Publications by authors named "Tamotsu Matsuhashi"

47 Publications

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Cancer Med 2021 May 15. Epub 2021 May 15.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.
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http://dx.doi.org/10.1002/cam4.3927DOI Listing
May 2021

Potent Acid Suppression With Vonoprazan vs Proton Pump Inhibitors Does Not Have Higher Association With Clostridioides difficile Infection.

Am J Gastroenterol 2021 May 13. Epub 2021 May 13.

Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan.

Introduction: Proton pump inhibitors (PPIs) are associated with the onset of Clostridioides difficile infection (CDI). Although a new potassium-competitive acid blocker, vonoprazan, consistently shows a more potent acid inhibitory effect in comparison to PPIs, the risk of CDI in vonoprazan-treated patients relative to those treated with PPIs is unknown. In this retrospective case-control study, using a nationwide hospital-based administrative database in Japan, we investigated the association of the onset of CDI in patients treated with vonoprazan.

Methods: A CDI case was defined as a case in which a patient was diagnosed and treated for CDI. For each CDI case, 3 non-CDI patients were extracted as controls. Information on the usage of acid suppressants in the 2 months before the onset of CDI and other confounding factors was collected. Relative associations of gastric acid suppressants with the onset of CDI were estimated.

Results: A total of 4,466 CDI cases and 13,220 of non-CDI controls were extracted. A multivariate conditional regression analysis revealed that PPI or vonoprazan use was modestly, but significantly associated with CDI (odds ratio [95% confidence interval]: PPI, 1.3 [1.2-1.4]; vonoprazan, 1.4 [1.2-1.7]). With PPI users as a reference, vonoprazan did not show a stronger association with CDI (odds ratio [95% confidence interval]: 1.07 [0.91-1.26]).

Discussion: We found a significant positive association between vonoprazan use and CDI; however, the magnitude of the association was not beyond that in PPI users. This is the first report on any potential adverse effects of vonoprazan.
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http://dx.doi.org/10.14309/ajg.0000000000001309DOI Listing
May 2021

Effects of anti-thrombotic drugs on all-cause mortality after upper gastrointestinal bleeding in Japan: A multicenter study with 2205 cases.

Dig Endosc 2021 Feb 21. Epub 2021 Feb 21.

Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan.

Objects: Although anti-thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti-thrombotic agents on in-hospital mortality following UGIB.

Methods: Information on clinical parameters, including usage of anti-thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high-volume centers in Japan between 2011 and 2018. The all-cause in-hospital mortality rate was evaluated according to the usage of anti-thrombotic agents.

Results: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty-five (29.3%) patients used anti-thrombotic agents. The all-cause in-hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end-stage malignancy, 96 deaths (bleeding-related, n = 22 ; non-bleeding-related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti-thrombotic users was significantly higher than that in non-users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti-thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non-users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%).

Conclusions: Although the usage of anti-thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti-thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti-thrombotic agents.
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http://dx.doi.org/10.1111/den.13961DOI Listing
February 2021

Effect of acid-reducing agents on clinical relapse in ulcerative colitis with pH-dependent-released 5-aminosalicylic acid: a multicenter retrospective study in Japan.

Intest Res 2021 Apr 18;19(2):225-231. Epub 2020 Aug 18.

Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Akita, Japan.

Background/aims: 5-Aminosalicylic acid (5-ASA) is a basic drug for inducing and maintaining remission for ulcerative colitis. One of its formulations has a coating with a pH-dependent degradation that ensures the release 5-ASA at the terminal ileum. No evidence has been shown concerning the effects of proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) on the clinical course of ulcerative colitis patients in remission. The present study assessed the effect of PPIs or H2RAs on the relapse of ulcerative colitis patients in clinical remission maintained by pH-dependent released 5-ASA.

Methods: Ulcerative colitis patients who had been prescribed time- or pH-dependent-released 5-ASA between January 2015 and December 2018 were enrolled in this multicenter retrospective study. The period of remission until relapse occurred was analyzed among the patients taking time-dependent-released 5-ASA or pH-dependent-released 5-ASA with/without PPIs or H2RAs.

Results: One hundred and nineteen patients were analyzed in this study. In the primary endpoint, the relapse rate was higher in patients taking pH-dependent-released 5-ASA and PPIs or H2RAs than in those taking the pH-dependent-released 5-ASA without PPIs or H2RAs, while the relapse rate was similar in patients taking the time-dependent-released 5-ASA with or without PPIs or H2RAs concomitantly. Patients with a short duration of disease and middle-aged patients more frequently showed relapse with PPIs or H2RAs than the other patients.

Conclusions: The coadministration of PPIs or H2RAs affects the clinical course of ulcerative colitis in remission maintained by pH-dependent-released 5-ASA.
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http://dx.doi.org/10.5217/ir.2020.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100376PMC
April 2021

Risks for Rebleeding and In-Hospital Mortality after Gastrointestinal Bleeding in a Tertiary Referral Center in Japan.

Digestion 2020 13;101(1):31-37. Epub 2019 Nov 13.

Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan,

Background: Gastrointestinal bleeding (GIB) is one of the most common medical emergencies. We investigated the overall mortality after GIB in our institute and analyzed the prognostic factors in upper GIB (UGIB) and lower GIB (LGIB) separately.

Summary: Between January 2010 and December 2018, 190 patients diagnosed with GIB in our hospital were retrospectively enrolled. Clinical records and biological data were collected. Risks for rebleeding and in-hospital mortality were assessed by a logistic regression analysis. Overall, the rebleeding rate and in-hospital mortality were 22.6 and 7.6%, respectively. GIB itself was not the direct cause of death in any cases. While older age (>65 years) was a significant risk factor for rebleeding in UGIB with an OR of 6.1 and 95% CI of 1.3-29.1, a poorer performance status (PS; ≥3) was a strong risk factor for rebleeding in LGIB, with an OR of 11.8 and 95% CI of 1.7-83.8. Poor PS and tachycardia (>100/min) were significantly associated with mortality in both UGIB and LGIB. In contrast, hypoalbuminemia (<3.0 g/dL) was associated with the mortality in LGIB alone. Key Messages: There were considerable differences in the risk factors for rebleeding and in-hospital mortality between UGIB and LGIB. The overall in-hospital mortality was 7.9% after GIB, including that a substantial portion of patients with GIB died from systemic complications after successful endoscopic hemostasis. Physicians need to diligently perform systematic treatment for GIB, which may be particularly important in societies of advancing aging, like Japan.
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http://dx.doi.org/10.1159/000504088DOI Listing
August 2020

Aggressive Inflammatory Myofibroblastic Tumor without Anaplastic Lymphoma Kinase Gene Rearrangement in the Rectum with Liver Metastasis.

Intern Med 2020 Feb 7;59(4):495-499. Epub 2019 Oct 7.

Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Japan.

Inflammatory myofibroblastic tumor is a rare intermediate-grade tumor. We herein report the case of an 81-year-old man with rectal ulceration and abnormal retroperitoneal soft tissue with a high serum level of IgG4. The administration of prednisolone reduced the retroperitoneal lesion; however, the rectal ulceration expanded. Surgical resection was performed. A histopathological examination revealed proliferating spindle cells accompanied by inflammatory cells and plasma cells. Liver metastasis emerged two months after surgical resection, and the histology of the proliferating spindle cells sampled by a fine-needle biopsy was similar to that of the rectal tissue. The patient ultimately died of inflammatory myofibroblastic tumor.
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http://dx.doi.org/10.2169/internalmedicine.3686-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056365PMC
February 2020

Chronological Changes in the Gastric Cancer Subsite in Akita, Japan: The Trends from the Data of a Hospital-Based Registration System.

Tohoku J Exp Med 2018 10;246(2):131-140

Department of Gastroenterology, Akita University Graduate School of Medicine.

With the decreasing global trend in the Helicobacter pylori infection rate, compositional changes in the gastric cancer subsites have occurred worldwide. However, the compositional changes in Asian countries, including Japan, remain to be clarified. The aim of this study is to investigate the latest chronological changes in the gastric cancer subsite using a hospital-based registration system in Akita prefecture in Japan. From 2007-2015, subsites of gastric cancers were coded according to the International Classification of Diseases for Oncology (ICD-03). The nine-year registration period was divided into the three 3-year periods: 2007-2009, 2010-2012, and 2013-2015. A total of 10,804 cases of gastric cancer were registered. The proportion of cardiac cancer among total gastric cancer slightly but significantly declined from 12.1% in 2007-2009 to 9.2% in 2013-2015 (P < 0.01). Among non-cardia cancer, the proportion of corpus cancer significantly increased from 41.3% to 50.2% during the study period (P < 0.01), while that of antropylorus cancer significantly decreased from 37.6% to 34.3% (P < 0.05). Such compositional changes in the gastric cancer subsite were observed largely in men, regardless of the histologic subtype of cancer. With the decreasing H. pylori infection rate, compositional changes in the gastric cancer subsite are occurring in Japan. While the proportion of cardia and antropylorus cancer is declining, that of corpus cancer is increasing, indicating diverse etiology of gastric carcinogenesis depending on the subsites. Identifying the most common sites of occurrence, may help to improve the efficiency of screening for gastric cancer.
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http://dx.doi.org/10.1620/tjem.246.131DOI Listing
October 2018

An investigation on endoscopic laryngopharyngeal surgery and related outcomes.

Wideochir Inne Tech Maloinwazyjne 2018 Sep 5;13(3):394-400. Epub 2018 Jul 5.

Department of Otorhinolaryngology and Head-and-Neck Surgery, Akita University, Graduate School of Medicine, Akita, Japan.

Introduction: Robotic surgery is used in Europe and the US for oropharyngeal/hypopharyngeal cancers. Although robots can successfully perform procedures that are too delicate for surgeons and quickly learn accurate techniques, robotic surgery is not still authorized for the craniocervical region in Japan. In Japan, endoscopic laryngopharyngeal surgery (ELPS) is widely performed. Because oropharyngeal/hypopharyngeal cancer can be resected at an early stage, we have contributed to an improvement in the survival rate.

Aim: To analyze clinical outcomes and risk factors of postoperative cervical lymph node metastases after ELPS.

Material And Methods: Fifty-two patients with 71 superficial oropharyngeal/hypopharyngeal cancers were included. A Sato-type arcuation laryngoscope was inserted, and oropharyngeal and hypopharyngeal fields were secured. We have recently been performing head and neck surgery using only a flexible endoscope because gastroscopy and arcuation-type forceps interfere with each other.

Results: The 5-year survival rate was 95.2%. The risk factors of lymph node metastases were examined. The depth of the tumor significantly affected lymph node metastases.

Conclusions: With a favorable 5-year survival rate and low functional impairment, ELPS is an extremely effective form of treatment. It can provide a clear field of view in the hypopharynx and has a low cost; hence, it should be further developed as a treatment method.
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http://dx.doi.org/10.5114/wiitm.2018.76956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174174PMC
September 2018

Phlegmonous Gastritis: A Report of Three Cases with Clinical and Imaging Features.

Intern Med 2018 Aug 30;57(15):2185-2188. Epub 2018 Mar 30.

Department of Gastroenterology, Graduate School of Medicine, Akita University, Japan.

Phlegmonous gastritis is a rare but often fatal acute pyogenic infection of the stomach. We herein report three cases of phlegmonous gastritis with different causes: the long-term placement of a nasogastric feeding tube, bacteremia associated with cellulitis in a diabetic patient, and an adverse reaction to paclitaxel/carboplatin chemotherapy for cancer of unknown primary cause, which were classified as primary, secondary, and idiopathic types, respectively. Coping with the increasing morbidity rate associated with the diverse background of such patients requires a thorough understanding of the clinical features and image findings associated with this entity.
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http://dx.doi.org/10.2169/internalmedicine.0707-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120850PMC
August 2018

A case of esophageal actinomycosis with a unique morphology presenting as a refractory ulcer.

Clin J Gastroenterol 2018 Feb 9;11(1):38-41. Epub 2017 Nov 9.

Department of Gastroenterology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita, Akita, Japan.

A 60-year-old man presented with odynophagia after bronchial artery infusion chemotherapy for pulmonary metastasis of hepatocellular carcinoma. Esophagogastroduodenoscopy (EGD) revealed an esophageal ulcer in the middle thoracic esophagus. An esophageal biopsy demonstrated no malignancy. However, the symptoms had not improved after a month. EGD was performed again and showed a white cord lump at the bottom of the same esophageal ulcer identified before, showing no improving tendency. A repeated biopsy of the lump revealed actinomycosis, and the symptoms were improved by the oral administration of ampicillin. We herein report a case in which esophageal actinomycosis with a unique morphology of refractory esophageal ulcer was rapidly improved by the administration of antibiotics.
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http://dx.doi.org/10.1007/s12328-017-0797-1DOI Listing
February 2018

Feasibility of colorectal endoscopic submucosal dissection (ESD) carried out by endoscopists with no or little experience in gastric ESD.

Dig Endosc 2017 Apr;29 Suppl 2:58-65

Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Akita, Japan.

Background And Aim: Colorectal endoscopic submucosal dissection (ESD) is recommended to be carried out only by endoscopists with sufficient experience in gastric ESD. However, early gastric carcinoma is less common in Western countries than in Japan, and endoscopic maneuverability differs between the stomach and colorectum. We assessed the feasibility of colorectal ESD carried out by endoscopists with no or little experience in gastric ESD.

Methods: We analyzed en bloc resection, R0 resection and perforation rates in 180 consecutive colorectal ESD carried out by three endoscopists who had no or <5 cases of experience in gastric ESD. We also identified factors associated with R0 resection failure.

Results: Overall en bloc and R0 resection rates were 93.3% (168/180) and 82.2% (148/180), respectively. All 11 cases with perforation were treated endoscopically. Dividing 180 cases into three learning phases (early, middle, or late phases), the en bloc and R0 resection rates increased from 88.3% and 75.0% in the early phase to 98.3% and 88.3% in the late phase, respectively. Perforation rate also improved from 10.0% to 3.3%. Factors associated with R0 resection failure were location at junctions (odds ratio: 6.8, 95% CI: 1.9-27.5), preoperative factors reflecting fibrosis (5.8, 1.9-19.0), and late phase (0.2, 0.1-0.7).

Conclusion: Endoscopists without experience in gastric ESD carried out colorectal ESD safely. In the early and middle phases (≤40 cases), they should treat mainly rectal lesions but may also resect lesions in the colon avoiding flexures. Lesions located at junctions and those with preoperative factors reflecting fibrosis should be resected after completing 40 procedures.
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http://dx.doi.org/10.1111/den.12814DOI Listing
April 2017

True Primary Enterolith Treated by Balloon-assisted Enteroscopy.

Intern Med 2015 1;54(19):2439-42. Epub 2015 Oct 1.

Department of Gastroenterology, Akita University Graduate School of Medicine, Japan.

Primary enterolith is a rare condition that can induce ileus and intestinal perforation. We report the first case of a true primary enterolith treated by balloon-assisted enteroscopy. The patient presented with a small intestinal ileus. After its improvement following the insertion of an ileus tube, radiography with amidotrizoate sodium meglumine detected a round, movable defect in the ileum measuring 42 mm diameter. The patient was diagnosed with a primary enterolith based on her past history. The enterolith was fractured and removed using balloon-assisted enteroscopy. This case suggests that balloon-assisted enteroscopy may be an effective non-invasive treatment option for enteroliths.
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http://dx.doi.org/10.2169/internalmedicine.54.5208DOI Listing
July 2016

Successful treatment with infliximab for refractory para-ileostomal ulceration in a patient with Behҫet's disease.

Clin J Gastroenterol 2015 Aug 9;8(4):193-6. Epub 2015 Jun 9.

Department of Gastroenterology, Akita University Hospital, Akita, Japan.

Behҫet's disease (BD) is a chronic disorder involving multiple organ systems including the small and large intestines. A 46-year-old female diagnosed with intestinal BD presented with ileocecal perforation and diffuse peritonitis and subsequently underwent ileocolic resection with ileostomy. After surgery, she suffered from refractory para-ileostomal ulceration associated with BD. Most importantly, however, treatment with infliximab was significantly effective in healing the ulceration. This is the first report of para-ileostomal ulceration associated with BD successfully treated with infliximab, suggesting the possible use of infliximab as a therapeutic option for para-stomal ulcers related to BD.
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http://dx.doi.org/10.1007/s12328-015-0576-9DOI Listing
August 2015

Mesenteric lymph node abscess due to Yersinia enterocolitica: case report and review of the literature.

Clin J Gastroenterol 2014 Feb 9;7(1):41-7. Epub 2014 Jan 9.

Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

We describe the case of a 74-year-old female with a mesenteric lymph node abscess caused by a Yersinia enterocolitica infection. She had been administered an immunosuppressive drug and was admitted to the hospital due to a high fever, right lower abdominal pain and advanced leukocytosis. We initially diagnosed her with lymphadenitis based on the symptoms and the imaging studies. However, conservative treatment with antibiotics did not yield any improvement, and abscess formation was suspected. Surgical treatment was performed, and the culture from the drainage fluid grew Y. enterocolitica. The histological findings suggested that an ulcerative lesion of the terminal ileum was the entry port of Y. enterocolitica. The pathogen infected the mesenteric lymph nodes and spread along the ileocecal lymphatic vessels, resulting in the formation of an abscess. We also provide a review of the previously published literature on lymph node abscesses due to Y. enterocolitica infections.
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http://dx.doi.org/10.1007/s12328-013-0452-4DOI Listing
February 2014

[Q & A. A colonic lesion discovered at the investigation of positive occult blood].

Nihon Shokakibyo Gakkai Zasshi 2013 Oct;110(10):1838, 1841-2

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October 2013

Duodenocolic fistula caused by a peptic stomal ulcer following distal gastrectomy.

Intern Med 2013 15;52(14):1579-83. Epub 2013 Jul 15.

Department of Gastroenterology, Akita University Graduate School of Medicine, Japan.

We herein describe the case of a 51-year-old man with a duodenocolic fistula (DCF) caused by a stomal ulcer. The patient complained of watery diarrhea, dysgeusia and malnutrition. His medical history included distal gastrectomy with Billroth I reconstruction for duodenal ulcer perforation. A combination study using endoscopy and contrast imaging confirmed the presence of DCF. Laparotomic fistulectomy was performed, which resulted in the patient's recovery from diarrhea and malnutrition. The histological findings suggested that the fistula had originated from a stomal ulcer. In patients with chronic watery diarrhea of obscure origin following gastrectomy, DCF is a possible cause of the diarrhea.
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http://dx.doi.org/10.2169/internalmedicine.52.0496DOI Listing
March 2014

Functional roles of TGF-β1 in intestinal epithelial cells through Smad-dependent and non-Smad pathways.

Dig Dis Sci 2013 May 10;58(5):1207-17. Epub 2013 Jan 10.

Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Background And Aims: Transforming growth factor-β1 (TGF-β1) is one of the growth factors expressed in the gut, and has been shown to play an important role in intestinal mucosal healing. We investigated the effects of TGF-β1 on the cellular functions of intestinal epithelial cells, and also evaluated its signaling pathways in these cells.

Methods: We used the rat IEC-6 intestinal epithelial cell line for these studies. The expression of TGF-β1/Smad signaling molecules was examined. We evaluated the effect of TGF-β1 on the proliferation and differentiation by the BrdU incorporation assay and real-time PCR. We manipulated the expression levels of Smad2 and Smad3 using an adenovirus system and small interfering RNA to examine the signaling pathways. The expression of Smad2 and Smad3 along the crypt-villus axis was also examined in the murine intestine.

Results: IEC-6 cells produced TGF-β1 and expressed functional TGF-β/Smad signaling molecules. The addition of TGF-β1 in the culture medium suppressed the proliferation and increased the expression of a differentiation marker of enterocytes, in a dose-dependent manner. The adenovirus-mediated and small interfering RNA-mediated studies clearly showed that the growth inhibitory effect and the promotion of differentiation were exerted through a Smad3-dependent and a Smad2-dependent pathway, respectively. IEC-6 cells exhibited upregulated expression of an inhibitory Smad (Smad7) as a form of negative feedback via a non-Smad pathway. Smad2 was predominantly expressed in villi, and Smad3 in crypts.

Conclusions: TGF-β1 regulates the cellular functions of intestinal epithelial cells through both Smad-dependent and non-Smad pathways.
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http://dx.doi.org/10.1007/s10620-012-2515-7DOI Listing
May 2013

Outcomes of patients receiving additional esophagectomy after endoscopic resection for clinically mucosal, but pathologically submucosal, squamous cell carcinoma of the esophagus.

Surg Today 2013 Jun 17;43(6):638-42. Epub 2012 Aug 17.

Department of Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.

Purpose: This study investigated the actual rate or extent of lymph node metastasis or the survival outcomes among patients that underwent esophagectomy with lymph node dissection after ESD for clinical mucosal, but pathological submucosal, esophageal cancer.

Methods: Seventeen patients that received esophagectomy with two- or three-field lymph node dissection as additional treatment after ESD for clinical mucosal, but pathological submucosal, esophageal cancer between 2006 and 2010 were analyzed. The rate and extent of lymph node metastasis and the patient outcomes were determined.

Results: The tumor depths were diagnosed as SM1 in 8 (47 %) patients and SM2 in 9 (53 %), based on the analyses of resected specimens. Lymphatic invasion was evident in 13 (76 %) patients, while venous invasion was detected in 5 (29 %). Five (29 %) patients had pathologically detected lymph node involvement. Seven (0.8 %) of the 890 dissected nodes showed cancer involvement. Three patients had one involved node in the mediastinum or abdomen, and 2 patients had 2 involved nodes in the abdomen. The patients were followed up for 11-71 months (median 23 months), and all were alive without recurrence at the final follow-up.

Conclusion: Twenty-nine percent of the patients diagnosed with clinically mucosal, but pathologically submucosal, thoracic squamous cell esophageal cancer after ESD had 1-2 cancer-involved lymph nodes in the lower mediastinum and abdomen. Esophagectomy with lymph node dissection is therefore considered to be a necessary and effective additional treatment for these patients.
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http://dx.doi.org/10.1007/s00595-012-0295-5DOI Listing
June 2013

Epimorphin protects hepatocytes from oxidative stress by inhibiting mitochondrial injury.

J Gastroenterol Hepatol 2011 Jan;26(1):201-6

Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.

Background And Aims: Many investigations have demonstrated that cell injuries caused by generation of reactive oxygen species (ROS) is a common mechanism of various hepatic disorders. Recently, we have demonstrated that epimorphin, originally cloned as a mesenchymal protein, protects cultured intestinal epithelial cells from ROS. We therefore examine whether epimorphin protects primary cultured hepatocytes from ROS-induced cell injury.

Methods: We explored the cell viability and the intracellular ROS levels of purified murine hepatocytes after exposure to 0.5 mM H(2)O(2) with or without pretreatment of epimorphin. Then, we observed mitochondrial permeability transition (MPT) and depolarization using confocal microscopy to make clear the mechanism that epimorphin inhibited cell injuries after exposure to H(2)O(2). In addition, to clarify the signaling pathways related to cell survival, we carried out Western blotting analysis with phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) polyclonal antibody to evaluate the inhibition of JNK by epimorphin. Finally, we evaluated the cell viability in hepatocytes administered JNK inhibitor.

Results: Epimorphin protected primary cultured hepatocytes from H(2)O(2)-induced cell injuries independent of intracellular ROS levels. Epimorphin also inhibited onset of MPT, depolarization of the mitochondrial membrane potential, and eventually cell killing. The cell protective function of epimorphin after exposure to H(2)O(2) was not dependent on Akt signaling but on JNK signaling.

Conclusion: Epimorphin can protect hepatocytes from MPT-dependent cell injury induced by ROS. Since hepatic disorders could be caused by MPT-dependent cell injuries with excessive ROS, epimorphin might open a new therapeutic avenue for hepatic disorders.
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http://dx.doi.org/10.1111/j.1440-1746.2010.06327.xDOI Listing
January 2011

Hamartomatous inverted polyp successfully treated by endoscopic submucosal dissection.

Intern Med 2008 15;47(4):259-62. Epub 2008 Feb 15.

Department of Gastroenterology, Akita University School of Medicine, Akita, Japan.

We report a case of gastric hamartomatous inverted polyps that are a rare histological type of gastric polyp and difficult to diagnose. Gastric submucosal tumor was detected by upper gastrointestinal X-ray series in 37-year-old man. Endoscopy revealed a submucosal tumor (SMT) , which eroded with a depression on its surface in the fornix. Endoscopic ultrasonography showed a heterogeneous tumor in the third layer. Endoscopic submucosal dissection (ESD) was performed to resect the tumor completely. The pathological diagnosis was a gastric hamartomatous inverted polyp. The patient was later discharged without any complications. Hamartomatous inverted polyps without a stalk are classified as the SMT type because the tumor is inverted down growth into the submucosal layer, otherwise polyps with a stalk are classified as the polyp type. All of the polyps were resected endoscopically, however, surgical resection was performed for those of the SMT type, because it is difficult to remove this type completely by en-block resection using conventional EMR technique. ESD method may be indicated for SMT-type hamartomatous inverted polyps.
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http://dx.doi.org/10.2169/internalmedicine.47.0360DOI Listing
April 2008

Effect of alcohol consumption on leptin level in serum, adipose tissue, and gastric mucosa.

Dig Dis Sci 2007 Nov 4;52(11):3066-9. Epub 2007 Apr 4.

Department of Internal Medicine and Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.

It has been reported that the stomach is a source of leptin, which is the product of the obese (ob) gene. In the present study, the effect of alcohol on leptin level in serum, gastric mucosa, and adipose tissue was studied to understand the relationship between appetite and alcohol consumption. Male Sprague-Dawley rats were administered 1 ml of 25% ethanol perorally. Leptin levels in the serum, gastric mucosa, and adipose tissue were measured. The serum leptin level was significantly decreased 3 and 6 hr after ethanol administration, although the gastric leptin level was not affected. The leptin level in the adipose tissue was significantly increased 3 hr after administration. We conclude that the decreased serum leptin level after ethanol administration might be due to suppression of leptin secretion from adipose tissue to the systemic circulation. These findings might be important for understanding the relationship between alcohol consumption and appetite.
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http://dx.doi.org/10.1007/s10620-006-9635-xDOI Listing
November 2007

Mechanical strain stress suppresses expression of HSP70 and wound restoration in gastric mucosal cells.

Dig Dis Sci 2007 Nov 28;52(11):3087-91. Epub 2007 Mar 28.

Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

The major heat shock protein, HSP70, is known to be involved in cytoprotection against environmental stresses mediated by their function as a "molecular chaperone." However, the influence of HSP70 on gastric mucosal healing under physical stimulation or stress is not completely understood. Rat gastric mucosal cells (RGM-1) were stably transfected with pBK-CMV containing the human HSP70 gene (7018-RGM-1) or pBK-CMV alone (pBK-CMV-12). Artificial wounds were created. Mechanical stretch was applied to 7018-RGM-1 cells or pBK-CMV-12 cells. The effect of mechanical stretch on HSP70 expression was assessed by Western blot analysis. Expression of HSP70 was decreased by mechanical stretch in pBK-CMV-12 cells. However, expression of HSP70 was not decreased by mechanical stretch in 7018-RGM-1 cells. Furthermore, the wound restoration of pBK-CMV-12 cells was suppressed under mechanical stretch condition. On the other hand, the wound restoration of 7018-RGM-1 cells was not affected by mechanical stretch. These results suggest that HSP70 plays an important role in gastric wound healing under physical stress.
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http://dx.doi.org/10.1007/s10620-007-9795-3DOI Listing
November 2007

MEK activation suppresses CPT11-induced apoptosis in rat intestinal epithelial cells through a COX-2-dependent mechanism.

Dig Dis Sci 2007 Oct 28;52(10):2757-65. Epub 2007 Mar 28.

Department of Gastroenterology/Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

Resistance to chemotherapeutic agents is one of the distinct features of cancer cells. We evaluate the role of activated MEK-ERK signaling in Camptotecin/irinotecan (CPT-11)-induced cell death using constitutively activated MEK1-transfected normal rat intestinal epithelial cells (IEC-caMEK cells). A CPT-11-induced inhibitory concentration of 50% was determined by WST assay. Apoptosis was evaluated by DNA staining and fragmented DNA analysis. Protein expressions were analyzed by western blotting. We also examined the role of cyclooxygenase-2 in the cell systems. IEC-caMEK cells possessed survival advantages compared to control cells. Apoptosis was remarkably suppressed in IEC-caMEK cells. Western blot analysis revealed increased expression of Bcl-2, Bcl-xL, Mcl-1, and COX-2 and decreased expression of Bak in IEC-caMEK cells. The COX-2 selective inhibitor ameliorated the antiapoptotic nature of IEC-caMEK cells. MEK activation suppressed CPT-11-induced apoptosis in IEC-caMEK cells via a COX-2- dependent mechanism. Therefore, MEK-ERK signaling may contribute to the drug-resistant nature of cancer cells.
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http://dx.doi.org/10.1007/s10620-007-9798-0DOI Listing
October 2007

Attenuation of gastric mucosal inflammation induced by aspirin through inhibition of selective type III phospshodiesterase in rats.

Dig Dis Sci 2007 May 20;52(5):1355-9. Epub 2007 Mar 20.

Department of Gastroenterology, Akita University of Medicine, 1-1-1, Hondo, Akita City, 010-8543, Akita, Japan.

Cilostazol, a selective type III phosphodiesterase inhibitor, is widely used for treatment of ischemic symptoms of peripheral vascular disease. Recent studies have reported that the mechanism of cilostazol is related to suppression of pro-inflammatory cytokine production and improvement of local microcirculation disturbances. The activation of inflammatory cells and pro-inflammatory cytokine production play critical roles in the pathogenesis of aspirin-induced gastric irritation. The aim of the present study was to determine whether cilostazol can ameliorate aspirin-induced gastric mucosal lesions in rats, reduce neutrophil accumulation, and reduce the production of pro-inflammatory cytokines. Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 ml/kg). Cilostazol (1-10 mg/kg, IP) was injected 30 min before aspirin administration. Also, we measured the gastric mucosal concentrations of myeloperoxidase and interleukin-1 beta, tumor necrosis factor-alpha, and cytokine-induced neutrophil chemoattractants-1, as an index of neutrophil accumulation, and the pro-inflammatory cytokines. Cilostazol ameliorated the gastric mucosal lesions induced by aspirin administration (P<0.01). The gastric contents of myeloperoxidase and pro-inflammatory cytokines were all increased after aspirin administration and significantly reduced by cilostazol treatment. In this study, we demonstrated that a selective type III phosphodiesterase inhibitor, cilostazol, reduced aspirin-induced gastric inflammation and damage via suppression of the production of proinflammatory cytokines. Cilostazol may be useful for preventing gastric mucosal lesions induced by aspirin.
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http://dx.doi.org/10.1007/s10620-006-9553-yDOI Listing
May 2007

Mitigation of stress-induced gastric mucosal lesions by a specific type IV phosphodiesterase inhibitor.

Dig Dis Sci 2007 Mar;52(3):711-6

Department of Internal Medicine-1, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.

Inhibition of type IV phosphodiesterase (PDE4) activity is beneficial in various inflammations. However, the effect of phosphodiesterase inhibitors on the development of stress-induced gastric mucosal lesions has not been reported. In the present study, we examined the effect of a specific PDE4 inhibitor (rolipram) on stress-induced gastric mucosal lesions. Rats were exposed to water-immersion stress with or without pretreatment with rolipram. Ulcer index and myeloperoxidase activity of the gastric mucosa were evaluated. Gastric mucosal lesions and mucosal myeloperoxidase activity were suppressed by treatment with rolipram without acid suppression. The effect of intraperitoneal administration of 2.5 mg/kg rolipram on suppression of mucosal lesions was almost equal to that of treatment with 200 mg/kg cimetidine. We demonstrated that a specific PDE4 inhibitor has a potent anti-ulcer effect presumably mediated by an increment in intracellular cAMP in inflammatory cells, in which this enzyme is abundantly and specifically expressed.
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http://dx.doi.org/10.1007/s10620-006-9528-zDOI Listing
March 2007

Protective effect of a novel rice extract against ethanol-induced gastric mucosal injury in rat.

Dig Dis Sci 2007 Feb 11;52(2):434-41. Epub 2007 Jan 11.

First Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita City, Akita, Japan.

The aim of this study was to investigate the protective action of rice extract on ethanol-induced mucosal damage in vivo and wound healing of epithelial cells in vitro. Also, the effect of rice extract on gastric mucosal prostaglandin E(2) level, HSP72 expression, gastric acid secretion, and contribution of vanilloid receptor-mediated action was studied. In addition, using cultured gastric mucosal cells (RGM-1), the effect of rice extract on cytoprotection and wound healing of epithelial cells was evaluated. Rice extract significantly reduced gastric mucosal damage produced by ethanol in vivo, and heat treatment (80 degrees C, 3 min) of this agent did not alter its protective effect. Rice extract also protected RGM-1 from ethanol-induced damage in a dose-dependent manner. Rice extract accelerated wound healing of gastric epithelial cells. Our results demonstrate that rice extract could be an alternative ulcer treatment that provides cytoprotection and enhancement of wound healing not dependent on acid secretion, prostaglandin E(2) level, HSP72 expression, or vanilloid receptors.
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http://dx.doi.org/10.1007/s10620-006-9571-9DOI Listing
February 2007

The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone (HSP-inducer).

Biochem Biophys Res Commun 2007 Feb 13;353(2):399-404. Epub 2006 Dec 13.

Department of Internal Medicine and Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan.

To elucidate the induction mechanism of HSP70 by geranylgeranylacetone (GGA), we investigated GGA specific binding proteins using a GGA-affinity column. Alteration of chaperone activity of HSP70 and binding affinity of HSP70 to heat shock factor-1 (HSF-1) was evaluated in the presence or absence of GGA. The binding domain of HSP70 to GGA was also analyzed. A 70-kDa protein eluted by 10 mM GGA from the GGA-affinity column was identical to constitutively expressed HSP70 on immunoblotting. GGA-binding domain of HSP70 was C-terminal of the protein as peptide-binding domain (HSP70C). The chaperone activity of HSP70 and recombinant HSP70C was suppressed by GGA. Furthermore, dissociation of the HSP70 from HSF-1 was observed in the presence of GGA. GGA preferentially binds to the C-terminal of HSP70 which binds to HSF-1. After dissociation of HSP70, free HSF-1 could acquire the ability to bind to HSE (the promoter region of HSP70) gene.
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http://dx.doi.org/10.1016/j.bbrc.2006.12.031DOI Listing
February 2007