Vito de Blasi

miR-135a-5p-mediated downregulation of protein tyrosine phosphatase receptor delta is a candidate driver of HCV-associated hepatocarcinogenesis

Background and aims HCV infection is a leading risk factor of hepatocellular carcinoma (HCC). However, even after viral clearance, HCC risk remains elevated. HCV perturbs host cell signalling to maintain infection, and derailed signalling circuitry is a key driver of carcinogenesis. Since protein phosphatases are regulators of signalling events, we aimed to identify phosphatases that respond to HCV infection with relevance for hepatocarcinogenesis. Methods We assessed mRNA and microRNA (miRNA) expression profiles in primary human hepatocytes, liver biopsies and resections of patients with HCC, and analysed microarray and RNA-seq data from paired liver biopsies of patients with HCC. We revealed changes in transcriptional networks through gene set enrichment analysis and correlated phosphatase expression levels to patient survival and tumour recurrence. Results We demonstrate that tumour suppressor protein tyrosine phosphatase receptor delta (PTPRD) is impaired by HCV infection in vivo and in HCC lesions of paired liver biopsies independent from tissue inflammation or fibrosis. In liver tissue adjacent to tumour, high PTPRD levels are associated with a dampened transcriptional activity of STAT3, an increase of patient survival from HCC and reduced tumour recurrence after surgical resection. We identified miR-135a-5p as a mechanistic regulator of hepatic PTPRD expression in patients with HCV. Conclusions We previously demonstrated that STAT3 is required for HCV infection. We conclude that HCV promotes a STAT3 transcriptional programme in the liver of patients by suppressing its regulator PTPRD via upregulation of miR-135a-5p. Our results show the existence of a perturbed PTPRD–STAT3 axis potentially driving malignant progression of HCV-associated liver disease.

Innovative surgical approaches for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with an increasing diffusion in Europe and the United States. The management of such a cancer is continuously progressing and the objective of this paper is to evaluate innovation in the surgical treatment of HCC. In this review, we will analyze the modern concept of preoperative management, the role of laparoscopic and robotic surgery, the intrao-perative use of three dimensional models and augme-nted reality, as well as the potential application of fluore-scence.

Scale-adaptive supervoxel-based random forests for liver tumor segmentation in dynamic contrast-enhanced CT scans

PurposeToward an efficient clinical management of hepatocellular carcinoma (HCC), we propose a classification framework dedicated to tumor necrosis rate estimation from dynamic contrast-enhanced CT scans. Based on machine learning, it requires weak interaction efforts to segment healthy, active and necrotic liver tissues.MethodsOur contributions are two-fold. First, we apply random forest (RF) on supervoxels using multi-phase supervoxel-based features that discriminate tissues based on their dynamic in response to contrast agent injection. Second, we extend this technique in a hierarchical multi-scale fashion to deal with multiple spatial extents and appearance heterogeneity. It translates in an adaptive data sampling scheme combining RF and hierarchical multi-scale tree resulting from recursive supervoxel decomposition. By concatenating multi-phase features across the hierarchical multi-scale tree to describe leaf supervoxels, we enable RF to automatically infer the most informative scales without defining any explicit rules on how to combine them.ResultsAssessment on clinical data confirms the benefits of multi-phase information embedded in a multi-scale supervoxel representation for HCC tumor segmentation.ConclusionDedicated but not limited only to HCC management, both contributions reach further steps toward more accurate multi-label tissue classification.

Short-term and middle-term evaluation of laparoscopic hepatectomies compared with open hepatectomies: A propensity score matching analysis

AIM To compare short-term results between laparoscopic hepatectomy and open hepatectomy using a propensity score matching. METHODS A patient in the laparoscopic liver resection (LLR) group was randomly matched with another patient in the open liver resection (OLR) group using a 1:1 allocated ratio with the nearest estimated propensity score. Patients of the LLR group without matches were excluded. Matching criteria included age, gender, body mass index, American Society of Anesthesiologists score, potential co-morbidities, hepatopathies, size and number of nodules, preoperative chemotherapy, minor or major liver resections. Intraoperative and postoperative data were compared in both groups. RESULTS From January 2012 to January 2015, a total of 241 hepatectomies were consecutively performed, of which 169 in the OLR group (70.1%) and 72 in the LLR group (29.9%). The conversion rate was 9.7% (n = 7). The mortality rate was 4.2% in the OLR group and 0% in the LLR group. Prior to and after propensity score matching, there was a statistically significant difference favorable to the LLR group regarding shorter operative times (185 min vs 247.5 min; P = 0.002), less blood loss (100 mL vs 300 mL; P = 0.002), a shorter hospital stay (7 d vs 9 d; P = 0.004), and a significantly lower rate of medical complications (4.3% vs 26.4%; P < 0.001). CONCLUSION Laparoscopic liver resections seem to yield better short-term and mid-term results as compared to open hepatectomies and could well be considered a privileged approach and become the gold standard in carefully selected patients.

New Approaches in Locoregional Therapies for Hepatocellular Carcinoma.

PurposeHepatocellular carcinoma (HCC) represent actually the fifth most common cancer worldwide, with liver transplantation and hepatic resection who represent the standard of care of curative treatment. Unfortunately, not all patient could benefit of curative treatment. For such patients, locoregional or systemic therapies represent a valid option in order to achieve the best survival possible.MethodsA review of most interesting paper actually present in literature on locoregional treatment for nonresectable nontransplantable HCC was performed.ResultsA detailed description on each different approach has been detailed in each chapter.ConclusionIn case of nontransplantable and nonresectable HCC, locoregional treatment represent a valid alternative in management of this patients.

Robotic Pancreaticoduodenectomy: Operative Steps (With Video).

Robotic pancreaticoduodenectomy represents actually an emerging procedure for robot-assisted surgery. Considering complexity, extensive dissection, and difficult restoration of the digestive continuity, it remains a challenge for surgeons. The embedded video (Supplemental Digital Content 1, http://links.lww.com/SLE/A146) reports our standardized technique for robotic pancreaticoduodenectomy. In conclusion, robotic pancreaticoduodenectomy is feasible and can be safely performed. Further evaluation with clinical trials is required to validate its real benefits.

A retrospective multicenter analysis on redo-laparoscopic anti-reflux surgery: conservative or conversion fundoplication?

BackgroundNearly 20% of patients who undergo hiatal hernia (HH) repair and anti-reflux surgery (ARS) report recurrent HH at long-term follow-up and may be candidates for redo surgery. Current literature on redo-ARS has limitations due to small sample sizes or single center experiences. This type of redo surgery is challenging due to rare but severe complications. Furthermore, the optimal technique for redo-ARS remains debatable. The purpose of the current multicenter study was to review the outcomes of redo-fundoplication and to identify the best ARS repair technique for recurrent HH and gastroesophageal reflux disease (GERD).MethodsData on 975 consecutive patients undergoing hiatal hernia and GERD repair were retrospectively collected in five European high-volume centers. Patient data included demographics, BMI, techniques of the first and redo surgeries (mesh/type of ARS), perioperative morbidity, perioperative complications, duration of hospitalization, time to recurrence, and follow-up. We analyzed the independent risk factors associated with recurrent symptoms and complications during the last ARS. Statistical analysis was performed using GraphPad Prism® and R software®.ResultsSeventy-three (7.49%) patients underwent redo-ARS during the last decade; 71 (98%) of the surgeries were performed using a minimally invasive approach. Forty-two (57.5%) had conversion from Nissen to Toupet. In 17 (23.3%) patients, the initial Nissen fundoplication was conserved. The initial Toupet fundoplication was conserved in 9 (12.3%) patients, and 5 (6.9%) had conversion of Toupet to Nissen. Out of the 73 patients, 10 (13%) underwent more than one redo-ARS. At 8.5 (1–107) months of follow-up, patients who underwent reoperation with Toupet ARS were less symptomatic during the postoperative period compared to those who underwent Nissen fundoplication (p = 0.005, OR 0.038). Patients undergoing mesh repair during the redo-fundoplication (21%) were less symptomatic during the postoperative period (p = 0.020, OR 0.010). The overall rate of complications (Clavien-Dindo classification) after redo surgery was 11%. Multivariate analysis showed that the open approach (p = 0.036, OR 1.721), drain placement (p = 0.0388, OR 9.308), recurrence of dysphagia (p = 0.049, OR 8.411), and patient age (p = 0.0619, OR 1.111) were independent risk factors for complications during the last ARS.ConclusionsFailure of ARS rarely occurs in the hands of experienced surgeons. Redo-ARS is feasible using a minimally invasive approach. According to our study, in terms of recurrence of symptoms, Toupet fundoplication is a superior ARS technique compared to Nissen for redo-fundoplication. Therefore, Toupet fundoplication should be considered in redo interventions for patients who initially underwent ARS with Nissen fundoplication. Furthermore, mesh repair in reoperations has a positive impact on reducing the recurrence of symptoms postoperatively.

Postoperative Infectious Complications Impact Long-Term Survival in Patients Who Underwent Hepatectomies for Colorectal Liver Metastases: a Propensity Score Matching Analysis

ObjectivePostoperative complications strongly impact the postoperative course and long-term outcome of patients who underwent liver resection for colorectal liver metastases (CRLM). Among them, infectious complications play a relevant role. The aim of this study was to evaluate if infectious complications still impact overall and disease-free survival after liver resection for CRLM once patients were matched with a propensity score matching analysis based on Fong’s criteria.MethodsA total of 2281 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were matched with a 1:3 propensity score analysis in order to compare patients with (INF+) and without (INF−) postoperative infectious complications.ResultsMajor resection (OR = 1.69 (1.01–2.89), p = 0.05) and operative time (OR = 1.1 (1.1–1.3), p = 0.05) were identified as risk factors of infectious complications. After propensity score matching, infectious complications are associated with overall survival (OS), with 1-, 3-, 5-year OS at 94, 81, and 66% in INF− and 92, 66, and 57% in INF+ respectively (p = 0.01). Disease-free survival (DFS) was also different with regard to 1-, 3-, 5-year survival at 65, 41, and 22% in R0 vs. 50, 28, and 17% in INF+ (p = 0.007).ConclusionInfectious complications are associated with decreased overall and disease-free survival rates.

Major Hepatectomy for Colorectal Liver Metastases in Patients Aged Over 80: A Propensity Score Matching Analysis

Background: The aim of this study was to evaluate the results of major hepatectomies for metastasis in elderly colorectal cancer patients, for whom limited data exist in the literature. Methods: From January 2006 to January 2013, 3,034 patients underwent hepatectomy for colorectal liver metastasis in 32 French surgical centers. Repeat hepatectomies were excluded from the study. Based on a 1: 4 propensity score matching model, 42 patients aged ≥80 (OG) were matched with 168 patients <80 years (YG) in order to obtain 2 well-balanced and homogeneous groups with regards to therapy and prognostic factors. Results: The unmatched cohort consisted of 744 patients (OG: n = 42; YG: n = 702). After PS matching, there was no difference in terms of general morbidity, rates of Dindo-Clavien score ≥III (OG: 16% vs. YG: 21%, p = 0.663), surgical morbidity (OG: 16% vs. YG: 21%, p = 0.663), reoperation (OG:10% vs. YG: 5%, p = 0.263), 90-day mortality (OG: 0% vs. YG:2%, p = 1), and total median hospital stay (OG: 12 vs. YG: 12, p = 0.972). Both groups experienced similar 3- and 5-year overall survival (82 and 82% OG vs.78 and 67% YG) and disease-free survival (40 and 35% OG vs. 45 and 35% YG at 3 and 5 years). Conclusions: No difference in perioperative and postoperative outcomes and disease-free and overall survival was found. Major hepatectomy in selected octogenarian patients is safe and feasible.

Real case of primitive embryonal duodenal carcinoma in a young man

We report here the case of a young man suffering from a rare germ cell tumour. The patient was a 25-year-old man who was referred to our centre for asthenia, stinging epigastric pain, and an iron deficiency anaemia. Gastroscopy revealed a circumferential vegetating lesion on the second portion of the duodenum. The lesion was indurated at the third portion of the duodenum, responsible for a tight stenosis. A computerized tomography-scan of the chest, abdomen and pelvis, and a pancreatic MRI showed a circumferential lesion with a bi-ductal dilatation (i.e., of the common bile duct and Wirsung’s duct) without metastatic localisation. The patient underwent a pancreaticoduodenectomy with lymph node dissection including all cellular adipose tissues of the hepatic pedicle from the hepatic common artery and of the retroportal lamina. Histological findings were suggestive of a duodenal embryonal carcinoma with pancreatic infiltration. This is the second published case highlighting the duodenal primitive localisation of an embryonal carcinoma with pancreatic infiltration.