This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e23. Learning Objective: Upon completion of this CME activity successful learners will be able to describe the (a) global and regional burden of pancreatic cancer and (b) recent epidemiological trends in pancreatic cancer. BACKGROUND & AIMS:We evaluated global and regional burdens of, risk factors for, and epidemiologic trends in pancreatic cancer among groups of different sexes and ages. METHODS: We used data from the GLOBOCAN database to estimate pancreatic cancer incidence and mortality in 184 countries. We examined the association between lifestyle and metabolic risk factors, extracted from the World Health Organization Global Health Observatory database, and pancreatic cancer incidence and mortality by univariable and multivariable linear regression. We retrieved countryspecific age-standardized rates (ASRs) of incidence and mortalities from cancer registries from 48 countries through 2017 for trend analysis by joinpoint regression analysis. RESULTS: The highest incidence and mortality of pancreatic cancer were in regions with very high (ASRs, 7.7 and 4.9) and high human development indexes (ASRs, 6.9 and 4.6) in 2018. Countries with higher incidence and mortality were more likely to have higher prevalence of smoking, alcohol drinking, physical inactivity, obesity, hypertension, and high cholesterol. From 2008From to 2017From , 2007From to 2016From , or 2003From to 2012, depending on the availability of the data, there were increases in incidence among men and women in 14 (average annual percent changes [AAPCs], 8.85 to 0.41) and 17 (AAPCs, 6.04 to 0.87) countries, respectively. For mortality, the increase was observed in 8 (AAPCs, 4.20 to 0.55) countries among men and 14 (AAPCs, 5.83 to 0.78) countries among women. Although the incidence increased in 18 countries (AAPCs, 7.83 to 0.91) among individuals 50 years or older, an increasing trend in pancreatic cancer was also identified among individuals younger than 50 years and 40 years in 8 (AAPCs, 8.75 to 2.82) and 4 (AAPCs, 11.07 to 8.31) countries, respectively. CONCLUSIONS: In an analysis of data from 48 countries, we found increasing incidence and mortality trends in pancreatic cancer, especially among women and populations 50 years or older, but also among younger individuals. More preventive efforts are recommended for these populations.

Unresolved inflammation can lead to tissue fibrosis and impaired organ function. Macrophage–myofibroblast transition (MMT) is one newly identified mechanism by which ongoing chronic inflammation causes progressive fibrosis in different forms of kidney disease. However, the mechanisms underlying MMT are still largely unknown. Here, we discovered a brain-specific homeobox/POU domain protein Pou4f1 (Brn3a) as a specific regulator of MMT. Interestingly, we found that Pou4f1 is highly expressed by macrophages undergoing MMT in sites of fibrosis in human and experimental kidney disease, identified by coexpression of the myofibroblast marker, α-SMA. Unexpectedly, Pou4f1 expression peaked in the early stage in renal fibrogenesis in vivo and during MMT of bone marrow-derived macrophages (BMDMs) in vitro. Mechanistically, chromatin immunoprecipitation (ChIP) assay identified that Pou4f1 is a Smad3 target and the key downstream regulator of MMT, while microarray analysis defined a Pou4f1-dependent fibrogenic gene network for promoting TGF-β1/Smad3-driven MMT in BMDMs at the transcriptional level. More importantly, using two mouse models of progressive renal interstitial fibrosis featuring the MMT process, we demonstrated that adoptive transfer of TGF-β1-stimulated BMDMs restored both MMT and renal fibrosis in macrophage-depleted mice, which was prevented by silencing Pou4f1 in transferred BMDMs. These findings establish a role for Pou4f1 in MMT and renal fibrosis and suggest that Pou4f1 may be a therapeutic target for chronic kidney disease with progressive renal fibrosis.

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

OBJECTIVES: Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection. RESULTS: In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202–4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity. DISCUSSION: Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.