Mucosal Pathology Research Articles

Tracheal Morphologic and Protein Alterations FollowingShort-Term Cigarette Mainstream Smoke Exposure to Rats

A short-term 5-day nose-only cigarette smoke exposure study was conducted in Fisher 344 rats to identify smoke-induced tracheal protein changes. Groups of 10 male and female 5 week old rats were assigned to 1 of 4 exposure groups. Animals received filtered air, or 75, 200 or 400 mg total particulate matter (TPM)/m3 of diluted 3R4F Kentucky reference cigarette mainstream smoke. Exposures were conducted for 3 hrs/day, for 5 consecutive days. Tracheas from half the rats were processed for pathology, and tracheas from the other half of the rats frozen immediately for proteomics. We hypothesized that smoke will activate tracheal inflammatory, apoptotic, proliferative, and stress-induced pathways. Mucosal epithelial toxicity from the inhaled material was evidenced by cilia shortening and loss of tracheal mucosal epithelium in smoke-exposed animals. Mucosal thinning occurred in all smoke-exposed groups with hyperplastic reparative responses in the 200 and 400 mg TPM/m3 groups. Tracheal lysates from control vs. treated animals were screened for 800 proteins using antibody-based microarray technology and subsequently the most changed proteins evaluated by Western blot. Tracheal proteins expressed at high levels that were markedly increased or decreased by smoke exposure depended on dose and gender and included caspase 5, ERK 1/2 and p38. Signaling pathways common between the morphologic and protein changes were stress, apoptosis, cell cycle control, cell proliferation and survival. Changes in identified proteins affected by smoke exposure were associated with tracheal mucosal pathology, may induce functional tracheal changes, and could serve as early indicators of tracheal damage and associated disease.

Surgical Management of Pneumosinus Dilatans Frontalis in the Setting of Chronic Rhinosinusitis and Type III Frontal Cell

Pneumosinus dilatans (PD) represents a rare lesion of unknown etiology in which progressive enlargement of an air-filled paranasal sinus results in cosmetic and functional complications. The absence of pathologic mucosa has traditionally been considered a hallmark of this disorder. A 24-year-old man presented with 2 years of chronic rhinosinusitis and recurrent, acute episodes of severe forehead pain with worsening outward prominence of the frontal sinus during air travel. Computed tomography and findings at surgery were notable for diffuse nonpolypoid inflammatory changes of the paranasal sinuses, a type III frontal sinus cell, and PD of the frontal sinus with severe deformity and thinning of the anterior table. A bicoronal approach was used for frontal sinus obliteration and cranioplasty. Excellent cosmetic and functional results were noted at the last follow-up. To our knowledge, this is the first report of PD frontalis presenting in the setting of chronic rhinosinusitis. Surgical management of this disorder requires consideration of both the functional and cosmetic issues.

The diagnostic utility of narrow band imaging magnifying endoscopy in clinical practice in a population with intermediate gastric cancer risk

Narrow band imaging (NBI) and NBI-magnifying endoscopy (ME) have been reported to facilitate the diagnosis of intestinal metaplasia (IM) and early gastric cancer (EGC) in high-risk populations. This study aimed at comparing the detection rate of focal gastric lesions by NBI against white light endoscopy (WLE), and examined the utility of NBI-ME in differentiating gastric mucosal pathology in a population with intermediate gastric cancer risk. Chinese patients aged 35-70 years undergoing diagnostic gastroscopy (GIF FQ260Z) by six experienced endoscopists were enrolled prospectively. The sequence of endoscopic evaluation was WLE followed by NBI. Focal lesions were re-examined by NBI-ME. The incremental diagnostic yield of NBI over WLE and ability of NBI-ME to differentiate gastric mucosal pathology were analyzed. Over a 30-month period, 458 patients (mean age: 52 years; men: 53.7%; Helicobacter pylori positive: 20.1%) were recruited. WLE detected a focal gastric lesion in 43.7% (200/458). WLE made a definitive diagnosis in 148 out of 200 patients (147 benign lesions and one gastric cancer), whereas NBI-ME correctly clarified the nature of the remaining 52 lesions (benign: 51; EGC: one). NBI detected an additional 69 out of 458 lesions (type 0_IIa: 91.3%; type 0_IIb: 8.7%) missed by WLE; the diagnoses based on NBI-ME were IM (67/69), EGC (1/69), and benign lesion (1/69). Interobserver agreement study revealed a κ statistic of 0.71. NBI detected IM missed by WLE. NBI-ME was useful in differentiating the pathology of focal gastric mucosal lesions.

Changes in Immunohistochemical Levels and Subcellular Localization After Therapy and Correlation and Colocalization With CD68 Suggest a Pathogenetic Role of Hsp60 in Ulcerative Colitis

In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed that Hsp60-classically a mitochondrial protein-was abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease.

Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques

AbstractIn SIV/HIV infection, the gastrointestinal tissue dominates as an important site because of the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells (DCs) in mediating immune activation and disease progression. We demonstrate that plasmacytoid DCs (pDCs) in the blood up-regulate β7-integrin and are rapidly recruited to the colorectum after a pathogenic SIV infection in rhesus macaques. These pDCs were capable of producing proinflammatory cytokines and primed a T cytotoxic 1 response in vitro. Consistent with the up-regulation of β7-integrin on pDCs, in vivo blockade of α4β7-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The up-regulation of β7-integrin expression on pDCs in the blood also was observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDCs influence immune activation in colorectal tissue after pathogenic immunodeficiency virus infections.

Evaluation of oral mucosal diseases: inter‐ and intra‐observer analyses

Essential to the diagnosis and management of oral mucosal diseases are visual evaluation and monitoring of the oral cavity. Digital photography has recently become an important clinical tool. The aims of this study were to (i) evaluate inter- and intra-observer differences between oral medicine and other dental specialists when assessing changes in oral mucosal pathology and (ii) assess the influence of calibration labels incorporated into the clinical images on the reliability and consistency of evaluation. Ten oral medicine specialists (OM) and 10 other dental specialists (DS) participated in the study. Pairs of images captured with an intraoral camera at two time points from 17 cases of mucosal diseases were presented to the participants. Each pair of photographs was presented with a calibration label (showing length and white to black hues) and again without one. The participants were asked to respond to a questionnaire evaluating changes in size, color, location, and severity for each image pair. Oral medicine specialists had better absolute agreement and consistency than DS when evaluating the changes in the images; however, these parameters did not exceed 52% in either group. The incorporation of a calibration label in the images increased agreement and consistency of evaluations in both groups. Follow-up evaluations of oral mucosal lesions are performed better by oral medicine practitioners compared to other dental specialists. The incorporation of a calibration label in the clinical images seems to enhance evaluation.

An analysis of oral biopsies extracted from 1995 to 2009, in an oral medicine and surgery unit in Galicia (Spain)

Objective: To conduct an analysis of the frequency of oral lesions in biopsies over a 14-year period in the Oral Medicine, Oral Surgery and Implantology Unit. Material and Methods: We conducted a retrospective study of biopsies removed from 1995-2009, recording data regarding age, sex, location of the lesions, biopsy types, anatomical and pathological diagnosis and definitive diagnosis. Results: Of the 562 patients studied, the average age was 51.8 years, with a standard deviation of 18.5 (range 5-96). The distribution by sex was 318 (56.6%) women and 244 (43.4%) men. The most common diagnostic category was mucosal pathologies in 37.9% of cases, followed by odontogenic cysts in 27.8%. Malignant tumors accounted for 3.9% of cases, oral squamous cell carcinomas were the most frequent malignancy, appearing in 22 cases. Bisphosphonate- related osteonecrosis of the jaws was the most common injury within the bone lesions group. Conclusion: Following the performance of 647 biopsies on 562 patients, we can say that the most common injury was radicular cysts (appearing in 108 cases), having found statistical differences in relation to the patients’ sex and age. Key words: Frequency, oral pathology, biopsy.

An Unusual Case of a Cheek Abscess in a Patient with Oral Submucous Fibrosis

Abscess formation in the soft tissues of the face is not an uncommonly encountered phenomenon in dental practice. However, the presence of oral mucosal pathologies can alter the manifestation of abscess formation. We report the illustration of a 51-year-old man, a known case of oral submucous fibrosis, who presented to us with a buccal abscess. After drainage of the abscess 2 days later, a piece of meat-bone was retrieved and found to be the causative factor. The paper discusses briefly the effects of such foreign body impaction and the clinician’s role in the management

Luminal Imaging in the 21st Century

AJR:197, July 2011 sive biopsy and intervention. But fluoroscopy endured because of its ability to gently image leaks, assess bowel motility, image the entirety of the bowel lumen, and quickly define difficult anatomy. Increasingly, imaging by fluoroscopy has been further supplanted by modern CT and MRI with tailored protocols that provide 3D cross-sectional imaging that vividly displays both intraluminal and extraluminal structures. Regarding CT, real concerns regarding radiation dose are starting to fade as low-dose techniques become more profound and commonplace. Many radiologists point to the increased objectivity of cross-sectional imaging, the rapidity of patient throughput, and perhaps economic gain as reasons for choosing cross-sectional imaging as the primary means to evaluate a range of diseases in the small and large bowel. Yet the shift to relatively static volumetric imaging has drawbacks, not the least of which include the erosion of our former hands-on visualization of dynamic bowel physiology and even our ability to diagnose certain classes of bowel disease. Performance of fluoroscopy promotes direct and enlightening interactions with patients, provides the sharpest available in-plane resolution for fine dense contrast etching that can reveal subtle mucosal pathology, allows interactive and natural patient positioning, can be low in radiation dose, and is the single best means to visualize in real-time subtle forms of intestinal dysmotility in response to contrast boluses and physical maneuvers. For example, many esophageal motility disorders are more readily diagnosed by real-time fluoroscopy than either optical endoscopic techniques or manometry. Unfortunately, quality fluoroscopy is a craft that demands not only a firm understanding of luminal disorders but also familiarity with the tricks of the trade to tailor examinations on the fly to suit the clinical question and bring out abnormalities in a visually compelling way. For a variety of reasons, Luminal Imaging in the 21st Century

Outcomes of middle meatal antrostomy after different surgical strategies

Conclusion: There was no significant difference in the postoperative outcomes between different surgical options for treating chronic maxillary sinusitis (CMS). Objective: We aimed to compare the improvement in symptoms, and changes in endoscopic and CT grade in patients undergoing different surgical management of the maxillary sinus ostium. Methods: In 32 patients (group A), the pathologic mucosa was radically removed with a power microdebrider. In 28 patients (group B), only part of the pathologic mucosa was removed; gross pathologic lesions were left in situ. In 38 patients (group C), only enlargement of the maxillary ostium was performed. Pre- and postoperative changes in symptoms, endoscopic polyp grade, and Lund-Mackay CT score were compared between groups. Results: In all groups, the symptoms were significantly improved after 1 month and throughout the follow-up period. Patients in groups A and B had meaningful improvement of the endoscopic polyp grade 1 month after surgery. The endoscopic grade of patients in group C at 1 and 3 months after surgery was not significantly different from the preoperative grade; however, there was a meaningful difference after 6 months. At 12 months after surgery, all groups had a significant decrease in the CT score (p < 0.01); however, there was no difference between groups.

Confocal laser endomicroscopy in gastrointestinal diseases

Confocal laser endomicroscopy (CLE) is a novel endoscopic technique permitting in vivo microscopy (optical biopsies) of the gastrointestinal mucosa. CLE has been studied in a multitude of diseases of the upper and lower gastrointestinal tract, including Barrett's esophagus, gastric inflammation and cancer, celiac disease, colorectal adenoma and carcinoma, and inflammatory bowel diseases. CLE has recently evolved and been studied for bile duct and liver imaging. CLE has shown overall high accuracy and enabled smart, targeted biopsies rather than untargeted sampling. Furthermore, the availability of real time microscopic information during endoscopy has immediate impact on therapeutic decisions and guides endoscopic interventions. CLE is also a unique tool for observation of (patho-)physiologic events in their natural environment (functional imaging) and has been linked to molecular imaging of gastrointestinal neoplasia in vivo, thereby broadening our understanding of mucosal pathology in clinical and basic science.

NSAID enteropathy detection by small bowel capsule endoscopy

Background and aims: The non-steroidal anti-inflammatory drugs (NSAID) induced mucosal lesions are well-known and well-defined in the gastroduodenal tract. Much less in known about the NSAID provoked alterations in the small bowel, however a significant proportion of the patients take NSAIDs with a daily frequency. The aim of our prospective pilot capsule endoscopy (CE) study was to evaluate the small bowel mucosal pathology in patients with continuous NSAID intake.

Characterization of a Three-Dimensional Mucosal Equivalent: Similarities and Differences with Native Oral Mucosa

The aim of this study was to create and characterize a tissue-engineered mucosal equivalent (TEM) that closely resembles native mucosa. TEM consists of human primary keratinocytes and fibroblasts isolated from biopsies taken from healthy donors and seeded onto a de-epidermized dermis and cultured for 14 days at the air/liquid interface. The structure of TEM was examined and compared with native nonkeratinizing oral mucosa (NNOM). The various components of the newly formed epidermal layer, basement membrane and underlying connective tissue were analyzed using immunohistochemistry. The mucosal substitute presented in this study showed a mature stratified squamous epithelium that was similar to that of native oral mucosa, as demonstrated by K19, desmoglein-3 and involucrin staining. In addition, the expression of basement membrane components collagen type IV, laminin-5 and integrin α6 and β4 in TEM proved to be consistent with native oral mucosa. The expression of PAS, Ki67, K10 and K13, however, appeared to be different in TEM compared to NNOM. Nevertheless, the similarities with native oral mucosa makes TEM a promising tool for studying the biology of mucosal pathologies such as oral mucositis or fibrosis as well as the development of new therapies.

Does imaging the oesophagus, stomach and duodenum with the ESO 2 pillcam compare favourably with conventional video-endoscopy in patients with dyspepsia?

IntroductionOesophageal capsule endoscopy (ESO 2) has been developed to image the oesophageal mucosa and compares with endoscopy (OGD).1 With a battery life of 30 min, the capsule transmits gastric and...

Comparison of COX-2, Ki-67, and BCL-2 expression in normal esophageal mucosa, Barrett’s esophagus, dysplasia, and adenocarcinoma with postablation mucosa and implications for ablative therapies

The neosquamous mucosa that replaces ablated esophageal endothelium after endoscopic mucosal ablation for Barrett's metaplasia or high-grade dysplasia (HGD) may retain buried glandular tissue. This study aimed to assess the neoplastic potential, cellular proliferation, and resistance to apoptosis of this buried glandular tissue by measuring COX-2, Ki-67, and BCL-2 expression in these tissues. A prospectively collected database was sourced for esophageal biopsy specimens with normal histologic appearance, Barrett's metaplasia, HGD, adenocarcinoma, and postablation mucosa comprising ablated Barrett's and ablated HGD. Quantitative analysis of cellular markers was achieved immunohistochemically using monoclonal antibodies for the COX-2 enzyme (suggesting increased neoplastic potential), Ki-67 antigen (suggesting cellular proliferation), and BCL-2 oncoprotein (suggesting oncogenic resistance to apoptosis). Grading was performed by independent, blinded observers, and the pre- and postablation cellular disparities were subsequently noted. The buried glandular elements of postablation mucosa demonstrated universally greater COX-2, Ki-67, and BCL-2 expression than normal esophagus. Barrett's esophagus and adenocarcinoma expressed significantly greater COX-2 and Ki-67 at the deep glandular level than postablation mucosa. HGD demonstrated greater Ki-67 expression than the postablation tissue but only within the superficial glands. Overall, the expression of COX-2 correlated significantly with Ki-67 expression in deep glandular tissue. Ablation of pathologic mucosa in Barrett's esophagus and HGD reduces the expression of some markers of neoplastic behavior. However, the buried glandular tissue of the postablation mucosa still exhibits a higher expression than normal esophageal epithelium. This has potential implications for the follow-up treatment of these patients because it is unclear whether the true risk of neoplastic progression is adequately reduced. A more comprehensive study is required to address this issue.

Inflammatory Bowel Disease-Associated Interleukin-33 Is Preferentially Expressed in Ulceration-Associated Myofibroblasts

Interleukin-33 (IL-33) is a novel member of the interleukin-1 family that induces mucosal pathology in vivo and may drive fibrosis development and angiogenesis. To address its potential role in inflammatory bowel disease, we explored its tissue expression in biopsy specimens from untreated ulcerative colitis patients, observing a 2.6-fold up-regulation of IL-33 mRNA levels, compared to controls. Immunohistochemical analyses of surgical specimens showed that a prominent source of IL-33 in ulcerative colitis lesions were ulceration-associated myofibroblasts that co-expressed the fibroblast marker heat shock protein 47, platelet-derived growth factor receptor (PDGFR)β, and, in part, the myofibroblast marker α-smooth muscle actin (SMA). In contrast, IL-33-positive myofibroblasts were almost absent near the deep fissures seen in Crohn's disease. A screen of known and putative activators of IL-33 in cultured fibroblasts revealed that the Toll-like receptor-3 agonist poly (I:C) was among the strongest inducers of IL-33 and that it synergized with transforming growth factor-β, a combination also known to boost myofibroblast differentiation. Experimental wound healing in rat skin revealed that the de novo induction of IL-33 in pericytes and the possible activation of scattered, tissue-resident IL-33(+)PDGFRβ(+)αSMA(-) fibroblast-like cells were early events that preceded the later appearance of IL-33(+)PDGFRβ(+)αSMA(+) cells. In conclusion, our data point to a novel role for IL-33 in mucosal healing and wound repair and to an interesting difference between ulcerative colitis and Crohn's disease.

Direct Inoculation of Mycobacteriumavium Subspecies Paratuberculosis Into Ileocecal Peyer’s Patches Results in Colonization of the Intestine in a Calf Model

The objective of this study was to develop an intestinal model of Mycobacterium avium subspecies paratuberculosis (Map) infection in the calf for evaluation of mucosal pathology and local and systemic immunologic responses. Map was inoculated into Peyer's patches of young calves using a right flank surgical approach in standing calves to exteriorize the ileocecal junction. Inoculum doses ranging from 10(3) to 10(9) colony-forming units of strain K10 Map were injected through the serosal surface into Peyer's patches of the distal ileum near the ileocecal valve. Fecal samples were collected for culture from each calf weekly until termination of the study. Calves were necropsied at 7, 30, 60, and 90 days after infection, when inoculation sites, lymph nodes, spleen, and peripheral blood were collected for evaluation. Ileocecal lymph nodes were consistently colonized by Map in the 10(5) to 10(9) groups. The ileocecal valve was also colonized in 10(7) and 10(9) groups. This correlated with fecal culture results as infected calves intermittently shed Map in their feces throughout the study. Granulomatous lesions with giant cells and acid-fast bacilli at the ileocecal junction, ileocecal lymph nodes, and lamina propria of high-dose animals (10(7) and 10(9)) were identified from each time point. Flow cytometry was used to detect antigen-specific production of interferon-γ and interleukin-4 locally (ileocecal lymph node) and systemically (peripheral blood mononuclear cells), which defined distinct immunologic profiles in low-dose and high-dose calves. This study demonstrates intestinal Map infection via Peyer's patch inoculation, a novel model with many shared features of natural Map infection.

Agreement between Endoscopic Ultrasound and Endoscopic Mucosal Resection Pathology in Staging Mucosal Esophageal Cancers

Agreement between Endoscopic Ultrasound and Endoscopic Mucosal Resection Pathology in Staging Mucosal Esophageal Cancers

Evidence of Intestinal Inflammation in Patients With Cystic Fibrosis

Treatment with pancreatic enzymes fails to completely correct malabsorption and gastrointestinal symptoms in patients with cystic fibrosis (CF). The aim of the present study was to examine the small intestine of patients with CF without overt evidence of gastrointestinal disease using capsule endoscopy (CE). Patients with CF received the agile patency capsule and, depending on the result of that procedure, then underwent standard CE using the PillCam SB capsule (Given Imaging, Yokneam, Israel). A stool specimen was taken on the same day as the CE for determination of the calprotectin level. Forty-two patients with CF ages 10 to 36 years were included; 29 had pancreatic insufficiency. One patient failed to excrete the patency capsule after 36 hours and was withdrawn from the study. Pulmonary function was mild to moderate with FEV1 68.5% +/- 16% predicted. Review of the CE videos showed that most of the patients had varying degrees of diffuse areas of inflammatory findings in the small bowel including edema, erythema, mucosal breaks, and frank ulcerations. There were no adverse events. Fecal calprotectin levels were markedly high in patients with pancreatic insufficiency, 258 microg/g (normal <50). Small bowel mucosal pathology may be detected using CE in most of the patients with CF. The high fecal calprotectin levels found are suggestive of mucosal inflammation, which may correlate with the CE findings. Additional study is required to examine the possible relation of these mucosal lesions, which may be part of a newly identified enteropathy associated with CF, with persistent intestinal malabsorption in many of these patients.

La rectocolite hémorragique chez le noir africain. Analyse de 20 cas au Burkina Faso

The authors conducted a study concerning ulcerative colitis in black patients, from 20 cases observed in Burkina Faso — 11 men and 9 women, with an average age of 31 and 15, respectively. Only one patient presented a family background of inflammatory bowl disease (IBD). A releasing or facilitating psychological factor was recognized in all the patients. The symptoms were dominated by glairybloody diarrhoea or diarrhoea streaked with blood (65% of cases), abdominal pains (50% of cases), anal diseases (35% of cases), wasting away (30% of cases) and clinical anaemia (25 of cases). Endoscopy showed pathological mucosa in all cases (100%), haemorrhages in 13 cases (65%), ulcerations in 13 cases (65%), pseudopolypus in one case (5%) and rectal polypus in 2 cases (10%). Histology was in favour of diagnosis in all the cases. The patients were treated with mesalazin and corticotherapy in 15 cases. Remission was obtained with a recurrence in 7 cases. Complications were observed. In conclusion, although ulcerative colitis is a rare entity with black patients; its incidence is growing in our country. The prescription of lower digestive endoscopy examination could allow a better diagnosis of this disease.