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Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

Background: Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure. Objectives: We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC. Design: Multicenter, retrospective cohort study. Methods: This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes. Results: Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0–8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9–3.2). An albumin level of3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126). Conclusion: An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders.

Abstract Background Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC. Methods TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application. Results Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P

Abstract To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE. Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed. Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance. Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Abstract Background Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. Methods We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. Results We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. Conclusions This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets. Graphical Abstract

Background/Aims: Programmed death-ligand 1 (PD-L1) expression in tumor cells is associated with a poor biliary tract cancer (BTC) prognosis; tumor-infiltrating immune cells in the tumor microenvironment are associated with a better prognosis. The effect of PD-L1 expression on immune cells on survival is unclear. We investigated the relationship between PD-L1 expression in immune cells and BTC prognosis. Methods: PD-L1 expression was evaluated using an anti-PD-L1 22C3 mouse monoclonal primary antibody, and its relationships with clinical characteristics and prognosis were analyzed using the Cox proportional hazard model to investigate the prognostic performance of PD-L1 in BTC. Results: Among 144 analyzed cases, patients with positive PD-L1 expression in tumor cells and negative PD-L1 expression in immune cells showed poorer overall survival rates than those exhibiting other expressions (tumor cells: hazard ratio [HR]=1.023, p

Abstract Gallbladder stones (GS) is associated with an increased risk of cardiovascular disease. However, the relationship between cholecystectomy for GS and acute coronary syndrome (ACS) is unknown. We investigated the ACS risk in patients with GS and its association with cholecystectomy. Data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013 was extracted. Overall, 64,370 individuals were selected through a 1:3 propensity score matching. Patients were stratified into two groups for comparison: the gallstone group, GS patients with or without cholecystectomy; and the control group, patients without GS or cholecystectomy. The gallstone group exhibited a higher risk of ACS than the control group (hazard ratio [HR], 1.30; 95% confidence interval [CI] 1.15–1.47; P

ObjectiveEarly chemoresistance and tumor mass progression are associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Circulating tumor cells (CTCs) have been studied as potential predictors of treatment response and prognosis in PDAC; however, this approach has yet to be applied in clinical practice. The aim of our study was to investigate the phenotypic characteristics of CTCs and determine their predictive value for PDAC progression.MethodsWe prospectively enrolled 40 patients who were pathologically diagnosed with PDAC and collected blood samples at diagnosis, 2 months after diagnosis, and during disease progression or recurrence. We used a microfabricated filter-based enrichment system to retrieve and analyze CTCs, which were classified using immunofluorescence staining (CD45, EpCAM, and vimentin).ResultsOur study included 20 women and 20 men (median age, 66 years). Overall, 45% of the patients (18/40) had disseminated disease, and 77.5% (31/40) received chemotherapy. Multivariate analysis revealed that the total CTC count and carbohydrate antigen 19-9 level at 2 months after diagnosis were associated with disease progression (P

Abstract The objective of this study was to evaluate the role of regional lymph node (LN) metastasis detected on preoperative CT and/or 18F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) scans in the prediction of early tumor recurrence after curative surgical resection of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 137 patients who underwent upfront surgery with R0 resection of PDAC between 2013 and 2016. Regional LN metastasis was identified using two criteria: positive findings for regional LN metastasis on either preoperative CT or FDG-PET scans (LNOR), or on both preoperative CT and FDG-PET scans (LNAND). A total of 55 patients had early tumor recurrence within 12 months after curative resection. Univariable and multivariable Cox proportional hazard regression analysis showed that preoperative carbohydrate antigen 19–9 (CA19-9) levels, preoperative locally advanced status, and regional LN metastasis (both LNOR and LNAND criteria) were significant risk factors for early recurrence. Positive LNOR and LNAND showed significantly poorer recurrence-free survival compared to negative regional LN metastasis groups (p = 0.048 and p = 0.020, respectively). Compared with the LNAND criteria, the LNOR criteria provided higher sensitivity (22.4% vs. 15.5%, p = 0.046) and a higher negative predictive value (61.9% vs. 59.8%, p = 0.046). The LNOR definition provided more sensitive and accurate performance in diagnosing preoperative regional LN metastasis.

Abstract Cholangiocarcinoma (CCA) is a fatal disease often detected late in unresectable stages. Currently, there are no effective diagnostic methods or biomarkers to detect CCA early with high confidence. Analysis of tumor‐derived extracellular vesicles (tEVs) harvested from liquid biopsies can provide a new opportunity to achieve this goal. Here, an advanced nanoplasmonic sensing technology is reported, termed FLEX (fluorescence‐amplified extracellular vesicle sensing technology), for sensitive and robust single EV analysis. In the FLEX assay, EVs are captured on a plasmonic gold nanowell surface and immunolabeled for cancer‐associated biomarkers to identify tEVs. The underlying plasmonic gold nanowell structures then amplify EVs’ fluorescence signals, an effective amplification process at the single EV level. The FLEX EV analysis revealed a wide heterogeneity of tEVs and their marker levels. FLEX also detected small tEVs not detected by conventional EV fluorescence imaging due to weak signals. Tumor markers (MUC1, EGFR, and EPCAM) are identified in CCA, and this marker combination is applied to detect tEVs in clinical bile samples. The FLEX assay detected CCA with an area under the curve of 0.93, significantly better than current clinical markers. The sensitive and accurate nanoplasmonic EV sensing technology can aid in early CCA diagnosis.

Background/Aims: Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. Methods: We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. Results: Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. Conclusions: We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

Background/Aims: Sphincterotomes are essential for endoscopic sphincterotomy (EST) and can also be used for cannulation in ERCP. A domestic new pull-type sphincterotome (Optimos™, Taewoong, Goyang, Korea) provides acceptable technical feasibility and safety, but there are no comparison results. Thus, this study compared the clinical performance and safety of Optimos™ sphincterotome to a conventional sphincterotome (CleverCut3™, Olympus, Tokyo, Japan) in patients who underwent ERCP. Methods: From April 2021 to July 2021, a randomized prospective comparative study was conducted on 104 consecutive patients who underwent ERCP in three medical centers. The primary endpoint was the clinical performance and safety of sphincterotomes during ERCP. Results: One hundred and four patients were assigned randomly to the Optimos™ group (n=51) or CleverCut3™ group (n=53). All demographic characteristics did not differ between the groups except the BMI. The technical success rate for cannulation, performance of EST, and total procedure time were similar in the two groups. The adverse events did not differ, even though two cases of post-ERCP pancreatitis occurred in CleverCut3™. On the other hand, in questionnaire analysis, CleverCut™ showed a better user’s convenience (median [interquartile range] 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.013) and manipulability (median [interquartile range], 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.039) than Optimos™, even though the other profiles did not reveal any differences. Conclusions: New domestic pull-type sphincterotome can offer comparable clinical performance and safety profiles to conventional sphincterotome, but it needs refinements to increase the user’s convenience and manipulability. Further improvement and innovation will be required to advance domestic medical devices.

The vacuum degree of Vacuum Interrupter (VI) will deteriorate because of gases emitted by arc heat, and leakage through the joints. It is important to select an appropriate maintenance criteria for a VI by monitoring the vacuum degree. However, monitoring of a VI installed inside a solid insulation apparatus in a transmission system is impossible. Only studies on the insulation deterioration because of the decrease of the vacuum degree have been conducted, and important factors such as the maintenance criteria have not been investigated. Moreover, most studies have only been performed using AC voltage, not DC voltage. Therefore, in this paper, AC and DC partial discharge were compared by monitoring of the vacuum degree in a distribution class VI to propose maintenance criteria according to voltage type. Through this, for efficient maintenance, maintenance criteria of VI for each voltage type are presented. The vacuum degree at which the dielectric strength rapidly decreases was confirmed according to voltage type. The coupling capacitor was installed directly on the floating shield of VI. Moreover, to measure the pattern and apparent charge of partial discharge according to the vacuum degree, phase resolved partial discharge (PRPD) for AC partial discharge and pulse sequence analysis (PSA) for DC partial discharge were adopted. It is found that maintenance should be performed when the vacuum degree is in the range of $10^{-3} \boldsymbol {\sim } 10^{-2}$ torr regardless of the voltage type. Moreover, the usefulness of the technology is higher at AC voltage than at DC voltage.

Abstract Chronic pancreatitis (CP) related main pancreatic duct (MPD) stricture has been a challenge for endoscopists. Fully covered self-expandable metal stents (FC-SEMS) has been tried in CP patients, but the efficacy and safety are still controversial. Thus, we aim to compare the long-term clinical efficacy of FC-SEMS vs. plastic stent placement in persistent MPD strictures secondary to CP. Between 2007 and 2018, 80 chronic pancreatitis patients (58 males, median age 49 years), who underwent endoscopic placement of FC-SEMS (n = 26) and plastic stent (n = 54) for persistent MPD strictures after at least 3 months of initial single plastic stenting, were retrospectively analyzed during a median follow-up duration of 33.7 months. As a result, MPD stricture resolution rate was statistically higher in FC-SEMS group (87.0% vs. 42.0%, p

Herein, a mucoadhesive patch for gastrointestinal tracts with active delivery, hyperthermia, and controlled drug release function using a magnetically actuated capsule is proposed to overcome the drug delivery and efficiency challenges of wireless structures. The proposed patch has excellent adhesion to the gastrointestinal tract and contains anticancer drug doxorubicin and magnetic nanoparticles. This enables hyperthermia and the controlled release of the loaded drug under an alternating magnetic field (AMF). In addition, it can be delivered to multiple intestinal target lesions using a magnetically actuated capsule. Characteristic analyses of the proposed patch are performed, such as morphology, adhesion force measurement with intestine, temperature change under an AMF, and drug release. The feasibility of the patch delivery into the gastrointestinal tract is verified through locomotion performance tests and ex vivo patch delivery experiments using a magnetically actuated capsule. Finally, through an in vitro therapeutic effect test, the death of tumor cells using the proposed patch is confirmed. As a result, the possibility that the multiple mucoadhesive patches can be delivered to target lesions in a digestive tract through a magnetically actuated capsule and can treat the lesions through hyperthermia and active drug release using an AMF stimulation is verified.

Background/AimsThe benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL.Methods : The records of patients who received gemcitabine-based FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors.Results : SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p

Background: The aim of this study was to evaluate the efficacy and safety of gemcitabine plus nab-paclitaxel (GnP) as second-line chemotherapy following first-line FOLFIRINOX treatment failure in advanced pancreatic cancer. Methods: This was a multicenter, single-arm, open-label, phase 2 trial done at three tertiary centers in South Korea from May 2018 to December 2019. Eligible patients were aged 20 years or older, had histologically confirmed advanced pancreatic ductal adenocarcinoma, and disease progression after receiving first-line FOLFIRINOX. Patients received a second-line GnP regimen as intravenous nab-paclitaxel at a dose of 125 mg/m 2 and gemcitabine at a dose of 1000 mg/m 2 , on days 1, 8, and 15 every 4 weeks until disease progression or unacceptable toxicity. The primary outcome was survival rate at 6 months and the secondary outcomes were median progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events. This study is registered with Clinicaltrials.gov. (NCT03401827) Results: Forty patients were enrolled in the study. The survival rate at 6 months was 72.5% [95% confidence interval (CI), 59.9–87.7], achieving superiority over prespecified assumed 6-month OS rate of 20% for best supportive care only ( p

BackgroundApproximately 80% of pancreatic ductal adenocarcinoma (PDAC) patients suffer from anorexia, weight loss, and asthenia. Most PDAC patients receive chemotherapy, which often worsens their nutritional status owing to the adverse effects of chemotherapy. Malnutrition of PDAC patients is known to be associated with poor prognosis; therefore, nutritional management during chemotherapy is a key factor influencing the outcome of the treatment. Mobile apps have the potential to provide readily accessible nutritional support for patients with PDAC. ObjectiveWe aimed to evaluate the efficacy of a mobile app–based program, Noom, in patients receiving chemotherapy for PDAC. MethodsWe prospectively enrolled 40 patients who were newly diagnosed with unresectable PDAC from a single university-affiliated hospital in South Korea, and randomly assigned them into a Noom user group (n=20) and a non-Noom user group (n=20). The 12-week in-app interventions included meal and physical activity logging as well as nutritional education feedback from dietitians. The non-Noom user group did not receive any nutrition intervention. The primary outcomes were the changes in the nutritional status and quality of life (QoL) from the baseline to 12 weeks. The secondary outcomes included the changes in the skeletal muscle index (SMI) from the baseline to 12 weeks. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Patient-Generated Subjective Global Assessment (PG-SGA) were used as paper questionnaires to assess the QoL and nutritional status of the patients. Intention-to-treat and per-protocol analyses were conducted. Regarding the study data collection time points, we assessed the nutritional status and QoL at the baseline (T0), and at 4 (T1), 8 (T2), and 12 (T3) weeks. Abdominal computed tomography (CT) imaging was conducted at the baseline and after 8 weeks for tumor response and SMI evaluation. The skeletal muscle area (cm2) was calculated using routine CT images. The cross-sectional areas (cm2) of the L3 skeletal muscles were analyzed. ResultsBetween February 2017 and January 2018, 48 patients were assessed for eligibility. Totally 40 patients with pancreatic cancer were included by random allocation. Only 17 participants in the Noom user group and 16 in the non-Noom user group completed all follow-ups. All the study participants showed a significant improvement in the nutritional status according to the PG-SGA score regardless of Noom app usage. Noom users showed statistically significant improvements on the global health status (GHS) and QoL scales compared to non-Noom users, based on the EORTC QLQ (P=.004). The SMI decreased in both groups during chemotherapy (Noom users, 49.08±12.27 cm2/m2 to 46.08±10.55 cm2/m2; non-Noom users, 50.60±9.05 cm2/m2 to 42.97±8.12 cm2/m2). The decrement was higher in the non-Noom user group than in the Noom user group, but it was not statistically significant (-13.96% vs. -3.27%; P=.11). ConclusionsThis pilot study demonstrates that a mobile app–based approach is beneficial for nutritional and psychological support for PDAC patients receiving chemotherapy. Trial RegistrationClinicalTrials.gov NCT04109495; https://clinicaltrials.gov/ct2/show/NCT04109495.

Abstract Recent studies have identified the mutational landscape of pancreatic cancer and suggested tumor‐specific subtypes. However, the major hurdle against personalized treatment is the difficulty to obtain sufficient cancer tissues from most inoperable cases. We investigated whether patient‐derived conditionally reprogrammed cells (CRCs) can be constructed using a small piece of tumor tissue using endoscopic ultrasound (EUS)‐guided fine needle biopsy (FNB). Thirty patients with pancreatic solid mass (mean size, 34.6 mm) were enrolled prospectively. Among 22 patients who were diagnosed with pancreatic ductal adenocarcinoma, we established patient‐derived pancreatic cancer cell lines from eight patients (36.4%). Immunofluorescence colony staining for CRCs showed that the cytoplasm of cancer cells was clearly stained with anti‐cytokeratin 19 monoclonal antibody. In the soft agar colony formation assay, CRCs formed colonies compared with the negative control by day 15. In vivo, implanted CRCs showed tumor engraftment and hematoxylin and eosin staining showed pancreatic cancer ductal structure. All established CRCs showed a KRAS mutation. In conclusion, we established patient‐derived pancreatic cancer cell lines with a small tumor tissue obtained by EUS‐FNB. With in vitro drug sensitivity and genomic studies, established patient‐derived cell lines can be used in identification of new targets for diagnosis and treatment of pancreatic cancer.

Background: The establishment of patient-derived models for pancreatic ductal adenocarcinoma (PDAC) using conventional methods has been fraught with low success rate, mainly because of the small number of tumour cells and dense fibrotic stroma. Here, we sought to establish patient-derived model of PDAC and perform genetic analysis with responses to anticancer drug by using the conditionally reprogrammed cell (CRC) methodology. Methods: We performed in vitro and in vivo tumourigenicity assays and analysed histological characteristics by immunostaining. We investigated genetic profiles including mutation patterns and copy number variations using targeted deep sequencing and copy-number analyses. We assessed the responses of cultured CRCs to the available clinical anticancer drugs based on patient responsiveness. Findings: We established a total of 28 CRCs from patients. Of the 28 samples, 27 showed KRAS mutations in codon 12/13 or codon 61. We found that somatic mutations were shared in the primary-CRC pairs and shared mutations included key oncogenic mutations such as KRAS (9 pairs), TP53 (8 pairs), and SMAD4 (3 pairs). Overall, CRCs preserved the genetic characteristics of primary tumours with high concordance, with additional confirmation of low-AF NPM1 mutation in CRC (35 shared mutations out of 36 total, concordance rate=97.2%). CRCs of the responder group were more sensitive to anticancer agents than those of the non-responder group (P < 0.001). Interpretation: These results show that a pancreatic cancer cell line model can be efficiently established using the CRC methodology, to better support a personalized therapeutic approach for pancreatic cancer patients. Funding: 2014R1A1A1006272, HI19C0642-060019, 2019R1A2C2008050, 2020R1A2C209958611, and 2020M3E5E204028211

Background/Aims Recent studies have revealed that contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) is beneficial in the differential diagnosis of malignant neoplasms of the pancreas and gallbladder from benign masses, in terms of the evaluation of microvasculature and real-time perfusion. In this study, we aimed to prove the clinical value of CEH-EUS in the differential diagnosis of pancreatic and gallbladder masses by direct comparison with that of conventional EUS. Methods We reviewed the sonographic images and medical information of 471 patients who underwent conventional EUS and CEH-EUS for the diagnosis of pancreatic and gallbladder masses at a single medical center (Severance Hospital, Seoul, Korea) between March 2010 and March 2016. Results The enhancement pattern of CEH-EUS of the pancreatic solid masses showed higher sensitivity and specificity in differentiating pancreatic adenocarcinoma and neuroendocrine tumors (82.0% and 87.9% for pancreatic adenocarcinoma and 81.1% and 90.9% for neuroendocrine tumors, respectively), and the area under the receiver operating characteristic curves was higher than that of conventional EUS. The enhancement texture of CEH-EUS of the gallbladder masses showed a higher sensitivity in differentiating malignant masses than that of conventional EUS; however, the difference between the areas under the receiver operating characteristic curves was not statistically significant. Conclusions CEH-EUS can complement conventional EUS in the diagnosis of pancreatic and gallbladder masses, in terms of the limitations of the latter.

The internal pressure of a vacuum interrupter (VI) is increased by arc heat, ceramic cracking, gas leakage, and manufacturing defects. Accordingly, the dielectric strength of VI rapidly decreases. To improve the reliability of power transmission, efficient maintenance through the real-time monitoring of the vacuum degree is essential. However, real-time monitoring of the vacuum degree is difficult, and related research is scarce. Additionally, due to the insulation problems of this technology, there are few commercially available products. Therefore, this paper proposes a method for real-time monitoring of the vacuum degree and an insulation supplement design for a distribution class VI. First, dielectric experiments were conducted to identify the section in which the dielectric strength of the VI rapidly decreased according to the vacuum degree. Second, for real-time monitoring of the VI, several factors were proposed through the partial discharge in the VI, while the capacitance characteristics of the VI were calculated to improve the signal of the internal partial discharge. Finally, to supplement the dielectric problems of the solid insulation high voltage apparatus that occur when real-time monitoring technology is applied, the insulation supplement design was performed through the finite element method (FEM).

Background/AimsWe aimed to investigate the incidence of second primary pancreatic cancer (PC) after colorectal cancer (CRC) and to identify risk factors associated with subsequent PC.Methods : The observed incidence of a subsequent PC in patients with CRC was standardized using a population with CRC from the Korean Central Cancer Registry (KCCR). The expected incidence rate of PC was obtained by assuming that the select group experienced the same cancer incidence as the corresponding general population in the KCCR.Results : The registry included 4,822 patients with CRC aged 45 to 74 years, representing 16,725.1 person-years of follow-up. Thirteen patients (0.3%) were diagnosed with a subsequent PC, and the overall age-adjusted incidence of second primary PC was 269.6 per 100,000 cases. In contrast, the overall incidence of primary PC in the general population was 18.68 per 100,000 individuals. The standardized incidence ratio of subsequent PC was 14.44, which was significantly higher in patients with CRC than in the general population. Sex, diabetes mellitus, smoking, body mass index, and a history of receiving chemotherapy as a treatment for CRC did not increase the risk of subsequent development of PC.Conclusion : sThe risk of a second primary PC was higher in patients with CRC. Further studies are needed to identify the risk factors and generate a screening strategy for cancer survivors.

BACKGROUND:Pancreatic pseudocysts (PC) and walled-off necrosis (WON) are common complications of severe pancreatitis. Endoscopic ultrasound (EUS)-guided drainage has replaced surgery as the standard treatment for PC/WON. We developed a novel lumen-apposing metal stent (LAMS) with an anti-reflux valve to prevent infectious complications caused by food reflux into the cyst cavity. This retrospective study investigated the efficacy and safety of EUS-guided drainage using this LAMS. METHODS:We investigated and compared the treatment outcomes and complications rates between EUS-guided drainage using a novel LAMS (n = 10) versus plastic stents (n = 18) from December 2013 to October 2016. Technical success was defined as successful stent placement without immediate complications. Clinical success was defined as resolution of the PC/WON and disappearance of symptoms. RESULTS:Among 10 patients in LAMS group, 4 patients had complicated PC and 6 patients had WON. In the plastic stent group, 15 and 3 patients had PC and WON, respectively. The median fluid collection size before treatment was 82.5 (interquartile range [IQR], 60.75-118.25) mm and 92.0 (IQR, 75.75-130.25) mm in the LAMS and plastic stent groups, respectively. There were no statistically significant differences in technical success rates (90% vs. 94.4%; p = 0.999), clinical success rates (80% vs. 77.8%; p = 0.999), and complication rates (20% vs. 27.8%; p = 0.999) between the two groups. CONCLUSIONS:Treatment outcomes of EUS-guided drainage using a novel LAMS were feasible despite the significantly high proportion of WON. The LAMS allowed acceptable treatment outcomes for EUS-guided drainage.

A converter valve unit, which converts Alternating Current (AC) to Directing Current (DC) and DC to AC, is one of the key elements of high voltage direct current (HVDC) transmission. The insulation design of a converter valve unit should be considered for air clearance according to the DC superimposed overvoltage and the insulator that maintains the insulation performance and the corona shield to suppress DC corona discharge. There is no prescribed standard for the insulation design of a converter valve unit. Moreover, insulation performance under an applied DC voltage has not yet been thoroughly investigated. Therefore, it is necessary to study the insulation design method of the converter valve unit. In this paper, consideration of the insulation design method on a ±200 kV converter valve unit in an HVDC converter hall is performed. The finite element method (FEM) is used to simulate the 3D model. Additionally, the safety factor (SF) is applied in accordance with the dielectric test in IEC 62271-1. As a result, an insulation design process on the converter valve unit is proposed and the insulation design is carried through the design factors. It is confirmed that design factors on the air clearance, insulator and corona shield have a significant effect on a highly reliable insulation design.

Capsule endoscopes (CEs) have emerged as an advanced diagnostic technology for gastrointestinal diseases in recent decades. However, with regard to robotic motions, they require active movability and multi-functionalities for extensive, untethered, and precise clinical utilization. Herein, we present a novel wireless biopsy CE employing active five degree-of-freedom locomotion and a biopsy needle punching mechanism for the histological analysis of the intestinal tract. A medical biopsy punch is attached to a screw mechanism, which can be magnetically actuated to extrude and retract the biopsy tool, for tissue extraction. The external magnetic field from an electromagnetic actuation (EMA) system is utilized to actuate the screw mechanism and harvest biopsy tissue; therefore, the proposed system consumes no onboard energy of the CE. This design enables observation of the biopsy process through the capsule’s camera. A prototype with a diameter of 12 mm and length of 30 mm was fabricated with a medical biopsy punch having a diameter of 1.5 mm. Its performance was verified through numerical analysis, as well as in-vitro and ex-vivo experiments on porcine intestine. The CE could be moved to target lesions and obtain sufficient tissue samples for histological examination. The proposed biopsy CE mechanism utilizing punch biopsy and its wireless extraction–retraction technique can advance untethered intestinal endoscopic capsule technology at clinical sites.

Acute pancreatitis is a common diagnosis worldwide, with gallstone disease being the most prevalent cause (50%). The American College of Gastroenterology recommends urgent endoscopic retrograde cholangiopancreatography (ERCP) (within 24 h) for patients with biliary pancreatitis accompanied by cholangitis. Most international guidelines recommend that ERCP be performed within 72 h in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, but the optimal timing for endoscopy is controversial. We investigated the optimal timing for ERCP in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, and whether performing endoscopy within 24 h is superior to performing it after 24 h. We analyzed the clinical data of 505 patients with newly diagnosed acute pancreatitis, from January 1, 2005 to December 31, 2014. We divided the patients into two groups according to the timing of ERCP: < 24 h (urgent) and 24-72 h (early).Among the 505 patients, 73 were diagnosed with biliary pancreatitis and a bile duct obstruction without cholangitis. The mean age of the patients was 55 years (range: 26-90 years). Bile duct stones and biliary sludge were identified on endoscopy in 45 (61.6%) and 11 (15.0%) patients, respectively. The timing of ERCP within 72 h was not associated with ERCP-related complications (P = 0.113), and the total length of hospital stay was not different between urgent and early ERCP (5.9 vs. 5.7 days, P = 0.174). No significant differences were found in total length of hospitalization or procedural-related complications, in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, according to the timing of ERCP (< 24 h vs. 24-72 h).

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is commonly used to obtain tissue external to the gastrointestinal tract. EUS-FNA is relatively safe, but occasionally adverse events have been reported. There is scarcity of data on risk factors of adverse events. The aim of this study is to identify risk factors associated with EUS-FNA.In this multicenter case-control study, we retrospectively reviewed 4,097 cases between 2009 and 2012 at 15 hospitals in Korea. Among the patients there were 104 cases (2.5%) who had adverse events of which 12 (0.29%) were severe. We matched 520 controls (1:5 ratios) stratified by hospital to analyze the potential risk factors.The most common adverse events were pancreatitis (45/104, 43.3%) and infection (46/104, 44.2%). Endoscopic retrograde cholangiopancreatography (ERCP) on the same day was a risk factor of all adverse events [OR = 2.41, 95% CI (1.41, 4.12)], pancreatitis [OR = 2.31, 95% CI (1.02, 5.25)], and infection [OR = 2.75, 95% CI (1.31, 5.78)]. More than 15 to-and-fro movements during puncture increased the risk of pancreatitis [OR = 2.30, 95% CI (1.11, 4.77)] and infection [OR = 3.65, 95% CI (1.55, 8.59)]. A higher number of punctures was positively correlated with pancreatitis [OR = 1.34, 95% CI (1.08, 1.67)] but negatively correlated with infection [OR = 0.66, 95% CI (0.48, 0.89)].EUS-FNA is a safe procedure in which serious adverse events are rare. We define some risk factors of adverse events during EUS-FNA, including ERCP on the same day, a higher number of punctures, and more than 15 to-and-fro movements.

PURPOSE:Several studies reported the increased risk of second primary pancreatic ductal adenocarcinoma (2nd PDAC) in cancer survivors. However, data on the characteristics of 2nd PDAC are insufficient. METHODS:This retrospective cohort study included 1759 patients with PDAC. They were classified as having 2nd PDAC or first primary PDAC (1st PDAC) according to a prior diagnosed cancer of different origin, at least 6 months before PDAC diagnosis. RESULTS:There were 110 patients (6.4%) with 2nd PDAC and 1606 (93.6%) patients with 1st PDAC. Patients with 2nd PDAC presented with older age (66.5 vs. 62.2 years, p < 0.001) and higher rate of resectability (26.4% vs. 15.9%, p = 0.004) at diagnosis than those with 1st PDAC. Multivariate analysis without considering resectable status showed that 2nd PDAC (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.94, p = 0.016) was associated with better overall survival. After adjusting for resectable status, however, 2nd PDAC (HR 0.85, 95% CI 0.66-1.09, p = 0.198) was no longer associated with overall survival. When subgroups were separately analyzed according to initial treatment modality, the effectiveness of surgery and chemotherapy were similar between 2nd and 1st PDAC (33.1 vs. 28.5 months, p = 0.860 and 10.8 vs. 10.7 months, p = 0.952). CONCLUSIONS:The proportion of resectable cases was significantly higher in 2nd PDAC. When surgery with curative aim was possible, the overall survival was increased even in patients with 2nd PDAC. These results suggest the importance of screening for second primary cancer in cancer survivors.

BACKGROUND AND AIMS:Although thicker needles theoretically allow more tissue to be collected, their decreased flexibility can cause mechanical damage to the endoscope, technical failure, and sample blood contamination. The effects of needle gauge on diagnostic outcomes of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) of pancreatic mass lesions remain unknown. This study compared procurement rates of histologic cores obtained from EUS-FNB of pancreatic masses using 25- and 22-gauge core biopsy needles. PATIENTS AND METHODS:From March 2014 to July 2014, 66 patients with solid pancreatic mass underwent EUS-FNB with both 25- and 22-gauge core biopsy needles. Among them, 10 patients were excluded and thus 56 patients were eligible for the analyses. Needle sequences were randomly assigned, and two passes were made with each needle, consisting of 10 uniform to-and-fro movements on each pass with 10 mL syringe suction. A pathologist blinded to needle sequence evaluated specimens for the presence of histologic core. RESULTS:The mean patient age was 65.8 ± 9.5 years (range, 44-89 years); 35 patients (62.5%) were men. The mean pancreatic mass size was 35.3 ± 17.1 mm (range 14-122.3 mm). Twenty-eight patients (50%) had tumors at the pancreas head or uncinate process. There were no significant differences in procurement rates of histologic cores between 25-gauge (49/56, 87.5%) and 22-gauge (46/56, 82.1%, P = 0.581) needles or diagnostic accuracy using only histologic cores (98% and 95%). There were no technical failures or procedure-related adverse events. CONCLUSIONS:The 25-gauge core biopsy needle could offer acceptable and comparable outcomes regarding diagnostic performance including histologic core procurement rates compared to the 22-gauge core biopsy needle, although the differences were not statistically significant. TRIAL REGISTRATION:ClinicalTrials.gov NCT01795066.

Ligand-dependent activation of the Hedgehog (Hh) signaling pathway has been implicated in both tumor initiation and metastasis of pancreatic ductal adenocarcinoma (PDAC). Prior studies in genetically engineered mouse models (GEMMs) have assessed the role of Hh signaling by cell autonomous expression of a constitutively active Gli2 within epithelial cells. On the contrary, aberrant pathway reactivation in the human exocrine pancreas occurs principally as a consequence of Sonic Hh ligand (Shh) overexpression from epithelial cells. To recapitulate the cognate pathophysiology of Hh signaling observed in the human pancreas, we examined GEMM where Hh ligand is conditionally overexpressed within the mature exocrine pancreas using a tamoxifen-inducible Elastase-Cre promoter (Ela-CreERT2;LSL-mShh). We also facilitated potential cell autonomous epithelial responsiveness to secreted Hh ligand by generating compound transgenic mice with concomitant expression of the Hh receptor Smoothened (Ela-CreERT2;LSL-mShh;LSL-mSmo). Of interest, none of these mice developed intraductal precursor lesions or PDAC during the follow-up period of up to 12 months after tamoxifen induction. Instead, all animals demonstrated marked expansion of stromal cells, consistent with the previously described epithelial-to-stromal paracrine Hh signaling. Hh responsiveness was mirrored by the expression of primary cilia within the expanded mesenchymal compartment and the absence within mature acinar cells. In the absence of cooperating mutations, Hh ligand overexpression in the mature exocrine pancreas is insufficient to induce neoplasia, even when epithelial cells coexpress the Smo receptor. This autochthonous model serves as a platform for studying epithelial stromal interactions in pancreatic carcinogenesis.

The importance of providing effective analgesia during sedation for complex endoscopic procedures has been widely recognized. However, repeated administration of opioids in order to achieve sufficient analgesia may carry the risk of delayed recovery after propofol based sedation. This study was done to compare recovery profiles and the satisfaction of the endoscopists and patients between conventional balanced propofol sedation and analgesia-oriented combination sedation for patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).Two hundred and two adult patients scheduled for ERCP were sedated by either the Conventional (initial bolus of meperidine with propofol infusion) or Combination (repeated bolus doses of fentanyl with propofol infusion) method. Recovery profiles, satisfaction levels of the endoscopists and patients, drug requirements and complications were compared between groups.Patients of the Combination Group required significantly less propofol compared to the Conventional Group (135.0 ± 68.8 mg vs. 165.3 ± 81.7 mg, P = 0.005). Modified Aldrete scores were not different between groups throughout the recovery period, and recovery times were also comparable between groups. Satisfaction scores were not different between the two groups in both the endoscopists and patients (P = 0.868 and 0.890, respectively).Considering the significant reduction in propofol dose, the non-inferiority of recovery profiles and satisfaction scores of the endoscopists and patients, analgesia oriented combination sedation may be a more safe yet effective sedative method compared to conventional balanced propofol sedation during ERCP.

Purpose: Cannulation of the major papilla is the most challenging part of endoscopic retrograde cholangiopancreatography (ERCP) for which physician-controlled wire-guided cannulation (PCWGC) and assistant-controlled wire-guided cannulation (ACWGC) are used as the cannulation techniques. PCWGC can reportedly save up to about 30% of the labor cost by reducing the number of assistants. This study aims to compare the safety and efficacy of PCWGC and ACWGC. Materials and Methods: Of the 2151 patients aged >20 years (4193 cases) who underwent ERCP at Yonsei University Medical Center between January 2015 and December 2016, 989 were included in this study. Results: Among efficacy outcomes, cannulation success rate, rate of precut sphincterotomy (PCWGC vs. ACWGC: 21.3% vs. 25.9%), bile duct cannulation time (PCWGC vs. ACWGC: median 3.0 minutes vs. 3.6 minutes), and total procedure time (PCWGC vs. ACWGC: median 13.6 minutes vs. 13.1 minutes) were not significantly different. Among safety outcomes, lower rates of post- ERCP pancreatitis were observed with PCWGC than with ACWGC (PCWGC vs. ACWGC: 5.8% vs. 8.8%, p=0.128). Among other post-ERCP adverse events (bleeding, perforation, and cholangitis), the difference was not significant between the groups. Radiation exposure (total dose area product, PCWGC vs. ACWGC: median 1979.9 μGym² vs. 2062.0 μGym², p=0.194) and ERCP cost excluding labor cost (PCWGC vs. ACWGC: $1576 vs. $1547, p=0.606) were not significantly different. Conclusion: Requiring less assistants, PCWGC showed comparable efficacy and safety to ACWGC. PCWGC can be considered as an alternative option, especially in facilities lacking manpower and resources. [ABSTRACT FROM AUTHOR]

Purpose Clinical prognostic criteria using preoperative factors were not developed for post-neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria. Materials and Methods Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system. Results One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, -0.012 to 0.142). Conclusion "Any degree of decrease in tumor size on CT" and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging. [ABSTRACT FROM AUTHOR]

Context: Considering the absence of methods to find pancreatic cancer early, surveillance of high-risk groups is needed for early diagnosis. Objective: The study aimed to investigate the effect in the incidence of pancreatic cancer and the differences between new-onset diabetes mellitus (NODM) and long-standing DM (LSDM) since NODM group is a representative high-risk group. Methods: The Korean National Health Insurance Service--National Sample Cohort between 2002 and 2013 data were used. Regarding 88 396 people with DM (case group), we conducted a 1:1 propensity score matching to select a matched non-DM population (control group). To investigate the interaction between DM and the time variable distinguishing NODM and LSDM, we performed a multivariate time-dependent Cox regression analysis. Results: The incidence of pancreatic cancer was higher in the DM group compared to the non-DM group (0.52% vs 0.16%; P < .001). The DM group had shown different risk of pancreatic cancer development according to the duration since the DM diagnosis (NODM hazard ratio (HR): 3.81; 95% CI, 2.97-4.88; P < .001; LSDM HR: 1.53; 95% CI, 1.11-2.11; P < .001). When the NODM and the LSDM groups were compared, the risk of pancreatic cancer was higher in the NODM group than in the LSDM group (HR: 1.55; P = .020). In subgroup analysis, NODM group showed that men (HR = 4.42; 95% CI, 3.15-6.19; P < .001) and patients who were in their 50 seconds (HR = 7.54; 95% CI, 3.24-17.56; P < .001) were at a higher risk of developing pancreatic cancer than matched same sex or age control group (non- DM population), respectively. Conclusion: The risk of pancreatic cancer was greater in people with DM than in a non-DM population. Among people with DM, NODM showed a higher risk of pancreatic cancer than LSDM. [ABSTRACT FROM AUTHOR]