An adult case of congenital duodenal diaphragm that was successfully treated by endoscopic resection using a grasping-type scissor forceps.

Congenital duodenal diaphragm (CDD) is a rare disease that is usually diagnosed in the neonatal period; however, it is sometimes diagnosed later in the adult period. A 39-year-old woman was referred to our hospital due to tarry stool and anemia. Emergent esophagogastroduodenoscopy (EGD) revealed an obstructing membranous structure with a small orifice in the second portion of the duodenum, together with dilatation of the bulbar part. The membranous structure was accompanied by a Dieulafoy-like vessel on the backside, which was considered to have caused tarry stool and anemia. The Dieulafoy-like vessel was successfully treated by endoscopic hemostasis. Based on the computed tomographic gastrography and barium duodenography findings, it was diagnosed as CDD. Later, endoscopic resection of the diaphragm was conducted by an endoscopic submucosal dissection (ESD)-based procedure, with the use of an electrosurgical grasping-type scissor forceps (ClutchCutter [CC]). There were no procedure-related complications. The definite diagnosis of CDD was made based on the observation of typical structures in a pathological examination. This is the first case report of adult CDD that was successfully treated by endoscopic resection using ESD-based techniques with a CC.

Interleukin-1ß as a Predictor of Glucocorticoid Response in Ulcerative Colitis.

BACKGROUND/AIM: Currently, there are no established biomarkers to differentiate between glucocorticoid (GC)-resistant and GC-sensitive ulcerative colitis (UC); however, interleukin (IL)-1ß could be one such candidate biomarker. The aim of this study was to investigate whether mucosally expressed IL-1ß could predict the response to GC in patients with UC. METHODS: A total of 27 mucosal tissue samples from 10 patients with GC-resistant UC (GC-resistant group), 9 patients with GC-sensitive UC (GC-sensitive group), and 8 control patients (control group) were analyzed by qRT-PCR for the expression of IL-1ß, GC receptor α (GRα), GRß, and other inflammatory mediators. Rachmilewitz endoscopic index (REI) between the GC-resistant and GC-sensitive groups was matched to avoid any potential influence of inflammation. RESULTS: The REI did not significantly differ between the GC-resistant and GC-sensitive groups. Mucosally expressed IL-1ß levels in the GC-resistant group were significantly higher than those in the GC-sensitive group. However, there were no significant differences in the expression levels of GRα, GRß, and other inflammatory mediators between the 2 groups. We could distinguish between the GC-resistant and GC-sensitive groups with a sensitivity of 90.0% and specificity of 77.8% based on mucosally expressed IL-1ß. CONCLUSIONS: Mucosally expressed IL-1ß can be used as a predictor of GC response in patients with UC.

[Retrospective Examination of Usefulness and Adverse Effects of Tapentadol in Patients with Cancer Pain during Anticancer Treatment].

We retrospectively examined 106 cases of tapentadol use in Japan in August 2014 for cancer pain at our hospital.The advantage of the opioid medication tapentadol is that its introduction is suitable in patients undergoing anti-cancer treatment because of the low incidence of gastrointestinal symptoms, with glucuronidation involved in the metabolism, and lack of interactions with other drugs.However, depending on the dosage form and presence of swallowing disorders, the administration should be considered carefully.

Continuous measurement of locomotor activity during convalescence and acclimation in group-housed rats.

Locomotor activity is affected by a range of factors in addition to experimental treatment, including the breeding environment. Appropriate convalescence and acclimation are important for animal experiments, because environmental changes and physical burden can result from surgery, transportation, and cage exchange. However, the duration that locomotor activity is affected by these factors is currently unclear, because it has traditionally been difficult to measure locomotor activity in multiple group-housed animals in any location other than the analysis room. In the present study, we analyzed the locomotor activity of group-housed rats using a nano tag® after surgery, transportation, and cage exchange. The nano tag®, a new device for analyzing activity, can measure locomotor activity in laboratory animals with no limitation on the number of animals in same cage. Any type of cage can be used for analysis, at any time of day, and in any location. Nano tags® were subcutaneously implanted in male rats (F344/NSlc, 6 weeks of age) and locomotor activity was continuously measured after surgery, transportation, and cage exchange. Significant activity changes were observed in rats after transportation and cage exchange, 9 days and 3 h after the event, respectively. The results suggest that continuous measurement of locomotor activity with nano tags® can be used to monitor changes in activity induced by environmental changes, and will be helpful for designing animal experiments analyzing locomotor activity.

[A New Twist on the Administration of Naldemedine for Opioid-Induced Constipation in an Outpatient].

Opioid-induced constipation(OIC)occurs with high frequency in patients with cancer undergoing pain treatment using opioids. Osmotic or irritant laxatives are usually used to prevent OIC. Recently, naldemedine has become operational for OIC. Although naldemedine achieved the desired effect, diarrhea is a little feared from the results of clinical phase III study(V9236 clinical trial). We herein report the use of naldemedine to alleviate diarrhea and expect the improvement of the quality of the bowel habits in outpatients with cancer undergoing pain treatment using opioids.

[Combinatorial Use of Rapid-Onset Opioid and Short-Acting Opioid Is Effective against Breakthrough Cancer Pain].

Breakthrough cancer pain is divided into "predictable breakthrough pain" and "unpredictable breakthrough pain". Uncontrolled breakthrough pain in cancer negatively affects the quality of life of the patients. The short-acting opioid(SAO) requires considerable time to produce analgesia, and is not adequate as a rescue drug. The rapid-onset opioid(ROO)immediately produces analgesia, but its appropriate usage is difficult. For instance, the frequency and interval of ROO usage is limited, making the optimization of dosage cumbersome. Therefore, ROO has not yet gained popularity. Here, we report that a combinatorial use of ROO and SAO is effective against breakthrough cancer pain, with SAO and ROO being suitable for "predictable breakthrough pain", and "unpredictable breakthrough pain", respectively. The effectiveness and safety of this combination were assessed for many patients with breakthrough cancer pain.

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).

Metformin enhances anti-tumor effect of L-type amino acid transporter 1 (LAT1) inhibitor.

BACKGROUND: In many cancer cells, L-type amino acid transporter 1 (LAT1) transports neutral amino acids with bulky side chain, which activate mammalian target of rapamycin (mTOR) to cause cell proliferation. An anti-diabetic drug, metformin, has been shown to activate AMP-activated protein kinase (AMPK), which leads to inhibition of mTOR. LAT1 inhibition in combination with metformin could result in more prominent suppression of mTOR activity. PURPOSE: Anti-proliferative effect of a newly developed LAT1 specific inhibitor JPH203 in combination with metformin is evaluated in 2 head and neck cancer cell lines, Ca9-22 and HEp-2 cells and in nude mice inoculated with Ca9-22 cells. RESULTS AND DISCUSSION: By MTT assay, 0.5 mM metformin inhibited proliferation of Ca9-22 cells to 70% of control. In the presence of 100 µM JPH203, proliferation of Ca9-22 cells was inhibited to 60% of control. By combining these 2 drugs, proliferation of Ca9-22 was significantly inhibited to 40% of control. However, this regimen was not very effective against HEp-2 cells. This combination also suppressed in vivo growth of Ca9-22 cells in a xenotransplant model. A combination of anti-LAT1 drug with metformin may be an effective anti-proliferative therapy for certain subsets of cancers.

Effects of Acotiamide on the Esophageal Motility Function in Patients with Esophageal Motility Disorders: A Pilot Study.

BACKGROUND AND AIM: Acotiamide is a newly developed prokinetic drug that is clinically used to treat functional dyspepsia (FD). The objective of this study was to assess the therapeutic effects of acotiamide in patients with esophageal motility disorders (EMDs). METHODS: Twenty-nine patients with both symptoms of FD and symptoms suspicious of EMDs were enrolled. Esophageal motility function was evaluated by high-resolution manometry before and after 2 weeks administration of acotiamide (100 mg) 3 times per day. RESULTS: Twenty-nine patients were diagnosed with achalasia (n = 4), esophagogastric junction outflow obstruction (EGJOO) (n = 6), absent peristalsis (n = 2), distal esophageal spasm (n = 4), frequently failed peristalsis (n = 7), weak peristalsis (n = 2) and 4 of them were found to be normal. An analysis in all 29 patients showed that acotiamide had no effects on based on distal contractile integral (DCI), basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP). Subgroup analysis, however, showed that acotiamide dramatically reduced IRP, from 19.5 (15.1-30.8) to 12.1 (5.6-16.4) mm Hg, and DCI, from 2,517.9 (1,451.0-8,385.0) to 1,872.5 (812.3-5,225.3) mm Hg·cm·s, in the 6 patients with EGJOO. CONCLUSIONS: Acotiamide potentially normalized impaired LES relaxation in patients with EGJOO, while having no effects on normal esophageal motility patterns. Acotiamide may be a promising treatment for EGJOO.

Short- and long-term outcomes of endoscopic resection of rectal neuroendocrine tumours: analyses according to the WHO 2010 classification.

OBJECTIVE: Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications. MATERIAL AND METHODS: One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated. RESULTS: Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate. CONCLUSION: Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours >1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery.

Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multicenter large-scale retrospective analysis of short- and long-term outcomes.

OBJECTIVE: The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection. MATERIALS AND METHODS: The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group. RESULTS: Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence. CONCLUSION: The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

Characteristics of hemorrhagic peptic ulcers in patients receiving antithrombotic/nonsteroidal antiinflammatory drug therapy.

BACKGROUND/AIMS: Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. METHODS: We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213). The patients who were not treated with antithrombotics/NSAIDs were categorized as the control (C) group (n=263). The clinical characteristics were compared between the groups. RESULTS: The patients in the AT group were significantly older than those in the C group (p<0.0001). The hemoglobin levels before/without transfusion were significantly lower in the AT group (8.24±2.41 g/dL) than in the C group (9.44±2.95 g/dL) (p<0.0001). After adjusting for age, the difference in the hemoglobin levels between the two groups remained significant (p=0.0334). The transfusion rates were significantly higher in the AT group than in the C group (p=0.0002). However, the outcome of endoscopic hemostasis was similar in the AT and C groups. CONCLUSIONS: Patients with hemorrhagic peptic ulcers receiving antithrombotic/NSAID therapies were exposed to a greater risk of severe bleeding that required transfusion but were still treatable by endoscopy.

[Gastric outlet obstruction caused by gastrostomy tube balloon in 3 cases].

We report 3 cases with unusual complications of gastric outlet obstruction caused by a gastrostomy tube balloon. All cases developed vomiting, and 2 cases were accompanied by hematemesis. Gastric ulcer was observed in 1 case, aspiration pneumonia was observed in 2 cases, and pancreatitis was observed in 1 case. This condition improved rapidly by correction of the position of the balloon in all cases. In patient vomiting during management for gastrostomy we need to consider migration of the gastrostomy tube balloon. Careful management of the gastrostomy tube balloon is important.

Randomized controlled trial: roxatidine vs omeprazole for non-erosive reflux disease.

BACKGROUND/AIMS: Proton pump inhibitor (PPI) therapy is considered as the first choice for treatment of non-erosive reflux disease (NERD). However, NERD is less sensitive to PPIs than erosive gastroesophageal reflux disease (GERD) and the differences between PPIs and H2 receptor antagonists are less evident in NERD than in erosive GERD. Since gastric acid secretion is lower in the Japanese population than in Western populations, we aimed to investigate whether PPI therapy is really necessary for NERD patients in Japan. METHODOLOGY: Thirty-three symptomatic endoscopically diagnosed NERD patients were randomly assigned to receive roxatidine acetate 75 mg twice daily (n = 16) or omeprazole 20 mg once daily (n = 17). Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale at baseline and after 4 and 8 weeks of treatment. RESULTS: Both roxatidine and omeprazole significantly improved the heartburn score at 4 and 8 weeks. The clinical response rates did not differ between roxatidine and omeprazole. Both roxatidine and omeprazole significantly relieved not only reflux but also abdominal pain and indigestion. The degrees of improvement did not differ between the two groups. CONCLUSION: Roxatidine relieved the symptoms of NERD patients with similar effectiveness to omeprazole. Therefore, roxatidine may be a good choice for NERD treatment.

[Intestinal tuberculosis of the terminal ileum causing obstructive ileus and tuberculous peritonitis and presenting numerous peritoneal small red nodules: a case report].

A 38-year-old woman suffering from lower abdominal pain was referred to our hospital. Abdominal computed tomography showed marked thickening of the terminal ileum to the cecum, localized collection of ascites, and multiple mesenteric lymphadenopathy. A barium contrast small bowel series showed solitary severe stenosis of the terminal ileum with marked swelling of the ileocecal valve, where colonoscopy could not pass through, suggesting that ileal stenosis was caused by intestinal tuberculosis. She also showed strongly positive tuberculin skin test. Laparoscopy-assisted ileocecal resection was performed for confirmation of diagnosis and removal of the stenotic intestinal lesion. Laparoscopically, numerous small red nodules scattered on the stenotic ileal serosa, peritoneum, and mesenterium. Histopathological examination revealed ileal tuberculosis causing ulcerative stricture, and mesenteric tuberculous lymphadenitis. The small red nodules were formed of hemorrhagic tuberculous nodules.

Duplication cyst of the small intestine found by double-balloon endoscopy: a case report.

A 35-year-old man was admitted due to bloody stool and anemia. The bleeding source could not be detected by esophagogastroduodenoscopy or colonoscopy. Double balloon endoscopy (DBE) revealed a diverticulum-like hole in which coagula stuck in the ileum at 1 meter on the oral side from the ileocecal valve. The adjacent mucosa just to the oral side of the hole was elevated like a submucosal tumor. The lesion was considered the source of bleeding and removed surgically. It was determined to be a cyst with an ileal structure on the mesenteric aspect accompanying gastric mucosa. The diagnosis was a duplication cyst of the ileum, which is a rare entity that can cause gastrointestinal bleeding. In the present case, DBE was used to find the hemorrhagic duplication cyst in the ileum.

Successful endoscopic hemostasis for bleeding from an acquired ileal diverticulum.

We herein report successful endoscopic hemostasis in a patient with a bleeding from acquired ileal diverticulum. A 65-year-old woman was introduced to our hospital after the sudden onset of painless hematochezia. When emergency colonoscopy was performed, the site of bleeding could not be identified because of extensive blood pooling in the colon and ileocecal region. After admission, repeat colonoscopy with a transparent hood device after bowel preparation disclosed oozing of blood from an ileal diverticulum approximately 15 cm proximal to the ileocecal junction. We performed endoscopic therapy with injection of a hypertonic saline-epinephrine solution and placement of additional hemoclips in the diverticulum. Since the latter treatment, the patient had no recurrent hematochezia, and occult blood tests in stool had been negative. In cases of lower gastrointestinal bleeding, bleeding from an acquired ileal diverticulum should be considered and the terminal ileum carefully observed.

Gastric mucosa-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma cell infiltration. case report.

This is the first case report of gastric mucosal-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma (ATLL) cell infiltration. A 43-yr-old Japanese woman who was seropositive for antihuman T cell leukemia virus-I antibody complained of epigastric pain in April, 1996. Endoscopy showed gastric ulcers in the antrum. Biopsy specimens showed Helicobacter pylori infection. Her symptoms were relieved by treatment with ranitidine. In March, 1998, she complained of epigastric pain and abdominal fullness. Smears of peripheral blood revealed atypical lymphocytes with nuclear irregularity, consistent with ATLL cells. She was diagnosed to have ATLL. Endoscopy revealed multiple gastric ulcers in the antrum and the angle. Biopsy specimens demonstrated small centrocyte-like cells forming lymphoepithelial lesions, with infiltrations of large atypical lymphoid cells of ATLL. On immunohistochemical staining, the small centrocyte-like cells were positive for B cell markers (L26, CD20), whereas the large atypical lymphoid cells were positive for T cell marker (UCHL-1, CD45RO). Her findings were attributed to gastric mucosal-associated lymphoid tissue lymphoma with gastric involvement with ATLL.