A. Lauro

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 transplantation for hepatocellular carcinoma under calcineurin inhibitors: reassessment of risk factors for tumor recurrence.

Objective:We assessed the effect of tacrolimus on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) and compared it with that of the other calcineurin inhibitor, cyclosporine. Introduction:HCC recurrence after LT can be favored by overexposure to cyclosporine. Tacrolimus is now the most widely used main immunosuppressant after LT; its possible effect on HCC recurrence has never been investigated. Materials and Methods:One hundred and thirty nine HCC patients who had LT were reviewed; 60 of them were administered tacrolimus, and 79, cyclosporine. The exposure to the drugs was calculated with the trapezoidal rule in each patient, using blood levels measured after transplantation and compared with HCC recurrence together with several clinical and pathologic risk factors. Results:HCC recurred in 12 of the 60 (20%) patients under tacrolimus in comparison with that in 9 of the 79 (11.4%) patients under cyclosporine; however, the proportion of poorly differentiated and more advanced tumors was significantly higher in the tacrolimus group than in the cyclosporine group. Exposure to tacrolimus was 11.6 ± 1.5 ng/mL in patients with recurrence and 8.6 ± 1.7 ng/mL in those without recurrence (P < 0.001). The optimal cut-off values of exposure identified with receiver operating characteristics analysis to categorize the risk of recurrence were 10 ng/mL for tacrolimus (area under the curve (AUC) = 0.913) and 220 ng/mL for cyclosporine (AUC = 0.752). In the tacrolimus group, high drug exposure independently predicted recurrence (P = 0.005). Multivariate analysis, including all patients (tacrolimus + cyclosporine) characterized higher exposure to immunosuppression (P = 0.01), alpha-fetoprotein levels (P = 0.001), tumor grading (P = 0.009), and microvascular invasion (P = 0.04) as independent predictors of HCC recurrence. Conclusions:Just as it is with cyclosporine, overexposure to tacrolimus increases the risk of HCC recurrence after LT. Careful management of calcineurin inhibitors is recommended in HCC patients.

The hepatic artery in liver transplantation and surgery: vascular anomalies in 701 cases

The purpose of this study is to report the variations in hepatic arterial supply of a mixed population of organ donors in which the anatomy was individually examined during the bench surgery, and patients who underwent a selective angiogram of the celiac axis and superior mesenteric artery. 
We reviewed the donor forms and/or angiograms of 701 patients. The donor forms were completed personally by one of the authors, while all the radiology images were obtained through studies performed by one single radiologist. The arterial anatomy was anomalous in 296 out of 701 cases with an overall incidence of hepatic artery anomalies of 42.22%. 
In this paper we describe previously unreported arterial anomalies of the hepatic artery, collecting the second largest series of hepatic artery anatomical variations of the English literature. This anatomical update can be useful for transplant and general surgeons, as well as vascular radiologists.

Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma

Background. Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors. Methods. We investigated the effect of an immunosuppressant schedule that minimizes the exposure to calcineurin inhibitors on patients transplanted for HCC to ascertain whether this can reduce the tumor recurrence rate. For this purpose, we conducted a matched-cohort study: 31 patients with HCC transplanted between 2004 and 2007 who received sirolimus as part of their immunosuppression (group A) were compared with a control group of 31 patients (group B) transplanted in the same period who had the same prognostic factors but were given standard immunosuppression based on tacrolimus. Results. Three-year recurrence-free survival was 86% in group A and 56% in group B (P=0.04). Although the prevalence of microvascular invasion G3-G4 grading and alpha-fetoprotein more than 200 ng/mL was identical in the two groups, exposure to tacrolimus was significantly higher in patients of group B (median, 8.54; range, 5.5–13.5) in comparison with those of group A (median, 4.6; range, 1.8–9.1) (P=0.0001). Conclusions. By using sirolimus, exposure to calcineurin inhibitors can be minimized, reducing the risk of HCC recurrence.

Can Antiplatelet Prophylaxis Reduce the Incidence of Hepatic Artery Thrombosis After Liver Transplantation

To ascertain whether postoperative antiplatelet therapy could reduce the incidence of hepatic artery thrombosis (HAT) after liver transplantation (LT), 838 consecutive adult whole‐graft LTs performed from April 1986 to August 2005 that survived beyond the first postoperative month were reviewed. Antiplatelet prophylaxis with aspirin (100 mg per day) was given following 236 LTs; the median starting time was 8 postoperative days (range, 1 to 29 days). Early HAT was observed in 29 cases. The median time of presentation was 5 postoperative days (range, 1‐28 days), and the effect of aspirin on this type of complication was therefore not assessable. A total of 14 cases of late HAT were observed (1.67 %). The median time of presentation was 500.5 days (range, 50–2,405 days). Late HAT occurred in 1 out of 236 (0.4 %) patients who were maintained under antiplatelet prophylaxis and in 13 out of 592 (2.2 %) who did not receive prophylaxis (P = 0.049). Risk factors for late HAT (grafts retrieved from donors who died of cerebrovascular accident and/or use of iliac conduit at transplantation) were present in 498 LTs: in this group the incidence of late HAT was significantly higher among cases who did not receive prophylaxis (12/338 vs 1/160; p = 0.037). There were no hemorrhagic complications associated with the use of aspirin. In conclusion,antiplatelet prophylaxis can effectively reduce the incidence of late HAT after LT, particularly in those patients at risk for this complication. Liver Transpl 13:651–654, 2007.

Abdominal Wall Transplantation with Microsurgical Technique

Many patients undergoing intestinal or multivisceral transplantation have a past history of complete midgut removal with the loss of the domain of the abdominal compartment or have severely damaged abdominal walls from repeated laparotomies, tumours or enterocutaneous fistulae. These patients may encounter severe abdominal wall closure problems at the end of transplantation, resulting in increased morbidity and mortality. It is, therefore, of paramount importance to properly cover transplanted organs in order to reduce postoperative complications.

Liver transplantations with donors aged 60 years and above: the low liver damage strategy

According to transplant registries, grafts from elderly donors have lower survival rates. During 1999–2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged ≥ 60 years and managed with the low liver‐damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D ≥ 60‐LLDS). Group D ≥ 60‐LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60‐no‐LLDS and 89 donors aged ≥60 years, group D ≥ 60‐no‐LLDS). In the donors proposed from the age group of ≥60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end‐stage liver disease score) were comparable among groups, but group D ≥ 60‐LLDS had a lower mean ischemia time: 415 ± 106 min vs. 465 ± 111 (D < 60‐no‐LLDS), P < 0.05 and vs. 476 ± 94 (D ≥ 60‐no‐LLDS), P < 0.05. After a median follow‐up of 3 years, the 1‐ and 3‐year graft survival rates of group D ≥ 60‐LLDS (84% and 76%) were comparable with group D < 60‐no‐LLDS (89% and 76%) and were significantly higher than group D ≥ 60‐no‐LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.

Prognostic factors for tumor recurrence after a 12-year, single-center experience of liver transplantations in patients with hepatocellular carcinoma.

Background. Factors affecting outcomes after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS) in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12%) patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP) levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Coxs proportional hazard model showed that only elevated AFP levels (Odds Ratio = 2.88; 95% C.I. = 1.43–5.80; P = .003), preoperative tumor treatments (Odds Ratio = 4.84; 95% C.I. = 1.42–16.42; P = .01), and microvascular invasion (Odds Ratio = 4.82; 95% C.I. = 1.87–12.41; P = .001) were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.

Intermittent inflow occlusion in living liver donors: impact on safety and remnant function.

Clamping of the portal triad accomplishes complete inflow occlusion. This maneuver is commonly used during liver surgery to minimize blood loss but is not widely used in living donors undergoing resection for liver transplantation. We compared outcomes in living donors who underwent resection with and without inflow occlusion. We reviewed data on 2 nonsimultaneous living liver donor cohorts. The first 20 donors (group 1) underwent resection without inflow occlusion. In the next 15 donors (group 2), inflow occlusion was used during parenchymal transection, using cycles of 10–15 minutes occlusion and 6 minutes reperfusion. In donors, we recorded type of resection; ischemia times; blood loss; transfusions; peak ALT, AST, bilirubin, and INR in the first 5 days; hospital length of stay (LOS), and major complications. In recipients, we recorded peak ALT. In group 1, 19 of 20 donors underwent right hepatectomy. In group 2, 8 donors underwent right hepatectomy, and 7 donors had left lobectomies. Total ischemic time ranged from 16–49 minutes (mean, 31 ± 9 minutes). In group 1, two donors received a total of 5 U of allogeneic blood. In group 2, no donor required transfusion. Mean peak ALT was significantly higher in group 1 (521 ± 336 U/L) than group 2 (322 ± 162 U/L; P = 0.03). Mean INR was significantly higher in group 1 (1.8 ± 0.2) vs. group 2 (1.5 ± 0.2; P = 0.001). There were 4 major complications in group 1 (incisional hernia, transient liver failure, biliary stricture, and biliary leak) and no major intraoperative or postoperative complications in group 2. Mean LOS was significantly longer in group 1 (7.9 ± 2.9 days) than group 2 (6.2 ± 1.1 days; P = 0.04). Mean peak ALT in recipients trended lower in group 2. In conclusion, inflow occlusion was associated with reduced blood loss and less ischemic injury to hepatic remnants in the donors and the grafts in the recipients. These benefits were associated with a diminished incidence of major complications and shorter LOS. Inflow occlusion should be an essential part of living donor hepatectomy. (Liver Transpl 2004;10:244–247.)

Intestinal transplantation for chronic intestinal pseudo-obstruction in adult patients.

Intestinal transplantation (ITx) has become a life‐saving procedure for patients with irreversible intestinal failure who can no longer be maintained on parenteral nutrition (PN). This report presents the results of our experience on ITx in patients suffering from chronic intestinal pseudo‐obstruction (CIPO). Between December 30, 2000 and May 30, 2003 six adult patients affected by CIPO underwent primary ITx at our Center. Pre‐transplant evaluation, indication for ITx and surgical technique are reported. On December 30 2003, the mean follow‐up was 25.0 months. No peri‐operative deaths occurred in the study population and five out of six patients are alive, with 1‐year patient and graft survival of 83.3% and 66.6%. Although our series is limited by the number of patients, our experience suggests that ITx transplantation should be considered in adult patients suffering from CIPO and PN life‐threatening complication.