Background: Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model to elucidate tumor resistance to therapy, due to their high capacity to resemble tumor characteristics. Materials and methods: We used viable tumor tissue from two cohorts of patients with mCRC, naive or refractory to treatment, respectively, for generating PDTOs. The derived models were subjected to a 6-day drug screening assay (DSA) with a comprehensive pipeline of chemotherapy and targeted drugs against almost all the actionable mCRC molecular drivers. For the second cohort DSA data were matched with those from PDTO genotyping. Results: A total of 40 PDTOs included in the two cohorts were derived from mCRC primary tumors or metastases. The first cohort included 31 PDTOs derived from patients treated in front line. For this cohort, DSA results were matched with patient responses. Moreover, RAS/BRAF mutational status was matched with DSA cetuximab response. Ten out of 12 (83.3%) RAS wild-type PDTOs responded to cetuximab, while all the mutant PDTOs, 8 out of 8 (100%), were resistant. For the second cohort (chemorefractory patients), we used part of tumor tissue for genotyping. Four out of nine DSA/genotyping data resulted applicable in the clinic. Two RAS-mutant mCRC patients have been treated with FOLFOXebevacizumab and mitomycinecapecitabine in third line, respectively, based on DSA results, obtaining disease control. One patient was treated with nivolumabesecond mitochondrial-derived activator of caspases mimetic (phase I trial) due to high tumor mutational burden at genotyping, experiencing stable disease. In one case, the presence of BRCA2 mutation correlated with DSA sensitivity to olaparib; however, the patient could not receive the therapy. Conclusions: Using CRC as a model, we have designed and validated a clinically applicable methodology to potentially inform clinical decisions with functional data. Undoubtedly, further larger analyses are needed to improve methodology success rates and propose suitable treatment strategies for mCRC patients.

Short-term patient survival (PS) after liver transplantation (LT) is predicted by MELD score. This SITO-AISF study aimed to identify, besides the MELD score, factors predicting 6- and 12-month PS after LT, in order to develop case-mix models. Primary endpoint was 6-month PS; secondary end-points were 6-month graft survival and 12 month PS. LT was considered futile if associated with 5 years PS < 50% and/or 6 months PS < 60%.

Ventral hernias often occur in transplanted patients because of weakness of the abdominal wall, poor muscle mass, and ascitis. In this report we describe the case of a re-recurrent ventral hernia seen emergently in a liver transplant recipient, who was treated using a singular 3-layer approach by placement of an intraperitoneal mesh, stressing technical aspects of the plasty as well as the importance of a sublay technique in the reinforcement of a previous prosthetic plasty.

Antifungal prophylaxis may be required in high-risk patients undergoing liver transplantation and for that reason we aimed to verify its role and its related impact on the graft. From January 2006 throughout 2012, 250 liver transplants were evaluated and 54 patients identified as being at higher risk were randomly selected to undergo the following schedule: 28 patients received liposomal amphotericin B and 26 received caspofungin. We evaluated, throughout 12 months, renal and liver function tests, bacterial and fungal infection episodes, and intensive care unit (ICU) stay, as well as the Th1 and Th2 cytokine network. Differences were analyzed according to non-parametric tests (two-tailed p values). Neither of the groups showed episodes of invasive fungal infection during the 12 months follow-up; however, patients receiving prophylaxis with liposomal amphotericin B had reduced episodes of bacterial infections coupled with an improved immune system response compared with those receiving caspofungin. Finally, a reduced stay in the ICU was also observed. In conclusion, even if the results of liposomal amphotericin B and caspofungin prophylaxis strategies did not differ in terms of invasive fungal infection rate, patients receiving prophylaxis with liposomal amphotericin B had a reduced ICU stay and an improved Th2 status, as well as a reduced number of post-transplant bacterial infections. Further studies are required to better address and evaluate these findings.

Aims: Retrospective study designed to describe results of the side-to-side cavo-cavostomy (STSCC) anastomosis through caval reconstruction, with particular emphasis on complications associated with this technique. All within a single Institution experience. Patients and methods: From June 1998 to January 2012, 577 cadaver liver transplants were performed at our Institution. 575 of which underwent STSCC in accordance with Belghiti's technique described elsewhere. Temporary porto-caval shunt was coupled to STSCC in 38 cases. Routine intraoperative Doppler ultrasonography was performed at the end of every procedure. Results: STSCC was feasible in all but 2 cases (99.66%) regardless of recipient's vena cava, anatomic factors, graft size or re-transplant status. Mean operative time for STSCC was 13 minutes (6-30 minutes). Though not necessarily considered a complication, there were 3 cases of caval stump thrombosis (0,52%). Complications strictly associated with this particular technique were limited to 4 patients (0,69%). The most significant one was the case of a patient that presented with acute post-operative Budd-Chiari syndrome that developed progressive deterioration due to liver failure. The patient could not be rescued with re-transplantation due to progressive brain damage and eventual cardiac arrest. The other three patients that developed direct complications attributed to STSCC were managed successfully. In one patient that developed outflow obstruction due to torsion from donor graft/recipient mismatch, the outflow was surgically improved by falciform ligament fixation. The second was only evident on biopsy by sinusoidal congestion and was managed non-operatively with measures to decrease central venous pressure. The third patient developed a pulmonary distress due to a decreased cardiac return consequence of a large sized graft, with subsequent severe haemodynamic instability requiring significant amount of pressors. The patient was managed non-operatively through a “positional” approach, by turning him 45 degree to the left in order to improve venous return to the heart. Twenty-five cases were done uneventfully with STSCC in patients undergoing re-transplantation. Conclusions: Side-to-Side Cavo-Cavostomy during piggyback liver transplantation has proven to be a safe and straightforward procedure, which can be performed even in a re-transplantation setting. In our experience this technique has shown a very low incidence of venous outflow obstruction. Maximal preservation of recipient inferior vena cava and temporary porto-caval shunt, improves decompression of inferior and splanchnic venous systems during the an-hepatic phase. In our opinion, STSCC helps overcome the outflow complications associated with traditional piggyback technique by using the orifices of one or more recipient hepatic veins as needed. Our study also indicates that donor graft to recipient mismatch is not an absolute contraindication when proper body size match is considered. A wide anastomosis with typical recipient hepatic veins inclusion and routine post-anastomotic Doppler Ultrasonography measurements are warranted.

BACKGROUND:Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) represents a severe condition that requires prophylaxis with specific immunoglobulin and lamivudine. Few studies have addressed the efficiency of other effective antiviral drugs posttransplantation or their impact on early renal function after transplantation. Herein, we have reported experience among seven transplanted patients prescribed Telbivudin (600 mg/d) while on the waiting list followed by treatment for 3 months after OLT.METHODS:Our series consisted of men with HBV-related end-stage liver disease. Once the patient started antiviral treatment, the viral load decreased rapidly while on the waiting list. All patients were evaluated for liver and renal functions immunosuppressive drug trough levels, CPK before (T0), as well as at 1 month (T1), and 3 months after liver transplant (T3).RESULTS:All patients received a CNI-based regimen. Their mean creatinine clearance (MDRD) was 72.5 mL/min at T0, 69.2 mL/min at T1, and 71.0 mL/min at T3. Neither CPK or serum transaminase levels increased throughout the study. Once HBV-DNA was cleared while on the waiting list, it remained negative throughout the follow-up period.CONCLUSION:Telbivudin prophylaxis for HBV was safe and effective without any significant deleterious effect on liver or renal function tests after liver transplantation.

Background and aims. Use of grafts from hepatitis B (HBV) core antibody (HBcAb(+)) individuals is a routine transplant practice. Herein, we have reported the results of 20 HBV-negative patients transplantated with a HBcAb-positive liver grafts in order to access the efficacy of HBV prophylaxis using immunoglobulin (IE) and antiviral drugs.Methods. From January 2004 to December 2009, we performed 168 liver transplantations including 38 HBcAb-positive grafts (22.6%) in 18 cases of HBV-positive recipients and 20 HBV-negative recipients. Histological data obtained from these last 20 grafts during retrieval showed an Ishak 1 score in three and no fibrosis in the other cases. HBV prophylaxis included infusion of 10,000 UI IG during the anhepatic phase and every 24 hours for the first 7 days irrespective of the antibody titer as well as lamivudin (100 mg) administred daily. Once discharged, outpatient management provided modulated IG infusions according to when the antibody titer was lower than 400 UI.Results. No patient displayed an HBV infection. The overall survival was 80%. Two patients died within the first month after transplantation due to septic complications; one patient succumbed at 24 months after transplantation because of a lymphoproliferative malignancy and another died due to an aggressive hepatitis C virus recurrence at 6 months post transplant.Conclusion. By using appropriate anti-HBV prophylaxis, HBcAb-positive grafts can be used safely for HBcAb-negative recipients.

1Unit of Hepatobiliary Surgery and Liver Transplantation, Cardarelli Hospital, Naples, Italy; 2I Division or Surgery, Mauriziano Umberto I Hospital, Turin, Italy; 3Unit of Pediatric Surgery, S. Andrea Hospital, Rome, Italy; 4Unit of Neurosurgery, San Camillo Forlanini Hospital, Rome (SINch), Italy; 5Departement of Cardiovascular Surgery, Ospedali Riuniti, Bergamo, Italy; 6Unit of Day Surgery, S. Maria Hospital, Terni, Italy; 7Departement of Surgery, Tor Vergata University, Rome (SICADS S.I.C.), Italy; 8Deparment of Anesthesia and Resuscitation, University of Milan, National Cancer Institute, Milan, Italy; 9CeVEAS, Modena, Italy; 10Division of Orthopedics and Traumatology, Polyclinic S. Orsola-Malpighi, Bologna, Italy; 11Infective Risk Program Agency, Regional Division, Emilia-Romagna, Bologna, Italy; 12Istituto Superiore di Sanita ISS, Rome, Italy; 13Departement of Otolaryngology, University of Siena, Siena (SIO e Ch CF), Italy; 14National Institute for the Infectious Diseases Lazzaro Spallanzani, Rome (SIMIT), Italy; 15Departement of Molecular Biology, University of Siena, Polyclinic Le Scotte, Siena (AMCLI), Italy; 16Departement of Pharmacology, University of Milan, Milan (SIC), Italy; 17II Faculty of Medicine, University La Sapienza, Rome, Italy