F. Ravazzoni

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.

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.

Cavo-portal transposition in rat: a new simple model

BackgroundLiver transplantation in presence of diffuse portal vein thrombosis is possible by using caval blood as portal inflow, through cavo-portal transposition. However, clinical results are heterogeneous and experimental studies are needed, but similar hemodynamic conditions are difficult to obtain, especially in small animals. Herein we describe a new simple model of cavo-portal transposition in rat.MethodsSpontaneous porto-systemic shunts are induced by subcutaneous transposition of the spleen. The presence of porto-caval shunts through the spleen permits the interruption of the main portal vein without splanchnic hemodynamic consequences. Cavo-portal transposition is achieved by anastomosing the inferior vena cava and the main portal vein after division of the pancreatic-duodenal vein.ResultsSelective angiography revealed total splanchnic blood diversion to the systemic venous circulation through the neoformed collaterals; macroscopical examination showed the absence of any signs of acute portal hypertension with normal liver and gut appearance.ConclusionThis model of cavoportal transposition is simple, effective and it simulates the clinical hemodynamic condition since the porto-systemic shunts induced by splenic subcutaneous transposition correspond to the physiological inframesocolic collaterals during chronic portal thrombosis in man.