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Background/Aims Surveillance of premalignant pancreatic cystic lesions (PCLs) are considered one strategy for early detection of pancreatic cancer (PC). However, current evidence to help determine malignant potential and surveillance interval of incidental PCLs is still limited. We investigated clinical features and prognosis of PC arising around PCLs and PC arising from PCLs. Methods Patients who were found to have PCLs on imaging studies from 2010 to 2022 and diagnosed with PC during the follow-up were retrospectively analyzed. They were divided into two groups; PC arising around PCLs and PC arising from PCLs. The primary outcome was overall survival (OS). The risks of mortality were estimated using Cox analysis. Results Of 60 eligible patients, PC arose from PCLs in 23 cases (38.3%), and arose around PCLs in 37 cases (61.7%) after a median follow-up of 4 years. The median age was 65.0 years and 62.0 years in each group. Many PCLs were located in head portion and not solitary. In the group of PC arising from PCLs, poorly-differentiated PC occurred in 1 case (4.3%), whereas in the group of PC arising around PCLs, poorly-differentiated PC occurred in 7 cases (18.9%). Contrary to the group of PC arising from PCLs, there were more patients who underwent non-surgical treatment than those who underwent surgery in the group of PC arising around PCLs. OS was better for PC arising from PCLs than for PC arising around PCLs (67.8% vs. 36.4% at 2 years; p=0.0127). Consistently, the adjusted hazard ratio for mortality comparing the two groups was 3.2 (95%CI: 1.4-8.2; p=0.0095). Conclusion More PCs arose around PCLs than from PCLs, and PC arising around PCLs had a worse prognosis than PC arising from PCLs. These findings could provide important insight into surveillance of incidental PCLs for early detection of PC. [ABSTRACT FROM AUTHOR]

Desmoid tumors are rare benign tumors with aggressive fibroblastic proliferation. Although desmoid tumors do not metastasize, they have locally aggressive features and can cause a urinary fistula. Here, we report a case of a 35-year-old woman with Gardner syndrome who was diagnosed with an intra-abdominal desmoid tumor 1 year previously and who presented with a newly developed cystic mass lesion on a computed tomography scan. The cystic mass lesion was clinically diagnosed as an 니rin이na from the right 니reterotumoral fistula; th니s, surgical resection of the mass lesion was planned. However, Tc-99m diethylenetriamine pentaacetic acid renal scintigraphy revealed bilateral ureterotumoral fist니las; hence, the treatment plan was changed to conservative management. [ABSTRACT FROM AUTHOR]

Intraductal papillary mucinous tumor (IPMT) of the pancreas can be divided into three clinically distinct subtypes: main duct type, branch duct type and mixed type. Although it has been reported that the branch duct type IPMT is less invasive than the main duct type IPMT, we experienced a number of branch duct type IPMT having a poor prognosis. In the present study we surveyed the survival and recurrence rates according to the subtypes. Sixty-seven IPMT cases were studied to investigate clinical behavior according to the duct types. Diagnostic findings and late results of treatment were reviewed in 27 cases of the main duct type IPMT and in 35 cases of the branch duct type IPMT. There was no statistically significant difference in the survival analysis between the main duct type IPMT and the branch duct type IPMT ( P = 0.93). Seven patients (25.9%) died among the main duct type IPMT while six patients (17.1%) died among the branch duct type IPMT ( P = 0.36). Tumor recurrence was noticed in four patients (18.1%) among 22 operated main duct type IPMT and in two patients (6.9%) among 29 operated branch duct type IPMT ( P = 0.35). The long-term follow up result of the branch duct type IPMT is similar to that of the main duct type IPMT. Therefore, it is not safe just to monitor the branch duct type IPMT without operation. Surgery, whenever possible, is clearly the gold standard for treatment of IPMT, regardless of duct type. [ABSTRACT FROM AUTHOR]

Background/Aims Endoscopic retrograde biliary drainage (ERBD) is widely used as a drainage method for biliary obstruction. Biliary stents can be divided into plastic stent (PS) and metal stent. There are several limitations for PS including insufficient luminal diameter and short patency period. Up to date, many methods have been studied to improve the disadvantages of PS. The aim of this study is to evaluate the effect of advanced hydrophilic PS system using novel surface modification technique via vacuum plasma in swine model of biliary stricture. Methods Using six in vivo swine bile duct stricture model made by using radiofrequency ablation electrode and stent insertion, we evaluated bio durability of hydrophilic PS. The advanced hydrophilic polyethylene (PE) PSs (10 Fr, 90 mm) using surface modification technique via vacuum plasma and PE PSs without hydrophilic surface modification were inserted in all swine models of biliary stricture. Results Total of 12 PSs were inserted into the biliary stricture of six swine models, and all these PSs were successfully retrieved at 1-, 3- and 5-month later. PE PSs with hydrophilic characteristic (PS+HC) showed less biofilm formation for 1 month and 3 months than PE PSs without hydrophilic characteristic (PS-HC) (p<0.05). PS+HC showed better patency rates for 1 month and 3 months of implantation than PS-HC in both light microscopic and scanning electron microscopy examination (p<0.05). There was statistically significant difference in histologic inflammation scores between PS+HC and PS-HC during the 5 months of implantation (p<0.05). Conclusions PS+HC using the new surface modification technique via vacuum plasma may reduce the biofilm formation and lumen stenosis. This may result less damage to surrounding tissues during PS implantation period and could be safer than PS-HC. To evaluate our results, future clinical studies for patients with biliary obstructive diseases should be required. [ABSTRACT FROM AUTHOR]

The author reflects on the clinical utility of microRNA (miRNA) as a pancreatobiliary cancers prognostic biomarker. Topics include miRNA genes that act as oncogenes and tumor-suppressor genes, miRNA 141 overexpression in malignant cholangiocytes, and microRNAs roles for anticipation of patient prognosis and for finding new therapeutic targets for cancer treatment.

Background/Aims: The objective of this study was to investigate the value of cyst fluid carcinoembryonic antigen (CEA) in combination with cytology and viscosity for the differential diagnosis of pancreatic cysts. Methods: We retrospectively reviewed our data for patients who underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and cyst fluid analysis. We investigated the sensitivity, specificity and accuracy of the combination of cyst fluid CEA, cytology and viscosity testing. Results: A total of 177 patients underwent EUS-FNA and cyst fluid analysis. Of these, 48 subjects were histologically and clinically confirmed to have pancreatic cysts and were therefore included in the analysis. Receiver operator curve analysis demonstrated that the optimal cutoff value of cyst fluid CEA for differentiating mucinous versus nonmucinous cystic lesions was 48.6 ng/mL. The accuracy of cyst fluid CEA (39/48, 81.3%) was greater than the accuracy of cytology (23/45, 51.1%) or the string sign (33/47, 70.2%). Cyst fluid CEA in combination with cytology and string sign assessment exhibited the highest accuracy (45/48, 93.8%). Conclusions: Cyst fluid CEA was the most useful single test for identifying mucinous pancreatic cysts. The addition of cytology and string sign assessment to cyst fluid CEA increased the overall accuracy for the diagnosis of mucinous pancreatic cysts. [ABSTRACT FROM AUTHOR]

Background/Aims Tumor-infiltrating lymphocytes (TILs) have been associated with prognosis in various cancers. However, their prognostic significance in resected gallbladder cancer remains largely unknown. Methods A total of 253 patients who underwent curative resection for gallbladder cancer were included in this study. H&E stained whole slide images of resected gallbladder cancers were analyzed using the Lunit SCOPE IO, an artificial intelligence (AI)-powered spatial TIL analyzer. Based on the density of intratumoral TILs (iTILs) in the cancer epithelium and stromal TILs (sTILs) in the cancer stroma, three immune phenotypes were defined at a 1 mm² grid level: immune-inflamed phenotype (IIP), immune-excluded phenotype (IEP), and immune-desert phenotype (IDP). The impact of these immune phenotypes on survival outcomes was then analyzed. Results The IDP was associated with shorter disease-free survival (DFS) (hazard ratio [HR] 1.019, 95% confidence interval [CI] 1.003–1.036), along with perineural invasion (HR 3.198, 95% CI 1.108–9.228) and stage III/IV (HR 8.531, 95% CI 3.005–24.223). Adjuvant therapy (HR 0.456, 95% CI 0.217–0.955) was associated with longer DFS. Notably, patients with a grid-level IDP proportion exceeding 50% showed significantly shorter DFS (HR 3.514, 95% CI 1.529–8.074) compared to those with less than 50%. IDP was also independently associated with shorter overall survival (OS) (HR 1.020, 95% CI 1.004–1.036), along with age (HR 1.041, 95% CI 1.006–1.077) and stage III/IV (HR 4.900, 95% CI 2.122–11.312). Conclusion The IDP, identified through AI-powered spatial TIL analysis, is predictive of shorter DFS and OS in resected gallbladder cancer patients. [ABSTRACT FROM AUTHOR]

Background/Aims Ampulla of Vater carcinoma (AVC) is a rare gastrointestinal tumor that is associated with a high mortality rate and it’s often diagnosed at later stages due to lack of clinical symptoms. Elucidating complex ecosystems and molecular features of AVC is pivotal to proactive cancer prevention and optimal therapeutic intervention. Methods We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve AVCbiopsies (N=8), and bulk RNA sequencing of surgically resected tissues (N=62) to investigate the transcriptomic signature in tumor microenvironment (TME) of AVC. Results We analyzed the single-cell transcriptome of 34,672 cells and epithelial cells were classified into 4 subtypes by consensus non-negative matrix factorization (cNMF) based on their gene expression profiles. Among them, the KRAShigh subtype showed more increased copy number variation than other subtypes and less differentiated with a high stemness score. Moreover, the high subtype was reversely related to overall survival (OS) and enriched with granzyme K＋ CD8 T cells. Deconvolution of bulk RNA-seq data validated the poor OS and progression-free survival (PFS) in the AVC patients with the high subtype. Also, it was revealed that this subtype was associated with early tumor recurrence in AVC. Conclusion We understood the heterogenous TME of AVC and found the prognostic biomarker to predict postoperative recurrence and survival in AVC. [ABSTRACT FROM AUTHOR]

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions: This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection. [ABSTRACT FROM AUTHOR]

Background/Aims: As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. Methods: Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. Results: Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. Conclusions: In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4 cm in size, are asymptomatic and lack worrisome features on preoperative images. [ABSTRACT FROM AUTHOR]

This study aimed to determine the clinical characteristics of immunoglobulin G4 (IgG4)-associated sclerosing cholangitis (ISC) and provide clinical clues differentiating ISC from primary sclerosing cholangitis (PSC) or hilar cholangiocarcinoma (CCC). Sixteen patients with ISC manifesting as hilar/intrahepatic strictures were analyzed for clinical characteristics and compared with patients with PSC and hilar CCC as disease controls for histology and serum IgG4 levels. Distinguished biliary imaging findings of ISC included multifocal biliary tree involvement ( n = 14), concentric bile duct thickening with preserved luminal patency ( n = 13), and relatively mild proximal dilatation, despite prominent bile duct thickening ( n = 11). Serum IgG4 levels were elevated in 12 patients (75%), but not in any of the 25 patients with hilar CCC. Ten patients (63%) had a past or concurrent history of autoimmune pancreatitis (AIP). The significant infiltration of IgG4-positive cells was observed with endobiliary or liver biopsy in 11 of 16 patients (69%) with ISC, but not in any patients with PSC or hilar CCC. Extrabiliary organ involvement, including sialadenitis, inflammatory pseudotumor of the liver and kidney, and retroperitoneal fibrosis, was present in seven patients. Marked improvement of biliary strictures and/or extrabiliary involvement was observed in all ISC patients after steroid therapy. ISC should be considered in the differential diagnosis of hilar/intrahepatic biliary strictures. Past or concurrent AIP or extrabiliary organ involvement strongly suggests the possibility of ISC. Significant infiltration of IgG4-positive cells on endobiliary or liver biopsy specimens, and/or elevated serum IgG4 levels, highly support the diagnosis of ISC and provide the rationale for steroid therapy. [ABSTRACT FROM AUTHOR]

Background and Aim: A high prevalence of intrahepatic stones in some areas of East Asia has been believed to be related with Clonorchis sinensis infection. The authors conducted a hospital-based case–control study to evaluate the role of Clonorchis sinensis infection as a risk factor for the development of gallstones in Korea. Methods: The cases of 138 patients with gallstones (intrahepatic 44, gallbladder 67, and extrahepatic 27) and matched controls underwent microscopy for C. sinensis, serological tests for C. sinensis using enzyme-linked immunosorbent assay, radiological examinations, and interviews concerning the history of eating raw freshwater fish. We assessed a relationship of three types of gallstones and variables regarding C. sinensis by using univariate and multivariate statistical analyses. Results: Univariate statistical analyses showed that radiological evidence of C. sinensis and recent history of eating raw freshwater fish were related to an increased risk of intrahepatic stones ( P = 0.0002 and 0.0039, respectively). According to multivariate statistical analyses, radiological evidence of C. sinensis was the only risk factor for intrahepatic stones (odds ratio = 7.835; 95% confidence interval = 1.671–36.724). Any evidence regarding C. sinensis was not related to an increased risk of either gallbladder or extrahepatic stones. Conclusion: Radiological evidence of C. sinensis was significantly associated with intrahepatic stones. [ABSTRACT FROM AUTHOR]

Background/Aims: For the management of hilar malignant biliary obstruction (HMBO), endoscopic biliary drainage (EBD) is preferred over percutaneous transhepatic biliary drainage (PTBD) because of its convenience. However, there is no established guideline for malignant hilar obstruction that requires multiple stenting. In this study, we compared the efficacy of bilateral metal stents (BMS) versus multiple plastic stents (MPS). Methods: In this retrospective study, we analyzed 102 patients who underwent EBD with either BMS or MPS due to HMBO caused by hilar cholangiocarcinoma between 1996 and 2018 at Samsung Medical Center. We compared the successful drainage rates, cholangitis events, overall complications, mortality, and conversion rates to PTBD between the two groups. Results: The successful drainage rates in the BMS group and the MPS group were 71.4% (25/35) and 65.6% (44/67), respectively, with no significant difference. The MPS group had a higher cholangitis risk (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.21 to 3.58) and higher 6-month mortality (HR, 2.91; 95% CI, 1.26 to 6.71) than the BMS group. There were no significant differences in overall complications or the conversion rate to PTBD between the groups. Conclusions: In patients with malignant HMBO, the BMS group showed better outcomes in terms of the cholangitis rate and 6-month mortality than the MPS group. Therefore, if possible, bilateral metal stenting is recommended for HMBO caused by hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background/Aims: Recent advances in understanding the genetics of pancreatic ductal adenocarcinoma (PDAC) have led to the potential for a personalized approach. Several studies have described the feasibility of generating genetic profiles of PDAC with next-generation sequencing (NGS) of samples obtained through endoscopic ultrasound-guided tissue acquisition (EUS-TA). The aim of this study was to find the best EUS-TA approach for successful NGS of PDAC. Methods: We attempted to perform NGS with tissues from 190 patients with histologically proven PDAC by endoscopic ultrasound-guided fine-needle aspiration and endoscopic ultrasound-guided fine-needle biopsy at Samsung Medical Center between November 2011 and February 2015. The medical records of these patients were retrospectively reviewed for parameters including tumor factors (size, location, and T stage), EUS-TA factors (needle gauge [G], needle type, and number of needle passes) and histologic factors (cellularity and blood contamination). The sample used for NGS was part of the EUS-TA specimen that underwent cytological and histological analysis. Results: NGS could be successfully performed in 109 patients (57.4%). In the univariate analysis, a large needle G (p=0.003) and tumor located in the body/tail (p=0.005) were associated with successful NGS. The multivariate logistic regression analysis revealed that the needle G was an independent factor of successful NGS (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; p=0.031). Conclusions: The needle G is an independent factor associated with successful NGS. This finding may suggest that the quantity of cells obtained from EUS-TA specimens is important for successful NGS. [ABSTRACT FROM AUTHOR]

Background/Aims: Biliary strictures remain one of the most challenging aspects after living donor liver transplantation (LDLT). The aim of this study was to assess long-term outcome of endoscopic treatment of biliary strictures occurring after LDLT and to identify risk factors of recurrent biliary strictures following endoscopic retrograde biliary drainage (ERBD) in LDLT. Methods: A total of 1,106 patients underwent LDLT from May 1995 to May 2014. We compared the risk factors between patients with and without recurrent biliary strictures. Results: Biliary strictures developed in 24.0% of patients. Technical success rate of ERBD for biliary stricture after LDLT was 66.2% (145/219). Among 145 patients managed by endoscopic drainage, stricture resolution occurred in 69 with median duration of stent indwelling of 13.6 months (range, 0.5 to 67.3 months), and stricture recurrence was seen in 20 (21.3%) out of 94. The median recurrence-free duration after final endoscopic success was 13.1 months (range, 0.5 to 67.3 months). Older donor age (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03 to 1.17; p=0.004) and non-B, non-C liver cirrhosis (HR, 5.10; 95% CI, 1.10 to 25.00; p=0.043) were associated with higher recurrence of biliary stricture. Conclusions: Long-term stricture resolution rate after ERBD insertion for biliary stricture occurring after LDLT was 73.4%. Clinicians should pay careful attention during following-up to decide when to remove ERBD in patients who have factors associated with recurrent biliary strictures. [ABSTRACT FROM AUTHOR]

Background/Aims: For the treatment of malignant biliary obstruction, endoscopic retrograde biliary drainage (ERBD) has been widely accepted as a standard procedure. However, post-ERBD complications can affect the lives of patients. The purpose of this study was to identify the predictive factors for these complications, including the patient's status, cancer status, and stent type. Methods: This was a retrospective analysis conducted in a single tertiary hospital from January 2007 to July 2017. The following variables were evaluated: sex, age, body mass index, cancer type, history of pancreatitis, gallbladder stone, previous biliary stenting, precut papillotomy, stent type, contrast injection into the pancreatic duct or gallbladder, cystic duct invasion by the tumor, and occlusion of the cystic duct orifice by a metal stent. Results: Multivariate analysis showed that contrast injection into the pancreatic duct was a risk factor for pancreatitis. Patients with a history of bile drainage showed a lower risk of pancreatitis. For cholecystitis, the analysis revealed contrast injection into the gallbladder and cystic duct invasion by the tumor as important predictive factors. Metal stents showed a greater risk of post-procedure pancreatitis than plastic stents, but did not affect the incidence of cholecystitis. Conclusions: Considering that contrast injection is the most important factor for both complications, a careful approach by the physician is essential in preventing the occurrence of any complications. Further, choosing the type of stent is an important factor for patients at a risk of post-procedure pancreatitis. [ABSTRACT FROM AUTHOR]

Background/Aims: The covered self-expandable metal stent (CMS) was developed to prevent tumor ingrowth-induced stent occlusion during the treatment of malignant biliary obstruction. However, complications such as cholecystitis, pancreatitis, and stent migration can occur after the endoscopic insertion of CMSs. The aim of the present study was to assess the efficacy and safety of a double-layered CMS (DCMS) for the management of malignant bile duct obstruction. Methods: DCMSs were endoscopically introduced into 59 patients with unresectable malignant extrahepatic biliary obstruction at four tertiary referral centers, and the patient medical records were retrospectively reviewed. Results: Both the technical and functional success rates were 100%. Procedure-related complications including pancreatitis, cholangitis, stent migration, and liver abscess occurred in five patients (8.5%). The median follow-up period was 265 days (range, 31 to 752 days). Cumulative stent patency rates were 68.2% and 40.8% at 6 and 12 months, respectively. At the final follow-up, the rate of stent occlusion was 33.9% (20/59), and the median stent patency period was 276 days (range, 2 to 706 days). Conclusions: The clinical outcomes of DCMSs were comparable to the outcomes previously reported for CMSs with respect to stent patency period and complication rates. [ABSTRACT FROM AUTHOR]

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis. [ABSTRACT FROM AUTHOR]

Background/Aims: Controversy remains over the optimal approach to preoperative biliary drainage in patients with resectable perihilar cholangiocarcinoma. We compared the clinical outcomes of endoscopic biliary drainage (EBD) with those of percutaneous transhepatic biliary drainage (PTBD) in patients undergoing preoperative biliary drainage for perihilar cholangiocarcinoma. Methods: A total of 106 consecutive patients who underwent biliary drainage before surgical treatment were divided into two groups: the PTBD group (n=62) and the EBD group (n=44). Results: Successful drainage on the first attempt was achieved in 36 of 62 patients (58.1%) with PTBD, and in 25 of 44 patients (56.8%) with EBD. There were no significant differences in predrainage patient demographics and decompression periods between the two groups. Procedure-related complications, especially cholangitis and pancreatitis, were significantly more frequent in the EBD group than the PTBD group (PTBD vs EBD: 22.6% vs 54.5%, p<0.001). Two patients (3.8%) in the PTBD group experienced catheter tract implantation metastasis after curative resection during the follow-up period. Conclusions: EBD was associated with a higher risk of procedure-related complications than PTBD. These complications were managed properly without severe morbidity; however, in the PTBD group, there were two cases of cancer dissemination along the catheter tract. [ABSTRACT FROM AUTHOR]

The use of advanced imaging technologies for the identification of pancreatic cysts has become widespread. However, accurate differential diagnosis between mucinous cysts (MC) and nonmucinous cysts (NMC) consisting of pseudocysts (NMC1) and nonmucinous neoplastic cysts (NMC2) remains a challenge. Thus, it is necessary to develop novel biomarkers for the differential diagnosis of pancreatic cysts. An integrated proteomics approach yielded differentially expressed proteins in MC that were verified subsequently in 99 pancreatic cysts (21 NMC1, 41 NMC2, and 37 MC) using a method termed GeLC-stable isotope dilution-multiple reaction monitoring-mass spectrometry (GeLC-SID-MRM-MS) along with established immunoassay techniques. We identified 223 proteins by nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC/MS-MS). Nine candidate biomarkers were identified, including polymeric immunoglobulin receptor (PIGR), lipocalin 2 (LCN2), Fc fragment of IgG-binding protein (FCGBP), lithostathine-1-alpha (REG1A), afamin (AFM), chymotrypsin C (caldecrin; CTRC), amylase, alpha 2B (pancreatic; AMY2B), lectin, galactoside-binding, soluble, 3 binding protein (LGALS3BP), and chymotrypsin-like elastase family, member 3A (CELA3A), which were established as biomarker candidates for MC. In particular, we have shown that a biomarker subset, including AFM, REG1A, PIGR, and LCN2, could differentiate MC not only from NMC (including NMC1) but also fromNMC2. Overall, the MS-based comprehensive proteomics approach used in this study established a novel set of candidate biomarkers that address a gap in efforts to distinguish early pancreatic lesions at a time when more successful therapeutic interventions may be possible. [ABSTRACT FROM AUTHOR]

Background/Aims: Several precut techniques have been used to gain biliary access for difficult cases. The aim of this study was to evaluate the success and complication rates of two precut techniques, transpancreatic septotomy (TPS) and needle knife infundibulotomy (NKI), in difficult biliary cannulation due to the presence of unintended pancreatic cannulation. Methods: Eighty-six patients who failed standard biliary cannulation were included. TPS was performed when we failed to achieve biliary access despite 5 minutes of attempted cannulation or when more than three attempted unintended pancreatic cannulations occurred. If deep cannulation was not achieved within 5 minutes for any duct, NKI was performed. If this failed, we crossed over to the other technique in the second attempt. Results: The initial total success rate of biliary cannulation was 88.4% (86.6% for the TPS group and 94.7% for the NKI group, p=0.447). After crossover of the techniques, the final success rate was 95.3%. The complication rate was 20.9% in patients with TPS and 15.8% in patients with NKI (p=0.753). Conclusions: The use of different strategies based on the presence of unintended pancreatic cannulation may help increase the success rate for difficult biliary cannulation without increasing complication rates. [ABSTRACT FROM AUTHOR]

Background/Aims: We investigated the efficacy of prophylactic pancreatic stent placement for preventing post-procedure pancreatitis in patients undergoing endoscopic papillectomy. Methods: This retrospective study included 82 consecutive patients who underwent endoscopic papillectomy for benign ampullary neoplasm at Samsung Medical Center between August 2002 and June 2011. The patients were subdivided into two groups, namely, those who received prophylactic pancreatic stent placement and those who did not. Patient demographics, baseline blood test, tumor characteristics, and endoscopic treatment data were collected. The primary endpoint was postprocedure pancreatitis. Results: There was no difference in the development of postprocedure pancreatitis between the stent group and the no stent group (6/54, 10.5% and 2/28, 7.14%, respectively; p=1.00). At baseline, there were no significant differences between the two groups in terms of their risk factors for pancreatitis except pancreatic duct dye injection. The stent group was more likely to have dye injection than the nonstent group (100% vs 42.8%, p<0.001). However, in a logistic regression analysis, no significant difference was observed in the risk factors for pancreatitis including dye injection. Conclusions: Our data suggest that routine prophylactic pancreatic duct stent placement in all patients undergoing endoscopic papillectomy may not be necessary and that large-scale prospective studies are required to identify the subgroup of patients who would benefit. [ABSTRACT FROM AUTHOR]

Purpose End-of-dose failure (EOD) is a clinically common observation and many cancer patients increase the frequency of opioid administration. Fentanyl matrix use is known to be effective in patients with chronic cancer pain. To measure the effectiveness of increase in a single dose of fentanyl matrix in patients whose pain was not controlled sufficiently, we perform this study. Materials and Methods A multi-center, open-label, prospective, observational study was conducted in 30 hospitals in Korea, between August and December 2008. Results A total of 452 patients were enrolled; 404 patients completed the study. The mean pain intensity decreased from 5.27 at the first visit to 3.37 at the end of the trial. There was a significant difference in pain intensity (p < 0.001) between the first and last visits. The percentage of pain intensity difference was 30.1%. The prevalence of EOD at the first visit was 73% from the 452 enrolled patients. After the use of fentanyl patch, EOD decreased from 73% to 56%. Pain intensity of patients experiencing EOD was 5.64 at the baseline compared to 4.27 in patients without EOD. On final visit, pain intensity in patients with and without EOD was 4.02 and 2.54, respectively. The observed adverse events were mainly nausea, asthenia, constipation and diarrhea. Conclusion This study demonstrated that increasing dose of fentanyl patch decreased pain intensity and decreased the rate of patients experiencing EOD. Thus, fentanyl patch may be an effective modality in cancer patients whose pain was previously not controlled sufficiently; the side effects were as could be expected with an opioid. [ABSTRACT FROM AUTHOR]

Objective: Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. Design: 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. Results: The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. Conclusions: AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed. [ABSTRACT FROM AUTHOR]

Background and Aim: In this study, we analyzed the clinical and pathological features of biliary intraductal papillary neoplasms (IPN-B) according to the location of the tumors. Methods: A total of 55 patients with IPN-B were analyzed. We divided them into three groups: common bile duct (CBD), hilar, and intrahepatic duct (IHD) groups. The clinical and laboratory findings, cell types, depth of invasion, malignancy, existence of stones, lymph node metastasis, recurrence, and survival rate were analyzed. Results: There was no difference in the depth of invasion, lymph node metastasis, and coexistence of stones between the three groups. There were four different cell types; the intestinal cell type was the most common type in each group. The gastric cell type was prevalent in the IHD and hilar groups (58.3% and 33.3%, respectively). Invasive colloid carcinoma mainly showed the intestinal cell type, and tubular carcinoma showed the pancreaticobiliary cell type. There was a trend that malignancy was more prevalent in the CBD group (94.1%) than in the hilar group (64.3%) and IHD group (79.2%), but there was no statistically significant difference. There was no difference in the recurrence rate and the 3-year survival rate between the three groups. Conclusion: IPN-B showed no difference in the malignancy and survival rates according to the location of the tumors. Because IPN-B show good prognosis after surgery, aggressive surgical resection for the treatment of IPN-B is recommended. [ABSTRACT FROM AUTHOR]

Background: Intraductal ultrasonography (IDUS) is a useful procedure for diagnosing microlithiasis in the bile duct but it is not easy to differentiate between tiny echogenicity and real microlithiasis. We compared the echogenicity seen on IDUS and the findings of bile microscopy (BM) of bile that was collected in the common bile duct (CBD) to determine whether the echogenicity seen on IDUS is real microlithiasis.Methods: This prospective study involved a total of 30 patients who experienced biliary pain (n = 11), acute cholecystitis (n = 11) or indeterminate pancreatitis (n = 8) without a filling defect or obstruction in the bile duct. IDUS was performed during endoscopic retrograde cholangiopancreatography (ERCP), followed by bile aspiration for BM. Endoscopic sphincterotomy (EST) was performed if definite echogenic materials were observed on IDUS.Results: Of the 30 patients, 23 (77%) had echogenic materials visible in the CBD on IDUS. Of these 23 patients, 13 (57%) were found to have biliary crystals by BM. The size of the echogenic materials was the only significant factor associated with BM positivity. Using the receiver operating curve, the optimal size of the echogenicity to differentiate real microlithiasis was 1.4 mm.Conclusions: Optimal concordance between IDUS and BM was observed when the size of the microlithiasis was greater than 1.4 mm; under these conditions the sensitivity and specificity were 71% and 75%, respectively. This information may be useful when deciding whether to perform endoscopic sphincterotomy. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe pancreatic involvement in von Hippel-Lindau (VHL) disease and to document the changes that occur in pancreatic lesions. We retrospectively analyzed the medical records and CT scans of 18 VHL patients who were diagnosed between 1994 and 2007 at the Samsung Medical Center. The clinical history with a detailed family history, biochemical test results, and imaging studies of the pancreas, adrenal glands, and kidneys were reviewed. Genetic analysis was performed in 12 patients. The changes in pancreatic lesions, such as an increase in cystic lesions, calcifications, and dilatation of the pancreatic duct, were analyzed in patients who had CT scans at least 1 year apart. Pancreatic lesions existed in 89% (16/18) of the patients. All 16 patients had multiple cystic lesions. Two patients had co-existing neuroendocrine tumors (NET), and two patients had co-existing serous cystadenomas (SCA). At least one of three features of pancreatic lesions (cystic lesions, calcifications, and dilatation of the pancreatic duct) progressed in all nine patients who had CT scans 1 year apart. Pancreatic involvement in VHL disease was relatively common in Korean patients. The most common type of pancreatic involvement was a multiple cystic lesion. NET and SCA existed in approximately 10% of VHL patients with pancreatic involvement. Pancreatic lesions in VHL disease progressed, at least according to radiological images. [ABSTRACT FROM AUTHOR]

The phase II study was conducted to evaluate the efficacy and safety of irinotecan as salvage single-agent chemotherapy in patients with advanced pancreatic cancer. Patients with measurable metastatic pancreatic cancer, progressive after previous gemcitabine-based chemotherapy were treated with irinotecan 150 mg/m2 every 2 weeks. Treatment was repeated until disease progression or unacceptable toxicity. Between March 2004 to February 2007, 33 patients were registered and treated with irinotecan monotherapy. The patients’ median age was 59 years (range 36–70) and two had an ECOG performance status of 2. A total of 167 chemotherapy cycles were delivered (median, 4; range 2–12). In an intent-to-treat analysis, three (9%) confirmed partial response and 13 patients with stable disease were observed for a disease control rate of 48%. The median progression-free and overall survivals were 2.0 months (95% CI, 0.7–3.3) and 6.6 months (95% CI, 5.8–7.4), respectively. Toxic effects were mainly gastrointestinal (nausea in 64% of patients, diarrhea in 36%), Toxicity profiles were generally predictable and manageable, and there was no treatment-related death. Second-line chemotherapy with single-agent irinotecan is marginally effective and well tolerated regimen for gemcitabine-pretreated patients with advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

To investigate the efficacy and safety of combination chemotherapy with biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin in the treatment of patients with advanced or metastatic gastric cancer. Chemonaive patients with histologically confirmed advanced or recurrent inoperable gastric cancer were enrolled in the present study. Treatment consisted of paclitaxel (75 mg/m2) and leucovorin (40 mg/m2) as a 2-h intravenous infusion, followed by 5-fluorouracil (2,400 mg/m2) as a 46-h continuous infusion. Cycles were repeated every 2 weeks. Thirty patients were enrolled in this study. There were 12 partial responses, giving an overall response rate of 40.0%. At a median follow-up of 10.6 months, the median time to progression and median overall survival were 3.9 and 8.8 months, respectively. The most common hematological toxicity was grade 1–2 anemia, which was seen in 83.3% of patients. No grade 4 leukopenia, thrombocytopenia, or anemia was noted. The most common non-hematological toxicity was anorexia, which was seen in 70% of patients, although grade 3 anorexia was noted in only 10% of cases. There was no severe treatment-related morbidity or death. Combination chemotherapy consisting of biweekly paclitaxel plus infusional 5-fluorouracil and leucovorin was effective and well tolerated in patients with advanced gastric cancers. [ABSTRACT FROM AUTHOR]

Studies in rats have shown that brain death decreases β-cell function and causes islet cell death during islet isolation and transplantation. Because a direct comparison of human islet cells between living and cadaveric donors has not been reported to date, we studied the effects of brain death on islet cell yield. A total of 36 pancreas specimens from 20 living donors and 16 cadaveric donors were used for analysis. Islets were isolated with a Ricordi chamber, and counted as equivalent islet numbers (EIN). Living donors were predominantly female, and cadaveric donors were mainly male. Although the cold ischemic time, pancreas distensibility and digestion time were not different, islet yield was observed to be higher in living donors compared with cadaveric donors (5800 ± 3500 vs. 1900 ± 2000 EIN/g pancreas). Islet isolation success rates (when defined as more than 2000 EIN/g) were 94.1% and 42.9%, respectively. Post-Ficoll islet recovery rates and purity were also better in living donors. However, islet viability and in vitro function of isolated islets showed no significant differences between the groups. These results suggested that brain death negatively affected the processes of islet isolation from the pancreas. [ABSTRACT FROM AUTHOR]

To identify differential findings of biliary cystic intraductal papillary mucinous tumor (IPMT) and biliary cystadenoma/cystadenocarcinoma on CT images. Records of 7 patients with biliary cystic IPMT and 17 patients with biliary cystadenoma/cystadenocarcinoma were accessed. A pathologist reviewed gross morphologic and microscopic findings and confirmed the diagnosis. Two radiologists who were blind to the pathologic diagnosis reviewed CT images regarding size of cystic mass, mural nodule, septa, calcification, dilatation of the proximal, and distal bile ducts to the tumor, and the results were analyzed using multivariate analysis. Mural nodule and dilatation of the bile ducts distal to the cystic tumor were more commonly seen in patients with cystic IPMT than in patients with biliary cystadenoma/cystadenocarcinoma and these are statistically significant, the P values being 0.029 and 0.016, respectively. Size of the cystic tumor, presence of septa, calcification, and dilatation of the bile duct proximal to the cystic tumor were not statistically different. Biliary cystic IPMT could be differentiated from biliary cystadenoma/cystadenocarcinoma on CT images based on the presence of mural nodules and dilatation of the bile ducts distal to the cystic tumor. [ABSTRACT FROM AUTHOR]

Background/Aims: No reliable nationwide clinical data about chronic pancreatitis (CP) was available in Korea. The etiology and clinical features of CP were investigated using a multicenter nationwide study. Methods: 814 cases of CP were enrolled retrospectively over the past 4 years at 13 hospitals. The following data were obtained from all patients: etiology, symptoms, complications, and surgery. Result: Alcohol (64.3%) was the major cause of CP and idiopathic CP (20.8%) was the second most common form. Mean patient age was 50.6 years and the male:female ratio was 6:1 (24:1 for alcoholic CP vs. 2:1 in idiopathic CP, p < 0.001). Diabetes (31.6%), pseudocysts (28.4%), biliary stricture (13.9%), and pancreatic ascites (6.6%) were the main complications. Of these, diabetes (35 vs. 26%) and pseudocyst (33.7 vs. 21.9%) were more frequent in alcoholic than in idiopathic CP. Pancreatic cancer developed in 25 patients (3.1%) during follow-up and their mean age was 59.1 years. Conclusions: In Korea, alcohol is the most common etiology of CP. Moreover, diabetes and pseudocysts are frequent complications, especially in alcoholic CP, and pancreatic cancer development is not infrequent. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The single agent gemcitabine is the standard first-line treatment for advanced pancreatic cancer. Recent studies of a combination of gemcitabine and 5-fluorouracil (5-FU) revealed that survival data were superior to those with gemcitabine or 5-FU alone. The administration of oral uracil-tegafur (UFT) is more convenient and simulates the effect of a continuous or protracted infusion of 5-FU. Therefore, we conducted a phase II study of gemcitabine combined with UFT in metastatic pancreatic cancer patients and assessed the efficacy and the toxicity of the regimen. Methods: Twenty-two pancreatic adenocarcinoma patients (18 males, 4 females) were enrolled from December 2000 to September 2002. The regimen consisted of gemcitabine 1,000 mg/m[sup 2] once weekly for 3 consecutive weeks, and oral UFT 390 mg/m[sup 2] /day (in 3 divided doses) on days 1–14. The cycle was repeated every 28 days. The objective tumor response was evaluated after 2 courses of chemotherapy. Results: 82 cycles were administered in total, with a median of 3 cycles per patient (range 1–6 cycles). The median age was 52 years (range 28–69 years). Response to treatment could be assessed in all patients. The objective response rate was 22.7% (95% CI, 7.8–45.4) with no complete response and 5 partial responses. Four patients (18.2%) had stable disease and 13 patients (59.1%) had a progression. The median time to progression was 4.2 months (range 0.9–13.6). The median overall survival was 5.8 months (range 0.5–13.6). Of 10 patients eligible for the assessment of clinical benefit response, 4 (40%, 95% CI 12.2–73.8) showed clinical benefit. Among 21 patients with baseline CA 19-9 levels, CA 19-9 was reduced by 50% or more in 12 patients (57.1%). The chemotherapy was generally well tolerated and the most common grade 3–4 toxic side effects were neutropenia (18.2%), anemia (4.5%), and diarrhea (4.5%). Conclusion: The combination chemotherapy with gemcitabine and UFT in metastatic pancreatic cancer was tolerable for most patients but showed modest response rates and clinical benefit. However, a randomized phase III study should be conducted in order to further test the efficacy of the regimen. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims Circulating tumor cells (CTCs) are cancer cells shed from either the primary tumor or its metastases, and they are regarded as the source of tumor recurrence and metastasis representing a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Thus, CTCs could provide a noninvasive alternative for diagnosis and assessment of the patient's stage and type of pancreatic cancer. In the present study, we investigated whether repeated collection and analysis of CTCs could be used to monitor disease progression or response to chemotherapy in PDAC patients. Methods Peripheral blood samples were serially collected before and after chemotherapy. To isolate CTCs from the millions of other blood cells, we used a lab-on-a-disc system equipped with fluid-assisted separation technology. Isolated CTCs from 3 mL of blood were immune-stained with EpCAM, cytokeratin, CD45, plectin-1 and DAPI, and then enumerated by using Bioview's automated imaging system. Results Total of 68 PDAC patients were enrolled as study patients. The median age of study patient was 67 years old and the median OS of study patients was 2.87 months. The clinical staging of study patients was the following; I (A, B) 5, II (A, B) 3, III 22 IV 38. The study patients received Gemcitabine based regimen FOLFIRNOX or TS-1 and the 14 patients (20.5%) could not receive chemotherapy due to the patients' wishes, old age or poor performance status. CTC were detected in 53 (78%) patients at the time of diagnosis. The number of CTCs dropped after 1st cycle of chemotherapy was observed in 38 patients (70%). Conclusions Understanding the biology and genetics of CTCs "cancer cells in transit" may give us unique insights into the mechanisms behind metastasis. Identification of CTC in peripheral venous circulation may allow us to characterize genomic signature of individual patient by a simple blood draw. [ABSTRACT FROM AUTHOR]

Background/Aims Tumor microenvironment and intratumoral heterogeneity are known to be playing important roles in tumor evolution and implicated in patient outcomes. Although the complex nature of the tumor microenvironment and intratumoral heterogeneity can be inferred to a certain degree using conventional next-generation sequencing analysis of bulk tumor tissues, precise deconvolution of the diverse the cell types present in the tumor is still difficult to be achieved. The aim of this study was to perform single cell analysis of primary and metastatic pancreatic ductal adenocarcinoma (PDAC) cells. Methods Metastatic PDAC patients were enrolled and each primary and metastatic PDAC cell was acquired using endoscopic ultrasound-guided fine needle aspiration or ultrasound- guided biopsy technique. We aligned reads generated by 10X Chromium Single Cell 3' reagent kits to the human reference genome (hg19) using the STAR and generated gene-barcodes count matrix using CellRanger (version 3.0.2) with default parameters. Principal component analysis was performed using 3,000 highly variable genes, and each significant principle component was determined by JackStraw and elbow plot. We used "FindClusters" functions with default parameter to identify clusters of cells. Each clusters were projected onto UMAP analysis using "RunUMAP" function. Results The median age of study patient was 6 years (range, 151 to 75 years) and the sex ratio was 1:2 (male, 7; female, 14). The median overall survival was 2.9 months (range, 0.5 to 8.8 months) and American Joint Committee on Cancer staging of study patients were the following: stage III, 6; stage IV, 15. The 17 patients (81%) received Gemcitabine/Abraxane or FOLFIRNOX as 1st line chemotherapy with. The advent of single-cell RNA sequencing (scRNA-seq) has given an unprecedented opportunity to understand the diversity of the cellular composition of a tumor and also provides information on tumor microenvironment composed of various cell types. Here, we present the preliminary results of scRNA-seq analysis of both nonmetastatic and liver-metastatic pancreatic cancer. Conclusions scRNA-seq reveals tumor microenvironment and intratumoral heterogeneity in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background/Aims Although metastases is the key determining factor of survival in pancreatic ductal adenocarcinoma (PDAC) patients, the genetic alteration behind the mechanism of metastases remains unclear. We aimed to identify the genetic alteration that endows metastatic potential to primary PDAC by comparing whole exome sequencing results of primary PDAC and paired liver metastases samples from living, treatment-naïve patients. Methods Whole exome sequencing analyses were performed for 11 paired sets of fine needle aspiration (FNA) samples from primary PDAC, percutaneous liver biopsy samples, and white blood cell (WBC) samples acquired form living, treatment-naïve PDAC patients with liver metastases (stage IV). Somatic mutation profiles, somatic copy number alterations profile, and tumor phylogeny were analyzed. Results Median age of study patients was 71 years old. Sex ratio was 5:6 (male:female). The median overall survival of study patients was 4.3 months. The first line chemotherapy regimens of enrolled patients were FOLFIRINOX ([3/11, 27.3%], Gemcitabine/Erlotinib [3/11, 27.3%], Gemcitabine/Abraxane [2/11, 18.2%], and Gemcitabine/Capecitabine [1/11, 9.0%]). Two patients (18.2%) could not receive chemotherapy due to the patients' wishes, old age or poor performance status. Average read depth per exon exceeded 100 times in all tumor samples and exceeded 50 times in all WBC samples. Proportion of exon areas with 10 times or higher read depth reached nearly 100%. Among 22 FNA or liver metastases samples, average purity and ploidy was 0.36 and 2.4, respectively. There were sharing mutations between primary cancers and liver metastasis, however, specific nonsharing mutations were existed. Conclusions Whole Exome sequencing of primary pancreatic cancer and liver metastasis revealed both shared genomic signature, interestingly, we could also find unique unshared mutations of liver metastasis. [ABSTRACT FROM AUTHOR]

Background/Aims Recent studies highlight the putative utility of tissue-specific vesicles in diagnosis and disease monitoring in pancreatic cancer. Exosomes are small extracellular vesicles released via the endocytic pathway by fusion of multivesicular bodies with the plasma membrane. Because exosomes contain an abundant of cell-specific biomolecules acting as a fingerprint of the cell of origin, they possess promising potential as novel biomarkers for early cancer detection. Therefore, we examined exosome-derived proteins and RNAs in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Methods For our study, 100 PDAC and 23 benign patients were enrolled to collect blood samples. A lab-on-a-disc "Exodisc" based on a centrifugal microfluidic filter system was used for the automatic enrichment and isolation of exosomes from plasma along with subsequent analysis by in situ enzyme-linked immunosorbent assay or fluorescence labeling for putative protein markers; CD9, CD63, CD81, GPC1, Caveolin1, Alix, Flot1, epidermal growth factor receptor, epithelial cell adhesion molecule (EpCAM). Clinical and laboratory data was reviewed. AI technique was applied to find out correlation between exosome analysis results and clinical parameters. Results The total of 100 patients with PDACs were enrolled as study patients. The median overall survival (OS) of study patients was 13.9 months. The clinical staging were the following: II (A,B), 12; III, 33; IV, 55. The first line chemotherapy regimen of study patients was Gemcitabine/Abraxane or FOLFIRNOX. Nine protein markers were examined with isolated exosomes from the patient plasma. PDAC patients were divided by two groups with good prognosis (OS ≥36 months) and poor prognosis (OS <36 months) after chemotherapy. As a result, the level of exosomal GPC1, CD63 and EpCAM was increased in the poor prognosis group. Conclusions We found some candidates of exosomal protein markers predicting chemotherapy response and prognosis. This is the first study investigating correlation between clinicopathology of PDACs and exosome markers via AI technique. [ABSTRACT FROM AUTHOR]

Background/Aims Recent studies about pancreatic ductal adenocarcinoma (PDAC) used resettable tumor, derived from surgical specimen, even though most PDACs were unresectable. From this point of view, study based on unresectable PDAC is important, and it is possible to obtain specimen using endoscopic ultrasound (EUS)-guided fine needle aspiration/ biopsy (FNA/B). Moreover, organoid was more similar to original tissue derived from patient with PDAC, than two-dimensional cell culture. Our study aimed to evaluate concordance between primary tissue and patient derived organoid using EUS guided FNA/B and clinicopathologic factors which impact on organoid platform. Methods We obtained PDAC tissue form EUS-guided FNA/B between June 2015 and August 2019 at Samsung Medical Center. To examine the PDAC patient-derived organoid, we performed three-dimensional high resolution immunofluorescent staining, chromosome spread and whole exome sequencing (WES). Results Two hundred seven PDAC samples were analyzed. We confirmed pancreatic ductal cancer cells stained with sox9 and cytokeratin antibodies, and also observed the aneuploidy detected by karyotyping. The WES data showed the high concordance between primary PDAC tissue and its organoid, and the enriched genetic alterations in organoids. Success rate of organoid culture was 41.1% (85/207). Because laboratory set up developed from 2017, success rate has increased every year since 2017: 29.2% (11/39) in 2015, 20.8% (11/53) in 2016, 26.7% (8/30) in 2017, 60.8% (31/51) in 2018, and 70.6% (24/34) in 2019. On multivariable logistic regression analysis, high cellularity of aspiration sample (>10 cluster) was prognostic factor associated with organoid success compared to low cellularity (<3 cluster; odds ratio, 2.76; 95% confidence interval, 1.06 to 7.22; p=0.038). Conclusions In our study, the concordance between primary PDAC tissue and its organoid seems to be high and its characteristics were well explained clinicopathologically. High cellularity of aspiration sample tended to be higher success rate of organoid culture. [ABSTRACT FROM AUTHOR]

Background/Aims Cachexia is frequently seen in pancreatic cancer (70%-80%) and associated with reduced survival, reduced treatment tolerance and reduction in quality of life. In recent studies, low-normal body mass index (BMI) has worse outcome (overall mortality) in cardiovascular, malignant, chronic disease (so-called obesity paradox). Skinfold thickness is strongly associated with body fatness than BMI. The aims of this prospective study were to find out significance of triceps skinfold (TSF) thickness correlation to overall survival (OS) and treatment response in patient with pancreatobiliary tract cancer along with other nutritional and body fatness parameters. Methods This is the prospective cohort study; newly diagnosed unresectable or borderline pancreatic and biliary tract cancers at Samsung Medical Center were enrolled as study patients. TSF using skin thickness caliper was measured on the half of right upper arm in every 3 weeks. BMI, body weight, and weight changes were also tracked along with TSF. The laboratory data and clinical data were monitored. This trial is registered with https:// clinicaltrials.gov (identifier: NCT03637569). Results The total of 310 patients were enrolled and there were 224 patients with pancreatic cancers and 86 patients with biliary tract caners. The first line chemotherapy regimen of pancreatic cancer patients was Gemcitabine/Abraxane or FOLFIRNOX and 19 patients (5.9%) could not receive chemotherapy due to patients' wishes, old age and poor performance status. The first line chemotherapy regimen of biliary tract cancer patients was Gemcitabine/Cisplatin. The median OS of pancreatic cancer and biliary tract cancer were 6.4 and 7.5 months respectively. Initial body weight, TSF and serum albumin level were the independent prognostic factors among the nutritional parameters and initial stage and Eastern Cooperative Oncology Group were also the independent prognostic factors as we can easily expect. Conclusions This study was the first prospective cohort study investigating OS and treatment response correlation to nutritional status in pancreatobiliary tract cancer. [ABSTRACT FROM AUTHOR]

The incidence of pancreatogenic diabetes has been increasing according to the increase of pancreatectomies. Autologous islet transplantation (IT) can be a preventive method, but the effects have not been established. We evaluated the glucose metabolism alter IT following distal pancreatectomy (DPx) for benign pancreatic tumors. Thirteen patients were followed-up for 24-month after DPx and IT. Islets were isolated from the normal part of resected pancreas, and implanted to the liver via portal vein 2days alter DPx. Thirteen controls matched for age, sex and DPx extent were compared to the IT group with respect to glucose, insulin, and HbA1c levels. Paired and unpaired t-tests were used for analysis. Means of preoperative age (control:IT 47:51 years), male number (2:0), BMI (23.9:23.2Kg/m²), fasting glucose (90.4:85.3mg/dL), HbA1c (5.4:5.3%), and abnormal glucose tolerance subjects (30.8:38.5%) were not significantly different between the two groups. Transplanted islets were 3300±1200 IEQ/Kg body weight. Alter 12months, fasting glucose levels significantly increased in both groups, and were not different between the groups. After 24-month, the fasting levels did not increase further in IT group (Figure). Glucose levels at 2-hour after 75g oral glucose tolerance test (OGTT[sub 2]) decreased at 24-month compared to those at 12-month in IT group, and they were lower than those of controls (Figure). Fasting insulin levels at 24-month were also higher in IT group (control:ITx 6.0±2.3:10.5±5.4µIU/mL, p=0.083), in spite of no statistical significance, HbA1c changes showed similar pattern with glucose levels. Glucose homeostasis was improved at 24-month as compared to 12-month, suggesting that transplanted islets can offer unidentified influence on the function of remaining islets. [ABSTRACT FROM AUTHOR]