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Sequential extended cholecystectomy (SEC) is currently recommended for T2 and higher gallbladder cancer (GBC) diagnosed after simple cholecystectomy (SC), but the value and timing of re-resection has not been fully studied. We evaluated the long-term oncologic outcomes of T2 GBC according to the type of surgery performed and investigated the optimal timing for SEC.Patients diagnosed with T2 GBC who underwent SC, extended cholecystectomy (EC), or SEC between 2002 and 2017 were retrospectively reviewed. Those who underwent other surgical procedures or those with incomplete medical records were excluded. Overall survival (OS) and disease-free survival (DFS) according to the types of surgeries and prognostic factors for OS and DFS were analyzed. Survival analysis was done between groups that were divided according to the optimal cutoff time interval between SC and SEC based on DFS data.Of the 226 T2 GBC patients, 53, 173, and 44 underwent SC, EC, and SEC, respectively. The 5-year OS rate was 50.1%, 73.2%, and 78.7%, and the DFS rate was 46.8%, 66.3%, and 65.2% in the SC, EC, and SEC groups, respectively. EC (p = 0.001 and p = 0.001) and SEC (p = 0.007 and p = 0.065) groups had better 5-year OS and DFS rates than the SC group. Preoperative CA 19-9 level 37 U/mL (HR 1.56; 95% CI 1.87-2.79; p 0.001) and N1 stage (HR 2.88; 95% CI 1.76-4.71; p 0.001) were associated with poorer prognosis. The optimal cutoff interval between SC and SEC was 28 days. Patients who underwent SEC ≤ 28 days after the initial cholecystectomy had better 5-year DFS rates than patients who underwent SEC after 28 days (75.0% vs. 52.8%, p = 0.023).SEC is recommended for T2 GBC diagnosed after SC, because SEC provides better survival outcomes than SC alone. A time interval of less than 28 days to SEC is associated with an improved DFS.

Surgical indications of main duct-involved intraductal papillary mucinous neoplasm (IPMN), especially for main pancreatic duct (MPD) of 5-9 mm, remain controversial. We aimed to predict malignancy risk of main duct-involved IPMN.Total 258 patients with main duct-involved IPMN between 2000 and 2017 in our institute were retrospectively analyzed. Main duct IPMN was classified into segmental and diffuse-type by dilated MPD pattern. Clinicopathologic features and predictive factors for malignancy were analyzed.Among 258 patients, 47 and 211 had pure main duct (segmental: 27, diffuse type: 20) and mixed type, respectively. Malignant IPMN presented higher in main duct type (66.0%) compared to mixed type (46.9%). The diffuse type (72.2%) had more invasive carcinoma than the segmental type (40.7%). Invasive IPMN risk increased proportionally to the MPD diameter (5 ≤ MPD10 mm vs 10 ≤ MPD 15 mm vs MPD ≥ 15 mm; 23.4% vs 40.0% vs 48.6%). Symptoms, elevated serum carbohydrate antigen, MPD ≥10 mm, mural nodule, thickened wall, and distal atrophy were independent predictive factors for malignancy. Patients with MPD of 5-9 mm with at least one predictive factor had 35.0% of malignancy risk.The invasive IPMN risk was different according to the dilated main duct pattern. Patients with main duct type, diffuse type, MPD ≥10 mm, and MPD 5-9 mm with at least one predictive factor should be candidates for immediate surgery.

A history of familial pancreatic cancer (FPC) increases the incidence of pancreatic cancer (PC) among first-degree relatives. We aimed to determine the incidence of FPC and analyze its clinical characteristics.Between 2010 and 2014, 1159 patients with PC were included in the study. We evaluated the incidence of FPC, clinicopathological features, and survival prognosis between FPC and non-FPC patients. We further analyzed the clinical outcomes of 389 patients with PC who underwent curative-intent surgery.Familial pancreatic cancer incidence was 3.1% (n = 36) among all patients with PC (n = 1159). FPC was diagnosed at an advanced clinical stage compared to non-FPC (P = .041). The tested variables and 5-year survival rate (5YSR) between FPC and non-FPC after propensity score matching had no differences (5YSR: 4.6% vs 2.6%, P = .834). Among PC patients who underwent curative-intent surgery (n = 389), FPC incidence was 1.8% (n = 7). FPC patients were older than non-FPC patients (75.3 ± 4.7 years vs 64.0 ± 9.9 years, P .001). 5YSR tended to differ between FPC and non-FPC (14.3% vs 22.5%, P = .07) groups.Familial pancreatic cancer is diagnosed at an advanced stage, and FPC that has undergone resection is associated with older age or worse prognosis. A prospective nationwide pedigree registration system was required.

Purpose:Pancreatic ductal adenocarcinoma (PDAC) subtypes have been identified using various methodologies. However, it is a challenge to develop classification system applicable to routine clinical evaluation. We aimed to identify risk subgroups based on molecular features and develop a classification model that was more suited for clinical applications.Experimental Design:We collected whole dissected specimens from 225 patients who underwent surgery at Seoul National University Hospital [Seoul, Republic of Korea (South)], between October 2009 and February 2018. Target proteins with potential relevance to tumor progression or prognosis were quantified with robust quality controls. We used hierarchical clustering analysis to identify risk subgroups. A random forest classification model was developed to predict the identified risk subgroups, and the model was validated using transcriptomic datasets from external cohorts (N = 700), with survival analysis.Results:We identified 24 protein features that could classify the four risk subgroups associated with patient outcomes: stable, exocrine-like; activated, and extracellular matrix (ECM) remodeling. The “stable” risk subgroup was characterized by proteins that were associated with differentiation and tumor suppressors. “Exocrine-like” tumors highly expressed pancreatic enzymes. Two high-risk subgroups, “activated” and “ECM remodeling,” were enriched in terms such as cell cycle, angiogenesis, immunocompetence, tumor invasion metastasis, and metabolic reprogramming. The classification model that included these features made prognoses with relative accuracy and precision in multiple cohorts.Conclusions:We proposed PDAC risk subgroups and developed a classification model that may potentially be useful for routine clinical implementations, at the individual level. This clinical system may improve the accuracy of risk prediction and treatment guidelines.See related commentary by Thakur and Singh, p. 3272

Supplementary materials

Supplementary table S1 to S14

BACKGROUND/PURPOSE We previously reported perioperative and oncologic outcomes of robot-assisted pancreatoduodenectomy (RAPD); however, the follow-up period in RAPD was relatively short, and disease-matched survival analyses were lacking. Therefore, this study investigated time trends of perioperative and long-term disease-matched outcomes of RAPD. METHODS Annual clinicopathologic outcomes of 328 patients with RAPD between 2015 and 2020 were analyzed and compared with 929 patients with open PD using the propensity score-matched (PSM) analysis based on postoperative pancreatic fistula (POPF) risk and oncologic variables in malignant patients. RESULTS Robot-assisted pancreatoduodenectomy cases increased from 10 (6.3%) in 2015 to 116 (50.2% of total PD) in 2020, with malignancy proportion increasing from 50.0% to 80.2%. POPF risk-based PSM analysis showed that compared with open PD, RAPD had younger patients (63.7 vs 65.6 years, P = .018), longer operation time (339.1 vs 290.0 min, P

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for whole exome sequencing (WES) and RNA sequencing analyses of PDAC samples, including tissue processing for proteogenomic analysis, DNA and RNA extraction, experimental procedures for WES and RNA sequencing, and WES and RNA sequencing data analyses.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for mass spectrometry-based proteomic analysis of PDAC samples, including sample preparation, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and data analyses (peptide/protein identification and quantitation).

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for cell-based assays for potential prognostic biomarkers in PDAC, including cell culture, viral transduction, and cell-based assays.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for assays for orthotopic PDAC mouse models, including mouse tumour tissue processing, ultrasound imaging, Masson-trichrome staining, and IHC analysis for immune cell markers.

The associated publication reports proteogenomic analysis of human pancreatic ductal adenocarcinoma (PDAC), where we provided significantly mutated genes (SMGs)/biomarkers, cellular pathways, and cell types as potential therapeutic targets to improve stratification of patients with PDAC. This protocol describes the detailed methods for bioinformatics analysis of PDAC subtypes, including tumour purity estimation, subtype prediction for tumour samples in previous cohorts, pathway enrichment analysis, kinase activity analysis, and pan-omics analysis.

To identify features on preoperative MR imaging with diffusion-weighted imaging (DWI) for predicting next-generation sequencing (NGS)-based tumor cellularity and patient outcome after surgical resection of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 105 patients with surgically resected PDAC who underwent preoperative MR imaging with DWI. Tumor cellularity was measured using molecular techniques and bioinformatics methods. Clinico-pathologic findings including tumor T stage for predicting disease-free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards model. Important MR imaging findings including apparent diffusion coefficient (ADC) value of PDAC and modified ADC value (the ratio of the ADC value of PDAC to the ADC value of the spleen) for predicting higher tumor cellularity (≥ 30%) and poor prognosis were also identified. The median DFS and OS were 12.0 months [95% confidence interval (CI), 8.0–17.0] and 22.0 months (95% CI, 18.0–29.0), respectively. Higher T stage (T3/4) [hazard ratio (HR), 7.720, (95% CI 1.072, 55.612); p = 0.048] and higher tumor cellularity [HR, 1.599 (95% CI, 1.003–2.548); p = 0.048] were significantly associated with worse DFS. Among MR imaging features, the modified ADC value was significantly associated with tumor cellularity [odds ratio, 0.068 (95% CI, 0.012–0.372); p = 0.002], and PDAC with lower modified ADC value [≤ 1.40 (cutoff value)] showed significantly shorter median DFS than PDAC with higher modified ADC value [8 months (95% CI, 4–12) vs. 16 months (95% CI, 10–29); HR, 1.713 (95% CI, 1.073–2.735), log-rank p = 0.024]. Higher NGS-based tumor cellularity may be a negative prognostic factor in pancreatic cancer after resection, and modified ADC value derived from DWI could be helpful in predicting tumor cellularity and patient surgical outcome with regard to recurrence.

Background Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. Methods We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct > 10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. Results Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs. 0.664, p = 0.014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, p = 0.255). Conclusions A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Background Lymph node (LN) metastasis is a well-known poor prognostic factor of pancreatic cancer. LN metastasis, through direct invasion of tumor cell to peritumoral lymph nodes (PTLN), is treated as the same as those which spread through lymphatic channels. This study aimed to evaluate the impact of PTLN invasion on the oncologic outcome of pancreatic cancer. Methods Five hundred and six patients who underwent operation for pancreatic ductal adenocarcinoma from 2012 to 2018 were reviewed. PTLN invasion was defined as direct invasion of tumor cells in contact with main tumor. Results Among the 506 patients, 112 patients (22.1%) had PTLN invasion. PTLN invasion group (PTLNI) showed better disease-free survival than regional LN metastasis group (RLNM) and combined LN metastasis group (CLNM) (PTLNI 21 vs RLNM 11 vs CLNM 12 months, P = .003). There was no significant difference between N0 and PTLNI (PTLNI 21 vs N0 23 months, P = .999). In multivariate analysis, conventional LN metastasis was a significant factor compared to N0, but PTLN invasion was not (hazard ratio 0.786 [0.507-1.220], P = .283). Conclusion Because PTLN invasion does not adversely affect survival in the same way as LN metastasis does, pancreatic cancer-may be overstaged if PTLN invasion were dealt in the same manner as a metastatic LN. Therefore, PTLN invasion should be disregarded from current nodal staging system.

Legumes are rich sources of essential nutrients, and their potential health benefits were reported in many studies. Several studies showed a positive effect of legumes on obesity, but randomised clinical trials are limited in the Korean population. The present intervention study investigated the impact of legumes on body weight in obese Korean subjects. A total of 400 participants (BMI ≥ 25 kg/m2) were randomised into two groups. The legume-enriched diet (LD) group replaced one-third of their refined rice consumption with legumes three times per day as a carbohydrate source. In contrast, the usual diet (UD) group consumed their UD. The mean weight loss at 12 weeks was 2·87 (sem 0·21) kg and 0·17 (sem 0·11) kg in the LD and UD, respectively, which was significantly different between the groups (P < 0·001). HDL-cholesterol and adiponectin levels were increased, and levels of glucose, insulin, TAG, and 8-epi-PGF2α and the homoeostasis model assessment of insulin resistance (IR) index value decreased at 12 weeks compared with baseline in the LD. The consumption of legumes may accelerate weight loss accompanied by regulation of adiponectin and 8-epi-PGF2α in obese subjects. In particular, legumes seemed to induce significant changes in BMI by increasing adiponectin in females. Additionally, increases in plasma adiponectin due to greater substantial weight loss may be related to the improvement in IR.

The preoperative biliary drainage (PBD) in ampulla of Vater (AoV) cancer is indiscriminately performed without logical backgrounds. This study was performed to evaluate the effect of PBD on short and long-term outcomes in AoV cancer.313 patients who underwent pancreaticoduodenectomy and were pathologically diagnosed as AoV cancer between January 2000 and December 2014 were reviewed.167 patients (53.4%) underwent PBD: Endoscopic drainage was performed in 106 patients (33.9%) and percutaneous drainage in 61 (19.5%). The postoperative complication rate of PBD group was significantly higher than that of upfront surgery group (48.5% vs. 38.4%, p = 0.045). The 5-year disease-free survival rate (5Y-DFSR) was significantly lower in PBD group compared to upfront surgery group (53.8% vs. 74.3%, p 0.001). Worse 5Y-DFSR of PBD group was more evident in T1/T2 stage (59.2% vs. 84.1%, p 0.001). In multivariate analysis with T1/T2 staged patients, PBD was independently associated with worse outcome (hazard ratio 2.145 [95% confidence interval, 1.202-3.826], p = 0.010).For T1/T2 AoV cancer, PBD adversely affected the short-term postoperative complication rate as well as the long-term oncologic outcomes. Therefore, especially in patients with T1/T2 AoV cancer, routine practice of PBD should be refrained and be reserved for selected cases such as cholangitis.

Monitoring metabolic biomarkers could be utilized as an effective tool for the early detection of gastric cancer (GC) risk.We aimed to discover predictive serum biomarkers for GC and investigate biomarker-related metabolism.Subjects were randomly selected from the Korean Cancer Prevention Study-II cohort and matched by age and sex. We analyzed baseline serum samples of 160 subjects (discovery set; control and GC occurrence group, 80 each) via nontargeted screening. Identified putative biomarkers were validated in baseline serum samples of 140 subjects (validation set; control and GC occurrence group, 70 each) using targeted metabolites analysis.The final analysis was conducted on the discovery set (control, n = 52 vs. GC occurrence, n = 50) and the validation set (control, n = 43 vs. GC occurrence, n = 44) applying exclusion conditions. Eighteen putative metabolite sets differed between two groups found on nontargeted metabolic screening. We focused on fatty acid-related energy metabolism. In targeted analysis, levels of decanoyl-L-carnitine (p = 0.019), L-carnitine (p = 0.033), and citric acid (p = 0.025) were significantly lower in the GC occurrence group, even after adjusting for age, sex, and smoking status. Additionally, L-carnitine and citric acid were confirmed to have an independently significant relationship to GC development. Notably, alkaline phosphatase showed a significant correlation with these two biomarkers.Changes in serum L-carnitine and citric acid levels that may result from alterations of fatty-acid-related energy metabolism are expected to be valuable biomarkers for the early diagnosis of GC risk.

We aimed to find a novel candidate gene related to the white blood cell (WBC) count in a Korean population. Since WBC count has been reported to have a relation to the risk of chronic diseases according to previous literature, WBC level prediction can be helpful for managing future risk of chronic disease development. In this aspect, a gene newly found in the present study is expected to be utilized as a tool for judging an individual's WBC level.Based on the 153 study participants' genotype data produced by the Korean Chip. The mono-adenosine diphosphate ribosylhydrolase 2 (MACROD2) rs6110695 AG polymorphism had a significant strong association with WBC count, thus, the MACROD2 gene emerged as a novel candidate gene for WBC count. To verify the effects of the single-nucleotide polymorphisms on WBC count, the participants were grouped according to the rs6110695 AA and AG genotypes.WBC to apolipoprotein A-I ratio, WBC count, granulocyte to lymphocyte ratio, monocyte to platelet ratio, and interferon-γ level were significantly higher in the AG genotype group than in the AA genotype group. Through the receiver operating characteristic curve analysis, the rs6110695 AA and AG genotypes were discriminated by the optimal WBC count cutoff value of 5.450. As expected, the results in the participants having a WBC count over 5.450 were similar to the AG genotype group.We revealed that the MACROD2 rs6110695 AG genotype has an association with increasing WBC count. Since, as previous literature described, WBC count is one of the main risk factors for chronic diseases, WBC count measurement in individuals with the rs6110695 AG genotype that was found in the present study may help manage future chronic disease risk.

Postoperative pancreatic fistula (POPF) is the most troublesome complication after pancreaticojejunostomy (PJ). This study aimed to compare the short-term outcomes of 2 different methods of duct-to-mucosa PJ; out-layer continuous suture anastomosis (OCA) and the modified Blumgart method (mBM).This retrospective cohort study enrolled patients who underwent curative-intent, open PD between 2015 and 2020. In mBM, 2 transpancreatic U-sutures were performed between the pancreatic margin and jejunum, with reinforced sutures in the central region. Patient demographics, diagnosis, intraoperative factors, postoperative complications, and POPF defined by the International Study Group on Pancreatic Fistula were investigated. Clinically relevant POPF (CR-POPF) included grades B and C POPF.A total of 184 patients underwent OCA, and 96 patients underwent mBM. The mBM group had more patients who underwent neoadjuvant therapy. The fistula risk scores were comparable between the 2 groups. Both groups showed no significant differences in CR-POPF and overall surgical complication rates. The total operation time was comparable, although the operation time for PJ was shorter in mBM.No significant differences were observed in the postoperative outcomes between each group; the operation time for PJ in mBM was shorter. Therefore, mBM may be considered for utilization in duct-to-mucosa PJ.

Objective: Ischemia in pancreatic islets is critical to beta cell function, however, clinical evidences on the implications for diabetes are lacking. Pancreatectomy can induce diabetes, but the mechanisms are not clearly elucidated. Therefore, we examined if cardiovascular disease (CVD) risk factors and intraoperative ischemia, which could cause perfusion insufficiency in pancreatic islets, are associated with insulin deficiency and diabetes after pancreatectomy. Methods: From 2 prospective cohorts of pancreatectomy since 2007, participants were enrolled who had pre-operative HbA1c < 7% without antidiabetes. As for proximal pancreatectomy, those were selected whose HOMA-R increased after surgery. Insulin secretion was assessed by changes in HOMA-B for 1 year (ΔB) . The participants were divided into low- and high-ΔB groups, with stratification by operation type, pre-operative HbA1c, HOMA-B, HOMA-R, and ΔR. Then CVD risk factors and intraoperative ischemic events were compared between the 2 groups, and evaluated for diabetes incidence. Results: A total of 237 patients were enrolled (men 44%, age 56 years, HbA1c 5.6% in average) . Low-ΔB (median -32% of baseline) and high-ΔB (5%) groups showed comparable baseline metabolic variables. According to logistic regression analyses and Cox regression model, a composite of IGT, hypertension, dyslipidemia and a reduction in intraoperative systolic BP significantly decreased HOMA-B after 1 year (RR, 9.52; 95% CI, 1.14-79.3) , and increased diabetes incidence (HR, 3.3; 95% CI, 1.2-8.9) , after adjustment with age, sex, BMI, HbA1c and operation. Conclusion: We observed that chronic ischemia suggested by CVD risk factors and intraoperative ischemic insult were linked to development of insulin deficiency and diabetes after pancreatectomy. Disclosure S.Moon: None. K.Park: None. H.Jang: None. J.Jang: None. H.Jung: Advisory Panel; Novo Nordisk, Research Support; Jeil Pharmaceutical Co., Novo Nordisk. J.Lee: None. H.Sohn: None. Y.Han: None. H.Kim: None. W.Kwon: None. Y.Yoon: None. H.Han: None. T.Oh: None. Funding National Research Foundation of Korea (2019R1A2C1007397)

BACKGROUND Among various prognostic factors of pancreatic cancer, preoperative clinical information is obtained by imaging modality. This study aimed to evaluate clinical usefulness of preoperative carbohydrate antigen and preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography as predictive biological markers for resectable pancreatic ductal adenocarcinoma. METHODS A total of 189 patients with PDAC who underwent preoperative PET-computed tomography were evaluated. Patients underwent neoadjuvant chemotherapy, and R2 resection was excluded. The correlation between SUVmax and clinicopathologic parameters was analyzed. The C-tree statistical method was used to estimate cutoff values of logCA19-9 and SUVmax for survival rate. A multivariate analysis was conducted to identify prognostic factors for overall survival. RESULTS The median duration of OS was 26 months, and the 5-year survival rate was 22.4%. The optimal cutoff values for CA19-9 level was 150 U/mL and SUVmax was 5.5. When subjects were divided into three groups according to the combination of CA19-9 level and SUVmax from C-tree (high-risk group, CA19-9 > 150 U/mL and SUVmax > 5.5; intermediate-risk group, CA19-9 ≤ 150 U/mL and SUVmax > 5.5 or CA19-9 > 150 U/mL and SUVmax ≤ 5.5; and low-risk group, CA19-9 ≤ 150 U/mL and SUVmax ≤ 5.5), there was a significant 5YSR difference (5.6%, 24.3%, and 36.5%, P < .001). The multivariate analysis revealed high SUVmax, high preoperative CA19-9 level, venous invasion, and adjuvant chemotherapy were prognostic factors of OS. CONCLUSIONS CA19-9 and SUVmax are strong prognostic biological factors in resectable PDAC. Moreover, patients with high CA19-9 level and SUVmax are not indicated for upfront surgery.

Background/Aims: We investigated chromosomal aberrations in patients with pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) by fluorescence in situ hybridization (FISH) to identify cytogenetic changes and molecular markers that may be useful for preoperative diagnosis. Methods: Tissue samples from 48 PDAC and 17 IPMN patients were investigated by FISH analysis using probes targeting chromosomes 7q, 17p, 18q, 20q, and 21q and the pericentromeric region of chromosome 18 (CEP18). Results: The PDAC samples harbored 17p deletion (95.8%), 18q deletion (83.3%), CEP18 deletion (81.2%), 20q gain (81.2%), 21q deletion (77.1%), and 7q gain (70.8%). The IPMN samples had 17p deletion (94.1%), CEP18 deletion (94.1%), 21q deletion (70.6%), 18q deletion (58.8%), 20q gain (58.8%), and 7q gain (58.8%). A significant difference in CEP18 gain was identified between the PDAC and IPMN groups (p=0.029). Detection of 17p or 18q deletion had the highest diagnostic accuracy (80.0%) for PDAC. Conclusions: Chromosomal alterations were frequently identified in both PDAC and IPMN with similar patterns. CEP18 gain and 17p and 18q deletions might be involved in the later stages of PDAC tumorigenesis. Chromosome 17p and 18q deletions might be excellent diagnostic markers. (Gut Liver 2020;14:509-520)

In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection.Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted.Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P 0·001; N2: HR 9·56, P 0·001). Among recurrences, 70·8 per cent were metastatic.Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo.Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P0,001; N2 HR 9,56, P0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

In the field of ophthalmology, optical coherence tomography (OCT) has proven to be a powerful imaging technique when it comes to diagnosing various eye-related diseases. This research article introduces a real-time automatic retinal layer segmentation algorithm based on intensity variation in the OCT images. The built algorithm is capable of detecting internal retinal layers like the internal limiting membrane (ILM), the retinal pigment epithelium (RPE) and the retinal nerve fiber layer (RNFL) with micrometer level precision, the algorithm uses openMP for parallelized computation for real-time visualization of the segmented retinal layers. The total execution time of the algorithm was evaluated using various image sizes and compared with the OCT frame rate to demonstrate the efficiency of real-time segmentation.

Optical polarizing thin film is an optical filter enables light waves of a specific polarization pass through while blocking light waves of other polarizations. Optical polarizing thin films control the brightness of back-light unit for LCD (liquid crystal display) panel, which is essential to produce LCD modules. Defect inspection of polarizing thin films is an important feature during the manufacturing process that is helpful to improve the product quality. In the current study, an automated defect inspection algorithm is introduced and incorporated with a well-known non-destructive and non-contact optical inspection method called spectral domain optical coherence tomography (SD-OCT) to pre-identify defective sub-surface as well as top-surface locations of optical polarizing thin films Polarizing thin films employed in this study consist of 6 layers. The tomographic information, layer information, and defective locations were sufficiently identified through the SD-OCT system owing high-axial resolution. The acquired results indicate the possible application of the proposed system in optical polarizing thin films for the quality assurance.

Background Simple laparoscopic cholecystectomy is sufficient for patients with early gallbladder cancer (GBC). However, because advanced GBCs of T2 or more advanced stages require more complex procedures such as liver resection and lymph node dissection, minimally invasive surgery (MIS) has not been popularized. To evaluate the applicability of MIS for GBC, we report the early outcomes of robotic extended cholecystectomies (RECs). Methods Thirteen patients who radiologically suspected to have T2 or more advanced stages of GBC underwent REC from February 2018 to April 2019. Thirty-nine patients who underwent open extended cholecystectomy were selected by 1:3 propensity score matching, and the differences of clinicopathologic features according to surgical methods were analyzed. Results Compared with open method, operation time, estimated blood loss, postoperative complication rate, and number of retrieved lymph nodes were not significantly different. In REC group, duration of hospital stay was shorter (6.6 vs 8.3 days, P = .002) and postoperative pain was significantly lower in the REC group (P = .024). Conclusion The early outcomes of REC were favorable with regard to early recovery and less pain, with similar number of retrieved lymph nodes. REC is a promising option for treatment of GBC, but further long-term survival studies are needed.

Background Circulating tumor DNA (ctDNA) is a promising biomarker for early tumor detection and minimal residual disease (MRD) assessment in early-stage cancer, but quantifying minute amounts of ctDNA is challenging and well-designed studies on ctDNA in early-stage cancer are still lacking. Here, we adapted a sensitive next-generation sequencing (NGS) technology and performed parallel analysis of pre- and postoperative ctDNA and matched tumor tissues in a prospective cohort of patients with resectable pancreatic ductal adenocarcinoma (PDAC). Methods In total, 70 consecutive patients undergoing curative resection for resectable PDAC were enrolled. We performed integrated digital error suppression-enhanced cancer personalized profiling by deep sequencing NGS of triple-matched samples (pre/postoperative plasma cell-free DNA [cfDNA], tumor tissue, and genomic DNA) targeting 77 genes. Results Preoperative ctDNA was detected in 37.7% of the evaluable patients, with a median variant allele frequency of 0.09%. Twelve additional oncogenic mutations were detected exclusively in preoperative ctDNA but not in tissue. When quantitative concentrations of ctDNA were estimated in haploid genome equivalents per milliliter (hGE/mL), the risk of early recurrence was high in patients with postoperative ctDNA >1 hGE/mL. cfDNA variants from 24.5% of patients had features compatible with clonal hematopoiesis. Conclusions An optimized NGS approach might add value beyond tissue analysis through the highly sensitive detection of minute amounts of ctDNA in resectable PDAC. Postoperative ctDNA concentration could be a tool for MRD assessment. Moreover, parallel analyses of matched tissues and leukocytes might be required to accurately detect clinically relevant ctDNA.

We aimed to use a genetic risk score (GRS) constructed with prediabetes and type 2 diabetes-related single nucleotide polymorphisms (SNPs) and an oxidative stress score (OSS) to construct an early-prediction model for prediabetes and type 2 diabetes (T2DM) incidence in a Korean population. The study population included 549 prediabetes and T2DM patients and 1036 normal subjects. The GRS was constructed using six prediabetes and T2DM-related SNPs, and the OSS was composed of three recognized oxidative stress biomarkers. Among the nine SNPs, six showed significant associations with the incidence of prediabetes and T2DM. The GRS was profoundly associated with increased prediabetes and T2DM (OR = 1.946) compared with individual SNPs after adjusting for age, sex, and BMI. Each of the three oxidative stress biomarkers was markedly higher in the prediabetes and T2DM group than in the normal group, and the OSS was significantly associated with increased prediabetes and T2DM (OR = 2.270). When BMI was introduced to the model with the OSS and GRS, the area under the ROC curve improved (from 69.3% to 70.5%). We found that the prediction model composed of the OSS, GRS, and BMI showed a significant prediction ability for the incidence of prediabetes and T2DM.

For proximal to middle bile duct cancer, it is controversial whether bile duct resection alone is sufficient, or whether hepatic or pancreatic resection should be accompanied by initial planning. This study aimed to determine the optimal surgical extent based on oncological outcomes in patients with proximal to middle bile duct cancer.Patients who underwent surgery for proximal to middle extrahepatic bile duct cancer, hilar resection, or combined resection of other organs were included. Clinicopathological characteristics and survival analyses were compared according to operation type.Among 156 patients in total, R0 rate was 56.7% for hilar resection and 82.7% for other organ resection. Although hilar resection was associated with shorter hospital stay and fewer overall complications, operation type did not affect overall survival (p = 0.259) and disease-free-survival (p = 0.774). Overall survival differed according to R status (5YSR 49.8 vs. 27.1%; p = 0.012).In proximal to middle extrahepatic bile duct cancer, surgery should be tailored to achieve R0 resection according to the extent of the disease rather than uniformly resecting extensively with other organ resections. Hilar resection could be selected if R0 resection is feasible, considering the lower morbidity with similar long-term survival.

In the era of effective chemotherapy on pancreatic ductal adenocarcinoma (PDAC) with distant metastasis, data on the effects of metastatectomy are lacking. So, we investigated the effect of metastatectomy on survival after metastasis in PDAC patients with isolated lung metastasis. This retrospective study analyzed 1342 patients who were histologically diagnosed with PDAC with distant metastasis from January 2007 to December 2018, of which 83 patients had isolated pulmonary metastasis. Additionally, 4263 patients were extracted from the National Cancer Database (NCDB) and analyzed. Log-rank test and Kaplan−Meier survival analysis were used to analyze survival after metastasis. The five-year survival rate was significantly higher in patients who underwent pulmonary metastatectomy than in those who received only chemotherapy or supportive treatment (60.6% vs. 6.2% vs. 0.0%, p < 0.001). A similar trend was observed in the NCDB (two-year survival rate, 27.4% vs. 15.8% vs. 4.7%, p < 0.001). In the multivariate analysis, lung lesion multiplicity (hazard ratio (HR) = 2.004, p = 0.017), metastatectomy (HR = 0.278, p = 0.036), chemotherapy (HR = 0.434, p = 0.024), and chemotherapy cycles (HR = 0.300, p < 0.001) had significant effects on survival. Metastatectomy with primary pancreatic lesions is recommended with effective chemotherapy in PDAC patients with isolated lung metastasis.

Bismuth-Corlette type IV Klatskin tumors have conventionally been considered unresectable. This retrospective study aimed to demonstrate the survival improvement of patients with type IV Klatskin tumors when resected and suggest possible radiological features for R0 resectability.Data on type IV Klatskin tumors diagnosed between 2008 and 2019 were reviewed retrospectively. Patients with distant metastasis, concomitant other cancers at the initial state, extensive vascular invasions, poor liver function, and poor general condition were excluded. The survival outcomes of patients and radiologic parameters of bile duct tumors were compared between the curative resection (R0, 1 resection) and non-resection groups.The demographic findings of patients with curative resection (n = 48) and non-resection (n = 111) were comparable. Both were potentially resectable in the initial state. The postoperative morbidity was 22.9% and the 90-day mortality 4.2%. There was a significant difference in the median survival among the curative-intended resection, palliative treatment, and supportive care groups (35, 16, and 12 months, respectively; P 0.001).In patients with type IV Klatskin tumor without extensive tumor invasion into adjacent tissues, including major vessels, surgical resection can be considered for better survival.IRB No. 2009-100-1157.

Background Serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been proposed as useful preoperative biomarkers of extrahepatic bile duct cancer (EBDC). This study investigated the accuracy of CEA and CA19-9 for preoperative diagnosis of EBDC. Methods Patients who underwent surgery for EBDC at a tertiary centre between 1995 and 2018 were studied, and those with concurrent hepatobiliary diseases (including gallbladder cancer, intraductal papillary mucinous neoplasms of pancreas), which could affect CEA or CA19-9 levels, were excluded. The control group included patients who underwent cholecystectomy for benign gallbladder diseases during the same period. Diagnostic accuracy was determined using sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Results After excluding 23 patients, 687 patients (488 men and 199 women, mean age 65.8 years) were compared with the control group of 2310 patients. Median CEA and CA19-9 levels were 1.8 μg/l and 47.0 kU/l in patients with EBDC. CEA (cut-off 5.0 μg/l) showed AUC of 0.541, sensitivity 9.0 per cent and specificity 99.2 per cent, whereas CA19-9 (cut-off 37.0 kU/l) showed AUC of 0.753, sensitivity 56.2 per cent and specificity 94.5 per cent. Sensitivity of CA19-9 was lower in early (T stages 0–II) than advanced (T stages III and IV) cancer (47.0 versus 64.9 per cent), and also lower in N0 stage cancer than lymph node metastasis (50.1 versus 68.8 per cent). Conclusion Serum CEA and CA19-9 showed low sensitivity limiting their usefulness as diagnostic biomarkers of EBDC., To investigate the diagnostic accuracy of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9, the authors analysed 710 patients for extrahepatic bile duct cancer. CEA showed relatively low, but CA 19-9 showed moderate sensitivity for the diagnosis; sensitivity was lower in early T stage and N0 cancer.

We report a proteogenomic analysis of pancreatic ductal adenocarcinoma (PDAC). Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. Messenger RNA-protein abundance correlations revealed potential prognostic biomarkers correlated with patient survival. Integrated clustering of mRNA, protein and phosphorylation data identified six PDAC subtypes. Cellular pathways represented by mRNA and protein signatures, defining the subtypes and compositions of cell types in the subtypes, characterized them as classical progenitor (TS1), squamous (TS2-4), immunogenic progenitor (IS1) and exocrine-like (IS2) subtypes. Compared with the mRNA data, protein and phosphorylation data further classified the squamous subtypes into activated stroma-enriched (TS2), invasive (TS3) and invasive-proliferative (TS4) squamous subtypes. Orthotopic mouse PDAC models revealed a higher number of pro-tumorigenic immune cells in TS4, inhibiting T cell proliferation. Our proteogenomic analysis provides significantly mutated genes/biomarkers, cellular pathways and cell types as potential therapeutic targets to improve stratification of patients with PDAC.

Background Single-incision robotic cholecystectomy (SIRC) is widely performed with both the da Vinci Xi system (Xi) and the da Vinci SP system (SP). But there are limited numbers of studies comparing these platforms. Methods Patients who underwent SIRC between 2019 and 2020 were enrolled. Patient demographics, intraoperative factors, postoperative complications, postoperative pain were compared using a one-to-one propensity score matching (PSM). Results Overall, 258 patients underwent SIRC with Xi and 72 with SP. After PSM, there were significant differences between the Xi and SP in operation time at console and numeric rating scale for postoperative pain, but no difference in total operation time and postoperative complications. The SP group showed more estimated blood loss. Conclusions Despite the statistical difference, clinical benefit was not significant. Both platforms can be safe and feasible to perform SIRC, but further investigation including the surgeon's workload and ergonomics is needed as a prospective study.

Purpose The clinical significance of margin status in pancreatic head cancer is still controversial due to the nonstandardized definition of R status and pathologic reporting. This study aims to evaluate the impact of the margin status including location and the role of radiation therapy in pancreatic head cancer. Methods A total of 314 patients who underwent curative-intent surgery for pancreatic head cancer between 2010 and 2017 were analyzed. Demographics, survival, and local recurrences were compared according to 2 definitions: 0-mm R1 as direct involvement and 1-mm R1 as close resection margin less than 1 mm. The specific margins were divided into 4 groups according to the location around the pancreas: pancreas transection, anterior surface, posterior surface, and vessel (superior mesenteric artery/superior mesenteric vein) margin. Results The 0-mm R1-rate was 15.6%, and increased to 36.3% in 1-mm R1. The median overall survival rate of 0-mm R0 vs. R1 was 26 months vs. 16 months (P = 0.052) and that of 1-mm R0 vs. R1 was 27 months vs. 18 months, respectively (P = 0.016). In individual margins, posterior, anterior surface, and pancreas transection margin involvement were associated with poor outcome, and the 1 mm posterior surface involvement was an independent risk factor for disease-free survival (hazard ratio, 1.63). Adjuvant radiation therapy had oncologic benefits, especially in R1 patients (P = 0.011) compared to R0 patients (P = 0.088). Conclusion Margin status, especially 1-mm R1 status is an important predictive factor, and involved posterior surface has a clinical impact. Patients with positive margins should be considered adjuvant radiation therapy.

It remains controversial whether central pancreatectomy (CP) can preserve the exocrine and endocrine function of the pancreas or not. This study aimed to evaluate the safety and efficacy of CP compared with distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for benign and low-grade malignant neoplasms. This retrospective study enrolled 219 patients who underwent elective CP (n = 55), DP (n = 70), or PD (n = 94) for benign and low-malignant neoplasms in a single university hospital between January 2000 and December 2015. Patients who underwent CP were propensity score matched to patients who underwent DP or PD at a 1:1 ratio, respectively. Peri- and postoperative outcomes, long-term endocrine/exocrine function, and pancreatic volume change 12 months postoperatively were prospectively evaluated. Of the 165 patients, 55 were included in each of the CP, DP, and PD groups. Significant differences between the CP and DP groups were observed in overall morbidity (CP: n = 18, 33% vs DP: n = 8, 14%; P = 0.041), clinically relevant postoperative pancreatic fistula (CP: n = 13, 24% vs DP: n = 4, 7%; P = 0.022), stool elastase level 12 months after surgery (CP: 151 μg/g vs DP: 245 μg/g; P = 0.003), and percentage change in the remnant pancreatic volume 12 months after surgery (CP: − 9.4% vs DP: + 7.5%; P

Supplemental digital content is available in the text., Objective The incidence of pancreatic adenocarcinoma (PA) approximates its prevalence, as the malignancy is almost consistently fatal within a year. Although the currently available adjuvant therapy seems to provide survival benefit, it is only moderate, and the standard regimen has not yet been established. Therefore, more biological resources to investigate the PA are needed. Methods Here, we established and characterized 10 human pancreatic cancer cell lines derived from primary tumor mass. Whole exome sequencing technique was used to identify driver mutations and aberrant pathways in each cell line. Results Five anticancer drugs were treated to find half maximal effective concentration (EC50), and the response was analyzed in reference to mutational status. Frame shift mutations in ARID1A gene and HER2 amplification were mutually related to better response to the anticancer drugs. In contrast, frame shift mutation in MSH6 gene was associated with resistance to anticancer drugs. Conclusions In summary, we established 10 pancreatic cancer cell lines and integrated various molecular aberrations and features of pancreatic cancer cells. Our biological resources are expected to contribute to facilitating research on PA.

Background: Although several prediction models for the occurrence of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) exist, all were established using Western cohorts. Large-scale external validation studies in Eastern cohorts that consider demographic variables including lower body mass index (BMI) are scarce. The purpose of this study was to externally validate POPF prediction models using nationwide large-scale Korean cohorts. Methods: Nine tertiary university hospitals in the Republic of Korea participated. Patients’ preoperative characteristics, intraoperative factors, and pathologic findings were evaluated. POPF grades were determined according to the 2016 International Study Group on Pancreatic Surgery definition. Three POPF risk models (Callery, Roberts, and Mungroop) were selected for external validation. Results: A total of 1,898 PD patients were enrolled. A non-pancreatic disease diagnosis [hazard ratio (HR), 1.856; 95% confidence interval (CI), 1.223–2.817; P=0.004), higher preoperative BMI (HR, 1.069; 95% CI, 1.019–1.121; P=0.006), and soft pancreatic texture (HR, 1.859; 95% CI, 1.264–2.735; P=0.002) were independent risk factors for clinically relevant POPF (CR-POPF). The area under the receiver operating characteristic curve (AUC) values were 0.61, 0.64, and 0.63 on the Callery, Roberts, and Mungroop models, respectively; all were lower than those published in each external validation study. Conclusions: Western POPF prediction models performed less well when applied to Korean cohorts. Thus, a large-scale Eastern-specific and externally validated POPF prediction model is needed.

Neoadjuvant treatment (NAT) followed by surgery is the primary treatment for borderline resectable pancreatic cancer (BRPC). However, there is limited high-level evidence supporting the efficacy of NAT in BRPC. PubMed was searched to identify studies that compared the survival between BRPC patients who underwent NAT and those who underwent upfront surgery (UFS). The overall survival (OS) was compared using intention-to-treat (ITT) analysis. A total of 1204 publications were identified, and 19 publications with 21 data sets (2906 patients; NAT, 1516; UFS, 1390) were analyzed. Two randomized controlled trials and two prospective studies were included. Thirteen studies performed an ITT analysis, while six presented the data of resected patients. The NAT group had significantly better OS than the UFS group in the ITT analyses (HR: 0.63, 95% CI = 0.53–0.76) and resected patients (HR: 0.68, 95% CI = 0.60–0.78). Neoadjuvant chemotherapy with gemcitabine or S-1 and FOLFIRINOX improved the survival outcomes. Among the resected patients, the R0 resection and node-negativity rates were significantly higher in the NAT group. NAT improved the OS, R0 resection rate, and node-negativity rate compared with UFS. Standardizing treatment regimens based on high-quality evidence is fundamental for developing an optimal protocol.

Purpose The measurement of stool elastase (SE) level is useful for evaluating pancreatic exocrine function. This study aimed to determine the risk factors for severe exocrine pancreatic insufficiency (EPI) after pancreatoduodenectomy (PD), and analyze serial changes in nutritional markers and weight based on the SE level. Methods Among patients who underwent PD for periampullary disease, patients whose preoperative and postoperative SE levels were measured were included in the study. The deteriorated (exocrine function) group comprised patients whose SE levels decreased from ≥100 µg/g preoperatively to

Purpose Although serum CEA and CA 19-9 have been widely utilized for the diagnosis of gallbladder cancer (GBC), few studies have examined the diagnostic performance of them. This study aimed to investigate the diagnostic performance of these 2 biomarkers and demonstrate their clinical usefulness in diagnosing GBC. Methods Between January 2000 and March 2020, a total of 751 GBC patients and 2,310 normal controls were included. Serum CEA and CA 19-9 were measured preoperatively. Receiver operating characteristic curves were obtained, and the sensitivity and specificity of each biomarker were evaluated. Results In terms of differentiating GBC from the control, the sensitivity and specificity of serum CEA at 5 ng/mL was 12.1% and 99.1%, respectively, and those of serum CA 19-9 at 37 IU/mL were 28.7% and 94.5%, respectively. The optimal cutoff values of CEA and CA 19-9 were set to 2.1 ng/mL and 26 IU/mL in the receiver operating characteristic curves, respectively. The sensitivities of CEA and CA 19-9 at new cutoff values slightly increased but remained low (CEA, 42.9%; CA 19-9, 38.2%). When differentiating early-stage GBC from advanced tumor, the sensitivity and specificity, were 14.2% and 96.1% for CEA (cutoff value, 5 ng/mL) and 33.6% and 90.1% for CA 19-9 (cutoff value, 37 IU/mL), respectively. Conclusion Serum CEA and CA 19-9 levels are not suitable for screening GBC patients from controls. New promising biomarkers with higher sensitivity should be explored.

To identify features on preoperative MR imaging with diffusion-weighted imaging (DWI) for predicting next-generation sequencing (NGS)-based tumor cellularity and patient outcome after surgical resection of pancreatic ductal adenocarcinoma (PDAC).This retrospective study included 105 patients with surgically resected PDAC who underwent preoperative MR imaging with DWI. Tumor cellularity was measured using molecular techniques and bioinformatics methods. Clinico-pathologic findings including tumor T stage for predicting disease-free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards model. Important MR imaging findings including apparent diffusion coefficient (ADC) value of PDAC and modified ADC value (the ratio of the ADC value of PDAC to the ADC value of the spleen) for predicting higher tumor cellularity (≥ 30%) and poor prognosis were also identified.The median DFS and OS were 12.0 months [95% confidence interval (CI), 8.0-17.0] and 22.0 months (95% CI, 18.0-29.0), respectively. Higher T stage (T3/4) [hazard ratio (HR), 7.720, (95% CI 1.072, 55.612); p = 0.048] and higher tumor cellularity [HR, 1.599 (95% CI, 1.003-2.548); p = 0.048] were significantly associated with worse DFS. Among MR imaging features, the modified ADC value was significantly associated with tumor cellularity [odds ratio, 0.068 (95% CI, 0.012-0.372); p = 0.002], and PDAC with lower modified ADC value [≤ 1.40 (cutoff value)] showed significantly shorter median DFS than PDAC with higher modified ADC value [8 months (95% CI, 4-12) vs. 16 months (95% CI, 10-29); HR, 1.713 (95% CI, 1.073-2.735), log-rank p = 0.024].Higher NGS-based tumor cellularity may be a negative prognostic factor in pancreatic cancer after resection, and modified ADC value derived from DWI could be helpful in predicting tumor cellularity and patient surgical outcome with regard to recurrence.

Legumes are rich sources of essential nutrients, and their potential health benefits were reported in many studies. Several studies showed a positive effect of legumes on obesity, but randomised clinical trials are limited in the Korean population. The present intervention study investigated the impact of legumes on body weight in obese Korean subjects. A total of 400 participants (BMI ≥ 25 kg/m2) were randomised into two groups. The legume-enriched diet (LD) group replaced one-third of their refined rice consumption with legumes three times per day as a carbohydrate source. In contrast, the usual diet (UD) group consumed their UD. The mean weight loss at 12 weeks was 2·87 (sem 0·21) kg and 0·17 (sem 0·11) kg in the LD and UD, respectively, which was significantly different between the groups (P < 0·001). HDL-cholesterol and adiponectin levels were increased, and levels of glucose, insulin, TAG, and 8-epi-PGF2α and the homoeostasis model assessment of insulin resistance (IR) index value decreased at 12 weeks compared with baseline in the LD. The consumption of legumes may accelerate weight loss accompanied by regulation of adiponectin and 8-epi-PGF2α in obese subjects. In particular, legumes seemed to induce significant changes in BMI by increasing adiponectin in females. Additionally, increases in plasma adiponectin due to greater substantial weight loss may be related to the improvement in IR.

BACKGROUND/PURPOSE The current study aimed to develop a prediction model using a multi-marker panel as a diagnostic screening tool for pancreatic ductal adenocarcinoma. METHODS Multi-center cohort of 1991 blood samples were collected from January 2011 to September 2019, of which 609 were normal, 145 were other cancer (colorectal, thyroid, and breast cancer), 314 were pancreatic benign disease, and 923 were pancreatic ductal adenocarcinoma. The automated multi-biomarker Enzyme-Linked Immunosorbent Assay kit was developed using three potential biomarkers: LRG1, TTR, and CA 19-9. Using a logistic regression model on a training data set, the predicted values for pancreatic ductal adenocarcinoma were obtained, and the result was classification into one of the three risk groups: low, intermediate, and high. The five covariates used to create the model were sex, age, and three biomarkers. RESULTS Participants were categorized into four groups as normal (n = 609), other cancer (n = 145), pancreatic benign disease (n = 314), and pancreatic ductal adenocarcinoma (n = 923). The normal, other cancer, and pancreatic benign disease groups were clubbed into the non-pancreatic ductal adenocarcinoma group (n = 1068). The positive and negative predictive value, sensitivity, and specificity were 94.12, 90.40, 93.81, and 90.86, respectively. CONCLUSIONS This study demonstrates a significant diagnostic performance of the multi-marker panel in distinguishing pancreatic ductal adenocarcinoma from normal and benign pancreatic disease states, as well as patients with other cancers.

Background Pancreatic resection has higher postoperative mortality and morbidity rates than other abdominal operations. Some centers have reported remarkable postoperative outcomes of minimally invasive surgery. This study investigated the chronological trends of pancreatectomies by analyzing a large-scale database. Methods The medical records of 5,175 patients who underwent pancreatic resection between 1961 and 2019 at a single institution were reviewed. To investigate the chronological change in survival outcomes of periampullary cancer, the survival data of 3,108 patients were analyzed. Results Patient age and the proportion with pancreatic cancer have increased over time. From 2015 to 2019, pancreatic cancer was the most common cause for resection (35.9%), followed by pancreatic cysts (24.8%) and common bile duct cancer (13.4%). The incidence of postoperative complications tended to decrease over time (26.0% from 2000 to 2004; 20.8% from 2015 to 2019). A comparison of survival outcomes of periampullary malignancies by period revealed that patients with pancreatic cancer significantly improved (5-year survival rate: 14.4% before 2000 vs. 15.2% from 2000 to 2009 vs. 29.0% after 2009, p Conclusions Postoperative outcomes of pancreatic resection have improved over the past few decades. To improve outcomes in the future, an active multidisciplinary approach and postoperative management are required.