Primary sclerosing cholangitis--an ulcerative colitis-associated illness with surgical consequences

Primary sclerosing cholangitis (PSC) is generally associated with ulcerative colitis (UC). The disease typically progresses slowly, but ultimately, and leads to cirrhosis, liver failure or bile duct cancer. PSC patients with simultaneous ulcerative colitis are also at higher risk for colorectal cancer. At the present time, there is no effective treatment for PSC, although preliminary data show encouraging results after treatment with ursodeoxycholic acid. However, there are no data concerning the delay or prevention of progress of the disease with this drug, because follow-up time is not yet long enough. Isolated bile duct strictures should be treated endoscopically. The possible effect of proctocolectomy on the course of PSC is controversial. Liver transplantation is the therapy of choice for PSC in its final stage. The 5-year survival rate (89%) is significantly better than after transplantation for other indications. Patients with ulcerative colitis have to be followed up by lifelong colonoscopy. Although the course of UC after transplantation is mostly asymptomatic, these patients are at higher risk for colorectal cancer.     

Risk indicators for inflammatory bowel disease

We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.     

Pericholangitis and sclerosing cholangitis are risk factors for dysplasia and cancer in ulcerative colitis

Known risk factors for the development of dysplasia and cancer in ulcerative colitis (UC) patients are: 1) increased extent and duration of disease and 2) increased age at symptom onset. This case-control study was performed to determine whether cholestatic liver disease is associated with neoplastic transformation. Twenty-nine UC patients with extensive disease of long duration and dysplasia or cancer detected in a cancer surveillance program were pair-matched to UC patients without neoplasia from a large inflammatory bowel disease registry matched on extent of disease, sex, and calendar year of disease onset. Of the 29 cases, 10 were found to have cholestatic liver disease; nine with pericholangitis and one with primary sclerosing cholangitis (PSC). Two controls had PSC. Cholestatic liver disease was a significant risk factor for the development of dysplasia or cancer (odds ratio 9.00, 95% confidence interval 1.14-71.0). Increased age at symptom onset also was found to be a significant risk factor for neoplasia (odds ratio 1.04 for each additional year, 95% confidence interval 1.00-1.08) that did not exhibit confounding or interacting effects with cholestatic liver disease. The degree of neoplasia (low-grade dysplasia, high-grade dysplasia, or cancer) did not appeared to affect the results. Therefore, cholestatic liver disease, either pericholangitis or PSC, was significantly associated with the development of dysplasia or cancer in UC patients and should be considered an important risk factor for neoplastic transformation.     

Differential effects of insulin-like growth factor-I and follicle-stimulating hormone on proliferation and differentiation of bovine cumulus cells and granulosa cells

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) has been suggested as a risk factor for the development of colorectal cancer in ulcerative colitis (UC); however, previous studies of this association have been limited by small numbers of patients with PSC or have been performed retrospectively. This study prospectively evaluates the risk and natural history of colonic tumorigenesis in patients with PSC and UC and compares it with patients with UC without PSC. METHODS: Twenty patients with PSC and UC and 25 control patients with UC were followed prospectively by colonoscopic surveillance using extensive mucosal biopsy sampling. All control patients with UC had disease extending beyond the sigmoid colon of > or = 8 years' duration; patients with PSC and UC were studied regardless of disease duration. RESULTS: Forty-five percent (9 of 20) of the patients with PSC and UC had dysplasia compared with 16% (4 of 25) of the control patients with UC (P < or = 0.002). Prior liver transplantation did not affect the risk of colonic dysplasia. The time course for progression to dysplasia was similar between the patients with PSC and UC and the patients with UC; however, the patients with PSC and UC were five times more likely to develop dysplasia. CONCLUSIONS: Patients with PSC and UC represent a subset of patients with UC who are at markedly increased risk for colonic neoplasia and who need close colonoscopic surveillance with extensive biopsy sampling.     

Sclerosing cholangitis and ulcerative colitis. Regional prevalence

The aim of the study was to determine the prevalence of primary sclerosing cholangitis (PSC) in a regional population of patients with ulcerative colitis (UC). Three hundred and five patients with UC followed over a 12 year period were examined for elevations of serum alkaline phosphatase (> 280 U/l). Twenty four such patients were found. If no cause of these elevations were found by initial investigations, endoscopic retrograde cholangiography was performed in order to determine whether they had PSC. Eleven patients were found to have PSC (3.6%), of whom five had progressive disease, including two deaths from cholangio-carcinoma, during a six-year observation period. We found no certain relation between the extent, duration or activity of ulcerative colitis and the presence of PSC. Alkaline phosphatases were elevated up to 3.7 times the upper reference level, the aminotransferases were only found to be mildly elevated.     

Failure of colonoscopic surveillance in ulcerative colitis

A prospective surveillance programme for patients with longstanding (> = 8 years), extensive (> = splenic flexure) ulcerative colitis was undertaken between 1978 and 1990. It comprised annual colonoscopy with pancolonic biopsy. One hundred and sixty patients were entered into the programme and had 739 colonoscopies (4.6 colonoscopies per patient; 709 patient years follow up). Eight eight per cent of examinations reached the right colon. There was no procedure related death. One Dukes's A cancer was detected. Forty one patients (25%) defaulted. Of these 25 remain well; 13 are unaccounted for, and one died from colonic cancer. One patient had colectomy for medical reasons, and another died of carcinoma of the pancreas. Retrospectively an additional 16 eligible patients were identified who had not been recruited. Of these, 14 remain well, two are unaccounted for. None developed colonic cancer. Four patients refused colonoscopy. All remain well. Over the same period seven other cases of colonic cancer were found in association with ulcerative colitis, two in patients who had erroneously been diagnosed as having only proctitis and were therefore not entered into the programme, but were found at operation to have total colitis, one in a patient with colitis of seven years duration, and four patients who had previously attended the clinic but had been lost to follow up before 1978 and then had represented with new symptoms during the surveillance period. Thus, of the nine colitis related cancers diagnosed in this centre during the study period only one was detected by the surveillance programme. The results of this large study, a a review of published works, cast doubts on the effectiveness of colonoscopic surveillance programmes in detecting colorectal cancer in patients with ulcerative colitis.     

What is the association of primary sclerosing cholangitis with sex and inflammatory bowel disease in Turkish patients?

BACKGROUND/AIMS: In the Western world, primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that is associated with inflammatory bowel disease (IBD), particularly chronic ulcerative colitis and, to a lesser degree, Crohn's disease. The goal of this study was to determine the prevalence of PSC in Turkish patients with IBD and chronic amebic colitis, a disease that is endemic in Turkey. METHODOLOGY: During a 10-year period, between 1986 and 1996, a total of 81 IBD (64 ulcerative colitis and 17 Crohn's disease) patients and 127 patients with chronic amebic colitis were seen and evaluated with radiologic, serologic, immunologic and pathologic tests. Whenever a clinical or biochemical finding suggested the presence of co-existent hepatic and/or biliary disease, the patient was further evaluated by liver biopsy, auto-antibodies and endoscopic retrograde cholangiopancreatography (ERCP) to determine whether they also had PSC or some other form of liver disease. As a disease control group, a total of 752 patients with clinical and/or laboratory evidence of pancreaticobiliary disease were also studied. In 86 of these 752 patients (10%), a primary disorder of the biliary tree was diagnosed by ultrasonography, computed tomography, peritoneoscopy, liver biopsy, ERCP and abdominal laparotomy. In addition, all 86 patients of the control group were evaluated endoscopically in order to determine whether they had any associated gastrointestinal condition of the upper or lower gastrointestinal tracts. After establishing final diagnoses of IBD, amebic colitis and PSC, these patients were evaluated with respect to their socio-economic status. A high protein diet (1.8 gram/kg/day) was administered to those patients with chronic amebic colitis and IBD during the active period of the disease. RESULTS: Of the 208 patients (81 with IBD and 127 with chronic amebic colitis), no cases of PSC were identified. Of the 86 patients in the control group with primary biliary tract disease, 45 had a biliary system malignancy, 14 had primary biliary cirrhosis (PBC), 16 had PSC, 3 had Caroli's disease, 6 had a common bile duct cyst, and 2 had gallbladder adenomatosis. All but 1 of the 16 patients with PSC were female. CONCLUSIONS: These data suggest that, in contrast to findings in Western Europe and the USA, in Turkey: 1) PSC is not regularly associated with idiopathic IBD; 2) most patients with PSC are female; 3) PSC accounts for only 18% of patients with a primary disorder of the biliary tree; 4) the incidence of small-duct primary sclerosing cholangitis is greater than that reported in the literature; and, 5) the incidence of IBD and PSC in Turkey is relatively lower than in other countries.     

Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ

BACKGROUND: No one has previously examined the relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. METHODS: A case-control study was performed with 129 cases of colorectal carcinoma in situ and 258 matched controls among examinees undergoing a health check-up in Tokyo from January 1991 to March 1993. RESULTS: There was a significant, positive association between serum total cholesterol levels and the risk of colorectal carcinoma in situ after adjustment for age, sex, body mass index, smoking status and alcohol consumption. Serum triglyceride levels were significantly and positively associated with colorectal carcinoma in situ risk regardless of adjustment for the above covariates. Although there was no clear relation between colorectal carcinoma in situ and fasting plasma glucose levels, a modest increase of colorectal carcinoma in situ risk was observed in the highest category (> or =116 mg/dl) of fasting plasma glucose levels. CONCLUSIONS: The findings suggest a positive association between serum total cholesterol levels and the risk of colorectal cancer, rather than an inverse relation. The strong association with serum triglyceride levels and the weak association with fasting plasma glucose levels support the hypothesis that hyperinsulinaemia may play an important role in colorectal carcinogenesis.     

Creativity of undergraduates with and without family history of alcohol and other drug problems

BACKGROUND: Colonoscopic surveillance is a standard procedure in many patients with long standing, extensive ulcerative colitis (UC), in order to avoid death from colorectal cancer. No conclusive proof of its benefits has been presented however. AIMS: To evaluate the association between colonoscopic surveillance and colorectal cancer mortality in patients with UC. PATIENTS: A population based, nested case control study comprising 142 patients with a definite UC diagnosis, derived from a study population of 4664 patients with UC, was conducted. METHODS: Colonoscopic surveillance in all patients with UC who had died from colorectal cancer after 1975 was compared with that in controls matched for age, sex, extent, and duration of the disease. Information on colonoscopic surveillance was obtained from the medical records. RESULTS: Two of 40 patients with UC and 18 of 102 controls had undergone at least one surveillance colonoscopy (relative risk (RR) 0.29, 95% confidence interval 0.06 to 1.31). Twelve controls but only one patient with UC had undergone two or more surveillance colonoscopies (RR 0.22, 95% confidence interval 0.03 to 1.74), indicating a protective dose response relation. CONCLUSION: Colonoscopic surveillance may be associated with a decreased risk of death from colorectal cancer in patients with long standing UC.     

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.     

A retrospective study of infantile hydrocephalus observed in Benin

The aetiology of ulcerative colitis (UC) is unknown. However, much interest has been devoted recently to the relationship between appendicectomy and ulcerative colitis. A case-control study was conducted, comparing appendicectomy rates between 110 patients with UC (group 1) and 136 patients attending an orthopaedic clinic free from UC (group 2). The appendicectomy rates were 0.9% (group 1) and 10.3% (group 2), respectively (P < 0.002). The present study shows that patients with ulcerative colitis had rarely undergone appendicectomy before the first manifestation of colitis. Further research on this relationship is called for.     

Incidence of inflammatory bowel diseases in the department of Puy-de-D?me in 1993 and 1994. EPIMICI. Epidémiologie des Maladies Inflammatoires Cryptogenetiques de l'Intestin group

The aim of this prospective epidemiological study was to investigate the incidence of Inflammatory Bowel Disease in the Puy-de-D?me county using the same methodology as EPIMAD's registry. METHODS: From 01/01/93 to 31/12/94, each gastroenterologist (n = 22) collected patients consulting for the first time with clinical symptoms compatible with inflammatory bowel disease. Data were reported on a questionnaire by an interviewer practitioner. The final diagnosis of Crohn's disease and ulcerative colitis was made in a blind manner by two expert gastroenterologists and recorded according to the Calkin's criteria as definite, probable, or possible diagnosis, or unclassifiable chronic colitis or acute colitis. RESULTS: 167 new cases were identified: 112 (67.1%) inflammatory bowel disease for the combined group of definite and probable cases with 79 Crohn's disease (70.5%), 29 ulcerative colitis (25.9%) of which 11 ulcerative proctitis (37.9%), 4 unclassifiable chronic colitis (3.6%) and 55 acute colitis (32.9%). The crude and age-adjusted incidence (per 10(5)/year) was respectively 6.6 and 5.7 for Crohn's disease and 2.4 and 1.9 for ulcerative colitis. The highest age-specific incidence rate for Crohn's disease was between 40-49 years (14.1) and for ulcerative colitis between 80-89 years (6.8). The female/male ratio was 0.8 for Crohn's disease and 1.1 for ulcerative colitis. The median age at the time of diagnosis was 42.6 years for Crohn's disease and 35.3 years for ulcerative colitis. CONCLUSIONS: These preliminary findings revealed a high incidence of Crohn's disease and low of ulcerative colitis in this county. However, these results must be managed carefully because these data were recorded only on two years and the inflammatory bowel disease classified possible and acute colitis require a follow-up.     

The safety of transurethral prostatectomy: a cohort study of mortality in 9,416 men

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. AIMS: To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. PATIENTS: Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. METHODS: A positive ANCA serology was determined with a standard indirect immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. RESULTS: There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). CONCLUSIONS: p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.     

Factors related to the presence of IgA class antineutrophil cytoplasmic antibodies in ulcerative colitis

OBJECTIVES: Few studies have assessed the IgA antineutrophil cytoplasmic antibody (ANCA) positivity in ulcerative colitis patients and there is no information about factors related to its synthesis and its status after colectomy. The aims of the study were to assess the serum IgA ANCA prevalence in ulcerative colitis patients, both nonoperated and operated, and to determine the clinical factors related to this positivity. METHODS: Fifty-four ulcerative colitis patients, 63 ulcerative colitis colectomized patients (32 with Brooke's ileostomy and 31 with ileal pouch anal anastomosis), and 24 controls were studied. Antineutrophil cytoplasmic antibodies were detected by specific indirect immunofluorescent assays. RESULTS: The percentage of IgA ANCA was significantly higher in patients with ileal pouch anal anastomosis (45%) than in patients with Brooke's ileostomy (22%). There were no differences related to the presence of pouchitis in ileal pouch anal anastomosis patients. Patients with nonoperated extensive colitis (47%) had a significantly higher percentage of IgA ANCA than patients with proctitis (19%). Total percentage of ANCA (IgA and/or IgG) tended to be higher in ulcerative colitis and in patients with ileal pouch anal anastomosis than in patients with Brooke's ileostomy. However, in ileal pouch anal anastomosis patients, ANCA positivity was mainly due to exclusive IgA production. CONCLUSIONS: A substantial percentage of ulcerative colitis patients, and especially colectomized patients with ileal pouch anal anastomosis, had IgA ANCA, suggesting that ANCA production in ulcerative colitis might be stimulated by an immune reaction in the intestinal mucosa.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

Neutrophil signaling alteration: an adverse inflammatory response after burn shock

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch-anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis. METHODS: Five groups of children and adolescents (age, <20 years) were studied, with the following histories: acute pouchitis and history of ulcerative colitis; chronic pouchitis and history of ulcerative colitis; pouchitis with Crohn's disease features and a history of ulcerative colitis; no pouchitis and a history of ulcerative colitis; and familial adenomatous polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels and titers were detected in postoperative sera by enzyme-linked immunosorbent assay, and positive results were subtyped by indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with familial adenomatous polyposis (p < 0.001). There was no significant correlation between the frequency of perinuclear antineutrophil cytoplasmic antibodies and ulcerative colitis patient subgroups (patients with and without pouchitis, 66% and 75%). Similarly, there was no significant correlation between the frequency of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis patient subgroups (patients with and without pouchitis, 19% and 8%). The frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with Crohn's disease features (50%), was increased, but this difference was not significant. CONCLUSIONS: There is a high frequency of perinuclear antineutrophil cytoplasmic antibodies in children and adolescents who undergo ileal pouch-anal anastomosis for ulcerative colitis, whether or not they have pouchitis. The frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this patient population. Additional studies will be required to determine whether the presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with the postoperative development of features of Crohn's disease.     

Cigarette smoking and the colorectal adenoma-carcinoma sequence: a hypothesis to explain the paradox

As recognized precursor lesions to colorectal cancer, colorectal adenomatous polyps have been studied to enhance knowledge of colorectal cancer etiology. Although most of the known risk factors for colorectal cancer are also associated with the occurrence of colorectal adenomas, cigarette smoking has had a strong, consistent relationship with colorectal adenomas but is generally not associated with colorectal cancer. The explanation for this paradox is unknown. With data collected in 1986-1988 during a large case-control study based on colonoscopy results in New York City, New York, the authors investigated the possibility that the paradox may arise because subjects with colorectal adenomas were included in the control group of cancer case-control studies. The authors found a statistically significant increased risk between heavy cigarette smoking (smokers with > or = 40 pack-years of smoking) and risk of adenoma (odds ratio (OR) = 1.61, 95% confidence interval (CI) 1.06-2.44). They saw no increased colorectal cancer risk from heavy cigarette smoking (OR = 1.02, 95% CI 0.52-1.99) using a "manufactured" control group to simulate a typical unscreened, population-based control group. When the authors compared these colorectal cancer cases with an adenoma-free control group examined by colonoscopy in a polytomous model with several case groups (newly diagnosed adenomas, carcinoma in situ, intramucosal carcinoma, and colorectal cancer), they found that the risk for 20-39 pack-years of smoking was elevated, although not statistically significant, and was similar for all four case groups. The risk for the highest smoking category (> or = 40 pack-years) was more strongly elevated in all four case groups, although it was statistically significant for only the newly diagnosed adenoma and the carcinoma in situ cases (adenomas, OR = 1.59, 95% CI 1.05-2.42; carcinoma in situ, OR = 2.05, 95% CI 1.01-4.15; intramucosal carcinoma, OR = 1.30, 95% CI 0.61-2.77; and colorectal cancer, OR = 1.30, 95% CI 0.64-2.65). While the authors' study is weakened by the lack of statistical significance concerning risk for colorectal cancer, these data offer some support for the hypothesis that the association between cigarette smoking and risk of colorectal cancer may have been masked by inclusion in the control group of subjects with adenomas. They also suggest that the major effect of smoking on the colorectal adenoma-carcinoma sequence occurs in the earlier stages of the formation of adenoma and the development of carcinoma in situ.     

Liver transplantation in a 29-year-old patient with gallbladder carcinoma complicating primary sclerosing cholangitis

Patients with primary sclerosing cholangitis (PSC) are at increased risk for cholangiocarcinoma. This tumor usually is a fatal complication, median survival after diagnosis is less than six months. In an asymptomatic 29-year-old patient with long-standing PSC and ulcerative colitis, routine abdominal ultrasound demonstrated an irregular mass, 11 x 13 mm, in the gallbladder. Cholecystectomy was performed, and histological examination demonstrated a moderately differentiated adenocarcinoma with infiltration of all layers of the gallbladder and invasion of local lymphatic vessels. Extensive diagnostic work-up failed to consistently demonstrate metastatic disease, and the patient was offered a liver transplantation. 24 months after the operation, the patient feels well and there is no indication of tumor recurrence. In carefully selected patients with gallbladder carcinoma complicating PSC, liver transplantation may be a therapeutic option.     

Military history of patients with inflammatory bowel disease: an epidemiological study among U.S. veterans

OBJECTIVES: The military history of patients with inflammatory bowel disease (IBD) contains types of exposure that are not available through other sources and may provide clues about the as-yet unknown etiology of IBD. We therefore sought to describe the epidemiology of IBD among veterans, with particular emphasis on their military history. METHODS: A case-control study compared 10,544 IBD patients and 42,026 controls with respect to age, gender, ethnicity, time period of military service, military duty in Vietnam, status as prisoner of war, and exposure to Agent Orange. RESULTS: Subjects with Crohn's disease were younger than those with ulcerative colitis or without IBD (odds ratio: 0.85; 95% confidence interval [CI]: 0.83-0.87). Both types of IBD affected female veterans significantly more often than male veterans, the relative female predominance being more pronounced in Crohn's disease than ulcerative colitis (0.70; 0.61-0.81 vs 0.83; 0.71-0.96). Whites were more prone to develop both types of IBD than nonwhites (2.46; 2.27-2.68 vs 2.11; 1.95-2.27). Military duty in Vietnam and a status as prisoner of war both exerted a protective influence against Crohn's disease (0.84; 0.75-0.96 and 0.60; 0.41-0.87, respectively), but not ulcerative colitis. CONCLUSIONS: The results are consistent with the hypothesis that exposure to poor sanitation decreases the future risk of developing Crohn's disease.     

Association between coronary heart disease and cancers of the breast, prostate, and colon

Coronary heart disease (CHD) and cancers of the breast, prostate, and colon are more common in industrialized countries than in the developing world, and to some degree, these conditions appear to share risk factors. To investigate whether there is an association between these cancers and a prior history of CHD, a hospital-based case-control study was conducted at Columbia-Presbyterian Medical Center in New York. The study was based on 252 breast cancer cases, 256 colorectal cancer cases, and 322 benign surgical controls, all of whom underwent biopsy or surgery between January 1989 and December 1992, and on 319 prostate cancer cases and 189 benign prostatic hypertrophy controls diagnosed between January 1984 and December 1986 (prior to widespread use of prostate-specific antigen screening). Medical records were reviewed on each, focusing on the preoperative anesthesia and surgical clearances. No association was found between a history of CHD and breast or colorectal cancer, but an elevated risk was found for prostate cancer (odds ratio, 2.00; 95% confidence interval, 1.18-3.39), using unconditional logistic regression with adjustment for appropriate confounders. No association was found between cigarette smoking and any of the three cancers. Aspirin use was protective for colorectal cancer (odds ratio, 0.35; 95% confidence interval, 0.17-0.73) but had no association with breast or prostate cancer. The study suggests that individuals with CHD are at elevated risk for prostate cancer but not breast or colorectal cancer. Etiological risk factors associated with CHD should be investigated with regard to prostate cancer. Patients with CHD may represent a high-risk group for prostate cancer and potential future targets for prostate cancer screening interventions.