Combined nephrotoxic effects of cyclosporine and endotoxin.

This study presents experimental evidence that cyclosporine (CsA) potentiates the nephrotoxicity of endotoxin. This study was motivated by clinical observations in 4 cyclosporine (CsA)-treated renal allograft recipients who developed severe, and sometimes irreversible, nephrotoxicity after infections. CsA or vehicle was administered intramuscularly to rabbits for 5 days, and subsequently both groups of animals received one dose of endotoxin intravenously. Compared with controls, CsA-treated animals demonstrated significantly higher elevations of blood urea nitrogen and serum creatinine 24 hr after endotoxin. By contrast, both groups of animals developed similar degrees of thrombocytopenia. Histologic evaluation of kidney tissues 24 hr after endotoxin revealed significantly greater tubular toxicity and a higher glomerular polymorphonuclear leukocyte (PMN) infiltration in CsA-treated animals. Semiquantitative scores of tubular damage correlated directly with the mean number of PMN/glomeruli in both groups of animals. Immunofluorescent microscopy of kidney tissues was negative for fibrinogen and for complement deposition in both CsA and control groups. We conclude that CsA enhances endotoxin nephrotoxicity in rabbits. This effect does not appear to be mediated by activation of coagulation factors. However, a role for PMN is suggested. CsA should be used with caution in patients with deteriorating renal function who are suspected of having severe bacterial infections.

Long-term prognosis of Zollinger-Ellison syndrome in multiple endocrine neoplasia.

BACKGROUND: The long-term prognosis of Zollinger-Ellison Syndrome (ZES) is not well defined. The findings of other endocrinopathies, the need for long-term surveillance, and the role of surgical treatment are controversial. METHODS: To help provide more information about these topics the records of 76 patients with ZES were reviewed. RESULTS: Nineteen patients with gastrinoma had multiple endocrine neoplasia (MEN). Fifteen had hyperparathyroidism from 14 years before to 38 years after the diagnosis of ZES. Three patients had pituitary adenomas. The unusual findings of pheochromocytoma were also seen in three patients. Sixteen patients were followed at least 10 years and 12 were followed for more than 20 years. Surgical cure was achieved in only one patient after a 12-year follow-up. The actual 5-, 10-, 15-, and 20-year survival rates of 94%, 75%, 61%, and 58%, respectively, were compared with patients with sporadic ZES with 5-, 10-, 15-, and 20-year survival rates of 62%, 50%, 37%, and 31%, respectively. CONCLUSIONS: Multiple endocrinopathies are common but are rarely diagnosed synchronously, mandating life-long surveillance for patients with ZES. Long-term prognosis is good. Survival is longer for patients with ZES and MEN compared with patients with sporadic ZES. Surgical cure is rare. Surgical excision without a single localized lesion does not seem justified.

Complications of laparoscopic cholecystectomy.

As laparoscopic cholecystectomy has become more widely practiced, the full spectrum of complications associated with this technique is being realized. We have performed 283 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 5.3% (15 of 283 patients; six major complications, nine minor complications). Major complications included one bile duct injury requiring laparotomy and t-tube insertion and two patients with retained stones. Symptomatic bile leakage occurred in three patients (1%). Two of these bile leaks were from accessory ducts entering the gallbladder bed; the third leak was secondary to a cystic duct leak. Eight patients (2.8%) required conversion to open cholecystectomy. Minor complications included three patients with subumbilical wound infections, two patients with urinary tract infections, one patient with costochondritis after operation, and three patients with prolonged hospital stays (more than 48 hrs) caused by ileus or fever. Several patients with life-threatening complications, including two patients who ultimately died, were transferred to our care from other centers. These included two patients with common duct injuries combined with duodenal perforations (one of whom died), one patient with a complete common duct transection, one patient with major common hepatic duct injury, and two patients with further instances of bile leakage. Laparoscopic cholecystectomy can be performed safely, and it can be associated with life-threatening complications. Prevention of complications is dependent on proper patient selection, meticulous technique, and an accepting attitude toward conversion to "open" cholecystectomy.

Normal pancreatic dimensions in the adult human.

Thirty cadaver pancreas specimens were dissected and carefully measured. The weights were recorded and averaged 91.8 g (range: 40.9 to 182 g). The glands were then divided into three segments using the common bile duct of the portal vein as sites of transection, and the various specimens were weighed. The data suggest that a pancreatectomy done to the left of the common bile duct will remove 90% of the gland and resection done to the left of the portal vein will remove about 60% of the gland. It is hoped that these data will be useful to surgeons in estimating the magnitude of pancreatic resection.

Cyclosporine-associated renal arteriopathy resulting in loss of allograft function.

Cyclosporine-associated arteriopathy was the cause of graft loss in 40 percent of all allografts that failed in a series of 200 consecutive cadaveric renal transplants. Arteriopathy was diagnosed by biopsy and renal uptake of indium 111m labeled platelets in the face of acute renal deterioration. A moderate thrombocytopenia and microangiopathic picture of hemolytic uremia was also present on peripheral blood smear. Immunofluorescence and histologic characteristics of the allograft biopsy specimens failed to show evidence for acute rejection: immunoglobulin M, immunoglobulin A, immunoglobulin G, C1q, C3, and C4 were not present, and there was no evidence of an interstitial or vascular mononuclear cellular infiltrate. Two clinical presentations have been described. In Group I (seven patients), anuria occurred rapidly within the first 2 weeks after transplantation. In Group II (nine patients) renal function gradually diminished 1 to 5 months after starting cyclosporine therapy. Fifteen of the 16 recipients had progressive and irreversible loss of renal function which was pathologically associated with fibrin deposition, intimal proliferation, and thrombotic occlusion of the cortical interlobular and arcuate arteries, with subsequent focal glomerular ischemia and cortical infarction. One recipient with rapid loss of renal function received an intraarterial allograft infusion of streptokinase and subsequent systemic heparinization, which resulted in return of normal allograft function. The syndrome of cyclosporine-associated arteriopathy has been linked to a lack of or reduced amounts of prostacyclin-stimulating factor or prostacyclin.

Biliary reconstruction without transanastomotic stent.

Twenty three operations for common bile duct (CBD) stricture were performed on 22 consecutive patients by a single surgeon without the use of transanastomotic stents. All strictures resulted from operative injury; four were acute (less than 1 month postinjury), and 18 were treated a mean of 44 months (2-124 months) after injury. All but two of these patients had had previous repair attempts. Mean follow-up after reconstruction was 72 months (17-128 months). Reconstructive procedures included hepaticojejunostomy seven, choledochojejunostomy ten, and choledochoduodenostomy six. Twenty one of the 22 patients (95%) have had excellent results, with stable liver function an no evidence of cholangitis or jaundice. Early postoperative complications (one abscess, one fistula) resolved. In two of the 22, stricture recurred at one and five months, requiring balloon dilatation in one and reoperation in the other. Both are now asymptomatic at 37 and 64 months. Reoperation was also required to remove an infected distal CBD stump in one patient 29 months after reconstruction, and another had mild intermittent cholangitis, now resolved. The only death occurred 70 months after reconstruction in a patient who developed biliary cirrhosis. These results suggest that biliary enteric anastomosis for acute and chronic bile duct strictures associated with benign disease can be performed without stenting, yielding low postoperative morbidity and excellent long-term patency.

The physiology of laparoscopic surgery: pulmonary function after laparoscopic cholecystectomy.

Changes in pulmonary function were studied via standard spirometry in 30 patients after laparoscopic cholecystectomy (LC) and compared with those in nine patients after traditional open cholecystectomy (OC). Studies performed presurgery and the morning after surgery included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory flow (FEF25%-75%). Age (43.9 +/- 2.6 years for LC and 42.3 +/- 3.2 for OC), sex, reasons for cholecystectomy, and smoking history were similar in both groups. The mean FVC decreased 23% after LC (3.57 +/- 0.18 L presurgery, range 0.56-5.62, versus 2.68 +/- 0.17 postsurgery, range 0.65-5.14) and 35.2% after OC (mean 3.52 +/- 0.29 presurgery, range 2.38-4.99, versus 2.24 +/- 0.24, range 1.23-3.49 postsurgery). FEV1 showed similar changes, with LC decreasing pulmonary function by 24.3% (2.76 +/- 0.14 L presurgery versus 2.01 +/- 0.12 postsurgery) compared with a 36.2% reduction in FEV1 after OC (2.86 +/- 0.29 L presurgery versus 1.81 +/- 0.21 L postsurgery). Forced expiratory flow decreased by 24.3% after LC and 40% after OC. Laparoscopic cholecystectomy provides less decrement in pulmonary function than traditional open cholecystectomy.

Diagnosis and management of bile leaks following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is now the standard of care for the elective management of gallstone disease. Recent studies have shown the morbidity of laparoscopic cholecystectomy to be similar to that of open cholecystectomy. Postoperative bile leaks have been recognized to be a troublesome problem following laparoscopic cholecystectomy. We present a retrospective review of 854 patients undergoing laparoscopic cholecystectomy at a single institution. Records were reviewed of all patients identified as having postoperative bile leaks. Between January 1990 and April 1991, we have cared for, or been referred, 15 patients with postlaparoscopic cholecystectomy bile leaks (9/854, 1.1% index patients and 6 referred). The location of bile leakage was determined to be the common bile duct (CBD) in two, cystic duct in five, and small accessory ducts located close to the gallbladder bed in the remaining eight. Most patients presented in the first week following laparoscopic cholecystectomy (mean 4.3 +/- 0.7 days, range 2-10) with worsening abdominal pain (13/13, 100%), nausea, and low-grade fever (mean 99.6 +/- 0.3 degrees F, range 96.8-102.2). Eleven of fifteen (66.7%) patients underwent technectium-99m imidodiacetic acid scanning (Tc-99m IDA) to determine the presence of a possible bile leak. All eleven scans were positive, indicating the presence of a bile leak. Thirteen patients underwent endoscopic cholangiography confirming the presence of biliary leakage (the remaining two patients underwent prompt laparotomy). Five patients were taken to the operating room for management of their leaks (two with common bile duct injuries, two cystic duct leaks, one accessory duct leak).(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of laparoscopic cholecystectomy. A prospective analysis of 100 initial patients.

Laparoscopic cholecystectomy quickly emerged as an alternative to open cholecystectomy. However its safety, efficacy, and morbidity have yet to be fully evaluated. During the first 6 months of 1990, we performed 100 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 8% (8 of 100 patients; 4 major, 4 minor). There were 81 women and 19 men, with a mean age of 46.1 years (range, 17 to 84 years). All patients had a preoperative history consistent with symptomatic biliary tract disease, and most had proved gallstones by sonography. This included four patients with acute cholecystitis. Mean operating time improved significantly from month 1 to month 6 (122 +/- 45.4 minutes versus 78.5 +/- 30 minutes, respectively), indicating a rapid learning curve. Mean hospital stay was 27.6 hours, reflecting a policy of overnight stay. Postoperative narcotic requirements were limited to oral or no medications in more than 70% of patients. A regular diet was tolerated by 83% of the patients by the morning following the procedure. Median time of return to full activity was 12.8 +/- 6.8 days after operation. In addition analysis of the hospital costs of these 100 cases demonstrates a modest cost advantage over standard open cholecystectomy (n = 58) (mean, $3620.25 +/- $1005.00 versus $4251.76 +/- $988.00). There was one minor bile duct injury requiring laparotomy and t-tube insertion, two postoperative bile collections, and one clinical diagnosis of a retained stone that passed spontaneously. Four patients required conversion to open cholecystectomy because of technical difficulties with the dissection. Although there is a significant learning curve, laparoscopic cholecystectomy is a safe and effective procedure that can be performed with minimal risk. Laparoscopic cholecystectomy should be performed by surgeons who are trained in biliary surgery and knowledgeable in biliary anatomy, and, as with all operations, it should be performed with meticulous attention to technique.