BBI Japanese Editor

TOKYO – The 87th Japan Gastroenterology Society general meeting, held in Tokyo this spring, was attended by approximately 5,000 physicians – but only a few industry representatives. The meeting was strongly directed toward education for physicians, with less participation by product and/or service suppliers.

Only a handful of companies, including Olympus, Aloka, some contrast agent suppliers and pharmaceutical companies, displayed their products on the exhibit floor. Pyloritek reagent strips and Helicobacter pylori test kits made by Serim Research, imported by Sakura Seiki and marketed by Sankyo, attracted considerable attention. The H. pylori test has been approved for reimbursement since last November, along with a technical fee for the evaluation.

This year's sessions left a strong impression that the U.S. is by far the leader in development of new medical technologies. Many presenters made references to the meager budgets allocated by the Japanese government for research programs on advanced technologies compared to those in the U.S.

Lectures presented at graduate courses on the last day of the meeting showcased the efforts of Japanese medical researchers.

Yoko Murata, assistant professor in the department of gastrointestinal endoscopy at Tokyo Women's Medical University, in her lecture, titled "Diagnostic Imaging for Digestive Organs, Mainly for the Esophagus," outlined recent trends among the Japanese population wherein cases of reflux esophagitis increased as a result of the westernization of Japanese dietary habits, although symptoms of lower acidity and milder inflammation are observed in comparison with the western patients.

Murata said that while the Los Angeles Classification is mainly employed for classifying endoscopic observations, reflux esophagitis is difficult to assess by means of that classification because of minimal mucosal damage observed among Japanese patients. A new category called Grade N is being recommended to encompass such cases where there are no endoscopic findings or those presenting merely color changes. Concern is mounting among physicians who are observing increasing occurrences of reflux esophagitis take place after dezymotization of Helicobacter pylori. Such cases are currently treated by administering proton pump inhibitors.

Concern also is mounting, Murata said, over increased occurrences of Barrett epithelialization in Japan, brought about by the increase of reflux esophagitis cases. Barrett epithelium with lengths less than 3 cm are distinguished as short segment Barrett esophagus (SSBE) and that with longer lengths is called long segment Barrett esophagus (LSBE). Canceration appears to occur more often with LSBE cases. Methods such as methylene blue dye or fluorescent dye endoscopies, as well as diacrisis between Barrett epithelium and cancer by means of optical coherence tomography (OCT), are recommended for early diagnosis of canceration of esophagus.

While the imaging of cancer(m) is difficult using conventional endoscopes, discrimination of cancer(m2) and cancer(m3) or deeper is reported to have become possible up to 84% by imaging the muscular layer of mucosa using thin probes, especially when used with 20 MHz RF energy. For diagnosis of lymph node metastasis, EUS-fine needle aspiration cytology is recommended. Demucosation is indicated for cases up to cancer (m3) for cases in which metastasis to lymph node is not observed, and excision including lymph node dissection for cases with cancers with sm2 or deeper. Surgical excision is indicated for cases where lymph node metastasis is a strong possibility.

Masahiro Tada, MD, of the division of gastroenterology at Saitama Cancer Center, said in his lecture, titled "Diagnostic Imaging of Cancer of the Stomach-Forefront of Treatment," that diagnosing cancer of the stomach in minute size is no longer rare due to widespread use of endoscopic examinations, and since metastasis to lymph node is not found in early stage cancers of the stomach, endoscopic treatment has become the primary choice of treatment. The primary task, therefore, is to ensure identification of cancer of the stomach in its early stages. Capsule endoscopy and virtual endoscopy that minimize patient discomfort are also pursued. Because cancer tissues show characteristic fluorescence patterns, a new method called optical biopsy by means of fluorescence endoscopy also is being investigated, he said.

Adverse effects of endoscopic treatment include bleeding and perforation. Bleeding is reported in around 1% of the cases. Hemostasis is typically made by means of clipping. A certain rate of residual lesions occur with endoscopic treatments, according to Tada. Of all early-stage stomach cancer cases, lymph node metastasis are observed in only about 20% of cases when diagnosed, leaving about 80% of the cases as treatable by means of endoscopy. Currently, however, only about 20% of such cases are actually treated by means of endoscopy, he said, while the majority of the cases are still treated by way of open surgery. The expansion of endoscopic treatments is currently under investigation, taking into account issues of adverse effects and residual lesions.

Also under investigation, he said, is the significance of sentinel lymph nodes (SLN). SNL is defined as the first lymph node vulnerable to metastasis; it is believed that the absence of metastasis in SNL is indicative of no metastasis to other lymph nodes altogether. This theory is contributing to increased cases of minimal surgical resections for treatments in breast cancer. The task for the future, Tada said, is to determine whether the existence of SLN could be used in determining methods of stomach cancer treatment.

S. Kudo, MD, of the center of gastroenterology at Yokohama Hokubu Hospital and Showa University School of Medicine, said during his lecture on "Diagnostic Imaging of Colorectal Cancer-Forefront of Treatment" that colorectal cancer continues to increase in Japan each year, with 80,000 cases and about 33,000 deaths from the disease annually. Examination of pit patterns, minute structures on the inner wall of the bowel, has become possible with the emergence of magnification endoscopes. Kudo said the pit pattern diagnosis, which provides a high correlation with pathological imaging, is seen as enabling technology in providing high-quality in vivo diagnosis. The term "pit pattern" is designated as the shape of opening at the epithelial duct (pit), roughly categorized into five patterns ranging from Type I to Type V.

The pit patterns observed by magnifying endoscopes, as well as by stereoscopic microscopes, have been found to correlate closely to pathological findings. In protuberance types, polypectomy will be the first choice of treatment, while in surface types, endoscopic mucosal resection or endoscopic piecemeal mucosal resection will be the basic treatment. The pit pattern diagnosis is therefore seen as an important approach for diagnosing colorectal cancer.

Osamu Matsui, MD, of the department of radiology in the Kanazawa University School of Medicine, described recent developments in diagnostic imaging practices in Japan and termed clinical implementations of various harmonic imaging methods and ultrasound contrast agent (Levovist) as a revolutionary advancement in ultrasound diagnosis. IVR angio-CT, systems which combine helical computed tomography (CT) and digital subtraction angiography, and multislice CT are both rapidly penetrating into key hospitals in Japan, Matsui said. They make possible dynamic studies of the entire liver during a short period of time in which patients can hold their breath, enabling highly objective detection and differential diagnosis of hepatic cancer.

Ferumoxide, a reticuloendothelial contrast agent, also is approved for general use in Japan. For magnetic resonance imaging, Gd-EOB-DTPA is used. Those organ-specific contrast agents are expected to contribute to unraveling new pathologies. Intra-arterial injection CT procedures, such as CT during arterial portography and CT during hepatic arteriography, are used to determine clinical approaches and selection of treatment methods. Surgeries, percutaneous ethanol injection therapy and transcatheter arterial embolization are the main methods of treatment for hepatic cancer.

K. Yamao and N. Ohashi of the department of digestive internal medicine at Aichi Cancer Center outlined diagnostic and treatment approaches for treating malignancies in the pancreas and biliary duct. Endoluminal ultrasonography (EUS) and perosal cholangio/pancreatic duct sogography, which attracted attention as a result of development of electronic endoscopes. EUS provides remarkably high-resolution ultrasound images compared to conventional extracorporeal ultrasound approaches. EUS is capable of using high-frequency waves (12 MHz and 20 MHz), with some models being capable of switching frequencies between 7.5/12 MHz and 7.5/20 MHz, and reduced outer diameters resulting into thin ultrasound probes enabling intraductal ultrasonography.

The most popular method of diagnosing diseases of the pancreas and bile duct in Japan is radial scanning ultrasound endoscopy. Since such endoscopes are equipped with high-frequency ultrasound oscillators (7.5/12 MHz), tomographic images across 360 degrees of angle toward the vertical direction against scope axis are available. While this approach requires a high level of skill that is not yet widespread nationwide, Yamao and Ohashi said the method excels over other imaging methods in diagnosing local advancements of tumors in pancreas, bile duct and cancer of papilla. It also excels in diagnosing choledocholithiasis. Endoscopic ultrasonography-guided fine needle aspiration is available for cytodiagnosis and biopsies.

For metallic stenting, self-expandable stents made of shape-memory alloy are mostly used in Japan. Those stents have the merits of being small in diameter while being introduced, expanding up to 8 mm when deployed. The cancer center introduced covered stents (with mesh covered by a sheet such as Gore-Tex) prior to treatment into the bile duct for pancreatic cancer patients for whom surgeries are no longer an option, followed by a therapy combining chemotherapy and radiation therapy. Occlusion of the stent is rarely experienced.

Papillary adenoma is regarded as a precancerous state for which endoscopic resection is indicated as the first choice of diagnosis in terms of a complete biopsy. The endoscopic biopsy, however, is limited in effect for diagnosing carcinoma in adenoma, and therefore, endoscopic resection of thelium is regarded as an appropriate approach of treatment.

(Next month: A look at genomic diagnosis and gene therapy in gastroenterology in Japan.)

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