Peri-Ampullary Metastasis From Endometrial Adenocarcinoma: A Rare Etiology of Obstructive Jaundice.

Endometrial cancer is the commonest gynecologic malignancy, of which adenocarcinoma is the most common histologic type. While most women who relapse present with local symptoms within 3 years of the initial diagnosis, metastatic disease usually involves the abdominal cavity and liver. Herein we present a rare case of a patient with a remote history of endometrial adenocarcinoma status-post curative surgical resection and adjuvant therapy who presented with obstructive jaundice proved to be secondary to peri-ampullary metastasis of uterine adenocarcinoma.

Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation.

BACKGROUND/AIMS: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end-stage autoimmune liver disease (ESALD), (ii) the correlation among auto-antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics. METHODS: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non-autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6-12 and > or = 24 months post-transplantation. Results were correlated with the HLA type of the recipient. RESULTS: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non-autoimmune) of the patients (five-fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA-DQ2 or HLA-DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post-transplantation. Post-transplantation, of the five patients with symptoms of 'classical' CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically 'silent' CD. CONCLUSIONS: Patients with ESALD, especially those who are HLA-DQ2 or HLA-DQ8 positive had a high prevalence of CD-associated antibodies. Both tTGAs and EMAs decreased post-transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.

Primary biliary cirrhosis: an infectious disease caused by Chlamydia pneumoniae?

BACKGROUND/AIMS: The etiology and pathogenesis of primary biliary cirrhosis (PBC) remain elusive. Both an infectious etiology and molecular mimicry have been implicated. The aim is to study the prevalence of Chlamydial antigens and RNA in the liver tissue of patients with PBC. METHODS: We compared the prevalence of Chlamydial antigen and RNA in 25 explants with PBC who underwent orthotopic liver transplantation with 105 explanted livers from other chronic liver disease. We also studied 14 liver biopsies from patients with early stages of PBC. Donor livers were also studied. RESULTS: In all 39 patients with PBC, Chlamydia pneumoniae antigens were present but not Chlamydia trachomatis, and only 9/105 (8.5%) of patients in the other categories were positive (P<0.01) for C. pneumoniae. Eight explanted PBC livers were tested for C. pneumoniae 16S RNA by in situ hybridization and were positive. CONCLUSIONS: The presence of C. pneumoniae antigen and RNA in liver tissue of patients with PBC suggests that C. pneumoniae antigen may trigger an immune response based on molecular mimicry.

The large GTPase dynamin is required for hepatitis B virus protein secretion from hepatocytes.

BACKGROUND/AIMS: The hepatocellular transport pathways and cellular proteins utilized during the packaging and secretion of hepatitis B virus are poorly understood. In this study, we tested if the large GTPase dynamin, a protein involved in vesicle formation and secretion at the trans-Golgi network in hepatocytes, is also used by hepatitis B virus (HBV) in secreting viral proteins. METHODS: Using HepG2.2.15 cells expressing the full-length HBV genome, we tested the effects of wild-type and mutant dynamin on the localization and secretion of two hepatitis B antigens, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Distribution of these two antigens was analyzed morphologically in cells transiently transfected with wild-type or mutant dynamin constructs, whereas secretion of the antigens was measured by testing for antigen levels in the media of transfected cells. RESULTS: Mutant dynamin was found to induce a striking redistribution of HBsAg and HBeAg to a perinuclear compartment, as well as a decrease in the levels of HBsAg and HBeAg present in cell culture media indicating a reduction in viral protein secretion. At the electron microscopy level, cells expressing the mutant dynamin showed a marked accumulation of viral particles in dilated cisternae of an uncharacterized cellular compartment. CONCLUSIONS: Intact dynamin function is required for secretion of HBV proteins from hepatocytes through an uncharacterized cellular compartment.

Etiology of nonresponsive celiac disease: results of a systematic approach.

OBJECTIVES: Nonresponse or relapse of symptoms is common in patients with celiac disease treated with gluten free diet. Refractory sprue (RS) is defined as initial or subsequent failure of a strict gluten-free diet to restore normal intestinal architecture and function in patients who have celiac-like enteropathy. The aims of this study were: 1) to identify causes of persistent symptoms in patients referred with presumed diagnosis of nonresponsive celiac disease (NCD); and 2) to characterize patients with true RS. METHODS: Patients were identified who had been systematically evaluated for NCD between January 1997, and May 2001. Patient records and small bowel biopsy results were reviewed. RESULTS: A total of 55 patients were referred with a presumed diagnosis of NCD. Six did not have celiac disease and had other diseases responsible for their symptoms. Diarrhea, abdominal pain, and weight loss were the most common reasons for evaluation in cases of NCD, whereas weight loss, steatorrhea, and diarrhea were the most common presenting features of RS (nine patients). Of the 49 patients with celiac disease, 25 were identified as having gluten contamination. Additional diagnoses accounting for persistent symptoms included: pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic cancer, fructose intolerance, protein losing enteropathy, cavitating lymphadenopathy syndrome, and tropical sprue. CONCLUSIONS: Based on this study, we conclude the following: 1) gluten contamination is the leading reason for NCD; 2) of NCD cases, 18% are due to RS; and 3) alternative diseases or those coexistent with celiac disease and gluten contamination should be ruled out before a diagnosis of RS is made.

Celiac Disease.

Individuals with celiac disease present with a wide array of symptoms and signs. Celiac disease can result in substantial injury to the small intestine, deleterious effects on other organ systems, and an overall doubling of mortality. The role of the gastroenterologist is primarily to make the diagnosis and then to ensure that patients with celiac disease receive up-to-date and accurate instructions on diet. It is our opinion that gastroenterologists should participate in the follow-up of what is in fact a form of inflammatory bowel disease. The failure to identify and treat patients with substantial problems may result in an excess of preventable morbidity and mortality. Intestinal biopsy is the definitive method of making the diagnosis of celiac disease, provided the patient has not excluded gluten from his or her diet, because exclusion of gluten results in negative serologic test results and normal small intestinal biopsy samples. The removal of gluten from the diet can result in a total recovery of gut function and a correction of most other consequences. The response is usually so complete that patients should consider themselves to be basically healthy as long as they stay away from the offending foods. However, the execution and maintenance of the "theoretically simple" exclusion of gluten is difficult. The condition is permanent and mandates adherence to a lifelong gluten-free diet; even small amounts of gluten can result in injury to the intestinal lining. The diet is restrictive and requires the patient to be careful about food choices. Therefore, patient education and motivation are crucial to a successful outcome. The correction of vitamin and mineral deficiencies may be helpful in aiding recovery; vitamin D and calcium supplementation often is recommended. No drug therapy has been proven to suppress the disease.