G. Bottino

Sister Joseph's nodule in a liver transplant recipient: Case report and mini-review of literature

BackgroundUmbilical metastasis is one of the main characteristic signs of extensive neoplastic disease and is universally referred to as Sister Mary Josephs nodule.Case presentationA 59-years-old Caucasian female underwent liver transplant for end stage liver disease due to hepatitis C with whole graft from cadaveric donor in 2003. After transplantation the patient developed multiple subcutaneous nodules in the umbilical region and bilateral inguinal lymphadenopathy. The excision biopsy of the umbilical mass showed the features of a poorly differentiated papillary serous cystadenocarcinoma. Computed tomographic scan and transvaginal ultrasonography were unable to demonstrate any primary lesion. Chemotherapy was start and the dosage of the immunosuppressive drugs was reduced. To date the patient is doing well and liver function is normal.ConclusionsThe umbilical metastasis can arise from many sites. In some cases, primary tumor may be not identified; nonetheless chemotherapy must be administrated based on patients history, anatomical and histological findings.

Sirolimus therapy in liver transplant patients: an initial experience at a single center.

Sirolimus (SRL) is an mTOR inhibitor that has been shown, in contrast to calcineurin inhibitors (CNI), to inhibit cancers in experimental models. Since February 2005, we introduced SRL in liver transplant patients in group a, in whom the primary disease was hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic or autoimmune liver cirrhosis, and group b, HCC-negative patients who developed posttransplantation cancers de novo. Of 18 patients in group a, 11 received SRL ab initio (subgroup a1), starting for 10 patients at 66.1+/-29.2 days after surgical healing and after 10 days in 1 case; the remaining 7 patients (subgroup a2) received SRL at 31.2+/-24.2 months. Three patients in group b, included 1 with Kaposis sarcoma, 1 with bladder cancer, and 1 with thyroid cancer. In this group, SRL was introduced at 80.8+/-40.4 months. In all patients but one, who received a single 5 mg loading dose, SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CNI drugs, present as primary therapy, were gradually tapered to low levels and eventually stopped. The following observations were drawn from this initial experience: (1) 4/21 (19.0%) patients had to discontinue SRL because of early and late side effects: thrombocytopenia (n=2) and headache with leukopenia and leg edema associated with knee joint arthralgia (n=2); (2) 14 patients (11 in group a and 3 in group b) are still on SRL monotherapy; (3) 1 HCC recurrence and 1 de novo pancreatic adenocarcinoma were observed at 14 and 16 months, respectively (at the time of transplantation, both patients were beyond the MIlan HCC criteria), and (4) 1 patient, from subgroup a1, died after 99 days due to pneumonitis and possible relation to SRL lung toxicity. In conclusion, SRL appeared to be an effective immunosuppressant that could be used as monotherapy in liver transplant patients. Any conclusion on SRL anticancer effects can only come from randomized large studies after long follow-up.

MELD score versus conventional UNOS status in predicting short-term mortality after liver transplantation*

The Model for End‐stage Liver Disease (MELD) provides a score able to predict short‐term mortality in patients awaiting liver transplantation (LT). In the early 2002, United Network for Organ Sharing (UNOS) has proposed to replace the conventional statuses 3, 2B, and 2A with a modified MELD score. However, the accuracy of the MELD model to predict post‐transplantation outcome is fairly elusive. In the present study we investigated the predictive value of the MELD score for short‐term patient and graft mortality in comparison with conventional UNOS status. Sixty‐nine patients listed at UNOS status 3 (n = 5), 2B (n = 55) or 2A (n = 9) who underwent LT were enrolled according to strict criteria. No donor‐related parameters affected 3‐month patient survival. Through univariate Cox regression, pretransplantation international normalized ratio (P = 0.049) and activated partial thromboplastin time (P = 0.032) were significantly associated with 3‐month patient survival, although not in the subsequent multivariate analysis. The overall MELD score was 17 ± 6.63 (median: 16, range: 4–34), increasing from UNOS Status 3 to 2A (r2 = 0.171, P = 0.0001). No significant difference occurred in the median MELD score between patients who underwent a second LT and those who did not (P =0.458). The inter‐rate agreement between UNOS status and MELD score after categorization for clinical urgency showed a fair agreement (κ = 0.244). The 3‐month patient and graft mortality was 15.94% and 20.29% respectively. The concordance statistic did not find significance between UNOS status and MELD score for 3‐month patient (P = 0.283) or graft mortality (P = 0.957), although the MELD score revealed a major sensitivity for short‐term patient mortality (0.637; 95%CI: 0.513–0.75). These findings suggest the need to implement MELD model accuracy for both inter‐rate agreement with UNOS Status and patient outcome.

Laparoscopic liver resection for hepatocellular carcinoma in cirrhotic patients. Feasibility of nonanatomic resection in difficult tumor locations

BACKGROUND: Surgical resection for hepatocellular carcinoma (HCC) in cirrhotic patients remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity. The aim of this study was to evaluate retrospectively our results for laparoscopic liver resection (LLR) for HCC including lesions in the posterosuperior segments of the liver in terms of feasibility, outcome, recurrence and survival. MATERIALS AND METHODS: Between June 2005 and February 2009, we performed 20 LLR for HCC. Median age of the patients was 66 years. The underlying cirrhosis was staged as Child A in 17 cases and Child B in 3. RESULTS: LLR included anatomic resection in six cases and nonanatomic resection in 14. Eleven procedures were associated in nine (45%) patients. Median tumor size and surgical margins were 3.1 cm and 15 mm, respectively. A conversion to laparotomy occurred in one (5%) patient for hemorrhage. Mortality and morbidity rates were 0% and 15% (3/20). Median hospital stay was 8 days (range: 5-16 days). Over a mean follow-up period of 26 months (range: 19–62 months), 10 (50%) patients presented recurrence, mainly at distance from the surgical site. Treatment of recurrence was possible in all the patients, including orthotopic liver transplantation in three cases. CONCLUSIONS: LLR for HCC in selected patients is a safe procedure with good short-term results. It can also be proposed in tumor locations with a difficult surgical access maintaining a low morbidity rate and good oncological adequacy. This approach could have an impact on the therapeutic strategy of HCC complicating cirrhosis as a treatment with curative intent or as a bridge to liver transplantation.

Predictability and Survival in Liver Replantransplantation: Monocentric Experience

Liver retransplantation is the only treatment for patients with hepatic graft failure. Due to the shortage of organs, it is essential to optimize its use. Between 1998-2010, our center performed retransplantations on 48 (12.8%) patients (re-OLT). The data are compared with those for a group of 374 patients who did not receive retransplantations (NO re-OLT). The re-OLT vs NO re-OLT groups did not significantly differ in mean age of recipients (47 vs 51 years), indications for transplantation (hepatitis C virus cirrhosis 54% vs 56%, alcoholic cirrhosis 25% vs 17%, hepatocellular carcinoma 14% vs 22%), mean Model for End-stage Liver Disease (25 vs 20), mean total cold ischemia time (385 vs 379 minutes), or mean age of donors (52 vs 49 years). The main causes of retransplantation were primary graft nonfunction (64%), arterial thrombosis (8%), biliary complications (6%), and hepatitis C virus recurrence (4%). The difference in overall patient survival was not statistically significant. The patients survival at 1, 3, 5, and 10 years for RE-OLT vs NO-reOLT was 56% vs 63%, 53% vs 60%, 46% vs 57%, and 44% vs 53%, respectively. Multivariate analysis identified Model for End-stage Liver Disease≥23 as a predictor factor of retransplantation (P=.04). Other variables predicting outcome included age of donors (≥65 years vs younger group), age of recipients (≥50 years vs younger group), cold ischemia (≥600 vs <600 minutes), and transplantation indications (hepatitis C virus, hepatitis B virus, alcohol, and others). The retransplantation performed between 8-15 days appeared to have worse results than those in other periods (0-7 days, 16-30 days, 1-6 months, >6 months). The incidence of re-OLT in the series (12.8%) was comparable to that in the literature, and primary graft nonfunction in the study represents the main cause of retransplantation. Our analysis showed that the indication of the first transplant and the age of the donor were not risk factors for re-OLT. Liver retransplantation is a concrete alternative lifesaver for patients with graft failure.

Preliminary Results of Liver Transplantation for Hepatocellular Carcinoma Among Allocation Organ Policy Strategies, Neoadjuvant Treatments, and Intention-to-Treat Analysis

We retrospectively evaluated the impact of our strategy for patients with hepatocellular carcinoma (HCC) according to an intention-to-treat analysis and drop-out probability. We evaluated only patients within the Milan criteria. We analyzed the outcomes of neoadjuvant strategies for HCC, organ allocation policy, and systematic application of strategies to increase the deceased donor pool as the current tendency to expand transplantability criteria for those patients. Kaplan-Meier survival probability rates at 1, 3, and 5 years according to an intention-to-treat analysis were 87.02%, 74.53%, and 65.93% for transplanted patients (n=108), and 50%, 14.29%, and 14.29% for the excluded or waiting list group (n=13), respectively (P< .0001). Drop-out risk at 3, 6, and 12 months was 2.40%, 8.59%, and 16.54%, respectively. During the same period, the mortality probability rates at 3, 6, and 12 months among patients without HCC awaiting orthotopic liver transplantation (OLT) were 3.60%, 9.50%, and 18.34%, respectively. Drop-out rate was lower among patients treated before OLT (P< .0001). On the basis of the neoadjuvant treatment results to reduce drop-out risk, we suggest avoiding the high priority for the HCC cohort, particularly within the first 6 months from entrance on the waiting list, because this approach can reduce the chances of patients with end-stage liver disease (ESLD) alone.

Laparoscopic resection vs laparoscopic radiofrequency ablation for the treatment of small hepatocellular carcinomas: A single-center analysis

AIM To compare survival and recurrence after laparoscopic liver resection (LLR) and laparoscopic radiofrequency ablation (LRFA) for the treatment of small hepatocellular carcinoma (HCC). METHODS Between June 1, 2005 and November 30, 2010, 46 patients (62.26 ± 8.55 years old; female/male: 12/34) treated for small HCC were enrolled following strict criteria. Patients with better liver function and larger tumors were referred for LLR (n = 24), while those with poorer liver function and multiple tumors were referred for LRFA (n = 22), and they were then followed for similar durations (44.74 ± 21.3 mo for LLR vs 40.27 ± 30.8 mo for LRFA). RESULTS The LLR and LRFA groups were homogeneous with regard to age, sex, etiology of liver cirrhosis, and AFP levels. The overall survival (OS) and disease-free survival (DFS) probability was 0.354 and 0.260, respectively. A significantly higher OS was observed in the LLR group (LLR: 0.442; LRFA: 0.261; P = 0.048), whereas no statistical difference was found for DFS (LLR: 0.206; LRFA: 0.286; P = 0.205). In the LRFA group was treated a greater number of nodules (LLR: 1.41 ± 0.77; LRFA: 2.72 ± 1.54; P < 0.001). Cox regression analysis found the number of intraoperative HCC nodules as the unique variable statistically significant for OS (hazard ratio: 2.225; P < 0.001). The rank-hazard plot showed a steeper increase of relative hazard for intraoperative nodules > 2. CONCLUSION Our preliminary results confirm the superiority of hepatic resection on thermoablation in the treatment of small HCC in selected patients, when both approaches are made laparoscopically. LLR showed better results compared to LRFA in terms of OS. These data need to be confirmed by further studies on a larger number of patients.

Role of Liver Transplantation in Bilio-Vascular Liver Injury After Cholecystectomy

BACKGROUND The aim of this study was to report 2 cases of liver transplantation (LT) for iatrogenic bile-vascular injury (BVI) sustained during cholecystectomy and to review the literature for LT after cholecystectomy. METHODS Between March 2001 and July 2013, within our institution, 12 patients were treated after cholecystectomy, 3 of 12 received LT, 1 for acute de-compensation in a cirrhotic patient and 2 after iatrogenic lesions. RESULTS The majority of iatrogenic injury occurred during video-laparocholecystectomy (63,6%; 7/11). Three patients of 12 (25%) received LT: the first patient developed acute de-compensation in chronic and after liver failure. The second patient developed recurrent cholangitis and secondary biliary cirrhosis. The third patient had undergone emergency hepatectomy because of bleeding and subsequent total hepatectomy with porto-caval shunt. Five of 12 (42%) patients were treated with bilio-digestive anastomosis: 1 patient with direct repair on T-tube; 2 patients (17%) with arterial vascular lesion requiring surgical treatment; and 1 patient treated with medical therapy. No deaths occurred. The post-operative morbidity included 1 re-intervention, 3 recurrent cholangitis, 1 anastomotic biliary stricture, 1 anastomotic bile leak, and cholestasis in 3 patients. The overall hospital stays were higher after LT. Median follow-up was 8.25 years (range, 2-14). CONCLUSIONS The management of iatrogenic injury during cholecystectomy depends on the time of recognition, extent of injury, experience of the surgeon, and the patients general condition. If safe repair is possible, BVI should be treated promptly, otherwise all patients should be treated in an experienced center.

The procedure outcome of laparoscopic resection for 'small' hepatocellular carcinoma is comparable to vlaparoscopic radiofrequency ablation

Background: The aim of this study was to compare the effectiveness of laparoscopic liver resection (LLR) and laparoscopic radiofrequency ablation (LRFA) in the treatment of small nodular hepatocellular carcinoma (HCC). Patients and Methods: We enrolled 50 cirrhotic patients with similar baseline characteristics that underwent LLR (n = 26) or LRFA (n = 24), in both cases with intraoperative ultrasonography. Operative and peri-operative data were retrospectively evaluated. Results: LLR included anatomic resection in eight cases and non-anatomic resection in 18. In LRFA patients, a thermoablation of 62 nodules was achieved. Between LLR and LRFA groups, a significant difference was found both for median diameters of treated HCC nodules (30 vs. 17.1 mm; P < 0.001) and the number of treated nodules/patient (1.29 ± 0.62 vs. 2.65 ± 1.55; P < 0.001). A conversion to laparotomy occurred in two LLR patient (7.7%) for bleeding. No deaths occurred in both groups. Morbidity rates were 26.9% in the LLR group versus 16.6% in the LRFA group (P = 0.501). Hospital stay in the LLR and LRFA group was 8.30 ± 6.52 and 6.52 ± 2.69 days, respectively (P = 0.022). The surgical margin was free of tumour cells in all LLR patients, with a margin <5 mm in only one case. In the LRFA group, a complete response was achieved in 90.3% of thermoablated HCC nodules at the 1-month post-treatment computed tomography evaluation. Conclusions: LLR for small peripheral HCC in patients with chronic liver disease represents a valid alternative to LRFA in terms of patient toleration, surgical outcome of the procedure, and short-term morbidity.

Model for End-Stage Liver Disease (MELD) Score and Organ Allocation From Cadaveric Donors for 198 Liver Transplantation Procedures Performed in a Single Center

Since February 2002, the United Network for Organ Sharing (UNOS) proposed to adopt a modified version of the Model for End-Stage Liver Disease (MELD) to assign priority on the waiting list for orthotopic liver transplantation (OLT). In this study, we evaluated the impact of MELD score on liver allocation in a single center series of 198 liver recipients (mean age of patients, 52.21+/-8.92 years), considering the relationship between clinical urgency derived from MELD score (overall MELD, 18.7+/-6.83; MELD <15 in 69 patients, MELD >or=15 in 129 patients) and geographical distribution of cadaveric donors (inside/outside Liguria Region, 125/73). The waiting time for OLT was 230+/-248 days, whereas the 3-month and 1-year patient survivals were 87.37% and 79.79%, respectively. No difference was observed for MELD score retrospectively calculated for patients who underwent OLT before February 2002 (n=71) compared with MELD score calculated for patients who received a liver thereafter (18.26+/-6.68 vs 18.94+/-6.92; P= .504). No significant difference was found in waiting time before and after adoption of MELD score (213+/-183 vs 238+/-278 days; P= .500), or by stratifying patients for MELD <15/>or=15 (225+/-234 vs 232+/-256 days; P= .851). Using the geographical distribution of donors as a grouping variable (outside vs inside Liguria Region), no significance occurred for MELD score (19.68+/-7.42 vs 18.17+/-6.42; P= .135) or waiting time (211+/-226 vs 242+/-261 days; P= .394). In our series, more OLTs were performed among sicker patients and no differences were found in the management of livers procured from cadaveric donors outside or inside Liguria Region. However, further efforts are needed to reduce the waiting time among patients with higher MELD scores.