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Diagnostic testing following fecal occult blood screening in the elderly.

BACKGROUND: Screening with a fecal occult blood test (FOBT) has been shown to reduce colorectal cancer mortality in controlled trials. Recently, Medicare approved payment for FOBT screening. We evaluated the pattern of diagnostic testing following the initial FOBT in elderly Medicare beneficiaries. Such follow-up testing would in the long run influence both the cost and the benefit of widespread use of FOBT. METHODS: Using Medicare's National Claims History System, we identified 24 246 Americans 65 years old or older who received FOBT at physician visits between January 1 and April 30, 1995. Prior to FOBT, these people had no evidence of any conditions for which FOBT might be used diagnostically. We examined relevant diagnostic testing in this cohort during the subsequent 8 months and determined what proportion of those received an evaluation recommended by the American College of Physicians. RESULTS: For every 1000 Medicare beneficiaries who received FOBT, 93 (95% confidence interval = 89-96 per 1000) had positive findings and relevant testing in the subsequent 8 months. Of these, 34% had the recommended evaluation of either colonoscopy or flexible sigmoidoscopy with an air-contrast barium enema. Another 34% received a partial colonic evaluation with either flexible sigmoidoscopy or a barium enema. The remaining 32% received other gastrointestinal (GI) testing without evaluation of the colonic lumen: computed tomography or magnetic resonance imaging of the abdomen (15%), upper GI series (10%), carcinoembryonic antigen (7%), and upper endoscopy (2%). Restricting the analysis to testing performed within 2 months of the initial FOBT yielded similar results. CONCLUSION: Following FOBT, many Medicare beneficiaries get further diagnostic testing, but only a small proportion receives the recommended evaluation. With this pattern of practice, population screening is likely to be more costly and less effective than estimated from controlled trials.

Aged↗

Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum.

OBJECTIVE: In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group. SUMMARY BACKGROUND DATA: The optimal treatment of large rectal carcinomas remains controversial; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. METHODS: Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy-proven lesions > 3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates. RESULTS: The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens. Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes. In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (< 5%). Cox-Mantel analysis of Kaplan-Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p = 0.031) for protocol versus control patients. CONCLUSIONS: This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.

Adenocarcinoma↗

Update on the cost-effectiveness of screening for colorectal neoplasia.

Colorectal cancer is an ideal target for population screening because it is a prevalent disease with an identifiable precursor lesion that, when treated, favorably alters the natural history of the disease. Several strategies for screening have illustrated efficacy, including fecal occult blood testing, sigmoidoscopy and colonoscopy. Cost-effectiveness analyses have been performed to determine whether the resources required to implement screening are justified by potential gains. The U.S. Preventive Services Task Force recently commissioned a study on the cost-effectiveness of colorectal cancer screening, which revealed that screening was cost-effective compared to no screening. However, it could not be confirmed which strategy would save the most life-years, nor which was most cost-effective. Since publication of this review, several additional cost-effectiveness analyses have been performed. These studies confirm that screening average risk patients at age 50 by a variety of available strategies is likely to be reasonable by current standards for resource utilization, and that either colonoscopy every 10 years (or once at age 65) or the combination of annual fecal occult blood testing with sigmoidoscopy every 5 years are viable alternatives. Additional economic analyses have examined the use of aspirin chemoprophylaxis to prevent colorectal cancer either alone or as an adjunct to screening strategies. These studies reaffirm the cost-effectiveness of colorectal cancer screening, but illustrate that aspirin chemoprophylaxis is unlikely to be associated with gains for which society would be willing to pay. At present, the decision to choose one colorectal screening strategy over another is based on availability of screening modalities, patient and provider preferences, and associated adherence to screening recommendations. Assessment of preference and development of interventions to increase adherence to screening should be a focus of research in the future.

Journal Article↗

Screening for colorectal cancer and other GI cancers.

Most of the major advances in the screening for gastrointestinal cancers this year were in the area of colorectal cancer screening. Currently, screening is recommended for the prevention of colorectal cancer in average and high-risk populations. For average risk populations, large randomized trials support the use of screening fecal occult blood testing, and case-control studies support the use of screening sigmoidoscopy. This year, several investigators have addressed issues related to the probability of identifying advanced lesions in the proximal colon following a positive screening flexible sigmoidoscopy. Similarly, two studies identified that villous histology in an index polyp was associated with an increased risk of recurrent colonic polyps. Additionally, two large trials provided new insight about the prevalence of mutations in the MLH1 or MSH2 mismatch-repair genes among patients with colorectal cancer. Lastly, a case-control study from Sweden provided the best evidence to date that surveillance colonoscopies for patients with long-standing ulcerative colitis may reduce cancer-related mortality. Although further work is needed, these studies have served to advance our knowledge of colorectal cancer screening substantially.

Colorectal Neoplasms↗

Spectrum of ulcerative colitis in north India.

We analyzed retrospectively the characteristics of 87 patients with ulcerative colitis seen in a tertiary care center in north India. Ulcerative colitis was diagnosed on the basis of clinical features, sigmoidoscopy, rectal biopsy, and exclusion of microbiological causes of colitis. Severe clinical disease was seen in 53 (60%) patients that correlated with extensive colonic involvement (p < 0.001), severe changes on sigmoidoscopy (p < 0.001) and histology (p < 0.001), erythrocyte sedimentation rate (ESR) of > 30 mm for the first hour, and serum albumin of < 3 g/dl (p < 0.001). Remission of the disease was maintained on sulfasalazine in 18 (20.7%) patients, whereas 47 (54%) required steroids. Proctocolectomy with ileoanal anastomosis was done in 22 (25.3%) patients in whom there was poor response to medical treatment. Postoperative complications were seen in seven (31.8%) patients, and death occurred in four (18.1%) patients. Ulcerative colitis thus commonly presents as severe disease, with the majority of patients requiring surgery due to poor response to medical therapy. This pattern of disease as seen in an academic referral hospital in north India is virtually indistinguishable from that seen in similar centers in the West. However, in our setting, proctocolectomy and ileoanal anastomosis is cost-effective in patients unresponsive to, or unable to afford, drug treatment.

Adult↗

The significance of rectal bleeding after pelvic radiotherapy.

BACKGROUND: Rectal bleeding after pelvic radiotherapy is often attributed to radiation proctitis and patients do not routinely undergo flexible endoscopy. AIMS: To assess the significance of bleeding after radiotherapy. METHODS: We maintained a prospective register of all such patients referred to our endoscopy unit. RESULTS: One hundred and thirty-nine men (median age 70 years; range 31-82), and 32 women (median age 61 years; range 30-81) were referred with rectal bleeding (median 2 years; range 0-21) after pelvic radiotherapy. Primary tumour sites were urological (n = 139), gastrointestinal (n = 7) and gynaecological (n = 25). Ninety patients had bleeding alone; 81 had other symptoms. One hundred and forty-one had typical radiation proctitis; in 65 this was the sole diagnosis; eight had cancer, nine had high-risk adenomas, and six had three or more small adenomas. Ninety-five other diagnoses were made. Eleven (73%) patients with advanced polyps or cancer required only flexible sigmoidoscopy to make the diagnosis, while four (27%) diagnoses were made only after colonoscopy; 47% of these patients had no other symptoms apart from rectal bleeding. CONCLUSIONS: After pelvic radiotherapy, clinical symptoms are not reliable in differentiating between radiation proctitis alone or more significant pathology. It is mandatory that all patients with new onset rectal bleeding are investigated with, at least, flexible sigmoidoscopy.

Adult↗

The outpatient evaluation of hematochezia.

OBJECTIVE: The objective of this study was to determine whether specific clinical symptoms associated with hematochezia are predictive of important GI pathology and whether full colonoscopic examination is necessary. METHODS: A total of 103 outpatients (> or = 45 yr) with hematochezia, defined as the passage of bright red blood per rectum, underwent anoscopy and colonoscopy. Before endoscopy, patients completed a detailed interview, quantitating the amount and frequency of bleeding, weight loss, use of aspirin/NSAIDs, change in bowel habits, family history, and prior GI illnesses. Based on this information, physicians were asked to predict whether the bleeding was from a perianal or more proximal site. At colonoscopy, pathology was stratified as either proximal or distal to the sigmoid/descending junction. Substantial pathology was defined as one or more adenomas > 8 mm, carcinoma, or colitis. RESULTS: Anoscopy demonstrated internal and external hemorrhoids in 78 and 29 patients, respectively. On colonoscopy, 36 patients had 43 substantial lesions. Thirty-seven of these lesions were distal to the junction of the descending and sigmoid colons and six were proximal lesions. Four patients had cancer; all were distal lesions. Patients with substantial lesions were more likely to give a history of blood mixed within their stool (p = 0.03), to have more episodes of hematochezia per month (p = 0.008), and to have a significantly shorter duration of bleeding before medical evaluation (p = 0.02) than did patients without such lesions. However, the physician's clinical assessment did not predict reliably which patients were likely to have substantial pathology. CONCLUSIONS: In patients with hematochezia, clinicians were unable to distinguish between those patients with and those without significant colonic lesions by history alone. Flexible sigmoidoscopy would have demonstrated most (95%) substantial lesions. The lesions that flexible sigmoidoscopy missed were an unlikely cause of bleeding in this small group of patients.

Ambulatory Care↗

A prospective study of endoscopy in HIV-associated diarrhea.

OBJECTIVE: Diarrhea commonly occurs in persons with human immunodeficiency virus (HIV) infection. The optimal use of endoscopic procedures remains poorly studied for patients with HIV-related diarrhea. The purpose of this study is to compare the diagnostic yield of a complete endoscopic work-up including an esophagogastroduodenoscopy and colonoscopy to a more limited approach of biopsies obtainable by flexible sigmoidoscopy. METHODS: A prospective study of 79 patients with HIV-related diarrhea. Upper endoscopy and colonoscopy were performed with tissue biopsies labelled according to location within the colon or small intestine. RESULTS: A new infection was diagnosed in 22 of 79 patients (28%). Biopsy of the left colon yielded an enteric pathogen in 17 of 22 patients (sensitivity: 77%) and in 15 of 15 patients with cytomegalovirus colitis (sensitivity: 100%). Combined left and right colonic biopsies had a sensitivity of 82%. Combined colonic and terminal ileum biopsies missed no pathogens. Duodenal biopsies yielded no additional pathogens beyond those identified by colonoscopy and terminal ileal biopsy. Patients with a new pathogen diagnosed had significantly lower CD4 lymphocyte counts as compared to patients without a new pathogen (p = 0.001). CONCLUSIONS: For patients with CD4 counts < 100/mm3 and unexplained AIDS-related diarrhea, flexible sigmoidoscopy with biopsy is a sufficiently thorough endoscopic evaluation.

AIDS-Related Opportunistic Infections↗

Is colorectal cancer screening necessary in the preoperative assessment of inguinal herniorrhaphy? A case-control study.

OBJECTIVES: The question of whether patients presenting for inguinal hernia repair require pre-operative assessment for colon cancer has remained unanswered. A case-control study is necessary to assess whether the prevalence of premalignant or malignant colonic lesions is higher in patients presenting with inguinal hernia compared to the general population. METHODS: Between 1990-2000, 614 inguinal herniorrhaphies were performed at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). We retrospectively studied the 149 (24%) patients from this group with no prior history of colonic polyps, malignancy, or gastrointestinal bleeding who had flexible sigmoidoscopy or colonoscopy performed during the peri-operative period. Comparison was made to 149 controls undergoing colonoscopy or sigmoidoscopy during the same time period for colon cancer (CRC) screening. RESULTS: The mean (+/-SEM) patient age was 67 +/- 0.7 (range 31-92) yr in the hernia patients and 66 +/- 0.8 (range 46-93) in the control group (p = 0.7). Eighty-two of the inguinal hernia patients had screening procedures performed preoperatively with a mean time (+/-SEM) of 1.4 +/- 0.14 yr, while endoscopy was performed in the post-operative period for the remaining 67 patients (average time 2.7 +/- 0.2 yr, p < 0.001). More patients underwent colonoscopy in the control group compared to the hernia cohort (p = 0.004). Seven (5%) patients in the hernia group were found to have colorectal cancer compared to six (4%) in the control group (p = 0.8). CONCLUSIONS: This study does not support previously published findings that patients with inguinal hernias are more likely to have premalignant colonic lesions. Patients with inguinal hernias should undergo screening for colon cancer at the same rate as the general population.

Adult↗

Colorectal cancer in Russian-speaking Jewish emigrés: community-based screening.

OBJECTIVES: Colorectal cancer (CRC) screening by fecal occult blood testing and flexible sigmoidoscopy is recommended by many authorities for those older than age 50. Ashkenazi Jews have been shown to have a higher level of CRC and polyps than the general population. A subset of Ashkenazi Jews, Russian-speaking Jewish immigrants to the United States (RJIs), have not been studied extensively for CRC and may have additional risk factors not found in other Ashkenazi populations. METHODS: A retrospective chart review was undertaken of fecal occult blood tests, endoscopy reports, and pathology reports of 132 RJIs and 124 non-RJI controls over age 50 between 1987 and 1999 at the Jewish Hospital of Cincinnati Medical Outpatient Clinic. RESULTS: Mean ages at the time of diagnosis or flexible sigmoidoscopy were 68 yr for RJIs and 66 yr for the non-RJI patients. Of the RJI patients, 38.7% had positive findings: 37 (28.0%) with lesions < 2 cm, five (3.8%) with lesions > 2 cm, and nine (6.8%) with CRC. Of the non-RJI control group patients, 16.9% had positive findings: 16 (12.9%) with lesions < 2 cm, three (2.4%) with lesions > 2 cm, and two (1.6%) with CRC. Age- and sex-matched statistical analysis revealed significantly greater CRC and significantly more polyps > 2 cm for the RJI patients (p < 0.003). This is higher than in other studies of Ashkenazis, which show a 2.3% incidence, and in statistics from the National Cancer Institute, which reveal a national CRC incidence rate for those over age 65 to be 0.30%. CONCLUSIONS: RJIs in our study have polyps > 2 cm and CRC at a rate of 10.6%, as compared with 4.0% for in-clinic controls and a national average of 0.30% for patients over age 65. This suggests a need for more aggressive screening of this patient population for CRC.

Aged↗

Utility of an upper echoendoscope for endoscopic ultrasonography of malignant and benign conditions of the sigmoid/left colon and the rectum.

OBJECTIVE: The majority of data on colonic endoscopic ultrasound (EUS) are limited to malignant lesions in the rectum and diseases of the anal sphincter. The forward-oblique-viewing upper echoendoscope has been mostly applied for staging rectal cancer. A front-viewing echocolonoscope is available but has not been widely used because of limited indications and the expense of buying another instrument. The purpose of our study was to evaluate the utility of a forward-oblique-viewing upper echoendoscope for EUS of malignant and benign lesions of the sigmoid/left colon and the rectum. METHODS: Thirty-two EUS exams were performed for a variety of indications in the rectum and the sigmoid/left colon. The patients were prepared for the exam in a manner similar to the performance of flexible sigmoidoscopy. Flexible sigmoidoscopy was performed in all cases before performing EUS. Surgical path data were reviewed in all cases if the patient had surgery after EUS. RESULTS: Twenty-six exams were done for staging of rectosigmoid carcinoma, follow-up after chemotherapy and/or radiation, or to look for recurrence after resection of colorectal cancer. Surgical pathology results were available in 20 patients. The accuracies of EUS were 85% for T staging and 80% for N staging. Six EUS exams were for benign causes, including evaluation for the presence of a perirectal abscess in two (no abscess found), to rule out rectal varices in one (EUS confirmed rectal varices), and evaluation of submucosal lesions. One patient subsequent to EUS imaging also underwent a linear EUS-guided fine-needle aspiration of a submucosal mass in the rectum with the fine-needle aspirate consistent with a myogenic tumor. CONCLUSIONS: The forward-oblique-viewing upper echoendoscope is a versatile instrument that can be applied for EUS imaging of malignant and benign indications not only in the rectum but also in the sigmoid/left colon.

Colon↗

Yield of colonoscopy in patients with nonacute rectal bleeding: a multicenter database study of 1766 patients.

OBJECTIVE: There are few data to guide the choice between colonoscopy and flexible sigmoidoscopy in patients with nonacute rectal bleeding, especially in younger age groups. Our aim was to determine the yield of colonoscopy for significant proximal large bowel disease in the absence of significant distal disease, with special reference to young patients. METHODS: This was a retrospective study of data collected prospectively in 1766 patients (median age 57 yr, 711 women). The endoscopic database (GI-Trac) contained 152 discrete fields for data input. Multiple logistic regression analysis was performed to identify variables independently associated with the presence of isolated significant proximal disease. RESULTS: Young patients had a higher percentage of normal examinations than did older patients. The incidence of diverticular disease, small polyps, large polyps, and cancer rose with increasing age. No patient aged <40 yr had an isolated proximal cancer, but 7% had other significant isolated proximal disease. There was no overall association between age and significant proximal disease in the absence of significant distal disease (p = 0.66). The only variable associated with isolated proximal disease was anemia (odds ratio = 1.81; 95% CI = 1.11-2.93; p = 0.02). CONCLUSION: The yield of colonoscopy (beyond the range of sigmoidoscopy) for neoplasia is low in patients aged <40 yr, but other significant disease may be missed if age is the only criterion determining colonoscopy use.

Adult↗

Physician-reported reasons for limited follow-up of patients with a positive fecal occult blood test screening result.

OBJECTIVE: Fecal occult blood testing (FOBT) screening can reduce colorectal cancer (CRC) mortality when patients with an abnormal result [FOBT(+)] undergo a complete diagnostic evaluation (colonoscopy or double-contrast barium enema with or without flexible sigmoidoscopy). The aim of this study was to determine common reasons for nonperformance of a complete diagnostic evaluation. METHODS: We identified 544 FOBT(+) patients, aged 50 yr or older, who had participated in a managed care organization-sponsored CRC screening program. The performance of a complete diagnostic evaluation was determined from a patient-specific follow-up form and managed care organization claims data. Physicians were asked to report whether patients submitted to a complete diagnostic evaluation. When an evaluation was not done, the physicians were also asked to state the reasons for nonperformance. RESULTS: A total of 248 (46%) patients did not undergo a complete diagnostic evaluation. Physicians provided reasons for nonperformance for 50% (123/248). Factors accounting for nonperformance of a complete diagnostic evaluation were classified as follows: primary care physician decision (50%); specialist decision (28%); patient decision (17%); and other (practice-related) (5%). Many failures to complete an appropriate diagnostic evaluation were due to providers deciding to repeat the FOBT, perform a sigmoidoscopy, or not to proceed with any further testing. CONCLUSION: Many patients with a positive FOBT do not receive a complete diagnostic evaluation. The reasons for nonperformance most frequently have to do with physician decision making. Many physician-related explanations do not conform to expert recommendations for appropriate follow-up.

Aged↗

Determinants of colorectal cancer screening in women undergoing mammography.

OBJECTIVES: Women who participate in screening for breast cancer are more likely to participate in screening for colorectal cancer. We studied such a motivated group of women to identify predictors of, and barriers to, participation in colorectal cancer screening by endoscopy. METHODS: We distributed surveys to 551 women > or = 50 yr of age while they were awaiting mammography at four sites in and around Boston, MA from June to September, 2000. The 40-question survey assessed knowledge, attitudes, and beliefs about, and behaviors toward, breast and colorectal cancer screening. Regression models were used to determine factors associated with having had sigmoidoscopy or colonoscopy. RESULTS: Seventy-nine percent of the women completed all or part of the survey. Half (221/438) reported ever having had sigmoidoscopy or colonoscopy. Of these, 93% did so at the recommendation of their primary care provider. Factors associated with participation in endoscopic screening included compliance with annual fecal occult blood testing, a family history of colorectal cancer, and indifference toward the gender of the doctor performing the endoscopy. CONCLUSIONS: Women undergoing mammography overwhelmingly cite the recommendation of their primary care provider as the reason for participating in colorectal cancer screening by endoscopy. Women who preferred a female endoscopist were less likely to have been screened. Whenever possible, primary care providers should offer women the choice of a female endoscopist for colorectal cancer screening.

Aged↗

The prevalence rate and anatomic location of colorectal adenoma and cancer detected by colonoscopy in average-risk individuals aged 40-80 years.

BACKGROUND: The role of screening colonoscopy for colorectal (CR) neoplasia in average-risk population, remains to be determined. OBJECTIVES: To evaluate the prevalence and anatomic location of CR adenoma and carcinoma and the morbidity of colonoscopy in individuals at average risk for CR cancer (CRC). METHODS: A retrospective prevalence study of subjects aged 40-80 yr, with no cancer-related symptoms, personal or family history of CR neoplasia, who underwent a colonoscopy. RESULTS: Enrolled were 1,177 persons; 183 aged 40-49 yr (young), 917 aged 50-75 yr, and 77 aged 76-80 yr (elderly). The prevalence of overall CR neoplasia, advanced neoplasia, and cancer was 20.9%, 6.3%, and 1.1%, respectively. In the 50-75 age group, the prevalence of overall adenoma, advanced neoplasia, and cancer was 21.3%, 6.7%, and 1.2%, respectively. Of the 206 neoplasia cases, 21-43% harbored proximal neoplasia beyond the reach of sigmoidoscopy, without distal lesions. Among the elderly, the prevalence of overall adenoma, advanced neoplasia, and cancer reached 26.0%, 14.3%, and 2.6%, respectively. In the young group, 9.8% had overall neoplasia, 1.1% had advanced adenoma, and none had CRC. Procedure-related morbidity rate was 0.1%, with no perforations, bleedings, or mortality. CONCLUSIONS: Screening colonoscopy in average-risk subjects demonstrated a considerable prevalence of CR neoplasia and proximal lesions beyond the reach of sigmoidoscopy. The morbidity rate was negligible. Primary screening colonoscopy should be considered in health programs for the average-risk population, beginning at the age of 50 yr. The significantly high rate of advanced and proximal neoplasia in the elderly, encourages the inclusion of healthy subjects aged 76-80 yr in future prospective studies.

Adenocarcinoma↗

Predictive value of rectal bleeding in screening for rectal and sigmoid polyps.

Overt rectal bleeding is a common symptom of colorectal cancer and polyps but also occurs in apparently healthy people. It is not known how often this represents bleeding from an undiagnosed rectal or sigmoid polyp or cancer. Three hundred and nineteen apparently healthy men aged over 50, selected by random sampling, were interviewed and underwent flexible sigmoidoscopy to at least 30 cm. Polyps of 10 mm or more in diameter were diagnosed in 12, one of whom also had an adenocarcinoma. Rectal bleeding during the previous six months was reported by 48, four of whom were found to have polyps; seven polyps and one cancer were diagnosed among the 271 who reported no rectal bleeding. Rectal bleeding had a specificity of 86%, a sensitivity of 33%, and a positive predictive value of 8% for rectal or sigmoid polyps or cancer. Restricting the analysis to those subjects who regularly inspected their stools did not improve the predictive value. Sigmoidoscopy in apparently healthy subjects with rectal bleeding will not result in the diagnosis of appreciable numbers of rectal and sigmoid polyps or cancers.

Gastrointestinal Hemorrhage↗

Colorectal leukotriene B4 synthesis in vitro in inflammatory bowel disease: inhibition by the selective 5-lipoxygenase inhibitor BWA4C.

The in vitro synthesis of leukotriene B4 (LTB4) was evaluated in colorectal biopsy specimens and resection tissue from patients with inflammatory bowel disease. The in vitro formation of LTB4 from biopsy tissues stimulated with calcium ionophore A23187 correlated with the degree of mucosal inflammation assessed at sigmoidoscopy, and with neutrophil infiltration measured as myeloperoxidase activity. Biopsy specimens from patients taking prednisolone formed less LTB4 than those from patients not on prednisolone, with comparable levels of inflammation seen at sigmoidoscopy. The formation of LTB4 was reduced dose-dependently by the acetohydroxamic acid 5-lipoxygenase inhibitor BWA4C, with no significant inhibition of prostaglandin E2 or thromboxane B2 synthesis. In inflamed colonic resection tissue from colitic patients, the IC50 for inhibition of LTB4 formation by BWA4C was 0.03 mumol/l, compared with an IC50 of 0.8 mumol/l for NDGA. Thus, BWA4C is a potent and selective inhibitor of LTB4 synthesis in colonic tissue from patients with ulcerative colitis. Acetohydroxamic acid 5-lipoxygenase inhibitors, exemplified by BWA4C, may be useful to evaluate the clinical importance of LTB4 in ulcerative colitis, and offer a novel therapy for the disease.

Benzeneacetamides↗

Ranitidine, diarrhoea, and lymphocytic colitis.

A 69 year old woman developed chronic diarrhoea while being treated with ranitidine. Sigmoidoscopy was performed after six weeks and showed typical histological features of lymphocytic colitis. Ranitidine was withdrawn and the diarrhoea resolved. Eight months later, a 72 hour oral rechallenge period of ranitidine, was performed immediately preceded (period 1) and followed (period 2) by sigmoidoscopy and biopsy. Diarrhoea recurred during the rechallenge period and resolved again within one day after drug withdrawal. The mean (SEM) intraepithelial lymphocyte count was not significantly different between periods 1 and 2 (11.9 (0.6) and 13.1 (0.4) per 100, respectively). An immunopathological study of 30 serial sections of biopsy specimens was performed for both periods 1 and 2. The expression of HLA-DR by the rectal epithelium was mild or absent in all sections from period 1, and was considerable in 25 of 30 sections from period 2 (p < 10(-9)). It is suggested that the oral intake of ranitidine was responsible for the diarrhoea and induced the immunopathological signs of activation of the rectal mucosal immune system during the rechallenge period.

Aged↗