Squamous Mucosa Research Articles

Osteosarcoma of the maxilla presenting as a chronic pyogenic abscess: A case report.

IntroductionOsteosarcoma of the maxilla is recorded as the least common of all bone malignancies. It exhibits a clinical behavior and natural history distinct from their counterparts of the trunk and extremities. Transformation from a chronic pyogenic abscess of the maxilla is even more unusual.Case summaryA 70 year old lady presented to our hospital with a hard, fixed and tender bony swelling in her left cheek. She had initially presented to a different hospital with a similar presentation which was excised after imaging and post excision was found to be a chronic pyogenic abscess. The swelling reappeared within one year and on re-excision was found to be a low grade paraosteal osteosarcoma of the hard palate. CECT and PET-CT work-up at our hospital showed a left maxillary sinus growth with prominent neck lymph nodes along with mediastinal lymphadenopathy and pulmonary metastasis. Final histopathology revealed ulcerated stratified squamous epithelium mucosa overlying a lesion suggestive of osteosarcoma.DiscussionComplete surgical excision with negative margins continues to be the mainstay of treatment, but osteosarcomas of maxillofacial region pose difficulties in obtaining tumour free margins because of their complex anatomy around the cranium. Surgery may be complemented by radiotherapy with or without chemotherapy. Small size of the tumour and low-grade histology have been assumed to reflect a better prognosis.ConclusionOsteosarcoma of maxillofacial region has variable appearance clinically as well as radiologically posing a diagnostic challenge for clinicians. Any chronic abscess or recurrent cheek swelling thus necessitates further suspicion and requires a full work-up to rule out this high risk malignancy.

Insights Into the Oral Microbiome and Barrett's Esophagus Early Detection: A Narrative Review.

Barrett's esophagus (BE) prevalence has increased steadily over the past several decades and continues to be the only known precursor of esophageal adenocarcinoma. The exact cause of BE is still unknown. Most evidence has linked BE to gastroesophageal reflux disease, which injures squamous esophageal mucosa and can result in the development of columnar epithelium with intestinal metaplasia. However, this relationship is inconsistent—not all patients with severe gastroesophageal reflux disease develop BE. There is increasing evidence that the host microbiome spanning the oral and esophageal environments differs in patients with and without BE. Several studies have documented the oral and esophageal microbiome's composition for BE with inconsistent findings. The scarcity and inconsistency of the literature and the dynamic phenomena of microbiota all warrant further studies to validate the findings and dissect the effects of oral microbiota, which are considered a viable proxy to represent esophageal microbiota by many researchers. This review aims to summarize the variability of the oral and esophageal microbiome in BE by using the example of Streptococcus to discuss the limitations of the current studies and suggest future directions. Further characterization of the sensitivity and specificity of the oral microbiome as a potential risk prediction or prevention marker of BE is critical, which will help develop noninvasive early detection methods for BE, esophageal adenocarcinoma, and other esophageal diseases.

Histologic Findings in Mucosa and Muscularis Propria Biopsied During Peroral Endoscopic Myotomy in Patients With Achalasia

BackgroundPeroral endoscopic myotomy (POEM) has been increasingly used to treat achalasia. Previous studies have reported high frequency of muscular eosinophilic infiltration in achalasia. Esophageal mucosal changes in achalasia have only been studied in esophagectomy specimens. Cardia mucosal changes in achalasia have not been reported previously. We aimed to further characterize the esophageal, gastric cardia, and muscularis propria changes in achalasia.MethodsThis was a pilot study. Patients with clinically and radiographically confirmed achalasia who underwent POEM were enrolled in the study. Mucosal biopsies were taken 1 cm proximal and 1 cm distal to the gastroesophageal junction, and muscularis propria biopsies were taken from the mid esophagus. Tissues were submitted for histological evaluation.ResultsEighteen patients (10 male and eight female, mean age: 60.7 (standard deviation (SD): 13) years) were enrolled in this pilot study. Nine patients had type II achalasia, two type III, one type I, five esophageal gastric outlet obstruction, and one unspecific type achalasia. The mean duration of symptoms prior to POEM was 79 (range 1 - 480) months. All patients had a dilated esophagus on examination, but no endoscopic evidence of Barrett’s esophagus. Esophageal, gastric cardia, and muscular biopsies were performed in 17, 13, and 17 patients, respectively. Basal hyperplasia, spongiosis, ballooning, and parakeratosis were seen in 92.3%, 100%, 100%, and 76.5% of cases, respectively. Intraepithelial lymphocytosis was seen in 70.5% of cases, and active esophagitis was seen in 23.5% of case. Six (35.3%) cases had few intraepithelial eosinophils, but none of them had > 15 eosinophils per high power field. Histologic findings in gastric cardia mucosa included carditis (69.2%), H. pylori gastritis (7.6%), and reactive gastropathy (15.4%). One case (7.6%) showed low-grade dysplasia arising from intestinal metaplasia in the cardia. Absence of ganglion cells in the muscular biopsies was noted in 88.2% of cases, and the remaining two showed rare residual ganglion cells with ganglionitis in one case (5.8%). Muscular atrophy and interstitial fibrosis were observed in 52.9% and 82.3% of the cases, respectively. Two cases (11.7%) had eosinophilic inflammation in the muscularis propria and one of them was accompanied by lymphocytic inflammation.ConclusionsMuscular biopsies in our study revealed loss of ganglion cells, supporting the view that achalasia is a primary esophageal disease with ganglion cell depletion. Squamous mucosa in achalasia showed changes mimicking reflux and lymphocytic esophagitis. Cardia mucosa in achalasia patients often were inflamed and uncommonly showed intestinal metaplasia and glandular dysplasia.

Prevalence of gastric ulcer syndrome in horses with different exercise intensity

Gastric ulcers or equine gastric ulcer syndrome (EGUS) is a common pathology in horses of different breeds. The objective of our research work was to investigate and determine the prevalence and severity of equine gastric ulcer syndrome (EGUS) in population of n = 28 riding horses with periods of physical activity and training intensity. Two breeds were presented in this study: English Thoroughbred (n = 15) and Ukrainian riding horse (n = 13). Horses were two age groups 3–7 and 8–16 years, including 17 mares and 11 geldings. Gastric endoscopy was performed as a diagnostic tool using a 3m video endoscope. Mucosal defects was evaluated using grading system proposed by (Equine Gastric Ulcer Council 0–4 grading system) ranging from 0 (normal mucosa with no lesions) to 4 (diffuse ulceration of mucosa with deep lesions). The study was conducted in two periods. Each period is related to different workload with mixed intensity in exercise during training program. The results of gastroscopic examination of the stomach indicate the prevalence of EGUS in 35.7 % during the first stage in horses with mild training. The severity of mucosal defect during this period which were related to grade 1 was shown in 10.7 % of horses, 2 – 21.4 %, 3 – 10.7 % and 4 – 0 %. Difference in results was found in the presence and severity of gastric ulcers between two periods in this study. During period of intermediate training the prevalence of EGUS was 46.4 % with severity of mucosal defect grade 1 presented in 14.2 % of affected horses, 2 – 28.5 %, 3 – 14.2 % and 4 – 3.5 %. Ulcerations on squamous gastric mucosa was diagnosed more often during each period (35.7 – 50 %) compare to glandular (7.1 – 10.7 %). The study confirms association between training intensity and gastric ulceration in two breed of horses. The prevalence and severity is dependent of the training intensity.

93 Effect of replacing part of concentrates with pelleted alfalfa on squamous gastric ulcers in exercised trotters.

Horses at heavy work have a high prevalence of Equine Squamous Gastric Disease (ESGD). Exposure of the squamous mucosa to HCl causes damages, which can be more severe with acids produced by bacterial fermentation of starch and soluble sugars at pH ≤ 4. Among low-starch feedstuffs commonly fed to horses, alfalfa ( Medicago sativa ) has the strongest buffering capacity, and promising data on its healing impact have been observed in preliminary trials. In this field study, the effect of alfalfa was investigated on ESGD prevention and healing in trained horses. In 4 training centers, 80 exercised trotters (“very heavy work” based on NRC 2007) and housed in individual boxes were followed for 42 d. Gastroscopies were performed on D0, D21, D42 by an equine practitioner in a blind assessment. ESGD severity was scored using the EGUS Council 0–4 scoring system. On D0, horses were divided into 2 homogeneous groups on each center based on ESGD initial score, age and sex. Horses in control group (CON; n = 40) kept their previous ration (hay ad lib and 6.6 ± 1.8kg pellets; 4.5 ± 1.5g starch/kg BW/d). In the alfalfa group (ALF; n = 40), 50% (vol/vol) of pelleted concentrates were replaced by pelleted dehydrated alfalfa (hay ad lib and 6.3 ± 1.6kg pellets; 2.3 ± 0.7g starch/kg BW/d). Rations were almost isoenergy and isoprotein per center. Training continued without difference between groups. Horses were categorized in “no or mild ulcerations” (NMU – grades 0, 1, 2) and “severe ulcerations” (SU – grades 3, 4). Among the NMU horses at D0 (n = 49), preventive effect of the diet was determined by comparing number of NMU and SU horses at D21 and D42 using a Chi-2 test. Curative effect was evaluated by comparing number of NMU and SU horses at D21 and D42 among the SU horses at D0 (n = 31). No significant effect of the diet was measured on ESGD prevention or healing. In our study, ALF rations remained higher in starch compared with previous studies. In addition, in the 2 trials that showed a beneficial effect of alfalfa, horses were not intensively trained and alfalfa was fed as fodder. Feeding alfalfa pellets may have limited the preventive effect associated with saliva and formation of a protective layer on top of the gastric chyme.

54 Evaluation of gastric health in cribbing horses fed a digestive support supplement

Cribbing is a stereotypic oral behavior whereby the horse places its incisors on a fixed object, arches its neck, pulls against the object, and emits an audible grunt. Cribbing behavior (CB) has been associated with gastrointestinal (GI) dysfunction and gastric ulceration. This randomized crossover study tested the hypothesis that dietary inclusion of a commercially available equine GI support supplement (Legends Gastrocare, Cargill, Wayzata, MN) would alter the GI environment and gastric ulcer severity in normal and cribbing horses. Mature Quarter Horses with CB (n = 4) and sex-matched non-cribbing controls (NCB; n = 4) were randomly assigned to receive either a GI support supplement (TRT) or placebo for 21 d, followed by a 2-wk washout period. Treatment groups were then switched and horses were treated for an additional 21 d. Before and after each treatment period, gastric and fecal pH were measured, and gastric ulcer severity was evaluated via endoscopic examination using an established grading system for squamous (0–4) and glandular gastric ulceration (0–1). Horses were acclimated for 2 wk before the start of the study, and throughout the study were individually stalled 16 h/d and fed bermudagrass hay (1.2% BW, DM basis) and concentrate (0.5% BW) and turned out in pairs in paddocks 8 h/d. Data were analyzed by mixed-model ANOVA with treatment, cribbing status (CB or NCB) and period included as fixed effects, and horse as a random effect. Data are presented as means ± SD. Fecal pH (6.5 ± 0.1) and gastric pH (2.9 ± 0.5) were similar between CB and NCB horses and were unaffected by TRT. Squamous mucosa ulcer scores did not differ between CB and NCB, and were unaffected by TRT. However, within CB horses, squamous ulcer severity scores were greater (indicating more severe ulceration) ( P = 0.003) with TRT (3.9 ± 0.6) than placebo (1.4 ± 0.3). Based on this pilot study, administration of a commercial GI support supplement did not alter gastric or fecal pH in normal or CB horses. Ongoing serum cortisol, serum gastrin, and microbiome analyses may help to explain the differences in gastric ulceration severity noted in CB horses when receiving TRT versus placebo. Collectively, these findings add to the growing body of literature regarding GI environment and pathophysiology in horses exhibiting CB.

Artificial intelligence aided measurement of cervical squamous epithelial thickness and its correlation with cervical precancerous lesions

Objective: To study the thickness of cervical squamous epithelia and its correlation with cervical precancerous lesions. Methods: We selected 495 HE slides of 209 cervical biopsies from January 2020 to June 2020 in the Department of Pathology, the First and Seventh Medical Center of the PLA General Hospital, including 173 slides with low grade squamous intraepithelial lesion (LSIL) and 214 slides with high grade squamous intraepithelial lesion (HSIL). Artificial intelligence labeling software was used to assist in measuring the epithelial thickness of normal cervical squamous epithelium, LSIL and HSIL of each slide. The thickest, thinnest, and middle widths of epithelial thickness were measured, respectively. Average epithelial thickness was defined as the sum of the above three widths divided by 3. The correlation statistical analysis was performed by combining the data of age and pathological diagnosis. Results: The average thickness of normal cervical squamous mucosa was (245.83±91.40) μm, which was (222.42±81.22) μm and was (195.95±66.59) μm in LSIL and HISL epithelial respectively (F=27.09, P<0.01). The average cell layers of normal cervical squamous epithelium was (15.5±4.2) layers, which of LSIL was (14.8±4.8) layers, and that of HSIL was (15.8±4.8) layers. The differences among normal, LSIL and HSIL were not statistically significant (P>0.05). Further statistical analysis was stratified by age (≤30 years, 31-40 years, 41-50 years, 51-60 years, and >60 years), the results of Pearson correlation analysis showed that the thickness of normal cervical squamous epithelial gradually thinned with age (correlation coefficient r=-0.141 9, P<0.05), while LSIL and HSIL epithelial thickness had significant correlation with age (P>0.05). In the subgroup of ≤50 years old, the epithelial thickness of normal squamous epithelium was the thickest, followed by LSIL, and HSIL epithelial thickness was the thinnest. The differences were statistically significant (P<0.05). While in the subgroup of >50 years, the differences were not statistically significant (P>0.05). Conclusions: The cervical squamous epithelium gradually becomes thinner with the degree of precancerous lesions increasing among patients of ≤50 years old. However, after age of 50 years, with the onset of menopause, the normal mucosal epithelium is becoming atrophy, so that mucosal thickness is no longer correlated with the extent of the lesion. In addition, it is suggested that the cervical vinegar white test performance during colposcopy is related to the protein changes in the mucosal epithelial cells, but not directly related to the thickness of the epithelial layer.

Osteonecrosis of mandible secondary to sickle cell crisis

<h3>Background</h3> Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy causing amino acid substitution in the B-hemoglobin chain of erythrocytes. SCD affects 1 in 500 African American children. SCD is associated with multiorgan morbidity and significant reduction in life expectancy. Vaso-occlusive crisis associated with SCD is characterized by acute pain and local tissue hypoxia and necrosis. The extremities, back, and chest are frequently affected, and jaw involvement is very rare. To the best of our knowledge, only 3 cases of jaw osteonecrosis secondary to SCD have been reported in the English-language literature. <h3>Case Summary</h3> A 38-year-old African American man with a history of SCD and avascular necrosis of the hips presented to an emergency department with severe pain in his back, legs, and chest due to a vaso-occlusive episode precipitated by physical overexertion. A few days later, the patient complained of left jaw pain and paresthesia. Computed tomography (CT) of the head with intravenous (IV) contrast, maxillofacial CT with IV contrast, and the remainder of the neurologic examinations were unremarkable. The oral medicine service was consulted, and physical examination of the patient demonstrated lingual gingival tissue swelling of the lower left molars. The mass was nonfluctuant with ulceration causing malalignment of tooth number 18. Bone biopsy revealed squamous mucosa with hemorrhagic foci, ulceration, and ectatic blood vessels with fragments of necrotic bone consistent with osteonecrosis. At the patient's 2-week follow-up visit, a small area of exposed necrotic bone was noted in the affected area. Maxillofacial CT without IV contrast showed mixed radiolucency and sclerosis with dehiscence along the lingual cortex of the posterior mandibular body and along the cortex of the retromolar trigone. Chlorhexidine gluconate 0.12% oral solution was prescribed, and debridement of the left posterior mandible and extraction of the lower left molars with local flap reconstruction were recommended by an oral and maxillofacial surgeon. The patient did not return for follow-up management. <h3>Conclusions</h3> Acute pain and chronic vasculopathy are significant complications of SCD. Jaw involvement in SCD is very rare, as illustrated in this case. It is important for oral health care professionals to understand the pathophysiology and clinical manifestations of SCD.

Bowen’s Disease of the Anal Canal Treated with Radiation Therapy: A Case Report

Bowen’s disease, also known as intraepithelial neoplasia, is a very slow-growing carcinoma in situ. It can progress to an invasive squamous cell cancer and infiltrate mucosa or skin in 3 to 5% of cases. The anal localization of this disease is very rare. Surgical resection is the standard of treatment. Radiotherapy keeps its place in recurrent or unresectable cases. We report a case of Bowen’s anal canal disease in order to verify the effectiveness of Radiotherapy. He is a 59-years-old patient diagnosed with Bowen’s anal canal disease at the National Institute of Oncology in Rabat. He was treated with exclusive radiotherapy at a dose of 60 Gray in 30 fractions over 49 days. The evolution was marked by a complete clinical and radiological response and preservation of the anal sphincter with an 18 months follow-up.

Detection of Barrett's Neoplasia with Near-Infrared Fluorescent Heterodimeric Peptide: Feasibility Results from a Phase 1 Study

Background: Esophageal adenocarcinoma is a molecularly heterogeneous disease that is rising rapidly in incidence and has a poor prognosis. Current methods of endoscopic surveillance in patients with Barrett’s esophagus (BE) using white light illumination are not sensitive to pre-malignant lesions that are flat in appearance and patchy in distribution. We aim to demonstrate specific binding by a peptide heterodimer to Barrett’s neoplasia in human subjects. Methods: Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800. The near-infrared (NIR)-labeled heterodimer was synthesized using current good manufacturing practices (cGMP) methods and performed pharmacology/toxicology study in animals using good laboratory practices (GLP). The NIR contrast agent was topically administered in the distal esophagus of patients with history of neoplastic BE undergoing endoscopic therapy or surveillance. Fluorescence images were collected using a flexible fiber accessory passed through the instrument channel of an upper endoscope. Fluorescence images were collected from n = 31 BE patients, and a deep learning model was used to segment the target (T) and background (B) regions to calculate the T/B ratio. Findings: Between August 2018 and November 2020, 25 human subjects were enrolled for safety study and 31 patients for either evaluation or therapy of Barrett’s neoplasia were recruited for imaging study. No adverse events attributed to the heterodimer were found. The mean T/B ratio in patients for HGD and EAC were significantly greater than that for BE with low grade dysplasia, without dysplasia, or squamous mucosa. At a T/B ratio of 1.5, 94.1% sensitivity and 92.6% specificity for detection of Barrett’s neoplasia was achieved with an AUC = 0.95. The presence of Barrett’s neoplasia was validated by pathological assessment of resected specimens. Interpretation: This “first-in-human” clinical study demonstrates feasibility to detect early Barrett’s neoplasia using a NIR-labeled peptide heterodimer. Trial Registration: This study was registered online at ClinicalTrials.gov (NCT03643068) Funding National Institutes of Health. Declaration of Interest: Authors (JC, TDW) are inventors on patents filed by the University of Michigan on the peptide heterodimer used in this study. Author (EJS) is an inventor on patents filed by the University of Washington on the multimodal scanning fiber endoscope (mmSFE) used in this study. The other authors disclose no conflicts. Ethical Approval: All study protocols were reviewed and approved by the Institutional Review Board (IRB) at Michigan Medicine

A clinically interpretable convolutional neural network for the real-time prediction of early squamous cell cancer of the esophagus: comparing diagnostic performance with a panel of expert European and Asian endoscopists

Intrapapillary capillary loops (IPCLs) are microvascular structures that correlate with the invasion depth of early squamous cell neoplasia and allow accurate prediction of histology. Artificial intelligence may improve human recognition of IPCL patterns and prediction of histology to allow prompt access to endoscopic therapy for early squamous cell neoplasia where appropriate. One hundred fifteen patients were recruited at 2 academic Taiwanese hospitals. Magnification endoscopy narrow-band imaging videos of squamous mucosa were labeled as dysplastic or normal according to their histology, and IPCL patterns were classified by consensus of 3 experienced clinicians. A convolutional neural network (CNN) was trained to classify IPCLs, using 67,742 high-quality magnification endoscopy narrow-band images by 5-fold cross validation. Performance measures were calculated to give an average F1 score, accuracy, sensitivity, and specificity. A panel of 5 Asian and 4 European experts predicted the histology of a random selection of 158 images using the Japanese Endoscopic Society IPCL classification; accuracy, sensitivity, specificity, positive and negative predictive values were calculated. Expert European Union (EU) and Asian endoscopists attained F1 scores (a measure of binary classification accuracy) of 97.0% and 98%, respectively. Sensitivity and accuracy of the EU and Asian clinicians were 97%, 98% and 96.9%, 97.1%, respectively. The CNN average F1 score was 94%, sensitivity 93.7%, and accuracy 91.7%. Our CNN operates at video rate and generates class activation maps that can be used to visually validate CNN predictions. We report a clinically interpretable CNN developed to predict histology based on IPCL patterns, in real time, using the largest reported dataset of images for this purpose. Our CNN achieved diagnostic performance comparable with an expert panel of endoscopists.

Toward improved endoscopic surveillance with multidiameter single fiber reflectance spectroscopy in patients with Barrett's esophagus.

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non-dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non-dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.

Novel In Vivo Mouse Cryoablation Model to Explore Unique Therapeutic Approaches for Premalignant Columnar Lesions

Patients with epithelial metaplasias have an increased risk of developing malignancies. In Barrett’s esophagus, neo-columnar epithelium develops proximal to the squamous-columnar junction (SCJ) in the esophagus as the result of prolonged exposure to bile and acid reflux. Patients require lifetime periodic surveillance, due to lack of effective eradication therapies. The shortage of innovative treatment options is mostly attributable to the paucity of adequate in vivo models of neo-columnar epithelium regeneration. This protocol describes the generation of a cryoablation model to study regeneration of neo-epithelia at the SCJ. Cryoablation of the columnar and squamous mucosa at the SCJ was achieved through local application of liquid N2O in wild-type and reporter mice in combination with acid suppression. Acid suppression alone, showed restoration of the SCJ with normal histological features of both the neo-columnar and neo-squamous epithelium within 14 days. As a proof of principle, mice were treated with mNoggin, an inhibitor of bone morphogenetic proteins (BMPs), which are involved in the development of columnar epithelia. Local application of mNoggin to the ablated area at the SCJ significantly reduced the development of the neo-columnar mucosa. Although this model does not faithfully recapitulate the exact characteristics of Barrett’s esophagus, it is a well-suited tool to study the mechanisms of therapeutic inhibition of neo-columnar regeneration. It therefore represents an efficient and easy platform to test novel pharmacological therapies for treatment of neo-epithelial lesions at the SCJ.

Endoscopic features of buried Barrett’s mucosa

Buried Barrett's mucosa is defined as intestinal metaplasia that is "buried" under the normal-appearing squamous epithelium. This can occur in Barrett's esophagus with or without previous endoscopic therapy. Dysplasia and neoplasia within buried Barrett's mucosa have also been reported. However, endoscopic features of buried Barrett's mucosa have not been described. At our tertiary referral center for Barrett's esophagus, several endoscopic features have been observed in patients who were found to have buried Barrett's mucosa on histology. These features are squamous epithelium which is (1) darker pink on white-light and darker brown on narrow-band imaging and/or (2) has a slightly raised or nodular appearance. It was also observed that either of these 2 features is frequently seen adjacent to a Barrett's mucosa island. This study aimed to (1) evaluate the diagnostic accuracy of these endoscopic features, and (2) evaluate the frequency of endoscopically identifiable buried Barrett's mucosa in patients with dysplastic Barrett's esophagus, before and after endoscopic eradication therapy. This was a retrospective analysis of a prospectively observed cohort of all cases of dysplastic Barrett's esophagus referred to St Vincent's Hospital, Melbourne. Endoscopy documentation software and histopathology reports of esophageal biopsy and EMR specimens between March 2013 and March 2019 were searched for terms "buried" or "subsquamous" Barrett's mucosa. Endoscopic reports, images, and histopathology reports of suspected buried Barrett's mucosa were then reviewed to apply the endoscopic features and correlate with the histologic diagnosis. In a cohort of 506 patients with dysplastic Barrett's esophagus, 33 (7%) patients (73% male, median age at referral 70.5 years) had buried Barrett's mucosa on histology. Twenty-seven (82%) patients had previous treatment for dysplastic Barrett's esophagus; radiofrequency in 2 (6%), EMR in 4 (12%), and both modalities in 21 (64%). Six (18%) had no previous treatment. Histologically confirmed buried Barrett's mucosa was suspected at endoscopy in 26 patients (79%). Endoscopic features were (1) darker pink or darker brown mucosa underneath squamous epithelium (24%), (2) raised areas underneath squamous mucosa (27%), and both features present concurrently (27%). These features were associated with adjacent islands of Barrett's esophagus in 48%. Forty-four cases of buried Barrett's mucosa were suspected endoscopically, and these were sampled by biopsy (50%) and EMR (50%). Buried Barrett's mucosa was confirmed in 26 cases, with a positive predictive value of endoscopic suspicion of 59%. Eighteen cases of endoscopically suspected buried Barrett's mucosa had no buried Barrett's mucosa on histology; inflammation or reflux was identified in 12 (67%) patients. Dysplasia was identified within buried Barrett's mucosa in 12 (36%) patients; 5 intramucosal adenocarcinoma, 1 high-grade dysplasia, and 6 low-grade dysplasia. Endoscopic features of buried Barrett's mucosa were observed in 11 of 12 cases harboring dysplasia or neoplasia, compared with 15 of 21 cases of buried Barrett's mucosa without dysplasia. In this retrospective analysis of prospectively observed patients with dysplastic Barrett's esophagus, buried Barrett's mucosa was identified in 7%, including treatment-naive patients. The proposed endoscopic features of buried Barrett's mucosa were seen in 79% of patients with histology confirmed disease. These endoscopic features may predict the presence of buried Barrett's mucosa, which may contain dysplasia or neoplasia. An overlap between the endoscopic features of inflammation, reflux, and buried Barrett's mucosa was observed. Future prospective studies are required to develop and validate endoscopic criteria for identifying buried Barrett's mucosa.

Interobserver and intraobserver reliability for 2 grading systems for gastric ulcer syndrome in horses.

BackgroundGrading of equine gastric ulcer syndrome (EGUS) is undertaken in clinical and research settings, but the reliability of EGUS grading systems is poorly understood.Hypothesis/ObjectivesInvestigate interobserver and intraobserver reliability of an established ordinal grading system and a novel visual analog scale (VAS), and assess the influence of observer experience.AnimalsSixty deidentified gastroscopy videos.MethodsSix observers (3 specialists and 3 residents) graded videos using the EGUS Council (EGUC) system and VAS. Observers graded the videos three 3 for each system, using a cross‐over design with at least 1 week between each phase. The order of videos was randomized for each phase.MethodsInterobserver and intraobserver reliability were estimated using Gwet's agreement coefficient with ordinal weights applied (AC2) for the EGUC system and the intraclass correlation coefficient (ICC) for the VAS.ResultsUsing the EGUC system, interobserver reliability was substantial for squamous (AC2 = 0.69; 95% confidence interval [CI], 0.57‐0.80) and glandular mucosa (AC2 = 0.72; 95% CI, 0.70‐0.75), and intraobserver reliability was substantial for squamous (AC2 = 0.80; 95% CI, 0.71‐0.90) and glandular mucosa (AC2 = 0.80; 95% CI, 0.74‐0.86). Interobserver reliability using the VAS was moderate for squamous (ICC = 0.64; 95% CI, 0.31‐0.96) and poor for glandular mucosa (ICC = 0.35; 95% CI, 0.06‐0.64), and intraobserver reliability was moderate for squamous (ICC = 0.74; 95% CI, 0.62‐0.86) and glandular mucosa (ICC = 0.56; 95% CI, 0.39‐0.72).Conclusions and Clinical ImportanceThe EGUC system had acceptable intraobserver and interobserver reliability and performed well regardless of observer experience. Familiarity and observer experience improved reliability of the VAS.

Effect of a novel fermented soy product on gastric ulcer scores in horses

Non-pharmaceutical methods are desirable to treat or prevent gastric ulceration in horses. This two-period, randomised, double-blinded placebo-controlled study was designed to evaluate the efficacy of dietary supplementation (25 g once daily in feed for 30 days) with Fermaid®Ease 187 (FE, Lallemand Australia Pty Ltd, Maroochydore, Australia) on gastric squamous and glandular mucosal ulcer scores in horses. Gastroscopy of 120 horses presented to the Veterinary Clinical Centre at Charles Sturt University (CSU; Bathurst, Australia) or at local training establishments identified 60 horses with spontaneous gastric ulcer disease (50%). Of horses eligible for inclusion, 29 horses were recruited and randomised to receive either the FE or placebo for 30 days. Effects were assessed by repeat gastroscopy (Day 31), at which time horses started the reciprocal treatment. Eleven horses successfully completed both treatment periods. Treatment with FE showed a significant decrease in squamous ulcer scores in period 1 (P=0.008), with a similar effect observed in period 2. No change was observed in squamous ulcer scores for horses receiving placebo treatment in period 1, but increased squamous scores were observed in horses receiving placebo treatment in period 2 (P=0.062). Squamous ulcer scores on Day 31 were significantly lower (P=0.005) following FE treatment than for horses receiving the placebo treatment. No effects were observed on glandular ulcer scores. This study supported the use of FE in horses predisposed to ulceration of the squamous gastric mucosa.

Esophageal Pityriasis Lichenoides Chronica

Abstract Casestudy: Pityriasis Lichenoides is an uncommon inflammatory skin condition of unknown cause that ranges from mild chronic form to a more severe acute eruption. The mild form, pityriasis lichenoid chronica (PLC), is characterized by the gradual development of symptomless, small scaling papules that spontaneously flatten and regress over weeks. The acute form is characterized by the sudden eruption of small scaling papules that develops into blisters and crusted red brown spots. This acute form is called pityriasis lichenoides et varioliformis acuta (PLEVA). Both forms usually involve the skin of the trunk and proximal extremities. Visceral involvement is not a well described phenomenon. We report a case of a 69-year-old female with significant history of PLC controlled by immunosuppressive therapy. The patient presented with odynophagia and dysphagia that occurred after a period of discontinuation of her PLC treatment. She underwent endoscopy which showed distal esophageal narrowing and stricture. Biopsy revealed squamous esophageal mucosa with marked intraepithelial lymphocytosis along with basal cell hyperplasia, acanthosis, vacuolation and prominent apoptosis in the epithelial cells. PAS, CMV and HSV stains showed no fungal or viral organisms. The esophagus is commonly involved in a number of dermatologic conditions including pemphigus vulgaris, erythema multiforme, epidermolysis bullosa, lichen planus and lichen sclerosis. The pattern of involvement is often in the form of “lymphocytic esophagitis”. To our knowledge, there are no reported cases in the literature on PLC involving the esophagus. While the diagnosis heavily relies on clinical history of PLC, awareness of potential involvement of the esophagus and attention to certain endoscopic and morphological details may better help classify esophagitis biopsies.

A PAX-8-positive Female Urethra Adenocarcinoma: A Case Report with Diagnostic Challenges in Intestinal- Type Adenocarcinoma

Abstract Introduction/Objective Female urethra adenocarcinoma (FUA) in women is extremely rare, representing 0.02% of all women’s cancers and &amp;lt;1% of cancers in the female genitourinary tract. Intestinal-type primary adenocarcinoma of the urethra is even rarer, with only one documented case to our knowledge. Furthermore, PAX-8 immunoexpression in this entity has not been reported. Here we report an intestinal-type primary urethral adenocarcinoma that developed from inflammation-related metaplasia in urethral diverticulum with positive PAX-8 staining. Methods Clinical chart review and microscopic examination on the lung, urethral, and vaginal wall biopsies and immunohistochemistry were performed. Results A 64-year-old female with a 32-pack-year history of tobacco use was found to have multiple pulmonary nodules on imaging. The tumor cells were positive for CK7, CK20, SAT-B2, and PAX-8 and negative for TTF- 1/Napsin and ER. Positive PAX-8 immunoexpression raised the possibility of a gynecologic/Mullerian primary. Subsequent colonoscopy and imaging showed no evidence of colorectal or uterine tumors. The patient began having hematuria with intermittent urinary retention, and cystoscopy showed a 4 x 3 cm mass involving bladder neck circumferentially and invading into the vaginal wall. Urethral and vaginal tumor biopsies were performed. Morphologic examination of the urethral biopsy demonstrated intestinal metaplasia of squamous mucosa with transition from a mature to dysplastic phenotype where the adenocarcinoma originated from. The vaginal wall biopsy showed the same morphology. The urethral and vaginal wall biopsies showed a similar immunophenotype as the pulmonary nodule biopsy. Conclusion FUA is a rare, aggressive tumor that occurs in Skene’s glands. In our current case, however, it appeared to arise from inflammation-related metaplasia in urethral diverticulum. Another important finding of the case is the positive PAX-8 expression. Therefore in PAX-8 positive tumors, primary adenocarcinoma of lower urinary tract should be in the differential, along with gynecologic/Mullerian tumors.

Primary Intestinal-type Adenocarcinoma of the Vulva Causing Secondary Extramammary Paget Disease

Abstract Casestudy A 65-year-old woman with a known history of anogenital extramammary Paget disease presented with a pedunculated lesion arising from the vulvar vestibule near the urethral meatus, discovered during a routine surveillance exam. Results Biopsy of the lesion revealed an adenocarcinoma with villoglandular architecture and pseudostratified columnar epithelium with goblet cells that is arising in direct continuity with the uninvolved squamous mucosa. In addition to the villoglandular component, an area of dyscohesive cells with signet ring morphology within a mucinous background was present. Biopsy of a lesion inferior to the index mass showed Paget disease with similar morphology to the invasive adenocarcinoma. By immunohistochemistry (IHC), the invasive adenocarcinoma was diffusely positive for CK20, CK7, and CDX-2 with patchy staining for p16. Metastasis was excluded by colonoscopy, mammography, and PET-CT. Additional IHC stains for GCDFP-15, GATA-3, PAX-8, S100, p63, and PSA were all negative on subsequent biopsies performed for mapping the extent of disease. These features supported a diagnosis of primary intestinal-type adenocarcinoma of the vulva and pointed to this tumor as a source of her Paget disease. Conclusion Primary intestinal-type adenocarcinomas of the vulva are extremely rare with only a small number of case reports in the literature. It is suggested that these tumors acquire a colorectal phenotype due to the cloacal origin of the vulvar vestibule. No standard treatment approach has been developed due to the rarity of this disease, but the majority of reported cases have had an indolent course. To the best of our knowledge, other than this case, there is only a single additional case report in the literature of secondary Paget disease arising from this tumor type. We underscore the propensity of this tumor to cause secondary Paget disease, mimicking spread from a colorectal primary site.

Crohn’s Disease of the Esophagus

A 33-year-old woman with a history of ileocolonic Crohn’s disease status-post ileocecal resection maintained in remission with infliximab monotherapy presented with persistent dysphagia and odynophagia. Esophagogastroduodenoscopy showed ulceration, inflammation, and edema throughout the proximal and midesophagus (Figures A and B). Esophageal biopsies demonstrated squamous esophageal mucosa with moderate active chronic inflammation, ulceration, and nonnecrotizing granulomas (arrows in Figures C and D) consistent with esophageal Crohn’s disease.