N. Cautero

Pancreatic metastases from renal cell carcinoma：The state of the art

Pancreatic metastases are rare, with a reported incidence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease.

Living Donor Liver Transplantation with Left Liver Graft

Small‐for‐size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year‐old patient underwent to LDLT at our institution. During the anhepatic phase a porto‐systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post‐operative course was characterized by good graft function. Small‐for‐size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult‐to‐adult living donor liver transplantation.

Long-term follow-up and outcome of liver transplantation from anti-hepatitis C virus-positive donors: a European multicentric case-control study.

Background. The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. Given the significant disparity between organ supply and demand for transplantation, it becomes essential to consider whether livers from anti-HCV-positive donors may be considered suitable for transplantation. Methods. Based on a multicenter European database, 694 patients with HCV-related cirrhosis underwent liver transplantation and 11% of them received the graft from anti-HCV-positive donors. Of this group, we selected 63 patients (study group) and, after a 1:1 case-control approach, compared them with 63 patients that received an anti-HCV-negative donor graft (control group). Only grafts with preperfusion liver biopsy results with a fibrosis score of not more than 1 were used for transplantation. Results. Patients who received anti-HCV-positive grafts had a cumulative survival rate of 83.6% and 61.7% at 1 and 5 years, respectively, vs. 95.1% and 68.2% for the control group. In comparing overall patient and graft survival, there was no statistically significant difference between the two groups (P=0.22 and 0.11). Recurrence of hepatitis C tended to be more rapid in the group of patients who received anti-HCV-positive grafts, although it did not reach statistical significance (P=0.07). Conclusions. We do not recommend the indiscriminate use of anti-HCV-positive donors, especially if HCV-RNA positive, as the use of this kind of graft could be linked to an advanced stage of fibrosis, the main risk factor we observed for earlier hepatitis C recurrence.

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.

Role Of Endogenous Opioids In Modulating Hsc Activity In Vitro And Liver Fibrosis In Vivo.

Background: Endogenous opioids modulate the growth of nervous and non-nervous cells. Hepatic stellate cells (HSCs) are the main cell phenotype involved in liver fibrogenesis, display molecular markers of neuronal cells and respond to neurotransmitters. Aim: To evaluate the role of endogenous opioids on liver fibrogenesis. Methods: Activated rat HSCs (passage 1–3) were used to evaluate cell proliferation and intracellular signalling pathway activation. Liver fibrosis was induced in rats by dimethylnitrosamine (DMN) administration. Results: Opioid receptors showed a different pattern of expression when measured in quiescent and activated (in vitro and in vivo) HSCs. The activation of opioid receptors increased HSC proliferation and collagen accumulation. Opioid receptor stimulation induced a calcium-dependent protein kinase Cα (PKCα)/extracellular regulated kinase (ERK)/phosphatidylinositol 3-kinase (PI3K) pathway activation that mediated the effect of endogenous opioids on HSC proliferation and collagen synthesis. In DMN-treated rats, the opioid antagonist naloxone reduced α-smooth muscle actin expression (as a marker of HSC activation) and collagen deposition, both measured by morphometry after 5 weeks of treatment. In both DMN-treated rats and human liver biopsies from chronic liver diseases, opioid receptors were observed in HSCs in area of active fibrogenesis. The endogenous opioid met-enkephalin increased its expression in zone 3 hepatocytes close to the area of necrosis after DMN administration and in the cellular target of chronic liver injury in human biopsies, and stimulated HSC proliferation and collagen synthesis. Conclusions: Endogenous opioids released during chronic liver injury participate in the process of liver fibrogenesis by stimulating HSC proliferation and collagen production in a paracrine manner.

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.

Liver Resection for Colorectal Metastases in Older Adults: A Paired Matched Analysis

To assess the safety and long‐term results of hepatic resection of colorectal liver metastases (CLM) in older adults.

Multicenter Italian Experience in Liver Transplantation for Hepatocellular Carcinoma in HIV-Infected Patients

BACKGROUND The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. PATIENTS AND METHODS We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. RESULTS HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. CONCLUSION LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

Multiple Ways to Manage Portal Thrombosis During Liver Transplantation: Surgical Techniques and Outcomes

BACKGROUND Portal vein thrombosis (PVT) is a well-recognized complication of chronic liver disease with a prevalence ranging from 1% to 16%. MATERIALS AND METHODS We performed a retrospective review of 447 consecutive patients who underwent liver transplantation (OLT) between October 2000 and December 2011 comparing 51 recipients with PVT (study group) with 399 without PVT (control group). The aim of this study was to determine the impact of pre-existent PVT on the surgical procedure, to identify specific preventable perioperative complications, and based on our studies and other works, to determine whether this group of patients are acceptable candidates for OLT. RESULTS Among the 51 patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we performed a thromboendovenectomy. There were six anastomoses at the confluence of the superior mesenteric vein (SMV) and one, with a venous graft interposition. In four complete thrombosis recipients we performed an extra-anatomic by pass between the main trunk of the SMV and the donor portal vein. Compared with the control group, regarding preoperative characteristics, PVT patients were older at the time of transplantation (P = .001) and had a higher use of TIPS (P = .02). The operative characteristics showed a longer warm ischemia time in the PVT group (46.9 ± 22.5 vs 39.3 ± 15 min; P = .004). There were significant differences in postoperative evaluations, nor in the complication rates. Overall survivals at 10 years were similar: 61.7% versus 65.3%; (P = .9). CONCLUSION Although PVT was associated with greater operative complexity, it had no influence on postoperative complications or overall survival.