Jeremy S. Ditelberg

Reversal of cirrhosis in a patient with primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.

A 48-year-old female presented with 8 weeks of generalized pruritis in April 1988. The serum alkaline phosphatase (ALP) was 909 IU; total bilirubin, 3.1 mg/dl; alanine aminotransferase (ALT), 187 U/L; serum albumin, 4.2 g/dl; and antimitochondrial antibody (AMA) positive, titer 1:320. Cholestyramine was prescribed and she was referred to Tufts–New England Medical Center. The patient had no other medical problems and took no other medications. Her physical exam was unremarkable. Neither liver nor spleen was palpable and there were no cutaneous stigmata of chronic liver disease. Hepatitis B surface antigen and hepatitis IgM A antibody were negative and hepatitis A IgG antibody was positive. Transferrin saturation was 48% and prothrombin time was normal. The results of a right upper quadrant ultrasound were normal. A liver biopsy done in May 1988 was consistent with stage III PBC (Figure 1a). Methotrexate, 15 mg per week orally (0.2 mg/kg/week), was prescribed. There was prompt resolution of pruritis and cholestyramine was discontinued. During the next 2 years the methorexate dose was increased to 20 mg per week (0.25 mg/kg/week). Serum bilirubin decreased to 1.2 mg/dl, ALP decreased slightly, to 702 IU, ALT fluctuated between 117 and 313 U/L, and albumin and prothrombin time remained normal, 4.2 g/dl and 10.2 sec, respectively (Figure 2). Ursodiol, 300 mg twice daily, was added in April 1990 and there was further improvement in blood tests. In December 1991, the serum bilirubin was 1.0 mg/dl; ALP, 128 IU; ALT, 50 U/L; albumin, 3.8 g/dl; and prothrombin time, 11.2 sec. However, a liver biopsy at that time showed continuing portal and periportal inflammation, bridging portal fibrosis, and early nodule formation consistent with stage IV PBC (Figure 1b). Spider nevi were now present on the patient’s chest. In October 1993, the serum bilirubin had risen to 2.6 mg/dl, the albumin had decreased to 2.9 g/dl, and the prothrombin INR

Gender and location of CRC in IBD: implications for surveillance protocols.

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Pericentral Liver Cell Necrosis Associated with the Use of High-Dose Intravenous Methylprednisolone

Glucocorticoids are one of the few (classes of) drugs that have not been associated with hepatic injury. Glucocorticoids are widely used to treat a variety of diseases, usually immunologically mediated, including autoimmune chronic hepatitis. Although their long-term use is associated with a wide variety of unwanted side effects, liver disease is not one of them. We now describe a patient who developed acute central hepatic necrosis while receiving high-dose intravenous methylprednisolone. His liver disease remitted after methylprednisolone was stopped. The temporal relationship between the central hepatic necrosis and the use of high-dose intravenous methylprednisolone suggests that methylprednisolone was the cause.

Mo1954 DNA Mismatch Repair Deficiency in Inflammatory Bowel Disease Associated Colorectal Carcinomas

Colorectal cancer (CRC) occurring in the setting of Inflammatory Bowel Disease (IBD) is relatively uncommon. Compared to sporadic CRC, the molecular pathogenesis of IBDassociated CRC has some distinctive features, particularly the timing of acquisition of genetic changes during progression through highgrade dysplasia. DNA mismatch repair (MMR) deficient sporadic CRC is a well-defined entity comprised of Lynch syndrome-associated cancers and cancers characterized by a CpG island methylator phenotype (CIMP). The latter cancers characteristically arise in sessile serrated adenomas/polyps. The role of MMR deficiency in IBD CRC is less well-established. We undertook this study to determine the frequency and clinical pathologic associations of MMR deficiency in IBDassociated neoplasia. Methods

Mo1562 Inflammatory Fibroid Polyp of the Stomach: Clinical and Pathologic Characteristics of 28 Consecutive Cases Seen Over a 44-Month Period

Purpose: Gastric adenomas of intestinal differentiation are much more common than the more recently described adenomas of gastric differentiation. The purpose of this study was to compare the incidence and age at which adenomas of gastric phenotype occur compared to the more common intestinal type gastric adenomas. Methods: We used a large national pathology database of patients who undergo upper endoscopy at community-based surgery centers to determine the relative prevalence and associations of gastric foveolar adenomas, pyloric gland adenomas, and intestinal type adenomas. We extracted pertinent demographic, clinical, endoscopic, and histopathologic information from all patients who had a diagnosis of one of these three types of gastric polyps between 1/1/2008 and 11/1/2011. Frequency distributions and simple odd ratios were used to determine the significance of the associations. Results: From a total of 640,991 patients who underwent upper endoscopy (median age 58 years; 59.8% women), we identified a total of 549 with a diagnosis of gastric adenoma. Of those 443 (81%) were intestinal type, 77 (14%) were foveolar adenomas, and 29 (5%) were pyloric gland adenomas. In each case, the diagnosis was made on H&E stain. Intestinal-type gastric adenomas resembled colonic adenomas with loss of mucin, enlarged and elongated pseudostratified nuclei, and typically associated intestinal metaplasia with Paneth cells. Pyloric gland adenomas were composed of densely packed pyloric glands lined by cuboidal or short columnar cells, and a, typically, unremarkable surface epithelium. Foveolar adenomas featured a surface-predominant villous or papillary architecture with larger than normal foveolar cells and elongated nuclei. There was no significant difference between the median age of the different type of polyps (72 years for intestinal type, 77 for foveolar, and 73 for pyloric gland). There was, however, a significant predominance of women (86.2%) among pyloric gland adenomas (OR=3.86, p<0.01), but not among foveolar adenomas (55.8% women). A small fraction of the study group was known to have FAP (3.4% of intestinaltype adenomas, 2.6% of foveolar adenomas, and none of pyloric gland adenomas). Conclusion: Among a large nationwide population with endoscopy and biopsy for gastric adenomas, intestinal-type adenomas predominate, but almost 20% are of gastric phenotype and may be under-recognized. Our data also reaffirms previous studies that demonstrate a female predominance among pyloric gland adenomas.