C. Loinaz

Successful treatment of mucor infection after liver or pancreas-kidney transplantation.

BACKGROUND Mucormycosis is a rare and opportunistic infection usually associated with hematologic diseases, diabetes mellitus, renal failure, solid tumors, and organ transplantation. METHODS We present five cases of mucor infection after transplantation (three after a series of 750 orthotopic liver transplantation and two after a series of 13 simultaneous pancreas-kidney transplantation in patients with type 1 diabetes) subjected to medical and surgical treatment and analyze the factors related to the development of this infection. RESULTS The clinical forms were two cutaneous (laparotomy wound or prior surgical drain site), two rhino-maxillary, and one pulmonary. As risk factors for mucormycosis all patients had pre- or posttransplantation diabetes, and showed at least one episode of acute rejection that required aggressive immunosuppression (2-7 g of methylprednisolone; also three patients were treated with antithymocyte globulin [ATG] monoclonal antibody [orthoclone and/or OKT3]). We also found renal failure, acidosis, malnutrition, and Candida and cytomegalovirus infections as factors related to mucor infection. Diagnosis of fungal infection was confirmed by exudate or fluid culture in three cases and by biopsy in two. All patients were treated with liposomal amphotericin B (from 3.5 to 5.6 g of total dose) and resection until the surgical margins were free of infection. All patients survived after this severe infection. CONCLUSIONS With an early diagnosis of mucormycosis by clinical findings, culture, or tissue biopsy, and aggressive treatment consisting of administration of liposomal amphotericin B and surgical resection of all infected tissue, excellent results are achieved.

Steroid withdrawal is safe and beneficial in stable cyclosporine-treated liver transplant patients

BACKGROUND In the immunosuppression of orthotopic liver transplant recipients, steroids are used despite their unspecific action and long-term side effects. Few studies have been carried out on steroid withdrawal and many aspects remain to be elucidated. METHODS A prospective study was performed to analyse the effect of steroid withdrawal on 86 patients with stable graft function, more than 1 year after orthotopic liver transplant. Thirty patients had chronic hepatitis in the graft. Seventy-two continued with cyclosporine (CsA) and 14 with CsA-azathioprine (AZA) therapy. The follow-up was 23.2 +/- 8.1 months (range 12-52 months). A paired t-test was used for statistical analysis. RESULTS No acute or chronic rejection occurred, and steroids were not reinstituted. There were no changes in serum transaminase levels, but bilirubin levels decreased (p < 0.01). At the end of the follow-up, we found improvements in blood pressure in hypertensive patients (systolic 156.1 +/- 8.4 mmHg vs. 139.4 +/- 8.7 mmHg, p < 0.001); body weight (72 +/- 13.5 kg vs. 70.8 +/- 13 kg, p < 0.05); serum cholesterol (211.3 +/- 42 mg/dl vs. 191.6 +/- 43.5 mg/dl, p < 0.001) and bone mineral density in lumbar spine (0.823 +/- 0.13 g/cm2 vs. 0.893 +/- 0.135 g/cm2, p < 0.001). Four of ten diabetic patients were no longer insulin-dependent and insulin requirements decreased in the remaining six. No significant biochemical changes were found in patients with hepatitis in the graft, and we found an improvement in inflammatory activity in the nine biopsied patients. CONCLUSIONS Steroid withdrawal with CsA monotherapy is feasible, safe and beneficial in patients who have stable liver graft function 1 year after orthotopic liver transplant. We consider that AZA therapy is not necessary unless drastic reduction of CsA levels is required because of renal dysfunction.

Incidence and risk factors for the development of lung tumors after liver transplantation

Tobacco and immunosuppression are risk factors for developing upper aerodigestive and lung tumors after transplantation. This study comprises 701 adult recipients who survived more than 2 months after transplant: 276 patients underwent orthotopic liver transplantation (OLT) for alcoholic cirrhosis (AC) and 425 for nonalcoholic disease. The aim is to analyze the incidence, clinical characteristics, risk factors, and outcome of patients who develop lung malignancies after OLT. Incidence of lung cancer was 2.1% (15 patients): 4.3% (12 patients) in the alcoholic group and 0.7% (three patients) in the nonalcoholic group (P < 0.001). Mean time from OLT to tumor diagnosis was 86 months. Thirteen patients were smokers; 12 patients were heavy drinkers; and 11 were drinkers and smokers. Squamous cell carcinoma was diagnosed in nine patients, large cell carcinoma in three, adenocarcinoma in two, and broncoalveolar in one. Tumor staging: 10 patients at stage IV; three at stage IIIB; and two at stage IIB. Tumor resection was performed in one patient, and three also received chemotherapy. Mean survival after tumor diagnosis was 5.4 months. There is a higher risk of lung cancer in smoker patients who have undergone OLT for AC, and have a very poor prognosis because tumors are diagnosed at advanced stages.

Advantages of the piggy back technique on intraoperative transfusion, fluid compsumption, and vasoactive drugs requirements in liver transplantation: a comparative study

INTRODUCTION The piggyback technique was first described in adult liver transplantation in 1989, although it has been used in conjunction with venous bypass, with cross-clamping the vena cava, or both. In this study, the inferior vena cava was not occluded at any time during the liver transplant. OBJECTIVE We compared the use of intraoperative blood products, fluid requirements, and vasoactive drugs among patients managed with bypass, without bypass, and with the piggyback technique. MATERIAL AND METHODS Between May 1986 and October 2002, 875 liver transplants included 50 patients divided into three groups (cases considered to be the preliminary series on each group): group A/piggyback (17 patients:34%), group B/ bypass (16 patients: 32%), and group C/no bypass (17 patients:34%). There were no differences in mean age, gender, UNOS or Child-Pugh score, and indications for liver transplantation. RESULTS Mean follow up was 134.63+/-32.19 months. At the end of the study, 91.3% of the patients are alive with no operative mortality. There were no differences in postoperative complications, postreperfusion syndrome rate, and postoperative renal failure. However, the number of packed red blood cell units consumed intraoperatively (12+/-7.43 vs 18.03+/-11.46 vs 17.59 +/- 23.8; P =.043), the need for intraoperative crystaloids (3.1 L+/-1.6 vs 6.8+/-4.8 vs 9.1 L+/-3.6; P=.001) and the requirement for vasoactive drugs (18% vs 38% vs 24%; P=.043) was notably lower in group A vs group B vs group C. Operative time was longer in group A (121.54+/-37.77 vs 78.73+/-11.89 vs 87.07+/-14.33 minutes). CONCLUSIONS The piggyback technique requires a longer operative time but offers the advantages of reducing the red blood cell requirements and preventing severe hemodynamic instability by virtue of reducing the need for vasoactive drugs and for a larger volume of intraoperative fluids.

Reuse of Liver Grafts after Early Death of the First Recipient

Abstract. Three cases are reported of reuse of a transplanted liver graft after early death of the first recipient due to cerebral hemorrhage. The good condition of the donors; the excellent biochemical evolution of the graft in the first recipients; total ABO compatibility and donor-recipient crossmatch; the absence of positivity to hepatitis B virus (HBV), hepatitis C virus (HCV), and bacteriologic cultures; and early death made reuse possible. The shortage of donors in relation to patients on the waiting list and the poor clinical condition of the second recipients made it necessary to adopt the decision to reuse the graft in an attempt to save their lives. The evolution of the patients and the reused grafts was satisfactory, and there were no complications that could be attributed to the fact that the graft had been transplanted before.

Etiopathogenesis and prognosis of centrilobular necrosis in hepatic grafts

The incidence, contributing etiopathogenetic factors, and prognostic significance of centrilobular necrosis were investigated in 270 hepatic transplants to 215 immunosuppressed patients in whom 837 biopsies were performed. Twenty-six (9.6%) grafts demonstrated centrilobular necrosis in one or more biopsy specimens. The immunological, clinical, histopathological, and evolutionary features of this patient group (group A) were compared with a control group of patients who had undergone 92 consecutive transplants with no necrosis (group B). Group A was younger (p < 0.01), had a higher average of warm and cold-ischemia time (p < 0.05), a higher incidence (p < 0.001) and earlier appearance of acute rejection episodes (p < 0.01), and a closer association with evolution to chronic rejection (A: 53.8% vs B: 13.1%, p < 0.001). Survival rates for grafts and patients with necrosis at 12 and 30 months were significantly lower (p < 0.001). The 26 grafts were distributed into three chronological subgroups according to when necrosis appeared: (1) First week--All these grafts were lost (four through primary graft nonfunction and one due to protal recurrent thrombosis); (2) Second week--seven grafts with associated acute rejection, with three evolving to chronic rejection; (3) After the second week (116 +/- 82 days)--five with isolated necrosis, two with associated acute rejection, four with associated ductopenia, and three with associated acute rejection and ductopenia. In 11 grafts the necrosis persisted and evolved to chronic rejection. In conclusion, these findings indicate that centrilobular necrosis is a histopathological sign associated with poor prognosis in most hepatic grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Advanced donor age increases the risk of severe recurrent hepatitis C after liver transplantation

The association between donor age and the severity of recurrent hepatitis C and, whether there is any donor age above which severity of recurrence increases significantly, were analyzed. A total of 131 liver grafts of hepatitis C virus (HCV)‐infected recipients were selected for the study. Distribution of donor age was compared between grafts with and without severe recurrence. The risk of developing severe recurrence as well as the hepatitis‐free, severe hepatitis‐free and HCV‐related graft survival was compared between different donor age groups. Mean donor age was higher for grafts with severe recurrence (P = 0.007). The risk of developing severe recurrence within 2 years post‐transplant increased with donors aged ≥50 years (RR = 1.34) and donors aged ≥70 years (RR = 1.61). Five‐year severe hepatitis‐free survival rates decreased progressively when donor age was over 50 years (P < 0.001). The study shows 50 and 70 years as the donor age cut‐off points above which the evolution of HCV‐infected recipients worsens.

Upper aerodigestive tract and lung tumors after liver transplantation

BACKGROUND The purpose of this study was to analyze the incidence, clinical characteristics, treatment, and outcome of upper aerodigestive (UAD) and lung de novo tumors after ortothopic liver transplantation (OLT). PATIENTS AND METHODS Between April 1986 and June 2002, we performed 851 OLT in 753 patients. We excluded pediatric, partial, and hepatorenal transplants and recipients who died within 2 months after OLT. Thus, we analyzed the incidence and outcome of these tumors in 605 patients after OLT. RESULTS We found 21 (3.5%) tumors in 20 (3.3%) recipients: 14 were UAD tumors (three in floor of the mouth, two in tonsil, one in tongue, one in pharynx, three in larynx, and four in esophagus) and seven were lung tumors. Nineteen patients were men and one was a woman, with a mean age at transplantation of 47.7+/-8.6 years. Mean time from OLT to tumor diagnosis was 61.7+/-35.1 years. As risk factors, 70% were heavy smokers, 75% were heavy drinkers, and 70% developed acute rejection. The incidence of these tumors was significantly higher in transplanted patients for alcoholic cirrhosis compared to the nonalcoholic cirrhosis (8.1% vs 0.8%; P<.0001). After surgical excision in 65% of patients, 1-, 2-, and 3-year patient survival were 47.6%, 37.0%, and 19.7%, respectively. CONCLUSION There is a significantly higher incidence of these tumors in male heavy drinkers and/or smokers who underwent OLT for alcoholic cirrhosis; in spite of aggressive surgical treatment, the prognosis is poor.

Choledochocholedochostomy conversion to hepaticojejunostomy due to biliary obstruction in liver transplantation.

Abstract. Choledochocholedochostomy with tutor (CC-T) or without (CC) is the technique of choice for biliary reconstruction in orthotopic liver transplantation (OLT), however, its rate of complications is high and does not decrease significantly over the years. Biliary obstruction is the most frequent complication and surgical treatment frequently involves conversion to hepaticojejunostomy (H-J). Out of 412 patients (448 OLTs) analyzed retrospectively, 74 (18%) presented biliary complications and 25 (6%) required conversion to H-J because of biliary obstruction, generally due to anastomotic stenosis (17 patients, 68%). Sixteen out of the 25 presented after the first 3 months, and in two patients, stenosis was secondary to arterial thrombosis. Anastomotic stenosis was more frequent in the CC group than in the CC-T group (9.9% versus 2.6%, p < 0.05). Sixteen patients (64%) underwent percutaneous dilatations, but the response was only transitory. There were no postoperative deaths. At the follow-up, three (12%) of the 17 surviving patients presented episodes of cholangitis which required percutaneous dilatations (1), revision of the H-J (1), or conversion to hepaticojejunoduodenostomy (1). Mean survival of patients with H-J was 70.9%, and the actuarial survival rate was 68% at 5 years. This does not differ from the actuarial survival in our series of transplanted patients (65%). CC or CC-T (in selected cases) is an adequate biliary reconstruction for OLT, in spite of the fact that a small number of patients will require conversion to H-J. H-J is an excellent technique of rescue in cases of biliary obstruction that are not possible to resolve by percutaneous dilatations.

Liver transplantation and transjugular intrahepatic portosystemic shunt

OBJECTIVE Describe the results of liver transplantation after installing Transjugular Intrahepatic Portosystemic Shunt (TIPS) and compare them with those of a control group in a comparative, longitudinal, retrospective study. MATERIALS AND METHODS Between April 1986 and October 2002, we performed 875 liver transplantations. Between January 1996 and October 2002, 26 transplantations were performed on TIPS carriers. This group was compared with a control cohort of 50 randomly selected patients who underwent transplantation in this period (non-TIPS carriers). Both groups were homogeneous with no significant differences between age, sex United Network for Organ Sharing (UNOS) score, Child stage, or etiology. RESULTS Actuarial survival rates at 1 and 3 years: TIPS group 96.15% and 89.29% versus control cohort 87.8% and 81%, respectively. In 73.9%, the TIPS was clearly effective; in 88.9%, a postoperative Doppler revealed normal flow. There were no statistically significant differences compared with time on the waiting list for transplant, duration of the operation, ischemia times, intraoperative consumption of hemoderivates, vascular or nonvascular postoperative complications, duration of stay in the intensive care unit, hospital stay, or retransplantation rate. CONCLUSIONS In our experience, TIPS insertion does not affect either the intraoperative or postoperative evolution and is not associated with an increased time on the liver transplant waiting list.