Basic Sciences, Miscellaneus : Coloproctology II

Hyperpigmented rugosity of skin associated with adenocarcinoma of the caecum.
Inamadar AC, Palit A, Yelikar BR
Postgrad Med J 2005 Apr;81(954):271.

Acute liver failure is a rare syndrome with rapid progression and high mortality. It is characterised by the onset of coma and coagulopathy usually within six weeks but can occur up to six months after the onset of illness. Viral hepatitis, idiosyncratic drug induced liver injury, and acetaminophen ingestion are common causes. This report describes the case of a 35 year old man who presented with acute liver failure shortly after binge drinking. Repeated history taking disclosed a gluteal disulfiram implant that the patient had received to treat his alcohol dependence. The patient recovered with maximum supportive care after surgical removal but without liver transplantation. This case illustrates that only meticulous history taking will disclose the sometimes bewildering causes of acute liver failure.

Reappraisal of Surgical Treatment for Radiation Enteritis.
Onodera H, Nagayama S, Mori A, Fujimoto A, Tachibana T, Yonenaga Y
World J Surg 2005 Mar 22;.

Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the standard surgical method is not universally agreed upon. Not only the short-term effect but also the long-term effect after a surgical intervention has been fairly well reported. To reassess the surgical therapy for radiation enteritis, we retrospectively analyzed 48 patients (5 males and 43 females, mean age 58.6 years) who had been operated on in our department. These patients were divided into two types according to the time of surgery or the clinical manifestation, and operative methods were analyzed. Patient's status such as bowel movement, body weight, and serum albumin value after surgery were analyzed, together with the patients survival. Our surgical methods were small intestinal resection for the intestinal obstruction, and pull-through reconstruction for proctitis. Two patients died of multiple organ failure caused by perforated peritonitis irrespective of emergent operation. Although the overall morbidity was 21.7%, there was no leakage when bowels were anastomosed. Overall survival after radiation-related complication in patients without previous neoplastic disease recurrence was 89%, 79%, and 69%, at 1, 3, and 5 years after surgery, respectively. Bowel motility, serum albumin level, and body weight recovered gradually soon after the operation and reached satisfactory levels within 6 months. Our analysis showed that small bowel injury should be treated by generous resection of the affected bowel followed by careful anastomosis of the disease-free ends, while rectal resection is best dealt with by restorative proctectomy. This may provide a good quality of life and minimize major postoperative complications such as leakage.

Neoadjuvant Imatinib in Gastrointestinal Stromal Tumor of the Rectum: Report of a Case.
Lo SS, Papachristou GI, Finkelstein SD, Conroy WP, Schraut WH, Ramanathan RK
Dis Colon Rectum 2005 Mar 24;.

Gastrointestinal stromal tumors are rare tumors of the gastrointestinal tract. Gastrointestinal stromal tumors involving the rectum are uncommon. We describe a case of a 43-year-old female with a gastrointestinal stromal tumor of the rectum who declined abdominoperineal resection. Neoadjuvant treatment with imatinib decreased her tumor size, permitting sphincter-sparing transanal excision. She had no evidence of disease for 24 months postoperatively until she recurred with lung metastases. Microdissection genotyping of the recurrent lesion revealed a deletion in exon 11. Further mutational analysis showed that her metastatic lesion was concordant with her primary rectal lesion, suggesting that systemic micrometastasis was previously present at initial diagnosis. Deletion in exon 11 predicts for response with imatinib treatment and is associated with a longer event-free and overall survival. Current studies are underway that may help us optimize the treatment for patients with gastrointestinl stromal tumors.

Surgical Salvage of Recurrent Rectal Cancer After Transanal Excision.
Weiser MR, Landmann RG, Wong WD, Shia J, Guillem JG, Temple LK, Minsky BD, Cohen AM, Paty PB
Dis Colon Rectum 2005 Mar 24;.

PURPOSE: This study examines surgical salvage of locally recurrent rectal cancer following transanal excision of early tumors. METHODS: Through retrospective review of a colorectal database we identified 50 patients who underwent attempted surgical salvage for local recurrence following initial transanal excision of T1 or T2 rectal cancer. Eight patients had resectable synchronous distant disease. Clinicopathologic variables were associated with extent of surgery required for salvage and outcome. RESULTS: Salvage procedures included abdominoperineal resection (31), low anterior resection (11), total pelvic exenteration (4), and transanal excision (3). One patient had unresectable disease at exploration, requiring diverting ostomy. Of the 49 patients who underwent successful salvage, 27 (55 percent) required an extended pelvic dissection with en bloc resection of one or more of the following structures: pelvic sidewall and autonomic nerves (18); coccyx or portion of sacrum (6); prostate (5); seminal vesicle (5); bladder (4); portion of the vagina (3); ureter (2); ovary (1); and uterus (1). Complete pathologic resection (R0) was accomplished in 47 of 49 patients. Of the eight patients with distant and local recurrence, two underwent synchronous resection and six had delayed metastasectomy. With a median follow-up of 33 months, 29 patients had recurred or died of disease at the time of this analysis. Five-year disease-specific survival was 53 percent. Factors predictive of survival included evidence of any mucosal recurrence on endoscopy, low presalvage carcinoembryonic antigen, and absence of poor pathologic features (lymphovascular and perineural invasion). Patients who required an extended pelvic resection had a worse survival rate. CONCLUSION: Pelvic recurrence following transanal excision of early rectal cancer is often locally advanced, requiring an extended pelvic dissection with en bloc resection of adjacent pelvic organs to achieve salvage. The long-term outcome in patients undergoing resection is less than expected, considering the early stage of their initial disease. When contemplating local excision for early rectal cancer, the risk of local recurrence, the extent and morbidity of surgery required for salvage, and the modest cure rate following salvage should be considered.

Probiotics: an ideal anti-inflammatory treatment for IBS?
Spiller R
Gastroenterology 2005 Mar;128(3):783-5.

Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease.
Oyama Y, Craig RM, Traynor AE, Quigley K, Statkute L, Halverson A, Brush M, Verda L, Kowalska B, Krosnjar N, Kletzel M, Whitington PF, Burt RK

Gastroenterology 2005 Mar;128(3):552-63.
BACKGROUND & AIMS: Crohn's disease (CD) is an immunologically mediated inflammatory disease of the gastrointestinal tract. Due to a high morbidity and/or an increase in mortality in refractory cases, a new treatment approach is needed. In theory, maximum immune ablation by autologous hematopoietic stem cell transplantation (HSCT) can induce a remission. METHODS: We conducted a phase 1 HSCT study in 12 patients with refractory CD. Candidates were younger than 60 years of age with a Crohn's Disease Activity Index (CDAI) of 250-400 despite conventional therapies including infliximab. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and CD34 + enriched. The immune ablative (conditioning) regimen consisted of 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin. RESULTS: The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea, and vomiting. The median days for neutrophil and platelet engraftment were 9.5 (range, 8-11) and 9 (range, 9-18), respectively. The initial median CDAI was 291 (range, 250-358). Symptoms and CDAI improved before hospital discharge, whereas radiographic and colonoscopy findings improved gradually over months to years following HSCT. Eleven of 12 patients entered a sustained remission defined by a CDAI < or =150. After a median follow-up of 18.5 months (range, 7-37 months), only one patient has developed a recurrence of active CD, which occurred 15 months after HSCT. CONCLUSIONS: Autologous HSCT may be performed safely and has a marked salutary effect on CD activity. A randomized study will be needed to confirm the efficacy of this therapy.

Outcome of transvaginal excision of large rectal adenomas: invited comment.
Holscher AH
Int J Colorectal Dis 2005 Apr 5;.

Gonyautoxin: new treatment for healing acute and chronic anal fissures.
Garrido R, Lagos N, Lattes K, Abedrapo M, Bocic G, Cuneo A, Chiong H, Jensen C, Azolas R, Henriquez A, Garcia C
Dis Colon Rectum 2005 Feb;48(2):335-43.
PURPOSE: The mayor symptoms of chronic anal fissure are permanent pain, intense pain during defecation that lasts for hours, blood in the stools, and sphincter cramps. It is subsequent to formation of fibrosis infiltrate that leads to an increased anal tone with poor healing tendency. This vicious circle leads to fissure recurrence and chronicity. This study was designed to show the efficacy of gonyautoxin infiltration in healing patients with anal fissures. METHODS: Gonyautoxin is a paralyzing phytotoxin produced by dinoflagellates. Fifty recruited patients received clinical examination, including proctoscopy and questionnaire to evaluate the symptoms. Anorectal manometries were performed before and after toxin injection. Doses of 100 units of gonyautoxin in a volume of 1 ml were infiltrated into both sides of the anal fissure in the internal anal sphincter. RESULTS: Total remission of acute and chronic anal fissures were achieved within 15 and 28 days respectively. Ninety-eight percent of the patients healed before 28 days with a mean time healing of 17.6 +/- 9 days. Only one relapsed during 14 months of follow-up. Neither fecal incontinence nor other side effects were observed. All patients showed immediate sphincter relaxation. The maximum anal resting pressures recorded after two minutes decreased to 56.2 +/- 12.5 percent of baseline. CONCLUSIONS: Gonyautoxin breaks the vicious circle of pain and spasm that leads to anal fissure. This study proposes gonyautoxin anal sphincter infiltration as safe and effective alternative therapeutic approach to conservative, surgical, and botulinum toxin therapies for anal fissures.

Relationship between surgeon caseload and sphincter preservation in patients with rectal cancer.
Purves H, Pietrobon R, Hervey S, Guller U, Miller W, Ludwig K
Dis Colon Rectum 2005 Feb;48(2):195-204.

PURPOSE: The aim of this study was to determine by means of a national database whether higher surgeon caseload correlates with greater utilization of sphincter-sparing procedures than of abdominoperineal resections in treatment of patients with rectal cancer. METHODS: Patients with a primary International Classification of Diseases-9 diagnosis code of rectal cancer who underwent a sphincter-sparing procedure or abdominoperineal resection were selected from the 1997 Nationwide Inpatient Sample, a database that represents 20 percent of all U.S. community hospital discharges. Multivariable logistic regression models were used on a 20 percent sample of this database to estimate the risk-adjusted relationship between surgeon caseload volume and the odds of receiving a sphincter-sparing procedure. All models were adjusted for age, gender, race, hospital region, and patient comorbidity. RESULTS: The study population (n = 477) was 70.4 percent white and 57.9 percent male with an average age of 67.6 years. The mean Deyo comorbidity score was 7.0. Patients treated by surgeons in the highest-volume category (>/=10 rectal cancer surgeries per year) compared with those treated by surgeons in the lowest-volume category (1-3 rectal cancer surgeries per year) were significantly more likely to undergo a sphincter-sparing procedure, after adjustment for other covariates (odds ratio = 5.05; 95 percent confidence interval, 2.5-10.22). CONCLUSION: This analysis suggests that rectal cancer patients treated by high-volume surgeons are five times more likely to undergo sphincter-sparing procedures than those treated by low-volume surgeon. This has significant implications for those seeking a sphincter-preserving option for the treatment of their rectal cancer.

Manometric Effect of Topical Glyceryl Trinitrate and Its Impact on Chronic Anal Fissure Healing.
Thornton MJ, Kennedy ML, King DW
Dis Colon Rectum 2005 Mar 24;.

INTRODUCTION: The duration of physiologic action of topical glyceryl trinitrate in the management of anal fissure has been the source of some controversy. This study was designed to assess the manometric effect of glyceryl trinitrate on internal sphincter resting tone with continuous monitoring. METHODS: Twenty-seven patients with a chronic anal fissure were assessed with fissure, pain, bleeding, and continence scores. Twenty-two were randomized to 1 cm of topical 0.2 percent glyceryl trinitrate paste, applied to the lower anal canal. Five patients were randomized to 1 cm of water-soluble lubricating jelly to the lower anal canal. Continuous stationary six radial channel water perfusion anorectal manometry was performed for 5 minutes before treatment and then for a further 30 minutes. The 22 glyceryl trinitrate patients were then advised to apply topical 0.2 percent glyceryl trinitrate, three times daily, for eight weeks. Twenty-four hours after completing treatment, all baseline assessments were repeated. The lubricant jelly cohort was discharged from the study after the initial assessment. RESULTS: During the initial manometric assessment, 21 glyceryl trinitrate patients (95 percent) had 20 percent or more reduction in mean and maximum anal resting pressure after treatment. However, there was no statistical difference at 20 minutes compared with 0 minutes (P > 0.1). After eight-week treatment, 16 patients (73 percent) reported symptom resolution and 15 (67 percent) were found to be healed on examination. Clinical healing and resolution of symptoms positively correlated with a higher pretreatment maximum anal resting pressure in the mid anal canal (P < 0.0001), lower fissure score (P < 0.0001), and greater percentage reduction of the maximum resting pressure after application of glyceryl trinitrate (P < 0.001). The mean and maximum anal resting pressure at Week 8 was not significantly different from the baseline values (P > 0.05). During continuous manometry, the anal resting pressure did not significantly change in the patients treated with lubricating jelly. CONCLUSIONS: In those patients with a lower fissure score, a higher mid anal canal anal resting pressure, and a greater resting pressure reduction after glyceryl trinitrate application, a favorable clinical outcome can be expected with glyceryl trinitrate treatment. However, because the physiologic response has resolved in fewer than 20 minutes, the dosing regime should be reassessed.

Management of Anal Canal Cancer.
Sato H, Koh PK, Bartolo DC
Dis Colon Rectum 2005 Mar 24;.

PURPOSE: Chemoradiotherapy has replaced radical surgery as the initial treatment of choice for anal canal cancer. The roles of these therapeutic modalities are discussed and recommendations on management of anal canal cancer are made based on currently available evidence. Areas for further studies also are identified.METHODS: Literature on management of anal canal cancer from January 1970 to July 2003 obtained via MEDLINE was reviewed. Reports on anal margin cancers were excluded.RESULTS: Randomized, prospective, Phase 3 trials in Europe and the United States showed that chemoradiotherapy with 5-fluorouracil and mitomycin C was superior in local control, colostomy-free rate, progression-free survival, and cancer-specific survival compared with radiation alone. In larger tumors, the addition of mitomycin C to radiotherapy and 5-fluorouracil improves local control, colostomy-free, and disease-free survival but is associated with more acute hematologic toxicity. Chemoradiotherapy, including Cisplatin and 5-fluorouracil, appeared to be equal or superior to surgery as salvage therapy in patients with residual disease six weeks after initial nonsurgical treatment.CONCLUSIONS: To improve treatment outcomes and reduce treatment-related toxicities, further studies are required to elucidate the optimal drug combination and doses, optimal radiation field, total dose, and fraction sizes. Randomized, multicenter trials are needed to define the treatment protocol that provides the highest rate of sphincter preservation with acceptable toxicity. Few studies addressed the treatment of metastatic disease, which remains a major cause of mortality.

Probiotic Therapy to Prevent Pouchitis Onset.
Gionchetti P, Rizzello F, Poggioli G, Morselli C, Lammers KM, Campieri M
Dis Colon Rectum 2005 Mar 24;.

Perioperative Topical Nitrate Preserves Sphincter Function in Patients Undergoing Transanal Stapled Anastomosis.
Lee J, Phillips RK
Dis Colon Rectum 2005 Mar 24;.

Prognosis After Anastomotic Leakage in Colorectal Surgery.
Branagan G, Finnis D
Dis Colon Rectum 2005 Feb 23;.

INTRODUCTION: Anastomotic leakage is a major complication of colorectal surgery causing a significant increase in 30-day mortality. The long-term prognosis of anastomotic leakage is poorly documented. This study was designed to assess whether anastomotic leakage affects five-year survival and local recurrence. METHODS: A total of 5,173 patients were recruited to the Wessex Colorectal Cancer Audit during the period September 1991 to August 1995 (prospective data, 5-year follow-up). The effect of anastomotic leakage on five-year survival and local recurrence was analyzed using Kaplan-Meier curves and the log-rank test. RESULTS: A total of 1,834 patients underwent a curative resection with an anastomosis (anastomotic leak = 71; 3.9 percent): 30-day mortality: 18.3 percent in the leak group, and 3.5 percent in the nonleak group (P < 0.001); local recurrence: 19 percent in the leak group, and 9.8 percent in the nonleak group (P = 0.018). A total of 1,201 patients underwent colonic anastomosis (anastomotic leak = 31; 2.6 percent). There was no significant difference in local recurrence or five-year survival between the leak and nonleak groups. A total of 633 patients underwent rectal anastomosis (anastomotic leakage = 40; 6.3 percent): 30-day mortality: 10 percent in the leak group, and 2 percent in the nonleak group (P = 0.014); cumulative five-year estimate of local recurrence: 25.1 (95 percent confidence interval, 9.6-40.5) percent in the leak group, and 10.4 (95 percent confidence interval, 7.7-13) percent in the nonleak group (P = 0.007). Cumulative five-year estimate of overall survival: 52.8 (95 percent confidence interval, 36.1-69.4) percent in the leak group, and 63.9 (95 percent confidence interval, 59.9-67.9) percent in the nonleak group (P = 0.19). CONCLUSIONS: After rectal anastomosis, an anastomotic leak is associated with a significant increase in local recurrence.

Quality of Life, Functional Outcome, and Complications of Coloplasty Pouch After Low Anterior Resection.
Remzi FH, Fazio VW, Gorgun E, Zutshi M, Church JM, Lavery IC, Hull TL
Dis Colon Rectum 2005 Mar 22;.

PURPOSE: The colonic J-pouch has been used to improve bowel function in patients undergoing low colorectal or coloanal anastomosis. However, a narrow pelvis, difficulties in reach, a long anal canal with prominent sphincters, or a fatty mesentery may turn this technique into a technically challenging procedure in certain patients. In these circumstances, "coloplasty" offers an alternative to a straight anastomosis. The purpose of this study was to compare the quality of life, functional outcome, and complications between patients undergoing coloplasty, colonic J-pouch, or straight anastomosis. METHODS: Altogether, 162 patients who underwent coloanal or low colorectal anastomosis between 1998 and 2001 were studied. Data collected included demographics, length of follow-up, technique and type of anastomosis, complications, quality of life, and functional outcome. Results were analyzed according to use of a coloplasty (n = 69), colonic J-pouch (n = 43), or straight anastomosis (n = 50). The choice of the technique was based on the surgeon's preference. Usually coloplasty or straight anastomosis was favored in male patients with a narrow pelvis or when a handsewn anastomosis was used. RESULTS: Quality of life assessment with the short form-36 questionnaire revealed better scores in coloplasty and colonic J-pouch groups. The coloplasty (1.0 +/- 1.7) and colonic J-pouch (1.0 +/- 1.2) groups had fewer night bowel movements than the straight anastomosis group (1.5 +/- 2.0) (P < 0.05). The coloplasty group also had fewer bowel movements per day than the straight anastomosis group (3.8 +/- 2.9 vs. 4.8 +/- 3.6; P < 0.05); also, less clustering and less antidiarrheal medication use were observed than in the straight anastomosis group. Colonic J-pouch patients with handsewn anastomosis had a higher anastomotic leak rate (44 percent) than the patients in the coloplasty with hand-sewn anastomosis group (3.6 percent). CONCLUSIONS: Coloplasty seems to be a safe, effective technique for improving the outcome of low colorectal or coloanal anastomosis. It is especially applicable when a colonic J-pouch anastomosis is technically difficult.

Controlled Lateral Sphincterotomy for Chronic Anal Fissure.
Cho DY
Dis Colon Rectum 2005 Mar 22;.

PURPOSE: This study assessed the usefulness of "controlled" lateral sphincterotomy for chronic anal fissures. METHODS: Of 225 patients with chronic anal fissure, 110 underwent traditional sphincterotomy to the level of the dentate line, and 115 underwent controlled sphincterotomy in three steps according to the degree of anal stenosis. In Step 1, the internal sphincter was divided to the proximal level of the fissure. If the anal canal was still stenosed, the division was extended to the level of the dentate line in Step 2. Step 3 was a bilateral internal sphincterotomy. The anal stenosis was evaluated under anesthesia using a new conical calibrator scaled in 1-mm diameter increments. Forty adults without anorectal disease were examined as controls. In a telephone follow-up, 102 patients in the traditional sphincterotomy group and 106 patients in the controlled sphincterotomy group responded. RESULTS: The normal group measured 34.6 +/- 1.4 mm (mean +/- standard deviation). Confounding effects of age, gender, body weight, and height were not significant. Based on the anal caliber measured in the normal group, anal stenosis is present with values of 31 mm and below (mean - 2SD of the control value). Of 115 patients in the controlled sphincterotomy group, 90 (78 percent) underwent sphincterotomy below the level of the dentate line, 18 (16 percent) underwent sphincterotomy to the level of the dentate line, and 7 (6 percent) underwent bilateral sphincterotomy. None had incontinence of feces or leakage of stool. Ten of 102 patients (10 percent) in the traditional sphincterotomy group and 2 of 106 patients (2 percent) in the controlled sphincterotomy group complained of minor incontinence, such as gas incontinence, minor staining, or urgency (P = 0.017). There was one recurrence in the traditional sphincterotomy group. CONCLUSION: Controlled lateral sphincterotomy could be a way of overcoming the risk of incontinence with lateral internal sphincterotomy for chronic anal fissure.

Hartmann's Colectomy and Reversal in Diverticulitis: A Population-Level Assessment.
Salem L, Anaya DA, Roberts KE, Flum DR
Dis Colon Rectum 2005 Mar 22;.

PURPOSE: This study was designed to assess the costs and outcomes of colostomy and colostomy reversal in patients with diverticulitis and examine the impact of such procedures on the health care system. METHODS: We employed a retrospective design and used a Washington State administrative database to identify patients undergoing operations with colostomy (1987-2002) who were followed over time. Descriptive and comparative analysis was performed, focusing on patients with diverticulitis. RESULTS: There were 16,556 patients who underwent colostomy and 5,420 (32.7 percent) were for diverticulitis and its related complications (mean age, 64.8 +/- 15.1 years; 53.2 percent female). In patients with diverticulitis, the rate of colostomy reversal was 56.3 percent (80 percent in patients less than 50 years, and 30 percent in patients over 77 years). The in-hospital mortality rate after colostomy reversal was 0.36 percent, and was 2.6 percent in those over 77 years of age. After colostomy reversal a second stoma was used in 3.4 percent, reoperation was required for bleeding complications in 0.6 percent, and infectious complications were noted in 2 percent. The length of time from colostomy to its reversal was approximately five months (138.1 +/- 164 days; interquartile range, 72-156). The relationship between the length of time from colostomy to reversal was evaluated and the adjusted odds of a second stoma being used at the time of colostomy reversal were 45 percent higher (odds ratio, 1.45; 95 percent confidence interval, 1.22, 1.73) for each increase in time interval (<3, 6-9, 9-12, >12 months). CONCLUSIONS: One-third of all colostomies were related to diverticulitis and only 56 percent were reversed. We identified a higher than expected mortality rate among older patients undergoing colostomy reversal. The impact of colostomy and reversal operations on both patients and the health care system is significant.

Efficacy of Topical Metronidazole (10 Percent) in the Treatment of Anorectal Crohn's Disease.
Stringer EE, Nicholson TJ, Armstrong D
Dis Colon Rectum 2005 Mar 22;.

PURPOSE: The aim of this study was to investigate the efficacy of 10 percent topical metronidazole in the treatment of symptomatic anorectal Crohn's disease. METHODS: Patients with symptomatic anorectal Crohn's disease were studied in a prospective, nonblinded, nonrandomized study to evaluate the efficacy of topical 10 percent metronidazole. Perianal Crohn's Disease Activity Index and each component (pain, discharge, induration, sexual dysfunction, and type of pathology) were recorded before treatment and at four weeks. Visual analog pain score (0-10) was recorded before treatment and at weekly intervals for up to four weeks. RESULTS: Fourteen patients were studied prospectively for four weeks. Mean Perianal Crohn's Disease Activity Index decreased from 8.8 +/- 0.9 before treatment to 4.1 +/- 0.7 after four weeks' treatment (P < 0.0001). Visual analog pain scores decreased from 5.4 +/- 0.7 before treatment to 2.4 +/- 0.5 at one week (P < 0.001) and to 1.0 +/- 0.4 after four weeks' treatment (P < 0.0001). Of the Perianal Crohn's Disease Activity Index components, significant decreases were noted in pain and discharge (P < 0.0001) and induration (P < 0.001). CONCLUSION: For patients with perianal Crohn's disease, topical 10 percent metronidazole decreases the Perianal Crohn's Disease Activity Index and anorectal pain.

A Scoring System for the Strength of a Family History of Colorectal Cancer.
Church JM
Dis Colon Rectum 2005 Mar 22;.

BACKGROUND: Family history of colorectal cancer is associated with an increased risk for the disease, although there are many combinations of family history that are hard to correlate with risk status. A scoring system for family history of colorectal cancer was designed to make risk more readily quantifiable. METHODS: A colonoscopy database was used to test the following points system: each first-degree relative with colorectal cancer = 3 points; each second-degree relative with colorectal cancer = 1 point. Families with one or more first-degree relative affected under 50 years of age = an extra 3 points. Families with one or more second-degree relative affected under 50 years of age = an extra 1 point. Families with multiple relatives on the same side of the family = an extra 3 points (first-degree relatives), 1 point (second-degree relatives), or 2 points (first-degree and second-degree relatives). Points were added and categories defined as follows: low risk, 1 to 4 points; medium risk, 5 to 7 points; high risk, 8 to 10 points; very high risk, >10 points. A control group of average-risk patients having screening colonoscopy was used. Categories were compared in number of adenomas, hyperplastic polyps, and cancers. RESULTS: The records of 992 patients were used to test the system. Mean adenomas per patient per group were 0.4 for controls, 1.0 for low risk, 1.0 for medium risk, 1.7 for high risk, and 1.7 for very high risk. Cancers per group were 2 of 196 for controls, 8 of 513 for low risk, 3 of 171 for medium risk, 3 of 84 for high risk, and 1 of 28 for very high risk. The score categories were combined to produce revised risk levels of low (score 1 to 7) and high (>7). Average adenomas per patient in the revised categories were 0.4 (control), 1.0 (low risk), and 1.7 (high risk). The odds ratio of having one to two adenomas was 1.73 (1.19-2.50, 95% confidence limits) in the low-risk group and 2.39 (1.41-4.01) in the high-risk group. Odds ratios for having three or more adenomas were 5.70 (2.44-13.32) in the low-risk group and 10.35 (3.97-26.97) in the high-risk group. CONCLUSION: In the two-category system proposed here of quantifying familial risk of colorectal cancer, patients having less than 8 points were at low risk and those with 8 or more were at high risk. Surveillance and chemoprevention protocols can be designed through use of these risk categories. A scoring system for family history of colorectal cancer can make risk assessment easier and facilitate both collaborative studies and patient triage into appropriate screening programs.

Local Injection of Infliximab for the Treatment of Perianal Crohn's Disease.
Poggioli G, Laureti S, Pierangeli F, Rizzello F, Ugolini F, Gionchetti P, Campieri M
Dis Colon Rectum 2005 Mar 10;.

PURPOSE: Perianal disease is a serious complication of Crohn's disease and its surgical management is still controversial. It has been suggested that the local injection of infliximab has resulted in some potential benefit. This pilot study analyzed the feasibility and safety of such therapy in selected patients with severe perianal Crohn's disease. METHODS: The study included 15 patients with complex perianal Crohn's disease in which sepsis was not controllable using surgical and medical therapy. Among them, four had previously undergone intravenous infusion of infliximab with no significant response, nine had contraindications for intravenous infusion, and two had associated stenosing ileitis and severe coloproctitis. The injection of 15 to 21 mg of infliximab, associated with surgical treatment, was performed at the internal and external orifices and along the fistula tract. Efficacy was measured by a complete morphologic evaluation using a personal score. RESULTS: No major adverse effects were reported. Ten of 15 patients healed after 3 to 12 infusions. CONCLUSIONS: Local injection of infliximab adjacent to the fistula tract of perianal Crohn's disease is safe and may help in fistula healing. A controlled, randomized trial is required to prove the value.

Gynecologic cancer as a "sentinel cancer" for women with hereditary nonpolyposis colorectal cancer syndrome.
Lu KH, Dinh M, Kohlmann W, Watson P, Green J, Syngal S, Bandipalliam P, Chen LM, Allen B, Conrad P, Terdiman J, Sun C, Daniels M, Burke T, Gershenson DM, Lynch H, Lynch P, Broaddus RR
Obstet Gynecol 2005 Mar;105(3):569-74.

OBJECTIVE: Women with hereditary nonpolyposis colorectal cancer syndrome have a 40-60% lifetime risk for colon cancer, a 40-60% lifetime risk for endometrial cancer, and a 12% lifetime risk for ovarian cancer. A number of women with hereditary nonpolyposis colorectal cancer syndrome will have more than one cancer in their lifetime. The purpose of this study was to estimate whether women with hereditary nonpolyposis colorectal cancer syndrome who develop 2 primary cancers present with gynecologic or colon cancer as their "sentinel cancer."METHODS: Women whose families fulfilled Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome and who developed 2 primary colorectal/gynecologic cancers in their lifetime were identified from 5 large hereditary nonpolyposis colorectal cancer syndrome registries. Information on age at cancer diagnoses and which cancer (colon cancer or endometrial cancer/ovarian cancer) developed first was obtained. RESULTS: A total of 117 women with dual primary cancers from 223 Amsterdam families were identified. In 16 women, colon cancer and endometrial cancer/ovarian cancer were diagnosed simultaneously. Of the remaining 101 women, 52 (51%) women had an endometrial or ovarian cancer diagnosed first. Forty-nine (49%) women had a colon cancer diagnosed first. For women who developed endometrial cancer/ovarian cancer first, mean age at diagnosis of endometrial cancer/ovarian cancer was 44. For women who developed colon cancer first, the mean age at diagnosis of colon cancer was 40. CONCLUSION: In this large series of women with hereditary nonpolyposis colorectal cancer syndrome who developed 2 primary colorectal/gynecologic cancers, endometrial cancer/ovarian cancer was the "sentinel cancer," preceding the development of colon cancer, in half of the cases. Therefore, gynecologists and gynecologic oncologists play a pivotal role in the identification of women with hereditary nonpolyposis colorectal cancer syndrome. LEVEL OF EVIDENCE: II-3.

Rhabdomyolysis associated with Crohn's disease, probably mediated by myositis.
Matsuda T, Inoue S, Furuya H
Anesth Analg 2005 Mar;100(3):898.

Prognostic scoring in colorectal cancer liver metastases: development and validation.
Schindl M, Wigmore SJ, Currie EJ, Laengle F, Garden OJ
Arch Surg 2005 Feb;140(2):183-9.

HYPOTHESIS: A prognostic scoring system for colorectal cancer liver metastases that is derived from unselected patients referred for hepatic resection would improve the applicability and increase the accuracy of prognostication. DESIGN: Retrospective analysis of prospectively documented data; validation against an unrelated cohort from another institution. The median follow-up was 16.4 months (95% confidence interval, 15.0-17.8 months) (original cohort). SETTING: Two tertiary referral centers at unrelated university hospitals. PATIENTS: Independent prognosticators of survival were derived from 337 patients with colorectal cancer liver metastases referred for consideration of liver resection, and prognostic scores were calculated in 269 patients (79.8%) (original cohort). Calculation of prognostic scores was also applied to 193 patients referred and treated in an unrelated institution (validation cohort). MAIN OUTCOME MEASURES: Kaplan-Meier survival curve analysis (log-rank test) between different prognostic groups in the original and the validation cohorts. RESULTS: Independent prognosticators of survival were Dukes stage, number of metastases, and serum concentrations of carcinoembryonic antigen, alkaline phosphatase, and albumin. Significant differences were found in cumulative overall survival between patients assigned to good, moderate, and poor prognoses in the original and validation cohorts (P<.05). Liver resection improved survival in all prognostic groups. However, no patient with poor prognosis and only 19.7% (13 of 66) of patients with moderate prognosis survived 5 years, compared with 62.5% (10 of 16) of patients with good prognosis (P<.001). CONCLUSIONS: This prognostic scoring system is derived from and can be applied to patients with colorectal cancer liver metastases at the time of referral for consideration of surgery. Patients with poor prognosis have no long-term benefit from curative liver resection and should therefore be considered for combined multimodal treatment.

Extracolonic manifestations of familial adenomatous polyposis after proctocolectomy.
Tulchinsky H, Keidar A, Strul H, Goldman G, Klausner JM, Rabau M
Arch Surg 2005 Feb;140(2):159-63; discussion 164.

HYPOTHESIS: Extracolonic manifestations have a major effect on the morbidity and mortality of patients with familial adenomatous polyposis following proctocolectomy. DESIGN: Case review study. SETTING: Colorectal unit, university-affiliated hospital. PATIENTS: Fifty patients (25 males and 25 females) with familial adenomatous polyposis WHO underwent proctocolectomy between January 1988 and October 2003. INTERVENTIONS: Ileal pouch-anal anastomosis (n = 41), Kock pouch (n = 1), end ileostomy (n = 6). Two patients underwent total colectomy with an ileorectal anastomosis. MAIN OUTCOME MEASURES: Clinical follow-up and telephone interview; contact with clinicians following up patients elsewhere. RESULTS: The patients' median age at surgery was 33 years. The mean length of follow-up was 74 months. Four patients were lost to follow-up. Extracolonic manifestations were diagnosed in 38 patients (76%). Twelve patients had 14 desmoid tumors: 7 were treated surgically and 7 medically (these patients received celecoxib and tamoxifen citrate therapy). Of the 41 patients who underwent upper gastrointestinal tract endoscopy, 11 developed duodenal and/or ampullary adenomas. Three patients had endoscopic polypectomy and 1 underwent a Whipple operation. Among the 29 patients who underwent pouchoscopy, 5 had pouch adenomas and 3 had adenomas that were found in the rectal stump. Two patients died--one of a huge mesenteric desmoid tumor and the other of an aggressive mesenteric malignant fibrous histiocytoma. CONCLUSIONS: Long-term morbidity and mortality were strongly related to the development of mesenteric tumors and ampullary-duodenal polyps. Early detection of desmoid tumors, duodenal, pouch, and rectal cuff adenomas by periodic computed tomography, gastroduodenoscopy, and pouchoscopy, respectively, may allow control by medical therapy, endoscopy, or limited surgical procedures. In most patients control of desmoid tumors was achieved using a combination of celecoxib and tamoxifen citrate therapy.

Epigenetics, mismatch repair genes and colorectal cancer.
Wheeler JM
Ann R Coll Surg Engl 2005 Jan;87(1):15-20.

The recent discovery of hypermethylation of the promoter of genes is a powerful epigenetic mechanism for the inactivation of tumour suppressor genes in colorectal and other cancers. Approximately 95% of hereditary non-polyposis colorectal cancers (HNPCCs) and 15% of sporadic colorectal cancers (CRCs) are replication error positive (RER(+)). Although DNA mutations are found in mismatch repair genes in the majority of HNPCC CRC, mutations are rare in sporadic RER(+) CRCs. We have shown that the principal cause of an RER(+) phenotype is hypermethylation of the promoter of hMLH1, resulting in the absence of hMLH1 protein. In contrast to sporadic RER(+) CRCs, we found that hypermethylation of hMLH1 does not occur in HNPCC CRC, suggesting the possibility of further differences between the two types of RER(+) tumours in the adenoma to carcinoma pathway. Other known tumour suppressor genes with few or no mutations may be candidates for epigenetic changes. One such gene is E-cadherin, and we described the first mutations of this gene in CRCs. Half of all CRCs were found to be hypermethylated in the Ecadherin promoter and this correlated with reduced E-cadherin expression. Epigenetic changes occur in CRCs and arise in different frequencies in separate genes. Hypermethylation of the promoter may be reversed and gene function restored to a cell, thus partially undoing the cancer phenotype.

Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal rule.
Rullier E, Laurent C, Bretagnol F, Rullier A, Vendrely V, Zerbib F
Ann Surg 2005 Mar;241(3):465-9.

OBJECTIVE: To assess oncologic outcome of patients treated by conservative radical surgery for tumors below 5 cm from the anal verge. SUMMARY BACKGROUND DATA: Standard surgical treatment of low rectal cancer below 5 cm from the anal verge is abdominoperineal resection. METHODS: From 1990 to 2003, patients with a nonfixed rectal carcinoma at 4.5 cm or less from the anal verge and without external sphincter infiltration underwent conservative surgery. Surgery included total mesorectal excision with intersphincteric resection, that is, removal of the internal sphincter, to achieve adequate distal margin. Patients with T3 disease or internal sphincter infiltration received preoperative radiotherapy. RESULTS: Ninety-two patients with a tumor at 3 (range 1.5-4.5) cm from the anal verge underwent conservative surgery. There was no mortality and morbidity was 27%. The rate of complete microscopic resection (R0) was 89%, with 98% negative distal margin and 89% negative circumferential margin. In 58 patients with a follow-up of more than 24 months, the rate of local recurrence was 2% and the 5-year overall and disease-free survival were 81% and 70%, respectively. CONCLUSIONS: The technique of intersphincteric resection permits us to achieve conservative surgery in patients with a tumor close to or in the anal canal without compromising local control and survival. Tumor distance from the anal verge is no longer a limit for sphincter-saving resection.

Patient perceptions of stool-based DNA testing for colorectal cancer screening.
Schroy PC 3rd, Heeren TC
Am J Prev Med 2005 Feb;28(2):208-14.

PURPOSE: Stool-based DNA (SB-DNA) testing is an emerging colorectal cancer screening strategy that offers a convenient, noninvasive, and potentially more acceptable alternative to existing screening tests. The objectives of this study were to compare patient perceptions of SB-DNA testing, fecal occult blood testing (FOBT), and colonoscopy, and elicit screening preferences. METHODS: A prospective survey was conducted between August 2001 and March 2003 of asymptomatic, mostly average-risk subjects aged >/=50 years who were participating in a multicenter comparison of SB-DNA testing and FOBT for detecting colorectal neoplasia. Subjects completed a 25-item questionnaire within 48 hours after undergoing a colonoscopy, which served as the standard. Respondents were asked to rate each of the three screening tests on various prep- and test-related features, using a five-point ordinal scale or yes/no format, and to select a preferred strategy. RESULTS: A total of 4042 subjects completed the survey (84% response rate). SB-DNA testing received the same or higher mean ratings than FOBT for most prep- and test-related features. When compared with colonoscopy, SB-DNA testing received higher ratings for all prep- and test-related features except perceived accuracy, where colonoscopy was rated higher. Overall, a higher percentage of patients preferred SB-DNA testing (45%) to both FOBT (32%) and colonoscopy (15%) for routine screening (p <0.001); 8% had no preference. CONCLUSIONS: Patients willing to undergo colonoscopy, SB-DNA testing, and FOBT perceive SB-DNA testing to have a number of advantages over the other two tests. Moreover, many such patients prefer SB-DNA testing to FOBT and colonoscopy for routine screening.

Antibacterial and antimycobacterial treatment for inflammatory bowel disease.
Ohkusa T, Sato N
J Gastroenterol Hepatol 2005 Mar;20(3):340-51.

Abstract A variety of medicines have been used for the treatment of inflammatory bowel disease. Antibacterial therapy has demonstrated promise by both improving symptoms and causing disease remission. The mechanism is unknown, but may be related to either eliminating a key pathogen, decreasing the number of bacterial secretory products or defective particles, a direct immunomodulating effect, or reducing secondary bacterial invasion. Historically, a large number of bacterial species have been suspected as being major contributors to the etiology of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. Many trials of antibacterial agents have been carried out in inflammatory bowel disease. Recently, treatments have focused on Gram-negative anaerobes and mycobacteria. The present paper briefly reviews antimicrobial and antimycobacterial treatments in inflammatory bowel disease.

Predicting relapse in patients with inflammatory bowel disease: what is the role of biomarkers?
Pardi DS, Sandborn WJ
Gut 2005 Mar;54(3):321-2.

Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease.
Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, Ricchiuti A, Marchi S, Bottai M
Gut 2005 Mar;54(3):364-8.

BACKGROUND AND AIMS: The clinical course of inflammatory bowel disease is characterised by a succession of relapses and remissions. The aim of our study was to assess whether the predictive value of faecal calprotectin-a non-invasive marker of intestinal inflammation-for clinical relapse is different in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Seventy nine consecutive patients with a diagnosis of clinically quiescent inflammatory bowel disease (38 CD and 41 UC) were followed for 12 months, undergoing regular clinical evaluations and blood tests. A single stool sample was collected at the beginning of the study from each patient and the calprotectin concentration was assessed by a commercially available enzyme linked immunoassay. RESULTS: In CD, median calprotectin values were 220.1 mug/g (95% confidence interval (CI) 21.7-418.5) in those patients who relapsed during follow up, and 220.5 mug/g (95% CI 53-388) in non-relapsing patients (p=0.395). In UC, median calprotectin values were 220.6 mug/g (95% CI 86-355.2) and 67 microg/g (95% CI 15-119) in relapsing and non-relapsing patients, respectively (p<0.0001). The multivariate Cox (proportional hazard) regression model, after adjustment for possible confounding variables, showed a twofold and 14-fold increase in the relapse risk, respectively, in those patients with CD and UC in clinical remission who had a faecal calprotectin concentration higher than 150 microg/g. CONCLUSIONS: Faecal calprotectin proved to be an even stronger predictor of clinical relapse in UC than in CD, which makes the test a promising non-invasive tool for monitoring and optimising therapy.

Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study.
Baron S, Turck D, Leplat C, Merle V, Gower-Rousseau C, Marti R, Yzet T, Lerebours E, Dupas JL, Debeugny S, Salomez JL, Cortot A, Colombel JF

Gut 2005 Mar;54(3):357-63.
BACKGROUND: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease. OBJECTIVE: To examine environmental risk factors prior to the development of inflammatory bowel disease in a paediatric population based case control study. METHODS: A total of 222 incident cases of Crohn's disease and 60 incident cases of ulcerative colitis occurring before 17 years of age between January 1988 and December 1997 were matched with one control subject by sex, age, and geographical location. We recorded 140 study variables in a questionnaire that covered familial history of inflammatory bowel disease, events during the perinatal period, infant and child diet, vaccinations and childhood diseases, household amenities, and the family's socioeconomic status. RESULTS: In a multivariate model, familial history of inflammatory bowel disease (odds ratio (OR) 4.3 (95% confidence interval 2.3-8)), breast feeding (OR 2.1 (1.3-3.4)), bacille Calmette-Guerin vaccination (OR 3.6 (1.1-11.9)), and history of eczema (OR 2.1 (1-4.5)) were significant risk factors for Crohn's disease whereas regular drinking of tap water was a protective factor (OR 0.56 (0.3-1)). Familial history of inflammatory bowel disease (OR 12.5 (2.2-71.4)), disease during pregnancy (OR 8.9 (1.5-52)), and bedroom sharing (OR 7.1 (1.9-27.4)) were risk factors for ulcerative colitis whereas appendicectomy was a protective factor (OR 0.06 (0.01-0.36)). CONCLUSIONS: While family history and appendicectomy are known risk factors, changes in risk based on domestic promiscuity, certain vaccinations, and dietary factors may provide new aetiological clues.

A steroid-refractory ulcerative colitis revealing Epstein-Barr virus/cytomegalovirus-positive colonic lymphoma.
Daniel F, Damotte D, Moindrot H, Molina T, Berger A, Cellier C
Int J Colorectal Dis 2005 Mar 4;.

Colon Polyps and Cancer.
Bond JH
Endoscopy 2005 Mar;37(3):208-212.

The role of endoscopy, in particular colonoscopy, clearly is paramount in the screening, diagnosis, and prevention of colorectal cancer. In preparation for writing this "state-of-the-art" review on colon polyps and cancer, a PubMed literature search linking the topic with endoscopy yielded an enormous number of papers published in peer-reviewed journals just in the past 12 months. I have selected a few of these to highlight that I believe are most germane to current issues of risk stratification, screening and surveillance, prevention, and the premalignant potential of different types of adenomas detected by endoscopy. Several of these papers address the advantages and limitations of direct colonoscopy screening for colorectal neoplasia, and discuss the emerging role of virtual colonoscopy screening.

Cervical emphysema, pneumomediastinum, and retropneumoperitoneum following sigmoidoscopy and rectal biopsy.
El Shallaly G, Raimes S
Int J Colorectal Dis 2005 Mar 2;.

Mesalazine-induced myopericarditis in a patient with ulcerative colitis.
Doganay L, Akinci B, Pekel N, Simsek I, Akpinar H
Int J Colorectal Dis 2005 Feb 22;.

Villous adenoma in a perforated colonic diverticulum.
Barr YR, Brazowski E, Leider-Trejo L
Int J Colorectal Dis 2005 Feb 10;.

Systemic lidocaine and mexiletine for the treatment of a patient with total ulcerative colitis.
Yokoyama Y, Onishi S
Gut 2005 Mar;54(3):441.

The toll-like receptor 4 (TLR4) Asp299Gly polymorphism is associated with colonic localisation of Crohn's disease without a major role for the Saccharomyces cerevisiae mannan-LBP-CD14-TLR4 pathway.
Ouburg S, Mallant-Hent R, Crusius JB, van Bodegraven AA, Mulder CJ, Linskens R, Pena AS, Morre SA
Gut 2005 Mar;54(3):439-40.

Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid.
Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, Laurberg S, Laiho P, Aaltonen LA, Orntoft TF
Gut 2005 Mar;54(3):374-84.

Critical issues in the identification and management of patients with hereditary non-polyposis colorectal cancer.
Lackner C, Hoefler G
Eur J Gastroenterol Hepatol 2005 Mar;17(3):317-22.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.
Lomer MC, Grainger SL, Ede R, Catterall AP, Greenfield SM, Cowan RE, Vicary FR, Jenkins AP, Fidler H, Harvey RS, Ellis R, McNair A, Ainley CC, Thompson RP, Powell JJ
Eur J Gastroenterol Hepatol 2005 Mar;17(3):377-384.

Systematic approach to the analysis of cross-sectional imaging for surveillance of recurrent colorectal cancer.
Faria SC, Tamm EP, Varavithya V, Phongkitkarun S, Kaur H, Szklaruk J, Dubrow R, Charnsangavej C
Eur J Radiol 2005 Mar;53(3):387-96.

Recurrent disease in colorectal cancer occurs in approximately 50% of patients who undergo a "curative" operation. Tumor recurrence may occur locally (at the anastomotic site), in the mesentery or mesocolon adjacent to the post-operative site, in the nodal echelon downstream to the post-operative site, and as distant metastases to the peritoneal cavity, liver or lung. Local recurrence at the anastomosis is frequently diagnosed at follow-up endoscopic examinations as part of screening for metachronous lesions. Other types of recurrences require imaging studies, most frequently CT or MR imaging to diagnose. We developed an approach to analyze imaging obtained after curative resection of colorectal cancer. Our approach is based on the knowledge of patterns of disease spread, of types of surgical procedures and of pathologic staging. Using this approach has the potential to detect recurrent disease at an early stage because the locoregional and nodal spread of this disease is predictable. Early diagnosis of recurrent disease, even in asymptomatic cases, allows for more effective treatment that can improve the long-term survival of these patients.

Validity of Pelvic Autonomic Nerve Stimulation With Intraoperative Monitoring of Bladder Function Following Total Mesorectal Excision for Rectal Cancer.
Kneist W, Junginger T
Dis Colon Rectum 2005 Feb 15;.

PURPOSE: This prospective study was designed to clarify whether the results of the intraoperative stimulation of parasympathetic pelvic nerves performed in 31 patients after mesorectal excision for rectal carcinoma allowed predictions in terms of the postoperative bladder function of the patients. METHODS: After monopolar stimulation of the splanchnic pelvic nerves using a constant voltage stimulator (Screener 3625(R)), intravesical pressure increase was measured manometrically. The results were related to the postoperative residual urine volume, requirement of recatheterization and long-term catheterization, just as to the results of the validated International Prostatic Symptom Scores and the Quality of Life Index caused by urinary symptoms. The median follow-up period was nine (range, 2-14) months. RESULTS: Parasympathetic nerve stimulation was performed at 61 sites and results in intravesical pressure increase up to 6 cm water column in median. In 11 patients (33.3 percent), a negative test result was achieved: 5 with unilateral and 6 with bilateral pressure increases of </= 2 cm water column. Recatheterization was necessary in four patients, and all of them showed negative neuromonitoring results. Two of these patients were discharged with an in situ urinary bladder catheter. Postoperative increased residual urine volumes (>/=100 ml) resulted more frequently in the group with negative test results (63.6 vs. 21.1 percent; P = 0.047), and the International Prostatic Symptom Score and Quality of Life Index showed the worst results (9.9 +/- 6.7 vs. 3 +/- 4.9, P = 0.021; 2.4 +/- 1.7 vs. 0.7 +/- 1.3, P = 0.021). CONCLUSIONS: Intraoperative neurostimulation and manometric measurement of bladder pressure may contribute to the identification of parasympathetic pelvic nerves during total mesorectal excision. This method is suitable for intraoperative recording of nerve preservation and therefore associated with postoperative bladder function.

The Influence of Specific Luminal Factors on the Colonic Epithelium: High-Dose Butyrate and Physical Changes Suppress Early Carcinogenic Events in Rats.
Wong CS, Sengupta S, Tjandra JJ, Gibson PR
Dis Colon Rectum 2005 Feb 10;.

Extent of Lateral Internal Sphincterotomy: Up to the Dentate Line or Up to the Fissure Apex?
Mentes BB, Ege B, Leventoglu S, Oguz M, Karadag A
Dis Colon Rectum 2005 Feb 10;.

PURPOSE: The aim of this randomized, prospective study was to compare the results of lateral internal sphincterotomy up to the dentate line or up to the fissure apex in the treatment of chronic anal fissure. METHODS: Adult patients with chronic anal fissure were randomly assigned to undergo lateral internal sphincterotomy to the level of the dentate line or to the level of the fissure apex. The patients were reexamined on postoperative Days 1, 7, 14, 28, and then at 2 and 12 months. RESULTS: The time required for relief of pain postoperatively was 2.08 +/- 1.44 days in the dentate line group, which was significantly shorter than that for the fissure apex group (4.72 +/- 4.86 days; P = 0.002). Objective healing was achieved in 23.7 percent and 17.6 percent at 14 days, 97.4 percent and 88.2 percent at 28 days, and 100 percent and 97.7 percent at 2 months in the dentate line and fissure apex groups, respectively (P > 0.05 for all comparisons). Only sphincterotomy up to the dentate line caused a significant change in anal incontinence (P = 0.016). Both groups had significantly lower anal resting pressures at 4 months postoperatively, compared with their corresponding preoperative levels (P = 0.005 and P = 0.007). The postoperative resting pressures did not differ significantly between the two groups (P = 0.273). By 12 months postoperatively, no treatment failures or recurrences were noted in the dentate line group (100 percent healing rate). In the fissure apex group, there was one nonhealing case and four recurrences, resulting in a 13.2 percent rate of treatment failure (P = 0.058). CONCLUSIONS: Sphincterotomy up to the dentate line provided a faster and definitive healing within the time limits of this study, but it was associated with a significant alteration in anal continence. In turn, sphincterotomy up to the fissure apex was free of significant disturbance of continence, but its healing effect was slower and it was prone to an insignificantly higher rate of treatment failure.

Outcome of Anterior Resection for Stage II Rectal Cancer Without Radiation: The Role of Adjuvant Chemotherapy.
Law WL, Ho JW, Chan R, Au G, Chu KW
Dis Colon Rectum 2005 Feb 10;.

BACKGROUND: This study aimed to evaluate the oncological outcome of patients who had Stage II rectal cancer and underwent curative nonsphincter-ablation surgery without adjuvant radiation. PATIENTS AND METHODS: During the study period from August 1993 to December 2002, 224 patients (141 men) with Stage II cancer underwent curative anterior resection or Hartmann's procedure without adjuvant radiation. Data were collected prospectively. The oncologic outcomes of these patients were studied and the risk factors for recurrence and survival were analyzed. RESULTS: The median age of the patients was 69 (range, 27-89) years and the median level of the tumor from the anal verge was 8 (range, 3-20) cm. Four patients (1.8 percent) died in the postoperative period and postoperative complications occurred in 74 patients (33 percent). The median follow-up time of the surviving patients was 43.6 months. The actuarial five-year recurrence rate was 25.4 percent, whereas the five-year actuarial local and systemic recurrence rates were 6.1 percent and 20 percent, respectively. On multivariate analysis, independent factors associated with a higher recurrence rate included lymphovascular invasion, perineural invasion, and absence of chemotherapy. The overall and cancer-specific survival rates of the patients were 71.1 percent and 81.1 percent, respectively. On multivariate analysis, only adjuvant chemotherapy (<ITALIC>P</ITALIC> = 0.024; hazard ratio = 6.04; 95 percent confidence interval, 1.27-28.74) and the absence of lymphovascular invasion (P = 0.002; hazard ratio = 3.77; 95 percent confidence interval, 1.63-8.77) were independent factors associated with significantly better cancer-specific survival. CONCLUSION: A low local recurrence rate can be achieved in patients with Stage II rectal cancer treated with nonsphincter-ablation surgery without adjuvant radiation. Postoperative chemotherapy is associated with a lower recurrence rate and higher survival rates. Further study is warranted to define the role of adjuvant chemotherapy in patients with rectal cancer.

Denervation of the Neorectum as a Potential Cause of Defecatory Disorder Following Low Anterior Resection for Rectal Cancer.
Koda K, Saito N, Seike K, Shimizu K, Kosugi C, Miyazaki M
Dis Colon Rectum 2005 Feb 10;.

PURPOSE: The aim of this study was to determine whether denervation of the sigmoid colon during low anterior resection contributes to the postoperative motility characteristics of the neorectum and to the defecatory function of patients. METHODS: Sixty-seven patients who underwent either low or ultralow anterior resection for rectal cancer were evaluated. In accordance with the length of denervated neorectum, each patient was assigned to either the short-denervation or long-denervation group, determined by whether the inferior mesenteric artery was divided. Colonic propagated contraction was then measured by means of intraluminal pressure monitoring. Transit time was calculated with orally administered radiopaque markers. RESULTS: Propagated contraction down to the neorectum was significantly less common in the long-denervation group (14/36) than in the short group (12/15, P < 0.05), whereas spastic minor contraction at the neorectum was significantly more common in the long-denervation group (21/36) than the in short group (3/15, P < 0.05). Colonic transit time below the sigmoid colon was significantly longer in long group (6.4 hours) than in the short group (3.4 hours, P < 0.01). Although motility disorder of the neorectum was correlated with clinical defecatory malfunctions, including multiple evacuations, urgency, and soiling, no significant correlation was noted between the length of the denervated neorectum and the defecatory disorders. CONCLUSIONS: Motility of the neorectum following low anterior resection appears degraded by intraoperative maneuvers that cause denervation of the remnant sigmoid colon. Motility disorder of the neorectum, but not the length of the denervated neorectum causing the disorder, correlates well with several defecatory malfunctions. This finding suggests that postoperative defecatory disorder as a result of low anterior resection is caused by many factors in addition to denervation of the neorectum.

Modified Two-Stage Ileal Pouch-Anal Anastomosis: Equivalent Outcomes With Less Resource Utilization.
Swenson BR, Hollenbeak CS, Poritz LS, Koltun WA
Dis Colon Rectum 2005 Feb 10;.

PURPOSE: A three-stage operative approach to ileal pouch-anal anastomosis is usually undertaken in patients presenting with severe colitis. Increasingly, however, we have performed a two-stage modified ileal pouch-anal anastomosis (colectomy followed by ileal pouch-anal anastomosis without ileostomy). The present study sought to evaluate the safety, results, cost, and length of hospital stay using this modified approach compared to that of the traditional three-stage ileal pouch-anal anastomosis. METHODS: Clinical and financial data were gathered by retrospective review of patients undergoing ileal pouch-anal anastomosis at our institution since 1995. Complications were defined as any event prolonging hospitalization or requiring readmission and were included in the analysis up to six months after final surgery. Functional performance was assessed as of the last clinic visit. Data were compared with Student's t-test and chi-squared analysis. Multivariate analysis was also used to assess risk factors. RESULTS: A total of 23 patients who underwent the two-stage modified procedure and 31 patients who had the three-stage procedure were identified. The two groups were found to be statistically comparable in terms of patient age, gender, duration of illness, and preoperative hematocrit. Follow-up was shorter in the modified group because of its more recent introduction (9.7 months vs. 30.5 months mean follow-up). Ninety-five percent of patients were on immunosuppressive medication before colectomy, but all were off it before the reconstruction. clinical outcomes after ileal pouch-anal anastomosis were equivalent in terms of the number of bowel movements, prevalence of fecal incontinence, and the use of hypomotility medications. No patients with the two-stage modified procedure had anastomotic complications requiring stoma creation. One patient in the three-stage group required re-creation of a stoma after stoma closure for perianal complications suggesting Crohn's disease. Total hospital cost was significantly less in the modified group: $27,270 vs. $38,184 (P = 0.0119). Length of stay was also shorter in the two-stage modified group although missing absolute statistical significance (21.0 days vs. 26.0 days, P = 0.0882). CONCLUSIONS: Interval ileal pouch-anal anastomosis reconstruction without a stoma (two-stage modified procedure) after colectomy is functionally equivalent to the traditional three-stage protocol in terms of clinical outcome. However, it has the advantage of overall lower hospital costs and probably a shorter length of hospital stay.

Prospective, Randomized Trial Comparing Intraoperative Colonic Irrigation With Manual Decompression Only for Obstructed Left-Sided Colorectal Cancer.
Lim JF, Tang CL, Seow-Choen F, Heah SM
Dis Colon Rectum 2005 Feb 15;.

BACKGROUND: This is a prospective, randomized, controlled trial comparing the outcome of intraoperative colonic irrigation with that of manual decompression for acutely obstructing colorectal cancers distal to the splenic flexure. METHODS: All patients admitted to our department from June 1999 to August 2002 with obstructing left-sided colorectal cancers were recruited. Patients were randomized intraoperatively and were excluded if deemed unsuitable for segmental resection and primary anastomosis. Twenty-five patients were randomized to receive colonic irrigation and twenty-eight to receive manual decompression. Perioperative parameters and outcome including mortality and anastomotic leak were recorded. RESULTS: Both groups of patients were comparable in terms of gender and age. The time taken for mobilization, decompression, and irrigation in the colonic irrigation group (median, 31 minutes) was significantly longer than that for the manual decompression group (median, 13 minutes) (P; = 0.0005). However, the total time of the operation was similar for both groups. Times for recovery of bowel function, of wound infection, and until discharge from the hospital were also similar. In the manual decompression group there were two cases of anastomotic leak (8 percent, 2/25) requiring reoperation but none (0/24) in the colonic irrigation group. However, this difference was not statistically significant. CONCLUSION: Manual decompression of proximal colon without irrigation is as safe as colonic irrigation in one-stage surgical management of obstructing left-sided colorectal cancer.

Transanal Endoscopic Microsurgery: A Systematic Review.
Middleton PF, Sutherland LM, Maddern GJ
Dis Colon Rectum 2005 Feb 10;.

PURPOSE: The aim of this study was to systematically review the evidence relating to the safety and efficacy of transanal endoscopic microsurgery, a relatively new technique used to locally excise rectal tumors, compared with existing techniques such as anterior resections and abdominoperineal resections or local excisions. METHODS: We conducted a systematic review of comparative studies and case series of transanal endoscopic microsurgery from 1980 to August 2002. RESULTS: Three comparative studies (including one randomized, controlled trial) and 55 case series were included. The first area of study was the safety and efficacy of adenomas. In the randomized, controlled trial, no difference could be detected in the rate of early complications between transanal endoscopic microsurgery (10.3 percent) and direct local excision (17 percent) (relative risk, 0.61; 95 percent confidence interval, 0.29-1.29). Transanal endoscopic microsurgery resulted in less local recurrence (6/98; 6 percent) than direct local excision (20/90; 22 percent) (relative risk, 0.28; 95 percent confidence interval, 0.12-0.66). The 6 percent rate of local recurrence for transanal endoscopic microsurgery in this trial is consistent with the rates found in case series of transanal endoscopic microsurgery (median, 5 percent). The second area of study was the safety and efficacy of carcinomas. In the randomized, controlled trial, no difference could be detected in the rate of complications between transanal endoscopic microsurgery and direct local excision (relative risk for overall early complication rates, 0.56; 95 percent confidence interval, 0.22-1.42). No differences in survival or local recurrence rate between transanal endoscopic microsurgery and anterior resection could be detected in either the randomized, controlled trial (hazard ratio,1.02 for survival) or the nonrandomized, comparative study. There were 2 of 25 (8 percent) transanal endoscopic microsurgery recurrences in the randomized, controlled trial, but no figures were given for recurrence after anterior resection. In the case series, the median local recurrence rate for transanal endoscopic microsurgery was 8.4 percent, ranging from 0 percent to 50 percent. The third comparison was cost of the procedures. Transanal endoscopic microsurgery had both a lower recurrence rate and a lower cost than local excision or anterior resection for adenomas. Although the effectiveness of transanal endoscopic microsurgery could not be established for carcinomas, costs were lower than those for either anterior resection or abdominoperineal resection. CONCLUSIONS: The evidence regarding transanal endoscopic microsurgery is very limited, being largely based on a single relatively small randomized, controlled trial. However, transanal endoscopic microsurgery does appear to result in fewer recurrences than those with direct local excision in adenomas and thus may be a useful procedure for several small niches of patient types-e.g., for large benign lesions of the middle to upper third of the rectum, for T1 low-risk rectal cancers, and for palliative, not curative, use in more advanced tumors.

Pelvic Sepsis After Extended Hartmann's Procedure.
Tottrup A, Frost L
Dis Colon Rectum 2005 Feb 15;.

PURPOSE: An extended Hartmann's procedure is occasionally useful in rectal resections, because anastomotic, perineal, and functional problems are eliminated. This study was designed to examine the occurrence of pelvic sepsis after this procedure and identify possible risk factors. METHODS: Medical records were available for 163 patients (89 females) undergoing rectal resection with colostomy and closure of the rectal remnant. Information about pelvic sepsis and possible risk factors was obtained by review of the medical records. RESULTS: Pelvis sepsis developed in 31 of 163 patients (18.6 percent). When the rectum had been transected <2 cm above the pelvic floor, 24 of 73 patients (32.9 percent) developed an abscess in contrast to 7 of 90 (7.8 percent) after higher transsection (P = 0.0001). Other risk factors were male gender and missing foot pulses. Only 61 percent of pelvic abscesses healed after a median of 59 days, leaving 39 percent unhealed after an observation period of 277 (range, 20-1,643) days. CONCLUSIONS: Surgical alternatives should be considered to an extended Hartmann's procedure when the level of transsection is <2 cm above the pelvic floor, particularly in males.

Long-Term Treatment of High Intestinal Output Syndrome With Budesonide in Patients With Crohn's Disease and Ileostomy.
Ecker KW, Stallmach A, Loffler J, Greinwald R, Achenbach U
Dis Colon Rectum 2005 Feb 15;.

PURPOSE: In a previous, controlled study, it was shown that orally administered budesonide increases the absorptive capacity of the intestinal mucosa in patients with ileostomies caused by Crohn's disease. This open, nonrandomized study was designed to analyze this functional, not inflammation-dependent steroid-effect in the long-term course comparing exposure, withdrawal, and reexposure. METHODS: Phase 1: 23 patients without inflammatory activity of the disease received oral budesonide (3 mg t.i.d.) for at least four weeks (36.7 weeks; standard deviation, 45.3 weeks) because of high intestinal output syndrome. Phase 2: Medication was stopped for four weeks. Phase 3: Medication as in Phase 1. In each phase the weight of the ileostomy bags was measured with a spring balance before emptying and documented in a diary. Mean values per day and per week were calculated and the differences statistically evaluated by the Wilcoxon-(Pratt)-test. RESULTS: Comparing the last week of Phase 1 to first week of Phase 2, a significant (P < 0.0001) increase of the intestinal output (295 g; standard deviation, 313 g) was observed after omitting budesonide. In contrast, comparing the last week of Phase 2 to Phase 3, a significant (P < 0.0001) decrease of the intestinal output by 323.7 g (standard deviation, 322.2 g) was noticed reaching the same level as in Phase 1. CONCLUSIONS: These data show that the functional, inflammation-independent effect of budesonide on the intestinal mucosa is strongly correlated to the administration of the drug and may be maintained long-term. These results should be confirmed by a larger number of patients.

Loop Ileostomy Closure After Restorative Proctocolectomy: Outcome in 1,504 Patients.
Wong KS, Remzi FH, Gorgun E, Arrigain S, Church JM, Preen M, Fazio VW
Dis Colon Rectum 2005 Feb 15;.

PURPOSE: Routine use of a temporary loop ileostomy for diversion after restorative proctocolectomy is controversial because of reported morbidity associated with its creation and closure. This study intended to review our experience with loop ileostomy closure after restorative proctocolectomy and determine the complication rates. In addition, complication rates between handsewn and stapled closures were compared.METHODS: Our Department Pelvic Pouch Database was queried and charts reviewed for all patients who had ileostomy closure after restorative proctocolectomy from August 1983 to March 2002.RESULTS: A total of 1,504 patients underwent ileostomy closure after restorative proctocolectomy during a 19-year period. The median length of hospitalization was three (range, 1-40) days and the overall complication rate was 11.4 percent. Complications included small-bowel obstruction (6.4 percent), wound infection (1.5 percent), abdominal septic complications (1 percent), and enterocutaneous fistulas (0.6 percent). Handsewn closure was performed in 1,278 patients (85 percent) and stapled closure in 226 (15 percent). No significant differences in complication rates and length of hospitalization were found between handsewn and stapled closure techniques.CONCLUSIONS: Our results demonstrated that ileostomy closure after restorative proctocolectomy can be achieved with a low morbidity and a short hospitalization stay. In addition, we found that complication rates and length of hospitalization were similar between handsewn and stapled closures.

Sutured Perineal Omentoplasty After Abdominoperineal Resection for Adenocarcinoma of the Lower Rectum.
De Broux E, Parc Y, Rondelli F, Dehni N, Tiret E, Parc R
Dis Colon Rectum 2005 Feb 15;.

PURPOSE: This study was designed to describe and evaluate the efficacy of sutured perineal omentoplasty on perineal wound healing after abdominoperineal resection for adenocarcinoma of the lower rectum.METHODS: Charts of patients who underwent abdominoperineal resection for adenocarcinoma of the rectum from June 1995 to December 2001 were reviewed for mortality, morbidity, and perineal healing. Abdominoperineal resection was accomplished according to Miles combined with total mesorectal excision. The omentum was pediculized on the left gastroepiploic artery and tightly sewn to the subcutaneous fatty tissue. The perineal skin was then closed primarily.RESULTS: A total of 104 patients were included in the study. The mean age at surgery was 65 (range, 13-91) years. The distance of the tumor from the anal sphincters was 0.45 +/- 0.9 mm (range, 0-50). During the study period, 92 patients (88 percent) had sutured perineal omentoplasty. The rate of primary perineal wound healing was 80 percent. Postoperative perineal wound complications consisted of perineal abscess in seven patients. Six of these patients had a sutured perineal omentoplasty (6 percent). Only four patients required a surgical drainage. Minor perineal suppuration occurred in four patients (4 percent), whereas partial perineal wound dehiscence occurred in eight patients (8 percent). All wounds healed completely at three months. Intestinal obstruction occurred in three patients (3 percent). No complication of the pedicled omentoplasty was observed.CONCLUSIONS: This study demonstrated that sutured perineal omentoplasty is possible in the majority of patients after abdominoperineal resection for adenocarcinoma of the lower rectum with excellent primary perineal wound healing.

Side-to-Side Stapled Anastomosis Strongly Reduces Anastomotic Leak Rates in Crohn's Disease Surgery.
Resegotti A, Astegiano M, Farina EC, Ciccone G, Avagnina G, Giustetto A, Campra D, Fronda GR
Dis Colon Rectum 2005 Feb 17;.

PURPOSE: Anastomotic configuration may influence anastomotic leak rates. The aim of this study was to determine whether a side-to-side stapled ileocolonic anastomosis produces lower anastomotic leak rates than those with a handsewn end-to-end ileocolonic anastomosis after ileocecal or ileocolonic resection for Crohn's disease. METHODS: A series of 122 consecutive patients underwent elective ileocecal or ileocolonic resection with ileocolonic anastomosis for Crohn's disease from January 1998 to June 2003: 71 had handsewn end-to-end anastomosis and 51 had side-to-side stapled anastomosis. The choice between the two anastomoses was left to the surgeon's preference. A retrospective analysis was performed to assess if there was any difference in anastomotic leak rates. RESULTS: The two groups were comparable in terms of age, gender, preoperative presence of abscess or fistula, history of smoking, and albumin levels. More patients were taking steroids in the handsewn group than in the stapled group. In the handsewn group there were 10 anastomotic leaks (14.1 percent) and in the stapled group there was 1 anastomotic leak (2.0 percent) (risk difference, +12.1 percent; 95 percent confidence interval, 1.7-22.2; P = 0.02). Anastomotic configuration was the sole variable that influenced anastomotic leak rates at univariate analysis. Mortality was 1.4 percent in the handsewn group and 0 percent in the stapled group. Complications other than anastomotic leak developed in 11 patients in the handsewn group and in 6 patients in the stapled group. Mean postoperative hospital stay was 12.3 days in the handsewn group and 9.7 days in the stapled group (P = 0.03). Excluding those patients who had an anastomotic leak, the difference was still present (handsewn group, 10.1 days; stapled group, 9.1 days; P = 0.04). CONCLUSION: Although confirmation from randomized, controlled trials is required, side-to-side stapled anastomosis seems to substantially decrease anastomotic leak rates in surgical patients with Crohn's disease, compared with handsewn end-to-end anastomosis. Postoperative hospital stay decreased in the stapled anastomosis group, and this was not entirely a result of decreased anastomotic leak rates.

Practice Parameters for the Management of Rectal Cancer (Revised).
Colon and Rectal Surgeons: Joe J. Tjandra, M.D., John W. Kilkenny, M.D., W. Donald Buie, M.D., Neil Hyman, M.D., Clifford Simmang, M.D., Thomas Anthony, M.D., Charles Orsay, M.D., James Ch
Dis Colon Rectum 2005 Feb 23;.

Postoperative Change of Mucosal Inflammation at Strictureplasty Segment in Crohn's Disease: Cytokine Production and Endoscopic and Histologic Findings.
Yamamoto T, Umegae S, Kitagawa T, Matsumoto K
Dis Colon Rectum 2005 Mar 2;.

Primary Perineal Wound Closure After Preoperative Radiotherapy and Abdominoperineal Resection has a High Incidence of Wound Failure.
Bullard KM, Trudel JL, Baxter NN, Rothenberger DA
Dis Colon Rectum 2005 Mar 2;.

PURPOSE: Neoadjuvant radiation therapy has been used increasingly to downstage rectal cancer and decrease local recurrence. Despite its efficacy, preoperative radiation therapy may inhibit healing and contribute to wound complications. This study was designed to evaluate perineal wound complications after abdominoperineal resection. METHODS: The clinical records of a consecutive series of patients who underwent abdominoperineal resection for rectal carcinoma between 1988 and 2002 were reviewed. Demographic data, disease stage, and use of preoperative radiation therapy were recorded. Major wound complications included delayed wound healing (>1 month), wound infection requiring drainage/debridement, or reoperation. RESULTS: A total of 160 patients underwent abdominoperineal resection with primary closure of the perineal wound (mean age, 63 +/- 12 years); 117 (73 percent) patients received preoperative radiation therapy; 114 received radiation therapy for rectal cancer (radiation therapy + chemotherapy = 107, radiation therapy alone = 7); 3 received radiation therapy for other pelvic malignancies. Median radiation dose was 5,040 (range, 900-5,400) cGY. Overall wound complication rate was 41 percent. Major wound complication rate was 35 percent. Delayed healing was the most common complication (24 percent), followed by infection (10 percent). Radiation therapy increased the risk of any wound complication (47 vs. 23 percent; P = 0.005), risk of a major wound complication (41 vs. 19 percent; P = 0.021), and risk of infection (14 vs. 0 percent; P = 0.015). Risk of wound complications did not correlate with age, gender, disease stage, smoking, or diabetes. CONCLUSIONS: Wound complications are frequent after abdominoperineal resection and primary closure of the perineum. Preoperative radiation therapy doubles the rate of total and major perineal wound complications. Alternatives to primary perineal closure should be considered, particularly after radiation therapy.

Colonic J-Pouch-Anal Anastomosis for Rectal Cancer: A Prospective, Randomized Study Comparing Handsewn vs. Stapled Anastomosis.
Laurent A, Parc Y, McNamara D, Parc R, Tiret E
Dis Colon Rectum 2005 Mar 2;.

PURPOSE: Colonic J-pouch-anal anastomosis performed after complete proctectomy and total mesorectal excision for adenocarcinoma of the rectum can be handsewn or stapled. Stapling the coloanal anastomosis is believed to shorten operating time and reduce morbidity, but there are no randomized trials comparing the techniques. METHODS: Between January 1999 and May 2001, all patients with rectal adenocarcinoma requiring total mesorectal excision were randomized intraoperatively to handsewn or stapled anastomosis. Mortality, intraoperative, and postoperative findings and functional results at 3, 6, and 12 months were analyzed. RESULTS: Thirty-seven patients (12 females; mean age, 60 +/- 10 years) were randomized (stapled group: n = 20; handsewn group: n = 17). The two groups were comparable for age, gender, distance between the tumor and the levator ani, tumor volume, and use of preoperative radiotherapy (3 in each group). Morbidity did not differ between stapled group (3/20) and handsewn group (4/17; P > 0.05). Mean +/- standard deviation operative time was shorter in stapled group (261 +/- 40 minutes) than in handsewn group (314 +/- 46 minutes; P = 0.0008), and median distance between the anastomosis and the anal verge was shorter in handsewn group (19 +/- 9 mm) than in stapled group (27 +/- 8 mm; P = 0.01). Three patients of handsewn group and none of stapled group developed an anastomotic stricture requiring a single digital dilation (not significant). Number of stools per 24 hours, urgency, incidence of fragmented stools, degree of continence, requirement for protective pad, and/or need to take medication at 3, 6, and 12 months were similar in both groups. CONCLUSIONS: Stapled coloanal anastomosis is significantly faster than handsewn CAA and has similar functional results. It should be the preferred technique when it is feasible.

Surveillance-Detected Hepatic Metastases From Colorectal Cancer Had a Survival Advantage in Seven-Year Follow-Up.
Child PW, Yan TD, Perera DS, Morris DL
Dis Colon Rectum 2005 Mar 2;.

Long-Term Outcome of Mesocolic and Pelvic Diverticular Abscesses of the Left Colon: A Prospective Study of 73 Cases.
Ambrosetti P, Chautems R, Soravia C, Peiris-Waser N, Terrier F
Dis Colon Rectum 2005 Mar 2;.

PURPOSE: The aim of of this study was to evaluate prospectively the long-term outcome of mesocolic and pelvic diverticular abscesses of the left colon. METHODS: Between October 1986 and October 1997, a total of 465 patients urgently admitted to our hospital with a suspected diagnosis of acute left-sided colonic diverticulitis had a CT scan. Of 76 patients (17 percent) who had an associated mesocolic or pelvic abscess, 3 were lost to follow-up. The remaining 73 patients (45 with a mesocolic abscess and 28 with a pelvic abscess) were followed for a median of 43 months. RESULTS: of the 45 patients with a mesocolic abscess, 7 (15 percent) required surgery during their first hospitalization versus 11 (39 percent) of the 28 patients with a pelvic abscess (P = 0.04). At the end of follow-up, 22 (58 percent) of the 38 patients with a mesocolic abscess who had successful conservative treatment during their first hospitalization did not need surgical treatment vs. 8 (47 percent) of the 17 who had a pelvic abscess. Altogether, 51 percent of the patients with a mesocolic abscess had surgical treatment versus 71 percent of those with a pelvic abscess (P = 0.09). CONCLUSIONS: Considering the poor outcome of pelvic abscess associated with acute left-sided colonic diverticulitis, percutaneous drainage followed by secondary colectomy seems justified. Mesocolic abscess by itself is not an absolute indication for colectomy.

Immediate Radical Resection After Local Excision of Rectal Cancer: An Oncologic Compromise?
Hahnloser D, Wolff BG, Larson DW, Ping J, Nivatvongs S
Dis Colon Rectum 2005 Mar 2;.

PURPOSE: Local excision for early-staged rectal cancers is controversial. Preoperative understaging is not uncommon and radical resection after local resection may be needed for a curative treatment. The aim of this study was to determine the frequency and outcome of radical resection (within 30 days) after local excision for rectal adenocarcinoma. METHODS: All locally excised rectal cancers (curative intent) that required radical surgery within 30 days were reviewed (1980-2000). T2-3N0-1 stage cancers were each matched to three primary radical surgery controls for stage, age (+/-5 years), gender, date (+/-1 years), and type (abdominoperineal resection or low anterior resection) of operation. T1N0-1 cancers were compared with stage-matched rectal cancers treated by either primary radical surgery (n = 78) or local excision alone (n = 77). RESULTS: Fifty-two locally excised rectal adenocarcinomas (29 transanal and 23 polypectomies) were followed by radical surgery (24 abdominoperineal resection and 28 low anterior resection) within 7 (range, 1-29) days. Radical surgery was performed because of a cancerous polyp (n = 42), positive margins (5), lymphovascular invasion (3), and T3-staged cancer (2). Twelve of 52 cancers (23 percent) were found to have nodal involvement and 15 of 52 (29 percent) showed residual cancer in the resected specimen. The T2-3N0-1 stage controls were well matched. No significant difference in tumor location, size, adjuvant therapy, or length of follow-up was noted. Local and distant recurrence occurred in 2 of 4 T2-3N1 tumors and in 2 of 11 T2-3N0 cancers and were comparable to the matched controls, as was survival, with the exception of shorter survival in T3N1 cases, but numbers were too small for a definitive conclusion. Length of follow-up was not different. For T1 cancers, the controls were also comparable regarding patient and tumor demographics and adjuvant therapy. Nodal involvement was 21 percent in T1 study cases and 15 percent in T1 primary radical-surgery controls, with a trend toward location in the lower third of the rectum in both groups (58 percent and 50 percent, respectively). Local recurrence rates were 3 percent in the study group, 5 percent for patients undergoing primary radical surgery, and 8 percent for local excision alone. Distant metastasis (11 percent, 12 percent, and 13 percent, respectively) and overall five-year survival were also not significantly different (78 percent, 89 percent, and 73 percent, respectively). CONCLUSIONS: Nodal involvement in attempted locally excised rectal cancers is not uncommon. Local excision of rectal tumors followed by radical surgery within 30 days in cancer patients does not compromise outcome compared with primary radical surgery. Even after radical surgery for superficial T1 rectal cancers, recurrence rates are not insignificant. Future improvements in preoperative staging may be helpful in selecting tumors for local excision only.

Topical 5-Fluorouracil in the Management of Extensive Anal Bowen's Disease: A Preferred Approach.
Graham BD, Jetmore AB, Foote JE, Arnold LK
Dis Colon Rectum 2005 Mar 2;.

PURPOSE: An alternative approach to anal Bowen's disease was investigated. The use of topical 5 percent 5-fluorouracil for large lesions and surgical excision of small lesions were evaluated. METHODS: A prospective study was undertaken for anal Bowen's disease in 11 patients over a six-year period. Before therapy all patients underwent anal mapping biopsy and colonoscopy. For one-half circumferential disease or greater, patients underwent topical 5 percent 5-fluorouacil therapy for 16 weeks. For smaller involvement, wide surgical excision was performed. All patients underwent anal mapping biopsy one year after completion of therapy. RESULTS: Of 11 patients, 8 (5 male) received 16 weeks of topical 5 percent 5-fluorouacil therapy. Three patients (3 female) underwent surgical excision for localized disease. All but one patient, who was HIV positive, were free of Bowen's disease one year after completion of therapy. One patient underwent total excision of a residual microinvasive squamous carcinoma after circumferential Bowen's dis-ease had resolved. One patient received eight additional weeks of topical 5-fluorouacil therapy for incomplete resolution. All patients were followed yearly, with a mean follow-up of 39 months and a range of 12 to 74 months. There have been no recurrences. There were no long-term side effects or morbidity from topical 5-fluorouacil or local excision. All colonoscopies were normal. CONCLUSION: Topical 5 percent 5-fluorouacil therapy is a safe and effective method to treat anal Bowen's disease. Wide local excision is appropriate for smaller, isolated areas of disease. Anal Bowen's disease was not associated with colonic or other neoplasms.

Growth in Epithelial Cell Proliferation and Apoptosis Correlates Specifically to the Inflammation Activity of Inflammatory Bowel Diseases: Ulcerative Colitis Shows Specific p53- and EGFR Expression Alterations.
Sipos F, Molnar B, Zagoni T, Berczi L, Tulassay Z
Dis Colon Rectum 2005 Feb 23;.

Eight Years Experience of High-Powered Endoscopic Diode Laser Therapy for Palliation of Colorectal Carcinoma.
Courtney ED, Raja A, Leicester RJ
Dis Colon Rectum 2005 Mar 2;.

Prevalence and Morphology of Pouch and Ileal Adenomas in Familial Adenomatous Polyposis.
Groves CJ, Beveridge IG, Swain DJ, Saunders BP, Talbot IC, Nicholls RJ, Phillips RK
Dis Colon Rectum 2005 Mar 2;.

Association Between Fecal Hydrogen Sulfide Production and Pouchitis.
Ohge H, Furne JK, Springfield J, Rothenberger DA, Madoff RD, Levitt MD
Dis Colon Rectum 2005 Feb 23;.

PURPOSE: The beneficial effect of antibiotics in pouchitis suggests that an unidentified fecal bacterial product causes this condition. A candidate compound is hydrogen sulfide, a highly toxic gas produced by certain fecal bacteria, which causes tissue injury in experimental models. We investigated hydrogen sulfide release and sulfate-reducing bac-terial counts in pouch contents to determine whether hy-drogen sulfide production correlates with pouchitis. METHODS: During incubation at 37 degrees C, the production of hydrogen sulfide, methylmercaptan, carbon dioxide, and hydrogen were studied using fresh fecal specimens obtained from 50 patients with ileoanal pouches constructed after total proctocolectomy for ulcerative colitis (n = 45) or for familial adenomatous polyposis (n = 5). Patients with ulcerative colitis were divided into five groups: a) no history of pouchitis (pouch for at least 2 years; n = 8); b) past episode(s) of pouchitis but no active disease for the previous year (n = 9); c) pouchitis in the past year but presently inactive (n = 9); d) ongoing antibiotic treatment (metronidazole or ciprofloxacin) for pouchitis (n = 11); e) currently suffering from pouchitis (n = 8). RESULTS: Release of hydrogen sulfide when pouchitis was active (6.06 +/- 1.03 mumol g(-1) 4 h(-1)) or had occurred in the past year (4.71 +/- 0.41 mumol g(-1) 4 h(-1)) was significantly higher (P < 0.05) than when pouchitis had never occurred (1.71 +/- 0.43 mumol g(-1) 4 h(-1)) or had been inactive in the past year (2.62 +/- 0.49 mumol g(-1) 4 h(-1)). Antibiotic therapy was associated with very low hydrogen sulfide release (0.68 +/- 0.29 mumol g(-1) 4 h(-1)). Pouch contents from familial adenomatous polyposis patients produced significantly less hydrogen sulfide (0.75 +/- 0.09 mumol g(-1) 4 h(-1)) than did any group of nonantibiotic-treated ulcerative colitis patients. Sulfate-reducing bacterial counts in active pouchitis (9.5 +/- 0.5 log(10)/g) were significantly higher than in those who never experienced pouchitis (7.38 +/- 0.32 log(10)/g), and these counts fell dramatically with antibiotic treatment. No statistically significant differences in carbon dioxide and hydrogen were observed among the groups not receiving antibiotics. CONCLUSIONS: Pouch contents of patients with ongoing pouchitis or an episode within the previous year released significantly more hydrogen sulfide than did the contents of patients who never had an attack of pouchitis and those with longstanding inactive disease. The response to therapy with metronidazole or ciprofloxacin was associated with marked reductions in hydrogen sulfide release and sulfate-reducing bacteria. These results provide a rationale for additional studies to determine whether the high sulfide production is a cause or effect of pouchitis. The lower hydrogen sulfide production by pouch contents of familial adenomatous polyposis vs. patients with ulcerative colitis suggests a fundamental difference in gut sulfide metabolism that could have implications for the etiology of ulcerative colitis as well as the pouchitis of patients with ulcerative colitis.

Metastatic Testicular Carcinoma From the Colon With Clinical, Immunophenotypical, and Molecular Characterization: Report of a Case.
Tiong HY, Kew CY, Tan KB, Salto-Tellez M, Leong AF
Dis Colon Rectum 2005 Mar 2;.

Ischemic Colitis Following Colonoscopy in a Systemic Lupus Erythematosus Patient: Report of a Case.
Versaci A, Macri A, Scuderi G, Bartolone S, Familiari L, Lupattelli T, Famulari C
Dis Colon Rectum 2005 Mar 4;.

Evaluation of P-POSSUM in Surgery for Obstructing Colorectal Cancer and Correlation of the Predicted Mortality With Different Surgical Options.
Poon JT, Chan B, Law WL
Dis Colon Rectum 2005 Feb 23;.

PURPOSE: This study examined the accuracy of Portsmouth Physiologic and Operative Severity Score for enUmeration of Mortality and Morbidity system (P-POSSUM) in predicting the mortality of patients who underwent operations for obstructing colorectal cancer. It also is attempted to analyze the actual mortality and the predicted P-POSSUM mortality of different surgical options for obstructing left-sided cancer. METHODS: Data on patients who underwent surgery for obstructing colorectal cancer during 1998 to 2002 were collected. Mortality predicted by P-POSSUM was compared to the actual mortality with the method of linear analysis. The accuracy of using P-POSSUM to predict mortality in this group of patients was assessed by Hosmer and Lemeshow goodness of fit test and Receiver Operator Characteristic curve analysis. The predicted and actual mortality of patients who underwent different surgical options also were analyzed. RESULTS: A total of 160 patients were included in the study and 18 patients died postoperatively. The operative mortality was 11.3 percent. P-POSSUM predicted overall mortality of 15 percent. The observed and predicted mortality was found to have no significant lack of fit (chi-squared = 5.98; degree of freedom = 3; P = 0.11). The area under Receiver Operator Characteristic curve analysis was 0.75. For patients with left-sided tumors, P-POSSUM predicted mortality and actual mortality of patients who had resection without anastomosis were both significantly higher than patients with single-stage resection and primary anastomosis ( P = 0.044 and 0.011, respectively). CONCLUSIONS: P-POSSUM system is valid for prediction of overall mortality in patients with operations for obstructing colorectal cancer. Estimation of P-POSSUM predicted mortality during operation and its ability to correlate with choice of procedure is an area that is worth further study in emergency colorectal surgery.

The transcriptional repressor SNAIL is overexpressed in human colon cancer.
Roy HK, Smyrk TC, Koetsier J, Victor TA, Wali RK
Dig Dis Sci 2005 Jan;50(1):42-6.

CARD15/NOD2 in a Tunisian population with Crohn's disease.
Zouiten-Mekki L, Zaouali H, Boubaker J, Karoui S, Fekih M, Matri S, Hamzaoui S, Filali A, Chaabouni H, Hugot JP
Dig Dis Sci 2005 Jan;50(1):130-5.

Crohn's disease (CD) is a heterogeneous disorder. A genetic linkage to chromosome 16 (IBD1) has been previously observed and replicated in unrelated populations. Recently, in this region, NOD2/CARD15 has been identified as a susceptibility gene. The aim of this report is to determine whether this gene is implicated in CD in a Tunisian population. One hundred thirty patients with CD and 90 healthy individuals were genotyped for the three common NOD2 variants (C2104T in exon 4, G2722C in exon 8, and 3020insC in exon 11). Furthermore, the 11 exons of the NOD2 gene were sequenced in 20 patients with CD. Results showed that the frequency of the CARD15 variants in the Tunisian population is significantly lower than that observed in the European and American population. Direct sequencing of CARD15 did not permit us to identify a characteristic mutation in our population. No association was confirmed between CD and the NOD2 gene in our Tunisian population. Furthermore, the NOD2/CARD15 gene has a variable association with CD in different populations. These results indicate the genetic variation of CD in different ethnic groups.

Spindle cell tumor of the distal rectum.
Bahadursingh AM, Vagefi PA, Howell A, Prather C, Longo WE
Dig Dis Sci 2005 Jan;50(1):37-41.

A case of chronic intestinal ischemia presenting as chronic diarrhea without abdominal pain.
Ginsburg PM, Brant SR
Dig Dis Sci 2005 Jan;50(1):18-23.

Interobserver agreement in the interpretation of anal intraepithelial neoplasia.
Lytwyn A, Salit IE, Raboud J, Chapman W, Darragh T, Winkler B, Tinmouth J, Mahony JB, Sano M
Cancer 2005 Feb 22;.

BACKGROUND: Anal carcinoma incidence is increasing, and is highest among men with human immunodeficiency virus (HIV) infection who have sex with men. Anal carcinoma and anal intraepithelial neoplasia (AIN) are ascertained on tissue histology, but requires invasive procedures. Screening for AIN using anal cytology was suggested. The authors evaluated agreement on cytologic and biopsy specimens from HIV-positive men undergoing anal carcinoma screening. METHODS: One hundred twenty-nine HIV-positive men with a history of anal-receptive intercourse underwent anal cytology, anoscopy, and biopsy. Four pathologists independently assessed cytology and biopsy specimens and reached consensus for discordant cases. RESULTS: Each pathologist evaluated 120 cytology and 155 biopsy specimens. The weighted kappa value for overall agreement was 0.54 (95% confidence interval [CI], 0.49-0.59) for cytology specimens and 0.59 (95%CI, 0.55-0.63) for biopsy specimens. The median kappa values for pairwise agreement among pathologists and for agreement with consensus were, respectively, 0.69 and 0.77 for cytology and 0.66 and 0.75 for biopsy. At least 3 pathologists were in agreement for 92 (76.7%) cytology and 134 (86.5%) biopsy specimens. Reliability for the Bethesda classification system was at least moderate, except for the cytologic category of atypical squamous cells of undetermined significance (kappa = 0.12). Fourteen of 29 (48.3%) cytology specimens and 36 of 47 (76.6%) biopsy specimens with consensus interpretation of high-grade squamous intraepithelial lesions (HSIL) were interpreted originally as HSIL by >/= 3 pathologists. The kappa value for agreement with consensus distinguishing HSIL from non-HSIL ranged from 0.55 to 0.88 for cytology specimens and from 0.76 to 0.94 for biopsy specimens. CONCLUSIONS: Agreement for cytologic and biopsy interpretations was generally at least moderate. Nevertheless, these results supported the need for disease indicators with greater reliabililty. Cancer 2005. (c) 2005 American Cancer Society.

The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma.
Shapira M, Ben-Izhak O, Linn S, Futerman B, Minkov I, Hershko DD
Cancer 2005 Feb 16;.

BACKGROUND: Loss of the cell-cycle inhibitory protein p27(Kip1) is associated with poor prognosis in colorectal carcinoma. The decrease in p27(Kip1) levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma. MATERIALS AND METHODS: The expression of Skp2, Cks1, and p27(Kip1) was examined by immunohistochemistry using highly specific antibodies on formalin-fixed, paraffin-embedded tissue sections from 80 patients with colorectal carcinoma. RESULTS: Overexpression of Skp2 and Cks1 strongly correlated with loss of p27(Kip1) and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27(Kip1) expression. CONCLUSIONS: Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma. Cancer 2005. (c) 2005 American Cancer Society.

Folate transport gene inactivation in mice increases sensitivity to colon carcinogenesis.
Ma DW, Finnell RH, Davidson LA, Callaway ES, Spiegelstein O, Piedrahita JA, Salbaum JM, Kappen C, Weeks BR, James J, Bozinov D, Lupton JR, Chapkin RS
Cancer Res 2005 Feb 1;65(3):887-97.

[Present treatment strategies for rectal carcinoma.]
Liersch T, Langer C, Ghadimi BM, Becker H
Chirurg 2005 Mar 1;.

In the last ten years, considerable progress has been achieved in the treatment of rectal cancer. According to improved interdisciplinary staging, rectal carcinomas can be treated based on a stage-dependent concept: "low-risk" pT1 (G1/G2) carcinomas can be cured by local full wall excision, while "high-risk" pT1 (G3/G4) and pT2 carcinomas require transabdominal resection. In contrast, locally advanced rectal cancers in cUICC-II/-III stages (T3/T4 or N(+)) should receive long-term, 5-FU-based, neoadjuvant chemoradiotherapy according to the excellent results of the CAO/AIO/ARO-94 trial of the German Rectal Cancer Study Group. High-quality resection must be based on radical oncologic principles such as "no-touch" technique, radicular dissection of vessels, and total mesorectal excision. Multimodal treatment is completed with adjuvant 5-FU-based chemotherapy. This therapeutic approach led to a reduction in the 5-year local recurrence rate to 6% and disease-free survival of approximately 68% in advanced rectal cancer (overall survival: 76%).

Pregnancy and Crohn's Disease.
Mottet C, Juillerat P, Gonvers JJ, Froehlich F, Burnand B, Vader JP, Michetti P, Felley C
Digestion 2005 Feb 4;71(1):54-61.

Crohn's disease commonly affects women of childbearing age. Available data on Crohn's disease and pregnancy show that women with Crohn's disease can expect to conceive successfully, carry to term and deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health. Generally speaking, pharmacological therapy for Crohn's disease during pregnancy is similar to pharmacological therapy for non-pregnant patients. Patients maintained in remission by way of pharmacological therapy should continue it throughout their pregnancy. Most drugs, including sulfasalazine, mesalazine, corticosteroids, and immunosuppressors such as azathioprine and 6-mercaptopurine, are safe, whereas methotrexate is contraindicated. Copyright (c) 2005 S. Karger AG, Basel.

Treatment of Postoperative Crohn's Disease.
Froehlich F, Juillerat P, Felley C, Mottet C, Vader JP, Burnand B, Michetti P, Gonvers JJ
Digestion 2005 Feb 4;71(1):49-53.

At 1 year after a first resection, up to 80% of patients show an endoscopic recurrence, 10-20% have clinical relapse, and 5% have surgical recurrence. Smoking is one of the most important risk factors for postoperative recurrence. Preoperative disease activity and the severity of endoscopic lesions in the neoterminal ileum within the first postoperative year are predictors of symptomatic recurrence. Mesalamine is generally the first-line treatment used in the postoperative setting but still provokes considerable controversy as to its efficacy, in spite of the results of a meta-analysis. Immunosuppressive treatment (azathioprine, 6-MP) is based on scant evidence but is currently used as a second-line treatment in postsurgical patients at high risk for recurrence, with symptoms or with early endoscopic lesions in the neoterminal ileum. Nitroimidazole antibiotics (metronidazole, ornidazole) are also effective in the control of active Crohn's disease in the postoperative setting. Given their known toxicity, they may be used as a third-line treatment as initial short-term prevention therapy rather than for long-term use. Conventional corticosteroids, budesonide or probiotics have no proven role in postoperative prophylaxis. Infliximab has not as yet been studied for use in the prevention of relapse after surgery. Copyright (c) 2005 S. Karger AG, Basel.

Maintenance of Remission in Crohn's Disease.
Gonvers JJ, Juillerat P, Mottet C, Felley C, Burnand B, Vader JP, Michetti P, Froehlich F
Digestion 2005 Feb 4;71(1):41-48.

When remission of Crohn's disease is achieved, the next goal is to maintain long-term remission. Aminosalicylates may be recommended for maintenance remission, even though the results are less consistent than those observed in ulcerative colitis. The benefit is mainly observed in the post-surgical setting and in patients with ileitis, and with a prolonged disease duration. Corticosteroids are not effective in maintaining remission and should not be used for this indication. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn's disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Mycophenolate mofetil could be considered a therapy in patients who are either allergic to azathioprine or in whom azathioprine failed to induce remission. The use of infliximab may change the future approach to maintenance therapy for Crohn's disease. Patients who responded clinically to infliximab have maintained their clinical response when receiving repeat infusions at 8-week intervals. In patients refractory to other therapies, infliximab may be effective in maintaining remission. Copyright (c) 2005 S. Karger AG, Basel.

Treatment of Gastroduodenal Crohn's Disease.
Mottet C, Juillerat P, Gonvers JJ, Michetti P, Burnand B, Vader JP, Felley C, Froehlich F
Digestion 2005 Feb 4;71(1):37-40.

Symptomatic gastroduodenal manifestations of Crohn's disease (CD) are rare, with less than 4% of patients being clinically symptomatic. Gastroduodenal involvement may, however, be found endoscopically in 20% and in up to 40% of cases histologically, most frequently as Helicobacter pylori-negative focal gastritis, usually in patients with concomitant distal ileal disease. In practice, the activity of concomitant distal CD usually determines the indication for therapy, except in the presence of obstructive gastroduodenal symptoms. With the few data available, it seems correct to say that localized gastroduodenal disease should be treated with standard medical therapy used for more distal disease, with the exception of sulfasalazine and mesalanine with pH-dependent release. Presence of symptoms of obstruction needs aggressive therapy. If medical therapy with steroids and immunomodulatory drugs does not alleviate the symptoms, balloon dilation and surgery are the options to consider. Copyright (c) 2005 S. Karger AG, Basel.

Extraintestinal Manifestations of Crohn's Disease.
Juillerat P, Mottet C, Froehlich F, Felley C, Vader JP, Burnand B, Gonvers JJ, Michetti P
Digestion 2005 Feb 4;71(1):31-36.

In each case of extraintestinal manifestations of Crohn's disease, active disease, if present, should be treated to induce remission, which may positively influence the course of most concomitant extraintestinal manifestations. For some extraintestinal manifestations, however, a specific treatment should be introduced. This latter part of disease management will be discussed in this chapter, in particular for pyoderma gangrenosum, uveitis, spondylarthropathy - axial arthropathy - and primarysclerosing cholangitis, which have also been described in quiescent Crohn's disease. Few new drugs for the treatment of extraintestinal manifestations of Crohn's disease have been developed in the past and only the role of infliximab has increased in Crohn's disease-related extraintestinal manifestations. Drugs specifically aimed at this treatment, stemming from a few randomized controlled studies or case series, are sulfasalazine, 5-ASA, corticosteroids, azathioprine or 6-mercaptopurine, methotrexate, infliximab, dapsone and cyclosporine or tacrolimus. Copyright (c) 2005 S. Karger AG, Basel.

Obstructive Fibrostenotic Crohn's Disease.
Froehlich F, Juillerat P, Mottet C, Felley C, Vader JP, Burnand B, Gonvers JJ, Michetti P
Digestion 2005 Feb 4;71(1):29-30.

Crohn's disease is often complicated by gastrointestinal strictures. Postoperative recurrence at the anastomotic site is common and repeated surgical interventions may be necessary. Medical treatment may relieve active inflammation (see chapter on active luminal disease) but fibrous strictures will not respond to this. Mechanical treatment methods consist of endoscopic balloon dilation, stricturoplasty or surgical resection. Fibrostenotic Crohn's disease does not respond to medical therapy and requires endoscopic or surgical treatment. Copyright (c) 2005 S. Karger AG, Basel.

Fistulizing Crohn's Disease.
Felley C, Mottet C, Juillerat P, Froehlich F, Burnand B, Vader JP, Michetti P, Gonvers JJ
Digestion 2005 Feb 4;71(1):26-28.

Fistulas are common in Crohn's disease. A population-based study has shown a cumulative risk of 33% after 10 years and 50% after 20 years. Perianal fistulas were the most common (54%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas. Copyright (c) 2005 S. Karger AG, Basel.

Severe and Steroid-Resistant Crohn's Disease.
Michetti P, Mottet C, Juillerat P, Felley C, Vader JP, Burnand B, Gonvers JJ, Froehlich F
Digestion 2005 Feb 4;71(1):19-25.

Patients with moderate to severe disease and patients with steroid-refractory or steroid-dependent disease differ in their management, as the latter groups usually include patients with less acute situations. Systemic corticosteroids represent the mainstay of the management of moderate to severe disease and remain the first-line therapy in this setting. Infliximab is the choice alternative for patients who do not respond to steroids or in whom steroids are contraindicated. Purine analogues, methotrexate and infliximab have shown efficacy in achieving steroid-free remission in patients with steroid-refractory or -dependent disease. Other fast-acting immunosuppressors showed little benefit. Surgery may be indicated in this setting. Nataluzimab may prove useful in patients refractory to infliximab. Copyright (c) 2005 S. Karger AG, Basel.

Therapy of Mild to Moderate Luminal Crohn's Disease.
Michetti P, Juillerat P, Mottet C, Gonvers JJ, Burnand B, Vader JP, Froehlich F, Felley C
Digestion 2005 Feb 4;71(1):13-18.

The management of luminal Crohn's disease, the most common form of initial presentation of the disease, depends on the location and the severity of the lesions. Mild to moderate disease represents a relatively large proportion of patients with a first flare of luminal disease, which may also be associated with perianal disease. As quality of life of these patients correlates with disease activity, adequate therapy is a central goal of the overall patient management. Treatment options include mainly sulfasalazine, budesonide and systemic steroids, while the role of mesalazine and antibiotics remains controversial. The role of biological therapies in mild to moderate disease has not been thoroughly evaluated and will not be discussed here. Copyright (c) 2005 S. Karger AG, Basel.

Drug Safety in the Treatment of Crohn's Dise