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A 57-year-old woman with a sudden-onset seizure was hospitalized. Brain magnetic resonance imaging findings led to a suspicion of leptomeningeal carcinomatosis (LMC) without a brain parenchymal tumor, and abdominal computed tomography showed a tumor in the pancreatic tail. Endoscopic ultrasonography-guided fine needle aspiration of the pancreatic mass revealed adenocarcinoma. Therefore, LMC from pancreatic ductal adenocarcinoma was strongly suspected. She received three courses of nab-paclitaxel plus gemcitabine and whole-brain radiation. Shortly thereafter, she developed a severe consciousness impediment and died. A pathological autopsy showed adenocarcinoma in a wide area of the leptomeninges.

OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Cases of foreign body ingestion are encountered relatively often in clinical settings; however, serious complications are rare. In such cases, mediastinal abscess due to esophageal perforation can become a life-threatening complication. Although highly invasive, surgery is often used as the first-line treatment. We herein report the case of a 65-year-old woman who presented with complaints of progressive odynophagia and dysphagia for 2 weeks following a fish meal. Enhanced cervicothoracic computed tomography demonstrated an enhanced round mass with peripheral contrasted margins. The mass was diagnosed as a mediastinal abscess resulting from esophageal perforation caused by a fish bone. Endoscopic ultrasound-guided abscess drainage (EUS-AD) was performed using a nasobiliary drainage tube (NDT). Two weeks later, the abscess had completely disappeared. EUS-AD was safe and effective in this case; furthermore, external drainage using NDT was suitable for this abscess located very close to the upper esophageal sphincter.

Objectives Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for solid pancreatic lesions has high diagnostic yield. However, few prospective multicenter studies have been performed. We performed a prospective cohort study to evaluate the efficacy and safety of EUS-FNA for diagnosis of solid pancreatic lesions. Methods This prospective cohort study involved five hospitals in Japan. The primary outcome was sensitivity of EUS-FNA for diagnosing malignant lesions. We also evaluated parameters of diagnostic sufficiency and the safety of EUS-FNA. Results In total, 246 patients were enrolled. The absolute values of the parameters evaluated showed no significant differences; however, the percentage changes in the white blood cell counts and C-reactive protein levels after examination were significantly higher, and the percentage change in hemoglobin concentrations was significantly lower. The minor and major complication rates at the time of puncture, 24 h, 7 days and 28 days were 4.1%, 2.8%, 1.6%, and 0.0%, respectively. The true complication rate was 1.2%. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 97.2%, 88.0%, 96.2%, 100%, and 81.4%, respectively. Conclusions EUS-FNA for solid pancreatic lesions has high diagnostic yield and is safe, consistent with previously studies.

Endoscopic ultrasound/ultrasonography‐guided biliary drainage (EUS‐BD) is a relatively new modality for biliary drainage after failed or difficult transpapillary biliary cannulation. Despite its clinical utility, EUS‐BD can be complicated by severe adverse events such as bleeding, perforation, and peritonitis. The aim of this paper is to provide practice guidelines for safe performance of EUS‐BD as well as safe introduction of the procedure to non‐expert centers. The guidelines comprised patient–intervention–comparison–outcome‐formatted clinical questions (CQs) and questions (Qs), which are background statements to facilitate understanding of the CQs. A literature search was performed using the PubMed and Cochrane Library databases. Statement, evidence level, and strength of recommendation were created according to the GRADE system. Four committees were organized: guideline creation, expert panelist, evaluation, and external evaluation committees. We developed 13 CQs (methods, device selection, supportive treatment, management of adverse events, education and ethics) and six Qs (definition, indication, outcomes and adverse events) with statements, evidence levels, and strengths of recommendation. The guidelines explain the technical aspects, management of adverse events, and ethics of EUS‐BD and its introduction to non‐expert institutions., Highlight Isayama and colleagues present the first clinical practice guidelines for endoscopic ultrasound‐guided biliary drainage (EUS‐BD), including indications, clinical results, procedures, devices and education. Their primary purpose is to improve the outcomes of EUS‐BD for biliary tract diseases by facilitating the safe introduction and performance of the procedure at non‐expert centers.

Background : Endoscopic-guided placement of metal stents for unresectable malignant hilar biliary obstruction (UMHBO) is performed using partial stent-in-stent or side-by-side (SBS) techniques. The latter involves placing sequential stents within the bile duct. Excessive dilation of the bile duct during stent placement can have serious effects on the surrounding organs. Methods : This study details seven cases of SBS placement of 8.0 mm metal stents for UMHBO. Histopathological examinations were performed to identify the effects on the bile duct and surrounding tissues. Results : The mean post-placement diameter of the bile ducts was 13.86 mm, and no compression necrosis or thrombi were observed in surrounding tissues. Cholangitis occurred in five cases, and death occurred as a result of cholecystitis in one case. Conclusion : The use of 8.0-mm stents for SBS is unlikely to have major negative effects on peribiliary tissues and blood vessels. However, post-placement cholecystitis can result in increased mortality; thus, gallbladder drainage should be considered.

There have been no reports of ruptured solid pseudopapillary neoplasm (SPN) into adjacent organs. A 22-year-old female was referred to our hospital for treatment of a pancreatic head tumor. Computed tomography (CT) examination at our hospital showed a 5-cm tumor containing air, although CT at a previous hospital revealed an 8-cm tumor without air. Thus, a spontaneous rupture of the tumor into the duodenum was suspected. Subtotal stomach preserving pancreaticoduodenectomy with combined resection of the portal vein was performed. Contrast radiography of resected specimen showed the medium injected into the tumor leaking out from the 2nd portion of the duodenum. Histologically, the patient was diagnosed as SPN. Microscopic invasion to the portal vein and duodenum were also confirmed. She did not experience any postoperative complications and has remained well without any signs of recurrence during 2 years of follow-up. Although there have been 14 studies reporting ruptured SPN, this is the first report of SPN that spontaneously ruptured into the duodenum. An extremely rare case of SPN of the pancreatic head that spontaneously ruptured into the duodenum was reported.

Background and Aims EUS-guided choledochoduodenostomy (EUS-CDS) using conventional tubular stents has been successfully performed. However, EUS-CDS carries a high risk of bile leakage with attendant adverse events. This study aimed to prospectively evaluate the long-term outcome of EUS-CDS using a dedicated lumen-apposing metal stent (LAMS). Methods Nineteen patients (mean age, 70.6 years; 12 men) with unresectable malignant diseases were treated in 5 tertiary referral centers. EUS-CDS was performed using a fully covered LAMS with a cautery-enhanced delivery system for EUS-CDS. Results All stents were successfully deployed without any adverse events. Jaundice improved in 79% of the patients within 7 days and finally in 95%. In 95% of patients the stents remained in good anastomotic position without migration or dislocation during the follow-up period (median, 184 days; range, 12-819). One patient had a fever the day after stent placement. During the follow-up period 5 patients had secondary stent obstruction because of food residue (n = 2), kinking (n = 1), suspected tumor ingrowth (n = 1), and spontaneous dislodgement (n = 1). Five patients developed obstruction in the second portion of the duodenum. The overall adverse event rate was 36.8% (7/19), mostly with mild severity. Conclusions This study revealed that the novel dedicated LAMS used has high technical and clinical success rates for EUS-CDS. The adverse events and patency rates are inferior to the historically reported data of a conventional transpapillary metal stent. Development of a more suitable dedicated LAMS is anticipated.

A 68-year-old man with a history of diabetes mellitus was admitted to our hospital with a diagnosis of acute pancreatitis. Abdominal computed tomography revealed a suspicious tumor in the body of the pancreas, along with a dilated main pancreatic duct and edema of the pancreatic tail. Endoscopic retrograde pancreatography was performed after treating the patient's pancreatitis. When a cannula tip was advanced beyond the stenosis, deep into the distal pancreatic duct, thick white pus was evacuated. A bacteriological examination of the aspirated pancreatic juice revealed Enterobacter cloacae, and a cytological examination revealed adenocarcinoma. The diagnosis was acute obstructive suppurative pancreatic ductitis associated with pancreatic carcinoma.

A new classification of magnifying endoscopy with narrow band imaging (ME-NBI) for diagnosing and staging superficial esophageal squamous cell carcinoma (SESCC) was proposed by the Japan Esophageal Society in 2011. This study aimed to compare the new classification with the conventional classifications (Inoue's classification and Arima's classification). This was a prospective analysis of data from a single cancer center involving 151 consecutive patients with 156 SESCCs that were endoscopically or surgically resected. Initially, only ME-NBI images were selected and reviewed independently by three experienced endoscopists. White light imaging (WLI) was then evaluated separately after an interval. The diagnostic performance of each classification and interobserver agreement were assessed, and the WLI findings that affect the diagnosis by the new classification were identified. The specificity for classifying invasive depth as epithelium (EP)/lamina propria mucosae (LPM) confined was higher with the new classification than with Inoue's classification (0.512 vs. 0.349; P = 0.02) and Arima's classification (0.512 vs. 0.279; P < 0.01). However, the sensitivity was lower (0.902 vs. 1.000; P < 0.01) compared with Arima's classification. The concordance rates of three evaluators (κ values) were 0.52 for the new classification, 0.50 for Inoue's classification, and 0.23 for Arima's classification. On multivariate analysis, thickness on WLI independently affected the accuracy of diagnosis with the new classification (OR 3.23; 95%CI, 1.30-8.03). The new classification is superior to conventional classifications with respect to specificity for diagnosing SESCC with depth EP/LPM. Thickness on WLI was a factor negatively affecting the diagnostic performance of the new classification.

Background and study aims The standard colonoscopy preparation regimen in Japan for afternoon procedures is sequential intake of 1 L of polyethylene glycol electrolyte lavage solution containing ascorbic acid (PEG-ASC), 0.5 L of clear liquid, 0.5 L of PEG-ASC, and finally 0.25 L of clear fluids (all at a rate of 0.25 L every 15 min). However, this regimen seems poorly tolerated and complicated for many patients compared to previous regimen of polyethylene glycol electrolyte lavage solution. The aim of this study was to evaluate an alternate regimen of 0.5 L of PEG-ASC followed by 0.25 L clear liquids, repeated 3 times. Patients and methods This was a single-blinded, non-inferiority, randomized controlled study. Subjects were randomized to the standard regimen or the alternate regimen using a web-based registry system. All patients were instructed to eat a pre-packaged, low residue diet and to take sodium picosulfate hydrate the day before colonoscopy. The Boston Bowel Preparation Scale was used to evaluate bowel cleansing, and a 3-point scale was used to assess mucosal visibility. The primary endpoint was successful bowel cleansing. The acceptability, tolerability, safety, and endoscopic findings of these two regimens were secondary endpoints. Results A total of 409 patients were randomized to either the standard regimen (n = 204, males 54.0 %, mean age 65.5 years) or the alternate regimen (n = 205, 54.6 %, 65.0 years). The rates of successful bowel cleansing were 71.1 % (64.3 – 77.2 %) with the standard regimen vs. 75.1 % (68.6 – 80.9 %) with the alternate regimen (95 % lower confidence limit, for the difference = – 4.6, non-inferiority P Conclusion The alternate regimen and standard regimen are clinically equivalent with respect to cleansing efficacy and acceptability, tolerability, safety, and endoscopic findings. These results are good news for patients with difficulty drinking the first liter of PEG-ASC.

A young woman with Li-Fraumeni syndrome (LFS) was referred to our hospital. On examination, multiple flat neoplasms were detected in addition to semi-pedunculated polyps. Restorative proctocolectomy was performed; one submucosal invasive cancer, two mucosal cancers, and several adenomas with high-grade dysplasia were detected. On immunohistochemical staining with p53, every part of all neoplasms, even the small adenomas, showed strong positive staining. Multiple flat neoplasms may be characteristic of patients with LFS and may have a much higher risk of rapid progression to invasive carcinomas than sporadic neoplasms. Thus, careful and frequent colonoscopy surveillance may be needed for patients with LFS.

Objective The endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a salvage method for failed selective biliary cannulation. Three puncture routes have been reported, with many comparisons between the intra-hepatic and extra-hepatic biliary ducts. We used the trans-esophagus (TE) and trans-jejunum (TJ) routes. In the present study, the utility of EUS-RV for biliary access was evaluated, focusing on the approach routes. Methods and Patients In 39 patients, 42 puncture routes were evaluated in detail. EUS-RV was performed between January 2010 and December 2014. The patients were prospectively enrolled, and their clinical data were retrospectively collected. Results The patients' median age was 71 (range 29-84) years. The indications for endoscopic retrograde cholangiopancreatography (ERCP) were malignant biliary obstruction in 24 patients and benign biliary disease in 15. The technical success rate was 78.6% (33/42) and was similar among approach routes (p=0.377). The overall complication rate was 16.7% (7/42) and was similar among approach routes (p=0.489). However, mediastinal emphysema occurred in 2 TE route EUS-RV patients. No EUS-RV-related deaths occurred. Conclusion EUS-RV proved reliable after failed ERCP. The selection of the appropriate route based on the patient's condition is crucial.

We investigated peptide cocktail vaccine OCV-C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8 and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, overall survival (OS) and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. The median DFS was 15.8 months [95% confidence interval (CI), 11.1-20.6] and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with KIF20A-specific CTL responses and without (p = 0.027), and between patients with KIF20A expression and without (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. OCV-C01 combined with gemcitabine was tolerable with a median DFS of 15.8 months, which was favorable compared with previous data for resected pancreatic cancer.

Patient: Female, 40 Final Diagnosis: Invasive ductal carcinoma arising in mucinous cystic neoplasm of pancreas Symptoms: None Medication: — Clinical Procedure: Surgical resection Specialty: Oncology Objective: Rare co-existance of disease or pathology Background: Mucinous cystic neoplasm (MCN) of the pancreas is a rare mucin-producing cystic neoplasm that has a characteristic histological feature referred to as ovarian-type stroma (OS) underlying the epithelium. Pancreatic ductal carcinoma arises from MCN as a precursor lesion, but data on progression pathways are limited. Case Report: A 40-year-old female was referred to our hospital for further investigation of a pancreatic cyst. Further examination showed a 7.0 cm multilocular cyst in the pancreatic tail and a solid mass in the thick septum of the cystic tumor. Distal pancreatectomy and splenectomy were performed. Histological examination revealed a moderately differentiated invasive ductal carcinoma (IDC) with a diameter of 0.5 cm in the thick septum of the cystic lesion and a cyst wall composed of epithelium with low-grade to severe dysplasia. The epithelium covered an OS. Pathological diagnosis was IDC arising in MCN of the pancreas. Immunohistochemical examination showed that MUC1 expression was negative in MCN but positive in IDC. KRAS mutation was observed in both MCN and IDC regions. Conclusions: We present a rare case of moderately differentiated pancreatic IDC arising in MCN. To elucidate the underlying progression pathway, we explored the correlation between KRAS mutation and MUC expression as a clinico-pathological parameter.

Background : Both endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) and tumor ablation using ethanol are very common procedures, and the utility of these therapies has already been reported in prominent journals. However, their effectiveness appears temporary and insufficient, especially EUS-CPN. We therefore have to consider new reagents for improving the results. The present study examined the best concentration of ethanol and povidone iodine mixed with atelocollagen for more effective therapies. Methods : The effects of the new reagents were confirmed in three live pigs. At first, we injected three kinds of reagents (including indigo carmine) in three separate areas of para-aortic tissue under EUS guidance in one pig. At more than 4 hours after injection, we checked ethanol injection sites after dissection. In next study, we performed EUS-guided injection of a total of six kinds of reagents (two kinds of ethanol, three kinds of povidone iodine, and control atelocollagen) into the livers of two living pigs. After 2 weeks, we examined tissue damage to the liver in the two pigs. Results : The 75% ethanol (absolute ethanol 3.75 mL + 1% atelocollagen 1.25 mL + a very small amount of indigo carmine) was seen like blue gel, and still remained in the para-aortic tissue. Brownish areas of povidone iodine mixed with 3% atelocollagen exhibited clear, regular borders with greatly reduced infiltration into surrounding tissue compared to others. Conclusion : We concluded that 75% ethanol mixed with 1% atelocollagen appears optimal for EUS-CPN. Povidone iodine mixed with 3% atelocollagen may be suitable for small tumor ablation therapy.

Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30-60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC.We conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed.Median overall survival (OS) was significantly shorter for patients with high CEA (5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45-2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71-1.40).The present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA.

Background There have been no reports showing the incidence of anastomotic stenosis of continuous hepaticojejunostomy (HJ) and identifying its risk factors for patients who underwent pancreaticoduodenectomy (PD). Method We retrospectively investigated 200 patients whose HJ was established by unified method, single layered continuous suture. HJ stenosis was diagnosed with endoscopic or radiologic examinations. Uni and multivariable unconditional logistic modeling were performed to explore the predictive factors and to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Results Sixteen patients (8.0%) were diagnosed as HJ stenosis. Multivariable analysis showed that body mass index (BMI) (OR: 1.24; 95% CI: 1.03–1.51), absence of preoperative biliary stenting (OR: 11.10; 95% CI: 1.22–101.12), operative time (OR: 1.74 per one hour increase; 95% CI: 1.01–2.98), age (OR: 1.58 per 10 years increase; 95% CI: 0.88–2.85), and absence of nodal metastasis (OR: 3.43; 95% CI: 0.90–13.12) correlated with HJ stenosis. Among these, BMI and preoperative biliary stenting were associated with stenosis with a lower P-value than the others (P = 0.026 and 0.033, respectively). Conclusions The incidence of HJ stenosis was 8.0%. Close attention would be needed especially for patients at high risk of HJ stenosis, such as high BMI or absence of preoperative biliary stenting.

Background and study aims: Endoscopic resection is one treatment option for residual or locally recurrent esophageal cancer after definitive chemoradiotherapy or radiotherapy alone. However, little is known about the clinical benefit of salvage endoscopic resection for these lesions. Therefore, the effectiveness and prognostic factors of salvage endoscopic resection were investigated. Patients and methods: A total of 37 patients with esophageal squamous cell carcinoma (SCC) who underwent salvage endoscopic resection after definitive chemoradiotherapy or radiotherapy alone were reviewed. The method of salvage endoscopic resection was endoscopic mucosal resection using a cap (EMR-C), strip biopsy, or endoscopic submucosal dissection. The effectiveness and prognostic factors of salvage endoscopic resection were retrospectively analyzed. Results: A total of 37 patients with 49 lesions underwent salvage endoscopic resection. Baseline clinical stages were I in 23 patients, II in 3 patients, III in 9 patients, and IV in 2 patients. The number of locoregional recurrences and residual lesions were 35 and 14, respectively. The curative en bloc resection rate was 53.1 % (26/49). The total incidence of complications was 18.9 % (7/37); all were successfully managed conservatively. The 3-year and 5-year overall survival rates were 72.9 % and 53.3 %, respectively, with a median follow-up period of 54 months. Baseline clinical T1 – 2 and N0 were significant factors for good prognosis in terms of overall survival on univariate analysis. Conclusions: Salvage endoscopic resection, especially EMR-C, is a safe and feasible procedure to control residual or recurrent superficial esophageal SCC after definitive chemoradiotherapy or radiotherapy alone. The present results showed that baseline clinical T1 – 2 and N0 before chemoradiotherapy or radiotherapy were significant prognostic factors.

Carbohydrate antigen 19-9 (CA19-9) is a widely used tumor marker for pancreatic ductal adenocarcinoma (PDAC). In addition, several studies have reported the utility of both pre- and postoperative CA19-9 levels as prognostic factors in resectable PDAC. However, little is known about the implications of post-adjuvant chemotherapy (AC) CA19-9 levels. The purpose of this study was to examine the utility of the post-AC CA19-9 level as a prognostic marker for relapse-free survival (RFS) in resectable PDAC.A total of 119 patients who completed AC were analyzed (normal post-AC CA19-9, n = 79; high post-AC CA19-9, n = 40). The upper limit of the normal (ULN) serum level of CA19-9 was 37 U/mL.Median RFS was significantly shorter for patients with high post-AC CA19-9 levels than for those with normal post-AC CA19-9 (10.4 months vs. 29.6 months, respectively; p 0.001). After adjustment, high post-AC CA19-9 level was an independent predictive factor for short RFS (hazard ratio for RFS, 2.72). Median overall survival was significantly shorter in patients with high post-AC CA19-9 levels than in those with normal postoperative CA19-9 levels (24.7 months vs. 92.1 months, respectively; p 0.001). The optimal cutoff value of post-AC CA19-9 levels for prediction of early recurrence was1.5 × UNL (55.5 U/mL), with a 74.2% positive predictive value.The present results show that high post-AC CA19-9 level is an independent prognostic factor for short RFS in patients with resected PDAC. In addition, it may be useful for predicting early recurrence.

Objective Some patients with malignant gastric outlet obstruction require combined biliary and gastroduodenal stenting (double stenting). However, biliary stent dysfunction can often disturb biliary route maintenance, thus making the optimal biliary stenting for these patients unclear. The present study was designed to assess the factors associated with the long-term maintenance of biliary drainage routes. Methods The clinical features and long-term outcomes were assessed in patients who underwent double stenting. Patients The outcomes were reviewed in 43 consecutive patients who successfully underwent endoscopic double stenting with metallic stents. Results An univariate analysis of all patients with biliary stent dysfunction showed the separate type of double stenting (two stents placed in a non-crossed position) to be the only predictive factor related to successful biliary re-intervention for stent dysfunction (odds ratio 73.67, p=0.001). A comparison of the clinical features in patients who underwent separate and cross (two stents placed in a crossed position) stenting showed the functional success rate to be higher for the separate (93.3%) than for the cross (61.5%) stent type, with the median times to biliary stent dysfunction differing significantly (330 vs. 298 days, respectively; p=0.048). The success rates of re-intervention in patients with separate and cross type stents were 88.9% and 0.0%, respectively (p=0.001), and the initial biliary route maintenance rates were 96.7% and 53.8%, respectively (p=0.002). Conclusion The separate type of double stenting may enhance successful biliary re-intervention for stent dysfunction and also maintain the initial drainage route longer. The biliary drainage outcomes should therefore be considered when choosing the type of double stenting.

Background Multiple studies have investigated sampling adequacy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic neuroendocrine neoplasms (pNENs). However, none have described the diagnostic performance of EUS-FNA for pNENs, or the influencing factors. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA, with post-operative pathological diagnosis as the gold standard, and factors predictive of inadequate EUS sampling. Methods From 1998 to 2014, a total of 698 patients underwent pancreatic resection and 1455 patients underwent EUS-FNA sampling for pancreatic lesions. A total of 410 cases underwent both surgical resection and preceding EUS-FNA. Of these, 60 cases (49 true pNEN, nine non-diagnostic, two misdiagnoses) were included. We studied diagnostic performance of EUS-FNA and factors that were associated with failed diagnosis. Results Of the 60 cases, EUS-FNA yield was 49 true-positive cases, two misdiagnoses, and nine non-diagnostic cases (including six suggestive cases). Sensitivity, specificity, and accuracy were 84.5, 99.4, and 97.3 %, respectively; including the six suggestive cases, diagnostic values were 94.8 % sensitivity (55/58), 99.4 % specificity (350/352), and 98.7 % accuracy (405/410). In multivariate analysis, sampling adequacy rates were significantly lower when lesions were located in the pancreatic head [odds ratio (OR) = 10.0] and in tumor-rich stromal fibrosis (OR = 10.45). Tumor size, needle type, tumor grading, presence of cystic component, and time period were not significant factors. Conclusions EUS-FNA offers high accuracy for pNEN. However, location of the tumor in the pancreatic head and presence of rich stromal fibrosis negatively impacts sampling adequacy. Electronic supplementary material The online version of this article (doi:10.1007/s00535-016-1164-6) contains supplementary material, which is available to authorized users.

Background The aim of this study was to examine the associations between postoperative clinicopathological features of intraductal papillary mucinous neoplasm (IPMN) and recurrence over a long follow-up period. Methods We retrospectively assessed 153 IPMN patients who underwent resection. Results The resected tumors showed low/intermediate-grade dysplasia (LGD/IGD), high-grade dysplasia (HGD), T1a (stromal invasion ≤5 mm), and invasive intraductal papillary mucinous carcinoma (IPMC), in 54.9%, 22.2%, 4.6%, and 18.3% of patients, respectively. The median follow-up period after surgery was 46.4 (6.0–216.3) months, with an overall recurrence rate of 17.0%; the recurrence rates by histological type were 6.0%, 5.9%, 42.9%, and 57.1% for LGD/IGD, HGD, T1a, and invasive IPMC, respectively. Multivariate analysis revealed that recurrences related with tumor location, mural nodule size, presence of invasive cancer, lymph node metastasis, IPMN in the remnant pancreas, and main pancreatic duct dilatation after surgery. Recurrence occurred within the remnant pancreas in all LGD-T1a patients and as extrapancreatic metastasis in all patients with invasive IPMC. Of the total recurrences, 15.4% occurred over 5 years postoperatively. Conclusions The postoperative follow-up protocol for patients with LGD-T1a should be similar to non-resected IPMN, and that for invasive IPMC should be the same as for pancreatic ductal adenocarcinoma patients.

Objective We previously published a nomogram for prediction of carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). The objective of the current study was to validate this nomogram in an external cohort of patients at multiple institutions. Methods The clinical details of 180 patients with IPMN who underwent a pancreatic resection at 3 hospitals were collected. Four significant predictive factors (sex, lesion type, nodule height, and pancreatic juice cytology) were analyzed. Results Of the 180 patients, 66 (36.7%) had a main pancreatic duct-type IPMN and 114 (63.3%) had a branch pancreatic duct-type IPMN. The final pathological diagnosis was benign IPMN in 95 (52.8%) patients and malignant IPMN in 85 (47.2%) patients. The area under the receiver operating characteristic curve for the model was 0.760. The area under the receiver operating characteristic curve of the IPMN nomogram for prediction of malignancy was 0.747 in main pancreatic duct-type IPMN and 0.752 in branch pancreatic duct-type IPMN. The sensitivity and specificity of the model were 80.0% and 57.9%, respectively, when the predictive probability of more than 10% was used to indicate the presence of carcinoma. Conclusions This nomogram for predicting the probability of carcinoma in patients with IPMN was accurate in an external validation patient cohort.

Evaluation of polyethylene glycol electrolyte lavage solution containing ascorbic acid (PEG-ASC) has been controversial in the point of its hyperosmolarity, especially in old population. So we therefore designed the present study to compare the efficacy, acceptability, tolerability, and safety of 1.5 L PEG+ASC and 2 L standard PEG electrolyte solution (PEG-ELS), not only in the general population, but also in patients of advanced age. Randomization was stratified by age ( years), and hematological and biochemical parameters were compared in each age group, especially with respect to the safety profile of each regimen. As a result, the 1.5-L PEG-ASC regimen had higher patient acceptability than the 2-L PEG-ELS regimen. Tolerability, bowel cleansing, and safety were similar between regimens. However, we demonstrated significant statistical changes in the hematological and biochemical parameters after taking bowel preparation solutions, not only in the PEG+ASC group, but also in the PEG-ELS group. No significant differences in the safety profile were found between subjects aged less than 70 years and those aged 70 years or more; nevertheless, regardless of age, proper hydration is needed throughout the bowel preparation process.

Endoscopic ultrasound (EUS) is a key modality for the evaluation of suspected pancreatic cystic neoplasms (PCNs), as the entire pancreatic gland can be demonstrated with high spatial resolution from the stomach and duodenum. Detailed information can be acquired about the internal contents of the cyst(s) [septum, capsule, mural nodules (MNs)], its relation with the main pancreatic duct (MPD), and any parenchymal changes in the underlying gland. PCNs comprise true cysts and pseudocysts. True cysts can be neoplastic or nonneoplastic. Here, we describe serous cystic neoplasm (SCN), mucinous cystic neoplasm (MCN), and intraductal papillary mucinous neoplasm (IPMN) as prototype neoplastic cysts, along with nonneoplastic lymphoepithelial cysts (LECs).

To clarify the incidence, clinicopathological features and prognosis of pancreatic invasive ductal carcinomas (IDCs) with different tumor origin sites in the pancreatic duct. Based on the relationship between the invasive cancer area (ICA) and the main pancreatic duct (MPD), IDCs less than 2 cm in diameter were classified into two groups: type I, in which the ICA and MPD were separated, and type II, in which the MPD passed through the ICA. The clinicopathological findings and prognosis of each type were compared in a total of 37 patients. The incidences of IDC types I and II were 18.9 and 81.1 %, respectively. Although there was no difference in local invasion, both node involvement and venous invasion tended to occur more frequently in type I IDC, and the three-year survival rate was significantly lower for type I (28.6 %) than type II (71.8 %) IDC. The prognosis of IDCs that originated in the branching pancreatic duct (BPD) distant from the MPD (type I) was worse than the prognosis of IDCs that originated in either the MPD or the BPD close to the MPD (type II). These data suggest that the progression and degree of malignancy of IDCs may vary depending on the site of tumor origin in the pancreatic duct.

Despite a low incidence, the mortality rate of pancreatic cancer (PC) is high. Early detection and optimal treatment based on the findings of various imaging modalities are essential to improve the survival rate of patients with PC. Multi-detector (MD) row computed tomography (CT) is currently the standard imaging modality for evaluating PC worldwide. However, 10% of PC tumors can be iso-attenuated on CT and thus invisible, especially when ≤2 cm. Endoscopic ultrasonography (EUS) can detect tumors that are

Background and Aim Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract. However, little is known about the clinical presentation of GIST, especially small lesions. The purpose of the present study was to clarify the efficacy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of GIST and to determine its clinical course. Methods Pathological and clinical records of GIST extracted from our institutional database between 1996 and 2012 were reviewed. All GIST cases were diagnosed pathologically by surgical specimen or EUS-FNA. To examine the efficacy of EUS-FNA for the diagnosis of GIST, the pathological findings of EUS-FNA were compared with the surgical findings from resected cases. Next, to clarify the clinical presentation of GIST, imaging findings and changes in tumor size over time were evaluated in follow up. Results Of 84 cases of GIST, 67 were resected surgically after EUS-FNA; tumor size was

Adenosquamous carcinoma of the pancreas (ASC) is a rare malignant neoplasm of the pancreas, exhibiting both glandular and squamous differentiation. However, little is known about its imaging features. This study examined the imaging features of pancreatic ASC.We evaluated images of contrast-enhanced computed tomography (CT) and endoscopic ultrasonography (EUS). As controls, solid pancreatic neoplasms matched in a 2:1 ratio to ASC cases for age, sex and tumor location were also evaluated.Twenty-three ASC cases were examined, and 46 solid pancreatic neoplasms (43 pancreatic ductal adenocarcinomas, two pancreatic neuroendocrine tumors and one acinar cell carcinoma) were matched as controls. Univariate analysis demonstrated significant differences in the outline and vascularity of tumors on contrast-enhanced CT in the ASC and control groups (P 0.001 and P 0.001, respectively). A smooth outline, cystic changes, and the ring-enhancement pattern on contrast-enhanced CT were seen to have significant predictive powers by stepwise forward logistic regression analysis (P = 0.044, P = 0.010, and P = 0.001, respectively). Of the three, the ring-enhancement pattern was the most useful, and its predictive diagnostic sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ASC were 65.2%, 89.6%, 75.0% and 84.3%, respectively.These results demonstrate that presence of the ring-enhancement pattern on contrast-enhanced CT is the most useful predictive factor for ASC.

Background and Aim Self-expandable metallic stents have mainly been used for the palliation of malignant gastric outlet obstruction (GOO). However, their use in long-term survivors and the feasibility, safety and benefit of additional intervention for stent dysfunction remain controversial. The present study examined the long-term benefits of endoscopic gastroduodenal stenting. Methods We reviewed 61 patients treated with Niti-S stents at several hospitals and estimated the efficacy of stent intervention, stent patency, eating period and factors related to poor effectiveness. Results All 61 first stent interventions and 14 additional stent interventions (11 second interventions and 3 third interventions) were successfully carried out. Clinical success rates were 83.6% and 85.7%, and median stent patency was 214 days and 146 days (P = 0.47), respectively. Fifty patients could be treated with a first stent only, and 11 patients received additional stents. At the time of study termination or death, 70.0% of the former group and 63.6% of the latter group maintained oral intake (P = 0.71), and each 86% and 100% among the group could maintain oral intake for a period exceeding half of their remaining lives after first stent intervention. Karnofsky performance status ≤50 (P = 0.03), ascites (P = 0.009), and peritoneal dissemination (P = 0.001) appeared to be factors related to poor effectiveness. Conclusions Despite the presence of factors related to poor effectiveness, endoscopic gastroduodenal stenting would be the first treatment of choice for GOO and provide long-term benefits. If stent dysfunction occurs, additional stent intervention enables continued oral intake safely.

Objectives This study investigated whether a risk assessment nomogram can predict the malignant potential of intraductal papillary mucinous neoplasms (IPMNs) and provide valuable information for the follow-up and counseling strategies of such patients. Methods We studied 126 of 589 patients with IPMN who were followed up for at least 36 months with annual endoscopic ultrasonography. We analyzed scores derived from our nomogram, incorporating the parameters of sex, lesion type, mural nodule height, and pancreatic juice cytology determined at the initial IPMN evaluation. Results The rate of malignant IPMNs was 5.5% (7/126). The initial average nomogram score was 19.8 (range, 0-55), and the final follow-up average was 23.8 (range, 0-109). When a cutoff score was set at 35 points, the sensitivity, specificity, and accuracy of the nomogram to assess malignancy risk were 87.5%, 96.6%, and 96%, respectively. The area under the receiver operating characteristic curve of malignant IPMN prediction during follow-up was 0.865. Conclusions The ability of the nomogram to predict malignancy in patients with IPMN was validated. Our findings can suggest that a follow-up for patients at high and low risk for cancer progression could be scheduled every 3 to 6 and 12 months, respectively.

Adenosquamous carcinoma of the pancreas (ASC) is a variant of pancreatic ductal adenocarcinoma (PDAC), but the prognosis remains unclear. The purpose of this study was to clarify the prognosis of ASC using a matched case-control design.We evaluated clinical characteristics of ASC treated between 2001 and 2011 in our institution. As controls, PDAC cases matched with ASC cases for sex, age, pretreatment Eastern Cooperative Oncology Group performance status, location, initial therapy and American Joint Committee on Cancer TNM staging for pancreatic cancer were also evaluated.Of the 914 cases of pancreatic neoplasm, 28 cases (3.06%) of ASC were identified, and 56 cases of PDAC were matched as controls. Median overall survival (OS) was significantly worse for ASC (8.38 months) than for PDAC (15.75 months; hazard ratio [HR], 1.94; 95% confidence interval, 1.07-3.51; P = 0.026). Of the 22 unresected cases, median OS was again significantly worse for ASC (4.67 months) than for PDAC (12.36 months; HR, 2.39; 95% confidence interval, 1.27-4.51; P = 0.007).These results demonstrate that ASC is more aggressive than PDAC.

Objective: This study was performed to compare health-related quality of life (HRQOL) of gemcitabine plus S-1 (GS), S-1 alone and gemcitabine alone as first-line chemotherapy for locally advanced or metastatic pancreatic cancer in the GEST (Gemcitabine and TS-1 Trial) study and to assess the impacts of adverse events and tumour response on HRQOL. Methods: Patients were randomly assigned to receive gemcitabine alone (1000 mg/m2 weekly for 3 of 4 weeks), S-1 alone (80, 100 or 120 mg/day twice daily for 4 of 6 weeks) or GS (gemcitabine at 1000 mg/m2 weekly plus S-1 at 60, 80 or 100 mg/day twice daily for 2 of 3 weeks). HRQOL was assessed using the EuroQoL-5D (EQ-5D) questionnaire at baseline and weeks 6, 12, 24, 48 and 72. EQ-5D scores, quality-adjusted life months (QALMs), quality-adjusted progression-free months (QAPFMs) and time until definitive HRQOL deterioration (TUDD) were compared among the three groups. The impacts of adverse events and tumour response on EQ-5D scores were analysed. Results: Including EQ-5D scores after death as 0, the mean profile was significantly better in the GS than gemcitabine group (difference, 0.069; p=0.003), but not the S-1 group (difference, −0.011; p=0.613). The mean profiles until death were similar in the three groups. QALMs, QAPFMs and TUDD were significantly longer in the GS than gemcitabine group (p

Background and study aims Anastomotic stricture is a late complication after biliary reconstructive surgery, but standard treatments are currently lacking. We selected patients who had undergone pancreaticoduodenectomy and Child’s procedure, and aimed to evaluate the safety and efficacy of temporary placement of fully covered self-expandable metal stents (FCSEMSs) to treat postoperative anastomotic stricture. Patients and methods This study retrospectively analyzed 13 patients who underwent treatment with FCSEMSs for anastomotic stricture between June 2011 and March 2016. We evaluated technical and clinical success, complications, duration of patency after FCSEMS removal, and re-stenosis. Results All of the anastomotic strictures were improved by FCSEMS placement and luminal patency was maintained throughout the follow-up period, with no complications. After 2 months, the FCSEMSs were removed endoscopically in nine patients, and in four patients the stent had been expelled spontaneously per rectum. Median duration of follow-up was 225 days (range 30 – 935 days). No re-stenosis occurred in any of the 13 cases following stent removal. Conclusion Deployment of FCSEMSs for anastomotic stricture offers a safe and promising treatment that may replace percutaneous transhepatic biliary drainage and deployment of multiple plastic stents as the first-line treatment.

EUS-guided biliary drainage (EUS-BD) was developed as a rescue method of ERCP. Recently, the usefulness of EUS-BD for the papilla tumors, duodenal stenosis by tumors, or altered anatomy patients were reported in many papers. EUS-BD is a good indication for difficult ERCP cases. In addition, “de novo EUS-BD” for malignant lower biliary obstructions is focused by experienced endosonographers now. The most different points in these two procedures are kinds of complications. Post-ERCP pancreatitis is a big problem in ERCP until now. All physicians made efforts to decrease post-ERCP pancreatitis for very long time, but still unresolved. EUS-BD is very low risk of pancreatitis, nearly zero. However, bile peritonitis is a common complication of EUS-BD. Which is the better procedure for malignant lower biliary obstructions? Hence, in this review, we will focus on de novo EUS-BD, not a rescue of the standard transpapillary drainage for lower biliary obstructions. We will not mention about de novo EUS-BD for hilar obstructions which is still controversial because of not enough evidence.

Endoscopic ultrasound (EUS) can demonstrate the detailed anatomy of the liver from the transgastric and transduodenal routes. Most of the liver segments can be imaged with EUS, except the right posterior segments. The intrahepatic vascular landmarks include the major hepatic veins, portal vein radicals, hepatic arterial branches, and the inferior vena cava, and the venosum and teres ligaments are other important intrahepatic landmarks. The liver hilum and gallbladder serve as useful surface landmarks. Deciphering liver segmentation and anatomy by EUS requires orienting the scan planes with these landmarkstructures, and is different from the static cross-sectional radiological images. Orientation during EUS requires appreciation of the numerous scan planes possible in real-time, and the direction of scanning from the stomach and duodenal bulb. We describe EUS imaging of the liver with a curved linear probe in a step-by-step approach, with the relevant anatomical details, potential applications, and pitfalls of this novel EUS application.

BACKGROUND AND STUDY AIM Malignancy in pancreatic neuroendocrine tumors (PNETs) is graded by assessing the resected specimens according to the World Health Organization (WHO) 2010 criteria. The feasibility of such grading using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens remains unclear. The aim of this study was to ascertain the optimal method of measuring the Ki-67 index in EUS-FNA specimens, using resected specimens as the criterion standard. PATIENTS AND METHODS A total of 58 consecutive patients diagnosed with PNETs between March 1998 and May 2011 were included. The study measured intratumoral Ki-67 index heterogeneity, concordance rates of PNET grading by EUS-FNA with grade of the resected tumor, optimal method of measuring the Ki-67 index in EUS-FNA specimens, and survival analysis based on EUS-FNA specimen grading. RESULTS Intratumoral dispersion of Ki-67 index in resected specimens was 0.033 for Grade 1 and 0.782 for Grade 2 tumors (P

The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis.Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]).The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.

Ultrasound using microbubble-based contrast agents is useful for vascular imaging. Directional eFLOW (D-eFLOW) is a novel technology for vascular assessment that provides high spatial and temporal resolution. The purpose of this study was to investigate the utility of endoscopic ultrasound (EUS)-guided D-eFlow before and after administration of an ultrasound contrast agent (USCA) for assessing the vascularity of solid pancreatic lesions. D-eFlow was compared to power Doppler EUS (PD-EUS) or color Doppler EUS (CD-EUS) before and after USCA injection. We also evaluated the Visual Vascular Assessment (ViVA) scale for the estimation of vascularity and investigated its reliability using the interclass correlation coefficient (ICC). From January 2007 to March 2007, 35 patients (mean age, 64.5 years old; age range, 28–81 years) underwent EUS followed by D-eFLOW EUS, PD-EUS, and CD-EUS before and after administration of USCA. The pancreatic parenchymal ViVA score, pancreatic vascular pattern, and ICC were evaluated for all lesions. Concerning the sensitivity for detection of the hypovascular pattern in pancreatic adenocarcinoma, D-eFLOW (before and after USCA) had similar sensitivity to PD-EUS (before and after USCA) and CD-EUS (before and after USCA). D-eFLOW after contrast showed the highest accuracy (82.3 %) and negative predictive value (53.8 %) among all the modalities investigated. There was a good correlation among the ViVA scores for D-eFLOW before contrast, those for D-eFLOW EUS, and those for PD-EUS and CD-EUS. The reliability of the ViVA scale was excellent with an ICC of 0.81. In conclusion, D-eFLOW EUS is a sensitive, reliable, and highly accurate method of assessment of pancreatic vascularity. D-eFLOW EUS with contrast was more sensitive than PD-EUS and CD-EUS for assessment of pancreatic vascularity.

Purpose The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m 2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m 2 /day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

The CDKN2A(p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (OR het=1.14, 95% CI 1.01-1.27, p=0.026, ORhom =1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/Blocus could represent a genetic link between diabetes and pancreatic cancer risk.

Aim: To reveal the impact of preoperative endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: We retrospectively reviewed 242 patients who underwent surgery for PDAC at our institution between January 1996 and July 2012. Among them, there were three patients with R2 resection and 30 patients with a follow-up period of less than 1 year, who were excluded because they did not meet the conditions for evaluating recurrence. Consequently, 209 patients were enrolled in the present study. The patients were divided into two groups: 126 patients who underwent preoperative EUS-FNA (FNA group) and 83 patients who did not (non-FNA group) undergo preoperative EUS-FNA. Results: There were no significant differences in baseline characteristics between FNA and non-FNA groups except mean age (66.6 ± 8.9 years vs. 63.5 ± 8.9 years, respectively, P = 0.02) and the administration rate of gemcitabine as adjuvant chemotherapy (42.9% vs. 18.1%, P < 0.01). Sampling adequacy of preoperative EUS-FNA was 99.2% (125/126) and sensitivity for diagnosis was 92.9% (117/126). The rate of complications related to EUS-FNA was 1.6% (2/126); two patients experienced reduction in hemoglobin (≥2.0 g/dL). These two patients did not have any apparent bleeding and could be managed conservatively. No severe complications were seen. We evaluated long-term outcomes of preoperative EUS-FNA, especially disease-free survival, needle-track seeding and recurrence. Kaplan-Meier analysis indicated no significant difference in disease-free survival between the two groups (P = 0.12). The site of recurrence was not significantly different between groups. Needle-track seeding was not observed in this study. Multivariate analysis of recurrence factors showed that preoperative EUS-FNA did not affect postoperative recurrence. Conclusion: Preoperative EUS-FNA for PDAC was shown to be a safe procedure with high diagnostic ability, and not a risk factor for postoperative recurrence.