SARS-CoV-2 Infection and Pancreatic β Cell Failure

SARS-CoV-2 infection primarily causes pulmonary symptoms; however, accumulating reports indicate that some patients with COVID-19 have multiple organ dysfunction or failure. Although diabetes is considered a risk factor for severe COVID-19, SARS-CoV-2 infection may also be a causal factor for diabetes mellitus in patients with COVID-19. According to the research reviewed in this paper, the pancreas and pancreatic β cells appear to be targets of SARS-CoV-2 and are damaged by direct or indirect effects of the infection. However, controversial results have been reported between study groups, mainly due to the limited number of cases with diabetes precipitated by COVID-19. In this review, we comprehensively discuss the published findings on the potential association between SARS-CoV-2 infection or COVID-19 and pancreatic β-cell damage leading to diabetes onset. These findings will further contribute to our understanding of the pathogenesis of diabetes mellitus

TYK2 signaling promotes the development of autoreactive CD8+ cytotoxic T lymphocytes and type 1 diabetes

Abstract Tyrosine kinase 2 (TYK2), a member of the JAK family, has attracted attention as a potential therapeutic target for autoimmune diseases. However, the role of TYK2 in CD8+ T cells and autoimmune type 1 diabetes (T1D) is poorly understood. In this study, we generate Tyk2 gene knockout non-obese diabetes (NOD) mice and demonstrate that the loss of Tyk2 inhibits the development of autoreactive CD8+ T-BET+ cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8+ T cells and the CD8+ resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in β-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET+ CTLs, inflammation in β-cells and the onset of autoimmune T1D in NOD mice. Thus, our study reveals the diverse roles of TYK2 in driving the pathogenesis of T1D

Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis

Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat diabetes, but their effects on nonalcoholic steatohepatitis (NASH) and the development of hepatocellular carcinoma (HCC) remain unclear. In this study, mice with streptozotocin- and high-fat diet-induced diabetes and NASH were subcutaneously treated with liraglutide or saline (control) for 14 weeks. Glycemic control, hepatocarcinogenesis, and liver histology were compared between the groups. Fasting blood glucose levels were significantly lower in the liraglutide group than in the control group (210.0 ± 17.3 mg/dL vs. 601.8 ± 123.6 mg/dL), and fasting insulin levels were significantly increased by liraglutide (0.18 ± 0.06 ng/mL vs. 0.09 ± 0.03 ng/mL). Liraglutide completely suppressed hepatocarcinogenesis, whereas HCC was observed in all control mice (average tumor count, 5.5 ± 3.87; average tumor size, 8.1 ± 5.0 mm). Liraglutide significantly ameliorated steatosis, inflammation, and hepatocyte ballooning of non-tumorous lesions in the liver compared with the control findings, and insulin-positive β-cells were observed in the pancreas in liraglutide-treated mice but not in control mice. In conclusion, liraglutide ameliorated NASH and suppressed hepatocarcinogenesis in diabetic mice. GLP-1 receptor agonists can be used to improve the hepatic outcome of diabetes

A snapshot of the 2020 conception of anatomic liver resections and their applicability on minimally invasive liver surgery. A preparatory survey for the Expert Consensus Meeting on Precision Anatomy for Minimally Invasive HBP Surgery

Background: The main aim of this survey was to analyze how liver surgeons perform liver resections and to define their conception of anatomic procedures within the incorporation of minimally invasive liver surgery (MILS). Methods: The survey was distributed among liver surgeons. It mainly focused on personal experience on open and MILS, methods and landmarks, and experience on anatomic resections and Glissonean approach. Results: A total of 445 valid answers from 54 countries was obtained. Surgeons performing MILS mainly have below 10 years of experience (81.8% of responders) and one third has never done complex MILS. New techniques, including indocyanine green demarcation are marginally used (<25%). More than 60% of surgeons do not make a full exposure of hepatic veins during MILS, mainly due to the risk of injury or not considering it to be of utility. Although 88% of responders agreed with the concept of anatomic resection as the "resection along the border/watersheds of each order division identified by the portal vein flow", only 55% of surgeons have ever performed MILS Glissonean approaches. Conclusions: Liver anatomy is not a static concept. Anatomic resections need training and precision. Standardization of complex anatomic resections by a minimally invasive approach should be encouraged

Glissonean approach for hepatic inflow control in minimally invasive anatomic liver resection: A systematic review

Background: The Glissonean approach has been widely validated for both open and minimally invasive anatomic liver resection (MIALR). However, the possible advantages compared to the conventional hilar approach are still under debate. The aim of this systematic review was to evaluate the application of the Glissonean approach in MIALR. Methods: A systematic review of the literature was conducted on PubMed and Ichushi databases. Articles written in English or Japanese were included. From 2,390 English manuscripts evaluated by title and abstract, 43 were included. Additionally, 23 out of 463 Japanese manuscripts were selected. Duplicates were removed, including the most recent manuscript. Results: The Glissonean approach is reported for both major and minor MIALR. The 1st, 2nd and 3rd order divisions of both right and left portal pedicles can be reached following defined anatomical landmarks. Compared to the conventional hilar approach, the Glissonean approach is associated with shorter operative time, lower blood loss, and better peri-operative outcomes. Conclusions: Glissonean approach is safe and feasible for MIALR with several reported advantages compared to the conventional hilar approach. Clear knowledge of Laennec's capsule anatomy is necessary and serves as a guide for the dissection. However, the best surgical approach to be performed depends on surgeon experience and patients' characteristics. Standardization of the Glissonean approach for MIALR is important

Landmarks and techniques to perform minimally invasive liver surgery: A systematic review with a focus on hepatic outflow

Purpose: In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). Methods: A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results: A total of 3372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. Conclusions: This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR

Expert Consensus Guidelines: How to safely perform minimally invasive anatomic liver resection

Background: The concept of minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was developed as a special program during the 32nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). Methods: Thirty-four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network method. Based on the literature review and experts' opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021. Results: Seven clinical questions were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round. Conclusions: The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts' opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR

The Tokyo 2020 terminology of liver anatomy and resections: Updates of the Brisbane 2000 system

Background: The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud's segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM-HBP Surgery Consensus)" was hosted on February 23, 2021. Methods: The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and two future research topics in the terminology session. The EC created seven tentative definitions and five recommendations based on the experts' opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations. Results: This paper presents seven definitions and five recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed. Conclusions: The PAM-HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system

Minimally invasive anatomic liver resection: Results of a survey of world experts

Background: Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR. Method: We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs). Results: All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound. Conclusion: Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons