Octogenarian Donors in Liver Transplantation.

INTRODUCTION: Due to the disparity between the number of patients on the list for liver transplantation and the availability of organs, the use of older donors has become necessary. The aim of this study was to investigate the outcomes of liver transplantation using octogenarian donors. METHODS: From December 2003 to February 2016, 777 liver transplantations were performed at our institution, 33 of them (4.2%) with donors 80 years old and above. Our policy for the acceptance of these donors is based on preoperative liver function tests, donor hemodynamic stability, and intraoperative normal gross aspect. Octogenarian grafts were deliberately not assigned to retransplantations or to recipients with multiple previous surgical procedures or extensive portal thrombosis. RESULTS: Mean donor age was 82.7 ± 2.1 years, with a range between 80 and 88. Only 12.1% suffered hemodynamic instability during the intensive care unit stay. Three donors (9.1%) had a history of diabetes mellitus. The mean Model for End-Stage Liver Disease score among recipients was 14.7 ± 5.6. Mean cold ischemia time was 302 ± 61 minutes. After a median follow-up of 18.5 months (range 7.5 to 47.5), no graft developed primary nonfunction. We observed hepatic artery thrombosis in 1 patient (3%) and biliary complications in 4 patients (12.5%). There was 1 case of ischemic-type biliary lesion, although it was related to hepatic artery thrombosis. Patient survival at 1 and 3 years was 90.3%, whereas graft survival was 92.6% and 86.4%, respectively. CONCLUSIONS: Excellent mid-term results can be obtained after liver transplantation with octogenarian donors with strict donor selection and adequate graft allocation.

Intraoperative Portal Flow of Less Than 1 Liter per Minute After Orthotopic Liver Transplantation Is Not Associated Per Se With an Increased Rate of Early Graft Dysfunction.

OBJECTIVE: The aim of this study was to determine whether a portal flow of <1,000 mL/min in orthotopic liver transplantation (OLT) is associated with a higher incidence of early graft dysfunction (EGD) and graft loss. METHODS: A retrospective study was performed of 540 OLTs carried out consecutively from December 2004 to December 2013. Patients were divided into 2 groups: group A, portal flow <1,000 mL/min; and group B, portal flow >1,000 mL/min. We studied the incidence of EGD and graft survival. A subanalysis was performed to define the minimum acceptable portal flow/100 g of liver weight to reduce the development EGD and graft loss. RESULTS: Group A included 29 patients and group B, 511 patients. Group A had significantly lower-weight donors and recipients, female recipients with cholestatic disease, lower MELD scores, and lower hepatic artery flow. EGD occurred in 7 patients in group A (24.1%) versus 101 patients in group B (19.8%; P = .43). No significant differences were found in 1- and 5-year graft survival. A portal flow of <80 mL/min/100 g of liver weight was related to a significantly higher risk of developing EGD (odds ratio, 4.35; 95% confidence interval [CI], 1.46-12.91; P = .008) and graft loss (hazard ratio, 4.05; 95% CI, 1.32-12.42; P = .014). CONCLUSIONS: Intraoperative portal flow of <1,000 mL/min in OLT was not related per se with a higher incidence of EGD or graft loss. Significantly higher risk of developing EGD and graft loss was associated with a portal flow of <80 mL/min/100 g of liver weight.

Donors older than 70 years in liver transplantation.

INTRODUCTION: Expansion of donor criteria has become necessary with the increasing number of liver transplantation candidates, as aged donors who have been considered to yield marginal organs. METHODS: Our database of 477 liver transplants (OLT) included 55 cases performed from donors at least 70 years old vs 422 with younger donors. We analyzed pretransplantation donor and recipient characteristics as well as evolution of the recipients. RESULTS: The old donor group showed significantly lower ALT (23 +/- 17 vs 48.9 +/- 67; P = .0001) and LDH (444 +/- 285 vs 570 +/- 329; P = .01). There was a trend toward fewer hypotensive events in the aged donor group (27.2% vs 40.5%; P = .07). No steatosis (>10%) was accepted in the old donor group. Cold ischemia time was statistically shorter for the aged donors (297 +/- 90 minutes vs 346 +/- 139 minutes; P = .03). With these selected donors, the results were not different for primary nonfunction, arterial and biliary complications, hospitalization, acute reoperation or acute retransplantation, and hospital mortality when donors > or =70 years old were compared to younger donors. Functional cholestasis, neither related to rejection nor to biliary complications, was seen more frequently in old donor recipients (40% vs 22%; P = .03). No differences in 1, and 3 year survivals were observed between recipients of donors over 70 years old and these of younger organs: 93.8% and 90.6% vs 90.7% and 82.8%, respectively. CONCLUSION: When using selected donors > or =70 years old the outcomes were comparable to those obtained with younger donors. Strict selection is necessary to achieve good long-term survival.

Risk factors for biliary complications after orthotopic liver transplantation with T-tube: a single-center cohort of 743 transplants.

BACKGROUND: Despite recent advances in organ preservation, surgical procedures, and immunosuppression, biliary reconstruction after orthotopic liver transplantation (OLT) remains as a major source of morbidity. The purpose of this study was to identify risk factors for the development of biliary complications (BCs) after end-to-end choledochocholedochostomy (EE-CC) with a T-tube as the standard technique for biliary reconstruction after OLT. METHODS: A total of 833 consecutive liver transplantations that took place from February 1996 to April 2010 were retrospectively reviewed. Patients with concomitant hepatic artery complications were excluded, as were those who underwent urgent retransplantation or died within 1 week after transplantation. Finally, the study group comprised 743 patients. RESULTS: The overall BC rate was 9.8% (73 patients), including stricture in 19 patients (2.6%) and bile leakage in 39 patients (5.2%). After univariate analysis, significant risk factors for BCs were surgery time >5 hours, arterial ischemia time >30 minutes, use of a classic transplant technique, transfusion of red blood cells ≥5 units, anti-cytomegalovirus treatment, and period of transplantation between 1996 and 2002. Stepwise logistic regression study was performed, including those variables with a value of P <.200. Multivariate analysis showed that pretransplant serum creatinine (odds ratio = 1.27; 95% confidence interval [CI], 1.03-1.57; P = .025) and arterial ischemia time >30 minutes (odds ratio = 2.44; 95% CI, 1.45-4.12; P = .001) were the only independent risk factors related to the development of BCs after biliary reconstruction with the T-tube. CONCLUSIONS: The performance of different variables in predicting occurrence of BCs was assessed with the use of receiver operating characteristic analysis. The area under the receiver operating characteristic curve of our model was 0.637 (95% CI, 0.564-0.710), and therefore we must conclude that other variables not included in our model may have influence in the development of BCs after OLT with an EE-CC with a T-tube as the procedure for biliary reconstruction.

Biliary complications in orthotopic liver transplantation using choledochocholedochostomy with a T-tube.

Despite significant advances in orthotopic liver transplantation (OLT), biliary tract reconstruction is still a major source of complications. Choledochocholedochostomy with a T-tube used to be the standard procedure for biliary reconstruction after OLT. However, many centers currently avoid use of the T-tube because of the high incidence of complications. Our aim was to study the biliary complications occurring at our center when end-to-end choledochocholedochostomy (EE-CC) over a T-tube was used as the standard procedure for biliary reconstruction. A retrospective review was conducted of all patients who underwent liver transplantation from February 1, 1996, to April 30, 2010. Only patients requiring any therapy to treat biliary complications were considered, whereas those with concomitant hepatic artery complications were excluded. The study cohort consisted of 743 patients who had EE-CC with a T-tube. Of these, 73 patients (9.8%) experienced any biliary complication. Anastomotic strictures occurred in 17 patients (2.3%), and non-anastomotic strictures in 2 (0.3%). Fifteen patients with anastomotic strictures were successfully treated by dilatation and stenting. Bile leakage was diagnosed in 39 patients (5.2%). Leakage occurred at the anastomosis in 15 patients (2%), and at the exit site of the T-tube in 24 patients (3.2%). Tube opening was the only treatment used in 30 patients with bile leakage (76.9%). Seven patients experienced leaks after elective T-tube removal (1%). Overall, repeat surgery to manage biliary complications was needed in 9 patients (1.2%). The mortality rate from biliary complications was 0.13%. In conclusion, EE-CC with a T-tube was followed by a low incidence of biliary complications. The complication rate after elective T-tube removal and the repeat surgery rate were extremely low. These results might challenge the current trend to avoid T-tube stenting in OLT.

A prospective, multicenter study of once-daily extended-release tacrolimus in de novo liver transplant recipients.

To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months (P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.

Advagraf de novo in liver transplantation: a single-center experience.

UNLABELLED: Advagraf, a prolonged release formulation of tacrolimus, is administered once daily in the morning. The aim of this study was to show the results obtained in our center, analyzing the safety, efficacy, blood trough levels, and drug doses. METHODS: We analyzed 50 consecutive recipients of a first liver transplantation with 6 months follow-up. Efficacy and safety variables were collected as the incidence of acute rejection episodes, patient and graft survivals, kidney function as well as incidences of diabetes mellitus and arterial hypertension de novo. RESULTS: The incidence of biopsy proven acute rejection episodes was 10% (n = 5), none 7 of which were steroid resistant and all resolved favorably. The rate of diabetes mellitus de novo was 22% (n = 11), 7 of whom required insulin. Hypertension developed in 9 patients (18%), all of whom were treated with a single drug. The mean serum creatinine level was 1.08 ± 0.25 mg/dL, with 3 patients (6%) displaying a value ≥ 1.5 mg/dL. Patient and graft survivals were 100%. CONCLUSION: Advagraf is an effective immunosuppressant in liver transplantation with a low incidence of biopsy-confirmed acute rejection episodes. The good results for patient and graft survival with few side effects make it a useful drug for de novo liver transplantation.

The safety and effectiveness of stepwise and low-dose administration of follicle stimulating hormone in WHO group II anovulatory infertile women: evidence from a large multicenter study in Spain.

PURPOSE: Our goal was to investigate the safety, effectiveness, and feasibility for the practicing physician of stepwise and low-dose administration of FSH in WHO group II anovulatory infertile women. METHODS: Infertile female patients (n = 234) suffering from WHO group II anovulation, and who failed to became pregnant with clomiphene citrate, were included in a multicenter, prospective, clinical study of treatment with a protocol of chronic low-dose and small incremental rises with urinary purified or highly purified FSH. Follicular development was monitored with ultrasonographic scans. RESULTS: The 234 patients received a total of 534 cycles of treatment, for a mean number of 2.3 treated cycles per patient. hCG was withheld in 65 (12.2%) cyles because of no response and in 28 (5.2%) cycles because of hyperresponse. Of the remaining 441 cycles, 419 (95%) were ovulatory, and in 198 (47.3%) of these cycles a single dominant follicle developed. There were 93 pregnancies (39.7% per patient), for a cycle fecundity rate of 17.4%. Cumulative conception rate after two treated cycles was 33.5%. There were 14 (15%) pairs of twins and 10 (10.8%) spontaneous miscarriages. The prevalence of complications was low with no cases of severe OHSS. Basal LH/FSH ratio was significantly higher in the pregnant group of patients than in nonpregnant women. CONCLUSIONS: Stepwise and chronic low-dose administration of FSH is a safe and effective method for treatment of WHO group II anovulatory infertility, mainly in those patients having high LH/FSH ratios.