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Background: Three-year colonoscopic surveillance after initial polypectomy may not be required for all patients. Those with multiple baseline polyps and large adenomas, implicated as predictors of colon cancer, merit close observation. Conversely, patients with single small adenomas may be subjected to early endoscopic surveillance unnecessarily., Methods: From our Adenoma Registry we evaluated patient and adenoma characteristics in 697 patients. All had an adenoma recurrence within 3 years of a positive baseline colonoscopy. Potential risk factors studied were age, gender, number of adenomas, size of largest adenoma and histology. We defined a significant outcome as size of 1 cm or greater, tubulovillous or villous histology, high-grade dysplasia, carcinoma in situ, invasive cancer, or 4 or more adenomas., Results: Having 3 or more adenomas on initial colonoscopy with at least 1 measuring 1 cm or larger greatly increased the chance of a significant finding on the first surveillance colonoscopy. Conversely, patients with 1 or 2 adenomas all measuring less than 1 cm were at extremely low risk of an important outcome within 3 years., Conclusions: Patients with 1 or 2 adenomas all measuring less than 1 cm are an identified low risk group and their first surveillance examination may be delayed beyond the standard 3 years.

Exisulind (sulindac sulfone; FGN-1), a metabolite of sulindac without known effects on prostaglandin synthesis, can promote apoptosis and inhibit tumorigenesis in preclinical systems. We performed a Phase I trial of this compound in patients with familial adenomatous polyposis (FAP) to examine the tolerability and safety of this drug in the cancer chemoprevention setting. Six patients each were treated with exisulind at doses of 200, 300, and 400 mg p.o. twice a day. Reversible hepatic dysfunction was noted in four of six patients treated at the 400-mg p.o., twice-a-day dose level, but in only one to two of six patients treated at each of the lower dose levels. The serum half-life of exisulind was 6-9 h; little drug accumulation was noted over time. A nonsignificant trend toward increased apoptosis in polyps was noted at the maximum tolerated dose, but no decrease in polyp numbers or significant effects on cellular proliferation was noted. After treatment, polyps tended to display a "halo" appearance grossly and mucinous differentiation histologically. The maximum safe dose of exisulind is 300 mg p.o. twice a day in patients with subtotal colectomies. Reversible hepatic dysfunction limits further dose escalation. A decrease in polyp numbers could not be demonstrated, but the trend toward increased apoptosis at the MTD and the observation of mucinous change histologically suggest that further investigation of drugs of this class might be warranted.

Introduction: Duodenal and periampullary cancer is the most common cause of cancer death in patients with familial adenomatous polyposis who have undergone colectomy. Endoscopic surveillance of upper gastrointestinal adenomas is recommended for patients with familial adenomatous polyposis but the timing and appropriate treatment of neoplasms is unknown. The purpose of this experiment was to report our experience with endoscopic and surgical treatment of advanced duodenal adenomas in patients with familial adenomatous polyposis., Methods: The records of all patients with familial adenomatous polyposis who had undergone surgical or endoscopic treatment for duodenal adenomas were identified. Data including endoscopic surveillance findings, type of intervention, pathology, and follow-up of the lesions were reviewed., Results: Ten neoplasms >1 cm were treated in eight patients (mean age at the time of diagnosis was 49 years). Nine lesions were histologically advanced. Five lesions involved the papilla. Endoscopic treatment was performed for six lesions. Four lesions recurred, and three were then treated surgically. Local resection was performed for five lesions. Four lesions recurred and two had further operative intervention. Pancreas-sparing duodenectomy was performed in three patients. At a mean follow-up period of 45.7 months, there has been no recurrence., Conclusions: Endoscopic eradication is an appropriate initial treatment for histologically advanced, noncancerous neoplasms or for patients who are not surgical candidates. Pancreas-sparing duodenectomy may be the treatment of choice for patients with carcinoma and those who have failed endoscopic therapy.

Screening for colorectal cancer, as called for by new guidelines from three different groups, should result in a lower mortality rate from this disease. This paper reviews the guidelines' similarities and differences and gives our recommendations for situations in which the data remain incomplete and controversy persists.

Background: Endoscopic surveillance is recommended for patients with familial adenomatous polyposis (FAP) because of the high prevalence of duodenal adenomas and the risk of periampullary cancer. The aim of this study was to assess the natural history of untreated duodenal and ampullary adenomas in FAP patients during surveillance., Methods: One hundred fourteen FAP patients who had 2 or more surveillance examinations were followed for a mean of 51 months (range, 10 to 151 months)., Results: Duodenal polyps progressed in size in 26% (25 of 95), number in 32% (34 of 106), and histology in 11% (5 of 45) of patients. Morphology and histology of the main duodenal papilla progressed in 14% (15 of 110) and 11% (12 of 105) of patients, respectively. The histologic progression was mild except for one patient who developed a periampullary cancer., Conclusions: A minority of FAP patients had progression of endoscopic features and histology of duodenal polyps or the main duodenal papilla when followed over 4 years. An endoscopic surveillance interval of at least 3 years may be appropriate for the majority of untreated patients with FAP. Factors that stratify patients as being at the highest risk of periampullary cancer and thus requiring more intensive surveillance are yet to be determined.

Background and Methods: Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period., Results: The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake., Conclusions: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.

Background: Screening sigmoidoscopy is an underutilized method for detecting early colorectal cancer, and patient discomfort is one reason for poor compliance in the general population. The possible benefit of a well-tolerated, low-cost antispasmodic medication, sublingual hyoscyamine, used before flexible sigmoidoscopy was assessed in a randomized, double-blinded, placebo-controlled trial., Methods: One hundred fifty patients were enrolled and randomized to receive two sublingual hyoscyamine tablets (0.125 mg/tablet) or the placebo 10 minutes before sigmoidoscopy. Patient comfort and the endoscopist's perception of the ease of insertion were measured using a 100 mm visual analog scale. The depth of sigmoidoscope insertion was measured in centimeters, and complications were recorded., Results: The median age was 55 years (range 25 to 83 years). There were 100 men (66.7%) and 50 women (33.3%). Approximately half (n = 76, 50.7%) had a prior sigmoidoscopy or colonoscopy. No statistical differences were found between treatment group means for age, gender, pain score, ease of insertion, or depth of insertion. The hyoscyamine group tended to have lower mean pain (32.4 vs. 37.7, p = 0.18) and difficulty (29.9 vs. 33.7, p = 0.31) scores and greater depth of sigmoidoscope insertion (51.3 vs. 47.7, p = 0.07); however, the differences were not statistically significant. The treatment groups differed with a higher percentage of the hyoscyamine group having a previous endoscopy (60.0% vs. 41.3%, p = 0.02); however, no significant differences were detected between mean pain scores as related to treatment when controlling for previous experience with endoscopy (p = 0.31)., Conclusions: In this study, hyoscyamine administered in the sublingual route did not significantly improve patient comfort, ease of insertion, or the depth of sigmoidoscope insertion during screening sigmoidoscopy. The search for alternative methods to improve patient comfort during screening endoscopy should continue.

Background & Aims: All patients with colorectal adenomas may not require identical follow-up. We aimed to determine if adenoma characteristics at initial colonoscopy could predict adenoma recurrence or characteristics at follow-up., Methods: The number of adenomas and the size, type, and degree of atypia in 479 patients in a polyp prevention trial were evaluated as predictors of the same characteristics at follow-up using odds ratios (ORs) with 95% confidence intervals (CIs). Multiple logistic regression analysis was performed to determine if several baseline characteristics were simultaneously associated with outcome., Results: Although several characteristics were significant predictors of recurrence univariately, by multivariate analysis, multiple adenomas at follow-up were more likely when patients had > or = 3 baseline adenomas (OR, 2.25; 95% CI, 1.20-4.21) or at least 1 tubulovillous adenoma (OR, 2.12; 95% CI, 1.12-4.02). No specific characteristic was associated with recurrence of high-risk polyps (> or = 1 cm, villous, severe atypia). Seventy percent of patients with 1 or 2 baseline adenomas had no recurrence, and only 3.3% had any adenomas of clinical concern., Conclusions: Number and type of baseline adenomas predict recurrent adenomas, but the recurrence is rarely of clinical concern. Patients with 1 or 2 tubular adenomas constitute a low-risk group for whom follow-up might be extended beyond 3 years.

Upper gastrointestinal polyps are rare but common in the gastrointestinal polyposis syndromes. Although the majority of upper gastrointestinal polyps have no prognostic importance, they must be distinguished from the minority with an associated cancer risk.

Background: Data from studies using rodents suggest that dietary calcium inhibits bile acid-induced mucosal damage and experimental carcinogenesis in the large bowel. However, in humans, the effect of dietary calcium and calcium supplementation on proliferation and carcinogenesis in the large bowel has been unclear., Purpose: To assess the effect of calcium supplementation on rectal mucosal proliferation in humans, we conducted a multicenter, randomized, placebo-controlled, double-blinded trial., Methods: Participants were part of a larger multicenter chemoprevention trial; all were at high risk for large-bowel neoplasia, with at least one large-bowel adenoma removed endoscopically within the 3 months before study entry but with no known polyps remaining. Subjects were randomly assigned to receive daily either 3000 mg of calcium carbonate (providing 1200 mg elemental calcium) or an identical-appearing placebo tablet. During a scheduled endoscopy 6-9 months after random assignment (approximately 1 year after the qualifying endoscopy), rectal mucosal samples were obtained from 333 patients (173 assigned to calcium and 160 assigned to placebo). Proliferating cell nuclear antigen (PCNA) labeling indices (LIs) were computed as the measure of proliferation in specimens from 146 patients receiving calcium and 129 patients receiving placebo. Bromodeoxyuridine (BrdU) labeling was used to measure proliferation in a smaller number of specimens (27 calcium-receiving and 31 placebo-receiving participants). For each scorable crypt having at least one labeled cell (or surrounded by crypts with at least one labeled cell), a crypt LI was calculated as the number of labeled cells divided by the total number of crypt cells. Crypt LIs were averaged to produce a participant's average LI., Results: The overall unadjusted mean PCNA LIs (+/- SE) were similar in the calcium and placebo groups (3.85% +/- 0.08% versus 3.92% +/- 0.08%, respectively, P = .30). The overall unadjusted mean BrdU LIs (+/- SE) were 3.88% +/- 0.30% in the calcium group and 3.54% +/- 0.21% in the placebo group (P = .54). PCNA labeling indices in the most luminal 40% of the crypt were small but, if anything, were higher in the calcium group. There was no patient subgroup within which calcium had an antiproliferative effect; the overall findings persisted among patients with high and low calcium intake, high and low fat intake, and high and low fiber intake., Conclusions: Calcium supplementation does not decrease rectal mucosal proliferation, as measured by PCNA (and BrdU) immunohistochemistry, in patients with previous large-bowel adenomas. This study, therefore, does not provide evidence for an anticarcinogenic effect of calcium.

Measures of rectal mucosal proliferation have been developed and used in research clinical settings, but their utility for larger-scale epidemiological studies remains uncertain. We assessed the suitability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA)-labeling indices (LIs) in the setting of a multicenter clinical trial of adenoma recurrence. Subjects at participating practices were asked to permit biopsy of normal rectal mucosa during a colonoscopy scheduled for other reasons. PCNA and BrdUrd labeling was performed, and corresponding LIs were computed. In general, subjects were willing to undergo biopsy during their scheduled procedures; less than 10% refused. Specimen preparation for PCNA was acceptable; the mean number of scorable crypts (+/- SE) was 12.99 +/- 0.37. Preparation for BrdUrd labeling was less successful, with a higher proportion of unscorable specimens and a lower mean number of scorable crypts. Among the 54 specimens with both LIs computed, the LI for PCNA was modestly higher than that for BrdUrd LI (4.1 +/- 0.2 and 3.7 +/- 0.2 respectively; P = 0.03). The rank order correlation between the two indices was 0.38). There was variation across centers in the PCNA LIs but few differences according to number of crypts scored. Measurement of rectal mucosal proliferation is feasible among endoscopy patients in large studies if PCNA is used; BrdUrd seems more difficult. The relationship between these two labels requires further study.

Mesenteric panniculitis (MP) is characterized by an abdominal inflammatory reaction and mesenteric fat necrosis. Clinically, MP manifests as recurrent abdominal pain, pyrexia, and space-occupying peritoneal masses. We report a patient with MP, severe enough to require immunosuppressant treatment, who developed a recurrent pleural effusion. Malignant mesothelioma was identified in the pleural space 3 yr after initial pleural investigation. This case is the second report of pleural effusion associated with MP. It is the first report in which thoracic mesothelioma and MP occurred together. MP has been associated with other malignancies.

A preoperative induction chemotherapy regimen consisting of two monthly courses of etoposide, doxorubicin, and cisplatin was given to 13 patients with nonmetastatic adenocarcinoma of the distal esophagus or gastroesophageal junction. Esophageal ultrasound examination was performed both before chemotherapy and again before surgery. Induction chemotherapy was poorly tolerated with 10 of the 13 patients experiencing at least one episode of severe neutropenia. Two of the 13 patients refused the second course of treatment. A symptomatic response to chemotherapy, defined as a reduction in the presenting symptom, was noted in 10 of the 13 patients (77%). Endoscopic improvement occurred in 9 of the 13 patients (69%). Esophageal ultrasound evidence of a reduction in either T or N stage was noted in only 2 of the 13 patients (15%), however, and neither of these responses was confirmed pathologically. Clinical evidence of disease progression was noted in 4 patients during chemotherapy. With a median follow-up of 31 months, the relapse-free and overall survivals are 25% and 31%, respectively. Despite significant toxicity, our chemotherapy regimen would be considered successful if assessed by symptomatic or esophagoscopic improvement. Esophageal ultrasound, careful pathologic staging, and our disappointing survival rates, however, suggest limited, if any, value for this approach.

A review of the endoscopy reports and pathology results from esophagogastroduodenoscopy (EGD) of all patients with familial adenomatous polyposis (FAP) undergoing such an examination was performed. Two hundred forty-seven patients were identified, with an overall prevalence of duodenal adenomas of 66 percent and of fundic gland polyps of 61 percent. Analysis of our more recent experience (1986 to 1990) shows the prevalence to be 88 percent and 84 percent, respectively. A normal-appearing papilla was adenomatous in 50 percent of cases. No case of periampullary carcinoma developed in patients under surveillance. Routine EGD is indicated for patients with FAP. Duodenal adenomas and fundic gland polyps will occur in the majority of patients.

Dieulafoy's vascular malformation is an underdiagnosed cause of massive, often recurrent upper gastrointestinal hemorrhage. Attempted endoscopic treatment of Dieulafoy's lesion has been recommended prior to surgery in many instances, but may occasionally be employed as primary therapy in patients that are not considered good "operative risks." Although generally considered safe and effective therapy for nonvariceal hemorrhage, combination therapy by injection and thermocoagulation techniques may result in perforation. We present a patient with a Dieulafoy's lesion of the stomach that illustrates both the efficacy and risks of combination endoscopic therapy for nonvariceal gastrointestinal hemorrhage.