Robotic wedge resection of a rare gastric perivascular epithelioid cell tumor: A case report.

BACKGROUND: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that can arise in many different organs with a broad spectrum of biological behavior, from indolent to aggressive progression. Only ten cases of gastric PEComas have been reported in the English literature, which were treated with endoscopic, laparoscopic, or open resections. Due to its rarity, the optimal surgical management and prognosis of this tumor are still uncertain. CASE SUMMARY: We present a case of robotic wedge resection of a 6.5 cm bleeding lesion of the gastric fundus located 3 cm below the esophago-gastric junction in a 55-year-old man. Biopsy revealed a malignant tumor with epithelioid cells focally positive for muscle markers desmin and smooth muscle actin. In addition, histology revealed that the tumor was positive for HMB-45, melan-A (MART-1), microphthalmia transcription factor and negative for pan-cytokeratin AE1/AE3, CD34, p40, DOG-1, CD117 (c-kit), S100, CD3, CD79a, caldesmon and myogenin. These markers suggested the possibility of a PEComa. The patient underwent a diagnostic laparoscopy via the da Vinci® Si™ system and robotic wedge resection. Final pathology confirmed a malignant gastric PEComa with negative margins. At his 11-mo follow-up visit, the patient remained disease-free. CONCLUSION: Gastric PEComa can be treated with a robotic R0 resection with acceptable postoperative and short-term oncological outcomes.

Porcine Isolated Liver Perfusion for the Study of Ischemia Reperfusion Injury: A Systematic Review.

BACKGROUND: Understanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated. METHODS: We systematically reviewed the current experimental setups for ILP and parameters of interest reflecting IRI. RESULTS: Isolated liver perfusion was never compared with transplantation in animals. Considerable variability exists between setups, and comparative data are unavailable. Experience so far suggests that centrifugal pump(s) with continuous flow are preferred to reduce the risk of embolism. Hepatic outflow can be established by cannulation of the inferior vena cava or freely drained in an open bath. Whole blood at approximately 38°C, hematocrit of 20% or greater, and the presence of leukocytes to trigger inflammation is considered the optimal perfusate. A number of parameters related to the 4 liver compartments (hepatocyte, cholangiocyte, endothelium, immune cells) are available; however, their significance and relation to clinical outcomes is not well described. CONCLUSIONS: Porcine ILP provides a reproducible model to study early IRI events. As all models, it has its limitations. A standardization of the setup would allow comparison of data and progress in the field.

Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model.

BACKGROUND: The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). METHODS: We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution. Livers were perfused for 4 hours without (control group, n = 10) or with HLSC-EV (treated group, n = 9). Bile production was quantified; perfusate samples were collected hourly to measure metabolic (pH, pO2, pCO2) and cytolysis parameters (AST, alanine aminotransferase, lactate dehydrogenase). At the end of perfusion, we assessed HLSC-EV engraftment by immunofluorescence, tissue injury by histology, apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, tissue hypoxia-inducible factor 1-α, and transforming growth factor-beta 1 RNA expression by quantitative reverse transcription-polymerase chain reaction. RESULTS: During hypoxic NMP, livers were able to maintain homeostasis and produce bile. In the treated group, AST (P = 0.018) and lactate dehydrogenase (P = 0.032) levels were significantly lower than those of the control group at 3 hours of perfusion, and AST levels persisted lower at 4 hours (P = 0.003). By the end of NMP, HLSC-EV had been uptaken by hepatocytes, and EV treatment significantly reduced histological damage (P = 0.030), apoptosis (P = 0.049), and RNA overexpression of hypoxia-inducible factor 1-α (P < 0.0001) and transforming growth factor-beta 1 (P = 0.014). CONCLUSIONS: HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

Negativization of viremia prior to liver transplant reduces early allograft dysfunction in hepatitis C-positive recipients.

Although early allograft dysfunction (EAD) negatively impacts survival from the first months following liver transplantation (LT), direct-acting antiviral agents (DAAs) have revolutionized hepatitis C virus (HCV) therapy. We investigated the EAD definition best predicting 90-day graft loss and identified EAD risk factors in HCV-positive recipients. From November 2002 to June 2016, 603 HCV-positive patients (hepatocellular carcinoma, 53.4%) underwent a first LT with HCV-negative donors. The median recipient Model for End-Stage Liver Disease (MELD) score was 15, and the median donor age was 63 years. At LT, 77 (12.8%) patients were HCV RNA negative; negativization was achieved and maintained by pre-LT antiviral therapy (61 patients) or pre-LT plus a pre-emptive post-LT course (16 patients); 60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared 3 different EAD definitions: (1) bilirubin ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on day 7 after LT or aspartate aminotransferase or alanine aminotransferase > 2000 IU/L within 7 days of LT; (2) bilirubin > 10 mg/dL on days 2-7 after LT; and (3) MELD ≥ 19 on day 5 after LT. EAD defined by MELD ≥ 19 on day 5 after LT had the lowest negative (0.1) and the highest positive (1.9) likelihood ratio to predict 90-day graft loss. At 90 days after LT, 9.2% of recipients with EAD lost their graft as opposed to 0.7% of those without EAD (P < 0.001). At multivariate analysis, considering variables available at LT, MELD at LT of >25 (OR = 7.4) or 15-25 (OR = 3.2), graft macrovesicular steatosis ≥ 30% (OR = 6.7), HCV RNA positive at LT (OR = 2.7), donor age > 70 years (OR = 2.0), earlier LT era (OR = 1.8), and cold ischemia time ≥ 8 hours (OR = 1.8) were significant risk factors for EAD. In conclusion, in HCV-positive patients, MELD ≥ 19 on day 5 after LT best predicts 90-day graft loss. Preventing graft infection by pre-/peri-LT antiviral therapy reduces EAD incidence and could be most beneficial in high-MELD patients and recipients of suboptimal grafts. Liver Transplantation 23 915-924 2017 AASLD.

The role of osmotic self-inflatable tissue expanders in intestinal transplant candidates.

Intestinal transplantation (ITx) is often associated with decreased abdominal domain, rendering abdominal closure difficult. Pre-transplant placement of tissue expanders (TE) can overcome this challenge; however it can be associated with life-threatening complications. This review aimed to comprehensively summarize all available literature on TE in ITx candidates and include the technical details of osmotic, self-inflatable TE -a technique undescribed before. PubMed, EMBASE and CCTR were searched until April 30, 2016. Based on structured data abstraction and detailed analysis, eighteen cases of TE (inflatable) in ITx candidates were found. Localisation of placement was: subcutaneously in 11; intraperitoneally in 4; 1 patient had 1 TE placed retromuscularly and 1 intraperitoneally; 1 patient had biplanar TE (intraperitoneally placed and extending retromuscularly) and in 1 localisation was unreported. Complication rate was high (61%), injection- or intraperitoneal-related, resulting in life-threatening infections/hematoma. With successful expansion, physiological graft protection -by skin+/-fascia- was always achieved. In completion of this review, we describe our own experience with two patients (7.5-, 34-year-old females), in whom osmotic TE were placed subcutaneously pre-ITx. No TE-related complications occurred and both patients underwent uncomplicated ITx with respectively primary skin and skin + fascia closure. The pros and cons of each TE type and placement are discussed, resulting in the overall conclusions that TE offer an important benefit in graft-protection following ITx. Osmotic TE are safer than conventional prostheses by avoiding percutaneous injections. Subcutaneous placement seems to be safer and more reliable.

Genetic and expression analysis of MET, MACC1, and HGF in metastatic colorectal cancer: response to met inhibition in patient xenografts and pathologic correlations.

PURPOSE: We determined the gene copy numbers for MET, for its transcriptional activator MACC1 and for its ligand hepatocyte growth factor (HGF) in liver metastases from colorectal carcinoma (mCRC). We correlated copy numbers with mRNA levels and explored whether gain and/or overexpression of MET and MACC1 predict response to anti-Met therapies. Finally, we assessed whether their genomic or transcriptional deregulation correlates with pathologic and molecular parameters of aggressive disease. EXPERIMENTAL DESIGN: One hundred three mCRCs were analyzed. Copy numbers and mRNA were determined by quantitative PCR (qPCR). Thirty nine samples were implanted and expanded in NOD (nonobese diabetic)/SCID (severe combined immunodeficient) mice to generate cohorts that were treated with the Met inhibitor JNJ-38877605. In silico analysis of MACC1 targets relied on genome-wide mapping of promoter regions and on expression data from two CRC datasets. RESULTS: No focal, high-grade amplifications of MET, MACC1, or HGF were detected. Chromosome 7 polysomy and gain of the p-arm were observed in 21% and 8% of cases, respectively, and significantly correlated with higher expression of both Met and MACC1. Met inhibition in patient-derived xenografts did not modify tumor growth. Copy number gain and overexpression of MACC1 correlated with unfavorable pathologic features better than overexpression of Met. Bioinformatic analysis of putative MACC1 targets identified elements besides Met, whose overexpression cosegregated with aggressive forms of colorectal cancer. CONCLUSIONS: Experiments in patient-derived xenografts suggest that mCRCs do not rely on Met genomic gain and/or overexpression for growth. On the basis of pathologic correlations and bioinformatic analysis, MACC1 could contribute to CRC progression through mechanisms other than or additional to Met transcriptional upregulation.