Anti-Yersinia antibodies are not associated with microscopic colitis in an American case-control study.

BACKGROUND: Microscopic colitis (MC), which consists of lymphocytic colitis and collagenous colitis, may be triggered by gastrointestinal infections. Studies have suggested a relationship between MC and Yersinia enterocolitica infection. We tested this hypothesis in a case-control study of American patients with MC. METHODS: Serum was collected from 47 patients with MC and 44 age- and gender-matched healthy controls at a large referral center in the mid-western United States. Anti-IgA and IgG antibodies to Y. enterocolitica were measured using an enzyme-linked immunosorbent assay (ELISA). Fisher's exact test was used to assess statistical significance. RESULTS: There were no differences between the two groups for seroprevalence of anti-Yersinia IgA (cases 2.1%, controls 2.3%, p = 1.00) or IgG antibodies (cases 4.3%, controls 6.8%, p = 0.67). There was no correlation between antibody titers and duration of MC diagnosis. CONCLUSION: Our data do not support the role of exposure to Y. enterocolitica in an American group of patients with MC.

A reduced segment II/III graft for neonatal liver failure with absence of detectable hepatocytes. A case report and literature review.

When hepatic failure occurs in newborns, most cases are because of viral hepatitis, metabolic diseases, and neonatal hemochromatosis. It is rare to have liver failure presenting in the first day after birth. We report a unique case of a newborn baby with liver failure in the first day of life who received a reduced segment II and III graft when she was 19 days old and became the youngest survivor of LDLT. Common and rare causes of liver failure in this age group were excluded by appropriate testing. She underwent a liver biopsy that showed a liver devoid of hepatocytes. Similar pathological findings were found in the explanted liver. She was discharged from the hospital with normal graft function three months after the transplant.

[Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma].

OBJECTIVE: To report the experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). METHODS: Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. RESULTS: Between January 1988 and February 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 were well without recurrence at 79, 82, 108, 128, 129 and 145 months. CONCLUSIONS: For patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC.

Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma.

This retrospective study reviews our experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. Between 1988 and 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 are well without recurrence at 5.7, 7.0, 8.7, 8.8, and 10.1 years. In conclusion, for patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC.

Older donor livers show early severe histological activity, fibrosis, and graft failure after liver transplantation for hepatitis C.

BACKGROUND: In hepatitis C virus (HCV)-positive liver transplant recipients, infection of the allograft and recurrent liver disease are important problems. Increased donor age has emerged as an important variable affecting patient and graft survival; however, specific age cutoffs and risk ratios for poor histologic outcomes and graft survival are not clear. METHODS: A longitudinal database of all HCV-positive patients transplanted at our center during an 11-year period was used to identify 111 patients who received 124 liver transplants. Graft survival and histological endpoints (severe activity and fibrosis) of HCV infection in the allografts were compared as a function of donor age at transplantation. RESULTS: By Kaplan-Meier analyses, older allografts showed earlier failure and decreased time to severe histological activity and fibrosis as compared with allografts from younger donors. By Cox proportional hazards analysis, older allografts were at greater risk for all severe histologic features and decreased graft survival as compared with younger allografts (P< or =0.02 for all outcomes). Analysis of donor age as a dichotomous variable showed that donors greater than 60 yr were at high risk for deleterious histologic outcomes and graft failure. An age cutoff of 60 yr showed a sensitivity of 94% and specificity of 67% for worse graft survival by receiver operating characteristics curve. CONCLUSIONS: Advanced donor age is associated with more aggressive recurrent HCV and early allograft failure in HCV-positive liver transplant recipients. Consideration of donor age is important for decisions regarding patient selection, antiviral therapy, and organ allocation.

Pathologist surgeon interface in idiopathic inflammatory bowel disease.

To accomplish the important tasks of establishing the diagnosis of inflammatory bowel disease and separating ulcerative colitis from Crohn's disease, there needs to be close cooperation among gastroenterologist, surgeon, and pathologist. Paying close attention to details of sampling and historical information plays a major role in this task, and an equally great role in identifying dysplasia and determining its significance. Important elements in this clinical-pathology interface are discussed in this article.

Positive serum cryoglobulin is associated with worse outcome after liver transplantation for chronic hepatitis C.

BACKGROUND: Recurrent hepatitis C virus (HCV) infection in patients after liver transplantation is an important clinical problem. Because serum cryoglobulins (CG) are known to be associated with an increased incidence of cirrhosis in nontransplant patients, the authors tested the hypothesis that CG would also predict aggressive recurrent HCV in patients after liver transplantation. METHODS: Using a longitudinal database, the outcomes of 105 allografts transplanted into 97 HCV-positive patients from 1991 through 2002 were analyzed on the basis of CG status using a retrospective cohort design. Fifty-nine CG-negative and 38 CG-positive patients were identified. Histologic outcomes and graft survival were analyzed using Kaplan-Meier estimates and Cox univariate and multivariate analyses. Both overall survival and HCV-specific survival (non-HVC-related deaths and graft losses censored) were analyzed. RESULTS: By Kaplan-Meier estimates, CG-positive patients showed earlier graft failure with decreased time to severe histologic activity and fibrosis as compared with CG-negative patients (P<0.05 for all outcomes). By univariate analysis, CG-positive patients had significantly higher risk ratios for shortened HCV-specific graft survival, severe activity-free survival, and severe fibrosis-free survival as compared with CG-negative patients (P<0.05 for all outcomes). In the multivariate model, CG was an independent predictor for severe activity-free, severe fibrosis-free, and HCV-specific graft survival (P<0.05 for all outcomes). CONCLUSIONS: CG-positivity is associated with severe recurrent HCV disease in liver transplant recipients.

Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease.

BACKGROUND: Atypical presentations of celiac disease appear to be at least as common as is the classic presentation of steatorrhea, diarrhea, and weight loss. OBJECTIVE: We examined the effect of a gluten-free diet on gastrointestinal symptoms in a cohort of US patients with celiac disease. DESIGN: A follow-up survey was conducted in 215 patients who were evaluated at the University of Iowa from 1990 through 1997 as having biopsy-confirmed celiac disease. The systematic survey asked detailed questions regarding gastrointestinal symptoms before and after the institution of a gluten-free diet in the patients, all of whom had been given the same dietary advice. RESULTS: The group consisted of 160 female and 55 male patients. Although diarrhea was the most frequent symptom in untreated celiac disease, steatorrhea occurred in only one-fifth of patients. Other complaints were common, and most responded to gluten exclusion. The benefit of gluten exclusion was equally apparent in men and women. Diarrhea responded in most patients, usually within days, and the mean time to resolution was 4 wk. Many patients had alternating diarrhea and constipation, both of which were responsive to the gluten-free diet. Most patients had abdominal pain and bloating, which resolved with the diet. CONCLUSIONS: Celiac disease causes a wide range of gastrointestinal symptoms. Clinicians must have a high level of suspicion to detect the atypical forms of celiac disease. With a gluten-free diet, patients have substantial and rapid improvement of symptoms, including symptoms other than the typical ones of diarrhea, steatorrhea, and weight loss.

Mechanisms of impaired gallbladder contractile response in chronic acalculous cholecystitis.

The mechanisms involved in the impaired gallbladder contractile response in chronic acalculous cholecystitis are unknown. To determine the mechanisms that may lead to impaired gallbladder emptying in chronic acalculous cholecystitis, gallbladder specimens removed during hepatic resection (controls) and after cholecystectomy for chronic acalculous cholecystitis were attached to force transducers and placed in tissue baths with oxygenated Krebs solution. Electrical field stimulation (EFS) (1 to 10 Hz, 0.1 msec, 70 V) or the contractile agonists, CCK-8 (10(-9) to 10(-5)) or K(+) (80 mmol/L), were placed separately in the tissue baths and changes in tension were determined. Patients with chronic acalculous cholecystitis had a mean gallbladder ejection fraction of 12% +/- 4%. Pathologic examination of all gallbladders removed for chronic acalculous cholecystitis revealed chronic cholecystitis. Spontaneous contractile activity was present in gallbladder strips in 83% of control specimens but only 29% of gallbladder strips from patients with chronic acalculous cholecystitis (P < 0.05 vs. controls). CCK-8 contractions were decreased by 54% and EFS-stimulated contractions were decreased by 50% in the presence of chronic acalculous cholecystitis (P < 0.05 vs. controls). K(+)-induced contractions were similar between control and chronic acalculous cholecystitis gallbladder strips. The impaired gallbladder emptying in chronic acalculous cholecystitis appears to be due to diminished spontaneous contractile activity and decreased contractile responsiveness to both CCK and EFS.

Emerging eosinophilic (allergic) esophagitis: increased incidence or increased recognition?

CONTEXT: Eosinophilic esophagitis is a disease of the esophagus with distinct histologic features (prominent intraepithelial eosinophils, particularly superficial with clustering) and characteristic endoscopic features (trachealization, white plaques). The presence of intraepithelial eosinophils had been recognized since 1982 as indicative of reflux esophagitis but little attention was initially paid to their numbers or location. Eosinophilic esophagitis has been recently described and there have been a number of reports that its incidence is on the rise. It had been our impression that eosinophilic esophagitis was being seen more frequently, perhaps resulting from some environmental change. OBJECTIVE: To investigate the increased prevalence of eosinophilic esophagitis. DESIGN: We analyzed a similar group of cases from 2005 (n = 150) as compared with 1990 (n = 115). Consecutive patients with mucosal esophageal biopsies from May through June of the respective years were included in the analysis. Patients with Barrett metaplasia or with carcinoma were excluded. The highest density of intraepithelial eosinophils for each patient was recorded as the number of intraepithelial eosinophils per single high-power field. The patients were categorized by the number of intraepithelial eosinophils per high-power field with those cases with greater than 20 intraepithelial eosinophils per high-power field representing eosinophilic esophagitis. RESULTS: There was no difference in the incidence of eosinophilic esophagitis between 1990 and 2005. CONCLUSIONS: The apparent increased incidence of eosinophilic esophagitis is largely a result of an increase in recognition rather than an increase in disease resulting from an environmental factor.

Hemosiderosis is associated with accelerated decompensation and decreased survival in patients with cirrhosis.

AIM: Although hepatic iron deposition unrelated to hereditary hemochromatosis is commonly observed in cirrhosis, its clinical significance is unclear. The aim of this study was to examine the outcomes of cirrhotic patients with and without hemosiderosis. METHODS: Patients with an initial liver biopsy demonstrating cirrhosis between January 1993 and December 1997 were identified using the Department of Pathology database. Based on iron staining, patients were characterized as siderotic or nonsiderotic. Charts were reviewed to determine outcomes. RESULTS: Siderotic patients had significantly higher Child-Pugh (CP) and model for end-stage liver disease (MELD) scores. Their median survival without transplant was 23 months vs. 85 months in the nonsiderotics (P<0.0001, confidence interval: 95%). On univariate analysis, siderosis was associated with a hazard ratio of 2.74 (P<0.0001). On multivariate analysis, the effect of siderosis was reduced but remained significant after correction for the CP or MELD score (hazard ratios 1.82 and 2.06, P=0.05 and 0.02, respectively). Child's A cirrhotics with hemosiderosis decompensated more rapidly and had shorter median survival than those without siderosis (P=0.007 and P=0.01, respectively). CONCLUSIONS: The presence of siderosis is associated with more advanced liver dysfunction. Even when the effects of baseline liver function are taken into account, siderosis is associated with decreased survival and more rapid decompensation in cirrhosis.

Chemical gastropathy: a distinct histopathologic entity in children.

BACKGROUND: Chemical gastropathy, also known as chemical or reactive gastritis, is a well-described histopathologic entity in adults. It is characterized by presence of foveolar hyperplasia, vascular congestion, lamina propria edema, and prominent smooth muscle fibers in the absence of inflammatory cells in the gastric antral mucosa. There are no data in children on this condition. METHODS: All children showing features of chemical gastropathy in antral biopsy specimens were identified from pathology database from 1997 to 2000. Antral biopsy specimens were reviewed to assess the diagnosis of chemical gastropathy using standard diagnostic criteria. Charts of the children diagnosed with chemical gastropathy were reviewed for clinical course, endoscopic findings, and risk factors. RESULTS: Twenty-one children (12 male, 9 female) with chemical gastropathy were identified. Common presenting symptoms were epigastric pain and vomiting. Eleven children were taking multiple medications, including nonsteroidal anti-inflammatory drugs. Endoscopy revealed esophagitis in 12, antral erythema in 7, and thick bile in the stomach in 7 children. Antral histology revealed foveolar hyperplasia in 19, congestion in 20, lamina propria edema and smooth muscle fibers in 16, and absence of inflammation in 19 patients. Acid suppression was the treatment in all patients. Mean follow-up duration was 11 months in 17 children. Symptoms resolved completely in 11 and partially in 6 patients. CONCLUSIONS: As in adults, chemical gastropathy occurs in children. The factors associated with chemical gastropathy in this survey were gastroesophageal reflux disease and intake of multiple medications, including nonsteroidal anti-inflammatory drugs.

Expression of antioxidant enzymes in diseases of the human pancreas: another link between chronic pancreatitis and pancreatic cancer.

INTRODUCTION: Chronic pancreatitis is a significant risk factor for pancreatic cancer and is associated with the generation of reactive oxygen species. Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species. There are three major types of primary intracellular antioxidant enzymes in mammalian cells: superoxide dismutase (SOD), catalase, and peroxidase, of which glutathione peroxidase is the most prominent. AIM: To determine the level of antioxidant enzymes in human pancreas from normal, chronic pancreatitis, and pancreatic cancer specimens. METHODOLOGY: Immunohistochemical analysis for manganese SOD, copper/zinc SOD, catalase, and glutathione peroxidase expression using the avidin-biotin-peroxidase complex method was performed on pancreatic specimens previously fixed in formalin and embedded in paraffin. A quantitative digital imaging methodology was used to examine antioxidant staining in the pancreatic tissue. Cytoplasmic regions of ductal and acinar cells were identified and digitized. Mean gray-level pixel values were then obtained for each of these regions. RESULTS: Cytoplasmic values of manganese SOD, catalase, and glutathione peroxidase were decreased in pancreatic cells from chronic pancreatitis specimens when compared with normal pancreas. In pancreatic carcinoma specimens, mean cytoplasmic gray-level values of all antioxidant enzymes were decreased when compared with normal pancreas. CONCLUSION: There appears to be a gradual decrease in antioxidant enzyme expression in pancreatic cells from normal pancreas to chronic pancreatitis to pancreatic cancer.

Ulcerative ileitis encountered at ileo-colonoscopy: likely role of nonsteroidal agents.

BACKGROUND & AIMS: Ileoscopy is increasingly practiced, but it is unclear what diagnostic and management decisions should ensue if ulcerations are encountered. METHODS: The lead author identified 40 patients with ulcerative ileitis during 1900 consecutive ileoscopies in a community practice. We analyzed the clinical, endoscopic, and histopathologic findings in these patients and related them to drug usage. RESULTS: Although most patients were asymptomatic, ileitis likely contributed to blood loss in 14 and to right lower quadrant pain in one. Endoscopy revealed multiple, discrete, fibrin-covered ulcerations in the prevalvular segment with patches of erythematous stippling, normal intervening mucosa, and occasional mucosal scars or webs. Histologic findings included focal superficial neutrophilic infiltrates, edema, mucosal hemorrhage, lymphatic dilatation, fibromuscular hyperplasia, prominence of the muscularis mucosae, and antral and Paneth cell metaplasia. Granulomas, fissure ulcers, and apoptosis were notably absent. No specific disease process developed in a median follow-up of 3.2 years. Thirty-three patients admitted recently taking nonsteroidal anti-inflammatory drugs (NSAIDs), notably: enteric-coated aspirin at 325 mg/day or less (19), selective cyclooxygenase-2 inhibitors (5), and nonacetylated salicylates (3). Three fourths of nonsteroidal users were taking agents with low or intermediate gastroduodenal toxicity. Lesions disappeared after drug withdrawal, and reappeared on resumption. CONCLUSIONS: Ileoscopy during colonoscopy may identify an ulcerative ileitis. This lesion likely contributes to gastrointestinal blood loss and other clinical manifestations, and likely is caused by NSAID use, including those usually associated with low toxicity or at low doses. Features of NSAID-ileitis overlap with Crohn's ileitis, but differentiation of the 2 entities is critical for appropriate management.

Liver transplantation for disulfiram-induced fulminant hepatic failure.

Disulfiram has been used as a popular adjunct in programs for alcohol rehabilitation. However, in rare cases, disulfiram has been reported to cause fulminant hepatitis. Disulfiram use and its associated complications in adolescents have received minimal attention in the literature. We report the first pediatric case of successful orthotopic liver transplantation for disulfiram-induced fulminant hepatic failure in a 16-year-old girl, who developed an idiosyncratic reaction associated with short-term, low-dose disulfiram use, as evidenced by her liver biopsy and explanted liver. This case report indicates that a high index of suspicion, and aggressive therapeutic interventions are necessary to recognize and manage disulfiram-induced fulminant hepatic failure in adolescents. Success of this case suggests that transplant centers should consider liver transplantation of an adolescent alcoholic patient with fulminant hepatic failure due to non-alcohol-related causes such as disulfiram. Orthotopic liver transplantation should be considered early in the management of disulfiram-induced fulminant hepatic failure.

Longitudinal measurement of methotrexate liver concentrations does not correlate with liver damage, clinical efficacy, or toxicity during a 3.5 year double blind study in rheumatoid arthritis.

OBJECTIVES: In patients with rheumatoid arthritis (RA), we examined whether methotrexate (MTX) and MTX polyglutamate accumulation in the liver correlated with clinical efficacy or clinical/laboratory toxicity. We also began preliminary examination of a new histologic index of liver histology (the Iowa Score) relative to the Roenigk grading system. METHODS: Forty patients with RA participated in a prospective, double blind, 3.5 year study of MTX treatment. Liver biopsies, liver MTX and MTX polyglutamate concentrations, laboratory tests, evaluation of disease activity, and evaluation of adverse events were done prospectively at baseline and at 1, 2, and 3.5 years. Biopsies were examined using the Roenigk grading system and an additional histological scoring system. Radiochemical ligand binding assays and HPLC methods were used to measure MTX and MTX polyglutamates. Statistical analysis included ANOVA, linear regression, and logistic regression modeling. RESULTS: No significant changes in the mean values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, albumin, or hemoglobin occurred. A significant percentage of patients had at least one abnormal alkaline phosphatase, AST, or ALT (25 to 52%), although most abnormalities were small and transient. Histological abnormalities did not progress using either the Roenigk or the Iowa score. The last abnormal AST, the number of abnormal AST and ALT, and female sex correlated with histological liver abnormalities (r2 = 0.41) using a new preliminary histologic scoring system (the Iowa Score). Amount of alcohol use correlated with fatty change, and the MTX dose at biopsy was associated with liver histological abnormalities (p = 0.03 and 0.049, respectively). Total liver MTX concentrations were stable from Year 1 to Year 3.5 and the percentage of higher order polyglutamates was relatively high (38 to 56%) relative to monoglutamates. No correlation of these concentrations with clinical response or toxicity, histology, or liver function tests could be documented. CONCLUSION: This analysis describes the accumulation and stabilization of MTX concentrations in the liver and examined correlations between MTX liver concentrations, patient demographics, liver histology, concomitant medications, and disease activity. No such correlations were found, decreasing the likelihood that MTX concentrations in serum would be useful measures to predict significant hepatotoxicity.