Juli Busquets

The impact of donor age on liver transplantation: influence of donor age on early liver function and on subsequent patient and graft survival.

BACKGROUND The urgent need to increase the organ donor pool has led to the expansion of criteria for donor selection. The aim of this study was to analyze the influence of donor age on early graft function, subsequent graft loss, and mortality after liver transplantation (LT). METHODS Data on LT were evaluated retrospectively in a population-based cohort of 400 LTs in 348 patients. Of these, 21 (5%) were from donors >70 years old. Pretransplantation donor and recipient characteristics and the evolution of recipients were analyzed. The influence of donor age as a risk factor was assessed using univariate and multivariate analyses. RESULTS Actuarial graft survival was 89% at 1 month after LT, 81% after 6 months, and 59% after 60 months. Multivariate analysis demonstrated that only donor age (>70 years old) was associated with a higher risk of long-term graft loss (relative risk [RR]=1.4, 95% confidence interval [CI]=1-1.9; P=0.03) and mortality (RR=1.7, 95% CI=1.2-2.3; P=0.01). Graft survival of septuagenarian livers was 80% at 1 month after LT, 56% after 6 months, and 25% after 54 months. Actuarial survival analysis (Kaplan-Meier curves) also demonstrated worse evolution in recipients of livers from old donors (log-rank test, P<0.001). CONCLUSIONS Advanced donor age is associated with lower graft and recipient survival.

Complete Versus Selective Portal Triad Clamping for Minor Liver Resections: A Prospective Randomized Trial

Objective:To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections. Summary Background Data:Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia. Patients and Methods:Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded. Results:No differences were observed in the amount of hemorrhage (671 ± 533 mL versus 735 ± 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 ± 4.6 versus 4.5 ± 2.7 μkat/L, P = 0.01) and AST (10.2 ± 8.7 versus 4.9 ± 2.1μkat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity. Conclusions:Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.

The deleterious effect of donor high plasma sodium and extended preservation in liver transplantation. A multivariate analysis.

The aim of this study was to analyze the donor risk factors associated with second orthotopic liver transplantation (reOLT) and graft loss after OLT within 1 month. A total of 649 OLTs performed in 11 centers in Spain during the period from 1992 to 1993 were analyzed retrospectively. Eleven donor and recipient variables were studied. Biochemical evolution of the OLT, biliary and arterial complications, patient status (alive, retransplanted, or dead), and follow-up were also recorded. Bivariate study demonstrated that extended preservation ( > 12 hr) was associated with increased biliary complications (P = 0.02), and lower prothrombin time (P = 0.04). In a logistic model regression for biliary complications, ischemia > 12 hr was an independent risk factor (odds ratio = 2.2, 95% confidence interval [CI] = 1.1-4.3). The multivariate Cox proportional model of potential risk factors showed that only urgent reOLT (relative risk [RR] = 2.7, 95% CI = 1.4-5.4) was independently associated with higher 30-day mortality. Donor plasma sodium > 155 mmol/L (RR = 1.4, 95% CI = 1.0-2.2) and incompatible ABO graft (RR = 3.2, 95% CI = 1.3-7.9) were independently associated with increased rate of reOLT before 30 days. Donor plasma sodium > 155 mmol/L (RR = 2, 95% CI = 1.1-3.6) and incompatible graft (RR = 3.3, 95% CI = 1.4-8.2) were independently associated with graft loss (death or reOLT) before 1 month. We conclude that cold ischemia should be kept less than 12 hr in order to avoid biliary complications. Donors over 60 years old or with plasma sodium > 155 should be carefully evaluated before OLT.

Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality

Abstract:  Background:  Splanchnic thrombosis is a surgical challenge in liver transplantation (LT). The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution.

A Double-blind, Placebo-controlled Trial of Ciprofloxacin Prophylaxis in Patients with Acute Necrotizing Pancreatitis

BackgroundThe use of prophylactic antibiotics in acute severe necrotizing pancreatitis is controversial.MethodsProspective, randomized, placebo-controlled, double-blind study was carried out at Bellvitge Hospital, in Barcelona, Spain. Among 229 diagnosed with severe acute pancreatitis, 80 had evidence of necrotizing pancreatitis (34/80 patients were excluded of the protocol). Forty-six patients without previous antibiotic treatment with pancreatic necrosis in a contrast-enhanced CT scan were randomly assigned to receive either intravenous ciprofloxacin or placebo. Five patients were secondarily excluded, and the remaining 41 patients were finally included in the study (22 patients received intravenous ciprofloxacin and 19 patients placebo).ResultsComparing the 22 with intravenous ciprofloxacin and 19 with placebo, infected pancreatic necrosis was detected in 36% and 42% respectively (p = 0.7). The mortality rate was 18% and 11%, respectively (p = 0.6). No significant differences between both treatment groups were observed with respect to variables such as: non-pancreatic infections, surgical treatment, timing and the re-operation rate, organ failure, length of hospital and ICU stays.ConclusionThe prophylactic use of ciprofloxacin in patients with severe necrotizing pancreatitis did not significantly reduce the risk of developing pancreatic infection or decrease the mortality rate. The small number of patients included in this study should be considered.

Nanofluidic Digital PCR for KRAS Mutation Detection and Quantification in Gastrointestinal Cancer

BACKGROUND Concomitant quantification of multiple mutant KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) alleles may provide information in addition to that provided by standard mutation-detection procedures. We assessed the feasibility of a nanofluidic digital PCR array platform to detect and quantify KRAS mutations simultaneously in clinically relevant samples. METHODS We assessed 2 groups of patients (colorectal and pancreatic disease): Group 1 consisted of 27 patients with colorectal carcinomas, 14 patients with adenomas, and 5 control individuals; group 2 consisted of 42 patients with pancreatic carcinoma, 4 with adenocarcinomas of the ampulla, and 6 with chronic pancreatitis). Digital PCR was performed with the Digital Array Chip (Fluidigm). RESULTS Nanofluidic digital PCR detected mutant alleles at 0.05% to 0.1%, depending on the variant analyzed. For the colorectal disease group, conventional PCR detected 9 (64%) of 14 adenomas that were positive for KRAS mutants, whereas digital PCR increased this number to 11 (79%) of 14. Sixteen (59%) of 27 carcinomas showed KRAS mutation with conventional PCR. Two additional cases were detected with digital PCR. In 5 cases (3 adenomas, 2 carcinomas), the total number of mutant alleles changed. For the pancreatic disease group, digital PCR increased the number of positive cases from 26 to 34 (81%) and identified ≥ 2 mutant alleles in 25 cases, compared with conventional PCR, which identified multiple KRAS mutant alleles in only 12 cases. A good correlation was observed between results obtained with tumor biopsies and those obtained with pancreatic juice. CONCLUSIONS Digital PCR provides a robust, quantitative measure of the proportion of KRAS mutant alleles in routinely obtained samples. It also allows a better classification of tumors, with potential clinical relevance.

Análisis de 500 trasplantes hepáticos en el Hospital de Bellvitge

Fundamento Se presenta la experiencia del programa de trasplante hepatico del Hospital de Bellvitge en 500 trasplantes realizados durante 15 anos, con el objetivo de poner de manifiesto los cambios que se han producido y exponer los resultados a largo plazo de esta terapeutica. Pacientes y metodo Se consideraron y compararon 5 grupos de 100 trasplantes consecutivos (I-V). Resultados Las indicaciones mas frecuentes fueron el hepatocarcinoma (23%), la cirrosis alcoholica (22,8%) y la hepatopatia cronica por virus C (18,8%). En 59 pacientes se llevaron a cabo 65 retrasplantes (13%), cuyas indicaciones mas frecuentes fueron la trombosis arterial (13 pacientes) y el fallo primario del injerto (10 pacientes). En 19 enfermos se realizo un trasplante combinado hepatorrenal. La causa mas frecuente de muerte del donante en el grupo I fueron los traumatismos craneales (80%), mientras que en el grupo V fue la enfermedad vascular (52%). Otras diferencias significativas entre estos grupos se observan en la proporcion de pacientes en estadio 2 y 3 de la clasificacion UNOS (el 45 frente al 19%), en el consumo de hemoderivados (29,6 [26] frente a 4,6 [5,3] concentrados de hematies), en la frecuencia de reintervenciones por hemoperitoneo (el 22 frente al 5%), en la estancia en UCI (13 [13] frente a 7,4 [11] dias) y en el hospital 40 [52] frente a 23,7 [17] dias), y en la incidencia de rechazo (el 46 frente al 20%) y de fallo primario del injerto (el 9 frente al 3%). Sin embargo, la prevalencia de infeccion (el 48 frente al 54,5%) y la incidencia de complicaciones biliares (el 26 frente al 20%) no han presentado variaciones significativas. La supervivencia actuarial de los pacientes trasplantados desde 1990 es del 83 y del 70% al ano y a los 5 anos, respectivamente. Conclusiones Se observa una mejoria notable y progresiva de los resultados del trasplante hepatico. Sin embargo, los tumores de novo, la recidiva de la hepatitis por virus C y el rechazo cronico pueden limitar los resultados a largo plazo.

Factors influencing mortality in patients undergoing surgery for acute pancreatitis: importance of peripancreatic tissue and fluid infection.

Objectives The aims of present study were to analyze the mortality risk factors in patients who had surgery for acute pancreatitis and to assess the importance of culturing peripancreatic tissue or fluid infection to ascertain the infection status. Methods Surgery was indicated both in patients with infected severe acute pancreatitis and in those with sterile pancreatitis with an unfavorable course. During surgery, cultures were taken of tissues (pancreatic necrosis and peripancreatic fat), intra-abdominal fluid, and bile. Results Of 107 patients operated on, fluid culture was analyzed in 94 patients, pancreatic necrosis in 61 patients, peripancreatic fat in 39 patients, and bile in 38 patients. Sterile pancreatitis with sterile ascites was found in 17 patients, sterile pancreatitis with infected ascites in 22, and pancreatic tissue infection in 60. Multivariate analysis demonstrated that sterile tissue cultures, age over 65 years, and fewer than 12 days between the beginning of pain and surgery were risk factors for mortality. Sterile pancreatitis with sterile ascites and sterile pancreatitis with infected ascites had similar postoperative mortality (41% and 50%, respectively); the group with pancreatic tissue infection had a lower mortality (20%). Conclusions Early surgery, advanced age, and sterility of tissue cultures have been demonstrated as mortality factors for acute pancreatitis. Intra-abdominal fluid may be infected in the presence of sterile necrosis.

Comparative Study of Celsior and Belzer Solutions for Hepatic Graft Preservation: Preliminary Results

HE SCARCITY OF donors and the increase in the number of transplant candidates have stimulated research to minimize the loss of donated organs. Preservation solutions are available to conserve the organs for a determinate period. In liver transplant (LT) Belzer and Brettschneider solutions give satisfactory results. However, graft malfunction remains a problem and other solutions are being examined. This randomized comparative study aims to examine the hepatic function of grafts perfused with Celsior solution (CS) and Belzer solution (BS) following liver transplant in adults.

Genetic and epigenetic markers in the evaluation of pancreatic masses

Background Methylation markers have shown promise in the early diagnosis of pancreatic carcinoma. The aim of this study was to assess the diagnostic utility of hypermethylation status of candidate genes in combination with KRAS mutation detection in the evaluation of pancreatic masses. Experimental design Sixty-one fine needle aspirates of pancreatic masses (43 pancreatic adenocarcinomas and 18 chronic pancreatitis) were studied. Methylation status of HRH2, EN1, SPARC, CDH13 and APC were analysed using melting curve analysis after DNA bisulfite treatment. KRAS mutations were also analysed. Results The methylation panel had a sensitivity of 73% (27 of 37, CI 95% 56 to 86%) and a specificity of 100% whenever two or more promoters were found hypermethylated. KRAS mutations showed a sensitivity of 77% (33 of 43, CI 95% 62 to 88%) and a specificity of 100%. Both molecular analyses added useful information to cytology by increasing the number of informative cases. When genetic and epigenetic analyses were combined sensitivity was 84% (36 of 43 CI 95% 69 to 93%) maintaining a 100% specificity. Conclusions Analysis of hypermethylation status of a panel of genes and KRAS mutation detection offer a similar diagnostic yield in the evaluation of pancreatic masses. The combined molecular analysis increases the number of informative cases without diminishing specificity.