Surgical diverticulitis: treatment options.

Acute diverticulitis requiring surgical intervention has conventionally been treated by resection with colostomy or delayed resection with primary anastomosis at a second admission. Our objective was to determine the outcome for treatment of diverticulitis with resection and primary anastomosis during the same hospitalization. We conducted a retrospective review of patients (n = 74) undergoing surgery for diverticulitis. Groups included: 1) resection with primary anastomosis (n = 33), 2) resection with colostomy followed by a takedown colostomy (n = 32), and 3) delayed resection with primary anastomosis at a second admission (n = 9). Despite local perforation primary anastomosis was often performed unless patients were clinically unstable or had fecal contamination. The operation was urgent in five (15%) patients in Group 1 as compared with 26 patients (88%) in Group 2. Serious intra-abdominal complications occurred in two patients (6%) in Group 1 as compared with nine patients (28%) in Group 2 and one patient (11%) in Group 3. Postoperative abscesses occurred in two patients in Group 1, five patients in Group 2, and one patient in Group 3. We have shown that resection with primary anastomosis for acute diverticulitis--even in selected patients requiring urgent operation--can be safely performed during the same hospital admission with a low complication rate.

Liver transplantation in polysplenia syndrome: use of a living-related donor.

Congenital anatomic anomalies often present technical obstacles during liver transplants. Biliary atresia is the most common indication for liver transplants in children, and approximately 7-10% of these patients have congenital anomalies comprising the "polysplenia syndrome." The polysplenia syndrome, which often includes abdominal situs inversus, is of particular concern in liver transplants because these anatomic anomalies result in a more complex hepatectomy, alterations in the placement of the donor grafts, and the need for additional vascular reconstruction. Earlier reports have shown mixed results for these patients who have undergone orthotopic liver transplants, reporting a high rate of postoperative complications and poor survival. The use of living-related donor grafts has produced excellent results in the general pediatric population. This is the first report of the successful use of a living-related donor graft for an orthotopic liver transplant to treat end-stage liver disease secondary to biliary atresia in a child with polysplenia syndrome.

Same admission colon resection with primary anastomosis for acute diverticulitis.

Current standard of care for complicated diverticulitis includes urgent resection with colostomy versus antibiotic treatment, followed by delayed resection with primary anastomosis at a second admission. In certain circumstances, it is possible to perform resection and anastomosis on the same admission for acute diverticulitis. A retrospective review was completed for patients undergoing surgery for diverticulitis from 1991 to 1998. Groups included: 1) sigmoid resection with primary anastomosis on same admission (n = 18); 2) resection with protective end colostomy (n = 16); and 3) in-patient antibiotic treatment alone, followed by a second admission for resection with primary anastomosis (n = 5). Four patients initially treated with antibiotics worsened symptomatically or developed radiographic evidence of perforation and required resection with colostomy. Five patients in Group 1 had abscesses or contained perforations based on radiographic studies. Findings on CT scans did not predict treatment. Group 1 patients had uneventful recoveries and few minor complications (wound infections and an incisional hernia). One anastomotic leak occurred in Group 2 after colostomy closure. Although there will continue to be a role for emergent operation for diverticulitis, same admission sigmoid resection with primary anastomosis after antibiotic treatment is safe, uses a shorter course of antibiotics, and has a low complication rate.

Effects of pravastatin on chronic rejection of rat cardiac allografts.

BACKGROUND: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits coronary transplant vasculopathy in the clinical setting. To further delineate the immune modulatory effect of this agent, it was tested in a rat cardiac transplant model of chronic rejection. METHODS: Rat heterotopic abdominal cardiac transplants were performed using a Lewis to Fischer 344 combination. Fischer 344 recipients received a brief course of cyclosporine to decrease the incidence of acute rejection. Experimental groups were treated with either high-dose (10 mg/kg) or low-dose (5 mg/kg) pravastatin for 120 days, while a control group did not receive pravastatin. The effect of pravastatin on chronic rejection of cardiac allografts was analyzed by histology, and the expression of laminin, fibronectin, macrophages, and T cells was assessed by immunohistochemistry. RESULTS: Coronary transplant vasculopathy was inhibited in both groups of pravastatin-treated animals, as compared with controls. Immunohistochemistry revealed that control animals had degraded laminin and fibronectin which paralleled the degree of tissue necrosis. In contrast, pravastatin-treated animals had modest amounts of extracellular matrix proteins retained within intermyocytes and endothelium, a pattern seen in native cardiac tissue. The pravastatin-treated groups also had fewer graft-infiltrating macrophages, specifically within the arterial intima and perivascular areas. CONCLUSIONS: Progressive chronic vascular rejection, a leading cause of allograft failure, can be inhibited by pravastatin in a well-defined rat cardiac transplant model. Pravastatin appears to inhibit the synthesis and subsequent degradation of extracellular matrix proteins and block the infiltration of macrophages to the graft, which emphasizes that this inflammatory cell plays a major role in the pathogenesis of transplant chronic rejection.

Fas ligand gene transfer to renal allografts in rats: effects on allograft survival.

BACKGROUND: Fas ligand (FasL) induces apoptosis of cells bearing its receptor Fas, and has been shown to be important in T-cell development and regulation and in immune privilege. We hypothesized that FasL expression by renal allografts might provide protection from rejection. METHODS: The murine FasL cDNA was cloned into a replication-defective adenovirus (AdV-FasL). Protein expression was confirmed by immunostaining of AdV-FasL-transduced HeLa cells. Allogeneic kidney transplants were performed between WF (RT1u) donors and Lewis (RT1) recipients. Donor kidneys were perfused in situ with saline alone (control), or 9 x 10(9) plaque-forming units of AdV-FasL. One native kidney was removed at the time of transplant and the other at 6 or 7 days. Uremic death was the endpoint, and deaths within 7 days of transplant were excluded. Transduced allografts were stained for FasL expression using a monoclonal antibody and tested for FasL mRNA production by reverse transcriptase-polymerase chain reaction and Northern blotting. RESULTS: Immunostaining of AdV-FasL-transduced allografts demonstrated efficient gene transfer lasting approximately 2 weeks, and FasL mRNA production in the AdV-FasL-transduced allografts was confirmed by Northern blotting and reverse transcriptase-polymerase chain reaction. Mean survival of animals with AdV-FasL-transduced renal allografts was 27.8 days vs. 11.6 days in control animals (P < 0.05). CONCLUSIONS: (1) Adenoviral vectors can successfully transduce rat kidneys with the FasL cDNA. (2) FasL gene transfer prolongs rat renal allograft survival.

Reduction of epidermal growth factor receptor phosphorylation by activated Mullerian inhibiting substance is vanadate-sensitive.

The carboxy-terminal domain of recombinant human Mullerian inhibiting substance (MIS) inhibits cellular proliferation in vitro and decreases epidermal growth factor (EGF)-dependent phosphorylation of the EGF receptor. Proteolytically cleaved and undissociated MIS is more potent than carboxy-terminal MIS alone, supporting a functional role for the amino-terminal region of the molecule. MIS does not block EGF binding to the EGF receptor, thus, MIS reduction of EGF receptor phosphorylation must occur distal to receptor ligand binding. The effect of proteolytically cleaved MIS on reduction of EGF receptor phosphorylation in membrane preparations is decreased by a specific phosphatase inhibitor, vanadate, thus implicating a membrane phosphatase in this MIS action at the EGF receptor.