared with the AA and AC genotypes combined. A decreased risk of proximal colon cancer in relation to the CC genotype of CYP7A1 A-203C, which probably renders less activity of the enzyme converting cholesterol to bile acids, is new evidence for the role of bile acids in colorectal carcinogenesis.

Assessment of Publication Bias in the Reporting of EUS Performance in Staging Rectal Cancer.
Harewood GC
Am J Gastroenterol 2005 Apr;100(4):808-16.

INTRODUCTION: Endoscopic ultrasound (EUS) has emerged as a promising diagnostic modality for locoregional staging of rectal cancer. However, as with any new technology, publication bias, the selective reporting of studies featuring positive results, may result in overestimation of the capability of EUS. The aim of this study was to systematically assess for publication bias in the reporting of the accuracy of EUS in staging rectal cancer. METHODS: A MEDLINE search for all published estimates of EUS accuracy in staging rectal cancer between 1985 and 2003 was performed. All retrieved studies were fully published in the English literature. Published studies were analyzed and the following information was abstracted: accuracy of EUS, year of publication, number of subjects studied, impact factor of journal, and type of journal (gastroenterology, surgery, radiology, other). RESULTS: Two hundred and two abstracts were reviewed; 41 publications met the stated criteria for inclusion. EUS T-staging accuracy was reported in 40 studies while EUS N-staging accuracy was reported in 27 studies. The experience of 4, 118 subjects was reported with an overall mean T-staging accuracy of 85.2% (median, 87.5%) and N-staging accuracy of 75.0% (median, 76.0%). There was a paucity of smaller studies expressing low EUS accuracy rates. Both T-staging and N-staging accuracy rates also declined over time with the lowest rates reported in more recent literature. CONCLUSION: The performance of EUS in staging rectal cancer may be overestimated in the literature due to publication bias. This inflated estimate of the capability of EUS may lead to unrealistic expectations of this technology. (Am J Gastroenterol 2005;100:1-9).

Ulcerative colitis activity index: a useful prognostic factor for predicting ulcerative colitis outcome.
Gurel S, Kiyici M
J Int Med Res 2005 Jan-Feb;33(1):103-10.

We evaluated the usefulness of various parameters in predicting the prognosis of ulcerative colitis. The records of 73 patients with ulcerative colitis were examined retrospectively. Patients were divided into two groups according to whether they had received only 5-aminosalicylic acid (5-ASA; n = 26) or glucocorticoids and/or azathioprine with or without 5-ASA (n = 47). The disease extent, endoscopic activity and ulcerative colitis activity index (UCAI) before therapy were recorded, together with the disease outcome. No statistically significant differences in outcome were observed in relation to therapy group, disease extent or endoscopic activity. UCAI had a significant effect on outcome, however: patients with lower UCAI values were more likely to remain in remission and less likely to require urgent surgery or experience a fatal outcome than those with higher UCAI values. This difference was apparent in both treatment groups. Thus a high pre-treatment UCAI may indicate a worse outcome.

Profile of soluble cytokine receptors in Crohn's disease.
Gustot T, Lemmers A, Louis E, Nicaise C, Quertinmont E, Belaiche J, Roland S, Van Gossum A, Deviere J, Franchimont D
Gut 2005 Apr;54(4):488-95.

INTRODUCTION: Soluble cytokine receptors (sCRs) modulate the in vivo activity of cytokines. Deficient sCR production could participate in the pathogenesis and course of Crohn's disease (CD). The aim of the study was to examine the profile of sCRs in CD patients and their modulation by infliximab and corticosteroids. METHODS: We prospectively examined active CD patients (aCD) treated with either infliximab (n = 21) or corticosteroids (n = 9), CD patients in clinical remission (rCD, n = 20), ulcerative colitis patients (UC, n = 24), and healthy subjects (HS, n = 15). Cultures of colonic biopsies were also examined from CD inflamed (n = 8), CD non-inflamed (n = 7), and healthy mucosa (n = 8). Levels of tumour necrosis factor alpha (TNF-alpha), soluble TNF receptor I (sTNFRI), soluble TNF receptor II (sTNFRII), interleukin 1beta (IL-1beta), soluble IL-1 receptor I (sIL-1RI), soluble IL-1 receptor II (sIL-1RII), IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 were measured using ELISA. RESULTS: Higher levels of sTNFRI (p<0.05, p<0.01), sTNFRII (p<0.01, p<0.01), sIL-1RI (p<0.05, NS), IL-6 (p<0.01, p<0.01), and sIL-6R (p<0.05, NS) were observed in aCD compared with rCD and HS. Interestingly, sIL-1RII (p<0.05, p<0.01) and sgp130 (p<0.01, p<0.01) were profoundly decreased in aCD compared with rCD and HS, and were negatively correlated with CRP. Deficient production of sIL-1RII was specific to CD (not observed in ulcerative colitis), and was further confirmed at the mucosal level. Infliximab decreased sTNFRII at one and four weeks (p<0.05) and enhanced sIL-6R levels at one week (p<0.05). Corticosteroids increased sIL-1RII levels at one week (p<0.05). CONCLUSION: CD is associated with dysregulated production of sCRs. Deficiency in sIL-1RII and sgp130 may be essential to CD pathogenesis. Their replacement through the use of fusion proteins could represent future alternative therapeutic strategies for CD.

Preventing neoplastic progression in ulcerative colitis.
Ullman TA
J Clin Gastroenterol 2005 Apr;39(4 Suppl 2):S66-9.

Patients with ulcerative colitis (UC) and Crohn's colitis carry an increased risk for developing colorectal cancer (CRC). Patients with more extensive colitis, greater duration of disease, concomitant primary sclerosing cholangitis, and a family history of CRC are at greatest risk among UC patients. Young age at disease onset and greater inflammatory burden have also been proposed as risk factors. Maneuvers that limit the impact of cancer in colitis include prophylactic colectomy, which is unacceptable to most UC and Crohn's colitis patients, and dysplasia surveillance. Although recommended in a number of practice guidelines, surveillance has not yet been demonstrated to reduce CRC mortality or morbidity. A number of factors, including low levels of agreement among pathologists interpreting surveillance specimens, patients lost to follow-up, failure to recommend colectomy once dysplasia has been discovered, and others, hinder the success of surveillance. In an effort to compensate for the limitations of surveillance, chemoprevention and newer endoscopic and molecular techniques are being assessed for their effectiveness in augmenting or replacing conventional surveillance.

Past and current theories of etiology of IBD: toothpaste, worms, and refrigerators.
Korzenik JR
J Clin Gastroenterol 2005 Apr;39(4 Suppl 2):S59-65.

While tremendous advances have improved the understanding of inflammatory bowel disease, with regard to environmental risk factors as well as the biochemical nature of the inflammatory process, a determination of primary etiology remains elusive. Numerous theories have been proposed in the past century concerning the cause of Crohn's disease and ulcerative colitis with implications for specific therapies. On further study, most of these ideas and therapies have failed to be accurate in theory or therapeutic approach. Others remain untested or are the focus of current investigation and controversy. This paper reviews the dominant theories of primary etiology. These hypotheses include infectious causes such as Mycobacteria paratuberculosis and measles. Allergic and nutritionally related causes have been the focus of considerable research. Microparticles, which is part of the concept behind toothpaste as a cause, have been suggested more broadly to be the principal factor initiating Crohn's disease. Several of these concepts rely on the idea that there is an increased intestinal permeability that is the central defect leading to Crohn's disease. Rather than being an excessive T cell driven process, Crohn's has been suggested to be an innate immune deficiency, leading to the use of colony stimulating factors to augment the intestinal barrier function and innate immunity. A variety of changes in the gut flora, ranging from a basic dysbiosis to the absence of helminths, have been proposed as the root cause of inflammatory bowel disease.

Bicarbonate secretion: a neglected aspect of colonic ion transport.
Binder HJ, Rajendran V, Sadasivan V, Geibel JP
J Clin Gastroenterol 2005 Apr;39(4 Suppl 2):S53-8.

Understanding of the mechanism of colonic electrolyte transport has markedly increased over the past three decades. This article provides a brief summary of the critical features of Na, Cl, and K transport in the large intestine and how these processes may be altered in diarrhea. Less understood is the mechanism of colonic HCO3 secretion. Recent progress in the regulation of HCO3 secretion in the distal colon is summarized with emphasis on the interrelationship between Cl-dependent, short-chain fatty acid (SCFA)-dependent, and cAMP-induced HCO3 secretion. cAMP down-regulates Cl-dependent HCO3 secretion, while SCFA stimulates HCO3 secretion but also inhibits both Cl-dependent and cAMP-induced HCO3 secretion. As SCFAs are the primary anions in stool, it is likely that SCFA-dependent HCO3 secretion is the primary mechanism of HCO3 secretion in the mammalian colon. Future studies will undoubtedly provide increased understanding of the mechanism of HCO3 secretion in health and disease.

Pathogenesis of diarrhea in ulcerative colitis: new views on an old problem.
Sandle GI
J Clin Gastroenterol 2005 Apr;39(4 Suppl 2):S49-52.

BACKGROUND: Whereas water movement into the intestinal lumen occurs secondary to Cl secretion in secretory diarrheal diseases, defects in key transport processes lead to profound decreases in colonic Na, Cl, and water absorption in ulcerative colitis. STUDIES AND RESULTS: Recent studies indicate reduced expression/activity of apical Na channels and basolateral Na, K-ATPase, leading to loss of electrogenic Na absorption in the distal colon and rectum. There is also likely to be a decrease in electroneutral NaCl cotransport, which is present throughout the colon. Preliminary work on basolateral K channel abundance and activity in colonic epithelial cells suggests that whole-cell K conductance is decreased in ulcerative colitis, leading to epithelial cell depolarization, and further limitation of Na absorption. In addition, there is a marked reduction in colonic epithelial resistance, which reflects a decrease in the integrity of intercellular tight junctions and the presence of apoptotic foci. CONCLUSIONS: Impaired Na and Cl transport, combined with enhanced epithelial "leakiness," results in a profound decrease in the capacity of the inflamed colon to absorb salt and water. Transport abnormalities in ulcerative colitis may at least partly reflect the effects of proinflammatory cytokines, raising the possibility of novel approaches to the restoration of colonic absorptive capacity in this disease.

Deficiencies in knowledge and familial risk communication among colorectal adenoma patients.
Schroy PC 3rd, Lal SK, Wilson S, Heeren T, Farraye FA
J Clin Gastroenterol 2005 Apr;39(4):298-302.

GOALS: Our primary objectives were to assess knowledge about familial risk and risk communication among colorectal adenoma patients. BACKGROUND: The first-degree relatives (FDRs) of colorectal adenoma patients diagnosed before the age of 60 years may be at increased risk of colorectal cancer and should begin screening by the age of 40 years. Adherence to this recommendation requires effective risk communication between physicians, affected patients, and their at-risk relatives. STUDY: We conducted a telephone survey of 129 consecutive English-speaking adenoma patients younger than 60 years treated by 11 endoscopists at two medical centers. Information regarding patient demographics, awareness of familial risk, and risk communication was elicited. RESULTS: A total of 71 eligible subjects responded to the survey. Few responders (n = 25, 33%) were aware that their FDRs were at increased risk of colorectal cancer, and only 56% of knowledgeable patients identified a physician as the source of information. Awareness was strongly associated (P < or = 0.001) with patient-initiated information-seeking behavior. Most knowledgeable patients (n = 20, 80%) reported that they had informed > or = 1 FDRs about their diagnosis, and most (68%) felt that it was the patient's responsibility to notify at-risk relatives. CONCLUSIONS: Most colorectal adenoma patients younger than 60 years are unaware of the familial implications of their diagnosis and therefore unlikely to notify at-risk FDRs.

Topical treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine: a single-blind randomized controlled trial.
Gionchetti P, D'Arienzo A, Rizzello F, Manguso F, Maieron R, Lecis PE, Valpiani D, Iaquinto G, Annese V, Balzano A, Varoli G, Campieri M
J Clin Gastroenterol 2005 Apr;39(4):291-7.

GOALS: Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects. BACKGROUND: To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC. STUDY: Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters. RESULTS: A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group. CONCLUSIONS: BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

Efficacy and safety of endoscopic balloon dilation of symptomatic upper and lower gastrointestinal Crohn's disease strictures.
Singh VV, Draganov P, Valentine J
J Clin Gastroenterol 2005 Apr;39(4):284-90.

GOALS: To evaluate efficacy and safety of endoscopic balloon dilation with or without intralesional steroid injection, of symptomatic upper gastrointestinal (UGI) and lower gastrointestinal (LGI) Crohn's disease (CD) strictures. BACKGROUND: Patients with CD commonly develop obstructive symptoms secondary to gastrointestinal strictures. When these do not resolve with medical management, surgery is usually the only alternative. Limited data are available on the safety and efficacy of endoscopic through-the-scope (TTS) balloon dilation of CD strictures. STUDY: We performed a retrospective review of TTS balloon dilations done on CD-related UGI and LGI strictures. Postdilation intralesional steroid injections were done at the discretion of the endoscopist. Stricture was defined as luminal stenosis <10 mm in diameter, through which a scope could not be passed. Technical success was defined as the ability of the scope to traverse the stricture postdilation. Long-term success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation. RESULTS: Over 4 years, we performed 29 stricture dilations on 17 patients (10 female, 7 male) with 20 strictures. The mean follow-up period was 18.8 months (range, 5-50 months). Stricture locations were as follows: rectal, 5; sigmoid colon, 2; colo-colonic anastomosis, 3; ileocolonic anastomosis, 4; ileum, 1; descending colon, 1; cecum, 1; and distal duodenal bulb, 3 patients. Technical success was achieved in 28 of 29 stricture dilations (96.5%). Ten strictures (34.5%) were dilated to <15 mm and 19 (65.5%) to > or = 15 mm diameter. Long-term success rate in the <15 mm group was 70%, and in > or = 15 mm group was 68.4%. Four quadrant steroid injections were done on 11 strictures. The recurrence rate in this group was 10% and that in the nonsteroid group was 31.3%. The overall long-term success rate was 76.5% by intent-to-treat analysis. Three perforations occurred (all colonic) during 29 stricture dilations, a complication rate of 10% with no mortalities. CONCLUSION: We report the first series of TTS balloon dilations with or without intralesional steroid injection, of both primary and anastomotic UGI and LGI strictures in CD patients. Long-term success was achieved in 76.5% patients with a complication rate of 10%. This mode of therapy appears safe and effective and can be considered as an alternative to surgery in selected patients with medically refractory CD-associated GI strictures. Success rates were better in patients who received four quadrant steroid injections. No difference was seen in stricture recurrence rate or complications based on diameter of TTS balloon used.

A polymorphism of the bactericidal/permeability increasing protein (BPI) gene is associated with Crohn's disease.
Klein W, Tromm A, Folwaczny C, Hagedorn M, Duerig N, Epplen J, Schmiegel W, Griga T
J Clin Gastroenterol 2005 Apr;39(4):282-3.

BACKGROUND: The bactericidal/permeability increasing protein (BPI) is involved in the elimination of gram-negative bacteria. A functionally relevant single nucleotide polymorphism of the BPI gene causes an amino acid exchange (Glu216Lys). STUDY: To evaluate whether this single nucleotide polymorphism contributes to the predisposition to inflammatory bowel disease, we compared the allele frequencies of 265 patients with Crohn's disease, 207 patients with ulcerative colitis, and 608 healthy controls. RESULTS: The Glu/Glu genotype frequency was decreased significantly in Crohn's disease patients as compared with controls (P < 0.027). No differences were obvious in patients with ulcerative colitis. CONCLUSIONS: Failure of the innate intestinal immune system could be involved in the pathogenesis of Crohn's disease via reduced/impaired defense against gram-negative bacteria.

Villous tumor of the rectum that started secreting watery fluid after colectomy.
Shimada Y, Iiai T, Shimizu H, Suda K, Maruyama S, Wakai T, Okamoto H, Hatakeyama K
J Gastroenterol 2005 Feb;40(2):214-5.

Expression level of thymidylate synthase is a good predictor of chemosensitivity to 5-fluorouracil in colorectal cancer.
Inoue T, Hibi K, Nakayama G, Komatsu Y, Fukuoka T, Kodera Y, Ito K, Akiyama S, Nakao A
J Gastroenterol 2005 Feb;40(2):143-7.

BACKGROUND: It is important to seek the appropriate chemotherapy drugs to effectively eliminate colorectal cancers. To avoid unnecessary medication and uncomfortable side effects, it is important to estimate the chemosensitivity of cancers to 5-fluorouracil (5-FU) before chemotherapy. METHODS: We examined thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions in 23 colorectal cancers, using quantitative reverse transcription-polymerase chain reaction (RT-PCR). We then evaluated the relationship between TS and DPD gene expression levels and the sensitivity of colorectal cancers to 5-FU, as determined by histoculture drug response assay (HDRA). RESULTS: A significant increase in the TS expression score was observed in 5-FU-sensitive colorectal cancers (0.57 +/- 0.19) compared to 5-FU-resistant ones (1.16 +/- 0.98; P = 0.029), whereas no significant differences in DPD expression scores were observed in 5-FU-sensitive colorectal cancers (0.86 +/- 1.19) compared to 5-FU-resistant ones (0.56 +/- 1.05; P = 0.603). CONCLUSIONS: TS mRNA may be useful as a predictor of the 5-FU chemosensitivity of colorectal cancers.

Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B cell activation and differentiation in patients with inflammatory bowel disease.
Nishiwaki T, Ina K, Goto H, Watanabe O, Tsuzuki T, Furuta R, Ando T, Hibi K, Kusugami K
J Gastroenterol 2005 Feb;40(2):128-36.

BACKGROUND: We investigated the possible roles of the interleukin (IL)-15 and IL-15 receptor (IL-15R) system in a heightened state of B-cell activation and differentiation in intestinal mucosa with inflammatory bowel disease (IBD). METHODS: The expression of IL-15 and IL-15Ralpha mRNA and protein in inflamed colonic mucosal tissues with IBD, and in control tissues was examined by reverse transcriptase-polymerase chain reaction and immunohistological methods. The effects of recombinant (r)IL-15 on the expression of IL-15Ralpha on lamina propria B cells and the production of immunoglobulin G (IgG) were analyzed in vitro, using lamina propria mononuclear cells (LPMCs) isolated from control tissues. RESULTS: The intensity of IL-15 and IL-15Ralpha mRNA was greater in the mucosal tissues of patients with IBD, especially in those of patients with ulcerative colitis (UC), than in control tissues. Compared to control tissues, mononuclear cells positive for IL-15Ralpha protein were observed in greater proportions in tissue sections from patients with IBD, especially in those from patients with UC, where IL-15Ralpha protein was localized to CD20-positive B cells to a significant degree. There were increases in the proportions of IL-15Ralpha-positive B cells and IgG-producing cells in rIL-15- or rCD40L-stimulated cultures of LPMCs, with stimulatory effects being greater in the presence of their combination. CONCLUSIONS: These data suggest that the IL-15 and IL-15R system may play important roles in the activation and differentiation of lamina propria B cells in patients with IBD, especially in those with UC.

Unemployment and Disability in Patients With Moderately to Severely Active Crohn's Disease.
Feagan BG, Bala M, Yan S, Olson A, Hanauer S
J Clin Gastroenterol 2005 May/June;39(5):390-395.

GOALS: Unemployment and disability rates in Crohn's disease patients from the ACCENT I trial were assessed. Factors associated with employment and disability status were explored. BACKGROUND: Limited data regarding unemployment and disability status in patients with active Crohn's disease are available. STUDY: Baseline data were used to assess unemployment and disability rates. Logistic regression analysis examined factors that were associated with employment and disability status. Analysis of variance was used to compare quality of life. RESULTS: The baseline full-and part-time employment rates were 48% and 13%, respectively, with 39% of patients unemployed and 25% receiving disability compensation. Only 14% of 225 unemployed patients felt well enough to work if a job were available. Younger age, female gender, shorter disease duration, and prior bowel resection predicted a higher likelihood of unemployment. Younger age and female gender also predicted a higher likelihood of not being employed full-time. Prior bowel resection predicted a higher likelihood of receiving disability compensation. Quality of life (Inflammatory Bowel Disease Questionnaire, Short Form-36) scores were significantly higher in employed patients. CONCLUSIONS: Patients with moderately to severely active Crohn's disease had low employment and high disability rates. Given their economic importance, assessment of these outcomes should be integrated into future evaluations of therapy, including clinical trials.

Crohn's disease patient characteristics in a tertiary referral center: comparison with patients from a population-based cohort.
Zankel E, Rogler G, Andus T, Reng CM, Scholmerich J, Timmer A
Eur J Gastroenterol Hepatol 2005 Apr;17(4):395-401.

OBJECTIVES: Data on the clinical presentation, effects of therapy and prognosis of patients with Crohn's disease are often based on patients from specialized referral centers. We assessed the extent of the selection based on the clinical and demographic characteristics. METHODS: All patients with Crohn's disease presenting to the University Hospital of Regensburg (Medical Department) were analyzed retrospectively with respect to demographic and disease specific characteristics. Only patients diagnosed <2 years before presentation were included in the main analysis. The original data from a population-based, prospectively assembled incidence cohort were available for comparison (EC-IBD, northern centers only, n=475). Age at diagnosis, disease location and behavior were categorized according to the Vienna classification. Differences were examined using chi-square tests. MAIN RESULTS: At the referral center, 394 patients were treated within a 5-year period. Of these, 116 patients fulfilled the inclusion criteria for the comparative analysis. Sixteen percent of the referral patients were diagnosed at age 40 or older, as compared with 32% in the population-based group (P<0.004). The distribution of disease location, sex, smoking behavior and positive family history was similar in both groups. Among the referral patients, more had fistulas (39% versus 20%, P<0.001). Also, more patients were receiving steroids (49% versus 27%) or other immunosuppressive therapy (12% versus 4%). The selection effects increase with duration of disease. CONCLUSIONS: Patients with late onset of disease, inflammatory only disease behavior and no need for immunosuppression are under-represented at a tertiary referral center.

Predictors of response to infliximab in luminal Crohn's disease.
Laharie D, Salzmann M, Boubekeur H, Richy F, Amouretti M, Quinton A, Couzigou P, Lamouliatte H, Zerbib F
Gastroenterol Clin Biol 2005 Feb;29(2):145-9.

AIMS: To identify predictive factors of response to infliximab in luminal Crohn's disease (CD). PATIENTS AND METHODS: All consecutive patients with luminal CD treated with infliximab between October 1999 and March 2003 in Bordeaux's referral centers were included. All had at least 3 months follow-up post infliximab infusion and no prior treatment with infliximab. Response rates were determined 2 and 8 weeks after infusion according to Crohn's Disease Activity Index (CDAI) (remission=CDAI<150 and response=CDAI decrease more than 100). RESULTS: Among 44 patients (33 female; mean age 35 +/- 14 yr.), 39 (88%) had a clinical response 2 weeks after infusion (79% in remission). At week 8, the rate of response was 61.4% and exclusive colonic involvement predicted sustained response to treatment (P=0.03). The probability of remission at 56 weeks was 21.4%. Multivariate analysis demonstrated that the only factor associated with response duration was initiating immunosuppressive (IS) therapy in women (RR=3.61 95%CI[1.25-10.41], P=0.017). CONCLUSION: Exclusive colonic involvement is the only predictive factor of sustained response to infliximab in luminal CD. At the time of infliximab infusion, initiation or modification of IS therapy may favor sustained response, at least in women.

Gastroenterologists as surgeons: what they need to know.
Ponsky JL
Gastrointest Endosc 2005 Mar;61(3):454.

Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: results from a national endoscopic database.
Harewood GC, Olson JS, Mattek NC, Holub JL, Lieberman DA
Gastrointest Endosc 2005 Mar;61(3):371-5.

BACKGROUND: The colonic biopsy is the only reliable method for identification of microscopic colitis in patients with chronic diarrhea and normal endoscopic findings. METHODS: The Clinical Outcomes Research Initiative national endoscopic database was analyzed to determine the rate at which colonic biopsy specimens were obtained in patients undergoing colonoscopy for the evaluation of diarrhea with no visible mucosal abnormality. RESULTS: Between January 2000 and December 2003, 5565 unique adult patients underwent colonoscopy for evaluation of diarrhea without detection of any mucosal abnormality. Colonic mucosal biopsy specimens were obtained in 4410 (79.2%) of these patients. The rates at which biopsy specimens were obtained differed among the sites where colonoscopy was performed; biopsy specimens were obtained from more patients undergoing colonoscopy in university-affiliated settings (86.8%) compared with Veterans Affairs Medical Centers (VAMC) (78.5%) or community sites (78.6%) ( p < 0.001). On multivariate analysis, biopsy specimens were more likely to be obtained in younger patients (OR 0.7: 95%CI[0.6, 0.8] for age >50 years vs. <50 years), women patients (OR 1.4: 95% CI[1.2, 1.6] in community setting; OR 4.1: 95% CI[1.6, 10.5] in VAMC setting), and patients seen in university-affiliated medical centers (university center OR 2.1: 95% CI[1.5, 3.0] vs. community setting). CONCLUSIONS: Biopsy specimens are obtained in four fifths of patients with diarrhea and normal colonoscopy findings to exclude microscopic colitis. Variation in biopsy practice exists among endoscopy site types and by gender. Clear guidelines are needed for the endoscopic approach to these patients.

Infliximab and Semen Quality in Men with Inflammatory Bowel Disease.
Mahadevan U, Terdiman JP, Aron J, Jacobsohn S, Turek P
Inflamm Bowel Dis 2005 Apr;11(4):395-399.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in reproductive age men with Crohn's disease. There is no available data on the effects of infliximab on semen quality. The aim of this study was to determine whether changes in semen quality occurred in men receiving infliximab. METHODS: In this prospective study, each patient served as his own control. Patients completed general health and fertility questionnaires and were assessed for disease activity. Two semen analyses were completed before infusion with infliximab and 1 semen analysis was completed 1 week after infusion. Mean semen parameters before infusion were compared with postinfusion parameters by paired t tests. RESULTS: Ten men completed the study. Seven were on maintenance infliximab (group 1) and 3 were receiving a first dose (group 2). Seven had Crohn's disease, 2 had indeterminate colitis, and 1 had ulcerative colitis. All group 1 patients were in remission. Group 2 patients had moderate or severe disease. In comparing pre- and postinfusion semen parameters in all 10 patients, there was a significant increase in semen volume (P = 0.013) after infusion with infliximab and a trend toward decreased sperm motility (P = 0.061). Group 1 had a significant increase in semen volume after infusion (P = 0.039) and a significant decrease in normal oval forms after infusion (P = 0.038). In comparing group 1 and group 2, there was a significant difference in sperm progression. CONCLUSIONS: Infliximab therapy in men may decrease sperm motility and the number of normal oval forms. Whether these findings translate into impaired fertility is an area for further study.

Rectal complications after modern radiation for prostate cancer: a colorectal surgical challenge.
Larson DW, Chrouser K, Young-Fadok T, Nelson H
J Gastrointest Surg 2005 Apr;9(4):461-6.

The operative management of rectal complications after radiation for prostate cancer has been incompletely studied. Our aim was to determine a logical surgical approach to these severe rectal complications. From an institutional database, we identified 5719 patients who were evaluated between 1990 and 2003 with a history of prostate cancer that was treated with radiation. Fourteen patients were identified from this group who underwent operative intervention for complications stemming from radiation. Charts were retrospectively reviewed for demographics, prostate cancer treatment, rectal symptoms, diagnostic techniques, operative interventions, and outcome. Ten patients (71%) had documented rectourethral fistulas. An additional four patients (29%) had either transfusion-dependent rectal bleeding or intractable fecal incontinence. Using a surgical algorithm, we proceeded with fecal diversion alone (20%), urinary and fecal diversion alone (50%), and primary repair with or without a tissue flap and fecal diversion (29%) in the 14 affected patients. Symptomatic improvement and resolution of these three complications occurred in 12 (85%) of patients. However, only 2 (15%) were able to retain their intestinal continuity to achieve this outcome. The introduction of a step-wise approach to this problem has resulted in symptomatic resolution in the majority of patients. However, this is achieved at the cost of permanent fecal and sometimes urinary diversion.

Alvimopan: An oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction-A 21-day treatment-randomized clinical trial.
Paulson DM, Kennedy DT, Donovick RA, Carpenter RL, Cherubini M, Techner L, Du W, Ma Y, Schmidt WK, Wallin B, Jackson D
J Pain 2005 Mar;6(3):184-92.

Abstract Alvimopan has been shown to reverse the inhibitory effect of opioids on gastrointestinal transit without affecting analgesia. We evaluated oral alvimopan, 0.5 or 1 mg, versus placebo, once daily for 21 days, in 168 patients with opioid-induced bowel dysfunction (OBD) who were receiving chronic opioid therapy (minimum, 1 month) for nonmalignant pain (n = 148) or opioid dependence (n = 20). The primary outcome was the proportion of patients having at least one bowel movement (BM) within 8 hours of study drug on each day during the 21-day treatment period. Averaged over the 21-day treatment period, 54%, 43%, and 29% of patients had a BM within 8 hours after alvimopan 1 mg, 0.5 mg, or placebo, respectively ( P < .001). Secondary outcomes of median times to first BM were 3, 7, and 21 hours after initial doses of 1 mg, 0.5 mg, and placebo, respectively ( P < .001; 1 mg vs placebo). Weekly BMs and overall patient satisfaction were increased after the 1-mg dose ( P < .001 at weeks 1 and 2 vs placebo, and P = .046, respectively). Treatment-emergent adverse events were primarily bowel-related, occurred during the first week of treatment, and were of mild to moderate severity. Alvimopan was generally well tolerated and did not antagonize opioid analgesia. Perspective Patients treated with chronic opioid therapy often experience opioid-induced bowel dysfunction as a result of undesirable effects on peripheral opioid receptors located in the gastrointestinal tract. Alvimopan, a novel peripheral opioid mu-receptor antagonist, has demonstrated significant efficacy for the management of opioid-induced bowel dysfunction without compromise of centrally mediated opioid-induced analgesia.


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