The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition.
Gastrin is a pro-proliferative, anti-apoptotic hormone with a central role in acid secretion in the gastric mucosa and a long-standing association with malignant progression in transgenic mouse models. However, its exact role in human gastric malignancy requires further validation. Gastrin expression is tightly regulated by two closely associated hormones, somatostatin and gastrin-releasing peptide, and aspects of their interaction may be deregulated during progression to gastric adenocarcinoma. Furthermore, agonists and antagonists of the receptors for all three hormones have shown modest clinical efficacy against gastric adenocarcinoma, which might provide useful information on the future combined use of these agents.
BackgroundMetastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M‐PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy.MethodsRetrospective analysis of outcomes data of UM patients receiving M‐PHP at two institutions was performed. Tumor response and toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) v4.03, respectively.ResultsA total of 51 patients received 134 M‐PHP procedures (median of 2 M‐PHPs). 25 (49%) achieved a partial (N = 22, 43.1%) or complete hepatic response (N = 3, 5.9%). In 17 (33.3%) additional patients, the disease stabilized for at least 3 months, for a hepatic disease control rate of 82.4%. After median follow‐up of 367 days, median overall progression free (PFS) and hepatic progression free survival (hPFS) was 8.1 and 9.1 months, respectively and median overall survival was 15.3 months. There were no treatment related fatalities. Non‐hematologic grade 3‐4 events were seen in 19 (37.5%) patients and were mainly coagulopathic (N = 8) and cardiovascular (N = 9).ConclusionsM‐PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.
IntroductionMurine hepatic NK cells exhibit adaptive features, with liver‐specific adhesion molecules CXCR6 and CD49a acting as surface markers.MethodsWe investigated human liver‐resident CXCR6+ and CD49a+ NK cells using RNA sequencing, flow cytometry, and functional analysis. We further assessed the role of cytokines in generating NK cells with these phenotypes from the peripheral blood.ResultsHepatic CD49a+ NK cells could be induced using cytokines and produce high quantities of IFNγ and TNFα, in contrast to hepatic CXCR6+ NK cells. RNA sequencing of liver‐resident CXCR6+ NK cells confirmed a tolerant immature phenotype with reduced expression of markers associated with maturity and cytotoxicity. Liver‐resident double‐positive CXCR6 + CD49a+ hepatic NK cells are immature but maintain high expression of Th1 cytokines as observed for single‐positive CD49a+ NK cells. We show that stimulation with activating cytokines can readily induce upregulation of both CD49a and CXCR6 on NK cells in the peripheral blood. In particular, IL‐12 and IL‐15 can generate CXCR6 + CD49a+ NK cells in vitro from NK cells isolated from the peripheral blood, with comparable phenotypic and functional features to liver‐resident CD49a+ NK cells, including enhanced IFNγ and NKG2C expression.ConclusionIL‐12 and IL‐15 may be key for generating NK cells with a tissue‐homing phenotype and strong Th1 cytokine profile in the blood, and links peripheral activation of NK cells with tissue‐homing. These findings may have important therapeutic implications for immunotherapy of chronic liver disease.
Propensity score matching showed that LLR for CRLM may provide R0 resection rates and long-term OS comparable to those for OLR, with lower blood loss and morbidity, and shorter postoperative hospital stay.
28Importance 29Wide spread implementation of laparoscopic hemihepatectomy is currently limited by its 30 technical difficulty, paucity of training opportunities and perceived long and harmful learning 31 curve. Studies confirming the possibility of a short and safe learning curve for laparoscopic 32 hemihepatectomy could potentially benefit the further implementation of the technique. 33Objective 34To evaluate the extent and safety of the learning curve for laparoscopic hemihepatectomy. 35
Design 36A prospectively collected single-center database containing all laparoscopic liver resections 37 performed in our unit between 2003-2015 was retrospectively reviewed. 38
Setting 39Tertiary referral center, specialized in laparoscopic hepato-pancreato-biliary surgery. 40
Participants 41Included were all patients in whom a total laparoscopic right or left hemihepatectomy 42 procedure was started (intention-to-treat analysis), including laparoscopic extended 43 hemihepatectomies and hemihepatectomies with additional wedge resections. 44
Main Outcome and Measures 45Primary endpoints were clinically relevant complications (Clavien-Dindo grade ≥III). Presence 46 of a learning curve effect was assessed with a risk adjusted cumulative sum analysis. 47
Results 48Out of a total of 531 consecutive laparoscopic liver resections, 159 patients underwent total 49 laparoscopic hemihepatectomy, 105 right and 54 left. In a cohort with 67 (42%) males, 50 median age of 64 years (IQR 51-73)) and 110 (72%) resections for malignant lesions, the 51 overall median operation time was 330 minutes (270-391) and median blood loss 500 ml 52
conversions. 58
Conclusions and Relevance 59Total laparoscopic hemihepatectomy is a feasible and safe procedure with an acceptable 60 learning curve for conversions. Focus should now shift to providing adequate training 61 opportunities for centers interested in implementing this technique.
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