Antonino Cavallari

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.

Improved Results of Liver Resection for Hepatocellular Carcinoma on Cirrhosis Give the Procedure Added Value

ObjectiveTo review a single-center experience to update the performance indexes of liver resection (LR). Summary Background DataSeveral therapies have been proposed in the treatment of hepatocellular carcinoma (HCC) on cirrhosis, although LR was the first to be widely applied. MethodsOf 408 patients with cirrhosis admitted for HCC in the period 1983 to 1998, 264 had a LR. Patient selection, surgical technique, 30-day deaths, long-term survival, recurrence rate, and recurrence treatment were reviewed after stratifying patients according to the year of surgery. Mean follow-up was 34.5 ± 29.1 months. ResultsThe number of Child A patients who underwent surgery after the discovery of the tumor at routine evaluation increased significantly from 64.5% to 87.9% during the study period. Procedures carried out without blood transfusions increased from 31.4% to 76.9%. The overall operative death rate was 4.9%. Actuarial survival rates were 63.1% and 41.1% after 3 and 5 years, respectively; actuarial tumor-free survival rates were 49.3% and 27.9% at the same intervals. After 1992, surgical deaths decreased from 9.3% to 1.3%. Actuarial survival rates increased from 52.9% and 32.3% to 71.7% and 49.4% after 3 and 5 years, respectively. There was no difference in the actuarial recurrence rate between the two periods, but the chance to treat recurrence increased over time from 22.4% to 53.7% with a concomitant, significant improvement in survival. ConclusionsLR represents a well-established therapy for HCC on cirrhosis. It remains one of the fundamentals in the multidisciplinary approach to this tumor and should be considered as the first option for patients with preserved hepatic function and limited disease. Today, LR should offer a surgical death rate of less than 1.5%, a 5-year survival rate of approximately 50%, and a 5-year tumor-free survival rate of 28% when performed in specialized centers.

Surgical resection versus percutaneous radiofrequency ablation in the treatment of hepatocellular carcinoma on cirrhotic liver

Objective:We sought to compare the experience of 2 different surgical units in the treatment of hepatocellular carcinoma (HCC) on cirrhosis with resection or percutaneous radiofrequency ablation (RFA), respectively. Summary Background Data:When allowed by the hepatic functional reserve, surgery is the therapy for HCC on cirrhosis; alternative treatments are proposed because of the high tumor recurrence rate after resection. RFA is being widely adopted to treat HCC. Methods:Over a 4-year period, 79 cirrhotics with HCC underwent resection in 1 surgical unit (group A) and another 79 had RFA at a different unit (group B). Patient selection, operative mortality, hospital stay, and 1- and 3-year overall and disease-free survival were analyzed. Results:Group A (surgery): mean follow-up was 28.9 ± 17.9 months; operative mortality was 3.8%, mean hospital stay 9 days; 1- and 3-year survival were, respectively, 83 and 65%. One- and 3-year disease-free survival were 79 and 50%. Group B (RFA): mean follow-up was 15.6 ± 11.7 months. Mean hospital stay was 1 day (range 1–8). One- and 3-year survival were 78 and 33%; 1- and 3-year disease-free survival were 60 and 20%. Overall and disease-free survival were significantly higher in group A (P = 0.002 and 0.001). The advantage of surgery was more evident for Child-Pugh class A patients and for single tumors of more than 3 cm in diameter. Results were similar in 2 groups for Child-Pugh class B patients Conclusions:RFA has still to be confirmed as an alternative to surgery for potentially-resectable HCCs.

Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: Key role of immunosuppression

To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)–based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 ± 86.4 ng/mL in recurrent vs. 169.9 ± 33.3 in tumor‐free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral‐ vs. non–viral‐related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha‐fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence‐free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered. (Liver Transpl 2005;11:497–503.)

Piggy‐back versus conventional technique in liver transplantation: report of a randomized trial

Abstract Liver transplantation with preservation of the recipient vena cava (the “piggy-back” technique) has been proposed as an alternative to the traditional method. We performed a randomized study on 39 cirrhotic patients, 20 who underwent the piggy-back technique (group 1) and 19 the traditional method using venovenous bypass (group 2) to evaluate the feasibility and true advantages of the piggy-back technique compared to the traditional method. Two patients were switched to the conventional technique due to the presence of a caudate lobe embracing the vena cava in one patient and a caval lesion in the other. Statistically significant differences between the two groups were only found for the warm ischemia time (48.5 ± 13 min for piggy-back vs 60 ± 12 min for the conventional method) and for renal failure (zero cases in group 1 vs four cases in group 2). We therefore believe that liver transplantation with the piggy-back technique can easily be performed in almost all cases, and that only a few, specific situations, such as a very enlarged caudate lobe, do not justify its routine use.

Liver Transplantation from Donors Aged 80 Years and Over: Pushing the Limit

Older donors are a growing part of the total donor pool but no definite consensus exists on the limit of age for their acceptance. From November 1998 to January 2003, in a retrospective case–control multicenter study, we compared the outcome of 30 orthotopic liver transplantations (OLTs) with octogenarian donors and of 60 chronologically correlated OLTs performed with donors <40 years. The percentage of refusal was greater among older than younger donors (48.2 vs. 14.3%; p < 0.001). Cold ischemia was significantly shorter in the older than younger groups. Recipients with hepatocarcinoma and older age received octogenarian grafts more frequently. No differences were seen in post‐operative complications and 6‐month graft and patient survival. However, long‐term survival was lower in patients transplanted with octogenarian donors (p = 0.04). Interestingly, the mortality related to hepatitis C recurrence was greater in patients with octogenarian donors. Accordingly, the long‐term survival of HCV‐positive patients who received older grafts was lower than those receiving younger grafts (p = 0.05). Octogenarian livers can be used safely but a careful donor evaluation and a short cold ischemia are required to prevent additional risk factors. However, hepatitis C recurrence is associated with a greater mortality in patients who received octogenarian grafts raising concerns whether to allocate these livers to HCV‐positive recipients.

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.

The Role of Lymphadenectomy for Liver Tumors: Further Considerations on the Appropriateness of Treatment Strategy

Objective:To evaluate the role of regional lymphadenectomy in patients with liver tumors. Background:Lymph node status is 1 of the most important prognostic factors in oncologic surgery; however, the role of lymph node dissection remains unclear for hepatic tumors. Methods:A total of 120 consecutive patients undergoing liver resections for primary and secondary hepatic tumors were prospectively enrolled in the study. “Regional” lymphadenectomy was carried out routinely after specimen removal. Incidence, site, and influence on survival of node metastases were analyzed. Results:Only 1 postoperative complication (intra-abdominal bleeding) was related to lymph node excision. Median number of dissected nodes was 6.8 ± 3.6. Periportal, pericholedochal, and common hepatic artery stations were always removed. Lymph node metastases were found in 17 (16.5%) patients. The percentage rises to 20.3% when considering only noncirrhotic patients. The incidence of lymph node metastases was 7.5% for hepatocellular carcinoma, 14% for colorectal metastases, 40% for noncolorectal metastases, and 40% for intrahepatic cholangiocarcinoma (P < 0.002). Median survival time was 486 ± 93.2 days among all patients with node metastases and 725 ± 29.7 among patients without node metastases. The 2-year survival was 37.1% and 86.7%, in the 2 groups (P < 0.05). The 2-year recurrence rate was 77.6% and 45.3%, respectively (P < 0.05). Conclusions:Regional lymphadenectomy is a safe procedure after liver resection, and it should be routinely applied in patients with primary and secondary hepatic tumors, particularly in those without chronic disease. A careful evaluation of node status is nevertheless advisable also in patients with hepatocellular carcinoma on cirrhosis.

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.)

Pulmonary complications of liver transplantation: radiological appearance and statistical evaluation of risk factors in 300 cases.

Abstract. The aim of this study was to evaluate the incidence, radiographic appearance, time of onset, outcome and risk factors of non-infectious and infectious pulmonary complications following liver transplantation. Chest X-ray features of 300 consecutive patients who had undergone 333 liver transplants over an 11-year period were analysed: the type of pulmonary complication, the infecting pathogens and the mean time of their occurrence are described. The main risk factors for lung infections were quantified through univariate and multivariate statistical analysis. Non-infectious pulmonary abnormalities (atelectasis and/or pleural effusion: 86.7 %) and pulmonary oedema (44.7 %) appeared during the first postoperative week. Infectious pneumonia was observed in 13.7 %, with a mortality of 36.6 %. Bacterial and viral pneumonia made up the bulk of infections (63.4 and 29.3 %, respectively) followed by fungal infiltrates (24.4 %). A fairly good correlation between radiological chest X-ray pattern, time of onset and the cultured microorganisms has been observed in all cases. In multivariate analysis, persistent non-infectious abnormalities and pulmonary oedema were identified as the major independent predictors of posttransplant pneumonia, followed by prolonged assisted mechanical ventilation and traditional caval anastomosis. A “pneumonia-risk score” was calculated: low-risk score ( < 2.25) predicts 2.7 % of probability of the onset of infections compared with 28.7 % of high-risk ( > 3.30) population. The “pneumonia-risk score” identifies a specific group of patients in whom closer radiographic monitoring is recommended. In addition, a highly significant correlation (p < 0.001) was observed between pneumonia-risk score and the expected survival, thus confirming pulmonary infections as a major cause of death in OLT recipients.