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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Highlight The incidence of anastomotic stenosis of continuous hepaticojejunostomy after pancreaticoduodenectomy was 8.0% among 200 patients investigated retrospectively by Asano and colleagues. Close attention is needed especially for patients who are at high risk of this complication, such as those with high body mass index or absence of preoperative biliary stenting. [ABSTRACT FROM AUTHOR]

Background: The best way to perform endoscopic stenting for hilar malignant biliary obstruction (HMBO) is under discussion. Recently, a 6‐mm covered self‐expandable metal stent (CSEMS) has become available. In this article, the results of side‐by‐side (SBS) 6‐mm CSEMS deployment for HMBO are reported. Methods: A total of 22 patients, 32 procedures of SBS 6‐mm CSEMS [16 fully covered (FCSEMS), 16 partially covered (PCSEMS)] deployment for HMBO, were prospectively enrolled from November 2011 to June 2015 and retrospectively analyzed. Technical and clinical success rates, stent patency period, complications, and re‐intervention success rates were analyzed. Results: The overall/FCSEMS/PCSEMS technical and clinical success rates were 96.9%/93.8%/100% and 93.5%/100%/87.5%, respectively. The mean stent patency period was 95/113/68 days. Early and late complication rates were 3.1%/0%/6.3% and 6.3%/12.5%/0%, respectively. Stent exchange was attempted in 12 procedures, and the stent exchange success rate was 83.3%/100%/75%. Conclusions: This is the first report of SBS 6‐mm CSEMS deployment for HMBO. This procedure has high technical and clinical success rates and the advantages of ease of performance and a high success rate of re‐intervention. Outcomes appear better with FCSEMS than with PCSEMS deployment. Since stent patency is still controversial, large‐sample studies are needed. Highlight Yoshida and colleagues report that side‐by‐side deployment of 6‐mm covered self‐expandable metal stents (SEMS) was efficient for hilar malignant biliary obstruction. The fully covered type (FCSEMS) had a good stent patency period. All occluded FCSEMS could be removed, and revision of the FCSEMS was achieved in six of seven cases. [ABSTRACT FROM AUTHOR]

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. Highlight This is the first study evaluating postoperative recurrence patterns of intraductal papillary mucinous neoplasms in detail over a long follow‐up period in accordance with the new International Consensus Guidelines 2012 for the Management of IPMN. On the basis of the results, Yogi and colleagues proposed new follow‐up protocols following resection. [ABSTRACT FROM AUTHOR]

Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo-controlled, double-blind phase II/ III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test was applied to the statistical analysis in this study to evaluate the time-lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington-Fleming P-value, 0.918; log-rank P-value, 0.897; hazard ratio, 0.87, 95% confidence interval [ CI], 0.486-1.557). Median survival time was 8.36 months (95% CI, 7.46-10.18) for the Active group and 8.54 months (95% CI, 7.33-10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 <20 mm in 19 patients, and ≥20 mm in 48 patients. For the diagnosis of small GIST<20 mm, sensitivity and positive predictive value of EUS-FNA were 81.3% and 100%, respectively. A total of 27 patients with GIST was follow up for more than 1 year. Tumor size increased significantly during follow up. However, generalized linear analysis showed that there was no significant relationship between tumor size and follow up period. Conclusions The present results showed that even small GIST can be correctly identified by EUS-FNA. Moreover, size of small GIST increased significantly during follow up. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Acinar cell carcinomas ( ACCs) of the pancreas are characterized by the histological and immunohistochemical features of acinar cell differentiation. Recently, BCL10, originally identified as a recurrent t(1;14)(p22;q32) translocation in MALT B-cell lymphoma, was found to be immunohistochemically positive in some solid tumors, including ACC. To evaluate its diagnostic efficacy, we performed BCL10 immunohistochemistry and evaluated molecular markers correlated to pancreatic tumor lineages (neuroendocrine markers and a mutation analysis of KRAS and GNAS) using samples from 126 pancreatic tumors (17 ACCs, 24 pancreatic ductal adenocarcinomas, 4 adenosquamous carcinomas, 9 intraductal papillary mucinous neoplasms, 10 mucinous cystic neoplasms, 44 neuroendocrine tumors, 9 serous cystic tumors and 10 solid-pseudopapillary neoplasms). BCL10 was exclusively expressed in normal acini. In pancreatic tumors, 14 of 17 (82%) ACCs and 2 of 4 (50%) adenosquamous carcinomas were positive, while the other subtypes were almost negative. We subsequently examined the diagnostic utility of BCL10 in endoscopic ultrasound-guided fine-needle aspiration ( EUS-FNA) specimens using 57 pancreatic tumors. BLC10 correctly identified ACCs (9/13) and adenosquamous carcinomas (2/4) but none of the other subtypes ( n = 41). Therefore, we suggested that BCL10 expression is a useful marker for acinar cell differentiation, particularly in the diagnosis of EUS-FNA specimens. [ABSTRACT FROM AUTHOR]

Background: Obtaining histological evidence of gallbladder carcinoma (GBC) is difficult due to its extraductal nature, and pathological confirmation remains challenging. We compared the diagnostic value and safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with endoscopic retrograde cholangiography (ERC) in patients with suspected GBC. Patients: Eighty-three patients with GBC were evaluated. Prior to definitive management, pathological evidence of GBC was obtained through either ERC cytopathologic sampling ( n = 33), EUS-FNA ( n = 24) or both ( n = 26). Results: Among the 83 patients, 59 (71.0%) with biliary obstruction were sampled using ERC with 47.4% (28/59) sensitivity. In 19 of the remaining 31 cases, EUS-FNA sampling had 100% diagnostic sensitivity. Likewise, 50 (60.2%) of the 83 patients with suspected GBC underwent EUS-FNA of regional lymph nodes or the gallbladder (GB) mass itself with 94.8% sensitivity. The overall diagnostic sensitivity rates of ERC and EUS-FNA were 47.4 and 96%, respectively ( P < 0.001). Post-procedural complications were seen in 6.7% of the ERC group (4/59, all were mild pancreatitis), and in none of the EUS-FNA group ( P = 0.10). Conclusions: Gallbladder carcinoma sampling using ERC and EUS-FNA should be incorporated into the diagnostic workup of GB lesions as complementary tools, and EUS-FNA should be applied in the setting of failed or not indicated ERC. [ABSTRACT FROM AUTHOR]

The insulin-like growth factor (IGF) signaling system plays a central role in cellular growth, differentiation and proliferation. Although the association between IGF1 gene polymorphisms and cancer risk has been evaluated for several carcinomas, this association has not yet been examined for stomach cancer. We investigated the association between IGF1 polymorphisms and the risk of stomach cancer in a Japanese population. A total of 703 patients with stomach cancer and 1462 non-cancer control subjects were enrolled in this case-control study. Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in multiple logistic regression models. We observed that the C allele in rs1520220 and the G allele in rs4764887 were significantly associated with stomach cancer risk in the per-allele model after adjusting for other risk factors (OR: 1.14 [95% CI: 1.00-1.30] and OR: 1.18 [95% CI: 1.02-1.36], respectively). We also observed a positive and dose-dependent association between the number of risk alleles and stomach cancer risk ( P-trend: 0.019) when examining the two loci in the same model. These associations were still seen after adjusting for potential confounders, including sex, age, smoking status, history of diabetes and family history of stomach cancer. We did not find any significant interaction between these factors and the number of risk alleles. In conclusion, we observed a significant association between IGF1 polymorphisms and stomach cancer risk among a Japanese population. Examination of the biological significance of IGF1 is warranted. ( Cancer Sci 2011; 102: 2231-2235) [ABSTRACT FROM AUTHOR]

Several studies have investigated a possible association between the ABO blood group and the risk of pancreatic cancer (PC), but this association has not been fully evaluated in Asian populations. The present study aimed to assess the impact of genotype-derived ABO blood types, particularly ABO alleles, on the risk of PC in a Japanese population. We conducted a case-control study using 185 PC and 1465 control patients who visited Aichi Cancer Center in Nagoya, Japan. Using rs8176719 as a marker for the O allele, and rs8176746 and rs8176747 for the B allele, all participants' two ABO alleles were inferred. The impact of ABO blood type on PC risk was examined by multivariate analysis, with adjustment for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). An increased risk of PC was observed with the addition of any non- O allele (trend P = 0.012). Compared with subjects with the OO genotype, those with AO and BB genotypes had significantly increased OR of 1.67 (CI, 1.08-2.57) and 3.28 (CI, 1.38-7.80), respectively. Consistent with earlier reports showing a higher risk of PC for individuals with the non-O blood type, the previously reported protective allele (T) for rs505922 was found to be strongly correlated ( r=0.96) with the O allele. In conclusion, this case-control study showed a statistically significant association between ABO blood group and PC risk in a Japanese population. Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk. ( Cancer Sci 2011; 102: 1076-1080) [ABSTRACT FROM AUTHOR]

Erlotinib combined with gemcitabine has not been evaluated in Japanese patients with unresectable pancreatic cancer. This two-step phase II study assessed the safety and pharmacokinetics of erlotinib 100 mg/day (oral) plus gemcitabine 1000 mg/m (i.v. days 1, 8, 15) in a 28-day cycle in the first step, and efficacy and safety in the second step. The primary end-point was safety. One hundred and seven patients were enrolled (first step, n = 6; second step, n = 101). The most common adverse event was RASH (compiled using the preferred terms rash, acne, exfoliative rash, dermatitis acneiform, erythema, eczema, dermatitis and pustular rash) in 93.4% of patients. One treatment-related death occurred. While interstitial lung disease-like events were reported in nine patients (8.5%; grade 1/2/3, 3.8/2.8/1.9%), all patients recovered or improved. The median overall survival, the 1-year survival rate and median progression-free survival were 9.23 months, 33.0% and 3.48 months, respectively. The overall response and disease control rates were 20.3% and 50.0%, respectively. In Japanese patients with unresectable pancreatic cancer, erlotinib plus gemcitabine had acceptable toxicity and efficacy that was not inferior to that seen in Western patients. ( Cancer Sci 2011; 102: 425-431) [ABSTRACT FROM AUTHOR]

Background: The objective of the present study was to use clinical and laboratory data to develop a model for predicting the presence of carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). Methods: Data were collected on 81 patients with IPMN who underwent a pancreatic resection between 1989 and 2008 at Aichi Cancer Center Hospital. Variables analyzed included age, gender, laboratory findings (serum amylase, carcinoembryonic antigen, and carbohydrate antigen 19-9 level), pancreatic juice cytology grade, and imaging studies. Factors associated with the presence of carcinoma were evaluated by univariate and multivariate logistic regression analysis. Results: Among the 81 patients with IPMN, 34 (42%) had malignant tumors (noninvasive carcinoma in 22 and invasive carcinoma in 12), and 47 (58%) had adenoma. On multivariate analysis, existing carcinoma was associated with female gender, main pancreatic duct IPMN, nodule size, and pancreatic juice cytology grade. Based on these variables, a predictive nomogram was developed. The area under the receiver operating characteristic curve (AUC) for the model was 0.903. The sensitivity and specificity of the model were 97.1 and 68.1%, respectively, in the validation study, for which the predictive probability of >10% was used to indicate the presence of carcinoma. Conclusions: The nomogram has high diagnostic predictability for carcinoma in patients with IPMN and for individual cancer probability. This instrument may help to identify patients who need a surgical procedure. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation is involved in colon carcinogenesis. Although the CpG island methylator phenotype (CIMP) is defined as a subset of colorectal cancers (CRCs) with remarkably high levels of DNA methylation, it is not known whether epigenetic processes are also involved in CIMP-negative tumors. We analyzed the DNA methylation profiles of 94 CRCs and their corresponding normal-appearing colonic mucosa with 11 different markers, including the five classical CIMP markers. The CIMP markers were frequently methylated in proximal CRCs ( p < 0.01); however, RASSF1A methylation levels were significantly higher in distal CRCs, the majority of which are CIMP-negative ( p < 0.05). Similarly, methylation levels of RASSF1A and SFRP1 in the normal-appearing mucosae of distal CRC cases were significantly higher than those in the proximal CRC cases ( p < 0.05). They were also positively correlated with age ( RASSF1A, p < 0.01; SFRP1, p < 0.01). Microarray-based genome-wide DNA methylation analysis of 18 CRCs revealed that 168 genes and 720 genes were preferentially methylated in CIMP-negative distal CRCs and CIMP-positive CRCs, respectively. Interestingly, more than half of the hypermethylated genes in CIMP-negative distal CRCs were also methylated in the normal-appearing mucosae, indicating that hypermethylation in CIMP-negative distal CRCs is more closely associated with age-related methylation. By contrast, more than 60% of the hypermethylated genes in CIMP-positive proximal CRCs were cancer specific ( p < 0.01). These data altogether suggest that CpG island promoters appear to be methylated in different ways depending on location, a finding which may imply the presence of different mechanisms for the acquisition of epigenetic changes during colon tumorigenesis. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has enabled clinicians to histologically diagnose pancreatic tumors. However, EUS-FNA specimens often result in tiny fragmented tissues, so auxiliary utilities are necessary. Using immunostaining of CK7, CDX2, neuroendocrine markers and KRAS mutation analysis, we examined 57 FNA cell block sections and 61 surgically-resected specimens (25 invasive ductal carcinomas, 25 endocrine tumors, and 11 acinar cell tumors). In the majority of the matched pairs, the diagnoses between EUS-FNA and surgical specimens were concordant using the following criteria: neuroendocrine markers negative, CK7 positive, and mutated KRAS gene for invasive ductal carcinomas; neuroendocrine markers diffusely positive, CK7 and CDX2 negative, and wild-type KRAS gene for well-differentiated endocrine tumors; and neuroendocrine markers no more than focal positive, CK7 and CDX2 with various staining patterns, and wild-type KRAS gene for acinar cell carcinomas. Expression of CK7 and/or CDX2 in addition to KRAS mutations were occasionally seen in endocrine carcinomas, but not in well-differentiated endocrine tumors, suggesting that ductal differentiation in an endocrine tumor may be a predictor of aggressive disease. The usefulness of these markers was confirmed using 13 additional pancreatic tumors, prospectively. Although minimal in selection, these markers are helpful in making diagnosis from EUS-FNA specimens of the major pancreatic tumors. [ABSTRACT FROM AUTHOR]

Background: Autoimmune pancreatitis (AIP) is often misdiagnosed as pancreatic cancer (PC). Both conditions accumulate F-fluorodeoxyglucose (FDG), so FDG positron emission tomography (FDG-PET) is not discriminatory. This study aimed to evaluate the pattern of FDG accumulation, and the change in FDG uptake after steroid treatment in AIP and PC. Methods: We compared FDG-PET patterns between 18 patients with AIP and 20 patients with PC, and also evaluated the short-term changes in FDG uptake after steroid therapy. Results: FDG uptake was observed in 88.9% in AIP and 90.0% in PC. FDG uptake in extra-abdominal lymph nodes was seen more frequently in AIP, and uptake in salivary glands, eyes and biliary ducts was seen only in AIP. Follow-up PET was performed in 6 AIP patients and in 3 PC patients. Changes in SUV after steroid therapy were estimated within 1 week in 5 AIP patients and in all 3 PC patients, retrospectively. In 4 AIP patients, the change in SUV was more than 10%. On the other hand, in PC, SUV increased or remained almost unchanged (within 10%). Conclusions: FDG-PET pattern at baseline, and a decrease in FDG uptake after a short steroid trial can be useful for discriminating AIP from PC. [ABSTRACT FROM AUTHOR]

Endoscopic biliary drainage (EBD) may be unsuccessful in some patients, because of failed biliary cannulation or tumor infiltration, limiting endoscopic access to major papilla. The alternative method of percutaneous transhepatic biliary drainage carries a risk of complications, such as bleeding, portal vein thrombus, portal vein occlusion and intra- or extra-abdominal bile leakage. Recently, endoscopic ultrasonography (EUS)-guided biliary stent placement has been described in patients with malignant biliary obstruction. Technically, EUS-guided biliary drainage is possible via transgastric or transduodenal routes or through the small intestine using a direct access or rendezvous technique. We describe herein a technique for direct stent insertion from the duodenal bulb for the management of patients with jaundice caused by malignant obstruction of the lower extrahepatic bile duct. We think transduodenal direct access is the best treatment in patients with jaundice caused by inoperable malignant obstruction of the lower extrahepatic bile duct when EBD fails. [ABSTRACT FROM AUTHOR]

A 46-year-old female patient was referred to our hospital for endoscopic treatment of stenotic pancreatogastrostomy. She had undergone pylorus-preserving pancreatoduodenectomy due to duodenal carcinoma of the papilla of Vater 5 years before referral. Two years after the operation, she had to be hospitalized several times during a 1-year period because of acute recurrent pancreatitis caused by stenosis of the anastomosis of the pancreatoduodenostomy. An endoscopic ultrasound (EUS)-guided rendezvous technique was selected to puncture the main pancreatic duct via a transgastric approach. We identified the dilated main pancreatic duct with a convex array echoendoscope from the lower gastric body near the anastomosis and successfully punctured the dilated main pancreatic duct. The guidewire passed through the stenosis to the gastric cavity and we could place a stent through the stenotic anastomosis. After the procedure, the patient has not experienced acute recurrent pancreatitis for 9 months. Pancreatogastrostomy has been the preferred method used to carry out post-pancreatoduodenectomy reconstruction. However, stenosis of the anastomosis has been reported as one of the late complications of pancreatogastrostomy. The main symptom of this complication is recurrent epigastralgia due to obstructive pancreatitis. As a result, patients are compelled to stay in the hospital for an extended duration with no oral intake allowed. Surgical resection of the stenosis is often the treatment of choice but can be troublesome due to post-operative adhesions. Here, we report a case of pancreatogastrostomy complicated by stenosis, which was treated using the EUS-guided rendezvous technique. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasonography (EUS) is the combination of endoscopy and intraluminal ultrasonography. This allows use of a high frequency transducer, which, due to the short distance to the target lesion, enables ultrasonographic images of high resolution to be obtained. Endoscopic ultrasonography is now a widely accepted modality for the diagnosis of pancreatobiliary diseases. It can be used to determine the depth of invasion of gastrointestinal malignancies, and often for visualizing lesions more precisely than other imaging modalities. The most important early limitation of EUS was the lack of specificity in the differentiation between benign and malignant changes. In 1992, EUS-guided fine needle aspiration (EUS-FNA) of lesions in the pancreas head has been made possible using a curved linear array echoendoscope. Since then, many researchers have expanded the indication of EUS-FNA to various kinds of lesions and also for a variety of therapeutic purposes. In this review, we particularly focus on the present and future roles of interventional EUS, including EUS-FNA and therapeutic EUS. [ABSTRACT FROM AUTHOR]

Background and Study Aims: The aim of this prospective study was to compare fine-needle aspiration guided by endoscopic ultrasonography (EUS-FNA) using 25-gauge and 22-gauge needles with the EUS-guided 19-gauge Trucut needle biopsy (EUS-TNB) in patients with solid pancreatic mass. Patients and Methods: Twenty-four consecutive patients with pancreatic mass underwent biopsies by both EUS-FNA and EUS-TNB. Three needles were compared with respect to technical success rate, tissue size obtained, overall diagnostic accuracy and accuracy for histological and cytological diagnosis. Results: The 25-gauge EUS-FNA was technically easier and obtained superior overall diagnostic accuracy than the 22-gauge and Trucut needles, especially in lesions of the pancreas head and uncinate process. Overall accuracy for the 25-gauge, 22-gauge and Trucut needle was 91.7%, 79.7% and 54.1%, respectively. Accuracy for cytological diagnosis irrespective the site of lesions with 25-gauge, 22-gauge and Trucut needles was 91.7%, 75.0%, and 45.8%, respectively. For uncinate masses, it was 100%, 33.3%, and 0.0%, respectively. These differences were significant. Among technically successful patients, the accuracy for histological diagnosis using the 25-gauge was significantly inferior ( P < 0.05) to 22-gauge and Trucut needles and the rates were 45.8%, 78.9% and 83.3%. Conclusions: The 25-gauge FNA needle was significantly superior in terms of technical success rate and overall diagnostic accuracy, especially for the head and uncinate lesions, compared to the 22-gauge and Trucut needles and could be considered ‘the best choice needle for cytological diagnosis’ of solid pancreatic lesions. If histological diagnosis is required, the 22-gauge FNA needle and Trucut needle may be advantageous for use in head/uncinate and body/tail lesions, respectively. [ABSTRACT FROM AUTHOR]

The putative impact of alcohol on pancreatic cancer (PC) risk remains controversial. Here, we conducted a case-control study in Japanese to assess the impact of alcohol in conjunction with polymorphisms in alcohol-metabolizing enzymes. Cases were 160 patients with pancreatic cancer at Aichi Cancer Center, Nagoya, Japan. Two control groups of 800 age- and sex-matched non-cancer subjects each were independently selected. The impact of alcohol and polymorphisms in aldehyde dehydrogenase 2 ( ALDH2) Glu504Lys, alcohol dehydrogenase ( ADH) 1B His48Arg, and ADH1C Arg272Gln on PC risk was examined with multivariate analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results showed no independent impact of alcohol or genotype on PC risk except former drinking. To avoid reverse causation, former drinkers were excluded in further analyses. In the analysis of the combined effects of alcohol consumption and genotype, significant impact of alcohol was seen for those subjects with ALDH2 Lys+ allele, ADH1B His/His, or ADH1C Arg/Arg (trend P = 0.077, 0.003, or 0.020, respectively), each of which is associated with a high concentration or rapid production of acetaldehyde. Analysis of genotype combinations showed that ‘ever drinking’ with both ADH1B His/His and ALDH2 Lys + was the most potent risk factor for PC relative to ‘never drinkers’ with both ADH1B His/His and ALDH2 Glu/Glu [OR (95% CI); 4.09 (1.30–12.85)]. These results indicate that alcohol has an impact on PC risk when the effects of alcohol consumption and metabolism are combined. Acetaldehyde may be involved in the mechanisms underlying PC development. ( Cancer Sci 2009; 100: 296–302) [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to identify factors that predict treatment outcome in patients with metastatic pancreatic cancer treated with gemcitabine, and then to use these factors to develop a practical prognostic index. Methods: A retrospective study was performed on 66 consecutive patients with histologically confirmed pancreatic adenocarcinoma who were treated with gemcitabine. Factors that predicted treatment outcome were identified by univariate and multivariate analyses using the Cox proportional hazards model. Results: Multivariate analysis identified Eastern Cooperative Oncology Group performance status, primary tumor location, and C-reactive protein as important independent predictive factors. Prognostic score was calculated using the following formula: score = (1 if performance status is 0 or 1; 2 if performance status is 2; and 5 if performance status is 3) + (1 if primary site is body or tail, 3 if primary site is head) + (1 if C-reactive protein is <1 mg/dL, 3 if C-reactive protein is 1–3 mg/dL, 6 if C-reactive protein is >3 mg/dL). Patients were accordingly divided into three groups: good (prognostic index = 3 or 4), fair (prognostic index = 5–7), and poor (prognostic index = 8). Median survival was 265, 155, and 65 days for each group, respectively ( P < 0.0001). The internally validated c-index (receiver operating characteristics area under the curve) of this model was 0.711. Applied to another data set, the externally validated c-index was 0.692. Prognosis was favorable in the good prognosis group, patients in the fair prognosis group were likely to benefit from gemcitabine, and those in the poor prognosis group were unlikely to benefit. Conclusion: This index improved predictive ability in patients with metastatic pancreatic cancer treated with gemcitabine, which may be helpful in counseling patients and making first treatment decisions. [ABSTRACT FROM AUTHOR]

Background and Aim: Despite aggressive multimodal treatments, survival rates for patients with pancreatic cancer remain disappointing. Local progression is problematic, and minimally invasive procedures allowing locoregional control are needed. In this study, we attempted endoscopic ultrasound (EUS)-guided injection of ethanol into the pancreas. Methods: Under EUS guidance, pure ethanol (2 mL) was injected into normal tissue of the pancreatic body in two anesthetized domestic pigs. Serum concentrations of amylase, aspartame aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase were measured before treatment and at 2 h, 48 h and 2 weeks after injection. Body weight and clinical signs were also observed. After the animals were euthanized, the pancreases were analyzed histologically. Results: EUS imaging allows real-time surveillance of the injection procedure. Mild diarrhea was noted in one animal, but no other adverse effects were observed. No marked changes in laboratory tests were noted. Histologically, parenchymal necrosis extending over a wide area was seen without severe inflammation. Conclusion: EUS-guided ethanol injection in the pancreas seems to be technically simple. More detailed assessments of the safety and dose–effect relationship issues associated with this procedure are required. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS-FNAB was performed was 62 years (range 26–82 years) and the median follow-up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS-FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed. [ABSTRACT FROM AUTHOR]

Background: It is well known that pancreatic cancer is rarely cured and is usually fatal. The clinicopathological features of small (greatest dimension ≤ 2 cm by histologic measurement) carcinoma of the pancreas (s-PC), were reviewed, paying special attention to new computed tomography (CT) finding that suggests the presence of s-PC. Methodology: Sixteen patients with s-PC have undergone curative surgery at Aichi Cancer Center Hospital during the past 11 years. Their preoperative diagnostic findings, pathological findings and postoperative prognoses were analyzed. Results: The most useful diagnostic clue was dilatation of the main pancreatic duct (MPD). It was difficult to identify the tumor in four patients because of pancreatitis accompanying the MPD obstruction. In three of these four cases, early phase-enhanced CT revealed a contrasting effect between the proximal and distal sides of the pancreatic parenchyma at the site of the MPD obstruction (black & white sign). The longest diameters of the tumors ranged from 0.9 to 2 cm (average 1.3 cm). Positive rates of capsular invasion, retroperitoneal invasion, and lymph node metastasis were 6.3% (1/16), 31.3% (5/16), and 18.8% (3/16), respectively. Six patients (37.5%) were classed at stage I, six (37.5%) stage II, three (18.8%) stage III, and one (6.2%) at stage IV according to pathological TNM classification. One patient died of the disease, and the cumulative 3- and 5-year survival rates were 88.9% and 59.3%, respectively. Conclusions: The presence of s-PC qualifies as early PC and has a good prognosis. The CT black + white sign will be useful in the diagnosis of s-PC accompanying pancreatitis. [ABSTRACT FROM AUTHOR]

There are few reports of late complications in patients who have undergone pancreatic resection with intraoperative radiation therapy (IORT), because carcinoma of the pancreas (PCa) and the bile duct (BCa) have a poor prognosis. The purpose of the present paper was to review gastrointestinal (GI) bleeding occurring with occlusion of the portal system (PVs) as a complication of IORT in patients surviving long term without recurrence. From 1990 to 1999, 45 patients underwent surgical resection of the pancreas with IORT. Eleven of these patients survived >3 years without recurrence, and occlusion of PVs was recognized in five patients at follow-up examination. Three of these five patients received repeated blood transfusions for GI bleeding. One patient had BCa and two had PCa, and pancreatoduodenectomy was carried out. The delivered radiation doses of IORT were 30 Gy (two patients) and 35 Gy (one patient). The postoperative periods to initial GI bleeding were 36, 26 and 9 months, respectively. In all cases, angiography revealed occlusion of PVs and the collateral circulation. The bleeding points were esophageal varix ( ), remnant stomach varix ( ) and a jejunal ulcer ( ), and blood transfusions were carried out totaling 44, 60 and 16 units, respectively. The GI bleeding disappeared spontaneously in , developed sporadically in and was stopped by metallic stent insertion in PVs in . During long-term follow up after pancreatectomy with IORT, it is necessary to monitor patients for GI bleeding. A clinical trial on optimum doses, long-term safety and benefit of IORT is necessary. [ABSTRACT FROM AUTHOR]

Gastrointestinal submucosal tumors (SMT) detected by barium meal study or endoscopy include various kinds of diseases and various degrees of malignancy. Endoscopic ultrasonography (EUS) can provide useful information about the differentiation of intra- and extra-wall lesions, location and originating layer, presumption of their histological nature, measurement of the actual size of the lesion, and the possibility of differentiating between a benign and a malignant lesion. However, EUS alone does not reveal the complete pathology. EUS fine-needle aspiration biopsy (EUS-FNAB) has been reported to be a useful tissue sampling method for pancreatic mass lesions, lymph nodes swelling, posterior mediastinal masses and also gastrointestinal submucosal tumors. The EUS-FNAB procedure is effective not only for the differential diagnosis of benignancy and malignancy, but also for the specific histopathological nature of gastrointestinal SMT using immunohistochemical staining. When used with MIB-1 (Ki-67) staining, and gene analysis in case of gastrointestinal stromal tumor, EUS-FNAB may indicate its prognosis and influence decisions regarding therapeutic strategy. Thus, EUS-FNAB is an indispensable procedure in the diagnosis of SMT. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS FNAB) is a relatively new technique for obtaining specimens with excellent imaging power. The convex type of echoendoscope used with EUS FNAB provides images perpendicular to the endoscope, which differ from those of popular radial echoendoscopes and, hence, require different usage techniques. Color flow imaging is used to avoid the vessels in and around the mass during puncturing. EUS FNAB for submucosal tumors is sometimes difficult because the needle slips easily, and the gastrointestinal wall tends to be stretched when pushing the needle, which can be solved by making a dimple on the wall before puncturing. Lesions of the pancreas head, especially those at the uncus, and lymph nodes near the superior mesenteric artery are also difficult because of their distance from the endoscope and the resultant bending of the needle. Tissue sampling is more successful when the angle between the endoscope and the needle is kept at just less than 45 degrees, as this helps to transmit the hand force to the needle effectively. The complication rate of EUS FNAB is reportedly 1–2%, and so the technique is considered a safe modality, except for cystic lesions of the pancreas. Recent histological evidence is needed before applying medical therapies, such as chemoradiation and surgery, especially when imaging modalities alone cannot supply the evidence of malignancy; hence increasing importance of EUS FNAB is expected. [ABSTRACT FROM AUTHOR]

The histologic characteristics of a case of epidermoid cyst formation with an epithelioid cell granuloma that developed in intrapancreatic accessory spleen were investigated, with the aim of clarifying its origin as well as etiologic factors. The patient, a 48-year-old male, was found to have a cystic lesion in the tail of the pancreas and renal cell carcinoma (clear cell carcinoma) during a medical check up. The pancreatic mass appeared to be a so-called ‘mucinous tumor’ on imaging, and combined resection of the body and tail of the pancreas and the spleen was performed together with a left nephrectomy. The lesion in the tail of the pancreas was then demonstrated to have accessory splenic tissue with cyst formation in its central region. The cystic wall was covered with stratified squamous epithelium and ductal epithelium with squamous metaplasia, and pancreatic islet cells were evident at various sites within the accessory spleen. Formation of epithelioid cell granuloma tissue was observed around the cysts. The epithelium of the cyst was positive for CA19-9 and negative for antibodies against mesothelial cells, whereas the pancreatic island cells were positive for insulin. These results suggested that cystic epithelium in the accessory spleen could be derived from pancreatic duct epithelium. Frequent recurrence of chronic inflammation and epitheloid cell granuloma formation may have resulted from an aberration of the ectopic remaining pancreatic tissue in the spleen. [ABSTRACT FROM AUTHOR]

The article presents a discussion on the use of endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) to determine local cancer staging and in the detection of small lesions. He mentions on several techniques used in using the procedure and asserts on its efficacy in treating the cancer. He states that EUS FNA was first applied to pancreatic mass lesions.

Endoscopic ultrasonography (EUS) has become an indispensable diagnostic procedure pairing endoscopy with transluminal high frequency ultrasonography. EUS provides images with a high resolution such that the depth of tumor invasion can be accurately determined. It also sees lesions outside of gastrointestinal tract, particularly those in pancreas, biliary system and periluminal lymph nodes. The most important limitation of EUS was lack of specificity, that is, the differentiation between benign and malignant lesions. In 1992, EUS-guided fine needle aspiration (EUS-FNA) was introduced with the sampling of a lesion in the pancreatic head using a convex EUS. Since then the indications of EUS-FNA have been expanded to include a variety of therapeutic uses. In addition, a convex EUS probe can also be used for detailed evaluation of the pancreatobiliary system, in lieu of a radial EUS. The vascular structures surrounding liver, biliary system and pancreas can be showed by a convex EUS system very clearly and easily compared with the more familiar radial EUS images. So we think a convex EUS is very useful for not only EUS-FNA but also screening and close examination for cancer with vascular invasion. [ABSTRACT FROM AUTHOR]

Examines the applications of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) in the gastrointestinal tract. Types of echo-endoscope for EUS FNA; Diagnostic purpose of EUS; Contraindications of endoscopy.

The authors reflect on the usefulness and safety of endoscopic ultrasonography-guided biliary drainage (EUS-BD). They discuss several EUS-BD procedures, including EUS-guided choledochoduodenostomy (EUS-CDS), hepaticogastrostomy (EUS-HGS), EUS-rendezvous and EUS-antegrade drainage, and the need to evaluate them appropriately. They examine the risk of complications resulting from EUS-BD.

Standard imaging techniques using a curved linear array echoendocope are summarized to facilitate the attainment of expertise in endoscopic ultrasonography and endoscopic ultrasound-guided fine needle aspiration, and to promote the widespread use of this diagnostic and therapeutic tool. Typical images of the mediastinal organs, the bilio-pancreatic systems and neighboring organs by scanning from the esophagus, stomach, duodenal bulb, and descending portion of the duodenum, are shown in a sequential manner. The basic techniques of endoscopic ultrasound-guided fine needle aspiration are also presented. [ABSTRACT FROM AUTHOR]

Standard imaging techniques using a radical scanning echoendoscope are summarized to facilitate the attainment of expertise in biliopancreatic endoscopic ultrasonography and to promote the widespread use of this diagnostic tool. Typical images of the biliopancreatic system and neighboring organs obtained by scanning from the stomach, duodenal bulb, and descending portion of the duodenum are shown in a sequential manner. Two methods of scanning from the descending portion of the duodenum, which is considered to be the most difficult, are presented (i.e. the Longitudinal Method and the Transverse Method). In addition, settings of the image control functions and the monitor are also detailed. [ABSTRACT FROM AUTHOR]