Hemorrhagic Colitis Caused by Everolimus in a Patient with Nonfunctional Pancreatic Neuroendocrine Neoplasms: A Case Report.

A 60-year-old woman was diagnosed with nonfunctional pancreatic neuroendocrine neoplasm with multiple liver metastases and was administered everolimus. Due to persistent epigastric pain and diarrhea, a colonoscopy was performed on the 14th day after the start of everolimus administration, which revealed small bleeding ulcers in the ileocecal region, transverse colon, and rectum. These adverse effects were attributed to the everolimus; it was immediately discontinued, and the patient's clinical symptoms and imaging findings improved. We concurred that the administration of calcium channel blockers resulted in the inhibition of everolimus metabolism and the disease onset. The everolimus was discontinued. There was no subsequent recurrence of hemorrhagic colitis.

A Prospective Multicenter Randomized Feasibility Trial of Double-guidewire Techniques for Difficult Biliary Cannulation Comparing a New Double-guidewire-supported Sphincterotome (MagicTome) to a Conventional Device.

Objective To evaluate the effectiveness and safety of the double-guidewire technique (DGT) using a new double-guidewire-supported sphincterotome (MagicTome) for patients who required endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation. Methods This prospective multicenter randomized feasibility trial involved patients with difficult biliary cannulation at any of the three study sites from June 2017 to October 2018. Patients were assigned to the DGT with MagicTome (MDGT) initially performed group and the conventional DGT (CDGT) initially performed group. The success rates of biliary cannulation by MDGT and CDGT and the ERCP-related complications were evaluated. Results Twenty-eight patients were included in this study. No significant difference was observed in the success rates of first attempts and crossover attempts between the groups (p=0.69 and p=1.00). Furthermore, no significant difference was observed in the success rate of biliary cannulation between MDGT and CDGT (62.5% and 75.0%, respectively; p=0.48). CDGT was successful in two of four patients with malignant biliary obstruction. MDGT was successful in all four patients with malignant biliary obstruction, including the two for whom CDGT was unsuccessful. Post-ERCP pancreatitis occurred in only one MDGT case. Conclusion MDGT is safe for biliary cannulation and can be used in cases where biliary cannulation by CDGT is difficult.

Pilot Study of Acupuncture's Antispasmodic Effect on Upper Gastrointestinal Tract during Endoscopic Submucosal Dissection for Early Gastric Cancer: Controlled Clinical Trial.

A prospective study was conducted in patients with early-stage gastric cancer to determine the efficacy and safety of acupuncture stimulation as an antispasmodic compared with conventional medication during the procedure of endoscopic submucosal dissection (ESD) of the upper gastrointestinal tract. This study was a prospective single blinded quasi-randomized controlled trial. Seventy-three patients who were scheduled to undergo ESD for gastric cancer at Aizu Medical Center between 19 February 2016 and 30 June 2016 were assessed for eligibility for the study. Sixty out of 73 patients were included in the study and assigned into two intervention groups: medication group (MG) and acupuncture group (AG). Ease of the procedure was evaluated using modified NIWA classification (MNC) by endoscopist considering the frequency and amplitude of the upper gastrointestinal peristalsis. For the statistical analysis, Mann-Whitney test was used to compare the differences of MNC values (baseline and end of procedure) between two groups. The difference of MNC found in the AG (-2.00 (-3.0 to -2.0)) was significantly greater than that in the MG (-1.00 (-2.0 to -1.0), p < 0.0001, Mann-Whitney test). We consider that acupuncture to the abdomen could be an alternative antispasmodic method during upper gastrointestinal endoscopic procedure.

Factors Affecting Technical Difficulty in Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography in Patients with Surgically Altered Anatomy.

Success rates of balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) for patients with a reconstructed intestinal tract after surgical procedures are unsatisfactory. We retrospectively investigated the factors associated with unsuccessful BE-ERCP. Ninety-one patients who had a reconstructed intestinal tract after gastrectomy or choledochojejunostomy were enrolled. Age, sex, operative method, malignancy, endoscope type, endoscopist's skill, emergency procedure, and time required to reach the papilla/anastomosis were examined. The primary endpoints were the factors associated with unsuccessful BE-ERCP selective cannulation, while the secondary endpoints were the rate of reaching the papilla/anastomosis, causes of failure to reach the papilla/anastomosis, cannulation success rate, procedure success rate, and rate of adverse events. Younger age (odds ratio, 0.832; 95% CI, 0.706-0.982; p = 0.001) and Roux-en-Y partial gastrectomy (odds ratio, 54.9; 95% CI, 1.09-2763; p = 0.045) were associated with unsuccessful BE- ERCP. The rate of reaching the papilla/anastomosis was 92.3%, the success rate of biliary duct cannulation was 90.5%, procedure success rate was 78.0%, and the rate of adverse events was 5.6%. In conclusion, Roux-en-Y partial gastrectomy and younger age were associated with unsuccessful BE-ERCP. If BE-ERCP is extremely difficult to perform in such patients after Roux-en-Y partial gastrectomy, alternative procedures should be considered early.

Validity of Endoscopic Ultrasound Findings of Chronic Pancreatitis: Evaluation from the Viewpoint of Disease Risk Factors.

BACKGROUND: The diagnosis of chronic pancreatitis (CP) using endoscopic ultrasound (EUS) criteria, referred to as the Rosemont classification (RC), has been widely performed. However, the validity of the RC, which was based on expert opinion, is still controversial. If EUS findings are associated with CP, then they should be associated with risk factors for CP. In this study, to verify the appropriateness of the RC and each EUS finding, we performed a retrospective analysis from the viewpoint of risk factors for CP. SUMMARY: Three hundred and forty-four patients were enrolled in this study. Clinical background characteristics that associate with CP were alcohol intake, smoking, history of acute pancreatitis (AP), and age. The correlation between EUS criteria for CP and clinical background was investigated. All EUS findings except the presence of cysts showed significant correlations with one or 2 of the 3 following factors: ethanol (EtOH) intake, smoking status, and history of AP. Results of the univariate and multivariate analyses showed that 3 factors (EtOH intake, smoking, and history of AP) other than age were positively correlated with the RC. Moreover, the risk of progression from normal to consistent CP to indeterminate and suggestive CP was found to increase with increasing EtOH intake. Key Messages: The RC and each EUS finding was validated from the viewpoint of risk factors for CP.

Interobserver Reliability of Endoscopic Ultrasonography: Literature Review.

Endoscopic ultrasonography (EUS) has been applied to the diagnosis of various digestive disorders. Although it has been widely accepted and its diagnostic value is high, the dependence of EUS diagnosis on image interpretation done by the endosonographer has persisted as an important difficulty. Consequently, high interobserver reliability (IOR) in EUS diagnosis is important to demonstrate the reliability of EUS diagnosis. We reviewed the literature on the IOR of EUS diagnosis for various diseases such as chronic pancreatitis, pancreatic solid/cystic mass, lymphadenopathy, and gastrointestinal and subepithelial lesions. The IOR of EUS diagnosis differs depending on the disease; moreover, EUS findings with high IOR and those with IOR that was not necessarily high were used as diagnostic criteria. Therefore, to further increase the value of EUS diagnosis, EUS diagnostic criteria with high diagnostic characteristics based on EUS findings with high IOR must be established.

Duodenal Stenosis Due to Carcinoma of the Lower Bile Duct: A Case Report.

An 83-year-old man was referred to our hospital for a detailed evaluation for vomiting. Esophagogastroduodenoscopy and abdominal computed tomography showed duodenal stenosis with wall thickness. Biopsy including endoscopic ultrasound-guided fine-needle aspiration of the thickened wall showed inflammation without malignancy. During the clinical course, wall thickening of the distal bile duct appeared. Biopsy under endoscopic retrograde cholangiography showed papillary adenocarcinoma. Surgery revealed that the tumor had widely invaded the duodenal wall from the outside; therefore, only gastrojejunostomy was performed. It was hypothesized that the cholangiocarcinoma had progressed to the serosal side, disseminated in the peritoneum, infiltrated the duodenal serosa, and caused duodenal stenosis.

Safety and efficacy of endoscopic ultrasound-guided fine needle aspiration for pancreatic masses: A prospective multicenter study.

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.

The Feasibility and Histological Diagnostic Accuracy of Novel Menghini Needle (EUS Sonopsy CY™) for Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy of Solid Pancreatic Masses: A Prospective Crossover Study Comparing Standard Biopsy Needles.

BACKGROUND AND OBJECTIVES: Recently, a 21G Menghini-type needle for EUS-guided fine-needle aspiration biopsy (EUS-FNAB) has been developed. The stylet of the EUS Sonopsy CY™ remains inside the needle during aspiration. Therefore, it is expected to obtain higher-quality histological core specimens without crushing the material or blood contamination. The aim of this study is to evaluate the feasibility and diagnostic accuracy of EUS-FNAB of solid pancreatic masses with this new biopsy needle. METHODS: A total of 30 patients with solid pancreatic masses who underwent EUS-FNAB with two different types of needles, EUS Sonopsy™ and ProCore™, were included in a prospective, randomized, controlled, crossover study. All the pancreatic masses were punctured with the two needles and were randomized regarding the order of the needle to be used. The primary outcome was to compare the diagnostic accuracy and the rates of tissue acquisition of the two needles. RESULTS: The tissue acquisition rate was not significantly different between the EUS Sonopsy CY™ needle and the ProCore™ needle (78.6% vs. 82.1%, P = 1.00). The histological diagnostic accuracy was also similar between the two needles (73% vs. 80%, P = .63). There was also no difference regarding the accuracy of cytology alone and the combination of both histological and cytological assessments between the EUS Sonopsy CY™ needle and the ProCore™ needle (90% vs. 87%, P = 1.00 and 90% vs. 90%, P = 1.00, respectively). CONCLUSIONS: EUS Sonopsy CY™ is a reliable device for EUS-FNAB of solid pancreatic masses.

New endoscopic ultrasonography criteria for malignant lymphadenopathy based on inter-rater agreement.

BACKGROUND AND AIMS: Various studies have been previously conducted on the diagnosis of lymphadenopathy as benign or malignant, but the results vary. These studies did not describe the inter-rater agreement on the EUS features of lymphadenopathy. In this study, we evaluate the inter-rater agreement on EUS features and propose EUS diagnostic norms for lymphadenopathy based on inter-rater agreement. METHOD: A total of 68 lymph nodes subjected to EUS-fine needle aspiration (FNA) were reviewed by five endoscopic experts. The EUS features evaluated lymph node size, shape, border, margin, echogenicity, homogeneity, and the hilum of the lymph node. Inter-rater agreement (multi-rater kappa statics) was performed. We established new criteria using results with a high degree of inter-rater agreement from EUS features and compared them with the former criteria. RESULT: There was a moderate agreement on shape, kappa (K) = 0.44 (95% confidence interval [CI]: 0.34-0.54), and fair agreement on echogenicity, homogeneity, border, and hilum of the lymph node, K (95% CI) = 0.33 (0.17-0.38), 0.34 (0.26-0.35), 0.22 (0.21-0.31), and 0.22 (0.11-0.26), respectively. This resulted in the establishment of new EUS diagnostic criteria using shape, long axis > 20 mm and short axis > 10 mm. New criteria were superior to old criteria (area under the curve 0.82 vs 0.52, P < 0.001). CONCLUSION: EUS diagnostic criteria for lymphadenopathy based on inter-rater agreement were more accurate than old criteria. This result will be useful for the diagnosis of lymphadenopathy.

Endoscopic Mucosal Resection Performed Underwater for Nonampullary Duodenal Epithelial Tumor: Evaluation of Feasibility and Safety.

OBJECTIVES: Recently, opportunities to encounter superficial nonampullary duodenal epithelial tumor (SNADET) have increased. EMR and ESD are performed to treat SNADET. However, the rate of perforation is higher than that of other gastrointestinal lesions, regardless of which method is used. Underwater EMR (UW-EMR) is immersion treatment of SNADET, which has low risk of perforation and can remove lesions safely and completely. In the present study, we retrospectively investigated patients in whom UW-EMR was performed to evaluate the feasibility and safety of UW-EMR for the treatment of SNADET. METHODS: The primary endpoint was to evaluate the feasibility of UW-EMR for the treatment of SNADET, and secondary objective was to determine the operation's safety. RESULTS: There were 14 participants, with a total of 16 lesions, who underwent UW-EMR between August 2015 and December 2017. Histological heteromorphism revealed that seven patients had low-grade adenoma, seven had high-grade adenoma, and two had adenocarcinoma. En bloc resection was performed in 14 lesions. In two patients, nodular lesions were observed in the scar and biopsy confirmed recurrences. There were no serious adverse events including bleeding or perforation. CONCLUSIONS: UW-EMR may be a safe and effective treatment method for SNADET, if its therapeutic indication is adequately considered.

A Case of Obstructive Jaundice Caused by Metastasis of Ovarian Cancer to the Duodenal Major Papilla.

Ovarian cancer often occurs distant metastasis to the peritoneum, liver, lungs, and lymph nodes. However, there has been no reported case of direct metastasis to the duodenal major papilla. We herein reported 72-year-old woman with history of ovarian cancer surgery 11 years ago presenting with obstructive jaundice. Abdominal CT showed a small mass in the distal bile duct. Forceps biopsy from the small mass was done under endoscopic retrograde cholangiography, and histologic examination revealed adenocarcinoma. Pancreaticoduodenectomy was performed and diagnosed immunohistochemically direct metastasis to the papilla from ovarian cancer. The duodenal major papilla is known to be rich in lymph vessels, and these lymph vessels are considered the likely pathway of metastasis in this case.

Simultaneous Gastric Metastasis From Renal Cell Carcinoma: A Case Report and Literature Review.

While some reports are available regarding metachronous gastric metastasis from renal cell carcinoma after treatment, there are few reports of primary lesion detection based on the diagnosis of a gastric metastatic lesion. The patient in this case was an 80-year-old woman who underwent upper gastrointestinal endoscopy after having developed anorexia 2 months earlier. A submucosal tumor with central umbilication was found in the gastric greater curvature. Endoscopic ultrasonography revealed a solid and hypoechoic mass with hypervascularity on color Doppler imaging that proliferated mainly within the submucosal layer. There was partial exposure of the tumor on the superficial layer. Biopsy was performed, as a neuroendocrine tumor was suspected; however, histopathological findings with immunostaining revealed gastric metastasis from clear renal cell carcinoma. Subsequently, contrast enhanced computed tomography showed right renal cell carcinoma and liver metastasis. Thus, molecularly targeted drug treatment was initiated by the Department of Urology. Our findings indicate that a primary lesion can be identified and prognosis can be assumed based on biopsy of the gastric metastatic lesion. Immunostaining of biopsy samples collected endoscopically could help achieve definite diagnosis.

Case Report of a Small Gastric Neuroendocrine Tumor in a Deep Layer of Submucosa With Diagnosis by Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Treatment With Laparoscopic and Endoscopic Cooperative Surgery.

Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by enterochromaffin-like cells of the stomach. Optimal management of GNETs has not yet been definitively determined. Endoscopic resection is approximately recommended for small GNETs associated with hypergastrinemia. However, endoscopic resection might present risk of perforation or positive vertical margin because neuroendocrine tumors occur in the deep mucosa, with some invading the submucosa. In this case, a patient with type A chronic atrophic gastritis had a small subepithelial lesion in a deep submucosal layer, and we diagnosed it as GNET using endoscopic ultrasound-guided fine-needle aspiration biopsy using a forward-viewing and curved linear-array echoendoscope. Moreover, our results show that laparoscopic and endoscopic cooperative surgery with regional lymph node dissection is a safe and feasible procedure for GNETs, especially those that cross to the muscularis propria. We suggest this approach as one therapeutic option for GNETs because it safely minimizes resection and is less invasive.

Significance of normal appearance on endoscopic ultrasonography in the diagnosis of early chronic pancreatitis.

BACKGROUND AND OBJECTIVES: The Rosemont classification (RC) was developed as a consensus-based standard for the diagnosis of chronic pancreatitis (CP) by endoscopic ultrasonography (EUS), however, it is more complicated than the conventional scoring system. We have noticed that in the early stages of CP, it is not unusual to observe pancreas with abnormal appearance coexisting with the areas of normal parenchyma. The aim of this study was to investigate the validity of a "normal" pancreas appearance and to evaluate the usefulness of modified diagnostic criteria in comparison to the traditional EUS criteria and the RC. PATIENTS AND METHODS: One hundred and seventy-seven patients who had undergone both EUS and endoscopic retrograde pancreatography (ERP) within 2 months were enrolled in the study, and patients with pancreatic cancer were excluded from the study. ERP findings were used as the gold standard for the diagnosis of CP. The EUS images obtained were classified according to both the RC and our new modified criteria. The latter includes an additional criterion to the modified traditional criteria: fine-reticular pattern (F-RP) was defined as a normal pancreatic parenchyma. We compared the accuracy between the new modified EUS criteria and the RC. RESULTS: (1) Normal or equivocal findings on ERP were obtained for 132 patients; 113 patients had F-RP on EUS. In contrast, F-RP was found in only 6 out of 45 CP cases on ERP (P < 0.0001). (2) We investigated the diagnostic capability of our new criteria for endoscopic retrograde cholangiopancreatography normal/equivocal pancreas compared to the traditional criteria. In cases where fewer than two points were defined as normal, the incidence of normal pancreas was significantly higher based on the new criteria than on the traditional criteria (P = 0.002). (3) No significant differences were found between the new criteria and the RC across all ERP grades. CONCLUSION: Our new proposed "normal-added EUS criteria" for diagnosing CP was equivalent to the RC.

Inflammatory Bile Duct Obstruction during the Healing Stage of Severe Acute Pancreatitis.

The patient was a 62-year-old woman with a history of severe acute pancreatitis complicated by walled-off necrosis (WON), who developed obstructive jaundice during the recovery phase from WON. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) revealed the complete obstruction of the distal bile duct, and endoscopic ultrasonography (EUS) revealed thickening of the duct wall, with a uniform distribution, and a relatively well-preserved layered structure. A cytopathological examination using ERCP showed no malignancy. The underlying etiology of this case may have been the formation of a cicatricial stricture during the resolution of WON, in addition to fibrosis caused by the spreading of inflammation from pancreatitis.

Early diagnosis of chronic pancreatitis: understanding the factors associated with the development of chronic pancreatitis.

The prognosis of advanced chronic pancreatitis (CP) is poor with the mortality rate approximately two-fold higher than the general population according to a survey of the prognosis of CP.　From this standpoint, the concept of early CP was propagated in Japan in 2009 to encourage the medical treatment for the earlier stages of CP.　That is, picking up the patients suspicious for early CP and then providing medical treatment for them are very important not only for patients, but also for health care economics.　In this review, we described some potential factors associated with the development of CP (alcohol, smoking, past history of acute pancreatitis, aging, gallstone, and gender) that are extremely important to discover patients with early-stage CP.

Efforts to improve the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for pancreatic tumors.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to obtain a definitive diagnosis of pancreatic tumors. Good results have been reported for its diagnostic accuracy, with high sensitivity and specificity of around 90%; however, technological developments and adaptations to improve it still further are currently underway. The endosonographic technique can be improved when several tips and tricks useful to overcome challenges of EUS-FNA are known. This review provides various techniques and equipment for improvement in the diagnostic accuracy in EUS-FNA.

Eosinophilic esophageal myositis diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report.

Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of eosinophilic infiltration into the squamous epithelium. In contrast, another disease concept termed "eosinophilic esophageal myositis (EoEM)" has been proposed, whereby there is eosinophilic infiltration into the muscularis propria instead. A 60-year-old man was referred to our hospital for chest pain, dysphagia, and several episodes of esophageal food impaction. Although EoE was suspected based on clinical features, biopsy specimens showed no mucosal eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy (EUS-FNA) revealed eosinophilic infiltration into the muscularis propria. Although the patient's symptoms gradually improved after steroid administration, complete remission was not achieved after 1 year of treatment. This case may reflect a disorder distinct from typical EoE based on eosinophilic infiltration of the muscularis propria but not the squamous epithelium, and we, therefore, diagnosed it as EoEM using the EUS-FNA findings as reference.