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Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation.In this phase II, multicenter, double-blind, dose-response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy.The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P0.001, one-tailed Cochran-Armitage trend test). As compared with the placebo group, the proportion of subjects with no peristalsis after administration was significantly higher in the 0.8% group (P = 0.015) and 1.6% group (P = 0.009). Adverse events in the L-menthol dose groups occurred with similar frequencies in the placebo group.L-menthol suppresses peristalsis in a dose-dependent manner, and the dose-response reaches a plateau at 0.8% L-menthol. Further Phase III studies are needed to establish the superiority of 0.8% L-menthol over placebo.

Two types of a shape memory alloy (SMA) catheter system with a mechanism for tip control and irrigation were evaluated in performing peroral pancreatoscopy (PPS) using an ultrathin-caliber endoscope. The selective cannulation of SMA catheters into the papilla was made possible in 18 of 19 patients with pancreatic diseases. Endoscopic sphincterotomy was necessary in six of seven patients with the two-directional catheter (2.6 mm) but in only one of 12 patients examined with the one-directional type (2.2 mm). In 17 of the 18 patients, the catheters were smoothly advanced to the desired positions in the main pancreatic duct, even to the distal pancreas, due to their controllable tip. PPS with adequate inspection of the ducts and lesions was successful in 16 of these 17 patients. Features of cancer (duct disruption, tumor infiltration) and chronic pancreatitis (smooth ductal surface, fine vascular network) could be distinguished. In this series, there were no obvious complications during or after the procedure. In our experience, the SMA catheter system is effective for PPS in patients with an intact papilla and without dilation of the main pancreatic duct. Further study will show the clinical benefits this technique may have in pancreatic diseases.

An immunocytochemical study using a monoclonal antibody showed the presence of gamma-glutamyl transpeptidase (gamma-GTP) in the bile duct epithelium of the normal adult rat liver, while a slight immunoreactivity for gamma-GTP could be observed on the membranes of bile canaliculi (the membranes of hepatocytes facing the lumen of bile canaliculi). In hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene, no immunoreactivity was detected in alpha-fetoprotein-positive cholangiolar "oval" cells, though it was detected on the membranes of bile canaliculi. In livers with hyperplastic nodules, gamma-GTP immunoreactivity was observed in clusters, with two different staining patterns. In one pattern, gamma-GTP was present not only on the membranes of bile canaliculi, but also on the membranes facing the Disse's space or the lateral cell surface of hepatocytes. In the other pattern, gamma-GTP immunoreactivity was seen on the membranes of the dilated bile canaliculi. In livers with developing hepatocellular carcinomas, the immunoreactivity was present on the membranes of irregularly dilated bile canaliculi in malignant cells.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Endoscopic laser treatment (ELT) has been proposed as one of the curative endoscopic therapies for early gastric cancer. We report our experience with ELT in 111 patients with early gastric cancer limited to the mucosa as diagnosed by endoscopy and/or endoscopic ultrasonography. Twelve patients subsequently underwent laparotomy after ELT and no residual tumor was found in 75% of these cases. Ninety-nine patients had no surgery for various reasons and follow-up information by endoscopy was available for 73 of them for a mean of 2.7 years (range 1 to 7 years). 81% of these patients were found to be tumor free. There was no difference in the success rate of ELT in relation to endoscopic classification, tumor location and histologic type of cancer. Recently, the indications for ELT decreased due to the development of endoscopic mucosal resection (EMR) enabling histological evaluation of a resection specimen. However, the technique of EMR cannot always be performed completely depending on the location and size of the lesions. Therefore, we employed ELT as an additional treatment technique after EMR therapy to achieve complete tumor destruction. Results in 13 patients where both techniques were employed showed complete tumor removal in 11 cases. At present, this combined application may be the most important role of laser irradiation for the treatment of early stage GI tract malignancies.

The ability of EUS to diagnose small pancreatic cancer is well known. In this study, we present our experience with EUS in the local staging of 29 patients with pancreatic carcinoma who underwent surgery. EUS was 79, 83 and 79% accurate in determining anterior (including gastric), duodenal and retroperitoneal (vascular) invasion by the tumor. Ultrasonography (48, 39 and 55%, respectively) and CT (38, 33 and 41%, respectively) were less reliable. EUS was equal to angiography in diagnosing vascular involvement. EUS was more effective in detecting splenoportal infiltration (sensitivity 88%, specificity 78%) than arterial involvement (accuracy 50%). EUS was also less reliable in determining the N stage (66%) and in stage grouping (72%). Although EUS is superior to ultrasonography and CT in the local staging of pancreatic carcinoma, further studies must show whether improved staging criteria will lead to better results.

Endoscopic hemostasis is widely performed for nonvariceal upper gastrointestinal (UGI) bleeding. As the aged Japanese population rapidly increases, the number of patients experiencing complications increases. The aim of this study was to evaluate the recent results of endoscopic hemostasis for nonvariceal UGI bleeding. A retrospective analysis of patients who underwent endoscopic procedures for nonvariceal UGI bleeding was performed. We performed 223 endoscopic procedures on 217 patients between January 1995 and July 2000, and 238 endoscopic procedures on 236 patients between January 2006 and September 2009 at the Kyoto Second Red Cross Hospital. We divided the patients into the 1995-2000 group and the 2006-2009 group. Patient characteristics, hemostasis methods chosen, rates of temporary hemostasis and rebleeding, and mortality were analyzed. There were many serious and actively bleeding cases in the 2006-2009 group (P0.001). The endoclip method and intravenous proton pump inhibitor were mainly used in the 2006-2009 group compared with the drug-injection method and intravenous H2 receptor antagonist in the 1995-2000 group (P0.001). Through these treatments, the two groups were able to obtain similar treatment outcomes. Through the progress of endoscopic management we obtained similar satisfactory results in the 2006-2009 group, which had multiple complicated cases, compared to the 1995-2000 group.

A case of basket catheter impaction was experienced during treatment for a common bile duct (CBD) stone. In cases of large CBD stones, mechanical basket lithotripsy or extracorporeal shock wave lithotripsy (ESWL) is usually carried out. However, once basket catheter impaction occurs, ESWL should be performed in the remaining basket catheter, which is passed through the patient's nose, and further ESWL basket lithotripsy must be carried out at a later time. On one occasion, a mechanical lithotripter was inserted along-side the conventional basket catheter through the incised papilla. This procedure is a safe and useful method for the clearance of CBD stones that cannot be removed with standard endoscopic procedures due to an impacted basket catheter.

Endoscopic ultrasonography (EUS) was performed in 23 patients with carcinoma of the ampulla of Vater (ampulla) and in 16 patients with common bile duct (CBD) carcinoma. These patients all underwent surgery. The layered structures of the duodenum, ampulla, and CBD, and the pancreas, portal vein, and regional lymph nodes were clearly identified by EUS using a transduodenal approach. With this technique, ampullary carcinoma appeared as a hypoechoic mass in 22 of 23 patients, and the 1 remaining cancer was not detected because of its small size. Carcinoma of the CBD also appeared as a hypoechoic mass in 12 of 16 patients. However, the remaining four appeared as hyperechoic masses. For these tumors, EUS had a high tumor detection rate (96 to 100%). In this regard, EUS was comparable to ERCP and was better than ultrasonography (US), CT, and angiography. Using EUS, we were also able to stage the extent of these tumors according to the involvement of the duodenal or CBD walls, invasion of the pancreas and portal vein, and spread to regional lymph nodes. The accuracy rates of cancer extent by EUS were 78% for ampullary carcinoma and 81% for CBD carcinoma when compared with surgical findings. We conclude that EUS is a valuable method for the detection and staging of tumors of the ampulla and CBD.

Monoclonal antibody (MAb) 170-5 was generated to the secretory granule membrane of rat parotid acinar cells. The MAb recognized integral membrane glycoproteins (SG 170 antigen) localized on the luminal side of the secretory granules with N-linked carbohydrates, molecular weights 92, 84, 76, 69, and 65 KD. Immunohistochemical studies indicated that the SG 170 antigen was found in the secretory granules of both exocrine and endocrine cells and in the lysosomes of various cells in the rat. Immunoelectron microscopy with immunogold revealed that the antigen was present on the membrane of the secretory granules, lysosomes, the Golgi vesicles, and condensing vacuoles in pancreatic and parotid acinar cells and in AR42J rat pancreatic tumor cells; the Golgi stacks exhibited no immunoreaction. The common localization of the antigen in the secretory granule membranes indicated that this antigen may play an essential role in regulated secretion. Employing HRP-labeled MAb 170-5, we followed the retrieval of the antigen after exocytosis in AR42J cells. The MAb was internalized specifically with antigen-mediated endocytosis. It was transported to endosomes, subsequently to the trans-Golgi network, and then packaged into secretory granules. However, the Golgi stacks revealed no uptake of the labeled antibody.

We examined the suitability of the freeze-substitution and paraffin embedding technique for the im-munolocalization of membrane-bound and soluble antigens in the rat at the light microscopic level. Frozen tissues were substituted at -80°C in methanol or acetone containg chemical fixatives, i. e., formaldehyde, glutaraldehyde, acrolein, hexamethylene diisocyanate (HMD), diethyl malonimide (DEM) and 1-ethyl-3- (3-dimethyl-aminopropyl) carbodiimide (water soluble carbodiimide, WSC). The following antigens were localized using monoclonal antibodies and antisera: A) membrane-bound antigens; γ-glutamyl transpeptidase (γ-GTP), common antigen of secretory granule membrane (SG 170 antigen) and Golgi associated antigen (GAA 108); and B) soluble antigens; branched-chain amino acid transferase type I isozyme (BAT), glutamate dehydrogenase (GDH), pancreatic amylase, proliferating cell nuclear antigen (PCNA), rat serum albumin and IgG.1) The freeze-substitution technique maintained an excellent tissue structure and conservation of antigenicity. By using this method, BAT was localized in mitochondria in iver cells, and γ-GTP was demonstrated in the secretory granule membrane of pancreatic acinar cells, although conventional fixation methods provided negative reaction. 2) In general, the membrane-bound antigens were localized in detail with a strong immunoreaction in the tissues substituted in solvent alone; however, for the localization of soluble antigens, tissues substituted in solvents containing chemical fixatives revealed a strong and precise antigen localization. 3) Formaldehyde and glutaraldehyde proved to be better fixatives concerning the conservation of structure and antigenicity than the other chemical reagents. 4) The choice of substitution solvent was important for the immunohistochemistry of some antigens. For example, methanol was suitable for PCNA, and substitution in acetone was essential for γ-GTP using one of the monoclonal antibodies to γ-GTP.

Microwave (MW) has the advantage of accelerating infiltration of fixatives into tissue blocks, but the disadvantage of causing the temperature of the fixatives and tissue blocks to rise. We tried to minimize the temperature elevation during MW irradiation by applying ultrasound (US) in combination with MW oven furnishing US generator. US was uneffective in reducing the rise of temperature, however, it was able to enhance the rapid tissue fixation. Electron microscopic examination showed that the fine structure of organs, such as liver, pancreas, submandibular gland, small intestine, and kidney, was well preserved. Characteristically, the matrix of mitochondria appeared electron-dense, and the marginal zone of zymogen granules in the pancreas was more electron-opaque than the core of the granule. The immunoreactivity of zymogen granules to anti-amylase antibody was strong. The deformation or disorder of cell structure due to the thermal effect and cavitation that can be caused by US was not seen. US can be useful for histologic and immunohistochemical study.

Monoclonal antibodies were prepared to branched-chain amino acid transferase (BAT) type I isozyme purified from rat kidney. Two stable clones producing specific antibodies to the enzyme were obtained. Specificity was confirmed by immunoblots of purified BAT after polyacrylamide gel electrophoresis and testing enzyme inhibition by the antibodies. In the immunohistochemical study, type I BAT was localized in the mitochondria of the proximal tubular cells of the rat kidney. In the liver, reaction was observed in the mitochondria of parenchymal cells. The cells surrounding the central veins exhibited strong immunoreaction. Immunoelectron microscopy using a rapid freezing and substitution technique revealed type I BAT localization in the mitochondria matrices of rat liver parenchymal cell. A faint reaction was present in the cytoplasm. Immunoblot analysis of mitochondrial and post-microsomal fractions from rat liver and kidney also indicated that the enzyme is chiefly present in the mitochondria.The monoclonal antibodies we prepared may provide a useful tool for studying changes in both isozyme pattern and localization of type I isozyme in the prenatal and neonatal rat and in tumor cells.

Peroral pancreatoscopy was developed to gain direct visualization of the pancreatic duct. Since then, various refinements have been made to pancreatoscopes. At present, precise observation is possible by means of electronic pancreatoscopes. Peroral pancreatoscopy is performed under duodenoscopic guidance (mother and baby scope system). Fiberoptic endoscopes, which are about 3 mm in tip diameter, are usually used for pancreatoscopy. In addition, electronic pancreatoscopes, which have a 2.6- or 3.4-mm tip diameter, are commercially available in Japan. Indications for pancreatoscopy include differential diagnosis of stenosis or filling defect in the main pancreatic duct. Diagnosis of surface spreading of tumor in patients with intraductal papillary mucinous neoplasm in the main pancreatic duct is also a diagnostic indication. Treatment of stones in the main pancreatic duct is a therapeutic indication for pancreatoscopy. Future improvements of pancreatoscopes are expected in image quality, insertion tube, and working channel.

Gastrointestinal carcinoma has been detected and diagnosed by barium meal X-ray study and endoscopic study with or without biopsy study. In particular, early and minute carcinoma can be detected only by endoscopic study. Due to the development and refinement of endoscopy, the diagnosis of early gastrointestinal (GI) carcinoma is now easily accomplished by endoscopic observation and biopsy study. Endoscopic detection of gastrointestinal lesions depends on the recognition of visible mucosal changes. However, the final diagnosis is performed by histopathological study of biopsy materials. Biopsy study is still very important to obtain the correct diagnosis of the lesion as carcinoma, dysplasia, adenoma, and hyperplasia, although it is sometimes possible to diagnose the lesion from the endoscopic investigation of mucosal surface details. In this chapter, endoscopic diagnosis of early carcinoma in the upper GI tract will be described.

History and Future Development of Endoscopy The History of Digestive Endoscopy Advances in Endoscopic Imaging and Diagnosis: Toward Molecular Imaging Further Development of Endoscopic Imaging: "Era of Light" Activities with Optics and Image Processing Technology Future Perspectives for Esophageal and Colorectal Capsule Endoscopy: Dreams or Reality? Oropharynx and Hypopharynx Endoscopic Diagnosis and Treatment of Superfi cial Cancer in the Oropharynx and Hypopharynx Esophagus Diagnosis of Esophageal and Gastric Carcinoma Using Transnasal Ultrathin Esophagogastroduodenoscopy Magnifying Endoscopic Findings with Narrow-Band Imaging System in the Esophagus Current Perspective on Endocytoscopic Diagnosis in the Esophagus Based on the Multicenter Study at the Endoscopic Forum Japan Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy (EUS-FNA) for Mediastinal Abnormalities via the Esophagus Endoscopic Submucosal Dissection for Esophageal Cancer Recent Advances in Diagnostic Endoscopy to Detect Early-Stage Upper GI Cancer and Therapeutic Endoscopy to Establish Minimally Invasive Endoluminal Treatment Barrett's Esophagus Endoscopic Diagnosis of Barrett's Esophagus and Esophageal Adenocarcinomas Narrow-Band Imaging in the Diagnosis of Barrett's Esophagus Magnifying Endoscopy in Combination with Narrow-Band Imaging and Acetic Acid Instillation in the Diagnosis of Barrett's Esophagus Stomach Screening for Gastric Cancer in Japan A New Diagnostic VS Classifi cation System Produced by Magnifi cation Endoscopy Plus Narrow-Band Imaging in the Stomach: Microvascular Architecture and Microsurface Structure Diagnosis of Gastric Cancer by Magnifying Endoscopy with Narrow-Band Imaging: Impact and Clinical Feasibility of Narrow-Band Imaging for Accomplishing Endoscopic Pathology Autofl uorescence Imaging Video-Endoscopy System for Diagnosis of Superfi cial Gastric Neoplasia The Diagnosis of Gastric Cancer and Adenoma Using Endocytoscopy Endoscopic Ultrasonography Diagnosis for Depressed Type Early Gastric Cancer: Tissue Characterization in Cases Associated with Fibrosis Indications for Endoscopic Submucosal Dissection of Early Gastric Cancers Features of Therapeutic Devices for Gastric Endoscopic Submucosal Dissection and Basic Techniques Future Prospects of Endoscopic Submucosal Dissection from the Product Development Standpoint Small Intestine Clinical Usefulness of Single-Balloon Enteroscopy for the Diagnosis and Treatment of Small-Intestinal Diseases Cutting Edge Technology in Enteroscopy: Entero Pro, the Endo Capsule Future Perspectives of Small Bowel Capsule Endoscopy Colon Screening for Colorectal Cancer in the Asia-Pacifi c Region: Are We Ready Yet? Establishment of a Standard Curriculum for Colonoscope Insertion Techniques Magnifying Endoscope Diagnosis and NBI Diagnosis in Colorectal Neoplasm Image Enhanced Endoscopy (IEE) Using NBI During Screening Colonoscopy: Usefulness and Application The Effi cacy of Narrow-Band Imaging (NBI) and Autofl uorescence Imaging (AFI) Colonoscopy for Patients with Ulcerative Colitis The Value of Narrow-Band Imaging Colonoscopy and Autofl uorescence Imaging Colonoscopy for Ulcerative Colitis Autofl uorescence Imaging Makes It Easy to Differentiate Neoplastic Lesions from Nonneoplastic Lesions in the Colon Endoscopic Ultrasonography Diagnosis for Colorectal Diseases Endoscopic Mucosal Resection and Endoscopic Piecemeal Mucosal Resection for Colorectal Neoplasia Strategy of Endoscopic Treatment for Colorectal Tumor: Recent Progress and Perspective Pancreatobiliary EST vs EPBD Endoscopic Sphincterotomy and Endoscopic Papillary Balloon Dilatation for Bile Duct Stones Strategy for the Endoscopic Treatment of Common Bile Duct Stones: Should We Cut or Dilate the Papilla? EST, EPBD, and EPLBD (Cut, Stretch, or Both?) Future Prospects of ERCP from the Product Development Standpoint Papillectomy Endoscopic Diagnosis and Resection Therapy of the Tumor of the Major Duodenal Papilla Stenting Indications and Technical Methods of Endoscopic Biliary Stenting Using the Doublelayer Stent Indications and Procedure of Biliary Metallic Stenting Plastic Stent Placement for Unresectable Malignant Extrahepatic Biliary Stricture Indication and Procedure of Pancreatic and Bile Duct Stenting Cholangioscopy and Pancreatoscopy The Role of Peroral Cholangioscopy in the Management of Biliary Tract Diseases Techniques and Indications of Pancreatoscopy Diagnosis of Pancreaticobiliary Diseases Using Cholangioscopy and Pancreatoscopy with Narrow-Band Imaging Utility of Video PTCS for Mucin-Producing Bile Duct Tumors EUS Standardization of Imaging Techniques in the Pancreatobiliary Region Using Radial Scanning EUS New Diagnostic Technique of EUS Using Contrast-Enhanced Agents Standard Scanning Techniques for EUS Examinations with Curved Linear Array Echoendoscopes Present Status and Future Perspectives of Endoscopic Ultrasonography-Guided Fine-Needle Aspiration Clinical Impact of EUS-Guided Fine-Needle Aspiration Development of Three-Dimensional Intraductal Ultrasonography in Diagnosis for Bile Duct Carcinoma Future of EUS Technology Appendix Memories of the Establishment of EFJ (Endoscopy Forum Japan) Endoscopy Forum Japan (EFJ)?History and Contents of the Meetings

We studied the distribution of gamma-glutamyl transpeptidase (gamma-GT) by use of a monoclonal antibody (MAb) against human kidney gamma-GT in human sweat glands. In the eccrine sweat gland, the enzyme was localized along the luminal membrane and small apocrine extrusions of the superficial cells of the secretory portion. The intercellular canaliculi between basal cells were occasionally immunoreactive. In the secretory portion of the apocrine gland, luminal membrane and apocrine extrusions of various sizes and stages at the apices of the secretory cells exhibited positive reactions. Immunoreaction was also seen in the Golgi area of the cuboidal secretory cells. No positive reaction was observed in the myoepithelial cells of either gland or in the excretory duct cells.

We have determined expression of human GGT gene encoding gamma-glutamyl transpeptidase (GGT) during fetal development of liver using the Northern-blot analysis with a cloned human GGT cDNA and immunohistochemistry with a monoclonal antibody. GGT mRNA could be detected as early as the 12th week of gestation. It then increased gradually to a peak of approx. threefold the amount at week 12, at week 40, just before birth. The size of the mRNA in the fetal liver was 2.7 kb and mRNA of the same size was detected both in the human fetal kidney and human hepatocellular carcinoma as well as normal adult liver. Immunohistochemical analyses show that GGT increased as the fetal liver developed in parallel with the increase in mRNA. Histochemically, GGT was shown to be located in the wall of bile canaliculi when synthesis was low in early development, but to be distributed, in addition, all over the cell membrane of the fetal hepatocytes when synthesis was high at the later stage of development.

The temperature during microwave irradiation in the core of tissue blocks, either 1cm or 2cm cubes of rat kidney and liver, was measured by plunging a sensor into the tissue blocks. The temperature of the tissue blocks was much higher than the outer media, i.e., chemical fixatives. Thus, the temperature of the outer media did not reflect that in the tissue block to be fixed. The temperature of tissue reached 40°C within 5-10sec of irradiation. The highest temperature of tissuee block at 15-second irradiation, for example, was 92.5°C (1cm cube of kidney) and 98°C (2cm cube of liver), using 4% PFA with CaCl2 as a fixative. Microwave fixation is a practical tool for the preparation of tissue spections for either histology or cytology. However, it must be required that the irradiation is controlled so as not to produce high temperature within specimens.

Gamma-glutamyl transpeptidase (γ-GTP) was localized in prenatal and neonatal rat kidneys using an immunohistochemical method with monoclonal antibodies to rat kidney γ-GTP. γ-GTP was demonstrated on the brush border and basolateral membrane of proximal convoluted tubules from the 18th fetal day. The basolateral membrane of proximal tubules revealed strong reaction at 1 and 3 days after birth. The reaction of basolateral membrane decreased with the maturation of nephrons, however, moderate reaction was still observed at 30 days of age in the S3 segment. Throughout the postnatal development of the kidney, the S3 exhibited the strongest immunostainingand S1 showed the weakest reaction, and proximal tubules in the deep layer of the cortex always provided a stronger reaction than those in the superficial layer of the cortex. Maturating cuboidal and squamous epithelial cells of descending Henle's loop showed a positive reaction on the luminal and lateral cell membranes. On immunoelectron microscopy, γ-GTP was found on the brush border, basolateral membrane, membranes of pinocytotic vesicles and apical invaginations in proximal tubular cells at 1-7 days after birth. However, tight junctions were devoid of the reaction. The development of basal infolding and localization of γ-GTP there seemed to relate closely to the development of surrounding capillaries. γ-GTP was localized on the cell membrane and occasionally in the cytoplasm of interstitial cells of renal interstitium.

Endoscopic ultrasonography (EUS) for the diagnosis and staging of early esophageal carcinoma is discussed. Based on the nine-layered structure of esophageal wall, which is in good correspondence with histological layers, depth of carcinoma invasion can be investigated. Ultrasound endoscopes and probes are used for the examination. Ultrasound probes with 20 MHz and 30 MHz transducers can demonstrate the clear images of early esophageal carcinoma by using water filling method, which can discuss the change of the esophageal wall from the surface layer. Although the early esophageal carcinoma is detected by endoscopic findings with or without the dye spraying method by iodine, the diagnosis of depth of carcinoma invasion is not easy. EUS can assist in the diagnosis of depth of carcinoma invasion. Confirming the depth of carcinoma invasion by EUS and the lesion is limited to the mucosa. Endoscopists can decide the indication for endoscopic resection of the lesions.

Our prospective clinical study of prospectively compared physicians' management of submucosal tumors (SMTs) with and without endoscopic ultrasound (EUS). It showed that EUS reduced further tests by more than 50%, but it is unclear whether it reduced the overall costs. The aim of this study was to determine whether EUS would reduce costs.Based on the data from the clinical study, a decision analysis was created to compare the direct hospital costs for diagnosing SMTs with and without EUS. Cost data from Germany, Canada, Japan, France, and the United States were used. Costs were expressed as a ratio of the cost of esophagogastroduodenoscopy (EGD). Average cost ratios for each procedure were as follows (sensitivity analysis ranges are 95% CIs): EGD = 1; large particle biopsy (LPB) 0.75 (0.22-1.24); endoscopic ultrasound (EUS) 2.0 (1.22-2.79); abdominal ultrasound (US) 0.77 (0.31-1.24); computed tomography (CT) 1.79 (0.64-2.95); magnetic resonance imaging (MRI) 3.54 (1.28-5.79); and ERCP 3.45 (0.82-6.07).Initial inputs show the "no EUS" strategy is less costly when cost data for all countries are averaged (expected cost 2.13 vs 2.71, expressed as a ratio of the cost of EGD]) and for all countries individually except Germany. In descending order, overall management costs were most sensitive to the relative costs of CT and EUS, the cost of LPB, and to the probability of no further testing when the "no EUS" strategy is used. However, threshold analysis showed that changes in only one variable, the ratio of the cost of EUS compared to CT (the "EUS/CT ratio"), were able to shift the optimal strategy from "no EUS" to "EUS." "EUS" becomes less costly only if the EUS/CT cost ratio is0.85 (i.e., if the cost of EUS is85% that of CT). If the potential for EUS to reduce severe complications caused by LPB of high risk lesions is incorporated, "EUS" is less costly if this risk is2% (range 1-5%).When used to diagnose SMTs, EUS may reduce the need for further tests but not necessarily costs. For this indication, the relative cost of EUS compared with CT is what most limits its potential value as a cost-minimizing test. The costs, economic impact, and hence the relative appropriateness of EUS and other procedures may vary in different health care systems.

It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations.One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE.The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct.Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.

Mucin-producing cholangiocarcinoma, which excretes excessive amounts of mucin into the biliary tract and causes obstructive jaundice and cholangitis due to the mucin retention, is rare. In this paper, we report two cases of this disease, which were demonstrated by peroral cholangioscopy (POCS). The radiologic features of these tumors show the diffuse dilatation of the bile ducts demonstrated by computed tomography (CT) and ultrasonography (US), the amorphous filling defects in the dilated bile ducts revealed by cholangiography. Their endoscopic features are mucin flowing out from the papilla of Vater during endoscopic retrograde cholangiography (ERC), and the papillary tumor with contiguous superficial spread in the bile ducts observed by cholangioscopy, although removal of mucin in the biliary tract is sometimes necessary before cholangioscopy in order to examine the lesion sufficiently. According to the previous reports, prognosis after curative resection of these tumors is better than that of ordinary type of cholangiocarcinoma. Therefore, it is important to examine the tumor extension in the bile ducts by cholangioscopy, although a selection of route inserting cholangioscope is controversial.

In patients with carcinoma of the bile duct, a primary tumor with tumor spread along the bile duct is frequently shown as a stricture of the bile duct with ductal irregularity and rigidity on ERCP. In patients in whom histological diagnosis is necessary, larger caliber peroral cholangioscopes with a larger working channel should be chosen because they have the advantage of simultaneous biopsy diagnosis. However, peroral cholangioscopy (POCS) has limitations to inspect mucosal tumor spread along the upstream ducts due to the tight stricture, to obtain sufficient biopsy material for confirming the diagnosis, and to identify submucosal tumor spread. With further improvement of techniques, the combined use of POCS with biopsy under direct vision and intraductal ultrasonography (IDUS) is expected to be the best way in the diagnosis of biliary tumors.

Development of technology has made it possible to produce the micromachine. In the field of endoscopy, wireless capsule endoscopy (CE) has been developed and opened up a new field in endoscopic study. The common indication in clinical cases is limited to the diagnosis of lesions in the deeper small intestine. Clinical application of this system is increasing at a remarkable rate, though target organs and endoscopic performance are limited. On the other hand, endoscopic ultrasound (EUS) technology has advanced rapidly during the last 20 years. The improvement of ultrasound scanners, including the size of the scanner, quality of image and plural changeable frequency has been successfully developed. On the basis of these technological advances, we can discuss the potential ability of developing a capsule ultrasound endoscopy.

Endoscopic ultrasound (EUS) was developed for the detection of small pancreatic cancer because the complete demonstration of the pancreas by conventional ultrasonography (US) was sometimes prevented by intestinal gas and echoic reduction due to the deeper position of the pancreas head and tail. In this article, the diagnosis, staging, limitations, and hazards of EUS for diagnosing pancreatic cancer are described.

Purpose: To clarify the usefulness of EOCT in the diagnosis of colorectal diseases compared with EUS using ultrasonic probes.

Background: Branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but the groups at high risk for developing PDAC during the follow-up period of BD-IPMN are not clear. Objectives: To identify the risk factors for PDAC development during the follow-up period of BD-IPMN. Subjects and Methods: We investigated 230 patients undergoing follow-up of BD-IPMN; the median follow-up period was 56.9 months, and the range was 3-276 months. Among these patients, 10 developed pancreatic cancer (PDAC, 7; intraductal papillary mucinous carcinoma [IPMC], 3). The 230 patients were divided into 2 groups: PDAC group, which included 7 patients; and non-PDAC group, which included 223 patients. The PDAC and non-PDAC groups were compared with respect to the following factors: sex; age; follow-up period; number of BD-IPMNs; size of BD-IPMNs; diameter of the main pancreatic duct (MPD); size of mural nodules; family history of pancreatic cancer (within the second degree of relationship); family history of digestive organ cancer, except pancreatic cancer (within the second degree of relationship); diabetes mellitus; adiposis (body mass index [BMI] ≥ 30 kg/m2); chronic pancreatitis; and history of smoking. A chi-square test and a t test were used for univariate analysis, and logistic regression was used for multivariate analysis. Results:Univariate analysis showed that adiposis (p = 0.016), chronic pancreatitis (p = 0.038), and a family history of pancreatic cancer (p = 0.006) were the factors significantly associated with PDAC development. Multivariate analysis of these 3 factors showed that adiposis (p = 0.000, odds ratio = 60.93, 95% confidence interval [CI] = 6.18-599.92), chronic pancreatitis (p = 0.023, odds ratio = 13.0, 95% CI = 1.42-119.35), and a family history of pancreatic cancer (p = 0.003, odds ratio = 21.1, 95% CI = 2.87-156.49) were independently associated with PDAC development. Conclusions: Our results showed that adiposis (BMI ≥ 30 kg/ m2), chronic pancreatitis, and a family history of pancreatic cancer (within the second degree of relationship) were risk factors for PDAC development during the follow-up period of BD-IPMN patients.