Clinicopathologic Features of Polypoid Lesions of the Gallbladder and Risk Factors of Gallbladder Cancer

It is difficult to differentiate benign and malignancy in polypoid lesions of the gallbladder (PLG) by solely depending on imaging studies. Therefore clinicopathologic features of benign and malignant polyps are compared in an attempt to identify the risk factors of malignant polypoid lesions. The medical records of 291 patients who were confirmed to have PLG through cholecystectomy were reviewed and analyzed for age, sex, symptom, associated gallstone, morphology of PLG, size of PLG, number of PLG, and preoperative tumor markers. Benign PLG was found in 256 patients (88.0%) and malignant PLG in 35 patients (12.0%). Compared with benign group, the malignant group were older (61.1 yr vs. 47.1 yr, P<0.001), more often accompanied with symptoms (62.9% vs. 28.9%, P<0.001). Malignant PLG tended to be sessile (60.0% vs. 10.5%, P<0.001), larger (28.0 mm vs. 8.6 mm, P<0.001) and single lesion (65.7% vs. 44.1%, P<0.016). Age over 60 yr (P=0.021, odds ratio [OR], 8.16), sessile morphology (P<0.001, OR, 7.70), and size over 10 mm (P=0.009, OR, 8.87) were identified as risk factors for malignant PLG. Careful decision making on therapeutic plans should be made with consideration of malignancy for patients over 60 yr, with sessile morphology of PLG, and with PLG size of over 10 mm

Correction to: Comprehensive proteome and phosphoproteome profiling shows negligible influence of RNAlater on protein abundance and phosphorylation

In the version of this article that was originally published [1], some information in the Acknowledgements section was omitted.This study was supported by the Collaborative Genome Program for Fostering New Post-Genome Industry (NRF-2017M3C9A5031397) and the Brain Research Program (Grant No. NRF-2017M3C7A1027472) through the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT) of Republic of Korea. This work was also supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. 2019R1C1C1006262). The Biospecimens and data used in this study were provided by the Biobank of Seoul National University Hospital, a member of Korea Biobank Network (SNUH2017-0021)

Defective Localization With Impaired Tumor Cytotoxicity Contributes to the Immune Escape of NK Cells in Pancreatic Cancer Patients

Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL, PBMC, and autologous tumor cells from 80 enrolled resectable PDAC patients to comprehend the NK cell defects within PDAC. Extremely low frequencies of NK cells (&lt;0.5%) were found within PDAC tumors, which was attributable not to the low expression of tumor chemokines, but to the lack of chemokine receptor, CXCR2. Forced expression of CXCR2 in patients' NK cells rendered them capable of trafficking into PDAC. Furthermore, NK cells exhibited impaired cell-mediated killing of autologous PDAC cells, primarily due to insufficient ligation of NKG2D and DNAM-1, and failed to proliferate within the hypoxic tumor microenvironment. Importantly, these defects could be overcome by ex-vivo stimulation of NK cells from such patients. Importantly, when the proliferative capacity of NK cells in vitro was used to stratify patients on the basis of cell expansion, patients whose NK cells proliferated &lt;250-fold experienced significantly lower DFS and OS than those with ≥250-fold. Ex-vivo activation of NK cells restored tumor trafficking and reactivity, hence provided a therapeutic modality while their fold expansion could be a potentially significant prognostic indicator of OS and DFS in such patients

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials

BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers.METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test.RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501).CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.</p

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) <= 2 cm: Study Protocol for a Prospective Observational Study

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery. Methods: ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017–2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan. Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach

마이크로 RNA 발현 양상에 따른 췌장암의 아형과 예후인자로서의 가치

학위논문 (박사)-- 서울대학교 대학원 : 의학과 외과학 전공, 2016. 8. 김선회.Background and Aim Altered microRNAs (miRNA) expression, a typical feature of many cancers, is reportedly associated with prognosis according to several studies. Although numerous studies on miRNAs in pancreatic ductal adenocarcinoma have also attempted to identify prognostic biomarkers, more large-scale clinical studies are needed to establish the clinical significance of the results. Present study aimed to identify prognosis-related molecular subtypes of primary pancreas cancers using miRNA expression profiling. Methods Expression profiles of 1,733 miRNAs were obtained by using microarray analysis of 104 pancreatic tumors of Korean patients. To detect subgroups informative in predicting the patients prognosis, unsupervised clustering method was applied and then the association of the molecular subgroups with survival time was analyzed. Then, classifiers to predict the subgroup using penalized regression models were identified. Results Three PDAC tumor subtypes associated with prognosis based on miRNA expression profiles were determined. These subtypes showed significantly different survival time for patients with the same clinical conditions. This demonstrates that this prognostic molecular subgroup has independent prognostic utility. The molecular subtypes can be predicted with classifiers of 19 miRNAs. Of the 19 signature miRNAs, miR-106b-star, miR-324-3p, and mir-615 were related to a p53 canonical pathway, and miR-324, miR-145-5p, miR-26b-5p, and miR-574-3p were related to a Cox-2 centered pathway. Conclusions This study demonstrated that pancreatic cancers may be classified into molecular subtypes based on their miRNA profiles and could be used to predict prognosis. Several classifier miRNAs can discriminate these prognostic molecular subtypes. Further studies are needed for validation.Introduction 1 Material and Methods 3 Results 8 Discussion 14 References 20 Tables 27 Figures 38 국문 초록 45Docto