Giovanni Varotti

Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence.

ObjectiveTo evaluate prognostic factors that could affect disease-free survival and recurrence after liver resection for hepatocellular carcinoma (HCC) on cirrhosis. Summary Background DataTumor recurrence is the main cause of poor survival after liver resection for HCC on cirrhosis. MethodsTwo hundred twenty-four liver resections for HCC on cirrhosis were retrospectively reviewed. Univariate and multivariate analyses were performed on several clinicopathologic variables to analyze factors affecting long-term outcome and intrahepatic recurrence. The relation between preoperative aminotransferase level and recurrence rate was evaluated in the overall group, and separately in HCV-positive and in HBsAg-positive patients. Median follow-up was 35.6 months. ResultsThe 1-, 3-, and 5-year overall survival rates were 83%, 62.8%, and 42.5%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 70.3%, 43%, and 27.4%, respectively. The 1-, 3-, and 5-year recurrence rates were 20.8%, 38.6%, and 54.4% respectively. Tumor recurrence appeared in 93 patients (41.5%) and was the main cause of death in 51 patients (56%). Number of nodules, tumor capsule, microvascular portal vein thrombosis, and preoperative serum aspartate aminotransferase (AST) level significantly affected disease-free survival and recurrence rates. On multivariate analysis, single nodules and preoperative AST level less than twice normal (2N) were related to a better 5-year disease-free survival and lower tumor recurrence. In particular, among HCV-positive patients the recurrence rate was strongly affected by the preoperative AST level. ConclusionsChild A patients with single nodules are the best candidates for liver resection. Tumor recurrence is strictly linked to the status of the underlying liver disease, and a preoperative AST level equal to 2N seems to be a sensitive cutoff among patients with different risks of recurrence. HCV-positive patients with AST levels above 2N have the highest risk for intrahepatic recurrence and should be monitored carefully or offered alternative treatments.

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.

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.

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.

Outcome of hepatic artery reconstruction in liver transplantation with an iliac arterial interposition graft

Abstract:  Background: In case of anomal hepatic arterial inflow, it can be necessary to perform revascularization of the liver allograft by iliac arterial interposition graft.

Venous outflow reconstructions with the piggyback technique in liver transplantation: a single-center experience of 431 cases

The ideal method of venous outflow reconstruction with the piggyback technique (PB) in orthotopic liver transplantation (OLT) is not well‐established. The complications related to PB in 431 primary OLTs were analyzed comparing the orifices used for the anastomosis (cuff of the recipient left and middle hepatic veins [LM], LM with a >1 cm cavoplasty [LM+], or also including the right hepatic vein [LMR]). Treatment strategies and outcome were also evaluated. Twenty patients (4.6%) experienced complications: 13 of 120 (10.8%) with LM, four of 225 (1.8%) with LM+, and three of 86 (3.5%) with LMR (LM versus LM+: P < 0.0001; LM versus LMR: P = NS; LM+ versus LMR = NS). Balloon dilation was successful in 10 of 13 cases in which it was attempted (77%). Eight patients required retransplantation (40%). Three patients (0.7%) died from causes linked to stenosis. Five‐year survival of patients with and without complications was 75% and 79%, respectively (P =NS); 5‐year graft survival was 50% and 76%, respectively (P = 0.001). The stump formed by the recipient left and middle hepatic veins with a transversal incision >1 cm of the caval wall constantly provides an adequate width for the caval anastomosis with the PB.

Prognostic Evaluation of the New American Joint Committee on Cancer/International Union Against Cancer Staging System for Hepatocellular Carcinoma: Analysis of 112 Cirrhotic Patients Resected for Hepatocellular Carcinoma

BackgroundIn 2002, the American Joint Committee on Cancer and the International Union Against Cancer redefined the T-classification for hepatocellular carcinoma, shifting the cutoff value for tumor size from 2 to 5 cm and giving more emphasis to vascular invasion.MethodsA retrospective cohort study was conducted on 223 consecutive patients with hepatocellular carcinoma observed between 1990 and 2002. One hundred twelve were resected and considered for retrospective analysis. Univariate and multivariate analyses were performed on several clinicopathologic variables. After classification according to each staging system, the long-term survival of different stages was compared. The prognostic value of each staging system was further evaluated by entering each stage, in turn, into the Cox regression model with other clinicopathologic variables. The median follow-up was 19 months.ResultsOn multivariate analysis, the viral etiology of cirrhosis and the presence of multiple nodules were independent prognostic factors. When the new staging system was entered into the multivariate analysis, it was the only independent factor (P = .02). When stratified according to the old tumor-node-metastasis system, there were no significant differences in the survival between stage I and II (P = .14) or between stage IIIA and IVA (P = .33); only the survival of stage II and IIIA was different (P < .01). When stratified according to the new tumor-node-metastasis system, there were significant differences between stage I and II (71.7% vs. 54.7%; P = .02).ConclusionsThe new staging system is a more reliable and objective method for T classification. It is easy to use in clinical practice and is better at stratifying curatively resected patients with respect to prognosis.

Impact of biliary complications in right lobe living donor liver transplantation.

Biliary reconstruction is one of the most challenging parts of right lobe living donor liver transplantation (RL LDLT), and biliary complications have been reported as the first source of surgical complications of this procedure. We reviewed biliary reconstruction and complications in 27 consecutive RL LDLTs. We compared the first 14 procedures (group 1) to the last 13 (group 2). Seven patients (25.9%) experienced a biliary complication (five leaks and two strictures). The incidence of biliary complications was 11.1% in RL grafts with a single duct and 55.5% in graft presenting multiple bile ducts (P = 0.03). Four of the 18 patients with a duct‐to‐duct reconstruction (22.2%) and three of the 11 patients with a Roux‐en‐Y reconstruction (27.3%) developed a biliary complication (P = ns). The incidence of biliary complications significantly decreased from 42.9% (n = 6) in the first group to 7.6% (n = 1) in the second group (P = 0.05). The overall 1‐year graft and patient survival were 57.1% and 64.3% in group 1 versus 100.0% and 100% in group 2 (P = 0.01; P = 0.006). Biliary complications remain one of the most important technical complications affecting RL LDLT. Nevertheless, attention and surgical refinement can lead to a significant reduction of the biliary complication rate, improving graft and patient survival.

Histological recurrent hepatitis C after liver transplantation: Outcome and role of retransplantation.

Impact of hepatitis C virus (HCV) recurrence on long‐term outcome after orthotopic liver transplantation (OLT) is highly variable, and the role of retransplantation is still debated. From 1996 to 2003, 131 OLT with histologically proven HCV recurrence and 6 months of follow‐up were retrospectively reviewed. One and 5‐yr overall survivals were 90.7 and 81.3%, respectively. The mean time of HCV recurrence was 10.1 ± 6.2 months in patients whose donors age was less than 70 yr old, and 6.6 ± 4.7 in patients whose donors age was more than 70 (P < 0.01). The mean time between OLT and HCV recurrence was 10.7 ± 8.2 months among patients still alive, and 5 ± 4.2 among the 20 who died (P = 0.02). In 16 (12.2%) patients, retransplantation was required for severe HCV recurrence; 5 are still alive and 11 (68.7%) died. The mean survival time was 16.2 ± 6 months if re‐OLT was performed within 12 months from first OLT, and it was 45.9 ± 10 months if re‐OLT was performed later (P < 0.01). In conclusion, donors older than 70 yr are at high risk of early HCV recurrence; expectancy of life is significantly reduced in case of histologically proven recurrence within 6 months. Outcome is quite dismal in patients with early HCV recurrence requiring retransplantation within 1 yr of first OLT. Liver Transpl 12:1104–1111, 2006.