Gaetano Vetrone

Trends in perioperative outcome after hepatic resection: analysis of 1500 consecutive unselected cases over 20 years.

Objective:To estimate risk factors affecting the early outcome after hepatic resection in a high volume center specialized in hepatobiliary surgery and to analyze the changing of results during 3 different periods of treatment. Design:Retrospective review. Patients:A series of 1500 consecutive patients who underwent hepatic resection. Methods:Postoperative morbidity and mortality were analyzed in relation to indications for surgery, period of operation, patient characteristics, and intraoperative variables. Patients were classified into 4 groups, according to the indication for surgery: primary liver tumors with cirrhosis (group 1, G1); other liver malignancies (group 2, G2); biliary malignancies (group 3, G3); and benign diseases (group 4, G4). Patients were also divided into 3 groups, according to the year of operation (period 1: June 1985 to October 1993; period 2: November 1993 to September 1999; period 3: October 1999 to September 2007). Results:Overall mortality and morbidity were 3% and 22.5%, respectively. Multivariate analysis revealed that blood transfusions, G1, and additional procedures were associated with an increased risk of postoperative complications, whereas blood transfusions, G1, G3, and extended hepatectomy were associated with an increased risk of postoperative mortality. G1 decreased, whereas G3, extended hepatectomies and additional procedures significantly increased between periods 2 and 3 (P < 0.05). The complication rate was significantly lower in period 2 (18.8%) compared with period 1 (23.8%) and period 3 (24.8%). Similarly, there was a significantly lower mortality rate in period 2 (1.6%) compared with period 1 (3.4%) and period 3 (4%). Conclusions:Slightly worse short-term outcomes in liver surgery were observed in recent years, with a concomitant increase of the aggressiveness of operative strategies. Nevertheless, the present results still justify an aggressive approach in liver resections.

The Role of Liver Resections for Noncolorectal, Nonneuroendocrine Metastases: Experience With 142 Observed Cases

BackgroundTo evaluate the role of liver resection for noncolorectal, nonneuroendocrine metastases, indications and results were retrospectively reviewed in 142 observed patients.MethodsA curative liver resection was performed in 83 cases (58.5%), and the remaining 59 patients received palliative treatments. The primary tumor site was gastrointestinal in 18, breast in 21, genitourinary in 15, leiomyosarcoma in 10, and other in 19. The mean number of metastases was 1.4. The mean diameter of the nodules was 5.7 cm. Liver metastases were synchronous in 11 (13.3%) cases and metachronous in the remaining 72 (86.7%).ResultsThere was no operative mortality. Postoperative morbidity was 20.5%. The median postoperative stay was 9.5 days. The 3- and 5-year actuarial survival rate was 49.5% and 34.3% in resected cases, respectively, whereas there were almost no survivors 3 years after diagnosis in unresected cases (P < .05). The 3- and 5-year disease-free survival was 41.4% and 23.8%, respectively. Among the 83 resected cases, the 3- and 5-year actuarial survival was 17.3% and 8.6% for metastases from gastrointestinal tumors, 53.9% and 24.6% from breast cancer, 63.7% and 36.4% from leiomyosarcoma, 50.4% and 37.8% from genitourinary neoplasms, and 55.6% and 42.4% from other sites, respectively. Fifteen patients (18.1%) survived longer than 5 years.ConclusionsLiver resection is an effective treatment for noncolorectal, nonneuroendocrine metastases; it allows satisfactory long-term survival with an acceptable operative risk in selected patients. Hepatic metastases from gastrointestinal carcinoma have the worst prognosis; those from genitourinary tumors show a better outcome. Patient selection is the key to achieving encouraging results.

Liver Transplantation for Recurrent Hepatocellular Carcinoma on Cirrhosis After Liver Resection : University of Bologna Experience

Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy.

Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long‐term survival and tumour recurrence in a single centre

Background : Differences in risk factors for survival and recurrence after liver resection for hepatocellular carcinoma (HCC) in patients with or without cirrhosis are not fully clarified.

Liver transplantation for hepatocellular carcinoma: Further considerations on selection criteria

The selection criteria in liver transplantation for HCC are a matter of debate. We reviewed our series, comparing two periods: before and after 1996, when we started to apply the Milan criteria. The study population was composed of patients with a preoperative diagnosis of HCC, confirmed by the pathological report and with a survival of >1 year. Preoperative staging as revealed by radiological imagining was distinguished from postoperative data, including the variable of tumor volume. After 1996 tumor recurrences significantly decreased (6 out of 15 cases, 40% vs. 3 out of 48, 6.3%, P < .005) and 5‐year patient survival improved (42% vs. 83%, P < .005). Not meeting the Milan criteria was significantly related to higher recurrence rate (37.5% vs. 12.7%, P < .05) and to lower 5‐year patient survival (38% vs. 78%, P < .005%) in the preoperative analysis, but not in the postoperative one. The alfa‐fetoprotein level of more than 30 ng/dL and the preoperative tumor volume of more than 28 cm3 predicted HCC recurrences in the univariate and mutivariate analysis (P < .005 and P < .05, respectively). The ROC curve showed a linear correlation between preoperative tumor volume and HCC recurrence. Milan criteria significantly reduced tumor recurrences after liver transplantation, improving long‐term survival. In conclusion, the efficacy of tumor selection criteria must be analyzed with the use of preoperative data, to avoid bias of the postoperative evaluation. Tumor volume and alfa‐fetoprotein level may improve the selection of patients. (Liver Transpl 2004;10:1195–1202.)

Intrahepatic cholangiocarcinoma: Primary liver resection and aggressive multimodal treatment of recurrence significantly prolong survival

Objective:To evaluate the results of surgical therapy for intrahepatic cholangiocarcinoma (ICC), the incidence and the management of recurrence, and to analyze the change in approach during 2 different periods. Design:Retrospective study. Patients and Methods:Patient and tumor characteristics, and overall and disease-free survival were analyzed in a series of 72 consecutive patients who underwent hepatic resection for ICC. Several factors likely to influence survival after resection were evaluated. Patients were divided into 2 groups according to the year of operation (before and after 1999). Management of recurrence and survival after recurrence were also analyzed. Results:The 3- and 5-year overall survival rates were 62% and 48%, whereas the 3- and 5-year disease-free survival rates were 30% and 25%, respectively. The median survival time was 57.1 months. Patient and histologic characteristics before and after 1999 were similar. Survival was significantly better among patients operated after 1999, who were node-negative, did not receive blood transfusion, and underwent adjuvant chemotherapy. The overall recurrence rates before and after 1999 were comparable (66.6% and 50%, P = 0.49). The most frequent site of recurrence was the liver. A significantly large number of patients received treatment for recurrence after 1999 (81.5%) compared with the first period (8.3%). The overall 3-year survival rate after recurrence was 46%. After 1999, there was a significant improvement in 3-year survival after recurrence (56%) compared with patients operated before 1999 (0%, P = 0.004); the median survival time from the diagnosis of recurrence increased from 20 months to 66 months in the second group. Conclusions:Although recurrence rate represents a frequent problem in ICC, an aggressive approach to recurrence can significantly prolong survival.

Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study.

The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPC+ group, n = 23) or not (IPC− group, n = 24) IPC (10‐min ischemia + 15‐min reperfusion). In 10 cases in the IPC+ group and in 12 in the IPC− group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPC+ group vs. the IPC− group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P = 0.002; and 283 vs. 685 U/L, P = 0.009). Alanine aminotransferases were lower in the IPC+ vs. the IPC− group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P = 0.016; 492 vs. 1,040 U/L, P = 0.008; and 386 vs. 735 U/L, P = 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPC− group (P = 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPC+, P = 0.007; IPC−, P = 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits. Liver Transpl 12:628–635, 2006.

Predictors of sustained virological response after antiviral treatment for hepatitis C recurrence following liver transplantation

Factors associated with sustained virological response (SVR) in patients treated for hepatitis C virus (HCV) recurrence after liver transplantation (LT) are unclear. Ninety‐nine HCV‐positive/hepatitis B surface antigen–negative patients received antiviral treatment (AVT) with interferon/peginterferon plus ribavirin for HCV recurrence after LT. Cyclosporine (CyA) or tacrolimus (TAC) was used as the main immunosuppressor in 37 (37%) and 62 (63%) patients, respectively. Twenty‐five patients (25%) achieved an SVR. Twenty‐seven donor‐related, recipient‐related, HCV‐related, and immunosuppression‐related variables were investigated for their association with SVR. In logistic regression analysis, donor age < 60 years (odds ratio = 4.45, 95% confidence interval = 1.39‐14.19, P = 0.01), viral genotype other than 1 (odds ratio = 4.97, 95% confidence interval = 1.59‐15.48, P = 0.006), and the use of CyA during treatment (odds ratio = 6.85, 95% confidence interval = 2.15‐21.73, P = 0.001) were predictors of SVR. Patients treated with CyA (SVR rate: 43%) and those treated with TAC (SVR rate: 14%) were comparable for all variables, except for a shorter ischemia time and shorter timing of AVT initiation in the TAC group (P = 0.02 and P = 0.005, respectively) and a greater use of anti‐CD25 antibodies, azathioprine, and mycophenolate mofetil in the CyA group (P = 0.03, P < 0.001, and P = 0.001, respectively). The rate of AVT discontinuation due to side effects was similar between groups (16% versus 8%, P = 0.3). In conclusion, the type of immunosuppression during AVT may predict SVR in patients treated for HCV recurrence after LT. Liver Transpl 15:782–789, 2009.

Causes of early acute graft failure after liver transplantation: analysis of a 17-year single-centre experience

Abstract:  Despite satisfactory overall results reported, early post‐operative period after liver transplantation (LT) still represents a critical time with persistently high rate of graft loss. We retrospectively reviewed our experience of 17 yr in LT, analysing the impact on grafts and patient survivals of the acute complications affecting the graft in the early period following LT. To evaluate the changes that occurred over the years in case of early acute graft failure (EAGF), the study population was divided into three equal groups of 223 patients corresponding to three different periods. Ninety (13.5%) experienced an EAGF. Causes of EAGF were hepatic artery thrombosis (HAT) in 32 cases (4.8%), primary graft non‐function in 29 cases (4.3%), caval stenosis in 19 (2.8%), early irreversible acute rejection in 6 (0.9%) and portal vein thrombosis in 4 (0.6%). The use of elderly donors and the introduction of the piggyback technique proved to be associated with a higher incidence of HAT and caval stenosis, respectively. Female recipients of male donors were independently associated with Primary graft non‐function. Of 90 patients with EAGF, 20 (22.2%) died within the first month after LT, 34 (37.8%) underwent retransplantation (ReLT) and 36 (40%) received conservative treatment. Conservative treatments increased from 3.6% in the first group to 47.0 and 66.8% in the second and third one (p = 0.000). One‐year graft and patient survival of patients with EAGF significantly improved over the three eras analysed. The incidence of EAGF remains consistent. Nevertheless, a better understanding of the clinical situations and changes in treatment strategies have led to significant improvements in terms of graft and patient survival rates, now close to the survival rate of EAGF‐free patients.

Liver Transplantation with the Meld System: A Prospective Study from a Single European Center

The efficacy of the Meld system to allocate livers has never been investigated in European centers. The outcome of 339 patients with chronic liver disease listed according to their Meld score between 2003 and 2005 (Meld era) was compared to 224 patients listed during the previous 2 years according to their Child score (Child era). During the Meld era, hepatocellular carcinomas (HCCs) had a ‘modified’ Meld based on their real Meld, waiting time and tumor stage. The dropouts were deaths, tumor progressions and too sick patients. The rate of removals from the list due to deaths and tumor progressions was significantly lower in the Meld than in the Child era: 10% and 1.2% versus 16.1% and 4.9%, p < 0.05. The 1‐year patient survival on the list was significantly higher in the Meld era (84% vs. 72%, p < 0.05). The prevalence of transplantation for HCC increased from 20.5% in the Child to 48.9% in the Meld era (p < 0.001), but between HCCs and non‐HCCs of this latter era the dropouts were comparable (9.4% vs. 14.9%, p = n.s.) as was the 1‐year patient survival on the list (83% vs. 84%, p = n.s.). The Meld allocation system improved the outcome of patients with or without HCC on the list.