Liver transplantation for metastatic wild-type gastrointestinal stromal tumor in the era of molecular targeted therapies: Report of a first case.

The gastrointestinal stromal tumor (GIST) is a digestive neoplasm of mesenchymal lineage. The treatment strategy for receptor tyrosine kinase-mutated GISTs is well defined. Wild-type GISTs (WT-GISTs) respond unsatisfactorily to specific kinase inhibitors. Moreover, evidence shows that repeat surgery has limited benefit. We report the case of a young female patient who was diagnosed with liver metastatic WT-GIST, after initial radical resection and adjuvant therapy with molecular targeted drugs. Due to the disease progression, a two-stage surgery was performed, with the removal of extrahepatic lesions followed by a total hepatectomy. The patient is disease-free after 4 years from liver transplantation (LT), performed under everolimus-based immunosuppression. The treatment of WT-GISTs remains a significant challenge due to the frequent resistance to tyrosine kinase inhibitors (TKIs). Liver transplantation might represent an effective treatment option for such disease.

Impact of aberrant left hepatic artery ligation on the outcome of liver transplantation.

The preservation of a graft's aberrant left hepatic artery (LHA) during liver transplantation (LT) ensures optimal vascularization of the left liver but can also be considered a risk factor for hepatic artery thrombosis (HAT). In contrast, ligation of an aberrant LHA may lead to hepatic ischemia with the potential risk of graft dysfunction and biliary complications. The aim of this study was to prospectively analyze the impact on the surgical strategy for LT of 5 tests performed to establish whether an aberrant LHA was an accessory or a replaced artery, thus leading to the design of a decisional algorithm. From August 2005 to December 2016, 395 whole LTs were performed in 376 patients. Five parameters were evaluated to determine whether an aberrant LHA was an accessory or a replaced artery. On the basis of our decision algorithm, an aberrant LHA was ligated during surgery when assessed as accessory and preserved when assessed as replaced. A total of 138 anatomical variants of hepatic arterial vascularization occurred in 120/395 (30.4%) grafts. Overall, the incidence of an aberrant LHA was 63/395 (15.9%). The LHA was ligated in 33 (52.4%) patients and preserved in 30 (47.6%) patients. After a mean follow-up period of 50.9 ± 39.7 months, the incidence of HAT, primary nonfunction, early allograft dysfunction, biliary stricture or leaks, and overall survival was similar in the 2 groups. In conclusion, once shown to be an accessory, an LHA can be safely ligated without clinical consequences on the outcome of LT. Liver Transplantation 24 204-213 2018 AASLD.

Traces of forgotten historical events in mountain communities in Central Italy: A genetic insight.

OBJECTIVES: Analysis of human genetic variation in mountain communities can shed light on the peopling of mountainous regions, perhaps revealing whether the remote geographic location spared them from outside invasion and preserved their gene pool from admixture. In this study, we created a model to assess genetic traces of historical events by reconstructing the paternal and maternal genetic history of seven small mountain villages in inland valleys of Central Italy. METHODS: The communities were selected for their geographic isolation, attested biodemographic stability, and documented history prior to the Roman conquest. We studied the genetic structure by analyzing two hypervariable segments (HVS-I and HVS-II) of the mtDNA D-loop and several informative single nucleotide polymorphisms (SNPs) of the mtDNA coding region in 346 individuals, in addition to 17 short tandem repeats (STRs) and Y-chromosome SNPs in 237 male individuals. RESULTS: For both uniparental markers, most of the haplogroups originated in Western Europe while some Near Eastern haplogroups were identified at low frequencies. However, there was an evident genetic similarity between the Central Italian samples and Near Eastern populations mainly in the male genetic pool. CONCLUSIONS: The samples highlight an overall European genetic pattern both for mtDNA and Y chromosome. Notwithstanding this scenario, Y chromosome haplogroup Q, a common paternal lineage in Central/Western Asia but almost Europe-wide absent, was found, suggesting that Central Italy could have hosted a settlement from Anatolia that might be supported by cultural, topographic and genetic evidence.

Metastatic breast cancer mimicking a hilar cholangiocarcinoma: case report and review of the literature.

BACKGROUND/AIMS: Breast cancer is the most common tumor in women and the first cause of death for malignancy in the female population. Bile ducts are not among the common sites of metastasis from breast cancer; few cases of obstructive jaundice due to metastatic breast cancer have been described in the literature and they mostly resulted from widespread liver metastases that eventually involved the bile ducts. We report an exceptional case of metastatic infiltration of the extrahepatic bile ducts in absence of liver metastases. CASE PRESENTATION: A 56-year-old woman who had undergone a right mastectomy 13 years earlier due to infiltrating ductal breast cancer and had remained tumor free, presented at a follow-up examination with obstructive jaundice.Imaging (computed tomography, magnetic resonance and endoscopic retrograde cholangiopancreatography) scans showed features that were suggestive of a primary tumor of the extrahepatic bile duct. At surgery, the intraoperative findings were also those of a tumor of the bile duct, however, an histological examination showed no evidence of malignancy in the mucosa, but did shown an infiltration of the external wall from adenocarcinoma. Immunohistochemistry analysis demonstrated that the tumor was metastatic breast cancer. CONCLUSIONS: Indeterminate stenosis of the extrahepatic bile ducts should be examined with suspicion in women with a history of breast cancer, and bile duct metastases are to be considered among the possible diagnoses. A differential diagnosis from cholangiocarcinoma is of paramount importance and mainly relies on pathology.

Bridging patients with hepatocellular cancer waiting for liver transplant: all the patients are the same?

Liver transplant (LT) is considered the best curative treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. The possibility to perform LT in HCC patients is limited by the liver grafts supply; indeed, the shortage of donors often leads to a long time on waiting list and then to dropout because of tumor progression. Bridging therapies are neo-adjuvant treatments given to patients on LT waitlist, with the aim to prevent tumor progression and to reduce dropout rate. Many bridging modalities have been proposed. The choice of each treatment is based on the characteristics of the patient, liver function, comorbidities and on the number, dimensions and localization of HCC. This review article describes several types of bridging therapies, focusing on the indications for different kind of patients.

Fast track program in liver resection: a PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: FT program (FT) is a multimodal approach used to enhance postoperative rehabilitation and accelerate recovery. It was 1st described in open heart surgery, then modified and applied successfully in colorectal surgery. FT program was described in liver resection for the 1st time in 2008. Although the program has become widely accepted, it has not yet been considered the standard of care in liver surgery. OBJECTIVES: we performed this systematic review and meta-analysis to evaluate the impact of using the FT program compared to the traditional care (TC), on the main clinical and surgical outcomes for patients who underwent elective liver resection. METHODS: PubMed/Medline, Scopus, and Cochran databases were searched to identify eligible articles that compared FT with TC in elective liver resection to be included in this study. Subgroup meta-analysis between laparoscopic and open surgical approaches to liver resection was also conducted. Quality assessment was performed for all the included studies. Odds ratios (ORs) and mean differences (MDs) were considered as a summary measure of evaluating the association in this meta-analysis for dichotomous and continuous data, respectively. A 95% confidence interval (CI) was reported for both measures. I was used to assess the heterogeneity across studies. RESULTS: From 2008 to 2015, 3 randomized controlled trials (RCTs) and 5 cohort studies were identified, including 394 and 416 patients in the FT and TC groups, respectively. The length of hospital stay (LoS) was markedly shortened in both the open and laparoscopic approaches within the FT program (P < 0.00001). The reduced LoS was accompanied by accelerated functional recovery (P = 0.0008) and decreased hospital costs, with no increase in readmission, morbidity, or mortality rates. Moreover, significant results were found within the FT group such as reduced operative time (P = 0.03), lower intensive care unit admission rate (P < 0.00001), early bowel opening (P ≤ 0.00001), and rapid normal diet restoration (P ≤ 0.00001). CONCLUSION: FT program is safe, feasible, and can be applied successfully in liver resection. Future RCTs on controversial issues such as multimodal analgesia and adherence rate are needed. Specific FT guidelines should be developed for liver resection.

Prevalence and clinical outcome of hepatic haemangioma with specific reference to the risk of rupture: A large retrospective cross-sectional study.

BACKGROUND: Prevalence and incidence of hepatic haemangioma are estimated from autopsy series only. Although benign and generally asymptomatic, hepatic haemangioma can cause serious complications. AIMS: The aim of the study was to assess the prevalence of hepatic haemangioma and to attempt to quantify the risk of major complications such as spontaneous rupture. METHODS: We retrospectively analyzed the radiology database of a Regional University Hospital over a 7-year period: the radiological records of 83,181 patients who had an abdominal computed tomography or magnetic resonance scan were reviewed. Diagnoses made at imaging were reviewed and related to clinical course. RESULTS: Hepatic haemangioma was diagnosed in 2071 patients (2.5% prevalence). In 226 patients (10.9%), haemangioma had diameter of 4 cm or more (giant haemangioma). The risk of bleeding was assessed on patients without concomitant malignancies. Spontaneous bleeding occurred in 5/1067 patients (0.47%). All 5 patients had giant haemangioma: 4 had exophytic lesions and presented with haemoperitoneum; 1 with centrally located tumour experienced intrahepatic bleeding. CONCLUSION: Giant haemangiomas have a low but relevant risk of rupture (3.2% in this series), particularly when peripherally located and exophytic. Surgery might be considered in these cases.

ALPPS Procedure for Extended Liver Resections: A Single Centre Experience and a Systematic Review.

AIM: To report a single-centre experience with the novel Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) technique and systematically review the related literature. METHODS: Since January 2013, patients with extended primary or secondary liver tumors whose future liver remnant (FLR) was considered too small to allow hepatic resection were prospectively assessed for the ALPPS procedure. A systematic literature search was performed using PubMed, Scopus and the Cochrane Library Central. RESULTS: Until July 2014 ALPPS was completed in 9 patients whose mean age was 60 ± 8 years. Indications for surgical resection were metastases from colorectal cancer in 3 cases, perihilar cholangiocarcinoma in 3 cases, intrahepatic cholangiocarcinoma in 2 cases and hepatocellular carcinoma without chronic liver disease in 1 case. The calculated FLR volume was 289 ± 122 mL (21.1 ± 5.5%) before ALPPS-1 and 528 ± 121 mL (32.2 ± 5.7%) before ALLPS-2 (p < 0.001). The increase in FLR between the two procedures was 96 ± 47% (range: 24-160%, p < 0.001). Additional interventions were performed in 4 cases: 3 patients underwent Roux-en-Y hepaticojejunostomy, and one case underwent wedge resection of a residual tumor in the FLR. The average time between the first and second step of the procedure was 10.8 ± 2.9 days. The average hospital stay was 24.1 ± 13.3 days. There was 1 postoperative death due to hepatic failure in the oldest patient of this series who had a perihilar cholangiocarcinoma and concomitant liver fibrosis; 11 complications occurred in 6 patients, 4 of whom had grade III or above disease. After a mean follow-up of 17.1 ± 8.5 months, the overall survival was 89% at 3-6 and 12 months. The recurrence-free survival was 100%, 87.5% and 75% at 3-6-12 months respectively. The literature search yielded 148 articles, of which 22 articles published between 2012 and 2015 were included in this systematic review. CONCLUSION: The ALPPS technique effectively increased the resectability of otherwise inoperable liver tumors. The postoperative morbidity in our series was high in accordance with the data from the systematic review. Age, liver fibrosis and presence of biliary stenting were predisposing factors for postoperative morbidity and mortality.

Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft's Function and Predict Survival after Liver Transplantation.

BACKGROUND: The reduction of insulin-like growth factor 1 (IGF-1) plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT). METHODS: From April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years), and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction) on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated. RESULTS: All patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1), and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p<0.0001). During the first year after LT, the IGF-1 concentration remained significantly lower in recipients transplanted with older donors (>65 years) or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320) and 30 (r = -0.3894, p = 0.0368) was found. After multivariate analysis, early (within 15 days) IGF-1 normalization [Exp(b) = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate. CONCLUSION: IGF-1 postoperative levels are correlated with the graft's quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT.