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When planning pancreaticoduodenectomy for pancreatic head cancer, the prevalence of anatomical variation of the proximal jejunal vein (PJV), the associated short-term surgical outcomes, and the level of PJV convergence to the superior mesenteric vein must be carefully analyzed from both technical and oncological points of view. The prevalence of the first jejunal trunk (FJT) and PJV located ventral to the superior mesenteric artery is 58%-88% and 13%-37%, respectively. Patients with the FJT had a larger amount of intraoperative bleeding and a higher proportion of patients requiring transfusions compared to those without a common trunk. The risk of transfusion was higher in patients with ventral PJV compared to those with dorsal PJV. Although less frequent, sacrificing the FJT can result in fatal venous congestion of the jejunum. Therefore, a well-planned approach for pancreaticoduodenectomy, based on preoperative evaluation of anatomical variation in the PJV, may help reduce intraoperative bleeding and postoperative morbidity. Additionally, the importance of invasion into the PJVs should be revisited in terms of resectability and oncological clearance.

This randomized clinical trial was performed to compare pain scales between intravenous patient-controlled analgesia (IV-PCA) and patient-controlled epidural analgesia (PCEA) in patients undergoing open surgical resection of major pancreatobiliary malignancies.One hundred ten patients were randomly assigned to the PCEA or IV-PCA group. We compared the numeric rating scale pain score during ambulation on postoperative day (PD) 2 and at rest (at 06:00, 12:00, and 18:00) from PD 1 to 7, the serum level of troponin I on PD 1, and the incidence of postoperative complications between the two groups.There were no significant differences in the pain scores during ambulation on PD 2, at rest up to PD 7, serum troponin I level, and postoperative complication rates. The incidences of nausea (20.4% vs. 6.3%; p = 0.039) and drowsiness (20.4% vs. 0%; p = 0.001) were higher in the IV-PCA group and the rate of dysuria (0% vs. 14.6%; p = 0.004) was higher in the PCEA group.PCEA showed no superiority over IV-PCA in terms of postoperative pain relief or morbidity after major open surgery for pancreatobiliary malignancies. The method of analgesia should be considered based the characteristics of the patient, surgeon, anesthesiologist, and institute.

Supported by the expanding indications for neoadjuvant therapy (NAT) for advanced pancreatic cancer (PC), the concept of resectability has evolved from being mostly based on the anatomical tumor extent to considering the biological and conditional factors relevant to prognosis. Therefore, it is more reasonable to define the “criteria for surgical resection” instead of using the “(technical) resectability criteria.” NAT has been used in resectable PCs (RPC) with a high risk of early systemic recurrence, as predicted by various biological or anatomical markers. Moreover, the indications for NAT followed by conversion surgery or adjuvant surgery for borderline resectable or locally advanced PC (LAPC) are gradually expanding. Therefore, it is important to define the RPC group that will benefit from NAT and the LAPC group that will benefit from post-NAT surgery. At diagnosis, population-based approaches, such as prognostic stratification and staging systems and personalized outcome-based approaches using prognostic prediction models can be used to determine the criteria for treatment options. Standardized indications for conversion surgery are needed for patients who are initially treated with NAT. In addition to imaging-based morphological criteria, biological criteria, including CA19-9, and various metabolic criteria can be used to establish predicted outcome-based criteria. Multicenter collaboration is required to develop a large database with standardized data collection for various biomarkers and response data after NAT to establish more accurate outcome prediction models to define the new resectability criteria.

Purpose Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.Materials and Methods Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.Results Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.Conclusion Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

SARS-CoV-2, like other RNA viruses, has a propensity for genetic evolution owing to the low fidelity of its viral polymerase. This evolution results in the emergence of novel variants with different characteristics than their ancestral strain. Several recent reports have described a series of novel SARS-CoV-2 variants. Some of these have been identified as variants of concern (VOCs), including alpha (B.1.1.7, Clade GRY), beta (B.1.351, Clade GH), gamma (P.1, Clade GR), and delta (B.1.617.2, Clade G). VOCs are likely to have some effect on transmissibility, antibody evasion, and changes in therapeutic or vaccine effectiveness. However, the physiological and virological understanding of these variants remains poor. We demonstrated that these four VOCs exhibited differences in plaque size, thermal stability at physiological temperature, and replication rates. The mean plaque size of beta was the largest, followed by those of gamma, delta, and alpha. Thermal stability, evaluated by measuring infectivity and half-life after prolonged incubation at physiological temperature, was correlated with plaque size in all variants except alpha. However, despite its relatively high thermal stability, alpha’s small plaque size resulted in lower replication rates and fewer progeny viruses. Our findings may inform further virological studies of SARS-CoV-2 variant characteristics, VOCs, and variants of interest. These studies are important for the effective management of the COVID-19 pandemic.IMPORTANCEThe global pandemic caused by SARS-CoV-2 continues to persist, due in part to mutations that have resulted in the emergence of different variants. Many of these variants have become more virulent and infectious than their ancestral strain, resulting in an ever-increasing spread. However, our virological understanding of these variants remains poor. Here, we directly compared the plaque size, stability, and replication kinetics of four SARS-CoV-2 variants of concern following prolonged incubation at physiological temperatures. Our observations may help to characterize each variant in terms of their interactions with host factors and responses to environmental conditions. We also believe that our evaluations will improve understanding of the emergence of new variants and contribute to controlling their spread.

Purpose Hospital-based clinical studies have limitations in holistic assessment of cancer treatment and prognosis, as they omit out-of-hospital patients including elderly individuals. This study aimed to investigate trends in initial treatment and corresponding prognosis of patients with exocrine pancreatic cancer (EPC) in Korea. Materials and Methods The Korea Central Cancer Registry data of patients with EPC from 2006 to 2017 were retrospectively reviewed. We defined the first course of treatment (FT) as the cancer-directed treatment administered within four months after cancer diagnosis according to Surveillance, Epidemiology, and End results (SEER) program. Results Among 62,209 patients with EPC, localized and regional (LR) SEER stage; patients over 70 years old; and ductal adenocarcinoma excluding cystic or mucinous (DAC) accounted for 40.6%, 50.1%, and 95.9%, respectively. "No active treatment" (NT, 46.5%) was the most frequent, followed by non-surgical FT (28.7%) and surgical FT (22.0%). Among 25,198 patients with LR EPC, surgical FT increased (35.9% to 46.3%) and NT decreased (45.0% to 29.5%) from 2006 to 2017. The rate of surgical FT was inversely related to age (55.1% [

BACKGROUND AND PURPOSE: In certain cases of pediatric patients with Moyamoya disease undergoing encephaloduroarteriosynangiosis (EDAS) treatment, the posterior auricular artery can be used as an alternative when the parietal branch of the superficial temporal artery is unavailable. In this study, anatomic variations of the superficial temporal and posterior auricular arteries in pediatric patients with Moyamoya disease and postoperative outcomes of posterior auricular artery-EDAS are explored. MATERIALS AND METHODS: Medical records of 572 patients with Moyamoya disease who underwent surgical procedures from 2007 to 2017 at the Seoul National University Children’s Hospital were reviewed. Anatomic classifications of the superficial temporal and posterior auricular arteries were based on previous classifications. Postoperative hemodynamic changes of posterior auricular artery-EDAS were analyzed using the Matsushima grade. Also, Karnofsky Performance Scale and mRS scores of posterior auricular artery-EDAS cases were reviewed to identify postoperative clinical outcomes. RESULTS: Among 1144 hemispheres, 24 were considered posterior auricular artery-EDAS candidates (2.1%). Of those, 10 hemispheres underwent posterior auricular artery-EDAS (41.7%, in total hemispheres 0.9%). Comparing the Matsushima grades of the superficial temporal artery-EDAS and posterior auricular artery-EDAS groups showed similar postoperative revascularization. Postoperative Karnofsky Performance Scale and mRS scores of patients having undergone posterior auricular artery-EDAS did not show deterioration. CONCLUSIONS: In approximately 2% of pediatric patients with Moyamoya disease for whom the superficial temporal artery is unavailable as the EDAS donor, the posterior auricular artery can be considered an alternative. On the basis of the results, the clinical outcome of posterior auricular artery-EDAS was not inferior to that of superficial temporal artery-EDAS. Hence, we suggest an in-depth consideration of the posterior auricular artery as the donor artery if the superficial temporal artery parietal branch is unavailable.

The superior mesenteric artery (SMA) first approach and meso-pancreas excision (MPE) during pancreatoduodenectomy (PD) for pancreatic head cancer have been suggested for complete local tumor control, less operative blood loss, and early determination of resectability. However, SMA-first approach is merely a mode of approach and the concept of MPE has been challenged due to its anatomical obscurity. Dissection around proximal mesenteric vessels, superior mesenteric vein and SMA, is a critical procedure point for local tumor control as tumor infiltration is frequently observed both at the time of initial diagnosis and recurrence. The meso-pancreas, which encompasses the soft tissue between the uncinated process and SMA, does not include all the aforementioned points of proximal mesenteric areas. Therefore, the authors propose a new terminology named, "en bloc proximal peri-mesenteric clearance (PPMC)", to describe the removal of all the lymph nodes including soft tissue around proximal mesenteric vessels, especially the SMA, to ensure complete local tumor control of pancreatic head cancer. The SMA-first approach applied either by the mesenteric approach or supra-colic approach can make this procedure more feasible. The extent of the circumferential dissection of the peri-SMA nerve plexus can be adjusted according to the primary disease. PPMC including the removal of all lymph nodes around the proximal SMA may be considered as a standard extent of PD for pancreatic head cancer.

Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related deaths in Korea. Despite the increasing incidence and high mortality rate of pancreatic cancer, there are no appropriate surgical practice guidelines for the current domestic medical situation. To enable standardization of management and facilitate improvements in surgical outcome, a total of 10 pancreatic surgical experts who are members of Korean Association of Hepato-Biliary-Pancreatic Surgery have developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. This is an English version of the Korean Surgical Practice Guideline for Pancreatic Cancer 2022. This guideline includes 13 surgical questions and 15 statements. Due to the lack of high-level evidence, strong recommendation is almost impossible. However, we believe that this guideline will help surgeons understand the current status of evidence and suggest what to investigate further to establish more solid recommendations in the future.

Background IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. Methods Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. Results Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the “Jang & Kim's modified anatomical classification,” 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010–4.433]). Conclusions This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

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)

Background Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small-cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited response to ICIs remain unclear. Patients and methods We carried out whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled before anti-programmed cell death 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy. Detailed clinical characteristics were collected on these patients. We designed a new method to estimate human leukocyte antigen (HLA)-corrected tumor mutation burden (TMB), a modification which considers the loss of heterozygosity of HLA from conventional TMB. We carried out external validation of our findings utilizing 89 NSCLC samples and 110 melanoma samples from two independent cohorts of immunotherapy-treated patients. Results Homology-dependent recombination deficiency was identified in 37 patients (18.7%) and was associated with longer progression-free survival (PFS; P = 0.049). Using the HLA-corrected TMB, non-responders to ICIs were identified, despite having a high TMB (top 25%). Ten patients (21.3% of the high TMB group) were reclassified from the high TMB group into the low TMB group. The objective response rate (ORR), PFS, and overall survival (OS) were all lower in these patients compared with those of the high TMB group (ORR: 20% versus 59%, P = 0.0363; PFS: hazard ratio = 2.91, P = 0.007; OS: hazard ratio = 3.43, P = 0.004). Multivariate analyses showed that high HLA-corrected TMB was associated with a significant survival advantage (hazard ratio = 0.44, P = 0.015), whereas high conventional TMB was not associated with a survival advantage (hazard ratio = 0.63, P = 0.118). Applying this approach to the independent cohorts of 89 NSCLC patients and 110 melanoma patients, TMB-based survival prediction was significantly improved. Conclusion HLA-corrected TMB can reconcile the observed disparity in relationships between TMB and ICI responses, and is of predictive and prognostic value for ICI therapies.

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.

Purpose Pancreaticoduodenectomy (PD) is recently performed in older cancer patients. The complication rate of PD is high. The present study was to compare the postoperative short- and long-term outcomes of PD in between older patients and younger patients. Methods Between 2000 and 2014, patients who underwent PD due to periampullary cancers were enrolled. Patients aged 75 years or over were included in the older group. Results Total 1,249 patients were enrolled in this study and 168 patients (13.5%) were included in the older group. Postoperative complication rates, duration of postoperative hospital stay, and 30-day mortality were comparable between the 2 groups, although the admission rate of intensive care unit postoperatively was higher in the older adult group (20.8% vs. 10.5%, P < 0.001). In terms of long-term outcomes, 5-year overall survival rate was lower in the older group (23.4% vs. 41.8%, P < 0.001), and 5-year cumulative recurrence rate was higher in the older group without statistical significance (63.9% vs. 57.9%, P = 0.095). However, there were no statistical differences of cumulative recurrence in pancreatic cancer patients (81.5% vs. 82.5%, P = 0.805). Conclusion PD for periampullary cancer is a safe and feasible treatment in the older patients. The treatment modality for obtaining better survival outcomes will be investigated.

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 Lymph-node (LN) metastasis is an important prognostic factor in resected pancreatic cancer. In this study, the prognostic value of American Joint Committee on Cancer (AJCC) 8th edition N stage, lymph-node ratio (LNR), and log odds of positive lymph nodes (LODDS) in resected pancreatic cancer was investigated. Methods Between January 2005 and December 2017, there were 351 patients with pancreatic cancer treated with R0 resection and adjuvant therapy at Seoul National University Hospital. Relationships between the three LN parameters and overall survival (OS) and recurrence-free survival (RFS) were evaluated using a log-rank test and Cox proportional hazard regression model. Each multivariate-adjusted LN parameter was internally validated by bootstrap-corrected Harrell’s C-index. Results The mean duration from surgery to adjuvant therapy was 47.6 ± 17.4 days. In total, the median OS and RFS was 31.7 (95% CI, 27.2-37.2) and 15.4 (95% CI, 13.5-17.7) months. The three LN classification systems were significantly correlated with OS and RFS in log-rank tests and multivariate-adjusted models (all p C–index = 0.65). LNR also showed the highest C-index in subgroup analysis, classified by adjuvant therapy modality. LNR and the AJCC 8th edition LN classification system were significantly associated with loco-regional recurrence (p = 0.026 and p = 0.027, respectively). Conclusions LNR, which showed the best prognostic performance and significant relationship with loco-regional recurrence, can help further stratify the patients and establish an active treatment plan.

Biliary tract cancer (BTC) has been inconsistently identified according to its location in epidemiological and clinical studies. This study retrospectively reviewed the treatment pattern and prognosis of BTC according to tumor location using the Korea Central Cancer Registry data of 97,676 patients with BTC from 2006 to 2017. The proportion of localized and regional Surveillance, Epidemiology, and End Results (SEER) stage was the highest in ampulla of Vater (AoV, 78.2%) cancer, followed by extrahepatic bile duct (BD, 68.3%), gallbladder (GB, 52.6%), and intrahepatic BD (49.5%) cancers. Overall, the “no active anti-cancer treatment” rate was the highest in intrahepatic BD (52.8%), followed by extrahepatic BD (49.5%), GB (39.6%), and AoV cancers (28.9%). The 5-year relative survival rate was the highest in AoV (48.5%), followed by GB (28.5%), extrahepatic BD (19.9%), and intrahepatic BD (10.8%) cancers, which significantly improved over time, except for intrahepatic BD cancer. In the localized and regional stage, older patients had a higher risk of receiving no active anti-cancer treatment in each tumor location after adjusting for period and sex. BTC statistics should be reported separately according to tumor location due to its distinct SEER stage distribution, treatment pattern, and prognosis. Care should be taken in elderly patients to reduce the rate of no active anti-cancer treatment.

Background: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking. Methods: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3. Results: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98). Conclusion: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms.

Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post-translational cancer hallmark and the consequences thereof remain elusive. Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In both cancer cell cultures and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycoproteomes revealed that fucosylation of the antioxidant PON1 is a critical component of the therapy-induced secretome. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Non-specific and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance.

In this Letter, the authors investigate the electrical characteristics of amorphous indium-tin-gallium-zinc-oxide (a-ITGZO) thin-film transistors (TFTs) under positive gate bias stress (PBS). An as-prepared a-ITGZO TFT exhibits a mobility of 26.05 cm 2 /V·s, subthreshold swing of 183 mV, threshold voltage of -0.33 V, and on/off ratio of 1.34 × 10 8 . These electrical characteristics deteriorate upon the application of PBS. The proposed experiments and simulations reveal that this deterioration can be attributed to the increase in the density of acceptor-like conduction band-tail states and donor-like Gaussian states within the bandgap of the a-ITGZO channel material.

OBJECTIVE: To establish an international core set of patient-reported outcomes (PROs) selected by both patients and healthcare providers (HCPs) from the United States (US), Europe, and Asia. SUMMARY BACKGROUND DATA: PROs are increasingly recognized in pancreatic cancer studies. There is no consensus on which of the many available PROs are most important. METHODS: A multicenter Delphi study among patients with pancreatic cancer (curative- and palliative-setting) and HCPs in 6 pancreatic centers in the US (Baltimore, Boston), Europe (Amsterdam, Verona), and Asia (Mumbai, Seoul) was performed. In round 1, participants rated the importance of 56 PROs on a 1 to 9 Likert scale. PROs rated as very important (scores 7-9) by the majority (≥80%) of curative- and/or palliative-patients as well as HCPs were included in the core set. PROs not fulfilling these criteria were presented again in round 2, together with feedback on individual and group ratings. Remaining PROs were ranked based on the importance ratings. RESULTS: In total 731 patients and HCPs were invited, 501 completed round 1, and 420 completed both rounds. This included 204 patients in curative-setting, 74 patients in palliative-setting, and 142 HCPs. After 2 rounds, 8 PROs were included in the core set: general quality of life, general health, physical ability, ability to work/do usual activities, fear of recurrence, satisfaction with services/care organization, abdominal complaints, and relationship with partner/family. CONCLUSIONS: This international Delphi study among patients and HCPs established a core set of PROs in pancreatic cancer, which should facilitate the design of future pancreatic cancer trials and outcomes research.

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.

Scintillation crystals are commonly used for direct detection of weakly interacting massive particles (WIMPs), which are suitable candidates for a particle dark matter. It is well known that the scintillation light yields are different for electron recoil and nuclear recoil. To calibrate the energies of WIMP-induced nuclear recoil signals, the quenching factor (QF) needs to be measured, which is the light yield ratio of the nuclear recoil to electron recoil. Measurements of the QFs for Na and I recoils in a small (2 cm × 2 cm × 1.5 cm) NaI(Tl) crystal are performed with 2.43-MeV mono-energetic neutrons generated by deuteron-deuteron fusion. Depending on the scattering angle of the neutrons, the energies of the recoiled ions vary in the range of 9–152 keV for Na and 19–75 keV for I. The QFs of Na are measured at 9 points with values in the range of 10–23% while those of I are measured at 4 points with values in the range of 4–6%.

We calculated the transition of edge pedestal properties in jϕ-α space for a KSTAR-like plasma and compared the results with those from the analytical transition model. The transition is from a critical equilibrium that is marginally stable to the peeling or the ballooning mode to another critical equilibrium when plasma parameters such as triangularity, elongation, and βp change. The transition should not be confused with the L-H transition. We have divided the transition into two. The first transition is when plasma parameters change for fixed pedestal width while the second transition is when the pedestal width changes for fixed plasma parameters. The direction of the first transition when triangularity or elongation increases is as such that jϕ decreases and α increases. The direction of the first transition with varying βp depends on the choice of how the temperature or the current density is modified. The direction of the second transition is determined from the stability condition of the new equilibrium after the first transition.

Backgrounds/aims We performed a retrospective, single-center cohort study to evaluate the impact of various treatment modalities and recent changes in treatment modalities, including the increased application of chemotherapy, on survival in patients with pancreatic cancer. Methods All patients with pancreatic cancer who were diagnosed and treated at Seoul National University Hospital between January 2007 and December 2014 were registered in a prospective clinical database and included in this retrospective study. All patients' radiologic imaging diagnoses were re-reviewed according to the National Cancer Center Network guidelines. The patients were divided into four groups according to their clinical stage, and each clinical stage group was further divided into four groups according to treatment modality. Results Overall, 475 (28.9%) patients had resectable pancreatic cancer, 129 (7.8%) patients borderline resectable pancreatic cancer, 384 (23.3%) patients locally advanced pancreatic cancer, and 658 (40.0%) patients metastatic pancreatic cancer. Among the patients with borderline resectable pancreatic cancer, the median survival was significantly longer in the neoadjuvant therapy (NAT)+surgery groups (24 months) than the surgery without NAT (16 months) group (p=0.049). A multivariate survival analysis revealed that compared with the surgery group, the 5-year mortality risk was decreased by 35% in the NAT+surgery group (24 vs. 20 months, p=0.045). Conclusions This retrospective cohort study showed that the rates of resectable and surgically treatable pancreatic cancer were 29.1% and 32.2%, which are higher than those reported previously, and aggressive NAT for select advanced-stage patients could lead to better survival outcomes.

We investigated the vascularity of intrahepatic cholangiocarcinoma (ICC) on computed tomography (CT) images and its association with ICC recurrence after surgery and prognosis after recurrence.In this retrospective study, the data of patients who underwent resection with curative intent for ICC between March 2001 and July 2017 were reviewed. Clinicopathologic factors including tumor vascularity (hypovascular, rim-enhancement, and hypervascular) on CT that could affect recurrence-free survival (RFS) were assessed. The association between the vascularity of recurrent ICC and survival after recurrence was also analyzed.Overall, 147 patients were enrolled and followed up for a median of 36.1 months of which, 101 (68.7%) experienced ICC recurrence. Hypervascularity of ICC showed better RFS than other vascularities [rim-enhanced image hazard ratio (HR), 3.893; 95% confidence interval (CI), 1.700-8.915, p = 0.001; hypovascular image HR, 6.241; 95% CI, 2.670-14.586, p 0.001]. The hypervascular recurrent ICC was also significantly associated with better survival after recurrence (log-rank test, p 0.001).Hypervascular ICC was associated with a longer RFS and better prognosis after recurrence. The vascularity of ICC on CT may be a noninvasive, accessible, and useful prognostic index, and should be considered while planning treatment.

International audience; The GBAR (Gravitational Behavior of Antihydrogen at Rest) experiment at CERN requires efficient deceleration of 100 keV antiprotons provided by the new ELENA synchrotron ring to synthesize antihydrogen. This is accomplished using electrostatic deceleration optics and a drift tube that is designed to switch from -99 kV to ground when the antiproton bunch is inside – essentially a charged particle “elevator” – producing a 1 keV pulse. We describe the simulation, design, construction and successful testing of the decelerator device at -92 kV on-line with antiprotons from ELENA.

COSINE-100 is a dark matter detection experiment that uses NaI(Tl) crystal detectors operating at the Yangyang underground laboratory in Korea since September 2016. Its main goal is to test the annual modulation observed by the DAMA/LIBRA experiment with the same target medium. Recently DAMA/LIBRA has released data with an energy threshold lowered to 1 keV, and the persistent annual modulation behavior is still observed at 9.5 σ . By lowering the energy threshold for electron recoils to 1 keV, COSINE-100 annual modulation results can be compared to those of DAMA/LIBRA in a model-independent way. Additionally, the event selection methods provide an access to a few to sub-GeV dark matter particles using constant rate studies. In this article, we discuss the COSINE-100 event selection algorithm, its validation, and efficiencies near the threshold.

BACKGROUND: In the World Health Organization (WHO) classification, gallbladder (GB) intraepithelial lesions are grouped as flat or tumoral, according to their morphological features. The purpose of this study was to investigate the relationship between the morphologies and clinical features of GB cancer (GBC) and to examine the feasibility of using morphologic classification as a prognostic factor. METHODS: From January 2000 to December 2012, the available pathologic slide reviews of 381 patients were analyzed at the Seoul National University Hospital. All pathologic slides were evaluated by two pancreato-biliary tract pathology experts. GBCs were categorized into eight groups (Flat: F1-2, Borderline, Tumoral: Tu1-5), according to the thickness of the mucosal lesion, histologic patterns of the mucosa under microscopy, invasion extent, and patient history of premalignant lesions. According to the morphologic classification, clinical features were compared and survival analysis was performed. RESULTS: In three groups, flat lesions comprised 179 (46.9%) cases and borderline and tumoral comprised 97 (25.4%) and 105 (27.5%) cases, respectively. More favorable pathologic and clinical results were found within the tumoral group. The borderline group had an intermediate tendency between flat and intraluminal in clinicopathologic parameters. In the curative resected T2 stage group, the borderline group demonstrated an intermediate trend compared to that of the flat and tumoral groups, but this was statistically insignificant (P=0.08). CONCLUSIONS: Flat type GBCs show worse prognosis than tumoral GBCs. The morphological classifications between flat and tumoral on the basis of 1 cm and by papillary feature is feasible. Tumor morphology can be used as a reference while deciding the treatment plan, especially in T2 GBC.

Hypersensitive response (HR) is a robust immune response mediated by plant nucleotide-binding and leucine-rich repeat receptor (NLR). However, the early molecular event linking NLR to cell death is obscure. Here we demonstrate that NLR targets plasma membrane H+-ATPases (PMA) generating electrochemical potential across the membrane. CCA309, an autoactive N-terminal domain of pepper coiled-coil NLR (CNL), associates with PMAs and its autoactivity is affected by silencing or overexpression of PMA. CCA309-induced extracellular alkalization accompanied with membrane depolarization is followed by calcium influx and cell death. CCA309 interacts with C-terminal regulatory domain of PMA and 14-3-3 negatively affects CCA309-induced cell death. Moreover, pharmacological experiments with fusicoccin, an irreversible PMA activator, confirmed that CC- and CNL-mediated cell death occurred through inhibiting PMA. We propose PMAs as the primary target of plasma membrane-associated CNL to disrupt electrochemical homeostasis leading to HR cell death.

BACKGROUND/PURPOSE The aim of the present study was to identify the types of recurrence in pancreatic ductal adenocarcinoma (PDAC) and discover the frequent location of the local recurrence. METHODS This study included 361 patients with PDAC who underwent curative-intent surgery between 2007-2014. RESULTS Among 361 patients, 75.1% (n = 271) developed recurrence during the follow-up period. The 5-year overall survival rate of recurred patients was 8.3%. The patterns of recurrence were classified as local (17.7%), systemic (62.0%), and loco-systemic (20.3%). According to the preoperative tumor locations, patients with uncinate and head cancer showed higher rates of local recurrence than those with body and tail cancer (47.8% vs 17.2%, P

We present results from a search for solar axions with the COSINE-100 experiment. We find no evidence of solar axion events from a data-set of 6,303.9 kg$\cdot$days exposure and set a 90\,\% confidence level upper limit on the axion-electron coupling, $g_{ae}$, at 1.70~$\times$~$10^{-11}$ for an axion mass less than 1\,keV/c$^2$. This limit excludes QCD axions heavier than 0.59\,eV/c$^2$ in the DFSZ model and 168.1\,eV/c$^2$ in the KSVZ model., 7 pages, 8 figures