Emilio Ramos

Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy

BACKGROUND Surgical resection has been the treatment of choice for hepatocellular carcinoma (HCC), but the resection rate remains low in cirrhotic patients and recurrence is common. Unfavorable results compared with benign disease and the shortage of organ donors have led to a restricted indication for orthotopic liver transplantation (OLT) for HCC. STUDY DESIGN The aim of this study was to analyze the results of our surgical approach to HCC in patients with cirrhosis. The first treatment strategy indicated in these patients was OLT. From January 1990 to May 1999, 85 patients underwent OLT and the remaining 35 had surgical resection. RESULTS One-, 3-, and 5-year survival rates were 84%, 74%, and 60% versus 83%, 57%, and 51%, respectively, in the OLT and resection groups (p = 0.34). Hepatic tumor recurrence was much less frequent in the OLT group than in the resection group. The 1-, 3-, and 5-year disease-free survival rates were 83%, 72%, and 60% versus 70%, 44%, and 31%, respectively (p = 0.027). In the multivariate Cox regression analysis, macroscopic vascular invasion was the only factor independently associated with death or recurrence after OLT (p = 0.006). After partial liver resection, the tumors significantly associated with mortality and recurrence in the multivariate analysis were solitary or multiple tumors greater than 2cm with microscopic vascular invasion (pathologic pT3) (p = 0.01). CONCLUSIONS Our results confirm that in cirrhotic patients, OLT may provide better outcomes than liver resection in carefully selected HCC and that longterm survival is similar to the results of OLT in cirrhotic patients without tumors.

The decade of polyomavirus BK-associated nephropathy: state of affairs.

In the last 10 years, better immunosuppression drugs have decreased the rates of acute rejection in kidney transplantation but have also led to the emergence of polyomavirus-associated nephropathy (PVAN). This occurs in 1% to 10% of patients with kidney transplantion and is caused by BK virus in more than 95% of cases. Less than 5% of cases are attributed to the JC virus. Initially, lack of recognition or late diagnosis of PVAN resulted in rapid loss of graft function in more than 50% of patients. In recent years, it has become clear that early diagnosis and timely reduction in immunosuppression is the only proven measure, which significantly affects the outcome of PVAN. Diverse interventions have been explored including the adjunctive use of cidofovir, leflunomide, fluoroquinolones, and intravenous immunoglobulins. Allograft histology is needed to definitively establish the diagnosis of PVAN, but is of limited sensitivity in the early stage of disease. Well-established techniques and protocols for systematic screening by urine cytology and quantitative molecular-genetic techniques allow now for timely intervention before irreversible parenchymal changes occur. Moreover, preemptive reduction in immunosuppression is most effective in presumptive PVAN as defined by surrogate markers (i.e., high BK virus viremia). In this setting, preservation of graft function can be considered the rule. Nevertheless, the recovery of BK virus-specific T-cell immunity may require prolonged periods during which cytopathic damage may continue to accumulate. Despite remarkable progress in the field, important challenges remain, such as the rare patient with PVAN refractory to any intervention and the newly recognized association of PVAN with urogenital tumors.

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.

Application of fibrin glue sealant after hepatectomy does not seem justified: results of a randomized study in 300 patients.

Objective:To evaluate the efficacy, amount of hemorrhage, biliary leakage, complications, and postoperative evolution after fibrin glue sealant application in patients undergoing liver resection. Summary Background Data:Fibrin sealants have become popular as a means of improving perioperative hemostasis and reducing biliary leakage after liver surgery. However, trials regarding its use in liver surgery remain limited and of poor methodologic quality. Patients and Methods:A total of 300 patients undergoing hepatic resection were randomly assigned to fibrin glue application or control groups. Characteristics and debit of drainage and postoperative complications were evaluated. The amount of blood loss, measurements of hematologic parameters liver test, and postoperative evolution (particularly involving biliary fistula and morbidity) was also recorded. Results:Postoperatively, no differences were observed in the amount of transfusion (0.15 ± 0.66 vs. 0.17 ± 0.63 PRCU; P = 0.7234) or in the patients that required transfusion (18% vs. 12%; P = 0.2), respectively, for the fibrin glue or control group. There were no differences in overall drainage volumes (1180 ± 2528 vs. 960 ± 1253 mL) or in days of postoperative drainage (7.9 ± 5 vs. 7.1 ± 4.7). Incidence of biliary fistula was similar in the fibrin glue and control groups, (10% vs. 11%). There were no differences regarding postoperative morbidity between groups (23% vs. 23%; P = 1). Conclusions:Application of fibrin sealant in the raw surface of the liver does not seem justified. Blood loss, transfusion, incidence of biliary fistula, and outcome are comparable to patients without fibrin glue. Therefore, discontinuation of routine use of fibrin sealant would result in significant cost saving.

Prognostic factors for mortality in Left colonic peritonitis : A new scoring system

BACKGROUND Perforating lesions of the colon affect a heterogeneous group of patients, often elderly, and usually present as abdominal emergencies, with high morbidity and mortality. The aims of this study were to assess the prognostic value of specific factors in patients with left colonic peritonitis and to evaluate the utility of a scoring method that allows one to define groups of patients with different mortality risks. STUDY DESIGN Between January 1994 and December 1999, 156 patients (77 men and 79 women), with a mean (SD) age of 63.2 years (15.5 years) (range 22 to 87 years), underwent emergency operation for a distal colonic perforation. Intraoperative colonic lavage was the first choice operation and it was performed in 74 patients (47.4%). There were three alternative procedures: the Hartmann operation was performed in 69 patients (44.2%), subtotal colectomy in 9, and colostomy in 4 patients. We analyzed specific variables for their possible relation to death including gender, age, American Society of Anesthesiologists (ASA) score, immunocompromised status, etiology, and degree of peritonitis, preoperative organ failure, time (hours) between hospital admission and surgical intervention, and degree of temperature elevation (38 degrees C). Univariate relations between predictors and outcomes (death) were analyzed using logistic regression. Multivariate logistic regression analysis was used to assess the prognostic value of combinations of the variables. Significant factors identified in univariate and multivariate logistic regression analyses were used to define a left colonic Peritonitis Severity Score (PSS). Factors that were significant only in univariate analysis scored 2 points if present and 1 if not. Variables significant in multivariate analysis were scored from 1 to 3 points. Patients were randomly split into two groups, one to calculate the scoring system and the other to validate it. RESULTS Overall postoperative mortality rate was 22.4%. Septic-related mortality was observed in 24 patients (15.4%). Age, peritonitis grade, ASA score, immunocompromised status, and ischemic colitis were significant for postoperative death in univariate analysis. But only ASA score and preoperative organ failure were significantly associated with postoperative mortality in multivariate logistic regression analysis. The PSS, as defined in this study, was related to outcomes of patients. Mortality rate increased from 0%, when PSS was 6 points (minimum possible score), to 100% in patients with a PSS of 13 (maximum possible PSS = 14). CONCLUSIONS Left colonic peritonitis continues to have a persistently high mortality in patients with septic complications. ASA score and preoperative organ failure are the only factors that are significantly associated with mortality in the multivariate analysis. The PSS classification may help uniformly define the mortality risk of patients with distal large bowel peritonitis, and may help to increase the comparability of studies carried out at different centers.

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.

Overactivation of the TGF‐β pathway confers a mesenchymal‐like phenotype and CXCR4‐dependent migratory properties to liver tumor cells

Transforming growth factor‐beta (TGF‐β) is an important regulatory suppressor factor in hepatocytes. However, liver tumor cells develop mechanisms to overcome its suppressor effects and respond to this cytokine by inducing other processes, such as the epithelial‐mesenchymal transition (EMT), which contributes to tumor progression and dissemination. Recent studies have placed chemokines and their receptors at the center not only of physiological cell migration but also of pathological processes, such as metastasis in cancer. In particular, CXCR4 and its ligand, stromal cell‐derived factor 1α (SDF‐1α) / chemokine (C‐X‐C motif) ligand 12 (CXCL12) have been revealed as regulatory molecules involved in the spreading and progression of a variety of tumors. Here we show that autocrine stimulation of TGF‐β in human liver tumor cells correlates with a mesenchymal‐like phenotype, resistance to TGF‐β‐induced suppressor effects, and high expression of CXCR4, which is required for TGF‐β‐induced cell migration. Silencing of the TGF‐β receptor1 (TGFBR1), or its specific inhibition, recovered the epithelial phenotype and attenuated CXCR4 expression, inhibiting cell migratory capacity. In an experimental mouse model of hepatocarcinogenesis (diethylnitrosamine‐induced), tumors showed increased activation of the TGF‐β pathway and enhanced CXCR4 levels. In human hepatocellular carcinoma tumors, high levels of CXCR4 always correlated with activation of the TGF‐β pathway, a less differentiated phenotype, and a cirrhotic background. CXCR4 concentrated at the tumor border and perivascular areas, suggesting its potential involvement in tumor cell dissemination. Conclusion: A crosstalk exists among the TGF‐β and CXCR4 pathways in liver tumors, reflecting a novel molecular mechanism that explains the protumorigenic effects of TGF‐β and opens new perspectives for tumor therapy. (Hepatology 2013; 58:2032–2044)

Comparative study of left colonic Peritonitis Severity Score and Mannheim Peritonitis Index

Prognostic evaluation of patients with left colonic perforation is useful in predicting mortality. The aims of this prospective study were to determine the prognostic value of the left colonic Peritonitis Severity Score (PSS) and to compare it with the Mannheim Peritonitis Index (MPI).

Hilar Dissection versus the “Glissonean” Approach and Stapling of the Pedicle for Major Hepatectomies: A Prospective, Randomized Trial

Objective A randomized study was conducted of hilar dissection and the “glissonean” approach and stapling of the pedicle for major hepatectomies to contrast their feasibility, safety, amount of hemorrhage, postoperative complications, operative times, and costs. Summary Background Data The “glissonean” approach is reported as requiring a shorter portal triad closure time; furthermore, the procedure seems to expedite the transection of the liver. Patients and Methods Between 1998 and 2001, 80 patients were enrolled in this study. The major liver resections included 15 extended right, 7 extended left, 42 right, and 16 left hepatectomies. The patients were randomly assigned to the hilar dissection group (G1; n = 40) or to the “glissonean” approach and stapling of the portal triad group (G2; n = 40). Results The groups were equally matched for age, sex, diagnosis, mean resected specimen weight, number of tumoral lesions, type of liver resection performed, and percentage of patients with margin invasion (G1: 4; 10% vs G2: 5; 12.5%). The duration of the 2 procedures was similar (G1: 247 ± 54 min vs G2: 236 ± 43 min; P = 0.4). However, the duration of the hilar dissection was shorter for G2 (50 ± 17 min) versus G1 (70 ± 26 min; P <0.001). By contrast, the duration of pedicular clamping was shorter for G1 (43 ± 15 min) versus G2 (51 ± 15 min; P = 0.015). No differences were observed in the amount of hemorrhage (G1: 887 ± 510 mL vs G2: 937 ± 636 mL; P = 0.7), and only 6 patients in G1 and 10 in G2 were transfused (P = 0.26). Morbidity rates were similar for both groups (G1: 23% vs G2: 33%; P = 0.3). Surgical injury of the contralateral biliary duct was not observed. However, 3 patients in G1 and 4 patients in G2 presented a biliary fistula that resolved spontaneously. Postoperative hospital stay was similar (G1: 8 [range, 6-24] vs G2: 9 [range, 5-31] days; P = 0.6). The postoperative levels of alanine transaminase (ALT) during the 2 first postoperative days were lower for G1 than G2. Cost of the surgical material was 1235.80 US for G1 and 1301.10 US for G2. Conclusions The 2 techniques are equally effective procedures for treating hilar structures. Although en bloc stapling transection is faster, hilar dissection was associated with a shorter pedicular clamping time, less cytolysis, and the materials required were less expensive.