Current Diagnosis and Treatment of Acute Pancreatitis in Korea: A Nationwide Survey.

Background/Aims: : Acute pancreatitis (AP) is a leading cause of emergency hospitalization. We present the current diagnostic and therapeutic status of AP as revealed by analysis of a large multicenter dataset. Methods: : The medical records of patients diagnosed with AP between 2018 and 2019 in 12 tertiary medical centers in Korea were retrospectively reviewed. Results: : In total, 676 patients were included; of these, were 388 (57.4%) males, and the mean age of all patients was 58.6 years. There were 355 (52.5%), 301 (44.5%), and 20 (3.0%) patients with mild, moderate, and severe AP, respectively, as assessed by the revised Atlanta classification. The most common etiologies of AP were biliary issues (41.6%) and alcohol consumption (24.6%), followed by hypertriglyceridemia (6.8%). The etiology was not identified in 111 (16.4%) patients at the time of initial admission. The overall mortality rate was 3.3%, increasing up to 45.0% among patients with severe AP. Notably, 70.0% (14/20) of patients with severe AP and 81.5% (154/189) of patients with systemic inflammatory response syndrome had received <4 L per day during the initial 24 hours of admission. Only 23.8% (67/281) of acute biliary pancreatitis patients underwent cholecystectomy during their initial admission. In total, 17.8% of patients experienced recurrent attacks during follow-up. However, none of the patients with acute biliary pancreatitis experienced recurrent attacks if they had undergone cholecystectomy during their initial admission. Conclusions: : This study provides insights into the current status of AP in Korea, including its etiology, severity, and management. Results: reveal disparities between clinical guidelines and their practical implementation for AP treatment.

A case report on the role of endoscopic retrograde cholangiopancreatography in the diagnosis of hemosuccus pancreaticus.

RATIONALE: Hemosuccus pancreaticus (HP) is a rare cause of gastrointestinal bleeding that sometimes leads to life-threatening conditions. However, the diagnosis of HP is often delayed due to its rarity and intermittent signs of bleeding, making it challenging to determine the source of bleeding in some patients. PATIENT CONCERNS: An 83-years-old man was transferred to our hospital for evaluation of the source of intermittent upper gastrointestinal bleeding involving melena and worsening anemia. DIAGNOSIS: HP was diagnosed via endoscopic retrograde cholangiopancreatography (ERCP) and sequential angiography using a multidisciplinary approach. INTERVENTIONS: Initial upper and lower gastrointestinal endoscopies did not reveal any source of bleeding. Emergency upper endoscopy performed when the patient had hematochezia and hypotension confirmed a spurt of bleeding from the major duodenal papilla. However, contrast-enhanced computed tomography and angiography could not identify the source of the bleeding from the major duodenal papilla. ERCP for inducing bleeding from the source and indicating the bleeding point was performed according to the decision of the multidisciplinary team. Immediately thereafter, sequential angiography was performed and HP, due to the rupture of a pseudoaneurysm of the splenic artery, was diagnosed. As a result, surgical resection of the pancreas could be avoided by accurately embolizing the bleeding focus of HP using a multidisciplinary team approach. OUTCOMES: The patient was discharged in a hemodynamically stable condition. There was no further gastrointestinal bleeding or procedure-related complication until 6 months after discharge. LESSONS: HP should be considered by endoscopists during the differential diagnosis of intermittent upper gastrointestinal bleeding in patients with a history of pancreatitis. A multidisciplinary team approach is an effective method to determine the source or location of bleeding, which may reduce mortality and morbidity by avoiding additional pancreatectomies.

The Safety and Efficacy of an Unflanged 4F Pancreatic Stent in Transpancreatic Precut Sphincterotomy for Patients with Difficult Biliary Cannulation: A Prospective Cohort Study.

Prophylactic pancreatic stenting effectively reduces the rate and severity of post-ERCP pancreatitis (PEP) in the precut technique; however, studies on the optimal type and duration of the stent are still lacking. This prospective study evaluated the incidence and severity of PEP and the rate of spontaneous stent dislodgement in patients undergoing transpancreatic precut sphincterotomy (TPS) accompanied by prophylactic pancreatic stenting with an unflanged plastic stent (4F × 5 cm) for difficult biliary cannulation. A total of 247 patients with naïve papilla were enrolled in this study, and data were collected prospectively. In the final analysis, 170 and 61 patients were included in the standard cannulation technique and TPS groups, respectively. The incidence of PEP in the standard cannulation technique and TPS groups was 3.5% and 1.6% (p = 0.679), respectively. The technical success rate of selective biliary cannulation in the TPS group was 91.8%. The spontaneous dislodgement rate of the prophylactic plastic stent was 98.4%. In conclusion, an unflanged pancreatic stent (4F × 5 cm) placement in TPS for patients with failed standard cannulation technique is a safe and effective measure due to low adverse events and few additional endoscopic procedures for removing the pancreatic duct (PD) stent.

Percutaneous endoscopic necrosectomy in a patient with emphysematous pancreatitis: A case report.

RATIONALE: Emphysematous pancreatitis, a rare complication of acute necrotizing pancreatitis with a high mortality rate, is associated with gas-forming bacteria. When using the step-up approach for treating emphysematous pancreatitis, it is preferable to delay drainage interventions for 4 weeks. However, percutaneous drainage may be necessary, even in the early phase of acute pancreatitis, for a patient whose sepsis deteriorates despite optimal medical management. Percutaneous drainage can then be followed by endoscopic necrosectomy through the percutaneous tract. PATIENT CONCERNS: A 52-year-old man was transferred to our hospital for treatment of sepsis and multiorgan failure associated with emphysematous pancreatitis. DIAGNOSIS: An abdominal computed tomography scan had shown pancreatic and peripancreatic necrosis, along with extensive gas bubbles. INTERVENTIONS: Despite optimal medical management, the patient's condition continued to deteriorate, and it became necessary to insert 2 percutaneous catheter drainages (PCDs), even though the patient was still in the early phase of pancreatitis. Each PCD was upsized and irrigated with sterile saline by an interventional radiologist twice a week. The infected necrosis around the tail of the pancreas was completely resolved after PCD. However, PCD through the transperitoneal route did not resolve necrosis around the pancreatic head. Following the PCDs, percutaneous pancreatic necrosectomy using an ultra-slim upper endoscope was performed, after which the patient recovered quickly and was discharged. OUTCOMES: Follow-up computed tomography was performed 12 weeks after the patient was discharged, and it showed complete resolution of the walled-off necrosis. The patient's condition improved without any fluid collection or complications. LESSONS: PCD can be used in the early phase of emphysematous pancreatitis for patients who continue to deteriorate due to sepsis. This can easily be followed, if necessary, by percutaneous pancreatic necrosectomy using an ultra-slim endoscope.

Clinical Impact of Preoperative Relief of Jaundice Following Endoscopic Retrograde Cholangiopancreatography on Determining Optimal Timing of Laparoscopic Cholecystectomy in Patients with Cholangitis.

BACKGROUND: About 10% of patients with gallbladder (GB) stones also have concurrent common bile duct (CBD) stones. Laparoscopic cholecystectomy (LC) after removal of CBD stones using endoscopic retrograde cholangiopancreatography (ERCP) is the most widely used method for treating coexisting gallbladder and common bile duct stones. We evaluated the optimal timing of LC after ERCP according to clinical factors, focusing on preoperative relief of jaundice. METHODS: A total of 281 patients who underwent elective LC after ERCP because of choledocholithiasis and cholecystolithiasis from January 2010 to April 2018 were retrospectively reviewed. We compared the hospital stay, perioperative morbidity, and rate of surgical conversion to open cholecystectomy according to the relief of jaundice before surgery. These enrolled patients were divided into two groups: relief of jaundice before surgery (group 1, n = 125) or not (group 2, n = 156). RESULTS: The initial total bilirubin level was higher in group 1; however, there were no significant differences in the other baseline characteristics including age, sex, American Society of Anesthesiologists score, previous surgical history, white blood cell count, C-reactive protein, and operative time between the two groups. There was also no significant difference in postoperative hospital stay between the two groups (4.5 ± 3.3 vs. 5.5 ± 5.6 days, p = 0.087). However, after ERCP, the waiting time until LC was significantly longer in group 1 (5.0 ± 4.9 vs. 3.5 ± 2.4 days, p < 0.001). There were no statistical differences in the conversion rate (3.2% vs. 3.8%, p = 0.518) or perioperative morbidity (4.0% vs. 5.8%, p = 0.348), either. CONCLUSIONS: LC would not be delayed until the relief of jaundice after ERCP since there were no significant differences in perioperative morbidity or surgical conversion rate to open cholecystectomy. Early LC after ERCP may be feasible and safe in patients with cholangitis and cholecystolithiasis.

Unilateral versus bilateral Y-type stent-in-stent metal stent insertions in inoperable malignant hilar biliary strictures: A multicenter retrospective study.

BACKGROUND: To date, there is controversy regarding unilateral versus bilateral stent placement in patients with malignant hilar biliary strictures (MHBSs). The aim of this study was to compare the clinical outcomes and complications of unilateral and bilateral (stent-in-stent method) stent placements for these patients. METHODS: We conducted a multicenter retrospective analysis of patients with inoperable MHBS who underwent endoscopic self-expandable metal stent (SEMS) placement from January 2009 to December 2019. Two groups classified according to the stent procedure method were compared for demographic, procedural, and postprocedure factors. Survival analysis for patency loss and overall survival was also conducted. RESULTS: A total of 236 subjects were included. A superior technical success rate was found in the unilateral stent group (98.8% vs. 82.5%, P < 0.001), whereas the clinical success rate was higher in the bilateral group (85.7% vs. 70.5%, P = 0.028). There was no significant difference with respect to complications or patency loss, and the bilateral group had better overall survival (P < 0.01). In the Cox proportional hazard model, MHBSs from lymph node compression were associated with a higher risk of death (HR = 9.803, P = 0.003). In contrast, bilateral SEMS insertion showed reduced postprocedural mortality (HR = 0.316, P = 0.001). CONCLUSIONS: Y-type stent-in-stent bilateral SEMSs are technically difficult but demonstrated more favorable overall survival for palliative bile drainage of inoperable MHBS patients compared to unilateral insertions.

A novel EPB41 p.Trp704* mutation in a Korean patient with hereditary elliptocytosis: a case report.

Objectives: Hereditary elliptocytosis (HE) is inherited in an autosomal dominant fashion, and the majority of HE-associated defects occur due to qualitative and quantitative defects in the RBC membrane skeleton proteins α-spectrin, ß-spectrin, or protein 4.1R. The complex EPB41 gene encodes a diverse family of protein 4.1R isoforms which are key components of the erythroid membrane skeleton that regulates red cell morphology and mechanical stability. The purpose of this study was to investigate the genome of a Korean patient with HE to discover the causative gene mutation using gene panel sequencing. Methods: An 89-year-old female presented to the Emergency Department and was diagnosed with pancreatitis and gallstones. A peripheral blood smear revealed that approximately 60% of the RBCs were abnormally shaped and appeared oval or elongated, from slightly egg-shaped to rod or pencil forms (elliptocytes). Targeted gene panel sequencing consisting of 33 genes related to inherited RBC disorders and Sanger sequencing were performed. Results: A heterozygous c.2112G > A of the EPB41 gene leading to premature termination codon (NM_001166005.1:c.2112G > A, p.Trp704*) was identified. This variant, which had not been previously reported to be related to HE, was confirmed by Sanger sequencing. Thus, the patient's diagnosis of HE-1 was genetically confirmed. Conclusion: The present study confirmed a novel mutation of the EPB41 gene that plays an important role in expanding the mutational distribution in HE-1. It could also be helpful for understanding the correlation between the genotype and phenotype in HE.

Eupatilin Ameliorates Cerulein-Induced Pancreatitis Via Inhibition of the Protein Kinase D1 Signaling Pathway In Vitro.

OBJECTIVE: The aim of this study was to investigate the effects of eupatilin on protein kinase D1 (PKD1) and nuclear factor kappa B (NF-κB) signaling pathways in cerulein-induced in vitro pancreatitis. METHODS: We used collagenase digestion to isolate pancreatic acinar cells from male C57BL/6 mice. In vitro acute pancreatitis was induced by treatment with a supramaximal dose of cerulein. Eupatilin was pretreated before stimulation with cerulein. RESULTS: Eupatilin significantly reduced cerulein-induced amylase release in pancreatic acini. Eupatilin treatment downregulated cerulein-induced expression of interleukin (IL)-1ß, IL-6, and CC chemokine ligands 2 and 5, but it upregulated expression of IL-4 and IL-10. We demonstrated that eupatilin pretreatment attenuated cerulein-induced necrosis in isolated pancreatic acinar cells. This effect of eupatilin was confirmed by lactic dehydrogenase assay, fluorescence-activated cell sorting analysis, and cytopathologic analysis. Eupatilin inhibited cerulein-induced activation of PKD1/NF-κB and the nuclear translocation of NF-κB. CONCLUSIONS: Our data demonstrated that eupatilin is a potential therapeutic candidate for the treatment of pancreatitis through its ability to reduce cellular necrosis and inflammatory responses by inhibition of the PKD1/NF-κB signaling pathway.

It is necessary to exam bottom and top slide smears of EUS-FNA for pancreatic cancer.

BACKGROUND: Despite many reports on the diagnostic yield of cytology from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), inter-slide differences are unknown. This prospective study aimed to compare diagnostic yield and cellular characteristics of bottom slides (BS) and top slides (TS) from EUS-FNA cytology performed without an on-site cytopathologist. METHODS: In patients with suspected pancreatic cancer on previous imaging explorations, a single endoscopist performed EUS-FNA and obtained 2 sets of cytology slide (8 BS and 8 TS), 1 cellblock slide, and 1 biopsy slide. Both slide sets were randomly assigned. A cytopathologist with more than 10 years of expertise in pancreatic cytopathology blindly inspected and compared two slide sets. RESULTS: In total, 73 specimens [42 head (57.5%), 16 body (21.9%), and 15 tail (20.5%)] were acquired for final analysis. Seventy-one cases were finally diagnosed with pancreatic cancer. The sensitivity and specificity of BS were 80.3% and 100.0%; and of TS 78.9% and 100.0%, respectively. In analyzing inter-slide difference, 66 cases (90.4%) showed consistent results between BS and TS. However, seven (9.6%) were positive only in one slide sets (4 BS and 3 TS). The proportions of specimens more than moderate and high cellularity were 75.3% and 60.3% in both slide sets (P> 0.99), and the proportion of artifact-free sets were 50.7%, and 52.1% for the BS and TS, respectively (P= 0.869). CONCLUSIONS: Although BS and TS exhibited highly consistent diagnostic yields in cytologic smears from EUS-FNA, the proportion of inter-slide discordance is clinically considerable. Both slide sets need to be examined if there is no on-site cytopathologist.

Effectiveness of cholangioscopy using narrow band imaging for hepatobiliary malignancies.

PURPOSE: Recently, cholangioscopy using narrow band imaging (NBI) has been used as a diagnostic modality for better visualization in hepatobiliary malignancies; however, there are few reports on it. Our aim is to evaluate the effectiveness of cholangioscopy using NBI in hepatobiliary malignancies. METHODS: Between January 2007 and December 2016, 152 cholangioscopies using percutaneous approach were conducted in total 123 patients. Among these, 36 patients were suspicious of hepatobiliary malignancies. Thirteen patients with an ambiguous margin on endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP), for whom NBI tipped the balance in diagnosis of lesion and decision of lesion extent by adding NBI, were involved in our study. RESULTS: Underlying diseases were all malignant in 13 patients (11 bile duct cancers, 1 liver cancer, 1 pancreas cancer with common bile duct invasion). In 7 cases with papillary type tumor, minute superficial spreading tumor was detected by NBI more easily, and NBI provided a better visualization of tumor vessel and margin evaluation in 4 cases with infiltrative tumor. In 2 cases with mucin-hypersecreting tumor, NBI showed better penetration through the mucin and gave us a much clearer image. Nine patients ultimately underwent surgical resection. The margins predicted by NBI cholangioscopy were consistent with the pathological margins on the resected specimens. CONCLUSION: In conclusion, cholangioscopy using NBI is very useful for evaluation of suspected hepatobiliary malignancies with an ambiguous margin on ERCP or MRCP. It can give us an accurate pathologic mapping, and this information seems to be essential before deciding on a treatment strategy.

Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity.

BACKGROUND: FOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC). METHODS: We reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012-2015. We established a modified Hryniuk model (http://www.rdicalc.com) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF). RESULTS: Among 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF. CONCLUSION: To preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.

Serum interleukin-6 is associated with pancreatic ductal adenocarcinoma progression pattern.

Several reports showed that interleukin-6 (IL-6) or -8 (IL-8) might be useful inflammatory biomarkers for pancreatic ductal adenocarcinoma (PDAC), although these clinical impact is still open to debate. The aim of this study was to elucidate whether serum levels of IL-6 and IL-8 at diagnosis could predict the tumor progression pattern of PDAC, especially in extensive hepatic metastasis.According to the tumor burden of hepatic metastasis at the last follow-up, tumor progression pattern was defined as follows: no or limited (unilobar involvement and 5 or less in the within liver, limited group) and extensive hepatic metastasis (bilobar or more than 5, progressed group). Fifty-three PDAC patients with initially no or limited hepatic metastasis were enrolled retrospectively.Around 42 (79.2%) were included in the limited and 11 (20.8%) in the progressed group. The median serum level of IL-6 in the progressed group was elevated significantly compared with the limited group. However, the median serum level of IL-8 was not. Furthermore, multivariate analysis revealed that the elevated serum level of IL-6 was an independent risk factor for progression to extensive hepatic metastasis (odds ratio 1.928, 95% confidence interval 1.131-3.365, P = 0.019), but IL-8 was not. However, higher IL-6 did not predict shorter survival.High serum IL-6 can be an independent risk factor for progression to extensive hepatic metastasis in PDAC patients.

Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer.

BACKGROUND: The adjunctive role of magnetic resonance imaging of the liver before pancreatic ductal adenocarcinoma has been unclear. We evaluated whether the combination of hepatic magnetic resonance imaging with multidetector computed tomography using a pancreatic protocol (pCT) could help surgeons select appropriate candidates and decrease the risk of early recurrence. METHODS: We retrospectively enrolled 167 patients in whom complete resection was achieved without grossly visible residual tumor; 102 patients underwent pCT alone (CT group) and 65 underwent both hepatic magnetic resonance imaging and pCT (magnetic resonance imaging group). RESULTS: By adding hepatic magnetic resonance imaging during preoperative evaluation, hepatic metastases were newly discovered in 3 of 58 patients (5%) without hepatic lesions on pCT and 17 of 53 patients (32%) with indeterminate hepatic lesions on pCT. Patients with borderline resectability, a tumor size >3 cm, or preoperative carbohydrate antigen 19-9 level >1,000 U/mL had a greater rate of hepatic metastasis on subsequent hepatic magnetic resonance imaging. Among 167 patients in whom R0/R1 resection was achieved, the median overall survival was 18.2 vs 24.7 months (P = .020) and the disease-free survival was 8.5 vs 10.0 months (P = .016) in the CT and magnetic resonance imaging groups, respectively (median follow-up, 18.3 months). Recurrence developed in 82 (80%) and 43 (66%) patients in the CT and magnetic resonance imaging groups, respectively. The cumulative hepatic recurrence rate was greater in the CT group than in the magnetic resonance imaging group (P < .001). CONCLUSION: Preoperative hepatic magnetic resonance imaging should be considered in patients with potentially resectable pancreatic ductal adenocarcinoma, especially those with high tumor burden.

Percutaneous transhepatic versus EUS-guided gallbladder drainage for malignant cystic duct obstruction.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been proposed as an alternative management strategy for acute cholecystitis caused by malignant cystic duct obstruction in patients for whom surgery is not an option. This study aimed to compare the results of EUS-GBD with those of percutaneous transhepatic gallbladder drainage (PTGBD) for palliative management of malignant cystic duct obstruction with acute cholecystitis or symptomatic gallbladder hydrops. METHODS: Between November 2013 and November 2015, 14 patients with acute cholecystitis or symptomatic gallbladder hydrops as a result of malignant cystic duct obstruction underwent EUS-GBD with covered metal stents. Nineteen patients with acute cholecystitis as a result of malignant cystic duct obstruction who received PTGBD served as a control group. Patients' medical records were reviewed retrospectively. RESULTS: The technical and clinical success rates of EUS-GBD were 85.7% (12/14) and 91.7% (11/12) and of PTGBD were 100% (19/19) and 86.4% (17/19), respectively. The groups had similar adverse event rates (28.5% and 21.1%, respectively). The average duration of stent patency in patients with EUS-GBD was 130.3 ± 35.3 days, and no patient required an additional procedure before death. In 6 of 17 patients (35.3%) with clinically successful PTGBD, the catheter was not removed until the end stage of life. CONCLUSIONS: EUS-GBD is a feasible, safe, and effective modality for the treatment of malignant cystic duct obstruction in patients who are not indicated for surgery. It enables improved long-term quality of life in patients with advanced-stage cancer.

The Efficacy of Clinical Predictors for Patients with Intermediate Risk of Choledocholithiasis.

BACKGROUND/AIMS: For the suspected choledocholithiasis, the American Society for Gastrointestinal Endoscopy has proposed guidelines to assign risk based on clinical predictors. The study aimed to assess the usefulness of clinical predictors of choledocholithiasis set forth by the guidelines in patients with intermediate risk of choledocholithiasis. METHODS: In 2014, 109 patients with intermediate risk of choledocholithiasis underwent endoscopic ultrasound. Their medical records were retrospectively reviewed. The gold standard for choledocholithiasis was endoscopic retrograde cholangiopancreatography or clinical follow-up. RESULTS: Based on endoscopic ultrasound findings, choledocholithiasis was suspected in 18 patients, and it was removed in 17 patients. Choledocholithiasis was absent in the remaining 91 who did not show any signs from endoscopic ultrasound. Among the 2 strong (common bile duct (CBD) diameter >6 mm and bilirubin 1.8-4 mg/dl) and 3 moderate (abnormal liver biochemical test other than bilirubin, age >55 years and gallstone pancreatitis) clinical predictors, 28.8% of patients with one of the strong predictors had choledocholithiasis; however, only 3.5% of patients with any one of the moderate predictors had choledocholithiasis. As a result, only strong clinical predictors showed predictability: increased bilirubin level (OR 3.23; 90% CI 0.85-12.28) and dilated CBD diameter (OR 5.83; 90% CI 1.93-17.57). CONCLUSION: Only strong clinical predictors of choledocholithiasis showed predictability for patients with intermediate risk of choledocholithiasis.

Risk Factors for Gallstone Formation in Resected Gastric Cancer Patients.

Previous studies reported increased incidence of gallstone formation after gastrectomy. However, there were few reports about factors other than surgical technique. The purpose of this study is to investigate the spectrum of risk factors of gallstone formation after gastrectomy. From June 2003 to December 2008, 1480 patients who underwent gastrectomy due to gastric cancer but had no gallstones before surgery were identified. Electronic medical records were retrospectively reviewed. Gallstones were assessed by computerized tomography or ultrasound performed as surveillance for recurrence. There were 987 men (66.7%) and the median age was 59.0 years. The median follow-up period was 47.0 months. According to the surgical technique, 754 (50.9%), 459 (31.1%), and 267 (18.0%) underwent subtotal gastrectomy with Billroth I (STG B-I) and Billroth II (STG B-II) anastomosis, and total gastrectomy (TG). Within the follow-up period, gallstone formation occurred in 106 of 1480 patients (7.2%), the only 9 patients (0.6%) experienced symptomatic cholecystitis. By multivariate Cox regression analysis, age (HR 1.02, 95% CI 1.00-1.04), male (1.65, 1.02-2.67), diabetes mellitus (2.15, 1.43-3.24), ≥4% decrease of body mass index after surgery (1.66, 1.02-2.70), STG B-II (1.63, 1.03-2.57), and TG (2.35, 1.43-3.24) compared with STG B-I were associated with gallstone formation. Common bile duct stone formation occurred in 20 of 1480 patients (1.4%) and was only associated with gallstones. After gastrectomy, there were considerable numbers of patients with newly developed gallstones; however, prophylactic cholecystectomy should not be routinely recommended. Gastrectomy (STG B-II or TG), old age, male sex, diabetes mellitus, and decreased body mass index were associated with gallstones.

Clinical impact of neoadjuvant treatment in resectable pancreatic cancer: a systematic review and meta-analysis protocol.

INTRODUCTION: Although the only curative strategy for pancreatic cancer is surgical resection, up to 85% of patients relapse after surgery. The efficacy of neoadjuvant treatment in resectable pancreatic cancer (RPC) remains unclear and there is no systematic review focusing fully on this issue. Recently, two prospective trials of neoadjuvant treatment in RPC were terminated early because of slow recruiting and existing randomised controlled trials (RCTs) have too small sample sizes. Therefore, to overcome probable biases, it would be more reasonable to include both RCTs and non-randomised studies (NRSs) with selected criteria. This review aims to investigate the effect of neoadjuvant chemotherapy (CTx) and chemoradiation therapy (CRT) in RPC using RCTs and specific NRSs. METHOD AND ANALYSIS: This systematic review will include conventional RCTs as group I, and quasi-randomised controlled trials, non-randomised controlled trials and prospective cohort studies as group II. Two groups will be assessed and analysed separately. Comprehensive literature search will use Medline, Embase, Cochrane library and Scopus databases. Additionally, we will search references from relevant studies and abstracts from major conferences. Two authors will independently identify, screen, include studies, extract data and assess the risk of bias. Discrepancies will be resolved by consensus with another author. An independent methodologist will categorise and assess NRSs to minimise heterogeneity. In each study group, meta-analysis will be conducted using a random-effect model and statistical heterogeneity will be evaluated using I(2)-statistics. Publication bias will be visualised with contour-enhanced funnel plots and analysed with Egger's test. In group I, cumulative meta-analysis will be considered because the CTx regimen and CRT protocol have changed. The quality of evidence will be summarised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. ETHICS AND DISSEMINATION: This review does not use primary data, and formal ethical approval is not required. Findings will be disseminated through peer-reviewed journals and committee conferences. TRIAL REGISTRATION NUMBER: CRD42015023820.

High Expression of MicroRNA-196a Indicates Poor Prognosis in Resected Pancreatic Neuroendocrine Tumor.

There is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery. For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by ≥2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data. Eight miRNAs (miRNA-27b, -122, -142-5p, -196a, -223, -590-5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow-up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732-153.789; P = 0.015). MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required.

Comparison of Endoscopic Ultrasonography, Computed Tomography, and Magnetic Resonance Imaging for Pancreas Cystic Lesions.

Consensus regarding which modality is optimal for the measurement of pancreas cystic lesions (PCLs) was not achieved although cyst size is important for clinical decisions. This study aimed to evaluate the properties of endoscopic ultrasonography (EUS) compared with computed tomography (CT) and magnetic resonance imaging (MRI) in measuring the size of PCL.A total of 34 patients who underwent all 3 imaging modalities within 3 months before surgery were evaluated retrospectively. The size measured by each modality was compared with the pathologic size as a reference standard using Bland-Altman analysis and intraclass correlation coefficients (ICCs).The mean size difference was 1.76 mm (ICC 0.86), 7.35 mm (ICC 0.95), and 8.65 mm (ICC 0.93) in EUS, CT, and MRI. EUS had the widest range of 95% limits of agreement (LOA) (-17.54 to +21.07), compared with CT (-6.21 to +20.91), and MRI (-6.82 to +24.12). The size by EUS tended to be read smaller in tail portion, while those by CT and MRI did not. When the size was more than 4 cm, the size on EUS was estimated to be smaller than on pathology (r = 0.492; P = 0.003).Although 3 modalities showed very good reliability for the size measurement on PCL compared with corresponding pathologic size, EUS had the lowest level of agreement, while CT showed the highest level among the 3 modalities. Therefore, the size estimated by EUS has to be interpreted with caution, especially when it is located in tail and relevantly large.

Initial Metastatic Site as a Prognostic Factor in Patients With Stage IV Pancreatic Ductal Adenocarcinoma.

Few studies have evaluated the presence of hepatic or peritoneal metastasis as a prognostic factor in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). This study aimed to elucidate the prognostic value of the initial metastatic, extrahepatic, or hepatic site in patients with metastatic PDAC. Between January 2007 and December 2013, the medical records of 343 patients with metastatic PDAC treated at Seoul National University Bundang Hospital were retrospectively reviewed. Patients were classified as having extrahepatic metastasis alone (EH), hepatic metastasis alone (LV), and both hepatic and extrahepatic metastasis (BOTH). The median age was 67 years; 207 patients were men. Patients were classified as having EH (111 patients), LV (106), and BOTH (126). Totally, 212 patients underwent chemotherapy with a FOLFIRINOX (23 patients) or gemcitabine-based regimen (189). On multivariate analysis, an ECOG score ≥2 (hazard ratio [HR]: 3.2, 95% confidence interval [CI]: 2.2-4.5), albumin < 35  g/L (HR: 1.6, 95% CI: 1.1-2.3), C-reactive protein > 10  mg/L (HR: 2.3, 95% CI: 1.6-3.2), neutrophil-lymphocyte ratio > 5 (HR: 1.4, 95% CI: 1.0-2.0), no chemotherapy (HR: 2.0, 95% CI: 1.0-4.1), and metastatic site (LV, HR: 2.1, 95% CI: 1.4-3.1; BOTH, HR: 2.2, 95% CI: 1.6-3.2) were significantly associated with shorter overall survival (OS). Considering the initial metastatic site, the median OS of patients with EH, LV, and BOTH were 7.5 (95% CI: 6.3-8.8), 4.8 (95% CI: 4.1-5.5), and 2.4 (95% CI: 1.9-2.9) months, respectively. The initial metastatic site is significantly and independently associated with OS in patients with metastatic PDAC, serving as an effective prognostic factor.