Glandular Mucosa Research Articles

Fosfomycin (Veterinary Medicinal Products): Summary.

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of fosfomycin (CAS No. 23155-02-4), using documents submitted for the ‟re-examination” of veterinary medicinal products. The data used for the assessment include ADME of fosfomycin Ca, residue of fosfomycin Ca and of fosfomycin Na, acute toxicity of fosfomycin Ca and fosfomycin Na. Data on subacute toxicity, reproductive and developmental toxicity, genotoxicity and microbiological effect are also included. The lowest-observed-adverse-effect level (LOAEL) in these toxicity studies was 175 mg (titer)/kg body weight (bw) per day based on adverse effects including diarrhea, autopsy findings such as erosion, hyperplasia, and exfoliation of glandular stomach mucosa, and histopathological findings such as erosion of the stomach and ileum mucosa observed as adverse effects in the 35-day subacute toxicity study in rats. Fosfomycin was not teratogenic in rats and rabbits. FSCJ considered that fosfomycin is not a genotoxic carcinogen. The toxicological ADI of fosfomycin was established to be 0.175 mg/kg bw per day by applying a safety factor of 1000 based on the LOAEL of 175 mg (titer)/kg bw per day. On the other hand, the microbiological ADI was calculated to be 0.019 mg/kg bw per day, which is lower than the toxicological ADI. Thus, FSCJ established the ADI for fosfomycin as 0.019 mg/kg bw per day.

Evaluation of Methods of Gastroesophegeal Reflux Disease Diagnosis in Thawra Teaching Hospital Elbaida –Libya

Gastroesophageal reflux disease (GERD) results from the reflux of gastric contents, causing symptoms and injury to esophageal tissue. In this study, we evaluate methods of diagnosis of GERD and pattern of clinical, endoscopic, and histological findings in consecutive individuals. Patients were referred to endoscopy unit of Thawra Teaching Hospital, Elbaida-Libya for various reasons, they have Questionnaire-based assessment scales and were examined for the presence of reflux esophagitis, via endoscopy, and microscopic via histopathology. We had 48 patients with mean age of 45.5, 30 female, 18 male. Total patients with microscopic esophagitis were 29 (60.4%), and without microscopic esophagitis 19 (39.6%). The RDQ with a score of ≥ 8 as the diagnostic criteria of GERD, is not a conclusive diagnosis of GERD in isolation, but is of value in determining the need for further investigation. A normal endoscopy does not exclude GERD when endoscopy is inconclusive, adjunctive evidence from biopsy findings can add confidence for a GERD diagnosis. The finding of glandular mucosa without intestinal metaplasia in the distal 2 cm of the tubular esophagus is regarded as normal but indicates a much chronic acid exposure of the lower esophagus.

OPCML is hypermethylated in a subset of patients with metaplastic changes in their esophagus

OPCML hypermethylation is considered a promising cancer biomarker. We examined methylation levels in the first exon of OPCML in two patient cohorts within the esophageal adenocarcinoma and gastric adenocarcinoma cascades and in a range of cell-lines using a custom PyroMark CpG assay. Methylation levels were significantly higher in esophageal tissue with histologically confirmed glandular mucosa as compared to tissue from normal esophagi or gastro-esophageal reflux disease. Higher levels of OPCML methylation were absent in the adjacent normal esophageal tissue of patients with glandular mucosa. Higher levels of methylation were confirmed in cell-lines derived from patients with adenocarcinoma, but also detected in two cell-lines with signs of dysplasia. We validated our assay by showing no differences in methylation levels in DNA extracted from blood of patients within the gastric adenocarcinoma cascade. OPCML hypermethylation is present in a subset of patients with metaplastic changes in their esophagus.

Potassium bromate – inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)

Potassium bromate (V), (KBrO3) exists as white crystals, crystalline powder or granules. It is highly soluble in water, tasteless and odourless. Potassium bromate is a strong oxidizing agent. In the past it has been used as food additive in flour milling, as an ingredient in fish-paste in Japan, in cheese making, in beer malting, as a component of cold hair wave liquid and an oxidizing compound. Moreover, bromate is formed as a by-product of water disinfection by ozonation and is frequently detected in tap and bottled water. In fact bromate is one of the most prevalent disinfection by-product of surface water. Occupational exposure to potassium bromate occurs mainly in production plants during packaging processes. In Poland, about 1 160 persons were exposed to this compound in 2016. Bromate caused many acute poisonings by accidental ingestion, mainly among children, and more often ingested for tentative suicide by young women, especially hairdressers. In the acute phase of poisoning, gastrointestinal disturbances, irreversible hearing loss, and acute renal failure were observed. Acute renal failure was associated with hemolytic uremic syndrome. There are no data on chronic intoxication of humans by potassium bromate and epidemiological studies on this subject. On the basis of the value of median lethal dose (LD50) per os in rat, potassium bromate has been classified as a compound belonging to the category „Toxic”. Major toxic signs and symptoms in animals after a single intragastric administration of potassium bromate were tachypnea, hypothermia, diarrhea, lacrimation, suppression of locomotor movement, ataxic gait, and animals lying in a prone position. At autopsy the major findings were strong hyperemia of glandular stomach mucosa and congestion of lungs. Microscopically, necrosis and degenerative changes of the proximal tubular epithelium and hearing cells of internal ear were found. It was stated that the compound is not irritating, corrosive or sensitizing. In subchronic and chronic exposure of rodents, potassium bromate led to liver and kidney dysfunction and tubular epithelial damage. Potassium bromate had mutagenic and clastogenic effects. It induced point mutations, structural chromosome aberrations, micronuclei in polychromatic erythrocytes in male mice, DNA oxidative damage by modification of deoxyguanosine to 8-hydroxydeoxyguanosine, and DNA double-strand breakage. Potassium bromate induced neoplasms in rodents and exerted promotion effect in comparison with well-known carcinogens. Besides from preneoplastic changes, expressed by high incidences of renal cell tumors and dysplastic foci, bromate induced solid neoplasms, such as adenomas and adenocarcinomas in a rat kidney and thyroid, and mesotheliomas of peritoneum and tunica vaginalis testis. The European Union classified potassium bromate as a substance that can cause cancer (Group 1.B), whereas IARC classified it as a presumably carcinogenic agent for human (Group 2.B). In principle, effects of bromate on reproduction and ontogenetic development of offspring were not observed. Animal studies suggest that a kidney is a critical organ in the exposure to potassium bromate. The results of subchronic exposure of male rats to potassium bromate administered with drinking water were used to calculate the value of MAC-NDS. The critical effects in kidney were: an increase of organ weight and dose-dependent histopathological alterations defined as epithelium urinary tract hypertrophy. The NOAEL value is 1.5 mg/kg b.w./day. For the calculation of the maximum allowable concentration (MAC) value, 5 uncertainty factors with total value of 24 were used. Based on this estimation it is proposed to accept the MAC-TWA value for potassium bromate at 0.44 mg/m3. The risks of kidney and thyroid cancer in condition of occupational exposure are 2.2 · 10-3 and 0.6 · 10-3, respectively. There is no reason to determine the value of short-term exposure limit (STEL) and the biological exposure index (BEI). „Carc.1.B” notation (carcinogenic substance) was proposed

Pathogenesis of equine squamous and glandular gastric disease

Recent publications have cast light on the marked differences between diseases in the squamous and glandular regions of the equine stomach. Until recently the focus regarding all aspects of gastric disease has been on disease of the squamous mucosa and findings have then been extrapolated to disease in the glandular region. Disease of the squamous mucosa is caused by acid and results in hyperkeratosis, erosions and ulceration. Many of the risks for development of squamous disease relate to factors that allow or promote a more acidic gastric pH or increase exposure of the squamous mucosa to this acid. We know that this is not the case for the glandular mucosa as the epithelial cells in this region in health have protective factors against acid. We now know that disease in the glandular region is inflammatory in origin and not ulcerative. It is proposed that the inciting cause to this lesion is reduced gastric glandular blood flow and it is speculated that it may be an extension of idiopathic inflammatory bowel disease; acid may then slow or inhibit healing. Lesions in the glandular mucosa vary in appearance and these differences may relate to differing aetiologies. Recommendations for management changes are different to squamous disease and primarily involve minimising stress. Treatment for glandular disease is more challenging, healing may take longer and requires alternative approaches to oral omeprazole monotherapy when compared with squamous disease.

Optical Biopsy of Head and Neck Cancer Using Hyperspectral Imaging and Convolutional Neural Networks.

Successful outcomes of surgical cancer resection necessitate negative, cancer-free surgical margins. Currently, tissue samples are sent to pathology for diagnostic confirmation. Hyperspectral imaging (HSI) is an emerging, non-contact optical imaging technique. A reliable optical method could serve to diagnose and biopsy specimens in real-time. Using convolutional neural networks (CNNs) as a tissue classifier, we developed a method to use HSI to perform an optical biopsy of ex-vivo surgical specimens, collected from 21 patients undergoing surgical cancer resection. Training and testing on samples from different patients, the CNN can distinguish squamous cell carcinoma (SCCa) from normal aerodigestive tract tissues with an area under the curve (AUC) of 0.82, 81% accuracy, 81% sensitivity, and 80% specificity. Additionally, normal oral tissues can be sub-classified into epithelium, muscle, and glandular mucosa using a decision tree method, with an average AUC of 0.94, 90% accuracy, 93% sensitivity, and 89% specificity. After separately training on thyroid tissue, the CNN differentiates between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy, 92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate medullary thyroid carcinoma from benign multi-nodular goiter (MNG) with an AUC of 0.93, 87% accuracy, 88% sensitivity, and 85% specificity. Classical-type papillary thyroid carcinoma is differentiated from benign MNG with an AUC of 0.91, 86% accuracy, 86% sensitivity, and 86% specificity. Our preliminary results demonstrate that an HSI-based optical biopsy method using CNNs can provide multi-category diagnostic information for normal head-and-neck tissue, SCCa, and thyroid carcinomas. More patient data are needed in order to fully investigate the proposed technique to establish reliability and generalizability of the work.

Recommendations for the management of equine glandular gastric disease

ForewordThe European College of Equine Internal Medicine (ECEIM) consensus statement recently made the distinction between disease of the squamous mucosa (Equine Squamous Gastric Disease; ESGD) and of the glandular mucosa (Equine Glandular Gastric Disease; EGGD) ( Sykes et al, 2015a ). Since its publication, a number of reports have furthered understanding of the pathology and management of EGGD, such that new clinical guidelines for the management of this condition were considered necessary. The following guidelines are the consensus views of subject specialist representing authors of the ECEIM consensus statement, authors of recent clinical research, and clinical specialists active in the management of horses with this condition. The recommendations were developed using an informal two-round Delphi process, considering published and unpublished research relating to EGGD using a round table forum and online discussion. Where research evidence was conflicting or absent, collective expert opinion based on the clinical experience of the group was applied. The opinions expressed are the consensus of views expressed by the authors. The expert group was organised by UK-Vet Equine with sponsorship from Luoda Pharma.

Metastatic Lobular Carcinoma of the Breast Mimicking Barrettʼs Esophagus

A 63 year-old female with a past medical history of lobular carcinoma of the breast who underwent mastectomy 5 years ago, hypertension, and hypothyroidism presents with a 4 year history of gastroesophageal reflux symptoms including post prandial epigastric abdominal pain, bloating, and burning sensation in the epigastric area non refractory to several trials of proton pump inhibitors. The patient was a non smoker with no alcohol use. Physical exam was unremarkable. EGD was conducted which demonstrated findings consistent with Barrett's esophagus extending 33 cm to 35 cm from the incisors. Round lesions were also noted consistent with peri-esophgeal lymph nodes at 28 cm from the incisors. One measuring 4x5 mm and the other larger lesion measured 5x13 mm. Under Doppler guidance, a 25 G FNA was used to obtain 4 passes of the larger lymph node. A biopsy of the tissue was obtained and VLE was performed on the mucosa. Endoscopic en bloc resection of the nodule was conducted utilizing hot snare technique. Pathology of the resected tissue demonstrated poorly differentiated adenocarcinoma that was estrogen receptor positive, progesterone and HER2neu negative consistent with metastatic lobular carcinoma of the breast. The patient was referred to oncology for further management and follow up. Among the population of adults in the United States it is estimated that approximately 5.6% have Barrett's esophagus, a serious complication of gastroesophageal reflux disease in which the normal tissue lining of the esophagus undergoes a metaplastic process replacing damaged squamous mucosa with metaplastic columnar mucosa. Diagnosis is typically made through endoscopic visualization and biopsy that demonstrates columnar mucosa extending above the GE junction. Metastasis of breast cancer to the esophagus is a known but rare occurrence often made difficult to diagnose because they are often located in the submucosa and are covered with normal appearing esophageal mucosa. The mechanism of esophageal spread from breast cancer is controversial with involvement of peri-esophageal lymph nodes through intra-mammary lymphatic channels has been suggested as the most likely origin. This case reinforces the importance of biopsy for neoplastic appearing masses of the esophagus especially in the context of unusual esophageal presentations and a known history of metastatic disease.Figure: Endoscopic imaging of the esophagus proximal to the GE junction demonstrating mucosa with irregular surface, loss of layered architecture and presence of glandular mucosa with irregular cribiform glands.Figure: H&E stain of GE junction demonstrating poorly differentiated carcinoma. The squamous epithelium shows reactive changes, and the rest of the glandular epithelium is inflamed showing mild acute and chronic inflammation.Figure: Immunohistochemical stains demonstrate estrogen receptor positive, progesterone receptor negative, and Her2 negative poorly differentiated metastatic adenocarcinoma of the breast.

Comparison of aloe vera and omeprazole in the treatment of equine gastric ulcer syndrome.

Anecdotally, aloe vera is used to treat gastric ulceration, although no studies have yet investigated its efficacy in horses. To test the hypothesis that aloe vera would be noninferior to omeprazole in the treatment of equine gastric ulcer syndrome. Randomised, blinded clinical trial. Forty horses with grade ≥2 lesions of the squamous and/or glandular mucosa were randomly assigned to one of two groups. Horses received either aloe vera inner leaf gel (17.6 mg/kg bwt) b.i.d. or omeprazole (4 mg/kg bwt) s.i.d. for approximately 28 days, after which a repeat gastroscopic examination was performed to determine disease resolution. Horses with persistent lesions were offered a further 28 days of treatment with omeprazole (4 mg/kg bwt s.i.d.) and were re-examined on completion of treatment. Efficacy analyses were based on 39 horses that completed the trial. Equine squamous gastric disease (ESGD) was observed in 38 horses; improvement and healing rates in these horses were 56% and 17%, respectively, in the aloe vera group, and 85% and 75%, respectively, in the omeprazole group. Healing was less likely to occur in horses with prolonged gastric emptying. Equine glandular gastric disease (EGGD) was less common than ESGD (n = 14) and numbers were too small to perform meaningful statistical analyses. The hypothesis that aloe vera would be noninferior to omeprazole was not supported. No placebo control group was included. Limited numbers preclude any comment on the efficacy of aloe vera in the treatment of EGGD. Treatment with aloe vera was inferior to treatment with omeprazole.

Manuka Honey Exerts Antioxidant and Anti‐Inflammatory Activities That Promote Healing of Acetic Acid‐Induced Gastric Ulcer in Rats

Gastric ulcers are a major problem worldwide with no effective treatment. The objective of this study was to evaluate the use of manuka honey in the treatment of acetic acid-induced chronic gastric ulcers in rats. Different groups of rats were treated with three different concentrations of honey. Stomachs were checked macroscopically for ulcerative lesions in the glandular mucosa and microscopically for histopathological alterations. Treatment with manuka honey significantly reduced the ulcer index and maintained the glycoprotein content. It also reduced the mucosal myeloperoxidase activity, lipid peroxidation (MDA), and the inflammatory cytokines (TNF-α, IL-1β, and IL-6) as compared to untreated control group. In addition, honey-treated groups showed significant increase in enzymatic (GPx and SOD) and nonenzymatic (GSH) antioxidants besides levels of the anti-inflammatory cytokine IL-10. Flow cytometry studies showed that treatment of animals with manuka honey has normalized cell cycle distribution and significantly lowered apoptosis in gastric mucosa. In conclusion, the results indicated that manuka honey is effective in the treatment of chronic ulcer and preservation of mucosal glycoproteins. Its effects are due to its antioxidant and anti-inflammatory properties that resulted in a significant reduction of the gastric mucosal MDA, TNF-α, IL-1β, and IL-6 and caused an elevation in IL-10 levels.

Risk Factors for Equine Gastric Glandular Disease: A Case-Control Study in a Finnish Referral Hospital Population.

BackgroundEquine gastric glandular disease (EGGD) is a term used to classify erosive and ulcerative diseases of the glandular mucosa of the equine stomach. Epidemiologic studies of risk factors for EGGD have not been reported.ObjectiveTo determine risk factors for EGGD.AnimalsCases (n = 83) had endoscopic evidence of EGGD; controls (n = 34) included healthy horses and horses with equine squamous gastric disease (ESGD) without EGGD.MethodsRetrospective case‐control study. The data were analyzed by multivariable logistic regression modeling. Analysis was performed on the full dataset. An additional analysis compared horses with glandular lesions (n = 43) against healthy horses (n = 22).ResultsOn first analysis, Warmblood breed (OR = 13.9, 95% CI 2.2–90.9, P = .005) and an increasing number of caretakers (OR = 7.3, 95% CI 0.98–55.6, P = .053) were associated with an increased risk of EGGD. On analysis of the subset of data, Warmblood breed (OR = 28.6, 95% CI 2.96–250.0, P = .004) and increasing number of riders (OR = 12.99, 95% CI 0.94–166.7, P = .056) were risk factors. The presence of sand in the colon appeared to have a protective effect against EGGD (OR = 0.195, 95% CI 0.04–1.0, P = .051 for sand versus not having sand).Conclusions and clinical importanceThis study suggests that Warmbloods are predisposed to EGGD and multiple handlers/riders might increase the risk of EGGD. Identification of risk factors allows speculation on potential pathophysiological mechanisms of EGGD.

Frecuencia de patologías gástricas en burros (Equus africanus asinus) en Córdoba, Colombia

El objetivo del presente estudio fue determinar la frecuencia de patologías gástricas en burros (Equus africanus asinus) del departamento de Córdoba, Colombia. Se evaluaron 137 estómagos de burros (73 machos enteros, 16 machos castrados y 48 hembras), con un rango de edad entre 1 y 25 años, en los cuales el estómago fue evaluado, caracterizado y fotografiado post mortem. Los datos de sexo, edad y patología fueron diligenciados en los formatos respectivos y posteriormente digitalizados. De la población total (137 burros), se encontraron úlceras gástricas y gastritis asociada en el 100 % de las muestras, edema antral en el 56,9 %, parásitos (Trichostrongylus axei) en el 10,2 % e impacción en el 5,8 %. Además, en un estómago se encontró Hemomelasma gastric (0,7 %). Se concluye que el 100 % de los animales evaluados presentó al menos algún tipo de patología gástrica. El tipo de gastritis con más incidencia fue la aguda (71,5 %), seguida en menor proporción por la forma crónica (28,4 %). El estudio demostró que había dependencia estadística significativa entre la edad y el grado de lesión de la mucosa glandular (p < 0,05). Así, se evidencia que existe una elevada frecuencia de patologías gástricas en los burros de las diferentes explotaciones pecuarias de Córdoba, en la cual las úlceras escamosas son las de mayor frecuencia, seguidas de las gastritis agudas y del edema antral; por eso es necesario realizar más investigaciones y concientización sobre el manejo de estas patologías en este tipo de animales.

Antioxidant, Anti-inflammatory, and Antiulcer Potential of Manuka Honey against Gastric Ulcer in Rats.

Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol-induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor-α, interleukin-1β, and IL-6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF-α, IL-1β, and IL-6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-α, IL-1β, and IL-6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels.

Clinical Application of Magnifying Endoscopy with Narrow-Band Imaging in the Stomach

Magnifying endoscopy with narrow-band imaging (M-NBI) can visualize superficial microanatomies in the stomach. The normal morphology of the microanatomy visualized by M-NBI differs according to the part of the stomach. The gastric fundic glandular mucosa appears as a regular honeycomb-like subepithelial capillary network (SECN) pattern with a regular collecting venule pattern and regular oval crypt opening with circular marginal crypt epithelium (MCE) pattern. The gastric pyloric glandular mucosa displays a regular coil-shaped SECN pattern and regular polygonal or curved MCE pattern. For a diagnosis of early gastric cancer using M-NBI, the vessel plus surface classification system was developed. This system is clinically useful for the differential diagnosis of focal gastritis and small depressed cancer and for determining the horizontal extent of early gastric cancer for successful endoscopic resection. Advantages of M-NBI over conventional endoscopic imaging techniques with white light include accurate diagnosis and cost effectiveness. This technique is a breakthrough in the endoscopic diagnostic field.

Esophageal Adenocarcinoma Masquerading as Hyperplastic Polyps

Introduction: We report a case with the rare occurrence of hyperplastic polypoid lesions in the background of Barrett's esophagus in associated with invasive adenocarcinoma of the esophagogastric junction (EGJ). Case Report: A 65 year old Caucasian male with chronic acid reflux presented with progressive dysphagia and weight loss. Exam was unremarkable except for a body mass index of 37. Lab studies showed mild anemia with hemoglobin of 12.5 gm/dl. Esophagogastroduodenoscopy (EGD) revealed a diffuse, polypoid growth involving the distal 14 cm of the esophagus. Histological exam revealed glandular mucosa with elongated hyperplastic foveolar epithelium and cystic changes, consistent with hyperplastic polyp. EGD was repeated and tissue specimen collected with cold snare as well as multiple 4 quadrant biopsies every 1 cm, histology revealed hyperplastic polyps in the background of intestinal metaplasia without dysplasia. Endoscopic ultrasonography (EUS) showed that the growth was limited to the mucosal layer, positron emission test (PET) scan showed increased uptake only in the distal esophagus. Patient was referred to surgery and underwent esophagectomy with proximal gastrectomy. Esophago-gastric continuity could not be achieved, thus a left sided esophageal spit fistula was created. Surgical specimen showed moderately differentiated adenocarcinoma with tumor invasion through muscularis propria into the serosal fat at the EGJ and multiple lymph nodes involvement. Discussion: Epithelial polypoid lesions of the esophagus and EGJ are uncommon. Most of these lesions reportedly occur at the EGJ (67%) followed by distal esophagus (30%). Among these lesions, hyperplastic polyps are quite rare and usually occur in the setting of long-standing gastro esophageal reflux disease. In the largest reported case series by Abraham et al., among 27 patients with hyperplastic esophageal and EGJ polyps, only 15% had concomitant Barrett's esophagus. There have been only two cases reported of hyperplastic polyps at EGJ where subsequent endoscopic mucosal resection showed foci of high grade dysplasia and adenocarcinoma. Our case is unique due to the presence of long segment Barrett's esophagus with concomitant circumferential, villiform polypoid growth where multiple repeat mucosal biopsies showed reactive changes. Due to the diffuse extensive nature of the lesion it was not amenable to safe endoscopic resection and thus required surgical resection which revealed an invasive adenocarcinoma of the EGJ. This case highlights the extremely rare occurrence of the hyperplastic polyps in the setting of Barrett's esophagus and invasive adenocarcinoma of the EGJ. It also underscores the fact that malignancy in this setting should always be suspected even when mucosal biopsies are negative.Figure 1Figure 2Figure 3

A Unique Case of Alpha-Fetoprotein-Producing Esophageal Adenocarcinoma

Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but has also been reported in patients with other malignancies, most notably of gastrointestinal origin. However, the organs of origin typically include gastric, pancreatic, and biliary, but rarely esophageal. Here, we report a case of an AFP-producing EAC. A 51 year-old previously healthy man presented with new onset severe acid reflux and a weight loss of 35 pounds over a 2 week duration. He also endorsed 2 days of non-bloody emesis, but denied dysphagia or regurgitation of undigested food. Physical exam was only remarkable for right upper quadrant tenderness. The patient was slightly anemic with a hemoglobin of 12.8 g/dL. Elevated labs included: AST 66 U/L, ALT 81 U/L, CEA 6.4 ug/L, CA 19-9 317443 U/mL, and AFP 2524 ng/mL. Hepatitis B surface antigen and hepatitis C antibody were non-reactive. Computed tomography (CT) scan of the abdomen revealed abnormal thickening of the esophagus and multiple masses throughout the liver consistent with metastatic disease. CT-guided biopsy of one of the masses revealed CDX-2 positive adenocarcinoma, suggesting gastrointestinal origin. Subsequent upper endoscopy revealed a large, partially-obstructing mass in the lower third of the esophagus, the assumed primary source. Biopsy of the mass revealed ulcerated glandular mucosa with high grade dysplasia, with likely underlying malignancy. One month later, the patient underwent palliative esophageal stent placement. He was scheduled to begin FOLFOX/Herceptin therapy, but expired a week later. EAC is typically found in the lower third of the esophagus, and is associated with Barrett's esophagus, smoking, obesity, and epidermal growth factor polymorphisms. A previous study attempting to determine possible tumor markers in patients with esophagus cancer reported serum AFP levels >5 ng/mL in up to 18% of EACs, with the highest reported AFP level being 320ng/mL. However, to the best of our knowledge, our case is only the 14th AFP-producing EAC to be thoroughly described in the English literature. Patients with EAC and cirrhosis often share common risk factors that make the differential diagnosis of liver masses and elevated AFP challenging. Some AFP-producing EACs contain cells resembling hepatic cells and are termed hepatoid EAC. Although not possible in our case, serial measurement of serum AFP level may be useful for monitoring clinical status and response to treatment. Most cases are treated with surgery and adjuvant chemotherapy but with disappointing results given the advanced presenting stage, high liver metastatic potential, and poor prognosis of AFP-producing EAC.Figure 1Figure 2Figure 3

Histology and ultrastructure of the uterus of African giant rat (Cricetomys Gambianus, Waterhouse) during oestrous cycle.

This study describes histology and ultrastructure of uterus in the African giant rat during oestrous cycle. Endometrial histology displayed glandular mucosa consisting of lamina epithelialis and lamina propria mucosae. Its epithelium varied between simple and pseudostratified columnar. The myometrium consisted of inner circular and outer longitudinal smooth muscles with medium sized arteries and veins in-between. The perimetrium contained simple squamous epithelium. Endometrial ultrastructures were variable during oestrous cycle. At mid oestrus, hemidesmosomes anchored undulating basement membrane of the mucosal epithelium. Preponderance spherical mitochondria, lipofuscin granules concentration, flocculent homogenous materials and indented nuclei were displayed. At mid metoestrus, late metoestrus/early dioestrus and mid dioestrus, the base of the mucosal columnar epithelium lain on relatively straight basement membrane and their cytoplasmic ultrastructure displayed variation to mid oestrus. Epithelial apex showed intermediate filament, microvilli and junctional complexes. The uterine glands occurred in variable numbers and sizes during oestrous cycle and shared similar ultrastructure. Mid dioestrus showed cell ultrastructure of uterine glands having apical accumulation of secretory vesicles. Some actively secreting uterine glands were lined by simple ciliated columnar epithelium mingled with pseudostratified epithelium. The findings of the study indicate that giant rat endometrial ultrastructure varies during oestrous cycle and glandular secretion is merocrine.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

Equine gastric glandular disease (EGGD) is a common condition, for which the underlying pathophysiology is undetermined. Endoscopic mucosal biopsies have been proposed as a method for adapting therapy. To evaluate diagnostic information obtained from endoscopic mucosal biopsies. Prospective, experimental study. Twenty-one horses undergoing elective humane slaughter were subjected to gross examination of the glandular mucosa. Glandular pathology was graded using EGUS Council guidelines from digital camera images. Mucosal biopsies were obtained using a 'single-bite' (1.8 mm; A and 2.4 mm; B) or 'double bite' technique (2.4 mm; C) using endoscopic biopsy instruments. Tissue was formalin fixed, processed and stained using standard protocols. Inflammatory infiltrates visualised histologically were graded (mild, moderate or severe) and compared with ulcer grade. Full thickness biopsies were also obtained adjacent to the biopsy site and of other visual lesions and inflammatory cell counts were compared with mucosal biopsies using ICC. Full thickness samples were artefact free and allowed visualisation of all layers. Mucosal biopsy samples contained mucosa in all samples, submucosa in 55% (C), 61% (A) and 66% (B) of samples and glands in 50% (B), 66% (A) and 100% (C). Samples from A were too small for histological assessment (33%) and tissue damage was commonly seen in A and B (n = 8 and n = 10) when compared with C (n = 3). Horses with normal glandular appearance (grade 0; n = 7) mostly demonstrated mild gastritis (n = 5). Severe gastritis was identified in mild EGGD (grade 1/2), whilst mild and moderate gastritis was identified in all EGGD grades. There was no histological evidence of ulceration or erosion. There was poor agreement between cell numbers and sampling techniques (ICC<0.29). These data show lack of ulcerative pathology and instead inflammation in EGGD. Lesion appearance is a poor indicator of underlying severity. Mucosal biopsies offer limited value in predicting underlying disease. Ethical animal research: This study was approved by the University of Nottingham Ethics and Welfare Committee. The study was performed on material collected at an abattoir. None. Competing interests: None declared.

Prognostic Validity of AgNOR in Pleomorphic Adenoma

Since the argyrophilic nucleolar organizer region (AgNOR) technique has successfully distinguished various grades of malignancies and enabled prognostic assessment, this paper traces its prognostic validity in predicting the behavior of pleomorphic adenoma (PA). Ten cases of recurrent PAs were compared, on the one hand, where AgNOR score of area fraction was measured before and after recurrence. The same findings were contrasted to ten cases of normal glandular mucosa. Diagnosing both pleomorphic adenomas was based on clinical and histological records of the archival submitted cases. The data were statistically analyzed by t-test, ANOVA, Tukey and Pearson's tests. The study concludes that AgNOR score lack the prognostic validity on testing PA, in terms of distinguishing and or predicting recurrence.

High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7.

BackgroundCarbonic anhydrase IX (CA9) is a transmembrane glycoprotein related to hypoxia. Increased CA9 expression has been associated with decreased survival and cancer progression and has been targeted as a potential therapy for several cancers, including esophageal cancer. The reported percentages of expression of CA9 in esophageal adenocarcinoma vary, and CA9 expression in precancerous esophageal lesions has not been well studied.MethodsIn this study, we investigated CA9 expression in esophageal cancers and in precancerous lesions and explored the association of CA9 expression with prognostic factors and with stem cell and tumorigenesis-related markers including BMI1, cyclin E, ki67, MCM4 and MCM7 expression. Previously constructed tissue microarrays consisting of samples of 7 tissue types (columnar cell metaplasia, Barrett esophagus, low- and high-grade dysplasia, esophageal adenocarcinoma, squamous epithelium, and squamous cell carcinoma) were used for the immunostaining of CA9, BMI1, cyclin E, Ki67, MCM4 and MCM7.Results and discussionCA9 high expression occurred more frequently in glandular mucosa with or without dysplasia than in squamous epithelium or squamous cell carcinoma. Survival duration of esophageal adenocarcinoma did not significantly differ between patients with high CA9 expression and those with low expression. High CA9 expression is significantly associated with BMI1, cyclin E, Ki67, MCM4 and MCM7 expression.ConclusionsHigh CA9 expression may be related to the acidic environment caused by gastroesophageal reflux disease in the gastroesophageal junction and associated with tumorigenesis through BMI1, MCM4 and MCM7.