Gastroenterology - Internal Medicine - Laboratories | Nagoya University GraduateSchool of Medicine

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Internal MedicineGastroenterology

Introduction

Our department is treating all sorts of digestive diseases based on the top-level knowledge and technology in Japan. Our team consists of four groups, Upper GI, Lower GI, Pancreaticobiliary and Hepatology. In the clinical field, Upper GI, Lower GI and Pancreaticobiliary groups are mainly dealing with the introduction and development of new endoscopic diagnosis and treatment, and Hepatology group is working on the novel treatment of viral hepatitis, liver cirrhosis and liver cancer. In the research field, in addition to the study of each group, we are working on the study of nutrition and gut microbiome from the standpoint of multi-organ including pancreas and liver, not only the small intestine and colon. As described above, in our department young doctors are proactively working on development of the tradition or newly established research from both clinical and basic aspects. Moreover, as part of globalization, we have been making a contribution as a national project by establishing endoscopy training centers for the improvement of endoscopic techniques in the Mekong region countries (Vietnam, Laos, Cambodia, Thailand and Myanmar) since 2012. We have also proactively engaged in the joint research with foreign countries.

Research Projects

①Upper GI Group

1)Molecular biological research on GISTs.
By analyzing not only well-known gene mutation but also micro-array method, we are studying molecular biological research in order to clarify the mechanism of GIST which are related to malignancy and prognosis.

2)Invasion depth diagnosis of upper gastrointestinal tract tumors using the ultra-high-frequency ultrasound miniature probe
In our department, we research by using the ultra-high-frequency ultrasound miniature probe (hereinafter referred to as the ultra-high-frequency probe) that is developed newly. Ultrasound become more high frequency, more high resolution. So it is expected that the new probe may diagnose depth invasion easily and exactly for early stage gastrointestinal cancer (esophageal cancer, gastric cancer, colon cancer , etc.) confined to the gastrointestinal tract surface compared with conventional ultrasound miniature probe which frequency is 5-20MHz. On this study, we compare the image which is visualized by using the new probe the endoscopic resection or surgical resection specimens of the upper gastrointestinal tract tumors to pathological findings for examining the possibility of invasion depth diagnostic accuracy and clinical application by the ultra-high-frequency probe.

3)Correlation between upper gastrointestinal disease and gut microbiota
We have analyzed about correlation between upper gastrointestinal disease and gut microbiota. Among them, we are especilally researching the change of gut microbiota in eradication of H. pylori.

4)Feasibility study of endoscopic all-in-focus image creation and analysis in the gastrointestinal tract.
The aim of this study is the development of the technique to enable the generation of all focus images that is correct in all for the observation and to overcome a drop of the diagnosis ability due to shallowness of focus in the endoscopy as part of medical-engineering collaboration, and to evaluate the feasibility of endoscopic all-in-focus image in clinical practice.

5)EUS-guided forceps biopsy from upper GI subepithelial lesions using a forward-viewing echoendoscope
The aim of this study is to evaluate the feasibility of endoscopic ultrasound-guided forceps biopsy (EUS-FB) from upper gastrointestinal subepithelial lesions using a forward-viewing echoendoscope.

6)Development of CAD system for gastrointestinal disease
We are developing computer-aided detection and diagnosis (CAD) systems for medical imagings of gastrointestinal disease.

②. Lower GI Group

1)Evaluation of gastrointestinal biomarkers using biopsy specimen
Frequency and distribution of biomarkers, such as Niemann-Pick C1-Like 1, in the gastrointestinal tract are evaluated and we would like to reveal the features of gastrointestinal diseases.

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2)The usefulness of Carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography using double-balloon endoscopy in patients with altered GI anatomy.
This study evaluates the usefulness of Carbon dioxide insufflation for endoscopic retrogradecholangiopancreatography using double-balloon endoscopy in patients with altered GI anatomy.

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3)Differential diagnosis between sporadic and colitis-associated neoplasm in patients with ulcerative colitis
Sporadic colorectal cancer (sCRC) develops in patients with ulcerative colitis (UC) as well as colitis-associated colorectal cancer (CAC). It is important to differentiate between sCRC and CAC. It is because accurate diagnosis determines surgical procedure.

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4)Evaluation of the efficacy and safety with Dexmedetomidine in double-balloon endoscopy
Patients who received double-balloon endoscopy (DBE) need sedatives, however DBEs areoften hampered by body motions or cardiopulmonary depression. Dexmedetomidine (DEX) has less respiratory depression effect and suppressive effect of body motion. In this study, we evaluate the efficacy and safety of sedation with DEX in DBE

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5)A prospective validation study for the Obscure Gastrointestinal Bleeding Score to predict the usefulness of double-balloon endoscopy in patients with obscure gastrointestinal bleeding
The purpose of this study is to build a new scoring system that predicts the necessity of double-balloon endoscopy in patients with OGIB. This scoring system consists of clinical profiles, laboratory data and capsule endoscopic findings. We also verify practical effectiveness of this scoring system prospectively in other patients with OGIB.

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6)Evaluation of insertability of endoscope in the examination of colonoscopy
The performance of endoscope has been improved, but it is difficult to insert colonoscope in some cases. We evaluate the factors that are related to insertability in the examination ofcolonoscopy.

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7) The explorative study on the relationship between the findings of double-balloon endoscopy and the levels of fecal markers in Crohn's disease
We make a measurement of fecal calprotectin in patients with Crohn's disease who take double-balloon endoscopy and evaluate the relationship between the findings of endoscopy and the scores of fecal calprotectin.

8)The observational study on clinical application of the stromal forming protein for tumor stromal marker
We evaluate the stromal forming protein in human blood serum or tumor stroma.

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9)A randomized trial of evaluation for the usefulness of cold polypectomy compared to conventional polypectomy for colorectal polyps
It is reported that cold polypectomy needs the shorter procedure time and has the lower frequency of adverse events such as delayed bleeding and perforation than conventional polypectomy. But this procedure has not been widely used in Japan. This is the prospective randomized controlled study to compare the safety and effectiveness of cold polypectomy with conventional polypectomy.

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Cold polypectomy technique
A. A small colorectal polyp(<10mm) suspected of adenoma
B. Resection by cold snare polypectomy without coagulation
C Hemostasis is not often necessary because early bleeding after cold polypectomy stops soon.

③Pnacreato-Biliary Group

1)Developing new diagnostic method for bilio-pancreatic lesions to use several applications and software of ultrasonography.
We try to discover a new imaging diagnostic method using transabdominal ultrasonography (US) and endoscopic ultrasonography (EUS). And we also search new biomarkers using cytological and histological specimen taken by EUS-FNA or ERCP.

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2)Combination of immunotherapy and chemotherapy for unresectable locally advanced pancreatic cancer patients.
The aim of this study is to assess the safety and observation of tumor control effect using the chemotherapy combination with immune cell therapy using EUS-FNA as a primary treatment.

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3)Combination of immunotherapy and chemotherapy for unresectable locally advanced pancreatic cancer patients.
The aim of this study is to assess the safety and observation of tumor control effect using the chemotherapy combination with immune cell therapy using EUS-FNA as a  primary treatment.

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4)Endoscopic diagnosis and treatment of Ampullary tumor
Our aims are how to diagnose ampullary tumor using ERCP technique and intra-ductal ultrasonography and how to perform less invasive endoscopic ampullectomy.

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5)Trans-papillary diagnosis and treatment of biliary disease
More precise and less invasive diagnosis of biliary disease using intra-ductal ultrasonography, trans-papillary forceps biopsy and so on. And how to less invasive and more suitable treatment of biliary stricture (malignancy and benign) and CBD stones.

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6)Multicenter prospective observatory study for pancreatic cystic lesion.
Our aim of this study is to elucidate the natural history of pancreatic cystic lesions especially intraductal papillary mucinous neoplasms (IPMN).

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7)Diagnosis, treatment, and natural history studies of autoimmune pacreatitis
We are analyzing pancreatic tissues of autoimmune pancreatitis (AIP) collected by EUS-guided FNA (EUS-FNA) biopsy in Nagoya University Hospital and Nagoya University-affiliated institutions and researching usefulness of EUS-FNA for a diagnosis of AIP which is less invasive and safe histologic diagnostic method.

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Histopathology of lymphoplasmacytic sclerosing pancreatitis.
A, H&E staining of tissue obtained by EUS-guided FNA biopsy .
B, The findings demonstrate replacement of the acinar structure by lymphoplasmacytic infiltration and fibrosis .
C, Abundant immunoglobulin G4–positive cells are found in the high-power field .

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EUS-FNA biopsy for AIP

8)Development of a Sensitive Method Detecting Pancreatic Fibrosis
We are developing a sensitive method to detect pancreatic fibrosis in order to obtain early diagnosis of chronic pancreatitis which is irreversible and progressive. This work is supported in part by the Research Committee of Intractable Pancreatic Diseases in Japan, provided by the Ministry of Health, Labour and Welfare of Japan. In addition to Endoscopic Ultrasound, the usefulness of measuring tissue elasticity using Transabdominal Ultrasound or MRI, new tests for pancreatic exocrine function and serum marker have been investigated. Strain elastography     Shear wave elastography (Endoscopic Ultrasound) (Transabdominal Ultrasound)

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Strain elastography
(Endoscopic Ultrasound)
Shear wave elastography
(Transabdominal Ultrasound)

9)Exploratory study of nutritional status influenced by correlation between pancreas and small intestine using a newly developed enteroscopy. Exploratory study of correlation between gut microbiota and digestive diseases.
Using newly developed enteroscopy, it’s now possible to observe small intestine safely with less patient’s pain. In order to clarify the nutritional status influenced by correlation between pancreatic function and small intestine, morphology and function of jejunum villous mucosa are evaluated in patients with pancreatic diseases. We are also analyzing gut microbiota of patients with digestive disease, using next-generation sequencer.

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10)Randomized Phase II Study of consecutive-day versus alternate-day treatment with S-1 as Second-line chemotherapy in advanced pancreatic cancer (SCOTCH trial).
As the second-line treatment in unresectable advanced pancreatic cancer, the multicenter randomized control trial is now being conducted to check the efficacy and safety of consecutive-day versus alternate-day treatment with S-1. Cooperative research institute is consisted in 20 our relevant centers.

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11)A study on the usefulness of the prototype small-diameter high-frequency ultrasonic probe
Intraductal-ultrasonography (IDUS) by the 20MHz ultrasound probe is conducted to diagnose for the pancreatobiliary diseases. Now we try more detailed examination using further high-frequency ultrasonic probe for the surgical specimen.

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12)Evaluation of EGJ (esophagogastric junction) function using elastography
Elastography which can evaluate to measure hardness is one of the ultrasonic diagnostic technology. We have studied the usefulness of evaluation of EGJ function to measure changes in hardness using elastography.

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④Hepatology Group

1. Research for pathophysiological mechanisms of viral hepatitis
i) Hepatitis C Virus (HCV): Multicenter studies of interferon (IFN)-based and IFN-free, combination of direct acting antivirals (DAAs) were conducted and investigated the efficacy, safety, and exploratory investigation for the factors associated with treatment response. Among these studies, correlation with host IL28B gene polymorphism, amino acid substitution in HCV core, NS5A lesions and treatment response of IFN-based regimen have been already reported. These analysis is also on the way in IFN-free treatment, and we also investigated the dynamics of immune reaction after viral eradication by treatment.
ii) Hepatitis B virus (HBV) Life cycle of HBV is more complicated compared with HCV, so the development of curative treatment against HBV is considered to be difficult. In liver unit, correlation between HBsAg dispperance, which is considered as clinical remission, and the viral mutation in HBV core lesion, and in patients with serum negativity of HBV-DNA by nucleos(t)ide analogues, which are standard regimens in HBV patients, correlations between serum HBV markers (HBsAg, HB core related antigen) and pathophysiology, and exploration of factors associated with hepaticarcinogenesis are now ongoing.....

2. Analysis for new treatment against hepatocellular carcinoma (HCC)
For the investigation of new treatment against hepatocellular carcinoma, efficacy and safety of new devices for radiofrequency ablation (RFA), prospective study for the standardization of transcatheter arterial chemoembolization (TACE), and the efficacy and safety of sorafenib for patients with advanced HCC and exploratory study for the factors associated with the treatment effect of sorafenib as multicenter study are done. 3. Correlation between inflammatory response and liver regeneration in animal model for acute liver failure There are no established treatment for promoting liver regeneration, effect of stem cells from human exfoliated deciduous teeth (SHED) as one of the most promising tool for this purpose was investigated as the collaboration with department of maxillofacial surgery. And the factors with strong effect were identified in the supernatant of culture of SHED, and investigated the efficacy and safety of these factors and whether strong anti-inflammation is essential for liver regeneration.

Faculty Members

FacultyPositionDepartment
Masatoshi Ishigami Lecturer Deaprtment of Gastroenterology and Hepatology
Osamu Watanabe Lecturer Department of Gastroenterology & Hepatology
Kazuhiko Hayashi Lecturer Deaprtment of Gastroenterology and Hepatology
Hiroki Kawashima Lecturer Department of Gastroenterology & Hepatology
Ryoji Miyahara Lecturer Department of Gastroenterology & Hepatology
Takashi Honda Assistant Professor Department of Gastroenterology & Hepatology
Masanao Nakamura Assistant Professor Deaprtment ofGastroenterology and Hepatology
Teiji Kuzuya Assistant Professor Deaprtment ofGastroenterology and Hepatology
Eizaburo Ohno Assistant Professor Deaprtment ofGastroenterology and Hepatology
Kohei Funasaka Assistant Professor Department of Gastroenterology & Hepatology
Kazuhiro Furukawa Assistant Professor Department of Endoscopy
Yoji Ishizu Assistant Professor Deaprtment ofGastroenterology and Hepatology
Takuya Ishikawa Assistant Professor Department of Gastroenterology & Hepatology
Takeshi Yamamura Assistant Professor Department of Endoscopy
Masanobu Matsushita Assistant Professor Department of Gastroenterology & Hepatology