CLINICAL EVALUATION OF PERORAL CHOLANGIOSCOPY FOR BILIARY DISEASE USING NARROW BAND IMAGING

Regarding peroral cholangioscopy (POCS) for biliary disease, due to the recent appearance of a video cholangioscope that can obtain high‐quality images, it is possible to observe subtle changes of the biliary mucosa. In addition to the conventional observation method using POCS, the biliary mucosa with also observed with narrow band imaging (NBI) in one case of chronic cholangitis and four cases of extra hepatic bile duct tumor (three surgical cases). In the conventional observation method, the vessels in the surface layer of the biliary mucosa could be observed more clearly using NBI. In one case in which a tumor was observed, the irregularity of the biliary mucosa became clear on NBI, and the vessels inside a papillary tumor could also be easily observed. In another case of bile duct tumor, the conventional observation method showed a region in the proximity of the tumor where the vessels could not be seen clearly, but they could be seen clearly on NBI. In all of the cases, the bile juice was seen as red on NBI, which disturbed the observation. With POCS using NBI, it was possible to observe the vessels and irregularities in the surface layer of the biliary mucosa more clearly than with conventional observation methods.     

ENDOSCOPIC DIAGNOSIS OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM USING PERORAL PANCREATOSCOPY WITH NARROW BAND IMAGING

A 77‐year‐old man was diagnosed with a pancreas cyst at another hospital. Abdominal ultrasonography revealed a cyst in the head of the pancreas and a small protrusion. These findings suggested intraductal papillary mucinous neoplasm. Cytologic finding of the pancreatic juice revealed a Class III lesion, and intraductal ultrasonography and peroral pancreatoscopy (PPS) were performed. An abnormal course of main pancreatic duct (MPD) prevented the insertion of an ultrasonography probe into the MPD, and PPS was performed. The mucosal surface of the MPD near the papillary area was normal, and narrow band imaging (NBI) clearly showed the vascular structure. When the PPS was inserted more deeply, many small protrusions were observed and NBI delineated the protrusions more clearly. Papillary protrusions were observed in the cyst, but NBI did not reveal any tumor vessels. These findings led to a diagnosis of benign intraductal papillary mucinous neoplasm lesion. Since then, follow‐up examinations have been made. Changes in the cyst and protrusion have not been observed.     

WHAT'S NEW IN CHOLANGIOSCOPY? IS NARROW BAND IMAGING CHOLANGIOSCOPY THE NEXT GENERATION?

Narrow band imaging (NBI) makes it possible to emphasize the imaging of certain features such as mucosal structures and mucosal microvessels in gastrointestinal tract diseases. Recently, video peroral cholangioscopy (POCS) has been developed as diagnostic endoscopy for better observation of bile duct lesions, but there is no report on POCS using NBI. Herein is described the efficacy of POCS using NBI for the observation of both fine mucosal structures and tumor vessels, resulting in correct target biopsy in patients with biliary tract diseases.     

EVALUATION OF NARROW BAND IMAGING FOR PERORAL CHOLANGIOPANCREATOSCOPY

Used with narrow band imaging (NBI), peroral cholangiopancreatoscopy (PCPS) was performed in eight patients with biliary and pancreatic diseases. The procedures were successfully performed in all patients without any complications after endoscopic sphincterotomy. Direct endoscopic diagnosis within both the bile and pancreatic ducts was well accomplished by the baby scope with NBI. NBI produced higher quality images and was able to show changes of the bile duct wall due to tumor growth. However, bile is seen as red on NBI, so sufficient cleaning of the bile duct is recommended. It is concluded that this procedures is considerably valuable and enables PCPS to easily detect biliary lesions.     

ROLE OF PERORAL CHOLANGIOSCOPY IN THE PREOPERATIVE DIAGNOSIS OF MALIGNANT MIDDLE and LOWER BILE DUCT CANCERS: A PRELIMINARY STUDY USING 10 FR PLASTIC STENT

To date, peroral cholangioscopy (POCS) with working channel for biopsy is a less than an essential means for endoscopic diagnosis of bile duct lesions. One of these reasons is that the durability of the baby scope is much improved, too delicate for use on tough lesions. Furthermore, in operable cases, it has a major disadvantage in that we cannot observe the proximal site of stricture. In this study, we introduced new methods to observe and perform the biopsy at proximal site of stricture using 10Fr plastic stent. After this method, we performed observation of proximal site of stricture without dilation and could diagnose precise incision line preoperatively in all cases. Importantly, all procedures were done within one week from the first endoscopic retrograde cholangiopancreatography (ERCP). Although further investigation and development of baby scopes are necessary, POCS using 10Fr plastic stent will make it possible to evaluate the hepatic site of spreading cancer in patients with middle or lower bile duct cancer.     

INFLAMMATORY PROTRUDING LESION IN THE INTRAHEPATIC BILIARY DUCT DIAGNOSED ON NARROW BAND IMAGING–VIDEOCHOLANGIOSCOPY

A 66‐year‐old woman who had a repeated history of cholangitis since undergoing choledocho‐jejunostomy for post‐cholecystectomy common bile duct stricture, was referred to Kyoto University Hospital for further examination of the stricture of left intrahepatic biliary duct (IHBD). Endoscopic retrograde cholangiography (ERC) showed obstruction of the left IHBD with slightly protruding lesion. Peroral cholangioscopy (POCS) with narrow band imaging (NBI) demonstrated that a protruding lesion with papillary surface had neither tumor vessels on the surface of the tumor nor microvessel in each papillary projection. Biopsy presented only inflammation. Pathological analysis of the resected left lobe also showed only inflammatory change. NBI‐videocholangioscopy appears to be useful for diagnosing biliary disease by evaluating the tumor vessels including microvessel in papillary projection.     

PERORAL PANCREATOSCOPY: CURRENT STATUS AND FUTURE EXPECTATIONS USING NARROW BAND IMAGING

Peroral pancreatoscopy (POPS) under duodenoscopic assistance provide direct visual assessment of the pancreatic duct, tissue sampling, and therapeutic interventions. Sometimes, pancreatoscopy can confirm accurate diagnosis, such as differential diagnosis of filling defects between intraductal tumors and stones. However, it is often difficult to differentiate malignant from benign strictures solely on pancreatoscopy. It is currently considered that intraductal papillary mucinous neoplasm (IPMN) is the most suitable indication of POPS. POPS has several problems: image resolution, fragility and maneuverability. Concerning image resolution, the quality has been improved with the development of a video pancreatoscope. Moreover, the recently developed endoscopic optical technology of narrow band imaging (NBI) is now available to video pancreatoscopy. This will allow direct visual assessment. Although currently POPS has several problems, further improvement will assist POPS to become a useful modality in combination with NBI.     

DIAGNOSTIC UTILITY OF PERORAL CHOLANGIOSCOPY AND TRANSPAPILLARY INTRADUCTAL ULTRASONOGRAPHY FOR BILE DUCT CARCINOMA

Recently, new diagnostic procedures such as video peroral cholangioscopy (POCS) and transpapillary intraductal ultrasonography (IDUS) have been available for diagnosis of biliary diseases. These new modalities are especially useful for diagnosis of minute bile duct lesions on cholangiogram and correct diagnosis of lateral extension of bile duct carcinoma. In this paper, showing some effective cases of POCS and IDUS, we present our diagnostic approach for bile duct carcinoma and discuss the future prospects of POCS and IDUS.     

A CASE OF CHOLESTEROSIS OF THE COMMON BILE DUCT DIAGNOSED BY PERORAL CHOLANGIOSCOPY

We experienced a case of cholesterosis of the common bile duct in which peroral cholangioscopy (POCS) was very useful for making a diagnosis. The patient was a 66‐year‐old man. He was admitted for examination of an asymptomatic mass in the pancreas. The mass was diagnosed as a serous cystic tumor of the pancreas. While examining the tumor, endoscopic retrograde cholangiopancreatography (ERCP) incidentally revealed a 7 mm irregular filling defect in the distal common bile duct. EST was then performed, followed by POCS, which revealed a clump of yellowish‐white Ip or Isp polyps in the distal bile duct. Histological examination of biopsy specimens taken under direct vision gave a diagnosis of cholesterol polyps containing foamy cells. POCS was useful for allowing direct observation of the characteristic color of cholesterol polyps, and for obtaining biopsy specimens under direct vision.     

NEW APPLICATION OF NARROW BAND IMAGING FOR CHOLANGIOPANCREATOSCOPY

The usefulness of narrow band imaging (NBI), which is based on the principle that the depth of light penetration depends on its wavelength, has been accepted for evaluating malignant or benign lesions in the pharynx, the upper, and lower gastrointestine. The purpose of the present paper was to investigate NBI for diagnosing biliopancreatic disease. Using NBI it has become easy to detect the surface microstructure of biliary mucosa and subjacent vascular network of the bile duct, and inflammatory scarring stenosis is visualized as a whitish scar and multiple inflammatory red spots. However, bile duct cancer was detected as a stenosis with abnormal subjacent vessels and irregular surface. Concerning pancreatic duct, NBI has clearly shown vascular network and spreading of branch‐type intraductal papillary mucinous neoplasm to the main pancreatic duct. In contrast, bile juice has been detected as red fluid and bleeding as black red. Therefore, it is important to flush the biliary system before observing with NBI.     

PERORAL CHOLANGIOSCOPY USING A NEW THINNER VIDEOSCOPE (CHF‐B260)

The CHF‐B260 videoscope has a 3.4 mm outer diameter, 1.2 mm forceps channel, and two‐way angulations function (70° up and 70° down). Peroral cholangioscopy (POCS) was performed using the CHF‐B260 in 13 patients who were admitted to our hospital between October 2002 and June 2004. The CHF‐B260 was successfully inserted into the bile duct in all cases. Clear images were obtained in 11 patients. Endoscopic images for two cases of malignant stricture due to metastasis of colon cancer and gallbladder cancer were not clear because of bleeding from the tumors. POCS was performed safely in all patients without any complications. POCS with the CHF‐B260 was very useful for the diagnosis of biliary disorders. If the outer diameter and biopsy channel of CHF‐B260 are improved, POCS will become even more effective for the diagnosis of biliary disorder.     

ENDOSCOPIC DIAGNOSIS OF INTRADUCTAL PAPILLARY‐MUCINOUS NEOPLASM OF THE PANCREAS BY MEANS OF PERORAL PANCREATOSCOPY USING A SMALL‐DIAMETER VIDEOSCOPE AND NARROW‐BAND IMAGING

Background: Intraductal papillary‐mucinous neoplasm (IPMN) is an intraductal tumor in which the mucin‐producing epithelium shows proliferated papillary and a wide variety of pathological changes ranging from hyperplasia to adenocarcinoma. Therefore, it is important to determine whether an IPMN is benign or malignant. In the present study of patients with IPMN, the protrusion was observed by a peroral pancreatoscopy (PPS) using a small‐diameter videoscope and narrow‐band imaging (NBI). We carried out the differential diagnosis of benign lesion to malignant lesion. Methods: Between April 2003 and May 2009, PPS using a small‐diameter videoscope by means of NBI was carried out on 21 hospitalized patients with IPMN (10 cases of adenocarcinoma, 11 cases of adenoma or hyperplasia; 14 males and seven females, with a mean age of 69.4 years). Results: Fifteen focal lesions of the 16 cases in the head of the pancreas (93.7%) and four focal lesions of the five cases in the pancreatic body (80%) were observable, whereas two lesions (adenocarcinoma in the pancreatic body, and adenoma in the uncus of pancreas) were not observable. Endoscopically, seven cases were classified as villous type and two cases as vegetative type, and nine cases were diagnosed as adenocarcinoma. Ten cases with sessile type or semipedunculated type were diagnosed as adenoma or hyperplasia. Vascular patterns and protrusions were detected more clearly in the NBI images than under white light observation. Conclusions: When combined with a videoscope and NBI, pancreatoscopy provided a clear image and was useful for evaluating whether the IPMN was benign or malignant.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER USING MAGNIFYING ENDOSCOPY WITH A COMBINATION OF NARROW BAND IMAGING AND ACETIC ACID INSTILLATION

Demarcation of early gastric cancers is sometimes unclear. Enhanced‐magnification endoscopy with acetic acid instillation and magnifying endoscopy with a narrow band imaging (NBI) system have been useful for recognition of demarcation of early gastric cancers. We report a patient with early gastric cancer who underwent a successful endoscopic submucosal dissection (ESD) by magnifying endoscopy with the combined use of NBI and acetic acid instillation. A 72‐year‐old man with early gastric cancer underwent ESD. Demarcation of the lesion was not clear, but magnifying endoscopy using the combination of NBI and acetic acid clearly revealed the demarcation. ESD was carried out after spots were marked circumferentially. We identified the positional relation between the demarcation and all markings. Resection of the lesion was on the outside of the markings. Histopathologically, the lesion was diagnosed as a well‐differentiated adenocarcinoma limited to the mucosa. The margins were carcinoma free. Magnifying endoscopy combining the use of NBI with acetic acid instillation is simple and helpful for identifying the demarcation of early gastric cancer. This method may be useful in increasing the rate of complete resection by ESD for early gastric cancer.     

ENDOSCOPIC MICROVASCULAR ARCHITECTURE OF THE PORTAL HYPERTENSIVE GASTRIC MUCOSA ON NARROW BAND IMAGING

Background: We evaluated the endoscopic microvascular architecture of the gastric mucosa in portal hypertension patients using the prototype of narrow band imaging (NBI). Material and Methods: The study included 103 Helicobacter pylori‐negative patients with chronic liver disease (22 without portal hypertension (group 1), 81 with portal hypertension (group 2)). Results: (i) Abnormality of collecting venules, reddening mucosa, red spots, a mosaic‐like pattern, and gastric antral vascular ectasia (GAVE) were observed on the gastric mucosa, and an obscure change in collecting venules (73% vs 14%; P < 0.001), reddening mucosa (49% vs 5%; P < 0.001), red spots (36% vs 5%; P < 0.01) and a mosaic‐like pattern (40% vs 5%; P < 0.01) were more frequently observed in group 2 than in group 1. (ii) On magnifying endoscopy with NBI, the mucosa with an obscure change in collecting venules was demonstrated as dilation of the capillaries surrounding the gastric pits in various degrees, and reddening mucosa was observed as extended and swollen gastric pits and various degrees of dilated and convoluted capillaries surrounding the gastric pits. Red spots were demonstrated as extended and swollen gastric pits, dilated and convoluted capillaries surrounding the gastric pits, and intramucosal hemorrhage around these capillaries. GAVE was recognized as partial and marked dilatation of the capillaries surrounding the gastric pits. Conclusion: Abnormality of collecting venules, swelling of gastric pits, dilatation of capillaries surrounding the gastric pits, intramucosal hemorrhage around capillaries, and partial and marked dilatation of the capillaries were observed on the gastric mucosa in portal hypertension patients.     

MAGNIFYING ENDOSCOPIC OBSERVATION WITH NARROW BAND IMAGING FOR SPECIALIZED INTESTINAL METAPLASIA IN BARRETT'S ESOPHAGUS WITH SPECIAL REFERENCE TO LIGHT BLUE CRESTS

Aim: Barrett's esophagus (BE) with specialized intestinal metaplasia (SIM) is at high risk of esophageal adenocarcinoma. Magnified endoscopy with narrow band imaging (ME‐NBI) can be useful for detecting this condition. In addition to pit patterns, light blue crests (LBC), blue‐whitish patchy areas on the metaplastic epithelia of the stomach, can predict SIM in BE under ME‐NBI observation. Methods: A total of 54 patients with BE underwent ME‐NBI to identify IM pits (tubular and villous pits) and LBC. Biopsy samples were taken for histological evaluation of IM, immunohistochemical staining for CD10, MUC2 and MUC5AC antigen, transmission electron microscopy and real‐time polymerase chain reaction (RT‐PCR) analysis of CD10 mRNA expression. Results: IM pit pattern with ME‐NBI for the diagnosis of IM yielded acceptable sensitivity, specificity and accuracy at 92%, 77% and 83%, respectively. However, the sensitivity, specificity and accuracy of LBC with ME‐NBI for IM were comparably high at 79%, 97% and 89%, respectively. Upon immunohistochemistry, all 19 metaplastic epithelia of LBC‐positive BE showed immunoreactivity against anti‐MUC2 antibody, whereas CD10 antigen was identified in 11 of the 19 LBC‐positive BE. Brush borders were seen on IM epithelia using electron microscopy. On real‐time PCR analysis, CD10 mRNA levels in the LBC‐positive BE were higher compared to those in the LBC‐negative BE. Conclusion: The appearance of LBC can be an accurate sign to predict SIM in BE and may be associated with high CD10 expression, possibly along with brush borders.     

MAGNIFICATION ENDOSCOPIC VIEW OF AN EARLY GASTRIC CANCER USING ACETIC ACID AND NARROW‐BAND IMAGING SYSTEM

A 62‐year‐old woman was referred to Mie University Hospital, Tsu, Japan, for examination of upper gastrointestinal tract. The conventional endoscopy showed a slightly depressed lesion on the greater curvature at the gastric body. The surface of surrounding non‐neoplastic mucosa using magnification endoscopy with acetic acid was gyrus‐villous pattern whereas the surface of the lesion was rough. Furthermore, magnification endoscopy using acetic acid and narrow‐band imaging system visualized clearer fine surface pattern of carcinoma. The lesion had a rough mucosa with irregularly arranged small pits. The lesion was resected completely by endoscopic mucosal resection with insulated‐tip electrosurgical knife. Narrow‐band imaging system with acetic acid may be able to visualize not only the capillary pattern but also the fine surface pattern of gastric carcinoma.     

MAGNIFYING OBSERVATION OF MICROVASCULAR ARCHITECTURE OF COLORECTAL LESIONS USING A NARROW‐BAND IMAGING SYSTEM

We reviewed the magnifying observation of the microvascular architecture of colorectal lesions and discuss the utility of the detailed observation of the microvascular architecture for differential diagnosis during narrow‐band imaging (NBI) colonoscopy. Angiogenesis is critical to the transition of premalignant lesions in a hyperproliferative state to the malignant phenotype. Therefore, diagnosis based on angiogenic or vascular morphologic changes might be ideal for early detection or diagnosis of neoplasms. In this review, we propose the term ‘meshed capillary’ for the distinction between non‐neoplastic and neoplastic lesions and the capillary classification ‘capillary pattern’ for the differential diagnosis of colorectal lesions. We believe that the combined use of NBI optical chromoendoscopy and real chromoendoscopy decreases the time and cost of screening colonoscopy. To assess the feasibility and efficacy of using the NBI system, further studies are required for colorectal lesions and other lesions of the gastrointestinal tract.     

STUDY OF THE TUMOR VESSELS IN DEPRESSED‐TYPE EARLY GASTRIC CANCERS USING NARROW BAND IMAGING MAGNIFYING ENDOSCOPY AND CDNA ARRAY ANALYSIS

Background: Since endoscopic mucosal resection has been applied to differentiated gastric cancers with invasion limited to the mucosal layer, the diagnosis of their differentiation is important. The degree of differentiation varies depending on the size and location of the tumors. Correct diagnosis by biopsy can be difficult because depressed‐type early gastric cancers sometimes contain mixed histology. Methods: Fifteen patients with depressed‐type early gastric cancers were observed by magnifying endoscopy with a narrow band lighting system. The fine mucosal vascular pattern was recorded and compared with the histological differentiation and features of vessels by staining with CD34. In some patients, cDNA array analysis was performed to determine differences among histological types. Results: Tumor vascular patterns were classified into two categories. Grid‐like network patterns not only characterized differentiated type but were also associated with high microvascular density. Short twig‐like patterns typified the undifferentiated type and a low vascular density. Differentiated types highly expressed some angiogenic factors, such as VEGFc and Flt‐4. Conclusions: Tumor vessel pattern of depressed‐type early gastric cancer obtained by narrow band imaging magnifying endoscopy reflects both the histological features and the degree of expression of angiogenic factors.     

FLAT AND SMALL SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS DETECTED AND DIAGNOSED BY ENDOSCOPY WITH NARROW‐BAND IMAGING SYSTEM

Reported herein is the case of a 65‐year‐old man who had completely flat and small squamous cell carcinoma in the esophagus. The subtle lesion was initially detected as a brownish area depicted by non‐magnified endoscopy with the narrow‐band imaging system (NBI). The lesion was predicted to be type 0‐IIb mucosal cancer due to assessment of morphologic change of intrapapillary capillary loop under magnified NBI observation. Endoscopic mucosal resection was performed for the lesion. The histological finding of the removed specimen indicated mucosal squamous cell carcinoma. Endoscopic observation with the NBI system was useful for detecting obscure squamous cell carcinoma and predicting the histological finding.