Pancreas transplantation in Ohio: a 15-year outcomes analysis.

BACKGROUND: Beginning in 1984, all pancreas transplantations performed in the state of Ohio have been tracked by the Ohio Solid Organ Transplantation Consortium (OSOTC). In this study the outcomes of these transplantations were compared across 3 eras to determine whether increasing experience has been beneficial. METHODS: Between July 1984 and December 1999, 765 kidney-pancreas (KPTx) and 76 pancreas only (Ptx) transplantations were performed. Outcomes measures for these 841 pancreas transplantations were compared over 3 eras, 1984 to 1989, 1990 to 1994, and 1995 to 1999. RESULTS: One-year patient survivals for KPTx patients were 87%, 92%, and 94% in the 3 eras, respectively. Graft survival at 1 year was also markedly improved between era 1 and era 3, increasing for PTx patients from 21% to 85% and for KPTx patients from 68% to 85%. Average waiting time increased from 132 to 318 days between era 1 and era 3. Conversely, average length of stay in hospital was significantly decreased from 34 to 18 days. The cost of the procedure, as measured by hospital charges, also decreased when compared in 1985 dollars as a technique to control for inflation. CONCLUSIONS: These data suggest that pancreas transplantation in Ohio has become a very successful and cost-effective therapeutic intervention for patients with type I diabetes with or without concomitant end-stage renal failure.

Laparoscopic right adrenalectomy after liver transplantation.

To our knowledge, laparoscopic right adrenalectomy has not been previously reported after orthotopic liver transplantation. The aim of this report is to demonstrate the feasibility of the laparoscopic approach in this technically challenging situation, and to outline some considerations unique to this clinical setting.

Laparoscopic hernia repair enhances early return of physical work capacity.

Several researchers have documented less postoperative pain and a quicker return to daily activities after laparoscopic herniorrhaphy. However, little objective data that validates this hypothesis exists. This study compares the rate of postoperative physical work capacity with return to preoperative levels, which is measured by a standard treadmill test in patients who underwent laparoscopic and conventional open hernia repair. Patients completed a 6-minute walking test preoperatively and 1 week postoperatively using a nonmotorized treadmill. The distance walked was recorded. If the distance that a patient achieved at 1 week was not within 0.02 miles of the preoperative values of the patient, the patient was asked to return at 1 month for repeat testing. Patients were enrolled prospectively in this study from October 1997 to February 1999. Sixty-six patients participated in the study (27 laparoscopic herniorrhaphies and 39 open herniorrhaphies were performed). There was no significant difference in age, body mass index, or preoperative distance achieved among the two groups. At 1 week, patients who underwent laparoscopic repair demonstrated a mean increase of 18 meters from preoperative distance (P = 0.07). In the open group, patients demonstrated a mean decrease of 90 meters at 1 week (P = 0.001). The change in distance at 1 week between the laparoscopic and the open groups was statistically significant (P = 0.001). However, at 1 month, there was no significant difference among the two groups. Measured using treadmill walking, laparoscopic hernia repair seems to offer an early advantage to open repair in return-to-physical-work capacity.

Pancreas transplantation in type 1 diabetes: hope vs reality.

Pancreas transplantation can improve quality of life for patients with type 1 diabetes by eliminating hypoglycemic and hyperglycemic episodes, the need for insulin injections, frequent self-monitoring of blood glucose levels, and dietary restrictions. Increasing evidence suggests that it may slow the progression of long-term diabetic complications. On the other hand, patients risk the adverse effects of lifelong immunosuppression.

Listeria monocytogenes tricuspid valve endocarditis with septic pulmonary emboli in a liver transplant recipient.

Listeria monocytogenes has long been known as a pathogen of immunocompromised hosts, including solid organ and bone marrow transplant recipients. Its principal manifestations include bacteremia and meningitis. Endocarditis due to Listeria is far less common and in general affects the left side of the heart. We here report an unusual case of Listeria tricuspid valve endocarditis and septic pulmonary emboli in a sulfa-intolerant liver transplant recipient with a history of relapsing cytomegalovirus (CMV) hepatitis and an indwelling Hickman catheter. The literature on Listeria endocarditis and infections in transplant recipients is reviewed. The possible relationship between susceptibility to Listeria infection and the discontinuation of trimethoprim-sulfamethoxazole prophylaxis is of interest.

Laparoscopic repair of recurrent ventral hernias.

Break down after repair of recurrent ventral hernias can exceed 50 per cent. Laparoscopic techniques offer an alternative. This study evaluated the efficacy of the laparoscopic approach for recurrent ventral hernias. A retrospective review on all patients with a recurrent ventral hernia who underwent laparoscopic repair at our institution from August 1995 to June 1997 was performed. Demographic, operative, postoperative, and follow-up data were collected. Thirty-one patients underwent an attempted laparoscopic ventral hernia repair. Sixteen were for recurrent hernias; 15 were successfully repaired laparoscopically. The patients were typically obese (mean body mass index, 30 kg/m2), had an average of 2.4 previous open repairs (range, 1-7), and six patients had previously placed intra-abdominal mesh. An average of 3.5 (range, 1-16) defects were found per patient with a mean total hernia size of 130 cm2 (6-480 cm2). In all cases, expanded polytetrafluoroethylene mesh (average, 299 cm2) was secured with transabdominal sutures. Postoperatively patients required an average of 19 mg of narcotics (MSO4 equivalent). Bowel function returned in 1.7 days. Length of stay averaged 2.0 days (1-4 days). There were two complications: cellulitis, which resolved with antibiotics, and skin break-down, which required mesh removal. With follow-up averaging 18 months (7-29 months), there is one recurrence; the case in which the mesh was removed. Laparoscopic repair of recurrent ventral hernia seems promising. Decreased hospital stays, postoperative pain, wound complications, and a low rate of recurrence are benefits of this technique.

Trends in bile duct injuries from laparoscopic cholecystectomy.

Bile duct injuries are a serious complication of cholecystectomy. Laparoscopic cholecystectomies (LC) were originally associated with an increased incidence of injuries. Patients referred to a tertiary center were reviewed to assess the trends in the number, presentation, and management. Seventy-three patients were referred over a 6-year period with a maximum of 17 patients referred in 1992, but the number has not declined substantially over time. The persistent number of referrals is a consequence of ongoing injuries. One third of injuries were diagnosed at LC, and the use of cholangiography has not increased. The number of cystic duct leaks has not decreased and they represent 25% of all cases. The level of injury has remained unchanged with Bismuth types I and II in 37% and types III and IV in 38%. Excluding patients with cystic duct leaks, 58% were referred after a failed ductal repair. Definitive treatment with biliary stenting was successful in 37%, and 34 patients (47%) required a biliary-enteric anastomosis. Complications occurred in 18 patients (25%) including seven with postoperative stricture or cholangitis. No biliary reoperations have been performed at a mean follow-up of 36 months.

Liver resection using total vascular exclusion.

BACKGROUND: Total vascular exclusion (TVE) is a technique of liver resection that includes controlling both the suprahepatic and infrahepatic vena cava in addition to portal inflow at the time of parenchymal transection. We report a series of 61 liver resections in 60 patients using this technique. METHODS: A retrospective review of 61 procedures in 60 patients using TVE between 1990 and 1997 was carried out. No patient had cirrhosis. Parameters analyzed included age, gender, diagnosis, procedure, operative time, clamp time, intraoperative transfusion requirements, postoperative laboratory studies, length of stay (intensive care unit, ward), mortality, and morbidity. RESULTS: TVE was sustained hemodynamically in all patients. The mean age of the 34 men and 27 women was 56 years (+/- 15 years); 21% were older than 70 years. Eleven percent of the patients had benign lesions; 70% of the malignant tumors were metastatic. Seventy-five percent of the procedures were major or extended lobectomies. The mean operative and clamp times were 330 +/- 83 and 39 +/- 13.2 minutes, respectively; 68% had clamp times of < 45 minutes. The mean intraoperative red blood cell units was 1.45 +/- 1.93, with a range of 0 to 8 units; 48% required no transfusion and 80% received 2 units or less. There was 1 perioperative death for a mortality rate of 1.6%. The morbidity rate was 36%, which included 4 patients with postoperative liver dysfunction. Complications were not associated with transfusion but with clamp times exceeding 45 minutes. Liver dysfunction occurred with clamp times more than 60 minutes, particularly if the remaining liver parenchyma was histologically abnormal or the remnant was small. CONCLUSIONS: TVE is hemodynamically safe, even in patients older than 70 years. Blood loss during parenchymal transection is minimal; mortality and morbidity are low. The optimal clamp time is less than 45 minutes. Liver dysfunction is associated with clamp times exceeding 1 hour, particularly if the remaining parenchyma is abnormal or small.

Transmission of Toxoplasma gondii infection by liver transplantation.

Toxoplasmosis is an important disease in immunocompromised hosts, particularly in patients with AIDS and in heart transplant recipients. Infection with Toxoplasma is less commonly seen in recipients of other solid organ transplants. We report a case of fulminant disseminated infection with Toxoplasma after liver transplantation. Despite numerous diagnostic studies including open lung biopsy, toxoplasmosis was diagnosed only at the time of autopsy and involved the brain, spinal cord, pituitary gland, lungs, and heart. Toxoplasmosis should be considered in the differential diagnosis of multiorgan failure in the early period after liver transplantation. If mismatched serologies could be identified then clinical suspicion might be higher and prophylactic or empirical therapy could be instituted. The United Network for Organ Sharing (Richmond, VA) should consider including serology for Toxoplasma in the testing of donors.

Fifty years of surgery for portal hypertension at the Cleveland Clinic Foundation. Lessons and prospects.

OBJECTIVE: The 50-year experience with surgery for the treatment of portal hypertension and bleeding varices at the Cleveland Clinic is reviewed. SUMMARY BACKGROUND DATA: A variety of procedures have been used to treat bleeding varices during the past 50 years. These include transesophageal ligation of varices or devascularization of the esophagus and stomach with splenectomy; portal-systemic (total) shunts; distal splenorenal (selective) shunts; endoscopic sclerotherapy; transjugular intrahepatic portal-systemic shunts; and liver transplantation. METHODS: Our experience with these procedures is reviewed in four time periods: 1946 to 1964, 1965 to 1980, 1980 to 1990, and 1990 to 1994. RESULTS: Our use of these procedures has changed as experience and new techniques for managing portal hypertension have evolved. Most ligation--devascularization--splenectomy procedures were performed before 1980; they provide excellent results in patients with normal livers and extrahepatic portal venous obstruction, but a major complication (40-50%) is rebleeding. Total shunts were performed most frequently before 1980; with patient selection, operative mortality was reduced to 8%, control of bleeding was achieved in more than 90%, but the incidence of encephalopathy was high (30%). Selective shunts provide almost equal protection from rebleeding with less post-shunt encephalopathy. We currently use selective shunts for patients with good liver function. Liver transplantation has been used since the mid 1980s for patients with poor liver function and provides good results for this difficult group of patients. CONCLUSIONS: The selection of patients for these procedures is the key to the successful management of portal hypertension.

The prevalence of coronary artery disease in liver transplant candidates over age 50.

The prevalence of angiographically proven coronary artery disease (CAD) in adults with end-stage liver disease who undergo evaluation for liver transplantation is unknown; also it is unclear if cholestatic liver disease represents an independent risk factor. Patients with end-stage liver disease over age 50 having liver transplantation were studied using coronary angiography. Arterial stenosis was graded as normal, mild (< 30%), moderate (30 to 70%), or severe (> 70%). Risk factors for CAD were also assessed (male sex, smoking, hypertension, diabetes, family history of premature heart disease). Complications related to the angiography and decision making based on the findings were recorded. Thirty seven patients (23 females) with a median age of 61 years (range 50 to 71) underwent angiography. Thirteen patients (35.1%) had cholestatic liver disease. Thirty patients had no history of heart disease. The overall prevalence of severe coronary artery disease was 16.2% (95% confidence interval [CI] = 6.2% to 32.0%). No association was detected between CAD and cholestatic liver disease (P = 0.72). After eliminating seven patients with a prior history of angina (n = 1), myocardial infarction (n = 1), or coronary revascularization (n = 5), the frequency of moderate or severe CAD was 13.3% (95% CI = 3.8% to 30.7%). No association was detected between unsuspected CAD and cholestatic liver disease (P = 0.61). Diabetes was the most important risk factor for moderate or severe disease (P = 0.01). Patients without risk factors had significantly less CAD than the group as a whole regardless of the liver disease type (P = 0.02). Two patients experienced transient renal insufficiency after the angiography. Three patients with severe CAD were denied transplantation. We conclude that CAD represents a significant problem in patients over age 50 undergoing liver transplant evaluation. Cholestatic liver disease was not associated with a significantly higher prevalence of moderate or severe CAD in our population. Diabetes was the most predictive risk factor, and those without risk factors do not require extensive preoperative cardiac evaluation.

Restoration of exocrine pancreatic function following pancreas-liver-kidney transplantation in a cystic fibrosis patient.

Pancreatic transplantation for endocrine replacement is well-established for insulin-dependent diabetes mellitus. Exocrine pancreatic function after pancreas transplantation has been maintained after orthotopic cluster transplants for malignancy, and restoration of adequate exocrine function in a previously deficient patient has been reported in a patient with chronic pancreatitis who developed labile diabetes and steatorrhea after pancreatectomy. We performed a triple organ transplant (pancreas, liver and kidney) in a patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to cystic fibrosis (CF) after he developed hepatic and renal failure. Pancreatic exocrine secretions were drained enterically to the jejunum. At 24-month follow-up, malabsorption is absent. The 3-day stool fat, stool trypsin and chymotrypsin are normal. Serum carotene is within the normal range. Exocrine pancreatic insufficiency in CF patients can be corrected by pancreas transplantation. However, routine use in CF is precluded by the risks of surgery and immunosuppression. For diabetic patients with pancreatic exocrine insufficiency who require another organ transplant (e.g., lung, liver, or kidney), simultaneous pancreas transplantation with the exocrine secretions directed into the upper gastrointestinal tract should be considered.

Orthotopic liver transplantation in two adults with Niemann-Pick and Gaucher's diseases: implications for the treatment of inherited metabolic disease.

Two adults were seen with cirrhosis caused by different lipid storage diseases. A 42-yr-old woman with Niemann-Pick disease type B had marked hepatomegaly, ascites and recent variceal bleeding. Her evaluation showed chronic bilateral pulmonary infiltrates, multiple stigmata of chronic liver disease including the recent cessation of menses, diuretic-resistant sterile ascites, hepatic encephalopathy and variceal bleeding. Five percent of normal sphingomyelinase activity was measured in peripheral leukocytes. A 42-yr-old man with Gaucher's disease and a history of bilateral hip replacements presented with hepatomegaly, jaundice, refractory ascites and renal insufficiency. His evaluation showed 20% to 23% of normal glucocerebrosidase activity in peripheral leukocytes. Both patients underwent orthotopic liver transplantation with resolution of all aspects of decompensated liver function. Assessment of the underlying metabolic defect before and 6 to 14 mo after transplantation showed that after transplantation the patient with Niemann-Pick disease had above normal hepatic sphingomyelinase activity, a less-marked increase in peripheral leukocyte enzyme activity and lower than normal hepatic sphingomyelin and cholesterol content. In contrast, the patient with Gaucher's disease had only a 61% increase in hepatic glucocerebrosidase activity but had an elevated hepatic glucocerebroside content that was only 15% of the pretransplant level and decreased peripheral leukocyte enzyme levels. These findings suggest that variable relationships may exist between posttransplant hepatic and peripheral leukocyte enzyme activities in the different lipidoses, which may have implications for recurrence of glycolipid-induced liver damage.

The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine-treated kidney and kidney-pancreas transplant recipients.

Lipoprotein profiles were measured before and two months after complete withdrawal of prednisone in 34 kidney and 9 kidney-pancreas transplant recipients subsequently maintained on cyclosporine and azathioprine. Withdrawal of steroid therapy was accompanied by a 17% reduction in total serum cholesterol levels. However, there was a parallel reduction in all other measured lipoprotein concentrations, including an 18% reduction in high-density lipoprotein cholesterol levels. In diabetic recipients of a kidney or kidney-pancreas transplant, the ratio of total to high-density lipoprotein cholesterol was unchanged after steroid withdrawal. In nondiabetic kidney transplant recipients, this ratio actually increased significantly following withdrawal of prednisone. These observations suggest that it is premature to presume that withdrawal of steroid therapy will reduce the cardiovascular risk related to hyperlipidemia in cyclosporine-treated kidney or kidney-pancreas transplant recipients.

Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients.

The effects of complete withdrawal of steroid therapy on blood pressure and other clinical variables were studied in 58 renal transplant recipients subsequently maintained on azathioprine and cyclosporine; 76% of the patients were hypertensive prior to withdrawal of steroids. Cessation of steroids was accompanied by a significant decrease in mean arterial blood pressure and by a reduction in the number of required antihypertensive medications; however, changes in blood pressure were variable among individual patients. Previously normotensive patients exhibited little further decline in blood pressure. Multivariate analysis of the entire cohort of patients showed that the reduction in blood pressure accompanying steroid withdrawal was directly related to the prior severity of hypertension and inversely related to the dose of cyclosporine. We conclude that steroids play an important role in the pathogenesis of posttransplant hypertension in the majority of renal transplant recipients. Withdrawal of steroids generally is accompanied by reduction in blood pressure, but the benefit is greatest in previously hypertensive patients receiving relatively low doses of cyclosporine.

Multiple pathways in the rejection of skin grafts.

We have analyzed the ability of CD4+ and CD8+ T cells to cause rejection of skin grafts in an Ir gene high responder strain. (DA.RT1u x DA.RT1c)F1 B rats (thymectomized, lethally irradiated, reconstituted with fetal liver cells) were grafted with ear skin of the recombinant strain, DA.RT1rl. The only allogeneic difference was a single class I MHC antigen. The B rats, which do not reject these grafts due to the absence of T cells, were reconstituted at various time intervals after skin grafting with either unsorted lymph node cells (LNCs), CD4+, CD8+ or CD4+ and CD8+ T cells. Unsorted LNCs given any time after graft placement always caused rejection (MST = 15d). CD4+ cells alone never caused rejection (MST greater than 60d, n = 8). CD8+ cells alone caused rejection if given within 3 weeks of graft placement. Thereafter, CD8+ cells alone lost their ability to cause rejection (MST greater than 60d, n = 6). B rats with grafts in place more than 3 weeks, when CD8+ cells alone were ineffective, rejected their skin grafts when given both CD8+ and CD4+ cells. These data suggest that there may be two T cell pathways in skin graft rejection. The first requires only CD8+ cells and causes rejection of a recently placed graft. The second pathway requires both CD4+ and CD8+ cells to reject long-standing grafts in which donor antigen-presenting cells have been putatively depleted and, therefore, may be dependent on host antigen-presenting cells.

Withdrawal of steroids after renal transplantation--clinical predictors of outcome.

Withdrawal of steroid therapy in renal transplant recipients is associated with a risk of acute allograft rejection. To define clinical risk factors for rejection associated with steroid withdrawal, we analyzed the clinical characteristics of 107 patients with drawn from steroid therapy at various times after transplantation. Both univariate and multivariate analyses suggested that the timing of steroid withdrawal is an important predictor of steroid withdrawal failure. Withdrawal of steroids was successful in only 13 of 32 patients (41%) in whom prednisone was discontinued shortly after transplantation. In contrast, steroid withdrawal has been successful in 59 of 75 patients (79%) in whom prednisone was discontinued at least 6 months after transplantation. Black race and donor-recipient racial mismatch also were significant predictors of rejection associated with steroid withdrawal. In patients undergoing steroid withdrawal at least 6 months posttransplant, serum creatinine concentration also correlated independently with the risk of rejection. Neither age, sex, HLA match, pretransplant PRA, source of the allograft (cadaver vs. living relative), acute tubular necrosis, nor the presence of diabetes was predictive of the outcome of steroid withdrawal.

Independent effects of cyclosporine and prednisone on posttransplant hypercholesterolemia.

To clarify the relative influences of cyclosporine (CsA) therapy, corticosteroid therapy, and other clinical variables on posttransplant hypercholesterolemia, total serum cholesterol levels were measured in 107 renal transplant recipients receiving one of three immunosuppression regimens: CsA and azathioprine (AZA) (group I); CsA, AZA, and prednisone (group II); or AZA and prednisone (group III). Multivariate analysis demonstrated that prednisone therapy, CsA therapy, patient age, and pretransplant cholesterol levels correlated independently with posttransplant cholesterol levels at last follow-up (ranging from 13 to 84 months after transplantation). In 32 patients successfully withdrawn from corticosteroid therapy and maintained on AZA and stable doses of CsA, serum cholesterol decreased from 6.55 +/- 1.1 mmol/L (253.5 +/- 43.1 mg/dL) to 5.27 +/- 1.2 mmol/L (203.9 +/- 45.6 mg/dL). Results of this analysis indicate that prednisone and CsA are independent factors in the pathogenesis of posttransplant hypercholesterolemia. Complete withdrawal of corticosteroids partially corrects hypercholesterolemia in CsA-treated renal transplant recipients.