A case of Mycobacterium mucogenicum infection in a liver transplant recipient and a review of the literature.

Bacterial, viral, and fungal infections can be devastating in a postoperative liver transplant recipient on multidrug immunosuppressive therapy. Various atypical (nontuberculous mycobacteria [NTM]) mycobacterial infections have been reported in the solid organ transplant population, but to our knowledge, no cases of Mycobacterium mucogenicum infections have been reported. Here, we report a case of a patient with end-stage liver disease secondary to primary biliary cirrhosis, model for end-stage liver disease score of 29, who underwent deceased-donor orthotopic liver transplantation, with her postoperative course complicated by multiple pleural effusions and peritonitis. Despite numerous courses of antibiotics, her condition did not improve. Acid-fast bacilli cultures grew M. mucogenicum, which was then treated with appropriate antimicrobical therapy. M. mucogenicum, a rapidly growing NTM that can be present in water contamination, should be recognized as a potential source of infection, especially in the immunocompromised population.

Mycophenolate mofetil decreases rejection in simultaneous pancreas-kidney transplantation when combined with tacrolimus or cyclosporine.

BACKGROUND: Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two "state-of-the-art" immunosuppression regimens in a prospective, randomized, single-center study. METHODS: Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neoral formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5 mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgbA1C, hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sandimmune formulation) and AZA-based immunosuppression. RESULTS: The incidence of biopsy-proven acute rejection was 11% in both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (HgbA1C, hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC to CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patients in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. CONCLUSIONS: The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.

Combined liver-pancreas transplantation in a patient with primary sclerosing cholangitis and insulin-dependent diabetes mellitus.

Combined liver-pancreas transplantation is a relatively uncommon procedure. We report successful combined liver-pancreas transplantation in a patient with primary sclerosing cholangitis and insulin-dependent diabetes mellitus and review the literature on this topic.

The use of the T tube after orthotopic liver transplantation.

An end-to-end choledochocholedochostomy (CD) over a T tube or a Roux-en-Y choledochojejunostomy (CDJ) have been the standard method of biliary reconstruction following orthotopic liver transplantation (OLTx). The objective of this study was to assess whether or not use of the T tube leads to increased biliary tract complications. Biliary tract complications were categorized as bile leak, stenosis, or obstruction that required therapeutic intervention. OLTx was performed in 161 patients over an 18-month period. Fifty-one patients were excluded from the study leaving a total of 110 patients for evaluation. Fifty-nine had their bile duct reconstructed over a T tube (CD T tube, group I) while the remaining 51 patients underwent bile duct reconstruction without a T tube (CD, group II). No difference was noted between groups I and II in their survival rate, rate of conversion to Roux-en-Y CDJ, or biliary complication rates. Our results indicate that CD (i.e., without a T tube) is both a safe and effective technique to reconstruct the biliary tract following hepatic transplantation. Routine use of a T tube with a CD anastomosis is unnecessary in most liver transplant patients. In addition, the omission of a T tube has reduced the number of radiological procedures performed at our center.

Adult living donor liver transplantation using a right hepatic lobe.

BACKGROUND: Living donor liver transplantation has gained wide acceptance as an alternative for children with end-stage liver disease. The standard left lateral segment used in this operation does not provide adequate parenchymal mass to broaden its application to larger children or adults. METHODS: We report two cases of adult to adult living donor liver transplantation using a right hepatic lobe in patients with chronic liver disease. RESULTS: Both recipients experienced excellent initial graft function and have normal liver function 4 and 9 months postoperatively. Both donors are alive and well and returned to normal life 4 weeks postoperatively. CONCLUSIONS: Our initial experience suggests that this technique is a safe and reliable option for adults with chronic end-stage liver disease. A conservative application of this procedure in the adult population could significantly reduce the mortality on the adult waiting list.

Fibrosing cholestatic hepatitis in renal transplant recipients.

Fibrosing cholestatic hepatitis in a specific histologic manifestation of hepatitis B virus infection consisting of periportal fibrosis, hepatocyte ballooning, cholestasis, a relatively scant inflammatory infiltrate, and marked overexpression of hepatitis B viral antigens in hepatocytes. Until recently, fibrosing cholestatic hepatitis had been reported only in recipients of liver allografts. In this report, we present two patient in whom this lesion developed following renal transplantation. Both patients had previous liver biopsies showing relatively mild histologic changes. In one patient, the lesion developed early after retransplantation, during the period of maximal immunosuppression. However, in the second patient this lesion developed after withdrawal of immunosuppression. In both cases, death occurred within a few months because of progressive liver disease. Since this lesion can develop in "relatively healthy" hepatitis B carriers following transplantation of organs other than liver, these patients should have careful monitoring of their liver disease. Moreover, since the disease may progress despite withdrawal of immunosuppression, these patients would clearly benefit from the development of more effective therapies for posttransplant hepatitis B.

Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus.

BACKGROUND: The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications. METHODS: A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia. RESULTS: The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months). CONCLUSIONS: MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.

The risk of transmission of hepatitis B from HBsAg(-), HBcAb(+), HBIgM(-) organ donors.

Liver allografts from HBcAb(+), IgM(-), HBsAg(-) donors can transmit HBV to uninfected recipients. We currently no longer accept these livers for transplantation while continuing to accept the kidneys. The purpose of this study is to determine the risk of donor-transmitted HBV infections from HBcAb(+), HBIgM(-), HBsAg(-) organ donors and determine if the risk of donor-transmitted HBV infections and their severity is dependent on the organ being transplanted. This study consists of a retrospective review of the posttransplant course of recipients of HBcAb(+), HBIgM(-), HBsAg(-) donors accepted at UCSF from 6/85 to 12/93. Transmitted HBV infection was defined as one in which the recipient changed from HBsAg(-) prior to transplantation to HBsAg(+) posttransplant, with no other source. There were 25 of 1190 donors who were HBcAb(+), HBIgM(-), HBsAg(-); 1/42 kidney, 3/6 liver, and 0/7 heart HBsAg(-) transplant recipients of organs from these donors became HBsAg(+) after transplantation. This difference in infection rate (liver vs. kidney and heart) is statistically significant. The clinical course of the liver recipients was also more severe. All of the patients who became infected were HBsAb(-) and HBcAb(-) prior to transplant. We conclude that (1) HBV can be transmitted from HBcAb(+), HBIgM(-), HBsAg(-) organ donors, (2) the rate of transmission is highest and severity of infection is worst in the liver recipients; and (3) we will continue to transplant kidneys from these donors, preferably into immunized recipients.

Thoracoscopic Nd:YAG laser resection of a solitary pulmonary nodule.

Advances in endoscopic surgical techniques and laser technology have expanded the role of thoracoscopy. We report a thoracoscopic resection of a benign pulmonary lesion. A 44-year-old man underwent a successful Nd:YAG laser-assisted thoracoscopic resection of a peripheral lung hamartoma. The patient's postoperative course was uncomplicated. Thoracotomy with its attendant morbidity was avoided. Continued success with thoracoscopic resection will have a significant impact on the management of select patients with peripheral, solitary pulmonary nodules.

Total vascular exclusion for major hepatectomy in patients with abnormal liver parenchyma.

BACKGROUND: Total vascular exclusion (TVE) of the liver has been used to increase the safety of hepatectomy and the feasibility of difficult resections. Until recently, however, concern about the detrimental effect of warm ischemia has limited the use of this technique to patients with normal liver parenchyma. OBJECTIVE: To compare surgical outcomes of 12 patients with abnormal livers (group 1) with outcomes of 48 patients with normal parenchyma (group 2), based on the hypothesis that uncontrolled bleeding may be more detrimental than planned hepatic ischemia. DESIGN AND SETTING: Retrospective analysis of 60 consecutive patients undergoing liver resection under TVE in a university medical center. PATIENTS: All 10 patients with cirrhosis had albumin levels of 30 g/L or higher and normal prothrombin times preoperatively; none had ascites. Two patients with cholestasis (one with cholangiocarcinoma and one with hepatocellular carcinoma) are included in group 1. INTERVENTION: All 12 group 1 patients and 44 of 48 group 2 patients underwent total or extended lobectomy, with TVE induced by clamping the hilum and the vena cava above and below the liver during parenchyma division. MAIN OUTCOME MEASURES: Hospital survival and selected surgical and laboratory parameters. RESULTS: Operative times, ischemic times, and blood loss (1975 +/- 1601 vs 1255 +/- 1291 mL) (P = .10) were comparable in both groups. Sixty-day operative mortality was zero in both groups. There was an increased rate of complications in group 1 (44% vs 17% [P = 0.06]). Transient abnormal liver function was observed in both groups. However, significant delay in restoration of normal function was observed in group 1 with respect to bilirubin levels and prothrombin time. CONCLUSIONS: Patients with cirrhosis can undergo successful resection using TVE. This conclusion must be limited to cirrhotic patients with good liver function. The trend toward increased blood loss may reflect greater difficulties in establishing hemostasis after reperfusion in group 1. While this group appears to have a higher risk for hepatic insufficiency, successful outcomes were achieved in all cases. Prospective study will be required to define the parameters for use of TVE in cirrhosis.

Management of major bile duct injury associated with laparoscopic cholecystectomy.

BACKGROUND: Bile duct injury is a major complication of laparoscopic cholecystectomy. The purpose of this study was to evaluate our management strategy and outcomes for the treatment of such injuries. METHODS: We studied 54 consecutive patients who had de novo bile duct injury (n = 20) or prior biliary injury repair (n = 34) associated with laparoscopic cholecystectomy. All patients were managed using a multidisciplinary approach. RESULTS: Definitive operation, almost always Roux-en-Y hepaticojejunostomy, was required in 85% of patients. We inserted external percutaneous biliary catheters in 98% of cases prior to surgery. There were no operative deaths, and the 30-day complication rate was 20%. Eight patients (15%) were managed nonoperatively. Overall, 96% of patients had no long-term, objectively definable biliary sequelae. CONCLUSIONS: Treatment of bile duct injury associated with laparoscopic cholecystectomy is optimally done using a multidisciplinary approach. Surgical reconstruction is required in most cases and can be safely accomplished with minimal morbidity and excellent long-term outcomes.

Thoracoscopic neodymium: yttrium aluminum garnet laser resection of a pulmonary metastasis.

BACKGROUND: Patients with a history of malignant disease and new pulmonary lesions often are considered for resection to establish a diagnosis and, with certain histologic subtypes, to improve survival. Standard operative therapy consists of thoracotomy and wedge resection of the lesion. Early and late postoperative morbidity is substantial and related primarily to the thoracotomy incision. METHODS: Advances in endoscopic surgical techniques and laser technology allowed for successful thoracoscopic resection of an isolated pulmonary metastasis in a 59-year-old man with a history of a T3N0M0 renal cell carcinoma. RESULTS: The margins of the specimen were free of tumor. The postoperative course was uncomplicated, and the patient was discharged on the fourth postoperative day. The morbidity associated with a standard thoracotomy was avoided, and an adequate resection was obtained. CONCLUSION: Continued success with thoracoscopic resection may have a significant impact on the management of selected patients with a history of malignant disease and new pulmonary lesions.

Dyslipidemia during sirolimus therapy in liver transplant recipients occurs with concomitant cyclosporine but not tacrolimus.

Since its approval as an immunosuppressive agent in renal transplantation, sirolimus (RAPA) recently has been used in the primary immunosuppression regimen at several liver transplant centers. One of the major side effects of RAPA is hypercholesterolemia, which is reported in up to 44% of patients. We describe our experience in 57 primary liver transplant recipients treated with RAPA and either cyclosporine A (CSA) or tacrolimus (TAC). We report the incidence and severity of hypercholesterolemia using a prednisone-free immunosuppressive regimen. Between January 2000 and September 2000, a total of 57 patients underwent transplantation at the University of Colorado Health Sciences Center (Denver, CO) with RAPA and either CSA or TAC. The initial 10 patients who underwent transplantation under this protocol were not administered corticosteroids, and the subsequent 47 patients were administered only 3 doses of methylprednisolone days 0, 1, and 2 postoperatively (1, 0.5, and 0.5 g, respectively). Total fasting cholesterol, high-density cholesterol, low-density cholesterol, and triglyceride levels were measured at monthly intervals. Mean serum cholesterol level was significantly greater in CSA patients (200 mg/dL) compared with TAC patients (158 mg/dL; P =.0003). Serum triglyceride levels were more than 2-fold greater with CSA (292 mg/dL) compared with TAC (134 mg/dL; P =.002). Hypercholesterolemia (cholesterol > 240 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (8 of 27 patients; 30%) compared with TAC-treated patients (2 of 30 patients; 6%; P <.05). Hypertriglyceridemia (serum triglyceride > 300 mg/dL) was present in 10 of 57 patients (18%) and was significantly more common in CSA-treated patients (9 of 27 patients; 33%) compared with TAC-treated patients (1 of 30 patients; 3%; P <.05). We conclude that (1) concomitant use of TAC with RAPA reduces the prevalence and severity of posttransplantation dyslipidemia, and (2) these findings have important implications in the prevention of complications of hypercholesterolemia in liver transplant recipients.