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Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n = 82), (2) recipients switched to FK506 for antirejection or rescue therapy (n = 61), and (3) recipients converted to FK506 for other reasons (n = 11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% > or = 2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P = 0.04); for PTA recipients, 84% versus 66% (P = n.s.); and for PAK recipients, 80% versus 14% (P = 0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV-positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P = n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

The study purpose was to identify risks, benefits and costs associated with an expanded donor protocol. The protocol design evaluated organs rescued using expanded donor criteria and weighed all costs associated with doing so. Costs were measured against conditions experienced with expanded and traditional criteria and recipient outcome. Traditional donors were between 5 and 55, with negative serologies, and no history of hypertension or diabetes. "Expanded donors" were between 55 and 75 or less than 5, with a history of hypertension, diabetes and/or sero-positive for Hepatitis C. During this study 73 donors met criteria from which 200 organs were transplanted. Defined costs and outcomes for recipients were tracked. Using expanded criteria: costs averaged 20% more per organ; OPO personnel spent an average of 6 hours more time on-site; an additional 12-14 hours in placement activity; and average organs per donor decreased. Heart patient and graft survival rates for traditional and expanded donor organs were comparable. Kidney patients transplanted from this pool experienced a decrease in patient (P = .14) and a significant decrease in graft (P = .02) survival rates. Patient (P = .05) and graft (P = .01) survival rates were significantly lower in liver patients transplanted with expanded donor organs. Two hundred transplants occurred using expanded donor criteria. Costs for the OPO increased appreciably. Heart and kidney utilization from these donors seems justified. It is thought that liver recipients' results were due to utilizing them in sicker patients. Recovery of organs from donors using expanded criteria appears to be a reasonable way of increasing organ supply.

The hepatic arterial blood supply is indispensable for the survival of the graft during liver transplantation. Inadequacies in the recipient hepatic artery mandate arterial reconstruction different from the preferred method of direct anastomosis. We report the use of the left gastric artery as an attractive alternative for reconstructing the arterial blood supply of a transplanted liver.

Nodular regenerative hyperplasia of the liver is an uncommon cause of portal hypertension. Patients with nodular regenerative hyperplasia have signs and symptoms of portal hypertension, without evidence of hepatocellular failure or encephalopathy. We report the case of a 44-year-old woman with recurrent esophageal bleeding and refractory ascites who had a history of hemosiderosis, hepatitis C, and chronic renal allograft rejection. Our preoperative diagnosis was cirrhotic end-stage liver disease and end-stage renal disease for which the patient underwent combined hepatic and renal transplantation. Her portal hypertension symptoms resolved, and her renal function has been normal for 18 months of follow-up. Histologic examination of the liver revealed nodular regenerative hyperplasia, and a review of the literature regarding the surgical management of patients with nodular regenerative hyperplasia revealed that various shunting procedures are generally recommended. After the failure of medical management in patients with nodular regenerative hyperplasia, portosystemic shunting may be indicated before proceeding to hepatic transplantation.

Doppler color flow imaging has been used to identify obstruction, rejection, and nonfunctioning renal allografts. When done in the immediate posttransplant period on poorly functioning kidneys, it allows early and accurate detection of surgically correctable changes such as arterial or venous thrombosis or early obstruction by blood, urine, or lymph. Further, it determines changes in intrarenal flow patterns that may indicate early transplant dysfunction, such as acute tubular necrosis and/or acute rejection as well as obstruction. Additionally, baseline values can be obtained in uncomplicated cases for serial follow-up. Between July 1980 and February 1991, 20 transplant patients had Doppler color flow imaging in the immediate posttransplant period. The kidney contour, perirenal collections, vessel flow patterns, and resistive indexes were assessed. In two patients, immediate surgical intervention salvaged the allograft. In several other patients with primary nonfunctioning kidneys, the study distinguished between acute tubular necrosis and obstruction due to external compression. We concluded that protocol Doppler color flow imaging is valuable in the immediate posttransplant period for determining surgically correctable complications.

The simultaneous recovery of the cadaveric liver and pancreaticoduodenal allograft is well established. The current technique for procurement enables the retrieval of both organs in most multiorgan donor operations. Vascular complications may account for 45 percent of pancreatic graft failures, most of which are thromboses of the portal vein caused by low flow in the entire pancreatic vasculature, a twisted venous anastomosis or an acutely angled arterial reconstruction that can contribute to the thrombosis and, thereby, to graft failure. Because a diabetic recipient may have severely atherosclerotic vessels, an interposition autograft of the internal iliac artery of the recipient is not recommended. Our modified vascular reconstruction prevents compromised arterial blood supply when donor arterial grafts (iliac, carotid or femoral) are not available and when direct splenic to SMA reconstruction is not feasible.

Optimal management of pancreatic abscess and septic complications of acute pancreatitis remains controversial. With the "open packing" approach, repeated closure of the midline fascia is complicated by loss of tissue integrity and suture strength. An improved zipper closure of the abdominal wall in six patients with pancreatic abscess is presented. Improvements included: (1) using a separating jacket-type zipper to allow maximal intraoperative exposure; (2) employing a removable tuck for expansion of the patch covering the wound; (3) substituting a nonmeshed polytetrafluoroethylene material for the polypropylene mesh to prevent adherence to the underlying viscera; and (4) creating a flap underneath the zipper teeth to protect the underlying tissue from injury. Satisfactory results were achieved with the improved zipper technique.

Situs inversus has been considered an absolute contraindication to liver transplantation due to technical difficulties. Associated vascular malformation and distorted anatomy may make the procedure even more complicated or impossible. Only three cases of patients with abdominal situs inversus who underwent successful liver transplantation have been reported in the English literature. We describe two additional patients with situs inversus who suffered from biliary atresia and underwent successful liver transplantation. The preoperative evaluation and the operative procedure are presented, and technical difficulties are discussed. Since biliary atresia is associated with polysplenia syndrome, including vascular malformation and visceral malposition, we suggest that each case be extensively evaluated preoperatively to determine the size requirement for the donor liver and the feasibility of reconstruction.

Infection combined with additional complications of arteriovenous fistulas is a serious threat to access in patients with upper-extremity polytef (polytetrafluoroethylene) grafts. We present three cases of infected access grafts that were treated with systemic antibiotics, excision of the grafts, and primary anastomosis of the arterialized vein to artery for access salvage. The new arteriovenous fistulas were used immediately, preventing interruptions in hemodialysis regimens. This technique of immediate reconstruction allows the surgeon to utilize the arterialized outflow vein and save other sites of access for future use.

Sixteen pancreatico-duodenal transplants were performed on 15 insulin-dependent diabetics, aged 25-46, during a 20-month period beginning May 1, 1988. Fourteen patients received a combined cadaveric pancreas/renal transplant with bladder drainage. One patient received a second pancreas transplant 24 hours after the first pancreas graft failed due to portal vein thrombosis. One patient received a pancreas graft 3 years after kidney transplantation. Complications included five cases of hematuria, two bladder leaks, two wound infections, one cytomegalovirus pneumonia, three cases of graft pancreatitis, one pseudocyst, one urine reflux pancreatitis requiring conversion to pancreatico-enterostomy, and two late deaths. Average time to discharge was 17 days following transplant, with 2.9 re-hospitalizations per patient and an average of 38 in-hospital days during the first 6-12 months. Seventeen rejection episodes occurred in 12 patients, diagnosed by declining urine amylase and pH and/or finding of rejection on kidney biopsy. Patient and kidney graft survival is 87 per cent. Pancreas graft survival is 81 per cent (1-20 months follow-up). All patients are insulin-independent and normoglycemic. Mean glycosylated hemoglobin concentration is 4.0 +/- 0.9 post-transplant vs. 7.5 +/- 0.6 pretransplant. Mean serum creatinine is 1.4 +/- 0.7 mg/dl. A new program of pancreas transplantation can be successful in carefully selected diabetic patients, with special attention to avoidance of preservation injury to the pancreas during multiorgan donor procurement. Combined pancreatic/renal transplantation is believed to be the therapeutic treatment of choice in Type I diabetic patients who have impaired renal function and have no significant cardiovascular disease.

After successful combined pancreaticoduodeno-renal transplant in an insulin-dependent diabetic, recurrent episodes of transplant pancreatitis were treated with Foley catheter drainage. The apparent cause of pancreatitis was increased pressure on the pancreatic duct due to infrequent voiding and a large bladder. A frequent voiding program partially relieved the pancreatitis, but final resolution necessitated conversion of the pancreaticoduodeno-cystostomy to a Roux-en-Y duodenojejunostomy at 6 months posttransplant. Both renal and pancreatic function are stable after 1 year, with no recurrence of pancreatitis since urinary undiversion. We believe pressure pancreatitis or urine reflux pancreatitis to be an infrequently reported cause of graft dysfunction in bladder-drained pancreas transplant recipients.

The nonshivering thermogenic response of the newborn to cold exposure and the potentially detrimental effects of the resultant hypermetabolic state have been documented by numerous animal and clinical studies. It is standard practice to protect the newborn infant from cold stress by controlling environmental temperature and preventing heat loss. Although these measures are well accepted, little attention has been paid to the effect of surgical factors, such as operative trauma, anesthetic agents, and muscle relaxants on nonshivering thermogenesis. The purpose of this investigation is to develop an experimental model to study the effect of surgical factors on the neonatal thermogenic response. Newborn rabbits were chosen as the experimental subject because these animals rely solely on nonshivering thermogenesis. One-hundred-eleven animals were studied. In the newborn rabbit, there was an inverse relationship between age and the percentage of brown fat. Body weight doubled in the first week of life, while the quantity of brown fat fell from a maximum of 2.9% of body weight in the first day of life to 1.56% at 7 days of age. It was possible to maintain the newborn rabbit in a warm environment for periods of up to 2 hours without changes in blood flow to the brown fat or oxygen consumption. The thermogenic response to cold did not appear to be altered in terms of oxygen consumption when the animals were lightly anesthetized with pentobarbital or paralyzed with metocurine and locally anesthetized. The rise in oxygen consumption was similar in awake, intact animals and those that received pentobarbital or metocurine and xylocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to better understand the mechanism of hypotension and bradycardia in newborn infants under halothane anesthesia, we studied the changes in the four determinants of cardiac output in newborn piglets given 0.5 and 1% end tidal halothane. Cardiac index (CI) was measured by thermodilution. Preload was estimated from the left ventricular diastolic dimension determined by echocardiography and from the left ventricular end-diastolic pressure. Total peripheral resistance index was calculated to assess afterload. Contractility was estimated from left ventricular peak dP/dT, and from left ventricular shortening fraction and mean rate of circumferential fiber shortening determined by echocardiography. All indices of contractility decreased to approximately 50% of baseline values during administration of 1% halothane, whereas heart rate (HR) was reduced to 74% of baseline. Preload and afterload did not change significantly. Mean arterial pressure (MAP) and CI decreased to 67% and 74% of control values, respectively. Smaller, proportional reductions in all variables occurred when 0.5% halothane was administered. Control values of MAP were the only measurements significantly related to piglet age. When five additional animals underwent atrial pacing at the control HR during 1% halothane anesthesia, MAP and CI decreased to 66 and 71% of control values, respectively. dP/dT/DP40, a dP/dT point measurement independent of preload and afterload changes, decreased to 49% of control during pacing. Therefore, the major effect of halothane in newborn piglets is its potent negative inotropic action, not peripheral vasodilation or bradycardia.

The incidence of posttransplant diabetes mellitus (PTDM) was compared in three groups of renal transplant recipients: nondiabetic patients who had been randomized between 1980 and 1983 to receive antilymphoblast globulin (ALG), azathioprine (AZA), and prednisone (P) (group 1) or cyclosporine (CsA) plus prednisone (group 2). Group 3 consisted of a more recent (1984-85) cohort who were given a combination of azathioprine, cyclosporine, and prednisone (+/- ALG). PTDM developed in 20 of 173 previously nondiabetic 18-55-year-old patients. Three of 47 patients (6.4%) in group 1, 4 of 58 patients (6.9%) in group 2, and 13 of 68 patients in group 3 (19.1%) developed PTDM. Thus in the two groups composing the concurrent prospective randomized trial (groups 1 and 2) the incidence of PTDM did not differ. The subsequent patients who were given a combination of ALG, azathioprine, cyclosporine, and prednisone developed a significantly greater incidence of PTDM even though the total dose of cyclosporine and prednisone were lower than in groups 1 and 2. PTDM usually occurred within two months of transplantation, and 11 of 17 patients who initially required insulin are still dependent upon exogenous insulin. The incidence of PTDM was not significantly affected by sex of the recipient, HLA-type, primary renal disease, rejection episodes, primary vs. secondary transplant, or prior splenectomy. The incidence of PTDM is greater in patients older than 45 (34.2% vs. 5.2%), and heavier than 70 kg (21.1% vs. 5.1%); in recipients of cadaveric allografts (15.7% vs. 4.6%); and in patients who were hospitalized for infections (22.4% vs. 4.7%). CsA levels tended to be higher in the group 2 and 3 patients who developed PTDM than in those who remained nondiabetic. One-year actuarial patient survival in those with PTDM was 83.3% vs. 98% (P less than .01) in the nondiabetic and graft survival was 77.1% vs. 87.1% (NS). The combination of Minnesota ALG, azathioprine, cyclosporine, and prednisone appears to predispose older, heavier recipients of cadaver allografts to the development of PTDM. The risk of PTDM must be weighed against the more usual results of improved patient and graft survival using this combination of immunosuppression.

Intraoperative autotransfusions for selected patients can ease demands on blood banks. In 33 cases (trauma, elective vascular, and cardiac procedures), we saved 80.7 L of blood with a cell washer blood recovery system (Cell Saver). In eight trauma cases, including three with intestinal perforation, cell washing salvaged 31.5 L of shed blood as a lifesaving emergency procedure. This stimulated interest in defining the limits of the instrumentation in cleansing blood of bacteria. In 18 in vitro experiments, discarded banked blood was inoculated with Escherichia coli to simulate light, moderate, or heavy bacterial contamination. Volumes of blood (500 ml) containing a total of 6.3 X 10(5), 4.8 X 10(7), or 3.2 X 10(10) bacteria were processed. The original blood, filtered blood, plasma supernate, effluent wash solution, and final washed packed red cells were cultured quantitatively in each experiment. The mean total number of E. coli retained in the final washed packed red cells was 1.4 X 10(5), 6.3 X 10(6), or 1.6 X 10(9) bacteria, or 23%, 13%, and 5% of each original inoculum. Additional washing with 10 L of saline did not remove significantly more bacteria (p greater than 0.20). Although emergency autotransfusion of blood contaminated with intestinal contents was lifesaving, we recommend caution since these results show that cell washing does not remove all bacteria. Further laboratory and clinical studies are needed to determine the levels of bacterial contamination of autotransfused blood that can be tolerated, and to determine adjunctive means of rendering contaminated or potentially contaminated blood safe for autotransfusion.

Recent studies have supported the possibility that mechanisms other than alterations in transcapillary oncotic pressure may contribute to edema formation in nephrotic syndrome. In a patient with a discrete, partial obstruction to lymphatic flow in the left upper extremity, the authors determined the transcapillary oncotic pressure differential in the obstructed, more edematous extremity and the contralateral, unobstructed extremity. The results demonstrate a normal transcapillary oncotic pressure gradient in the unobstructed extremity, while in contrast, the gradient in the obstructed extremity was reduced. Clinically, the edema resolved completely in conjunction with resolution of the nephrotic syndrome. The authors conclude, therefore, that the obstructed extremity may be more susceptible to edema formation because of inability to increase lymphatic flow during periods of hypoalbuminemia to levels sufficient to reduce the interstitial oncotic pressure gradient. Furthermore, the normal gradient in the unobstructed extremity supports the view that other mechanisms, such as intrinsic alterations in renal sodium reabsorption, may be involved in edema formation because edema was present without demonstrable alterations in the transcapillary oncotic pressure differential and plasma volume was increased in this patient.

Cyclosporine administration prolongs the survival of immediately vascularized allografts. However, its role in the prevention of rejection of dispersed pancreatic islet allografts is uncertain, and some studies have suggested that it may be harmful. We performed total pancreatectomies in 21 mongrel dogs, followed by intrasplenic autotransplantation of islet-enriched, dispersed pancreatic tissue prepared by means of ductal perfusion and collagenase digestion. Ten dogs received no other therapy (controls) and 11 received orally administered cyclosporine from the day before to 30 days after transplantation. Therapeutic blood levels of cyclosporine were documented by means of high-pressure liquid chromatography. There was no difference in engraftment in six of 10 controls, and eight of 11 cyclosporine-treated dogs remained normoglycemic for more than 30 days. Intravenous glucose tolerance test results (K values), fasting serum insulin levels, and insulin secretion in response to a glucose challenge were similar in the two groups. There were two late treatment failures in the control group and one in the cyclosporine-treated group. We were unable to detect an adverse effect of cyclosporine on the engraftment or function of canine islet autografts. We conclude that cyclosporine remains a promising drug for use in studies of islet transplantation in human beings.