Katsutoshi Obara

Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading

AIM To evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for grading pancreatic neuroendocrine tumors (PNETs). METHODS A total of 22 patients were diagnosed with PNET by EUS-FNA between October 2001 and December 2013 at Fukushima Medical University Hospital. Among these cases, we targeted 10 PNET patients who were evaluated according to the World Health Organization (WHO) 2010 classification. Surgery was performed in eight patients, and chemotherapy was performed in two patients due to multiple liver metastases. Specimens obtained by EUS-FNA were first stained with hematoxylin and eosin and then stained with chromogranin, synaptophysin, CD56, and Ki-67. The specimens were graded by the Ki-67 index according to the WHO 2010 classification. Specimens obtained by surgery were graded by the Ki-67 index and mitotic count (WHO 2010 classification). For the eight specimens obtained by EUS-FNA, the Ki-67 index results were compared with those obtained by surgery. In the two cases treated with chemotherapy, the effects and prognoses were evaluated. RESULTS The sampling rate for histological diagnosis by EUS-FNA was 100%. No adverse effects were observed. The concordance rate between specimens obtained by EUS-FNA and surgery was 87.5% (7/8). For the two cases treated with chemotherapy, case 1 received somatostatin analog therapy and transcatheter arterial infusion (TAI) targeting multiple liver metastases. Subsequent treatment consisted of everolimus. During chemotherapy, the primary tumor remained unconfirmed, although the multiple liver metastases diminished dramatically. Case 2 was classified as neuroendocrine carcinoma (NEC) according to the Ki-67 index of a specimen obtained by EUS-FNA; therefore, cisplatin and irinotecan therapy was started. However, severe adverse effects, including renal failure and diarrhea, were observed, and the therapy regimen was changed to cisplatin and etoposide. TAI targeting multiple liver metastases was performed. Although the liver metastases diminished, the primary tumor remained unconfirmed. These chemotherapy regimens had immediate effects for both unresectable neuroendocrine tumor (NET) and NEC cases. These two subjects are still alive. CONCLUSION EUS-FNA was effective for PNET diagnosis and Ki-67 index grading for WHO 2010 classification, enabling informed decisions on unresectable PNET treatment by identifying NET or NEC.

Guidelines for sedation in gastroenterological endoscopy

Recently, the need for sedation in gastrointestinal endoscopy has been increasing. However, the National Health Insurance Drug Price list in Japan does not include any drug specifically used for the sedation. Although benzodiazepines are the main medication, their use in cases of gastrointestinal endoscopy has not been approved. This has led the Japan Gastrointestinal Endoscopy Society to develop the first set of guidelines for sedation in gastrointestinal endoscopy on the basis of evidence‐based medicine in collaboration with the Japanese Society for Anesthesiologists. The present guidelines comprise 14 statements, five of which were judged to be valid on the highest evidence level and three on the second highest level. The guidelines are not intended to strongly recommend the use of sedation for gastrointestinal endoscopy, but rather to indicate the policy as to the choice of appropriate procedures when such sedation is deemed necessary. In clinical practice, the final decision as to the use of sedation should be made by physicians considering patient willingness and physical condition.

Efficacy of Steroid Pulse Therapy for Autoimmune Pancreatitis Type 1: A Retrospective Study

Autoimmune pancreatitis (AIP) is treatable with steroids, but relapse is frequent. The efficacy of steroid pulse therapy has been shown for various autoimmune diseases, but has not become established therapy. In this study, we reviewed the efficacy of steroid pulse therapy in 24 subjects who were diagnosed with AIP type 1 at our hospital. Patient characteristics, time-course of serum IgG4, and the cumulative relapse-free survival rate were compared between patients who received oral steroid therapy (oral group) and those who were treated with steroid pulse therapy (pulse group). Serum IgG4 was reduced significantly after therapy in both groups and the 5-year cumulative relapse-free survival rates in the two groups did not differ significantly (oral group 46.9%, pulse group 77.8%). However, in a subset of cases with diffuse pancreatic swelling, this rate was significantly lower in the oral group (33.3% vs. 100.0%, p = 0.046). These results suggest that steroid pulse therapy is effective for prevention of relapse in AIP patients with diffuse pancreatic swelling.

Intraductal ultrasonographic anatomy of biliary varices in patients with portal hypertension.

Background and Objectives: The term, portal biliopathy, denotes various biliary abnormalities, such as stenosis and/or dilatation of the bile duct, in patients with portal hypertension. These vascular abnormalities sometimes bring on an obstructive jaundice, but they are not clear which vessels participated in obstructive jaundice. The aim of present study was clear the bile ductal changes in patients with portal hypertension in hopes of establishing a therapeutic strategy for obstructive jaundice caused by biliary varices. Materials and Methods: Three hundred and thirty-seven patients who underwent intraductal ultrasound (IDUS) during endoscopic retrograde cholangiography for biliary abnormalities were enrolled. Portal biliopathy was analyzed using IDUS. Results: Biliary varices were identified in 11 (2.7%) patients. IDUS revealed biliary varices as multiple, hypoechoic features surrounding the bile duct wall. These varices could be categorized into one of two groups according to their location in the sectional image of bile duct: epicholedochal and paracholedochal. Epicholedochal varices were identified in all patients, but paracholedochal varices were observed only in patients with extrahepatic portal obstruction. Conclusion: IDUS was useful to characterize the anatomy of portal biliopathy in detail.

Feasibility of esophageal stent fixation with an over-the-scope-clip for malignant esophageal strictures to prevent migration

Background and study aims  Fixation of an esophageal self-expandable metal stent (SEMS) with an over-the-scope-clip (OTSC) system for a benign stricture to prevent migration has been reported. However, the efficacy of SEMS fixation with an OTSC for malignant esophageal stricture remains unclear. The aim of this retrospective study was to evaluate the feasibility of SEMS fixation with an OTSC for a malignant esophageal stricture. Patients and methods  Twelve patients who underwent esophageal SEMS placement and fixation with an OTSC for a malignant esophageal stricture were included in this retrospective study. The primary endpoint was technical success. The secondary endpoint was clinical success, which was defined as an improvement of at least 1 grade in the dysphagia score 1 week after SEMS placement or changes in the dysphagia score from before SEMS placement to 1 week after SEMS placement. Results  The technical success rate was 100 %. The clinical success rate was 92.3 %. In 6 mild stricture cases in which a standard peroral endoscope could be used, no migration of the SEMS was observed. The median dysphagia score before and at 1 week after SEMS placement was 3 (range 2 – 4) and 0 (0 – 4), respectively, which indicated improvement at 1 week after SEMS placement compared with before SEMS placement ( P  = 0.002). There were no adverse events associated with placement of SEMS and deployment of an OTSC. Conclusions  SEMS fixation with an OTSC is feasible for prevention of migration due to a malignant esophageal stricture.

Potential application of interventional endoscopic ultrasonography for the treatment of esophageal and gastric varices

Interventional endoscopic ultrasonography (EUS) has been developed mainly for the treatment of pancreaticobiliary disorders (e.g. cyst drainage for pancreatic pseudocysts, biliary drainage for malignant biliary obstruction, and celiac plexus neurolysis). Recently, the application of interventional EUS has been expanded to a new field, the treatment of gastrointestinal varices. There have been several studies examining this new technique for the treatment of esophageal and gastric varices. In the present review, we have summarized the current status of interventional EUS for the treatment of esophageal and gastric varices (e.g. EUS‐guided coil deployment for gastric varices) and clarified the clinical feasibility of this procedure.

Change in gastric emptying eight weeks after endoscopic submucosal dissection in patients with early gastric cancer

Background: Gastric emptying after endoscopic submucosal dissection (ESD) for early gastric cancer is not clear. The aim of this study was to evaluate changes in gastric emptying from before ESD to 8 weeks after ESD. Methods: In total, 54 patients with early gastric cancer were enrolled in this study. A breath test with carbon 13 (13C) was conducted before ESD and at 1 and 8 weeks after ESD. The Tlag and T1/2 values were analyzed at each time point. The primary outcomes were the changes in the Tlag and T1/2 values from before ESD to 1 and 8 weeks after ESD. The secondary outcomes were the factors associated with the changes in the Tlag and T1/2 values. Results: Gastric emptying was delayed at 1 and 8 weeks after ESD compared with before ESD (Tlag P = 0.002, P < 0.001; T1/2 P = 0.005, P = 0.001, respectively). The changes in the Tlag and T1/2 values from before ESD to 1 week after ESD were greater for proximal stomach lesions than for distal stomach lesions (P = 0.028, P < 0.001). Proximal stomach lesions were identified as the significant factor that influenced changes in the Tlag and T1/2 values from before ESD to 1 week after ESD in the multivariate analyses (Tlag P = 0.003, T1/2 P = 0.005). Conclusions: ESD induced delayed gastric emptying until 8 weeks after ESD. Proximal stomach lesions were also associated with decreased emptying 1 week after ESD.

Peptic Ulcers in Fukushima Prefecture Related to the Great East Japan Earthquake, Tsunami and Nuclear Accident

Objective Due to the Great East Japan Earthquake, which occurred in March 2011, many residents of Fukushima Prefecture were affected by a radiation accident in addition to suffering loss or damage from the earthquake and the subsequent tsunami. The aim of this study was to evaluate the actual condition of patients with peptic ulcers related to the disaster. Methods Patients with peptic ulcers at six hospitals in three different regions of Fukushima Prefecture during the two months following the disaster and the corresponding period of the year before and the year after the disaster were enrolled in this study. Changes by period and region in the number of esophagogastroduodenoscopy (EGD) examinations and the number of peptic ulcer patients were evaluated as the primary endpoints. Changes in the frequencies of hemorrhagic ulcers were evaluated by period and by region as secondary endpoints. Results The numbers of EGDs and peptic ulcer cases compared to the previous year decreased in 2011 and then increased in 2012. However, the ratio of hemorrhagic ulcers to peptic ulcers was higher in 2011 (51.9%) than in 2010 (38.1%) and 2012 (31.1%), and the 2011 hemorrhagic ulcer ratio was the highest at 63.6% in the coastal area. Regarding bleeding cases during 2011, the rate at 1 month after the disaster (64.1%) was higher than the rate at 2 months after the disaster (40.5%) (p=0.033). Conclusion The number of patients with peptic ulcers did not increase immediately following the disaster in Fukushima Prefecture. However, the rate of bleeding patients increased soon after the disaster, especially in the coastal area.

Efficacy and safety of sedation during endoscopic submucosal dissection of gastric cancers using a comparative trial of propofol versus midazolam

Background and study aims  Proper sedation is necessary for the safe and satisfactory completion of endoscopic submucosal dissection (ESD) for early gastric cancer. This study was conducted as a comparative trial of efficacy and safety, comparing propofol-based sedation and midazolam-based sedation during ESD of early gastric cancer patients. Patients and methods  This study examined 64 lesions in 58 patients treated using ESD with midazolam plus pentazocine between July 2013 and January 2014 (group M) and 237 lesions in 216 patients treated by ESD using propofol plus pentazocine between February 2014 and December 2015 (group P). The two groups were compared in terms of the frequency of body movement during ESD as the primary outcome and in terms of the procedure time, en bloc resection rate, intraoperative change in cardiorespiratory dynamics, and postoperative awareness as the secondary outcomes. Body movement was defined as movement by a patient that required interruption of the procedure or restraint of the patient’s body trunk, and addition of a sedative agent. Results  The median frequency of body movement during ESD was significantly lower in group P (0 times) than in group M (3 times) ( P  < 0.001). No significant difference was found for the mean procedure time (117 min in group P; 127 min in group M). Although no significant difference was found in the incidence of hypoxemia, bradycardia, or bradypnea, the incidence of hypotension was significantly higher in group P (31.5 %) than in group M (6.9 %) ( P  = 0.004). Patients in group P had significantly higher postoperative awareness immediately after ESD and at 1 hour after ESD ( P  = 0.002 and 0.022, respectively). Conclusion  These results demonstrate the efficacy and safety of propofol-based sedation for gastric ESD.

Gastric endoscopic submucosal dissection using sodium carboxymethylcellulose as a new injection substance

AIM To investigate the feasibility of endoscopic submucosal dissection (ESD) using sodium carboxymethylcellulose (SCMC) for gastric cancer. METHODS During October 2011 through April 2013, 98 lesions from 98 patients who underwent ESD using SCMC (ESD-SCMC) for early gastric cancer were enrolled in this study.　Two endoscopists, who had each performed fewer than 30 ESD procedures (less-experienced ESD physicians), performed ESD-SCMC under the supervision of two experts.　The primary outcome was the en bloc resection rate.　Secondary outcomes included the complete resection rate, the procedural time, the bleeding rate after SCMC injection, and complications.　Patient characteristics, time necessary for hemostasis after SCMC injection, rate of treatment completion by less-experienced ESD physicians alone, and the effects of SCMC during ESD and on resected specimens were also evaluated. RESULTS The en bloc resection rate was 100%.　Among these resections, 87.8% of the cases were completed by a less-experienced ESD physician alone.　The complete resection rate was 98.0%.　The mean total procedural time was 75.4 min.　The mean incidence of intraoperative bleeding following SCMC local injection was 1.7 times.　No bleeding was observed after SCMC injection in 29.6% of cases (29/98).　Five complications occurred: one case of microperforation (1.0%) and four cases of postoperative bleeding (4.0%).　SCMC remained in the submucosa.　The submucosa was readily manipulated when the deep submucosa was dissected, even after placing the specimen on a slide. CONCLUSION ESD-SCMC is feasible for the resection of early gastric cancer.