Akira Aso

Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors

Abstract Background and aim: Pancreatic neuroendocrine tumors (pNETs) are histologically categorized according to the WHO 2010 classification by their mitotic index or Ki-67 index as G1, G2, or G3. The present study examined the efficacy of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis and grading of pNET. Methods: We retrospectively reviewed 61 pNETs in 51 patients who underwent EUS between January 2007 and June 2014. All lesions were pathologically diagnosed by surgical resection or EUS-FNA. We evaluated the detection rates of EUS for pNET and sensitivity of EUS-FNA, and compared the Ki-67 index between EUS-FNA samples and surgical specimens. EUS findings were compared between G1 and G2/G3 tumors. Results: EUS showed significantly higher sensitivity (96.7%) for identifying pNET than CT (85.2%), MRI (70.2%), and ultrasonography (75.5%). The sensitivity of EUS-FNA for the diagnosis of pNET was 89.2%. The concordance rate of WHO classification between EUS-FNA and surgical specimens was 69.2% (9/13). The concordance rate was relatively high (87.5%, 5/6) in tumors <20 mm but lower (57.1%; 4/7) in tumors ≥20 mm. Regarding EUS findings, G2/G3 tumors were more likely to be large (>20 mm), heterogeneous, and have main pancreatic duct (MPD) obstruction than G1 tumors. Multivariate analysis showed large diameter and MPD obstruction were significantly associated with G2/G3 tumors. Conclusions: EUS and EUS-FNA are highly sensitive and accurate diagnostic methods for pNET. Characteristic EUS findings such as large tumor size and MPD obstruction are suggestive of G2/G3 tumors and would be helpful for grading pNETs.

Low-frequency of bacteremia after endoscopic submucosal dissection of the stomach.

Background:  Mainstream therapy for early gastric cancer in Japan has now shifted from endoscopic mucosal resection (EMR) to endoscopic submucosal dissection (ESD). Although bacteremia is reported as being infrequent and transient in gastric EMR, there are no reports of it being investigated in gastric ESD. This study aimed to determine the frequency of bacteremia in gastric ESD.

Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis.

Tocilizumab is a monoclonal antibody against human interleukin-6 receptor which blocks the binding of interleukin-6 to its receptor. Tocilizumab is effective for the treatment of inflammatory disorders including rheumatoid arthritis. We report a case of multiple ulcers in the small and large intestines, which occurred during tocilizumab therapy. A 57-year-old woman started to use tocilizumab for rheumatoid arthritis. Three months later, she complained of hematochezia. Double-balloon endoscopy revealed multiple small aphthoid ulcers in the small and large intestines. One month after the woman had recovered, she was given tocilizumab again. The woman had hematochezia and abdominal pain again 2 weeks later. Colonoscopy revealed multiple round, discrete punched-out ulcers in the terminal ileum, and vast deep ulcers from the cecum to the descending colon. Bioptic histopathology and cultivation showed non-specific findings. Six weeks after discontinuation of tocilizumab, ulcers in the small and large intestine dramatically improved, leaving ulcer scars. This disease course and the results of examination made us strongly suspect that tocilizumab induced multiple ulcers in the small and large intestines. Interleukin-6 is a pleiotropic cytokine and involved in intestinal mucosal wound healing as well as in inflammatory processes. It is possible that tocilizumab inhibited tissue repair of the intestine and caused intestinal ulcers.

Basic principles and practice of gastric cancer screening using high-definition white-light gastroscopy: Eyes can only see what the brain knows.

Endoscopic diagnosis of gastrointestinal tumors consists of the following processes: (i) detection; (ii) differential diagnosis; and (iii) quantitative diagnosis (size and depth) of a lesion. Although detection is the first step to make a diagnosis of the tumor, the lesion can be overlooked if an endoscopist has no knowledge of what an early‐stage ‘superficial lesion’ looks like. In recent years, image‐enhanced endoscopy has become common, but white‐light endoscopy (WLI) is still the first step for detection and characterization of lesions in general clinical practice. Settings and practice of routine esophagogastroduodenoscopy (EGD) such as use of antispasmodics, number of endoscopic images taken, and observational procedure are customarily decided in each facility in each country and are not well standardized. Therefore, in the present article, we attempted to outline currently available evidence and actual Japanese practice on gastric cancer screening using WLI, and provide tips for detecting EGC during routine EGD which could become the basis of future research.

Key endoscopic ultrasound features of pancreatic ductal adenocarcinoma smaller than 20 mm

Abstract Background and study aims. Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis compared with other solid pancreatic tumors. Diagnosis of PDAC in the earliest possible stage is important to improve the prognosis. Although endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been the gold-standard modality for diagnosing pancreatic lesions, its diagnostic yield is not satisfactory for pancreatic tumors smaller than 20 mm. The purpose of this study was to determine the EUS findings that are useful for differentiating PDAC from other solid pancreatic tumors when the lesions are smaller than 20 mm. Patients and methods. We performed a retrospective review of 126 patients with pancreatic tumors smaller than 20 mm who had undergone EUS. According to the final pathological diagnoses, they were categorized into either the PDAC or non-PDAC group. We, then, compared the EUS findings between the two groups. Results. Among the 126 patients, we diagnosed PDAC in 75 patients and non-PDAC in the remaining patients, including neuroendocrine tumor in 43 patients, intraductal papillary mucinous carcinoma in 3 patients, solid pseudopapillary neoplasm in 2 patients, and inflammatory pseudotumor in 3 patients. Of all EUS findings, three factors were significantly indicative of PDAC: an irregular tumor edge, main pancreatic duct dilation, and tumor location in the pancreatic head. The predicted probability for PDAC was 80%, 92.6%, and 74.1%, respectively. Conclusions. EUS could be a useful modality for differentiating PDAC from other solid pancreatic tumors, when the diagnostic yield of EUS-FNA is unsatisfactory, even for lesions smaller than 20 mm.

Large area of walled-off pancreatic necrosis successfully treated by endoscopic necrosectomy using a grasping-type scissors forceps.

Endoscopic necrosectomy (EN) for walled‐off pancreatic necrosis (WOPN) is less invasive than surgical treatment and has become the first choice for pancreatic abscess. EN is usually carried out with several devices including snares, baskets, and grasping forceps. Occasionally, we have encountered cases in which EN has not been satisfactorily carried out, and there is pressure for further innovation in EN. Here, we describe a case of a large area of WOPN that was successfully treated by EN with endoscopic submucosal dissection and associated techniques, which facilitated removal of necrotic tissues. A 60‐year‐old man was referred to our hospital for WOPN as a complication of necrotizing pancreatitis. As a result of his complicating conditions including ischemic heart disease, uncontrollable arrhythmia, chronic renalfailure, and persistent pleural effusion, he was deemed a poor surgical candidate. Although EN with conventional devices was carried out for five sessions, we could not remove the dense and massive necrotic tissues. At the sixth EN session, the Clutch Cutter device (Fujifilm, Tokyo, Japan) was used to remove the necrotic tissues, without major complications. This is believed to be the first report of EN using the Clutch Cutter for successful treatment of WOPN.

Prospective, randomized, double‐blind, placebo‐controlled trial of ulinastatin for prevention of hyperenzymemia after double balloon endoscopy via the antegrade approach

Double balloon endoscopy (DBE) allows the entire small intestine to be viewed using a combination of antegrade and retrograde approaches. Acute pancreatitis is a serious complication of antegrade DBE with no effective prophylactic treatment currently available. Ulinastatin has been shown to be effective for the prevention of pancreatitis following endoscopic retrograde cholangiopancreatography. We therefore assessed the efficacy of ulinastatin for hyperenzymemia after antegrade DBE.

Small-Sized, Flat-Type Invasive Branch Duct Intraductal Papillary Mucinous Neoplasm: A Case Report

Recent improvements in diagnostic modalities are increasing the frequency of detection of small-sized branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). International consensus guidelines for IPMN recommend surveillance without immediate resection for small-sized (<3 cm) BD-IPMNs without malignant features on imaging. Our patient is the first to have undergone resection of a small-sized BD-IPMN containing invasive cancer, but without malignant features on imaging. We herein report a case involving a 70-year-old man with a small cystic lesion in the pancreas head detected by health screening ultrasonography. Detailed examination revealed that the cystic lesion was a BD-IPMN measuring about 2 cm, with no malignant features. However, cytological examination of the pancreatic juice showed atypical cells with high-grade dysplasia storing intracytoplasmic mucin, indicating malignant BD-IPMN. Pathological examination of the resected specimen showed a BD-IPMN measuring 16 mm with an associated invasive carcinoma that invaded the pancreatic parenchyma over a distance of 11 mm. In this patient, invasive cancer was present within a small BD-IPMN with no high-risk stigmata on imaging. Cytological examination of the pancreatic juice allowed for the detection of pancreatic cancer in such a small-sized IPMN. Although routine endoscopic retrograde cholangiopancreatography (ERCP) with cytology is not recommended in all patients with BD-IPMNs, ERCP may contribute to the detection of small pancreatic cancers in select cases. Accumulation of cases of pancreatic cancer within small BD-IPMNs may help establish the indications for ERCP with cytological examination for the purpose of early detection of small pancreatic cancer.

Differences in routine esophagogastroduodenoscopy between Japanese and international facilities: a questionnaire survey

The mortality rate of gastric cancer (GC) is close to the incidence rate worldwide. However, in Korea and Japan, the mortality rate of GC is less than half of the incidence rate. We hypothesized that good‐quality routine esophagogastroduodenoscopy (EGD) contributes to a high detection rate for early GC (EGC) and improves mortality in these countries.

Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).