Michihiro Yoshida, Itaru Naitoh, Kazuki Hayashi, Naruomi Jinno, Yasuki Hori, Makoto Natsume, Akihisa Kato, Kenta Kachi, Go Asano, Naoki Atsuta, Hidenori Sahashi, and Hiromi Kataoka. Gut and Liver 2021;15:476-85. https://doi.org/10.5009/gnl20238

Diagnostic reference levels (DRLs) are required to optimize medical exposure. However, data on DRLs for interventional fluoroscopic procedures are lacking, especially in gastroenterology. This study aimed to prospectively collect currently used radiation doses and help establish national DRLs for fluoroscopy-guided gastrointestinal procedures in Japan. This multicentre, prospective, observational study collected actual radiation dose data from endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), balloon-assisted enteroscopy (BAE), enteral metallic stent placement, and enteral tube placement from May 2019 to December 2020. The study outcomes were fluoroscopy time (FT: min), air kerma at the patient entrance reference point (K_a,r: mGy), air kerma area product (P_KA: Gycm²), and radiation dose rate (RDR: mGy/min). Additionally, the basic settings of fluoroscopy equipment and the factors related to each procedure were investigated. This study was registered in the UMIN Clinical Trial Registry (UMIN 000036525). Overall, 12959 fluoroscopy-guided gastrointestinal procedures were included from 23 hospitals in Japan. For 11162 ERCPs, the median/third quartile values of K_a,r (mGy), P_KA (Gycm²), and FT (min) were 69/145 mGy, 16/32 Gycm², and 11/20 min, respectively. Similarly, these values were 106/219 mGy, 23/41 Gycm² and 17/27 min for 374 interventional EUSs; 53/104 mGy, 16/32 Gycm² and 10/15 min for 523 metallic stents; 56/104 mGy, 28/47 Gycm², and 12/18 min for 599 tube placements; and 35/81 mGy, 16/43 Gycm² and 7/15 min for 301 BAEs, respectively. For the overall radiation dose rate, the median/third quartile values of RDR were 5.9/9.4 (mGy/min). The RDR values at each institution varied widely. This study reports the current radiation doses of fluoroscopy-guided gastrointestinal procedures expressed as DRL quantities. This will serve as a valuable reference for national DRL values. This work was supported by a clinical research grant from the Japanese Society of Gastroenterology.

The revised Atlanta classification is widely used for the evaluation of acute pancreatitis (AP) severity. However, this classification cannot be used within 48 hours of AP onset. The aim of this study was to investigate the predictive factors of mortality in patients with AP on admission. We evaluated the association between AP mortality and clinical parameters at the time of admission in patients with AP from April 2013 to December 2017 at one university hospital and one tertiary care referral center. A total of 203 consecutive patients were enrolled. Nine patients (4.4%) died despite multidisciplinary treatment. In a multivariable analysis, hematocrit ≥ 40% (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01–1.13; P = 0.021), blood urea nitrogen (BUN) ≥ 40 mg/dL (OR, 1.26; 95% CI, 1.11–1.42; P < 0.001), base excess < -3.0 mmol/L (OR, 1.15; 95% CI, 1.04–1.26; P = 0.004), and inflammation extending to the rectovesical excavation (OR, 1.19; 95% CI, 1.10–1.30; P < 0.001) on admission were significantly associated with mortality. Among the imaging findings, inflammation extending to the rectovesical excavation was the only independent predictive factor for mortality in AP. This simple finding, obtained on computed tomography without contrast agent on admission, might be a promising prognostic factor for AP.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)–related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography–related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4–SC from cholangiocarcinoma and/or primary SC.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are being increasingly used to treat advanced malignancies. ICI-induced pancreatic injury (ICI-PI), which is an immune-related adverse event that may be a risk factor of ICI-associated pancreatitis, is not well documented in the literature. METHODS: Consecutive patients who received ICIs for advanced malignancies from August 2015 through October 2022 were analyzed for the incidence of ICI-PI based on the Common Terminology Criteria for Adverse Events and ICI-associated pancreatitis. The imaging, clinical, and pathological findings of ICI-associated pancreatitis were also assessed. RESULTS: This study enrolled 843 patients. In multivariable analyses, dual or simultaneous immunotherapy and ≥10 cycles of ICI administration were significant predictive factors for all grades of pancreatic injury, including grade ≥3. Notably, patients who received simultaneous immunotherapy exhibited a higher incidence of grade ≥3 pancreatic injuries compared with those receiving asynchronous immunotherapy in univariable analysis (P = 0.032). One-fifth of the patients (16/70) with grade ≥3 pancreatic injuries had imaging evidence of pancreatitis similar to mild acute pancreatitis. ICI-associated pancreatitis was observed in 5.7% (48/843) of patients, including 1.8% (15/843) with moderate-to-severe pancreatitis (grade ≥2). Symptomatic cases (0.36%, 3/843) were treated with steroids with favorable outcomes. Immunohistochemistry for CD4 and CD8 revealed greater infiltration of CD8⁺ than CD4⁺ lymphocytes. DISCUSSION: Simultaneous immunotherapy and dual immunotherapy are risk factors of ICI-PI. Although most patients diagnosed with ICI-PI and ICI-associated pancreatitis were asymptomatic and had a low mortality likelihood, long-term outcomes, including endocrine and exocrine function, should be carefully monitored.

Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates various cancer progression. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on Autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX‐LPA axis in malignant ascites in PDAC, and to determine whether ATX works as a molecular target for treating peritoneal dissemination. In a PDAC peritoneal dissemination mouse model, the amount of ATX was significantly higher in ascites than in serum. An in vitro study using two PDAC cell lines, AsPC‐1 and PANC‐1, showed that ATX‐LPA signaling promoted cancer cell migration via the activation of the downstream signaling, and this increased cell migration was suppressed by an ATX inhibitor, PF‐8380. An in vivo study showed that PF‐8380 suppressed peritoneal dissemination and decreased malignant ascites, and these results were validated by the biological analysis as well as the in vitro study. Moreover, there was a positive correlation between the amount of ATX in ascites and the degree of disseminated cancer progression. These findings demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC.