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, 150were 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 inter-val [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 recom-mended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

BACKGROUND/OBJECTIVES: Limited studies reported that quercetin inhibited adipogenesis and neovascularization by inhibiting matrix metalloproteinases (MMPs) activity, but such mechanisms have not been elucidated in animal experiments. In this study, we investigated the inhibitory effects of quercetin on weight gain and adipose tissue growth through the regulation of mRNA expressions of adipogenic transcription factors and MMPs in mice fed a high-fat diet (HFD).MATERIALS/METHODS: Five-wk-old C57BL/6J mice were fed a normal diet (ND), HFD, HFD containing 0.05% of quercetin (HFQ0.05), or HFD containing 0.15% of quercetin (HFQ0.15) for 16 wks. Glycerol-3-phosphate dehydrogenase (GPDH) activity was measured using a commercial kit. The mRNA expressions of transcription factors related to adipocyte differentiation were determined by real-time polymerase chain reaction (PCR). The mRNA expressions of MMPs and concentrations of MMPs were measured by real-time PCR and enzyme-linked immunosorbent assay kit, respectively. RESULTS: Quercetin intake reduced body weight gain and epididymal adipose tissue weights (P < 0.05). GPDH activity was higher in the HFD group than in the ND group but lower in the quercetin groups (P < 0.05). The mRNA expressions of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, peroxisome proliferator-activated receptor γ, and fatty acid-binding protein 4 were lower in the quercetin groups than in the HFD group (P < 0.05). Similarly, the mRNA expression and concentrations of MMP-2 and MMP-9 were significantly lower in the quercetin groups than in the HFD group (P < 0.05). CONCLUSION The study confirms that quercetin suppresses body weight gain and adipogenesis by inhibiting transcription factors related to adipocyte differentiation and MMPs (MMP-2 and MMP-9), in mice fed a HFD.

Purpose: Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC. Materials and Methods: We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC). Results: We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l 1 regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively. Conclusion We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC.

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<0.001; immune cells: HR=0.983, p=0.021). PD-L1 expression in tumor cells was an independent predictor of poor overall survival (HR=1.024, p<0.001). In contrast, PD-L1 expression in immune cells was a predictive marker of good prognosis (HR=0.983, p=0.018). Conclusions PD-L1 expression in immune cells may be used as an independent factor to evaluate the prognosis of patients with BTC.

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: and Purpose: The Mini Mental State Examination, 2nd edition: Expanded version (MMSE-2: EV) involves an immediate recall (IR) of story memory (SM). A full version of SM has been developed and standardized; it includes delayed recall (DR) and recognition tests in addition to IR to increase its clinical utility as an independent story recall test. This study was conducted to provide norms for the full version of SM in the Korean version of MMSE-2: EV for clinical use. Methods: A total of 1,168 participants (496 males and 672 females) were included in the study. The ages ranged from 19 to 90 years, and the education level ranged from illiterate to post-graduate. Regression analysis was used to evaluate the relative contributions of demographic variables (age, education, and sex) on the SM measures. Results: We stratified age into 11 groups, and categorized the education level into 6 groups.It was found that the IR, DR, and recognition scores of SM were affected by age, education level, and sex. We provided corrected means and standard deviations of the IR, DR, and recognition scores of the SM for the demographic variables. Conclusions The results indicate the importance of considering demographic variables in interpreting the full version of SM measures. The normative data we have provided in this study should be useful in clinical and research settings for detecting the impairment in verbal memory.

Background/Aims: The 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<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19-9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell’s C-index of the final prognosis prediction model was 0.62. Conclusions SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabine-based FL.

Pancreatic cancer has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancer (LAPC) is considered as unresectable because of involvement of celiac and/or mesenteric vessels. The treatment of LAPC is a challenge. Current guidelines suggest systemic therapy. However, the majority of patients will never experience conversion to surgical resection. Thus, in these patients, ablation is an alternative therapy for local control, which causes local destruction while ideally avoiding injury to surrounding healthy tissue. Irreversible electroporation (IRE) is an energy delivery system, effective in ablating tumors by inducing irreversible membrane destruction of cells. IRE demonstrated to be safe in previous studies. However, it is not free from complications, even serious. Here, we reported two cases of the IRE in LAPC patients.
Electroporation ; Humans ; Membranes ; Pancreatic Neoplasms ; Prognosis

Serine protease inhibitor Kazal-type 1 (SPINK1) is a gene expressed from pancreatic acinar cell which its mutation is known to be associated with chronic pancreatitis (CP) and pancreatic cancer. We report a case of a 47-years-old female with nausea and weight loss with yellow discoloration of skin. Initial imaging and endoscopic study led us to an impression of chronic pancreatitis with pancreatic cancer with common bile-duct dilation. Biopsy result was confirmed with pancreatic adenocarcinoma and additional imaging revealed lymph node and bone metastasis. Our genetic analysis revealed 194+2T>C mutation of SPINK1. Biliary obstruction was successfully decompressed by stent insertion and underwent chemotherapy and radiotherapy. Although there is accumulating evidence of association between SPINK1 mutation and CP, the relationship between SPINK1 mutation and pancreatic cancer in CP patient is an emerging concept. Genetic analysis should be considered in patients with young age especially when diagnosed with both CP and pancreatic cancer.
Acinar Cells ; Adenocarcinoma ; Biopsy ; Drug Therapy ; Female ; Genes, vif ; Humans ; Jaundice, Obstructive ; Lymph Nodes ; Nausea ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Pancreatitis, Chronic ; Radiotherapy ; Serine Proteases ; Skin ; Stents ; Weight Loss

PURPOSE: Patients with liver cirrhosis are considered to be at risk for additional adverse events during endoscopic retrograde cholangiopancreatography (ERCP). The present study was designed as a propensity-score matched analysis to investigate whether cirrhotic liver increases the risk of bleeding complications in patients undergoing ERCP. MATERIALS AND METHODS: In total, 8554 patients who underwent ERCP from January 2005 to December 2015 were retrospectively analyzed. To adjust for the imbalance between patients with and those without liver cirrhosis, 1:3 propensity score matching was performed according to age and sex. RESULTS: Liver cirrhosis was identified in 264 (3.1%) patients. After propensity score matching, a total of 768 patients were included in each of the cirrhotic (n=192) and non-cirrhotic groups (n=576). Post-procedure bleeding (10.9% vs. 4.7%, p=0.003) was more frequently observed in patients with liver cirrhosis than in those without. In multivariate analyses, liver cirrhosis was identified as an independent risk factor associated with post-ERCP bleeding (p=0.003) after further adjustment for prothrombin time, antiplatelet/coagulant, duration of ERCP, and stent insertion. Child-Pugh (CP) class C was found to be associated with an increased incidence of post-ERCP bleeding in patients with cirrhosis (odds ratio 6.144, 95% confidence interval 1.320–28.606; p=0.021). CONCLUSION: The incidence of post-ERCP bleeding in patients with liver cirrhosis was higher than that in patients without liver cirrhosis. In particular, CP class C cirrhosis was significantly associated with post-ERCP bleeding.
Cholangiopancreatography, Endoscopic Retrograde ; Fibrosis ; Hemorrhage ; Humans ; Incidence ; Liver Cirrhosis ; Liver ; Multivariate Analysis ; Propensity Score ; Prothrombin Time ; Retrospective Studies ; Risk Factors ; Stents