Colon Gland Research Articles

Confocal endomicroscopy in patients with ulcerative colitis

Confocal endomicroscopy is a new technology that provides microscopic images of cellular morphology in the gastrointestinal tract in vivo. In particular, confocal microendoscopy allows histological diagnosis during the endoscopic examination. We examined patients with ulcerative colitis (UC) using confocal endoscopy and investigated the features of confocal endomicroscopic images of inflamed and non-inflamed rectal mucosa. Seventeen patients with UC, 12 in the active phase and 5 in the non-active phase, and 14 non-UC control patients who had colon polyps or colon cancer underwent colonoscopy, during which fluorescence images of the rectal mucosa were obtained with confocal endomicroscopy. Histological findings of rectal biopsy specimens were compared with the microendoscopic images. Confocal microendoscopy allowed observation of cellular and subcellular structures. The crypts of normal colonic mucosa were small, round and regularly arranged, and the crypt lumens of the colonic glands were small and round. The crypts of colonic mucosa in non-active UC were small, round and slightly irregular in arrangement and the crypt lumens of the colonic glands were small and round. Inflammatory cells and capillaries were visible in the lamina propria. The crypts of colonic mucosa in active UC were large, variously shaped and irregular in arrangement. The crypt lumens of the colonic glands were large and the crypt structure could not be recognized in some areas. Numerous inflammatory cells and capillaries were visible in the lamina propria. Images taken with the confocal microendoscope provided information that was equivalent to conventional histology, and improve our understanding of the differences in rectal tissues (crypts, capillaries and inflammatory cells) between normal controls and active and non-active UC patients during ongoing endoscopy.

Confocal Microendoscope Images Provide Information Equivalent to Histological Findings in Inflammatory Bowel Disease

Background and Aims: Confocal endomicroscopy is a new technology that provides microscopic images of cellular morphology in the gastrointestinal tract in vivo. In particular, the confocal microendoscopy allows histological diagnosis during the course of endoscopy. We examined patients with ulcerative colitis (UC) or Crohn’ disease (CD) using confocal endoscopy and investigated the features of confocal endomicroscopic images of inflamed and non-inflamed rectal mucosa. Methods: Fifteen patients with UC, 10 in the active phase and 5 in the non-active phase, 5 CD and 14 control patients who had colon polyps or colon cancer underwent colonoscopy, during which fluorescence images of the rectal mucosa were obtained with the confocal endomicroscopy. Histological findigs of rectal biopsy specimens were compared with the images of the microendoscopy. Results: The confocal microendoscopy allowed the observation of cellular and subcellular structures. The crypts of colonic mucosa in controls or CD patients were small, round and regularly arranged and the crypt lumens of colonic glands were small and round. The crypts of colonic mucosa in non-active UC were small, round and slightly irregular in arrangement and the crypt lumens of colonic glands were small and round. Inflammatory cells and capillaries were visible in lamina propria. The crypts of colonic mucosa in active UC were large, variously shaped and irregular in arrangement. The crypt lumens of colonic glands were large. The structure of crypts could not be recognized in some areas. Numerous inflammatory cells and capillaries were visible in lamina propria. Conclusions: Images taken with the confocal microendoscope provided information that was equivalent to those of conventional histology, and allow an understanding of the differences in rectal tissues (crypts, capillaries and inflammatory cells) between normal controls, CD patients, active and non-active UC patients during ongoing endoscopy.

Pancreatic endocrine carcinoma presenting with gastric varices derived by left-sided portal hypertension: a case report

We herein report a 71-year-old man with pancreatic carcinoma presenting as gastric varices caused by an obstruction of the splenic vein compressed by the tumor, which also invaded the spleen, stomach, transverse colon, left kidney, and left adrenal gland. A complete resection of distal pancreatomy and lymph node dissection with splenenctomy, left adrenalectomy, left nephrectomy, and partial resection of transverse colon and stomach were performed. After the resection, the gastric varices completely disappeared without any interventional therapy. The gastric varices observed in this case were considered to be derived from left-sided portal hypertension secondary to splenic vein occlusion, which is an uncommon complication mostly associated with pancreatitis and pancreatic carcinoma. Now that 17 months have passed after his operation, the patient is alive and in satisfactory condition without any signs of recurrence.

Developmentally regulated expression of matrix metalloproteinases during fetal rat colon morphogenesis

To investigate the role of matrix metalloproteinases (MMPs) during gastrointestinal tract development, the expression of gelatinases (MMP-2 and MMP-9) was investigated during fetal rat colon morphogenesis. Fetal rat colons were separated into epithelial and mesenchymal fractions without cross contamination using a chelating agent and a dissecting microscope. Gelatinase activity measured using fluorescently labeled gelatin was higher in the mesenchymal than in the epithelial fraction; the developmental profile revealed that, in both fractions, gelatinase activity was enhanced during colon morphogenesis. During colonic gland formation, there was prominent MMP-2 activity, elevated MMP-2 mRNA expression, and an increase in the level of the active form of MMP-2 in the mesenchymal fraction. The mRNA expression of the tissue inhibitor of metalloproteinase 2 corresponded with an elevation in the level of the active form of MMP-2; the mRNA expression of the cell surface activator of MMP-2, membrane type matrix metalloproteinase 1, did not increase significantly. MMP-9 activity was low; only the pro-form was observed in the epithelial fraction at the end of fetal life. These results suggest that, during colon morphogenesis, MMP activity is under strict spatio-temporal control, and that the activity of MMP-2, which is regulated at both the transcriptional and proteolytic activation levels, is very much involved in rat colon morphogenesis.

Distribution of neuroendocrine cells in the small and large intestines of the one-humped camel (Camelus dromedarius)

The distribution and relative frequency of neuroendocrine cells in the small and large intestines of one-humped camel were studied using antisera against 5-hydroxytryptamine (5-HT), cholecystokinin (CCK-8), somatostatin (SOM), peptide tyrosine tyrosine (PYY), gastric inhibitory polypeptide (GIP), neuronal nitric oxide synthase (nNOS), gastrin releasing peptide (GRP), substance P (SP), and neurokinin A (NKA). Among these cell types, CCK-8 immunoreactive (IR) cells were uniformly distributed in the mucosa, while others showed varied distribution in the villi or crypts of the small intestine. Immunoreactive cells like 5HT, CCK-8, and SOM showed peak density in the villi and crypts of the small intestine and in the colonic glands of the large intestine, while cells containing SP were discerned predominately in the crypts. 5-HT, CCK-8 and SOM cells were mainly flask-shaped and of the open-variety, while PYY and SP immunoreactive cells were mainly rounded or basket-shaped and of the closed variety. Basically the distribution pattern of the endocrine cells in the duodenum, jejunum and colon of the one-humped camel is similar to that of other mammals. Finally, the distribution of these bioactive agents may give clues as to how these agents aid in the function of the intestinal tract of this desert animal.

Adenocarcinoma Originating from a Mature Teratoma of the Testis

Malignant transformation in testicular teratomas has been reported very rarely in the literature. Although testicular teratomas in childhood are regarded as benign neoplasms, these tumors, if left untreated until advanced ages, may present the risk of malignant transformation. We report a case of differentiated adenocarcinoma originating from colonic glands in primary testicular teratoma.

Detection of tissue abnormalities in normal mucosa surrounding colorectal cancer using an endocytoscopy system

The endocytoscopy system is a novel diagnostic technique that provides extremely high-magnification imaging of the gastrointestinal mucosa. We are currently using a prototype Olympus endocytoscope for clinical research in gastrointestinal tumors. In one surgical specimen obtained after resection of a cancer of the transverse colon, focal abnormalities of colonic glands were detected 7 cm away from the primary tumor, within macroscopically normal mucosa. Our finding, which was confirmed by histopathological examination, suggests the need for further clinical investigation to assess whether endocytoscopy is able to identify premalignant changes in apparently normal mucosa. This could potentially be useful for accurate evaluation before planning minimally invasive therapy.

Calreticulin regulates cell proliferation and migration in gastric cancer cell line AGS

Calreticulin (CRT) is a multi-functional protein regulates various cellular functions, such as calcium homeostasis and intracellular adhesion. Moreover, high CRT expression levels have been observed in several cancer tissues including hepatoma, neuroblastoma, mammary gland cancer, bladder cancer and colon cancer. These observations imply that high CRT expression levels might correlate with carcinogenesis processes in these cancers. However, effects of alteration of CRT expression levels in human gastric cancer have never been reported. To further determine the significance of CRT in human gastric cancer, stable CRT-overexpressed and CRT-konockdown AGS gastric cancer cell lines were established. By MTT assay and cell cycle analysis, we showed that the proliferation rate is higher in CRT-overexpressed cells but lower in CRT- knockdown cells. In addition, CRT-overexpressed cells have higher wound healing and migration rate than CRT-knockdown cells. Our data first demonstrated that CRT might play an essential role on facilitating gastric cancer cell proliferation and migration, therefore might be an important target for future research of human gastric cancer.

3006: Sonographic features of a Peutz–Jeghers-like polyp

A 52-year old male was admitted to our hospital because of a diarrhea and melena. He was operated for in esophageal cancer at 50 years old. Transabdominal ultrasound showed a target sign (multiple concentric rings sign) in the pelvis and a polyp of 3 mm in size on its tip. This polyp had a tree-like structure on B-mode scan. Color Doppler and B-flow disclosed blood vessels distributed like arborization. It was a Peutz–Jeghers-like polyp of 4535 mm in size by the operation. Microscopically, the specimens of the tumor show arborizing smooth muscle, so called “tree-like branching”, separating hyperplastic and adenomatous colonic glands to the lobules.

Reactive Syringofibroadenomatous Hyperplasia in Peristomal Skin with Formation of Hybrid Epidermal-Colonic Mucosa Glandular Structures, Intraepidermal Areas of Sebaceous Differentiation, Induction of Hair Follicles, and Features of Human Papillomavirus Infection

We report a case of reactive syringofibroadenomatous hyperplasia in peristomal skin. The patient was a 62-year-old woman who had undergone abdominoperineal resection of the rectum for rectal adenocarcinoma with subsequent colostomy 2 years earlier. Clinically, a nodule and small, whitish, warty lesions developed at the outer margin of the stoma extending onto the adjacent skin. Following a clinical suspicion of adenocarcinoma, recurrent at the colostomy site, a 5 x 4 x 3-cm excision of the peristomal skin and the affected portion of the stoma was performed and submitted for histologic examination. The biopsy revealed a peculiar composite lesion of reactive syringofibroadenomatous hyperplasia and the excised part of the stoma. Several unusual histopathological features were detected in the syringofibroadenomatous part of the lesion such as the formation of plentiful hybrid epidermal-colonic mucosa glandular structures, intraepidermal areas of sebaceous differentiation, koilocytic changes, induction of rudimentary hair follicles, and intradermal mucinous lakes. The cellular composition of the glandular structures was mainly similar to that seen in a normal colonic mucosa epithelium. They also contained occasional Paneth cells. Being located at a distance from the stoma, these accentuated colonic mucosa epithelial glands reaching the epidermis may be a diagnostic pitfall prompting the consideration of adenocarcinoma involving the stoma. The rudimentary follicles and sebaceous differentiation were probably induced by an altered stroma and/or human papillomavirus (HPV): HPV, type 36 was identified by PCR using consensus primers followed by sequencing of the PCR products.

A Mechanistic Basis for the Role of Cycle Arrest in the Genetic Toxicology of the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking of meat, induces tumors of the prostate, colon, and mammary gland when fed to rats. PhIP is readily absorbed and efficiently metabolized to a genotoxic derivative by CYP1 enzymes. Although metabolism and mutational potential of PhIP have previously been well characterized, the intervening cellular and genomic responses to the chemical are not fully understood. We have examined the cellular response to PhIP exposure in human mammary epithelial MCF10A cells, which retain characteristics of normal breast epithelial cells. Because these cells fail to activate PhIP, they were cocultured with a human lymphoblastoid cell line MCL-5, which constitutively expresses CYP1A1, and have been transfected to express human CYPs1A2, 2A6, 3A4, and 2E1. The MCL-5 cells were irradiated (2,000 rads) prior to coculture, rendering them unable to replicate yet still retaining metabolic competency. MCF10A cells were treated (in the presence of MCL-5 cells) with PhIP (1-100 microM) and harvested at various time-points. Compared to DMSO control, treatment (24 or 48 h) with PhIP resulted in a significant dose-dependent fall in cell number. Cells treated for 48 h then cultured in the absence of PhIP (and MCL-5 cells) for a further 6 days showed a much greater dose-dependent reduction in cell number. Flow cytometric analysis indicated that PhIP treatment (48 h) resulted in a dose-dependent accumulation of cells in the G1 population. Western blotting revealed elevated expression of p53 and the cyclin dependent kinase inhibitor p21WAF1/CIP1 after PhIP treatment. Levels of MDM2, a negative regulator of p53, and the hypophosphorylated form of RB were also elevated, consistent with the triggering of G1 cell cycle checkpoint. These cell cycle effects are critical, as they enable cells to effect genome repair, accept mutation, or eliminate excessively damaged cells.

Expression pattern of epithelial cell adhesion molecule on normal and malignant colon tissues

To investigate the expression pattern of epithelial cell adhesion molecule (Ep-CAM) on normal and malignant colon tissues to evaluate its diagnostic and therapeutic significance. cDNA encoding Ep-CAM extracellular domain was cloned by reverse transcription-polymerase chain reaction (RT-PCR) from excised malignant colon tissues and inserted into a glutathione S-transferase (GST)-tagged vector. Ep-CAM-GST fusion protein was induced by isopropyl-beta-D-thiogalactopyranoside (IPTG) and purified with glutathione-sepharose. The Ep-CAM-GST fusion protein was mixed with Freund's adjuvant and Balb/c mice were immunized with it. Sp2/0 myeloma cells were fused with the spleen cells of the immunized mice. After having selected by indirect ELISA, the anti-Ep-CAM monoclonal antibodies (MAbs) were generated and the corresponding ascites were obtained. Finally, the human colon carcinoma tissue array prepared from seventy individual patients was stained with the anti-Ep-CAM MAbs. The isolated Ep-CAM cDNA sequence was identical to the data in GenBank. The expressed fusion protein was almost soluble and had a molecular weight (MW) of 53 ku. Four MAbs against Ep-CAM were obtained and designated as FMU-Ep1, FMU-Ep2, FMU-Ep3 and FMU-Ep4 respectively. Among them, FMU-Ep4 could recognize the natural Ep-CAM on Colo205 and SW480 cells, and all of them could be used for immunohistochemical staining of tissue sections. It was found that Ep-CAM was distributed differently in normal and various malignant colon tissues, including squamous cell carcinoma, signet-ring cell carcinoma and adenocarcinoma. In normal colon gland epithelia, Ep-CAM antigen was mainly distributed on the basolateral membrane and in the region between the basolateral membrane and the cytoplastic part near the nuclei, whereas the expression pattern of colon malignancies was mainly on the whole surface of epithelia and the expression was much higher than the normal colon tissues. The staining pattern of tissue array showed in adenocarcinoma and papillary adenocarcinoma, and the expression of Ep-CAM was increased from grade I to grade III. MAbs against Ep-CAM might be useful for research on the structure and function of Ep-CAM and may have diagnostic and therapeutic value to various colon carcinomas.

A RARE PRESENTATION OF COLITIS CYSTICA PROFUNDA

A 51 yrs old women who underwent a screening colonoscopy. She has no significant gastrointestinal symptoms. Her past medical history was significant for Hypertension and she was treated with atenelol. She has a 1.2 cm pedunculated polyp in descending colon which was snared with standard setting. Histology of that polyp was 'mucus-containing cysts partially lined with colonic epithelium located in the submucosa is diagnostic of colitis cystica profunda'. In the colon the presence of histologically benign mucus-containing cysts partially lined with colonic epithelium located in the submucosa is diagnostic of colitis cystica profunda. Most instances of colitis cystica profunda are localized polypoid lesions located in the rectum. Diffuse or segmental colonic involvement may occur occasionally, usually in association with inflammatory bowel disease or diffuse colonic infections. Circumstantial evidence strongly suggests that colitis cystica profunda follows mucosal ulceration of varied etiologies and is probably due to submucosal entrapment of colonic glands following healing of ulceration. At the present time localized colitis cystica profunda is considered to be closely related to the solitary rectal ulcer syndrome, prolapsing mucosal folds in diverticular disease, and inflammatory cloacogenic polyp. All of these conditions are linked to mucosal prolapse and represent parts of the spectrum of what has recently been called the “mucosal prolapse syndrome.” Colitis cystica profunda has also been reported following radiation therapy and self-inflicted rectal trauma. There is also evidence that submucosal entrapment of colonic glandular tissue may be a complication of surgery due either to mechanical displacement of glandular tissue. In an early report six of nineteen patients with localized rectal colitis cystica profunda had previous rectal surgery.

Efficacy of aldosterone receptor antagonism in heart failure: Potential mechanisms

Results of the Randomized Aldactone Evaluation Study and the Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study indicate aldosterone receptor antagonism, together with angiotensin-converting enzyme inhibition and loop diuretics, is a most effective strategy in reducing risk for all-cause and cardiovascular-related mortality and morbidity in patients with symptomatic heart failure. Responsible mechanisms are likely multifactoral. As a circulating hormone, aldosterone has well-known endocrine properties that contribute to the pathophysiology of congestive heart failure. This includes Na+ resorption at the expense of K+ excretion in such tissues as kidneys, colon, sweat, and salivary glands. Mg2+ excretion at these sites is likewise enhanced by aldosterone, whereas adrenal aldosterone secretion is regulated by extracellular Mg2+. Other endocrine actions of aldosterone receptor-ligand binding include: a reduction in biologically active cytosolic-free Mg2+, with intracellular Ca2+ loading in nonepithelial cells such as peripheral blood mononuclear cells; its influence on endothelial cell function; and its central actions, including the choroid plexus, activity of the hypothalamic paraventricular nucleus, and autonomic nervous system. De novo generation of aldosterone within the cardiovasculature is recognized and findings suggest its auto/paracrine properties contribute to tissue repair. Each of these actions is interrupted by aldosterone receptor antagonism and therefore may contribute to its salutary response in heart failure.

P0620 TUMOR NECROSIS FACTOR (TNF) INDUCES MATRIX METALLOPROTEINASE-9 (MMP-9) EXPRESSION AND ACTIVITY IN MOUSE COLON

Introduction: TNF is a cytokine that regulates growth, migration, differentiation and apoptosis in normal and diseased intestinal epithelium through complex signaling mechanisms. MMP-9 belongs to a family of endopeptidases involved in tissue injury, repair, and tumorigenesis. MMP-9 is elevated in patients with inflammatory bowel disease (IBD), and its inhibition in murine models of colitis ameliorates disease severity. Since sustained MAP kinase activation is necessary for epithelial cell growth inhibition by TNF and MMP-9 expression, we investigated TNF regulation of MMP-9 expression and the involved TNF receptors in intestinal epithelium. Methods: Young adult mouse colon (YAMC), TNFR1−/ −, or TNFR2−/ − mouse colon epithelial (MCE) cells were treated with TNF (100 ng/ml) or EGF (10 ng/ml) for various times (1–24 h). Cellular lysates, total RNA and conditioned media were analyzed for MMP-9 expression by Western blot analysis, 2-D Difference Gel Electrophoresis and MALDI-TOF, or gene microarray and gelatin zymography, respectively. MMP-9 was studied by immunodetection in mouse colon after TNF injection (104 U/mouse) or in 2 models of IBD with increased endogenous TNF production, IL 10−/ − colitis and mice receiving water with dextran sulfate sodium (5% wt/vol) for 7 days. All were compared to appropriate controls. Results: TNF increased MMP-9 expression 6-fold in YAMC cells at 4 hours by gene microarray and proteomic screening assays. Furthermore, conditioned media derived from TNF-treated cells showed a 20-fold increase in both the active and pro-forms of MMP-9 and a decrease in MMP-2 expression by gelatin zymography. By comparison, EGF enhanced MMP-2 by 3–5-fold but had no effect on MMP-9 expression. TNF increased MMP-9 expression in TNFR2−/ −MCE but not TNFR1−/ −MCE cells, indicating TNFR1 is required for this effect. Treatment of mice with exogenous TNF increased MMP-9 expression in the epithelial and surrounding stromal cells at the base of colonic glands. Induced colitis, either in IL 10−/ − deficiency or exogenous dextran sulfate sodium administration, increased MMP-9 expression similarly. MMP-9 was increased in IL 10−/ − mice with colitis more than 20-fold compared to background control mice. Conclusion: In the mouse colon, MMP-9 expression is increased by TNF or colitis through TNFR1 in epithelial and surrounding stromal cells. Increased expression of MMP-9 through TNFR1 may contribute to epithelial damage, defective epithelial remodeling and tumorigenesis in IBD.

“Invasive Pattern” Disclosed with Magnifying Chromo-Endoscopy Is an Indication for Surgical Treatment of Sessile Colorectal Polypoid and Non-Polypoid Lesions

Background: by using magnifying colonoscopy it is possible to diagnose a typical pit pattern called invasive pattern (type V) which consists of irregular, distorted colonic gland crypts in a demarcated area. Such pattern is strongly associated with submucosal invasive cancer. Aims: to evaluate the effectiveness of magnifying chromo-endoscopy in differentiating the “invasive pattern” from the rest (“noninvasive patterns”) and assess the correlation with histopathological findings. Methods: a total of 53 sessile or flat colorectal lesions were evaluated in our hospital from December 2002 to October 2003 using chromoendoscopy with 0.4% indigo carmine and magnifying colonoscopy (Olympus CF-Q160Z). Pit pattern was classified as “invasive pattern” or “noninvasive pattern” during colonoscopy procedures. All lesions, endoscopically or surgically resected, were histologically evaluated and compared with the pit pattern diagnosis performed previously. Results: Of the 19 lesions endoscopically diagnosed as having an invasive pattern, 94.7% were submucosal invasive cancers (sm slight: 8.7%, sm deep: 86.0%), while in the remaining 34 lesions, endoscopically diagnosed as having a noninvasive pattern, 97.7% were intramucosal lesions (adenoma: 84.0%, m cancer: 13.7%). Conclusions: among the lesions which were endoscopically diagnosed as having an “invasive pattern” a high percentage was invasive cancer, especially sm deep invasive cancer, where surgical resection is undoubtedly the adequate treatment. On the other hand, the lesions, which were endoscopically diagnosed as having a “noninvasive pattern” were mostly intramucosal lesions, where endoscopic resection is feasible.

Increased expression of minichromosome maintenance protein 2 in active inflammatory bowel disease.

Minichromosome maintenance protein 2 (Mcm2) is an accurate indicator of cell cycle entry in tissue samples, but its expression in inflammatory bowel disease (IBD) has not previously been investigated. We have used immunohistochemistry to assess the expression of Mcm2, in comparison to the existing proliferation marker Ki-67, in active IBD and IBD without inflammatory activity. For this experimental study, sections from colonic biopsy and resection specimens of 48 patients with IBD (5 inactive/quiescent Crohn's disease (CD), 13 active CD, 19 inactive/quiescent ulcerative colitis (UC) and 11 active UC) and 15 normal controls were immunostained with antibodies to Mcm2 and Ki-67. The percentage of immunopositive epithelial nuclei was determined by calculating a labelling index (LI) for entire glands and for gland thirds (superficial, middle and basal). The Mcm2 LI was significantly increased in the superficial third of glands in active vs. inactive/quiescent UC (P < 0.0001) and active vs. inactive/quiescent CD (P = 0.001). The Mcm2 LI was significantly greater than the Ki-67 LI in active IBD, both in entire glands (P < 0.0001) and in the superficial third of glands (UC, P = 0.001; CD, P = 0.0002). Mcm2 LIs for entire glands were significantly higher in UC (all cases) compared to CD (all cases) (P = 0.032). There is increased cell cycle entry, as indicated by expression of Mcm2 and to a lesser extent Ki-67, in the superficial third of colonic glands in active IBD compared to inactive/quiescent IBD. Detection of Mcm2 may contribute to improved histological assessment of small tissue biopsies and may enable the development of a direct stool-based test for detection of active IBD and potentially for assessment of disease activity.

Colorectal xanthomas with polypoid lesion: report of 25 cases.

Little attention has been paid to colorectal xanthoma. To clarify the clinical and pathological features of colorectal xanthoma, we report 28 colorectal xanthomas biopsied from 25 patients. All were composed of typical xanthoma cells and showed polypoid configuration. Median age of the patients was 64 years and there were 15 men and 10 women. Diabetes mellitus, constipation, and hyperlipidemia were found in two, one, and seven patients, respectively. Seventeen (60.7%) of the 28 polyps were located in the sigmoid colon and the remaining 11 in the rectum. Twenty-three polyps (82.1%) were sessile. Twelve (60.0%) of twenty polyps that were recorded were reddish in color. Only two polyps revealed a yellowish tone. Microscopically, foamy cells were present in the lamina propria, but the submucosa did not contain foamy cells. Immunohistochemically, the foamy cells invariably expressed extensive positivity for CD68. The colonic glands showed a deformity in the case with moderate to intense density of the foamy cells. The surface epithelium showed a hyperplastic change in 22 (78.6%) xanthomas. The colonic glands in four xanthomas were also associated with hyperplastic changes. The basement membrane of the surface epithelium was often thickened. Cell debris and proliferation of the capillaries were observed just below the surface epithelium in 19 (67.9%) and 22 (78.6%) xanthomas, respectively. Previous mucosal minute injury was suggested as the pathogenesis of colorectal xanthomas. Colorectal xanthomas were not identical to gastric and esophageal xanthoma, endoscopically or microscopically. We prefer the term "xanthomatous polyp" rather than xanthoma in the colorectal region. They may be regarded as a novel type of colorectal non-neoplastic polyp.

Expression of gastric gland mucous cell-type mucin in normal and neoplastic human tissues.

Gastric gland mucous cells produce class III mucin, which is also found in Brunner's glands and mucous glands along the pancreaticobiliary tract, and in metaplasia and adenocarcinomas differentiating towards gastric mucosa. Recently, we showed that class III mucin possesses GlcNAcalpha1-->4Galbeta-->R, formed by alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT). Examining the tissue-specific expression of mucin epitopes is useful to clarify cell-lineage differentiation and to identify the site of origin of metastatic carcinomas in histological specimens. Formalin-fixed, paraffin-embedded tissue sections from esophagus, stomach, colon, liver, pancreas, lung, kidney, prostate, breast, and salivary gland resected for carcinoma, as well as salivary gland adenoma, colon adenoma, and metastatic adenocarcinoma of lymph nodes from stomach, pancreas, colon, and breast, were immunostained for MUC6, alpha4GnT, and GlcNAcalpha1-->4Galbeta-->R. These were all expressed in normal, metaplastic, and adenocarcinoma tissues of stomach, pancreas, and bile duct, and in pulmonary mucinous bronchioloalveolar carcinomas. Cells expressing alpha4GnT uniformly expressed GlcNAcalpha1-->4Galbeta-->R. Only MUC6 was expressed in normal salivary glands, pancreas, seminal vesicles, renal tubules, and colon adenomas, and in normal tissue and adenocarcinomas of prostate and breast. No tissues showed immunoreactivity for alpha4GnT alone. Immunohistochemistry (IHC) profiles were similar for metastatic carcinomas and primary carcinoma tissues. The IHC profiles for MUC6, alpha4GnT, and GlcNAcalpha1-->4Galbeta-->R may be diagnostically relevant.

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

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. 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. 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. 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.