Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV ...infection are still poorly understood. Recently, the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) was identified as a DNA sensor. In this study, we investigated the functional role of cGAS in sensing HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss‐of‐function and gain‐of‐function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes, and HBV‐infected human liver chimeric mice. Here, we show that cGAS is expressed in the human liver, primary human hepatocytes, and human liver chimeric mice. While naked relaxed‐circular HBV DNA is sensed in a cGAS‐dependent manner in hepatoma cell lines and primary human hepatocytes, host cell recognition of viral nucleic acids is abolished during HBV infection, suggesting escape from sensing, likely during packaging of the genome into the viral capsid. While the hepatocyte cGAS pathway is functionally active, as shown by reduction of viral covalently closed circular DNA levels in gain‐of‐function studies, HBV infection suppressed cGAS expression and function in cell culture models and humanized mice. Conclusion: HBV exploits multiple strategies to evade sensing and antiviral activity of cGAS and its effector pathways.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are often discovered at a small size. No clear consensus exists on the management of NF-PNETs ≤ 2 cm. The aim of our study was to ...determine the prognostic value of indicators of malignancy in sporadic NF-PNETs ≤ 2 cm. Methods Eighty patients were evaluated retrospectively in 7 French University Hospital Centers. Patients were managed by operative resection (operative group OG) or observational follow-up (non-OG NOG). Pathologic characteristics and outcomes were analyzed. Results Sixty-six patients (58% women) were in the OG (mean age, 59 years; 95% CI, 56.0–62.3; mean tumor size, 1.6 cm; 95% CI, 1.5–1.7); 14 (72% women, n = 10) were in the NOG (mean age, 63 years; 95% CI, 56–70; mean tumor size, 1.4 cm; 95% CI, 1.0–1.7). All PNETs were ranked using the European Neuroendocrine Tumor Society grading system. Fifteen patients (19%) had malignant tumors defined by node or liver metastasis (synchronous or metachronous). The median disease-free survival was different between malignant and nonmalignant PNETs, respectively: 16 (range, 4–72) versus 30 months (range, 1–156; P = .03). On a receiver operating characteristic (ROC) curve, tumor size had a significant impact on malignancy (area under the curve AUC, 0.75; P = .03), but not Ki-67 (AUC, 0.59; P = .31). A tumor size cutoff was found on the ROC curve at 1.7 cm (odd ratio, 10.8; 95% CI; 2.2–53.2; P = .003) with a sensitivity of 92% and a specificity of 75% to predict malignancy. Conclusion Based on our retrospective study, the cutoff of 2 cm of malignancy used for small NF-PNETs could be decreased to 1.7 cm to select patients more accurately.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
In laparoscopic cholecystectomy (LC), achievement of the Critical View of Safety (CVS) is commonly advocated to prevent bile duct injuries (BDI). However, BDI rates remain stable, probably ...due to inconsistent application or a poor understanding of CVS as well as unreliable reporting. Objective video reporting could serve for quality auditing and help generate consistent datasets for deep learning models aimed at intraoperative assistance. In this study, we develop and test a method to report CVS using videos.
Method
LC videos performed at our institution were retrieved and the video segments starting 60 s prior to the division of cystic structures were edited. Two independent reviewers assessed CVS using an adaptation of the doublet view 6-point scale and a novel binary method in which each criterion is considered either achieved or not. Feasibility to assess CVS in the edited video clips and inter-rater agreements were evaluated.
Results
CVS was attempted in 78 out of the 100 LC videos retrieved. CVS was assessable in 100% of the 60-s video clips. After mediation, CVS was achieved in 32/78(41.03%). Kappa scores of inter-rater agreements using the doublet view versus the binary assessment were as follows: 0.54 versus 0.75 for CVS achievement, 0.45 versus 0.62 for the dissection of the hepatocystic triangle, 0.36 versus 0.77 for the exposure of the lower part of the cystic plate, and 0.48 versus 0.79 for the 2 structures connected to the gallbladder.
Conclusions
The present study is the first to formalize a reproducible method for objective video reporting of CVS in LC. Minute-long video clips provide information on CVS and binary assessment yields a higher inter-rater agreement than previously used methods. These results offer an easy-to-implement strategy for objective video reporting of CVS, which could be used for quality auditing, scientific communication, and development of deep learning models for intraoperative guidance.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chronic HBV infection is a major cause of liver disease and cancer worldwide. Approaches for cure are lacking, and the knowledge of virus-host interactions is still limited. Here, we perform a ...genome-wide gain-of-function screen using a poorly permissive hepatoma cell line to uncover host factors enhancing HBV infection. Validation studies in primary human hepatocytes identified CDKN2C as an important host factor for HBV replication. CDKN2C is overexpressed in highly permissive cells and HBV-infected patients. Mechanistic studies show a role for CDKN2C in inducing cell cycle G1 arrest through inhibition of CDK4/6 associated with the upregulation of HBV transcription enhancers. A correlation between CDKN2C expression and disease progression in HBV-infected patients suggests a role in HBV-induced liver disease. Taken together, we identify a previously undiscovered clinically relevant HBV host factor, allowing the development of improved infectious model systems for drug discovery and the study of the HBV life cycle.
Virtual reality (VR) and augmented reality (AR) in complex surgery are evolving technologies enabling improved preoperative planning and intraoperative navigation. The basis of these technologies is ...a computer-based generation of a patient-specific 3-dimensional model from Digital Imaging and Communications in Medicine (DICOM) data. This article provides a state-of-the- art overview on the clinical use of this technology with a specific focus on hepatic surgery. Although VR and AR are still in an evolving stage with only some clinical application today, these technologies have the potential to become a key factor in improving preoperative and intraoperative decision making.
Background
Laparoscopic repeat liver resection (LRLR) still represents a challenge for surgeons especially in case with previous open liver surgery. The aim of the study is to perform a systematic ...review of the current literature to investigate the feasibility of LRLR after open liver resection (OLR) for liver diseases.
Methods
A computerized search was performed for all English language studies evaluating LRLR. A meta-analysis was performed to evaluate the short-term outcomes in comparative studies between LRLR with previous laparoscopic liver resection (LLR) and OLR.
Results
From the initial 55 manuscripts, 8 studies including 3 comparative studies between LRLR after OLR and LLR were investigated. There was a total of 108 patients. Considering initial surgery, the extent of initial liver resection was major liver resection in 20% of patients in whom it was reported. In all the patients, the most frequent primary histology was hepatocellular carcinoma, followed by colorectal liver metastasis. A half of reported patients had severe adhesions at the time of LRLR. The median operative time for LRLR was ranged from 120 to 413 min and the median blood loss ranged from 100 to 400 mL. There were 11% of the patients conversions to open surgery, hand-assisted laparoscopic surgery, or tumor ablation. The overall postoperative morbidity was 15% of all the patients, and there was no postoperative mortality. The median postoperative hospital stay was ranged from 3.5 to 10 days. The meta-analysis shows that LRLR after OLR is associated with a longer operative time and a more important blood loss compared to LRLR after LLR. However, no difference between LRLR after OLR and LLR was shown as far as hospital stay and morbidity rate are concerned.
Conclusions
LRLR after OLR has been described in eight articles with favorable short-term outcomes in highly selected patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Considering the increase in overall life expectancy and the rising incidence of hepatocellular carcinoma (HCC), more elderly patients are considered for hepatic resection. Traditionally, ...major hepatectomy has not been proposed to the elderly due to severe comorbidities. Indeed, only a few case series are reported in the literature. The present study aimed to compare short-term and long-term outcomes between laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH) in elderly patients with HCC using propensity score matching (PSM).
Methods
We performed a multicentric retrospective study including 184 consecutive cases of HCC major liver resection in patients aged ≥ 70 years in _8 European Hospital Centers. Patients were divided into LMH and OMH groups, and perioperative and long-term outcomes were compared between the 2 groups.
Results
After propensity score matching, 122 patients were enrolled, 38 in the LMH group and 84 in the OMH group. Postoperative overall complications were lower in the LMH than in the OMH group (18 vs. 46%,
p
< 0.001). Hospital stay was shorter in the LMH group than in the OMH group (5 vs. 7 days,
p
= 0.01). Mortality at 90 days was comparable between the two groups. There were no significant differences between the two groups in terms of overall survival (OS) and disease-free survival (DFS) at 1, 3, and 5 years.
Conclusion
LMH for HCC is associated with appropriate short-term outcomes in patients aged ≥ 70 years as compared to OMH. LMH is safe and feasible in elderly patients with HCC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To analyze pathologic and perioperative outcomes of laparoscopic vs. open resections for rectal cancer performed over the last 10 years. A systematic literature search of the following databases was ...conducted: Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), EMBASE, and Scopus. Only articles published in English from January 1, 2008 to December 31, 2018 (i.e. the last 10 years), which met inclusion criteria were considered. The review only included articles which compared Laparoscopic rectal resection (LRR) and Open Rectal Resection (ORR) for rectal cancer and reported at least one of the outcomes of interest. The analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement checklist. Only prospective randomized studies were considered. The body of evidence emerging from this study was evaluated using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. Outcome measures (mean and median values, standard deviations, and interquartile ranges) were extracted for each surgical treatment. Pooled estimates of the mean differences were calculated using random effects models to consider potential inter-study heterogeneity and to adopt a more conservative approach. The pooled effect was considered significant if p <0.05. Five clinical trials were found eligible for the analyses. A positive involvement of CRM was found in 49 LRRs (8.5%) out of 574 patients and in 30 ORRs out of 557 patients (5.4%) RR was 1.55 (95% CI, 0.99-2.41; p = 0.05) with no heterogeneity (I.sup.2 = 0%). Incorrect mesorectal excision was observed in 56 out of 507 (11%) patients who underwent LRR and in 41 (8.4%) out of 484 patients who underwent ORR; RR was 1.30 (95% CI, 0.89-1.91; p = 0.18) with no heterogeneity (I.sup.2 = 0%). Regarding other pathologic outcomes, no significant difference between LRR and ORR was observed in the number of lymph nodes harvested or concerning the distance to the distal margin. As expected, a significant difference was found in the operating time for ORR with a mean difference of 41.99 (95% CI, 24.18, 59.81; p <0.00001; heterogeneity: I.sup.2 = 25%). However, no difference was found for blood loss. Additionally, no significant differences were found in postoperative outcomes such as postoperative hospital stay and postoperative complications. The overall quality of the evidence was rated as high. Despite the spread of laparoscopy with dedicated surgeons and the development of even more precise surgical tools and technologies, the pathological results of laparoscopic surgery are still comparable to those of open ones. Additionally, concerning the pathological data (and particularly CRM), open surgery guarantees better results as compared to laparoscopic surgery. These results must be a starting point for future evaluations which consider the association between ''successful resection" and long-term oncologic outcomes. The introduction of other minimally invasive techniques for rectal cancer surgery, such as robotic resection or transanal TME (taTME), has revealed new scenarios and made open and even laparoscopic surgery obsolete.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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