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Chemokines are small protein inflammatory mediators that were classically known for their elicitation of inflammatory cells out of the vasculature. However, more contemporary studies show that these ubiquitous factors impinge on many facets of biology, including hematopoiesis, angiogenesis, and mitogeneis. The elucidation of mechanisms involved in the immunopathogenesis of liver disease has magnified the importance of chemokines in this organ. Accordingly, a number of in vitro and in vivo studies have highlighted the importance of chemokine biology in both acute and chronic liver disease, and a variety of liver diseases have been shown to involve chemokines and their receptors during the initiation and main tenance of liver pathology. A greater understanding of the role chemokines play during liver disease may permit the employment of therapies that target or enhance chemokines in the liver. This review will highlight the current clinical and experimental research in the immunopathogenesis of acute and chronic liver diseases.

Postsurgical gastroparesis syndrome (PGS) is characterized by postcibal nausea and vomiting and is associated with functional gastric dysmotility. Patients frequently present with marked weight loss and malnutrition requiring hospitalization and prolonged parenteral nutrition. Typically, these patients fail to respond to prokinetic agents. Gastric reoperations are frequent and usually unsuccessful. Near-completion gastrectomy (NCG) has proved useful in small series of patients, but long-term follow-up has been lacking. The purpose of this study is to assess the safety and durability of NCG in a large group of patients with PGS. Eighty-one patients with documented PGS who failed to respond to prokinetic drug therapy were treated with NCG over an 11-year period. NCG was standardized with a 55-cm Roux-en-Y reconstruction. Patients were evaluated by a retrospective chart review and a prospective phone interview that compared pre- and postoperative health status based on a standardized severity of symptoms score. There were no operative deaths or complications related to the anastomosis. Average patient follow-up was 56.1 months (range, 2-142 months). Fifteen patients died of unrelated causes, and 14 patients were lost to follow-up. The remaining 52 patients showed a significant overall decrease in severity of symptoms score largely due to reduction in gastrointestinal symptoms and to a smaller but significant reduction in systemic symptoms. Nearly 80 per cent of patients reported long-term relief of symptoms. NCG is the procedure of choice for carefully selected patients with documented. Low morbidity and durable results can be anticipated in the majority of patients.

Hyperacute rejection following orthotopic liver transplantation remains an extremely unusual occurrence. In this study, we examined a porcine model of liver transplantation in which recipient animals were sensitized prior to transplantation with three serial full-thickness skin grafts. Three experimental groups were studied. Group I recipients (n = 6) were specifically sensitized against their liver donors with biweekly skin grafts followed by hepatic grafting. Group II recipients (n = 6) underwent third-party skin graft sensitization prior to liver transplantation. Group III recipients (n = 6) underwent liver grafting without sensitization. Mixed lymphocyte cultures were done before each skin graft and prior to transplantation. Lymphocytotoxic antibody (LCTA) titers were measured before the first skin graft, at weekly intervals thereafter, intraoperatively, and daily postoperatively until death. Intraoperative and postmortem liver biopsies were obtained in all recipients. Five of six recipients in Group I died within 4 hr of hepatic revascularization. The remaining animal survived for four days. Mean survival time in group I was 0 +/- 0.7 days. In contrast, MST in groups II and III were 4.0 +/- 1.2 and 6.2 +/- 1.3 days, respectively. The MST in group I was significantly shorter than in groups II and III (P less than 0.026 and P less than 0.005, respectively). There was no significant difference in survival between groups II and III. MLC reactivity between recipients and skin donors increased progressively following each skin graft, reaching a peak just prior to liver transplantation. LCTA titers also increased following each skin graft, reaching peak levels immediately prior to hepatic grafting. Intraoperative LCTA titers decreased within 2 min of graft revascularization and were undetectable within 4 hr. In group III (unsensitized recipients), MLC reactivity was low and at no time was LCTA detectable. Histologic examination of the livers from group I recipients showed parenchymal hemorrhage, endophlebitis, and neutrophil infiltration. Histologic examination of postmortem liver biopsies from animals in groups II and III revealed acute cellular rejection. In conclusion, hyperacute rejection resulting in graft failure and recipient death can be consistently produced in a porcine model of hepatic transplantation by donor-specific sensitization of the recipient. It is postulated that high titers of donor-specific antibody are required to exceed the liver's capacity for antibody absorption and elimination and produce the clinical picture of hyperacute rejection.

Because absorption of cyclosporine (CyA) given orally immediately after liver transplantation is unreliable, the drug is usually given intravenously until external biliary drainage is discontinued. Intravenous CyA, however, is associated with serious side effects, making its use potentially hazardous. We report the results of a new strategy in which we used oral CyA exclusively and refed bile to enhance oral CyA absorption. Thirty-two liver transplant recipients with indwelling T tubes were studied. All were given sequential quadruple drug immunosuppression with antilymphoblast globulin, azathioprine, and steroids. Oral CyA and refeeding of bile was started when renal function was stable. By the second posttransplant week, satisfactory CyA levels were achieved, and antilymphoblast globulin therapy was stopped. There were significant associations between oral CyA dose and CyA level and between quantity of refed bile and CyA level (p less than 0.001). CyA dose and quantity of bile refed were covariates, however, and in multiple regression analysis, only the quantity of refed bile was significant (p = 0.001). CyA levels did not correlate with rejection. The incidence of rejection was 63%. At a mean follow-up of 9 months, 28/32 (88%) patients were alive, and actuarial 1-year patient survival was 84%. Current graft and renal function are excellent (serum bilirubin, 1.0 +/- 0.1 mg/dl; serum creatinine, 1.2 +/- 0.1 mg/dl). We conclude that intravenous CyA can be avoided in virtually all liver-transplant recipients by administration of oral CyA with bile in the early posttransplant period.

Although general surgeons receive little training in the management of gynecologic conditions, they should be able to make intraoperative decisions about unexpected gynecologic abnormalities encountered during abdominal exploration. This report examines the six most common gynecologic problems found during abdominal exploration (salpingitis, tubo-ovarian abscess, ectopic gestation, endometriosis, uterine mass, and ovarian mass) and reviews their proper management with particular emphasis on conserving reproductive function.