Ileal-pouch anal anastomosis is sometimes performed inappropriately in Crohn's disease patients. The aim of this study was to evaluate long-term results in this subset. In 54 ileal-pouch anal anastomoses performed between 1985 and 1997 for CUD the patient was eventually diagnosed as having Crohn's disease in seven cases. A retrospective review was performed. Definitive diagnosis was established on histopathology, endoscopy, and clinical presentation. The principal outcome factors were pouch failure, reason for failure, and functional results in cases of retained pouch. Patients ranked their quality of life between 1 and 10. We found three failures due to pelvic abscess, anoperineal disease, and anovulvar fistula. The pouch was excised in the latter patient; four patients retained their pouch. Functional results were good in the four (7 year follow-up): 7.25 bowel movements per day, ability to discriminate flatus from feces in three, soiling in one, urgency in one, perianal pad in one, ability to differ bowel movement for 66 min, diet, and antidiarrheal medication all four, pouchitis in one, sexual troubles in one woman, no urinary or obstetric trouble. Quality of life was judged satisfactory by six of the seven patients. Our 13% rate of inadvertent ileal-pouch anal anastomosis is higher than results usually reported. This difference is explained by the diagnostic criteria, whose validity is controversial. Three-stage surgery to decrease inadvertent restorative coloproctectomy is worth considering. Even if results are good when the pouch is functioning, Crohn's disease remains a contraindication to ileal-pouch anal anastomosis because of its high rate of failure and excision.

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Cdc25 phosphatases are important in cell cycle control and activate cyclin-dependent kinases (Cdk). Efforts are currently under way to synthesize specific small-molecule Cdc25 inhibitors that might have anticancer properties. NSC 95397, a protein tyrosine phosphatase antagonist from the National Cancer Institute library, was reported to be a potent Cdc25 inhibitor. We have synthesized two hydroxyl derivatives of NSC 95397, monohydroxyl-NSC 95397 and dihydroxyl-NSC 95397, which both have enhanced activity for inhibiting Cdc25s. The new analogues, especially dihydroxyl-NSC 95397, potently inhibited the growth of human hepatoma and breast cancer cells in vitro. They influenced two signaling pathways. The dual phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was induced, likely due to inhibition of the ERK phosphatase activity in Hep 3B cell lysate but not the dual specificity ERK phosphatase MKP-1. They also inhibited Cdc25 enzymatic activities and induced tyrosine phosphorylation of the Cdc25 target Cdks. Addition of hydroxyl groups to the naphthoquinone ring thus enhanced the potency of NSC 95397. These two new compounds may be useful probes for the biological functions of Cdc25s and have the potential for disrupting the cell cycle of growing tumor cells. [Mol Cancer Ther 2005;4(4):595 -602]

Hepatic encephalopathy (HE) is a common complication of acute and chronic liver disease associated with exposure of brain tissue to excessive levels of ammonia produced by intestinal bacteria. Clinical manifestations range from subtle neurologic abnormalities to coma. Because development of HE can reduce survival probability, guidelines for evaluating patients for liver transplantation suggest that patients who develop HE should be considered for transplantation. Various patient factors before transplantation, including the presence of HE and reduced nutritional status, may increase the risk of poor outcomes after transplantation. Therefore, effective management of HE before transplantation, while minimizing the potential impact of negative predictive factors, may improve transplantation outcomes. The most common HE treatments are directed toward reducing systemic ammonia levels, thereby reducing brain exposure to this neurotoxin. The administration of nonabsorbable disaccharides is considered as a first-line therapy for HE, and the antibiotics neomycin and metronidazole are frequently administered, despite a lack of clinical data supporting their efficacy. These agents are associated with adverse events that may reduce nutritional status in patients awaiting transplantation and could contribute to poor posttransplantation outcomes. The nonsystemic antibiotic rifaximin has demonstrated efficacy for the treatment of HE and has a favorable safety profile. Given these data, nonsystemic antibiotics may also provide a safe and effective option for treating HE in the pretransplant setting. This article reviews treatments for HE and the potential impact these treatments may have on pretransplantation status of patients awaiting liver transplantation and on posttransplantation outcomes.

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