Endoscopic intermuscular dissection (EID) for removing early rectal cancers and benign fibrotic rectal lesions.

In the current era of screening colonoscopy and increasing incidence of early rectal cancer, interventional endoscopy moves toward resections in deeper planes than the submucosal layer. Several reports support the use of endoscopic intermuscular dissection (EID) instead of endoscopic submucosal dissection (ESD) for the removal of deeply invasive rectal submucosal cancers. The resection plane into the intermuscular space, the space between the longitudinal (external) and circular (internal) muscle layer, allows radical removal of rectal invasive submucosal cancers. Furthermore, the technique offers the potential for dissection of scarred and severe fibrotic lesions in the rectum by cutting deeper and performing a partial myectomy avoiding the narrow submucosal space. We present 23 cases of EIDs both for deeply invasive rectal cancers and benign rectal lesions. This is the first report in the literature of EID resections for malignant and benign disease, including cases of severely fibrotic rectal lesions.

Virtual histology of colorectal lesions using laser-scanning confocal microscopy.

BACKGROUND AND STUDY AIMS: Histological examination of gastrointestinal lesions is currently based on light-microscopic examination of thin-slice specimens, with hematoxylin and eosin staining. A study of the use of laser-scanning confocal microscopy (LCM) to obtain immediate microscopic images of untreated specimens for examining colorectal lesions was carried out. A probe-type LCM prototype endomicroscope that can be passed through the working channel of an endoscope has also been developed. MATERIALS AND METHODS: The study materials consisted of colorectal lesions resected either endoscopically or surgically at Showa University Northern Yokohama Hospital. One hundred untreated specimens were examined using LCM. The histopathological findings in the lesions were seven cases of normal colonic mucosa, five hyperplastic polyps, 68 adenomas with low-grade dysplasia, 10 adenomas with high-grade dysplasia, and 10 adenocarcinomas. An argon laser beam with a wavelength of 488 nm was used for the LCM study. Observation of the resected normal colonic mucosa (in vitro) and the rectal mucosa of a healthy volunteer (in vivo) was possible using the endomicroscope. The LCM images for each specimen were compared with the hematoxylin-eosin-stained histopathological cross-sections. RESULTS: The LCM images corresponded well with the conventional hematoxylin-eosin light-microscopic images. The nuclei were not visualized in normal mucosa or hyperplastic polyps. In adenomas with high-grade dysplasia and carcinomas, nuclei were more often visible than in adenomas with low-grade dysplasia. The rate of visualization of nuclei was significantly different ( P < 0.01) between these two groups (60.0 % vs. 10.3 %). In LCM images using endomicroscope, it was possible to recognize the orifices of the colonic glands and goblet cells both in vitro and in vivo. CONCLUSIONS: Laser-scanning confocal microscopy provides immediate images that correspond well with those of hematoxylin-eosin staining. An improved probe-type LCM endomicroscope is being developed which should provide better histological images of colorectal lesions in vivo.

Newly developed 3D endoscopic system: preliminary experience.

Although there have been earlier reports on the use of three-dimensional endoscopic systems in the gastrointestinal tract, real-time three-dimensional imaging has not previously been described. This paper presents experience in three cases with a novel endoscopic system for three-dimensional observation in clinical situations. Case 1 was a hyperplastic gastric polyp, the shape of which was considerably enhanced in comparison with two-dimensional endoscopic viewing. Case 2 was an advanced esophageal cancer, in which the sense of depth was improved in the esophagus. Case 3 was a depressed early gastric cancer, the shape of which was also enhanced. Between July 2001 and March 2002, three experienced endoscopists also used this new system in a further 34 patients. A three-dimensional endoscopic environment was visible with the system in all patients, and all of the endoscopists were able to obtain visual information regarding spatial depth. This experience suggests that the three-dimensional video-endoscopic system used here can be of value in gastrointestinal endoscopy.

Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover proteins, and radiologic and endoscopic findings.

BACKGROUND: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the treatment of Crohn's disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohn's disease. METHODS: A 12-week multicenter, open trial of Infliximab was carried out and involved 25 patients with moderate to severe Crohn's disease who were resistant to conventional treatment. Patients received a single 2-h intravenous infusion of Infliximab at a dose of 1, 3, 5 or 10 mg/kg bodyweight. Clinical evaluation of this treatment response was defined as a reduction in the index of the inflammatory bowel disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an increase in serum levels of rapid turnover proteins as well as improvement of radiologic and endoscopic findings at 4 weeks. RESULTS: The IOIBD score was reduced after 4 weeks in 66.7% of the group receiving 1 mg/kg Infliximab, 71.4% in the group receiving 3 mg/kg, 80.0% in the group receiving 5 mg/kg, and 85.7% in the group receiving 10 mg/kg. Improvement was better maintained over 12 weeks in the 5 and 10 mg/kg groups compared with the 1 and 3 mg/kg groups. Similar results were obtained for the CDAI scores. Serum levels of rapid turnover proteins significantly increased to within the normal ranges after infusion in all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of radiologic and endoscopic findings. CONCLUSIONS: A single infusion of Infliximab was effective for the treatment of Japanese patients with Crohn's disease. Serum rapid turnover proteins reflected the clinical response to antibody for TNF-alpha well.

Endoscopic mucosal resection of the colon: the Japanese technique.

Early colorectal neoplasms, especially flat-type and depressed-type lesions, should be treated with an EMR technique. In general because depressed-type lesions, in contrast to flat-type or protruded-type lesions, tend to invade the submucosa rapidly, they ought to be treated by EMR at an early stage. Histopathologically in the case of lesions that only minimally invade the submucosa without vessel invasion (sm1a and sm1b without vessel invasion), a treatment can be completed with EMR. Massive submucosal invasive cancers ought to be resected by surgical treatment because of the risk of recurrence or metastasis. In addition, pit pattern diagnosis with magnifying colonoscopy is useful to determine a therapeutic method for colonic neoplasms. Lesions with the type VN pit pattern represent malignancy and usually invade the submucosa massively, so it is better to treat them surgically from the outset. Endoscopic mucosal resection should be conducted under fully controlled endoscopy to prevent complications. EMR is a superior therapeutic method and will be performed frequently in the future. It is necessary for colonoscopists to determine a suitable therapy for each colorectal neoplastic lesion. They also need to master the EMR technique in the correct manner.

Intracytoplasmic localization of cathepsin D reflects the invasive potential of gastric carcinoma.

BACKGROUND: The present study was undertaken to investigate the role of cathepsin D in the invasiveness of human gastric cancer. METHODS: Immunohistochemical cathepsin D staining was performed in samples from 29 early gastric adenocarcinomas (papillary or tubular adenocarcinoma) and 15 gastric adenomas, and their adjacent nonneoplastic gastric mucosa. We classified the patterns of cathepsin D immunostaining into four types; type A, fine granular staining in the apical portion: type B, intense coarse granular staining in the apical portion; type C, fine granular staining in the basal portion; and type D, diffuse granular staining throughout the cytoplasm. RESULTS: All of the nonneoplastic mucosa showed an apical cytoplasmic distribution pattern (type A or type B). However, 20% (2/10) of low-grade gastric adenomas and 60% (3/5) of high-grade gastric adenomas showed an abnormal staining pattern. i.e., types C and D. Moreover, 82% (9/11) definite intramucosal gastric adenocarcinomas, and the majority of gastric adenocarcinomas with submucosal invasion [83% (15/18) of those in the mucosal part and 100% (14/ 14) of those in the invasive submucosal part] showed an abnormal staining pattern (types C and D). Interestingly, most of the carcinoma cells invading the stroma and lymphatics showed the type D staining pattern. CONCLUSIONS: These results indicate that an abnormal cytoplasmic staining pattern of cathepsin D may reflect the invasive potential of gastric carcinoma cells.

Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer.

Nonpolypoid colorectal neoplasms are grossly classified into three groups: slightly elevated (small flat adenomas), laterally spreading, and depressed. Flat adenomas are not invasive until they are rather large, whereas depressed lesions can invade the submucosa even when they are extremely small. Nonpolypoid lesions are difficult to detect and are often overlooked. Keys to detect them are their slight color change, interruption of the capillary network pattern, slight deformation of the colonic wall, spontaneously bleeding spots, shape change of the lesion with insufflation and deflation of air, and interruption of the innominate grooves. Spraying of indigo carmine dye helps to clarify the lesions. A pit pattern analysis with a zoom colonoscope is useful for the diagnosis and staging of early colorectal cancer. Small flat adenomas are thought to be precursors of protruded polyps and lateral spreading tumors, whereas depressed lesions are thought to grow endophytically and become advanced cancers. Small depressed lesions are treated with an endoscopic mucosal resection (EMR) technique; but when they massively invade the submucosa, surgical resection is indicated. Laterally spreading tumors are not as invasive despite their large size and therefore are good indications for the EMR or piecemeal EMR method. Small flat adenomas need not be treated urgently, as almost none is invasive. Accurate diagnosis with dye-spraying and zoom colonoscopy is vital for deciding the treatment strategy.

Early colorectal cancer: flat or depressed type.

The present review describes the changes in views about the early forms of colorectal cancers. In 1985, a concept of 'flat adenoma' was born in Japan. At around the same time, depressed type early colorectal cancers started to be reported by Japanese colonoscopists. Neither flat adenomas nor depressed lesions have been frequently reported in Western countries, but increasing numbers of such cases are now described. The problem is that flat adenomas and depressed lesions seem to have been confused by many researchers. The biological aggressiveness of these lesions is quite different. The rate of submucosal invasion is very high in depressed lesions, but fairly low in small flat adenomas. Some adenomas may even look depressed at first, but such lesions should not be mistaken for truly depressed lesions. Ignorance or resistance to the concept may inhibit the detection of flat or depressed lesions. Differences of diagnostic criteria between Japanese and Western pathologists may influence the apparent frequency of mucosal cancers, but not that of invasive carcinomas. Many small adenomas do not grow if followed, but depressed lesions grow rapidly and invade the deeper layers and, as a result, may look elevated as a whole. Many cases in previously published papers suggest that small depressed carcinomas of the large intestine may develop without a precursory stage of an adenomatous polyp. At least two carcinogenic pathways, one through adenomatous polyps and one de novo, should be recognized. In addition, the importance of small depressed cancers should be emphasized.

Endoscopic diagnosis and treatment of early colorectal cancer.

Colorectal adenomas and early cancers are grossly classified into three groups: protruded, flush or slightly elevated (so-called flat adenomas), and depressed. Protruded lesions and flat adenomas are not invasive until they are rather large, whereas depressed lesions can invade the submucosa even when very small. It is not difficult to detect protruded and flat adenomas, but depressed carcinomas are often overlooked. Keys to the detection of depressed carcinomas are a slight color change, bleeding spots, interruptions of the capillary network pattern, slight deformation of the colonic wall, shape change of the lesion with insufflation and deflation of air, and interruption of the innominate grooves by the lesion. Spraying of indigo carmine dye helps to clarify the lesions. Pit pattern analysis with magnifying colonoscopy is useful for diagnosis of early colorectal cancer. Pit pattern analysis and histologic examination suggest that depressed carcinomas probably have arisen de novo, without going through an adenomatous step. Some adenomas appear at first to have a depression, but such cancer-mimicking adenomas with pseudodepression must be distinguished from depressed carcinomas because they are quite different in nature. Protruded and flat adenomas can usually be removed with polypectomy or hot biopsy techniques. Depressed carcinomas are treated with an endoscopic mucosal resection (EMR) technique; but when they massively invade the submucosa, surgical resection is indicated. Some neoplastic lesions, which we call laterally spreading tumors, extensively and circumferentially spread along the colonic wall, although they are short in height. They tend to have a rather benign nature despite their large size; therefore EMR or a piecemeal EMR method is indicated.

The problem of "flat" colonic adenoma.

In this article, differences between depressed-type early cancers and the so-called flat adenomas are clarified.

[Endoscopic treatment in colorectal lesions--especially on endoscopic mucosal resection].

Protruded polyps can usually be treated with conventional polypectomy technique. Slightly elevated lesions without malignant findings are treated with hot biopsy method if they are small enough (less than 5 mm). In order to treat flat or slightly depressed lesions or slightly elevated lesions larger than 5 mm, endoscopic mucosal resection (EMR) technique has been invented. Cancers confined to the mucosa or those only minimally invading the submucosa can be completely removed with this method. However, if histological analysis of the resected specimen shows that the cancer invades the submucosa massively or permeating the vessels, surgical treatment should be added, because otherwise there would be risk of cancer residue or metastasis. When a lesion is suspected to be a submucosal cancer by endoscopic findings and pit pattern analysis from the beginning, then surgical resection is the treatment of choice. Laterally spreading tumors, especially the homogeneous granular type, are good indication for EMR or endoscopic piecemeal mucosal resection (EPMR). It is important to remove the lesion completely confirming that the resection margin is covered with normal pits.

[Reversal of portal-systemic encephalopathy by shunt-preserving disconnection of portal and systemic circulation].

Obliteration of portal-systemic shunts surgically or by interventional radiological techniques is fairly effective in reversing intractable portal-systemic encephalopathy (PSE), but is often associated with ascites accumulation and/or formation of esophageal varices. This study reports four patients with incapacitating PSE who were treated by interventional radiological techniques via percutaneous transhepatic route. One case had the shunt embolized directly. In the other three the blockage was placed on the proximal part of the splenic vein, whereby disconnecting the mesenteric-portal blood flow from the systemic circulation while preserving the shunt. The patient of shunt closure showed transient correction of encephalopathy, but developed massive ascites and esophageal varices, encephalopathy recurred, resulting in death from hepatic failure two months after the procedure. In the cases of shunt-preserving disconnection of portal and systemic circulation (SPDPS) immediate and permanent clearing of encephalopathy was achieved without manifestation of ascites or esophageal varices during the follow-up period of 10 to 31 months. The difference of portal pressure between before and after the procedure was 18 mmHg in the shunt-closed patient and 3 mmHg in SPDPS group. We conclude from this limited experience that SPDPS can be an effective and safe method in treating PSE in adequately selected patients.

[Small nodular lesions of the pancreas: differential diagnosis with ultrasound angiography].

Ultrasound angiography (USAG), sonographic imaging of the blood flow in an organ or tissue obtained by carbon dioxide infusion into the supplying artery, was performed on 28 pancreatic nodular lesions less than 3 cm in diameter. The hemodynamics of tumors observed with USAG were divided into three groups: hypovascular, isovascular, and hypervascular, compared with the adjacent pancreatic tissue. Most of hypovascular nodules were duct cell carcinoma (sensitivity 94.1%, specificity 90.4%), while isovascular lesion was the characteristic of inflammatory masses (sensitivity 100%, specificity 95.8%). Hypervascular cases included all of the mucin producing tumors and islet cell tumors but only one case of duct cell carcinoma. So you can almost exclude duct cell carcinoma as an diagnosis in vascular rich tumors (negative predictive value 83.6%). These results were compared with those on conventional x-ray angiograms and incremental CT scans. Ultrasound angiography enabled us to detect more slight differences of tumor vascularity than the other modalities. Thus we conclude that USAG can be a useful diagnostic aid in small mass lesions of the pancreas.

[Clinical utility of receptor imaging in the assessment of liver function].

Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

[Hepatic receptor imaging with Tc-99m GSA: estimates of liver function in acute liver disease].

Technetium-99m galactosyl human serum albumin (TcGSA) is a synthesized radiolabeled analog ligand to asialoglycoprotein receptor, which resides only at a mammalian hepatocyte. TcGSA studies were performed on 16 patients with various acute liver disease and 3 controls with normal livers. Dynamic data were obtained by a gamma camera during 35 minutes after an intravenous injection of 3 mg (185 MBq) of TcGSA. The parameters of TcGSA time activity curves were obtained by dividing radioactivity of the liver by that of the liver plus heart at 15 min (Receptor Index), and by dividing radioactivity of the liver at 15 min by that at 3 min post injection (Clearance Index). The two parameters correlated well with prothrombin time, clinically estimated staging, and severity of acute liver disease. We have concluded that liver function study by the newly developed receptor imaging with TcGSA can be a sensitive and promising tool in estimating the severity and prognosis of acute liver disease.

Small hepatocellular carcinoma: diagnosis with US angiography with intraarterial CO2 microbubbles.

Ultrasonographic (US) angiography enhanced with intraarterial CO2 microbubbles, a contrast material used in US imaging, was performed of 103 histologically proved hepatocellular carcinomas (HCCs) smaller than 3 cm in diameter in 95 patients. The detection rate for hypervascular HCC with US angiography was compared with the rate of detection with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil. Sensitivity in detection of hypervascular HCCs with US angiography was 86% (89 of 103 HCCs), compared with 63% (44 of 70 HCCs) detected with conventional angiography, 70% (23 of 33 HCCs) with DSA, and 82% (75 of 91 HCCs) with CT with iodized oil. US angiography depicted small hypervascular HCCs, especially those less than 1 cm in diameter, and helped clarify vascularity as isovascular or hypovascular in angiographically undetectable HCCs. Findings at US angiography assisted the choice of a therapeutic strategy for treatment of HCC, such as transarterial therapy, percutaneous ethanol injection therapy, or resection.