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Surveillance colonoscopy and biopsy in patients with ureterosigmoidostomy.

Colonoscopy with biopsy was included in the surveillance of 19 patients with ureterosigmoidostomy, because of the high incidence of colonic carcinoma reported in such cases. The patients were examined 1-6 times, at intervals of 1-2 years, 4-36 years after the urinary diversion. Random biopsies from the distal colon and rectum showed only discrete changes, and no dysplasia. Polyps with dysplastic changes were found close to ureteral anastomoses in three patients. For routine check-up of the rectosigmoid region and the ureteral implantation sites, examination with a flexible sigmoidoscope seems to be adequate and preferable, giving easy access to the risk zone for the development of cancer. Caution should be exercised, however, when performing biopsy close to the ureteral orifices.

Adult↗

Transdermal nicotine for active ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

Administration, Cutaneous↗

Transdermal nicotine as maintenance therapy for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. METHODS: We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. CONCLUSIONS: Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.

Administration, Cutaneous↗

Results of screening colonoscopy among persons 40 to 49 years of age.

BACKGROUND: The prevalence of colorectal lesions in persons 40 to 49 years of age, as identified on colonoscopy, has not been determined. METHODS: We reviewed the procedure and pathology reports for 906 consecutive persons 40 to 49 years of age who voluntarily participated in an employer-based screening-colonoscopy program. The histologic features of lesions that were identified and removed on endoscopy were categorized according to those of the most advanced lesion removed proximally (up to the junction of the splenic flexure and the descending colon) and the most advanced lesion removed distally. An advanced lesion was defined as an adenoma at least 1 cm in diameter, a polyp with villous histologic features or severe dysplasia, or a cancer. RESULTS: Among those who underwent colonoscopic screening, 78.9 percent had no detected lesions, 10.0 percent had hyperplastic polyps, 8.7 percent had tubular adenomas, and 3.5 percent had advanced neoplasms, none of which were cancerous (95 percent confidence interval for cancer, 0 to 0.4 percent). Eighteen of 33 advanced neoplasms (55 percent) were located distally and were potentially within reach of a sigmoidoscope. If these results are applicable to the general population, at least 250 persons, and perhaps 1000 or more, would need to be screened to detect one cancer in this age group. CONCLUSIONS: Colonoscopic detection of colorectal cancer is uncommon in asymptomatic persons 40 to 49 years of age. The noncancerous lesions are equally distributed proximally and distally. The low yield of screening colonoscopy in this age group is consistent with current recommendations about the age at which to begin screening in persons at average risk.

Adenoma↗

Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin.

BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.

Adult↗

Initial experience with a steerable, phased vector array ultrasound catheter in the GI tract.

BACKGROUND: EUS requires a significant capital outlay. The ability to perform high-resolution phased array scanning and Doppler interrogation by using a catheter that interfaces with a standard US console could increase the accessibility of EUS. Recently, an electronic phased-array US catheter was developed for intracardiac use. To date, this technology has not been applied to the GI tract. The aim of this study is to determine the feasibility and imaging characteristics of a new phased array scanning US catheter in the GI tract. METHODS: Swine were placed under general anesthesia. This study used a 100 cm, 10F, torquable catheter with 4-way tip deflection to greater than 90 degrees. The catheter tip houses a phased vector array transducer with variable frequency (5.5-10 MHz) and variable focal distance. It has pulsed/color and power Doppler capability. The probe was passed through a therapeutic flexible sigmoidoscope into the upper GI tract. Acoustic coupling was achieved via a condom filled with water or by gastric water infusion. Needle visualization experiments were performed with a second endoscope (also passed per oral) with a standard EUS-guided fine needle aspiration needle. RESULTS: Acoustic coupling was easily achieved. Resolution of the GI wall into characteristic layers (esophagus 5, stomach 7) was demonstrated. At 5.5 MHz, tissue resolution and Doppler imaging were excellent to greater than 10 cm from the transducer. A 22-gauge EUS-guided fine needle aspiration needle was easily visualized at depth greater than 4 cm. Flow in gastric, hepatic, and pancreatic parenchymal vessels approximately 1 mm diameter was visualized by using power and color Doppler. CONCLUSIONS: This 10F array US catheter is capable of high-resolution two-dimensional imaging of the gut wall as well as high-quality Doppler imaging. The Doppler capabilities of this equipment may have new GI applications.

Animals↗

Oral prednisolone metasulphobenzoate in the treatment of active ulcerative colitis.

BACKGROUND: Corticosteroids are one of the mainstays of treatment for active ulcerative colitis, but they are associated with numerous side effects. The sparingly absorbed corticosteroid prednisolone metasulphobenzoate is used topically in the treatment of distal disease. A targeted-release oral preparation (Predocol) has been developed to allow delivery of this drug to the whole colon. We have studied the effect of oral Predocol on inflammation as measured by 99Tc(m)-HMPAO leucocyte scintigraphy in patients with symptomatic and sigmoidoscopic relapse of known extensive ulcerative colitis. METHODS: Fourteen patients were recruited and received Predocol 47.1 mg twice daily, 8 for 7 days and 6 for 14 days. Scintigraphy was performed prior to and at the end of treatment. Each segment of colon was graded (0-4) and individual scores summed to give a total scintigraphic score. RESULTS: Total scintigraphic score improved by a mean of 2.5 (P = 0.027). Mean individual scores improved in the rectum by 0.7 (P = 0.038) and in the descending colon by 0.8 (P = 0.033). CONCLUSIONS: Predocol is an oral preparation of a poorly absorbed salt of prednisolone that is effective in reducing inflammation over short treatment periods in patients with active ulcerative colitis.

Administration, Oral↗

Pain produced by electric stimulation of the rectum in patients with irritable bowel syndrome: further evidence of visceral hyperalgesia.

BACKGROUND: Visceral hyperalgesia is most likely a phenomenon of substantial clinical importance and may also play a role in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the manifestation of visceral hyperalgesia in IBS patients by nociceptive electric stimulation of the rectosigmoid junction and rectum. METHODS: Twelve IBS patients fulfilling the Rome criteria and 9 healthy controls were studied. Visceral single and repeated electric burst stimuli were applied with a bipolar electric stimulator inserted through the sigmoidoscope. The sensation (ST) and pain detection (PDT) thresholds were determined in response to single and repeated stimuli at the rectosigmoid junction, and PDT to repeated stimuli at four different positions in the rectum. Cutaneous single and repeated electric stimuli were applied to the lateral aspect of the foot, determining ST and PDT. RESULTS: Cutaneous stimulation showed no significant differences for ST and PDT between patients and controls. The rectosigmoid junction showed significantly lower ST for single stimuli (P<0.01) and a significantly lower PDT for single and for repeated stimuli (P<0.05 and P<0.02) in IBS patients. In the rectum the IBS patients had a significantly lower PDT than controls (P<0.001). CONCLUSIONS: For cutaneous electric stimulation no differences in the pain thresholds between the two groups were found, showing that there is no generalized hyperalgesia in IBS patients. The IBS patients had a specific decrease of the pain thresholds in the rectum and rectosigmoid junction, indicating visceral hyperalgesia. These results point to central visceral hyperexcitability as an important factor in the pathophysiology of IBS.

Abdominal Pain↗

The impact of an educational workshop on colorectal screening practices.

Since its establishment in 1983, the Virginia Colorectal Cancer Control Project has emphasized the importance of routine screening of asymptomatic adults for colorectal cancer. This has been accomplished through educational workshops that are offered to primary care physicians. These workshops provide didactic information on current concepts in screening and individualized instruction on the use of the flexible sigmoidoscope. Eleven workshops have been conducted since the fall of 1984. During the spring of 1986, a survey was mailed to workshop participants to determine whether changes had occurred in their screening practices. A total of 115 physicians responded to the survey. Prior to the workshop, 86 physicians performed the digital rectal examination; now 100 do. Prior to the workshop, 68 physicians performed the fecal occult blood test; now 89 do. Prior to the workshop, 34 physicians used a flexible scope; now 71 do. Participants found the workshop to be extremely effective in providing individualized instruction.

Colorectal Neoplasms↗

The case for colorectal cancer screening.

There is strong evidence that sigmoidoscopic screening can reduce the risk of colorectal cancer mortality by as much as 70%, but the case for extensive fecal occult blood testing is less convincing. Flexible sigmoidoscopy performed once every five to 10 years in patients aged 50 to 75 appears to be warranted; however, many practical barriers to widespread implementation still need to addressed.

Adenoma↗

Systematic review of the effects of n-3 fatty acids in inflammatory bowel disease.

BACKGROUND: n-3 Fatty acids are purported to have health effects in patients with inflammatory bowel disease (IBD), but studies have reported mixed results. OBJECTIVE: We aimed to synthesize published and unpublished evidence to determine estimates of the effect of n-3 fatty acids on clinical outcomes in IBD and whether n-3 fatty acids modify the effects of or need for treatment with other agents. DESIGN: Computerized databases were searched for studies of n-3 fatty acids in immune-mediated diseases from 1966 to 2003. We also contacted experts in the nutraceutical industry to identify unpublished studies; however, none were identified. RESULTS: Reviewers identified 13 controlled trials that assessed the effects of n-3 fatty acids on clinical, sigmoidoscopic, or histologic scores; rates of induced remission or relapse; or requirements for steroids and other immunosuppressive agents in Crohn disease or ulcerative colitis. Most clinical trials were of good quality. Fewer than 6 were identified that assessed the effects of n-3 fatty acids on any single outcome of clinical, endoscopic, or histologic scores or remission or relapse rates. Consistent across 3 studies was the finding that n-3 fatty acids reduce corticosteroid requirements, although statistical significance was shown in only 1 of these studies. CONCLUSION: The available data are insufficient to draw conclusions about the effects of n-3 fatty acids on clinical, endoscopic, or histologic scores or remission or relapse rates.

Controlled Clinical Trials as Topic↗

Microgranulomas in grossly normal rectal mucosa in Crohn's disease.

Rectal biopsies of sigmoidoscopically normal mucosa from 99 patients with Crohn's disease of the ileum, colon, or both were studied histologically, with particular reference to the presence of granulomas. Among the 14 cases of granulomas, some were of the usual sarcoid type and could easily be detected. Other microgranulomas were less well defined and were found only by mid- or high-power microscopic screening of serial sections. The morphologic characteristics, the relationship to ordinary Crohn's-disease granulomas and the possible significance of microgranulomas are discussed.

Biopsy↗

Pathologic features of initial adenomas as predictors for metachronous adenomas of the rectum.

BACKGROUND: Colorectal cancer is the third most common cancer in the world, arising mostly from pre-existing adenomatous polyps (adenomas) of the large bowel. Patients with colorectal adenomas are at increased risk of colorectal cancer because of a high recurrence rate for adenomas. We followed a cohort of 1490 patients with rectal adenomas to determine whether recurrence might be related to pathologic characteristics of the initial adenomas. METHODS: The patients were identified in Haining County, China, from 1977 through 1978 by means of examination with a 15-cm rigid sigmoidoscope. They were followed by endoscopic examination at years 2, 4, 6, 11, and 16 after their initial polypectomy. New adenomas in the rectum were identified in 280 patients in these follow-up examinations. RESULTS: Statistically significant twofold to threefold elevated risks of metachronous (recurrent) adenomas were observed for patients who had more than two initial adenomas or whose most advanced initial adenoma was more than 1.0 cm in size, was of villous/tubulovillous type, or showed moderate to severe dysplasia. Much stronger associations were observed for advanced metachronous neoplasms, which are defined as cancers or adenomas with severe dysplasia, with multivariate adjusted relative risks (95% confidence interval) of 4.2 (1.8-9.9) for a large initial adenoma (>1.0 cm), 8.1 (4.2-15.6) for villous/tubulovillous architecture, and 14.4 (5.0-41.3) for severe dysplasia. In particular, patients who had a large (>1.0 cm) adenoma with severe dysplasia at baseline had a relative risk of 37 (7.8-174.7) of developing advanced metachronous neoplasms compared with patients who had small adenoma(s) with mild dysplasia. CONCLUSIONS: The risk of metachronous adenomas is closely related to the pathology of initial adenomas, thus allowing identification of a high-risk group of adenoma patients for close surveillance after their initial polypectomy.

Adenoma↗

Abdominosacral resection for carcinoma of the midrectum: ten years experience.

Abdominosacral resection allows curative resection of midrectal cancer with excellent preservation of sphincter function. In the last ten years 427 patients underwent resection for rectal carcinoma at University Hospital by one surgeon. (SAL) The operation, selected by preoperative sigmoidoscopic measurement, was anterior resection (AR) in 239, abdominosacral resection (ASR) in 100, and abdominoperineal resection (APR) in 88. Operative mortality was 1.7% for AR, 2% for ASR and 2.3% for APR. All patients were completely continent of stool and flatus after AR and ASR. Follow-up is complete in 194 of 195 patients treated five to ten years ago. Five year survival for curative resection (no distant metastases) was 67.3% after AR (66/98), 58.3% after ASR (21/36), and 50% after APR (15/30). For patients without tumor in lymph nodes, survival rates were 78.3% for AR, 64.3% for ASR and 63.2% for APR. With involvement of regional nodes, survival fell to 41.4% for AR, 37.5% for ASR and 27.3% for APR. For lesions at 5-8.5 cm, five year survival was 61.1% for ASR and 58.3% for APR. No statistical difference in survival time was noted when patients were matched for age, sex, level of lesion and extent of spread. Pelvic recurrences were detected in 16.7% after ASR, 15.3% after AR and 33.3% after APR. All of the pelvic recurrences after ASR and the majority of those after AR and APR occurred in patients with tumor invasion of perirectal fat. These data strongly support the applicability of ASR as an important advance in the treatment of midrectal cancer. Although technically demanding, ASR has permitted preservation of anal continence without sacrifice of long-term cure in approximately 50% of patients who would otherwise have required APR.

Abdomen↗

Abdominosacral resection for midrectal cancer. A fifteen-year experience.

From 1966 to 1981, 646 patients underwent resection for primary adenocarcinoma of the rectum by one surgeon (S.A.L.) in one hospital. The operation, selected by preoperative sigmoidoscopic measurement, was anterior resection (ASR) in 320 patients, abdominosacral resection (ASR) in 175 patients, and abdominoperineal resection (APR) in 151 patients. The operative mortality rate was 2% following each of the operations. Anastomotic complications occurred in less than 2% after AR and in 9.7% after ASR. All patients were completely continent of stool and flatus after AR and ASR. Follow-up is complete in 419 of 427 patients treated from 1966 to 1976. Five-year survival for curative resection (no distant metastases) was 66.2% after AR (129/195), 62.9% after ASR (56/89), and 43.4% after APR (33/76). For patients with no tumor in lymph nodes, survival rates were 73.9% in AR, 75% for ASR, and 59.5% for APR. With involvement of regional lymph nodes, survival fell to 45.2% in AR, 37.9% for ASR, and 17.7% for APR. Pelvic recurrence was detected in 13.3% after AR, 14.6% after ASR, and 13.2% after APR. The authors believe that for midrectal cancer, ASR is the most reliable sphincter-saving procedure. It affords maximum exposure for wide resection of the tumor and safe anastomosis without disrupting the anal sphincters and their innervation. Sphincter preservation can be consistently preserved with no apparent increase in the risk of local recurrence or death from cancer.

Abdomen↗

Endoscopic decompression of acute colonic obstruction. Avoiding staged surgery.

Colostomy is the traditional treatment for acute obstruction of the sigmoid colon. This entails two or three surgical procedures in a high-risk group of patients. Presented is a nonsurgical approach used in three patients with acute colonic obstruction. Decompression of the bowel was achieved with a tube introduced proximal to the obstruction with the aid of a flexible sigmoidoscope. In a fourth patient, in whom the obstruction was next to the splenic flecture, the procedure failed. In all instances where decompression was successful, a one-stage procedure--primary resection and anastomosis--was performed.

Acute Disease↗

Performance of flexible sigmoidoscopy by a clinical nurse specialist.

According to the National Cancer Institute, 138,200 new cases and more than 55,000 deaths from colorectal cancer occurred in the U.S. in 1995. A high percentage of early cancers can be detected by screening asymptomatic persons older than age 50 with a digital rectal exam, fecal occult blood testing, and sigmoidoscopy. Evidence suggests that a decrease in mortality from colorectal cancer is associated with regular screening by sigmoidoscopy in an average risk population. As the population ages, more persons are eligible for colorectal cancer screening. Physician endoscopists are not available in all areas, and changes in reimbursement rates have caused some to discontinue this service. For these reasons, the Veterans Administration Medical Center in Buffalo, NY, developed a Colorectal Cancer Screening Program managed by a gastroenterology Clinical Nurse Specialist (CNS). Through study and supervision, the CNS has become proficient in the performance of 60-cm flexible sigmoidoscopic techniques and the diagnosis of multiple colon disorders, including sessile and pedunculated polyps, diverticulosis, tumors, hemorrhoids, and other conditions.

Colorectal Neoplasms↗

Retroperitoneal fibrosis presenting as colonic dysfunction: CT diagnosis.

In a patient who presented with pelvic pain and changed bowel habits, barium enema and sigmoidoscopic examinations demonstrated a nonspecific asymmetric narrowing of the colon at the rectosigmoid junction with normal mucosal appearance. Computed tomography revealed the etiology to be retroperitoneal fibrosis with pelvic extension and entrapment of the colon at this level. The importance of CT in diagnosis of this unusual manifestation of retroperitoneal fibrosis is discussed.

Colonic Diseases↗