Body Mucosa Research Articles

Changes of gastric mucosal mast cells in patients with functional dyspepsia after Hylicobacter pylori infection

Objective To investigate the changes of gastric mucosal mast cells in patients with functional dyspepsia (FD) after Helicobacter pylori (H.pylori) infection, and to explore the correlation between the changes and dyspeptic symptoms. Methods From November 2012 to March 2014, 32 patients with FD and 16 asymptomatic patients (control group) from Beijing Jishuitan Hospital were enrolled. H. pylori infection situation was examined. The mucosal biopsies from gastric antrum and gastric body were taken for histological examination. The mast cells of gastric mucosa were detected by immunohistochemical stain. T test was performed for statistical analysis. Results Among 32 FD patients, 17 had H. pylori infection (one with gastric body involved, two with gastric antrum involved, 14 with both gastric antrum and gastric body involved), and 15 had no H. pylori infection. Among 16 asymptomatic patients, 12 had H. pylori infection and four had no H. pylori infection. Among FD patients, the percentage of degranulated mast cells in gastric mucosa with H. pylori infection group was (61.45±24.86)%, which was higher than that without H. pylori infection group ((48.34±21.63)%), and the difference was statistically significant (t=-2.145, P=0.036). The percentage of degranulated mast cells in gastric mucosa with H. pylori infection group was (29.73±12.99)%, which was higher than that without H. pylori infection group ((20.77±10.86)%), and the difference was statistically significant (t=-2.856, P=0.006). In H. pylori infection group, the percentage of degranulated mast cells in gastric body mucosa of FD patients was (66.99±18.85)%, which was higher than that of asymptomatic patients in control group ((46.77±8.43)%), and the difference was statistically significant (t=3.642, P=0.002). The ratio of degranulated mast cells in gastric body mucosa and the density of mast cells in gastric antrum mucosa of prandial distress syndrome (PDS) patients, the density of mast cells in gastric body mucosa of epigastric pain syndrome (EPS) patients and the ratio of degranulated mast cells in gastric body mucosa and the degree of degranulation of mast cells of PDS and EPS patients were all higher than those of asymptomatic patients in control group, and the differences were statistically significant (t=2.750, 3.601, 2.799, 9.522 and 5.755, all P<0.05). Conclusions The dyspeptic symptoms of FD patients with H. pylori infection is correlated with the changes of mast cells. With the infection of H. pylori, dyspeptic symptoms of different subtypes of FD may be correlated with the changes of mast cells in different gastric region. H. pylori infection may cause the dyspeptic symptoms of FD patients by increase the number and activation of mast cells. Key words: Helicobacter pylori; Mast cells; Functional dyspepsia; Dyspeptic symptom

Protein-Losing Hypertrophic Gastropathy, Menetrierʼs Disease, Successfully Managed With Long-Acting Octreotide

Protein-losing gastro-enteropathies are characterized by excessive loss of protein into the gastrointestinal tract. Ménétrier's disease (MD) is a rare disease characterized by extreme foveolar hyperplasia with glandular atrophy in a patient with gross enlargement of gastric folds or ruggae. Little is understood about the pathogenesis of this disease and treatment has mostly consisted of dietary therapy (low-fat, high-protein, medium-chain triglyceride diet.) This case describes a patient with MD successfully managed with Octreotide until he developed intussusception of a large gastric adenoma which required an emergent gastrectomy. A 52 yo AA male was diagnosed with MD after evaluation of a large gastric mass/thickened fold incidentally noted on imaging. An EGD confirmed thickened and large gastric folds. Gastric biopsies demonstrated dilated hyperplastic foveolar glands with stromal edema making the diagnosis of MD (Figure 1, 2). His course was complicated by several hospitalizations for DVTs treated with anticoagulation, severe intra-abdominal hemorrhage due to a complicated LVP, complicated pancreatic fluid collections, volume over load, and severe symptomatic anemia. Labs revealed a hemoglobin of 2.6 g/dL (MCV 58), ferritin 8 ng/ml, iron of < 5 mcg/dL, and Albumin of 0.9 g/dL. For several weeks his Albumin persistently ranged between 0.9 - 1.3 g/dL. Further evaluation revealed an elevated alpha-1-antitrypsin stool clearance >59 ml/day. He was started on octreotide 100mg BID SQ x6 months and subsequently transitioned to long acting Octreotide 20mg IM q4weeks. His albumin increased from 0.9 g/dL to 2.9 g/dL over the following 12-months. His anemia, microcytosis, and iron deficiency normalized. All of his clinical manifestations of hypoalbuminemia resolved and he regained significant muscle mass. Unfortunately, almost 19-months after making the diagnosis of MD he developed a gastric outlet obstruction due to a large fungating gastric adenoma filling and markedly distending the duodenum necessitating an emergent gastrectomy. He recovered well from surgery and continues to do well upon on follow up. Our case demonstrates the potential role of Octreotide as treatment or bridge to surgery for management of patients with protein losing gastropathies as well as as a gastric outlet obstruction from a gastric adenoma, an uncommon complication of this rare disease.Figure: Endoscopic appearance of the stomach showing mucosa edema and polypoid changes of the gastric fundus and body.Figure: Gastrectomy is performed. A, Grossly, there is hypertrophy of the fundal and body mucosa with sparing of the gastric antral mucosa; B-D, histologically, the body and fundal mucosa shows edematous, mildly inflamed lamina propria with hyperplastic.

Analysis of Gastric Body Microbiota by Pyrosequencing: Possible Role of Bacteria Other Than Helicobacter pylori in the Gastric Carcinogenesis.

BackgroundGastric microbiota along with Helicobacter pylori (HP) plays a key role in gastric disease. The aim of our study is to investigate the difference of human gastric microbiota between antrum and body according to disease (control vs. gastric cancer) and HP status.MethodsEach antrum and body biopsy was collected from 12 subjects at Seoul National University Bundang Hospital. Gastric microbiota was analyzed by bar-coded 454 pyrosequencing of the 16S rRNA gene. Twelve subjects consisted of HP-negative control (n = 2), HP-negative cancer (n = 2), HP-positive control (n = 3), and HP-positive cancer (n = 5). The analysis was focused on non-HP urease-producing bacteria (UB) and non-HP nitrosating or nitroreducing bacteria (NB) between antrum and body.ResultsGastric body samples showed higher diversity compared to gastric antrum mucosa samples but there was no significant difference. The mean of operational taxonomic units was higher in HP(−) cancer than HP(+) cancer (antrum, 273.5 vs. 228.2, P = 0.439; body, 585.5 vs. 183.2, P = 0.053). The number of non-HP UB and non-HP NB was higher in HP(−) cancer groups than the others. These differences were more pronounced in the body (P = 0.051 and P = 0.081, respectively). Analysis of overlap of non-HP UB and non-HP NB revealed the higher composition of Streptococcus pseudopneumoniae, S. parasanguinis, and S. oralis in HP(−) cancer groups than the others, only in the body (P = 0.030) but not in the antrum (P = 0.123).ConclusionsHigher diversity and higher composition of S. pseudopneumoniae, S. parasanguinis, and S. oralis in HP(−) cancer group than the other groups in the body suggest that analysis of microbiota from body mucosa could be beneficial to identify a role of non-HP bacteria in the gastric carcinogenesis.

Expression of Leucine-rich Repeat-containing G-protein Coupled Receptor 5 and CD44: Potential Implications for Gastric Cancer Stem Cell Marker.

BackgroundThe human leucine-rich repeat-containing G-protein coupled receptor (LGR) 5 and CD44 are one of the candidates for the marker of gastric cancer stem cells. We compared the expressions of two genes among control, dysplasia and cancer groups.MethodsWe compared the mRNA expression of LGR5, CD44 and CD44v8–10 and immunohistochemistry (IHC) of LGR5 and CD44 in gastric antral mucosa of 45 controls, 36 patients with gastric dysplasia, and 39 patients with early gastric cancer. Additionally, IHC of LGR5 in gastric body mucosa was analyzed. Normal mucosa adjacent to dysplastic or cancer lesions was used for the quantitative real-time–PCR and IHC.ResultsImmunoreactivity of LGR5 in base of antral mucosa was higher in non-cancerous tissues of cancer than those of control (P = 0.006), whereas the expression of LGR5 mRNA was not different among the three groups. Immunostaining of LGR5 was much stronger in the antrum than in the body of stomach (P < 0.001). Although there was no difference in antral immunointensity of LGR5 according to the severity of intestinal metaplasia, stronger immunostaining was found in the body with an aggravation of intestinal metaplasia (P trend < 0.001). The expression of CD44v8–10 mRNA was higher in cancer patients than control subjects and patients with dysplasia (P = 0.018 and 0.009) while the expression of CD44 mRNA was higher in the control groups than the others.ConclusionsIHC of LGR5 in crypt base and CD44 may be used for gastric CSC markers. LGR5 expression may be associated with the developing of corporal intestinal metaplasia. The expression of CD44v8–10 mRNA would be more suitable for gastric cancer stem cell marker than CD44 or LGR5 mRNA.

A Sweet Case of Crohnʼs

We report a case of Crohn's disease and Classical Sweet's syndrome, highlighting a unique presentation. RA is a 19 year old male with Crohn's disease on 6-mercaptopurine (6-MP) and mesalamine for over 2 years who was transferred from an outside hospital for evaluation of neutropenic fever and skin lesions. On arrival, patient was febrile and tachycardic with pancytopenia: WBC: 1.2, Hb7.6, Hct 23.7, Plt 85, ANC 340. He reported a 4 day history of initially painless erythematous lesions on various parts of his body and oral mucosa. He also had night sweats, fevers, and chills, but denied diarrhea, bloody stools, or abdominal pain. Dermatologic exam revealed painful hemorrhagic dusky, necrotic papules surrounded by a pink violaceous rim on the dorsum of his hands, upper lip, left eyelid, left cheek, and right knee (Image 1); as well as 3 shallow erythematous ulcers on his tongue. CRP 24, ESR >140. HIV, HSV, VDRL were negative. Skin and bone marrow biopsies were obtained. Patient was started on vancomycin and zosyn and 6-MP and mesalamine were held. Despite antibiotic therapy, skin lesions progressed to draining hemorrhagic ulcers with edema and spreading necrosis (Image 2) with continued fluctuating fevers. Given the clinical course and progression of skin lesions, the diagnosis of Sweet's syndrome was considered. Malignancy work-up was negative and bone marrow biopsy was consistent with drug induced myelosuppression secondary to 6-MP. Skin biopsy revealed neutrophillic infiltrate consistent with Sweet's syndrome. The patient was started on prednisone 60mg with significant improvement in skin lesions (Image 3). Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, is an uncommon inflammatory disorder characterized by abrupt painful, edematous, and erythematous skin lesions often associated with fever and leukocytosis. It is often missed on presentation as it closely resembles severe infections, such as pyoderma gangrenosum and ecthyma gangrenosum. There are 3 subtypes of Sweet's syndrome. This case describes Classical Sweet's syndrome in a young male, which is the subtype associated with IBD and usually seen in older females, given that malignancy was ruled out. Sweet's syndrome responds rapidly to systemic steroids and even topical steroids in milder cases. This case also stresses the importance of continued monitoring for cytopenia in IBD patients on chronic myelosuppressive therapy.Figure 1Figure 2Figure 3

Protective effect of intranasal vaccination of horses with a modified live equine herpesvirus type 1 vaccine

Mucosal immunity in the nasal cavity is considered to play an essential role in protecting horses from disease caused by equine herpesvirus type 1 (EHV-1), and immunoglobulin A (IgA) antibody in the nasal secretions is a key component of this mucosal immunity. Although intranasal administration of live or killed EHV-1 vaccines has been attempted with the aim of protecting horses from viral challenge, induction of virus-specific IgA after these vaccinations was not observed, and only slight mitigation of clinical signs was observed after viral challenge. Here, we measured immunological responses and performed a challenge experiment in horses intranasally immunized with a modified live EHV-1 vaccine (Nisseiken, Tokyo, Japan) that was originally licensed for intramuscular injection. Horses (n ¼ 3) were intranasally inoculated with the vaccine (1.3 106 plaque-forming units [pfu]/10 mL/head) twice with a 4-week interval. Control horses (n ¼ 2) were inoculated in the same way with dilution medium. Four weeks after the second dose had been given, the horses were challenged by intranasal inoculation of EHV-1 (strain 10-I-224, 4.0 106 pfu/10 mL/head). Sequential nasal wash samples were concentrated by ultrafiltration and subjected to ELISA to measure EHV-1-specific IgA. Viral nasal shedding and viremia were monitored by virus isolation and real-time PCR. The results of real-time PCR were considered negative if there were � 10 gene copies in the analyzed sample. EHV-1-specific IgA levels in the nasal wash increased in all of the vaccinated horses after two intranasal doses of vaccine, whereas those in the control horses remained stable. Serum virus-neutralizing titers also increased in the vaccinated horses. After viral challenge, pyrexia over 39.0 � C was observed at 1 day post-inoculation (dpi) in both of the control horses. In contrast, none of the vaccinated horses was pyretic (over 39.0 � C) throughout the experiment, although one horse had a temperature of 38.7 � C at 7 dpi. Viral nasal shedding in the control horses was detected at 1 to 6 dpi, with a highest mean gene copy number of 103.8. In contrast, viral nasal shedding in the vaccinated horses was detected only at 1 to 2 dpi, with a highest mean gene copy number of 102.3. Viremia was detected in all horses at 5 to 11 dpi, with individual durations of 2 to 6 days. Intranasal immunization of horses with the live EHV-1 vaccine resulted in the production of EHV-1-specific IgA in the nasal mucosa and virus-neutralizing antibody in the whole body. Virus replication in the nasal mucosa after viral challenge was lower in vaccinated horses than in control horses; virus-specific IgA induced by the intranasal vaccination might have been responsible for this. The absence of pyrexia over 39.0 � C in the vaccinated horses indicated that the immunity induced by intranasal vaccination was effective in protecting horses from EHV-1-induced pyrexia.

H. PYLORI INFECTION, ENDOSCOPIC, HISTOLOGICAL ASPECTS AND CELL PROLIFERATION IN THE GASTRIC MUCOSA OF PATIENTS SUBMITTED TO ROUX-EN-Y GASTRIC BYPASS WITH CONTENTION RING: a cross sectional endoscopic and immunohistochemical study.

Morbid obesity treatment through vertical gastroplasty Roux-en-Y gastric bypass initially used a contention ring. However, this technique may create conditions to the development of potentially malign alterations in the gastric mucosa. Although effective and previously performed in large scale, this technique needs to be better evaluated in long-term studies regarding alterations caused in the gastric mucosa. To analyze the preoperative and postoperative endoscopic, histological and cell proliferation findings in the gastric antrum and body mucosa of patients submitted to the Roux-en-Y gastric bypass with a contention ring. We retrospectively evaluated all patients submitted to Roux-en-Y gastric bypass with a contention ring with more than 60 months of postoperative follow-up. We compared the preoperative (gastric antrum and body) and postoperative (gastric pouch) gastric mucosa endoscopic findings, cell proliferation index and H. pylori prevalence. We evaluated cell proliferation through Ki-67 antibody immunohistochemical expression. In the study period, 33 patients were operated with the Roux-en-Y gastric bypass using a contention ring. We found a chronic gastritis rate of 69.7% in the preoperative period (gastric antrum and body) and 84.8% in the postoperative (gastric pouch). H. pylori was present in 18.2% of patients in the preoperative period (gastric antrum and body) and in 57.5% in the postoperative (gastric pouch). Preoperative cell proliferation index was 18.1% in the gastric antrum and 16.2% in the gastric body, and 23.8% in the postoperative gastric pouch. The postoperative cell proliferation index in the gastric pouch was significantly higher (P=0.001) than in the preoperative gastric antrum and body. Higher cell proliferation index and chronic gastritis intensity were significantly associated to H. pylori presence (P=0.001 and P=0.02, respectively). After Roux-en-Y gastric bypass with contention ring, there was a higher chronic gastritis incidence and higher cell proliferation index in the gastric pouch than in the preoperative gastric antrum and body. Mucosa inflammation intensity and cell proliferation index in the postoperative gastric pouch were associated to H. pylori presence and were higher than those found in the preoperative gastric antrum and body mucosa.

Histopathological features of mucosa atrophy in atrophic body gastritis

Introduction: Gastric mucosa atrophy became a major issue in gastric pathology because of its connection with risk lesions for gastric cancer. Although gastric atrophy is frequently associated with different diseases, it has been included in many studies simply as a generic pathological condition, and different causes of gastric atrophy are omitted. Objective: To study the histopathological features of gastric mucosa atrophy inH. pylori- negative patients with atrophic body gastritis (ABG). Material and methods: Consecutive cases of patients diagnosed with ABG, and presenting normal or just lightly inflamed antral mucosa, were studied. Patients with gastrointestinal cancer and those with history of prior gastrointestinal surgery were excluded. The presence of intestinal metaplasia and pseudoantral (PSA) metaplasia in atrophic body mucosa was assessed. Results: During the period of 2004-2006 a total of 7,309 patients underwent gastroesophageal endoscopy with biopsies of the gastric mucosa; 3,556 (48.6%) were males, and 3,713 (51.4%) females. Among them, 105 had the diagnosis of ABG confirmed, with 32 (30.5%) males, and 73 (69.5%) females (p < 0.001). Intestinal metaplasia and/or PSA metaplasia were identified in all patients. As isolated lesions, PSA metaplasia was more frequent than intestinal metaplasia, respectively 42 (40%) vs. four (3.8%) cases. In most patients (56.2%) both types of metaplasia occurred simultaneously, and no differences were observed among genders (p = 0.67). Conclusion: Gastric mucosa atrophy in ABG shows distinctive histopathological features which should be considered in studies on the relationship between gastric mucosa atrophy and gastric cancer.

White Gastric Mucosa in a Dialysis Patient

Question: An asymptomatic 66-year-old Japanese man underwent esophagogastroduodenoscopy for screening purposes. The patient had been undergoing hemodialysis for >30 years and had been diagnosed with dialysis-related amyloidosis of the tongue 8 years previously (Figure A). He had been taking lanthanum carbonate, an orally administered phosphate binder, for 5 years, in addition to taking rabeprazole, sarpogrelate, carvedilol, calcitriol, celecoxib, D-sorbitol, brotizolam, and warfarin. Esophagogastroduodenoscopy revealed slightly granular, white mucosa in the gastric body (Figure B, C). Laboratory testing revealed renal dysfunction and anemia owing to chronic renal failure. Electrolytes, including sodium, potassium, chloride, calcium, and magnesium, were all within their normal ranges. Testing for Helicobacter pylori from biopsy specimens of the stomach was proven negative histologically. What is the diagnosis? Look on page 323 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Gastric mucosal biopsies in non ulcer dyspepsia: A histopathologic study

Background: Non-ulcer dyspepsia (NUD) is a major health problem and one of the most common causes of morbidity and economic loss. The aim of the study was to determine the pattern of gastric mucosal histopathologic alterations and frequency of Helicobacter pylori in patients with NUD.Materials and Methods: Patients presenting to Gastroenterology Out Patient Department over a period of one year with symptoms of dyspepsia but without any endoscopic lesion were taken up for the study and evaluated by obtaining two gastric mucosal biopsy specimens each from antrum and body mucosa. The specimens were processed and examined histologically using the updated Sydney system.Results: Gastric biopsies from 102 patients (63 females and 39 males) with NUD were studied. Histological examination of gastric mucosal biopsies showed that 82.3% of NUD patients had histopathological features of gastritis. Chronic infl ammation was present in 84 (82.3%), activity was seen in 63 (61.7%), glandular atrophy was seen in 10 (9.8%) and intestinal metaplasia was seen in 4 (3.9%) patients with NUD on gastric biopsy. Maximum number of patients with NUD had Sydney score of less than 5 (68.6%).H pylori were identifi ed on gastric mucosal biopsies in 49 (48.0%) patients with NUD based on H &amp; E and Geimsa stained sections.Conclusion: NUD is a clinical problem which occurs in both sexes in all age groups; prevalence being low below 20 years of age. Patients with this condition have a high frequency of gastric mucosal inflammation and H pylori infection.Asian Journal of Medical Sciences Vol.7(2) 2015 80-84

PTH-192 Gastric adenocarcinoma of diffuse type develops on a healthy-looking mucosal background, unlike intestinal type gastric adenocarcinoma

Introduction Intestinal type gastric adenocarcinoma develops in an inflammatory and atrophic background with profound loss of secretory cells. Little is known about background gastric mucosa in diffuse type adenocarcinoma. Method Total gastrectomy specimens from non-tumoural body mucosa were selected from 22 patients with diffuse type gastric adenocarcinoma. A frequency-matched group of 22 specimens from patients with intestinal type gastric adenocarcinoma were included as comparison. Well-oriented sections were immunostained for H/K ATPase (parietal cells) and Pepsinogen I (chief cells). Absolute mucosal cell density (per mm 2 ) was measured and expressed as mean (±SD). Inflammatory changes were scored by a semi-quantitative method in both groups. Results The background densities of parietal cells (PC) and chief cells (CC) were significantly higher in diffuse type than intestinal type cancers, being 665 (±216) vs. 412 (±170) cells/mm 2 , p .001; and 847 (±259) vs. 443 (±206) cells/mm 2 , p .001, respectively. Glandular layer was significantly thicker in diffuse type [811 (±161) µm] vs. intestinal type [610 (±140) µm, P .001]. In contrast, length proportion of intestinal metaplasia was higher in intestinal type than diffuse type [23% (±30) vs 4% (±13), p .005]. Mucosal inflammation was less in diffuse versus intestinal type adenocarcinoma expressed by infiltration score of mononuclear cells ( p = 0 .011) and reactive changes ( p = 0 .005), but not in polymorphonuclear cell. Secretory cell densities and inflammation were inversely correlated in both cancer types. Conclusion The background mucosa in diffuse type gastric adenocarcinoma is much healthier than that of intestinal type adenocarcinoma, with more functional secretory cells, thicker gastric glands, less atrophy, less inflammation and less intestinal metaplasia. This suggests the existence of separate aetiological pathways leading to these distinct types of gastric adenocarcinoma. Disclosure of interest None Declared.

A Viral Outcome

Abstract Lichen planus is a muco-cutaneous inflammatory disease of unknown origin which affects various regions of the body, mostly skin and oral mucosa. The association of lichen planus with chronic hepatitis C infection is well known, but a primary presentation of chronic hepatitis C infection with lichen planus is quite rare. In this report, a middle aged woman is presented, who had features of isolated severe ulcerating lichen planus of the tongue in whom an eventual diagnosis of chronic hepatitis C infection was made; one which responded to antiviral therapy. Keywords: Lichen planus, Hepatitis C, tongue lesions, inflammatory lesions, muco-cutaneous disease

Familial atypical multiple mole melanoma syndrome in an adult Indian male-case report and literature review.

Familial atypical multiple mole melanoma syndrome (FAMMMS) is an autosomal dominant genodermatosis characterized by multiple melanocytic nevi, usually more than 50, and a family history of melanoma. It is known to be associated with carcinoma of pancreas and other malignancies involving gastrointestinal tract, breast, lung, larynx, and skin in the kindred. There is no published report of FAMMMS in dark-skinned individuals. We report a case of FAMMMS in a dark-skinned adult Indian male, who had multiple extensive nevi all over the body and oral mucosa; associated with malignant melanoma, squamous cell carcinoma (Marjolin's ulcer), and carcinoma of pancreas. His father had died of carcinoma of lung and his sister had a partial phenotypic expression. The clinical presentation of the case is discussed with review of literature.

Effects of different periods of gastric ischaemia in the viability of the tissue of body, fundus and antrum region of rabbit stomach.

BACKGROUND: Despite the rich vascular arcade of the stomach, gastric ischemia represents an important medical challenge and can be the consequence of obstructive or non-obstructive vascular processes of pathological or iatrogenic origin. AIM: To assess the effects of acute gastric ischaemia on the different regions of the stomach. METHOD: Fifteen New Zeland rabbits were divided into three groups: group 1, animals were observed during 3 h; group 2, during 6 h; group 3, during 12 h. Rabbit stomachs were subjected to devascularization of the greater and lesser curvatures. After predetermined time, the stomachs were removed for macro and microscopic studies. RESULTS: Haemorrhagic necrosis was more marked in the gastric fundus and body. In contrast, the antropylorus remained preserved in 80% of the animals. Necrosis of the gastric body and fundus mucosa were observed in all animals after 6 h and 12 h of ischaemia. CONCLUSION: Acute gastric ischaemia in rabbits produces haemorrhagic necrosis of the gastric fundus and body even in a short period of time. Beside this, the antropyloric region was significantly more resistant to ischaemia.

Pernicious anemia in young: A case report with review of literature

Pernicious anemia (PA) is characterized by Vitamin B12 deficiency which arises due to lack of intrinsic factor as a result of autoimmune destruction of gastric body mucosa and loss of gastric parietal cells. Generally it is considered as a disease of the elderly as its prevalence is 0.1% in general population and 1.9% in subjects over the age of 60 years. Pernicious anemia in age group below 30 years is less common (<4%). Clinical presentation of Pernicious anemia is insidious and varied ranging from subtle anemia to serious neurological manifestations with a future risk of developing neoplastic changes in stomach. It is considered as a “great pretender” because of its wide spectrum of clinical manifestations. But once diagnosed treatment is easy with parenteral replacement and maintenance of cobalamin.

A Rare Case of Hemorrhagic Gastritis Caused By Sevelamer-Induced Necrosis

Case Report: A 64 year-old-male with history of ESRD, currently on hemodialysis presented with chief complain of nausea, bloody emesis and diffuse abdominal pain. His home medications were aspirin, hydralazine, gabapentin and sevelamer (4000 mg TID). He denied any history of NSAID use. On presentation, he was febrile, tachycardic and hypotensive. His labs were remarkable for Hb of 7.8, WBC of 10.3 and Cr of 7.7. The patient was resuscitated with normal saline and 1 unit of PRBC. CT abdomen showed pneumatosis with intramural air in the gastric fundus (Figure 1) Upper endoscopy revealed diffuse, severely friable mucosa in the gastric body, biopsy of which revealed pale yellow sevelamer crystals (Figure 2) deposited in the lamina propria of the body of the stomach. Sevelamer was discontinued and he was started on a low phosphate diet and a proton pump inhibitor. He was also advised to obtain a repeat EGD in 1 month.Figure 1: Pneumatosis with intramural air in posterior wall of the fundus of the stomach.Figure 2: Hematoxylin and eosin stain of ulcer bed with sevelamer crystals.Discussion: Sevelamer is anion exchange resin used to treat hyperphosphatemia in patients with ESRD. On hematoxylin and eosin stain, the crystals are 2-toned in appearance with bright pink accentuations on a rusty yellow background. There is very little literature on the mechanism of sevelamer mediated gastric mucosal injury. Sodium polysyterene sulfonate, a cation exchange resin used to treat hyperkalemia, is known to cause mucosal ischemia and ulceration by direct toxicity. Being an exchange resin, it is likely that sevelamer crystals cause mucosal injury by a similar mechanism of direct toxicity. To our knowledge, this is the first reported case of hemorrhagic gastritis due to sevelamer induced necrosis in the literature.

Ovarian Cancer Metastatic to the Stomach: A “Reverse Krukenberg” Tumor

Introduction: Gastric cancer is a common cause of mortality in the United States, but metastatic tumoral involvement of the stomach is rare, with an estimated prevalence of 0.7-5.4% of all gastric malignancies. Breast, lung, esophagus, and malignant melanoma represent the most common primary sites. Metastatic ovarian carcinoma comprises less than 2% of all secondary gastric cancers. Case Report: A-52 year-old female with a past medical history of metastatic serous epithelial ovarian carcinoma was admitted with a 1 week history of dull epigastric pain, nausea with small volume hematemesis, dark stool output from her colostomy, and fatigue. Her course had been complicated by perforation of the splenic flexure due to tumor invasion 2 months prior to presentation and she was status-post cytoreductive surgery and transverse loop colostomy. Laboratory testing showed her hemoglobin to be 6.5 g/dL, compared to 11.1 g/dL 1 week prior, and fecal occult blood testing was positive. CT scan showed significant thickening of the gastric wall as well as a peritoneal fluid collection adjacent to the greater curvature. Given her presentation gastroenterology was consulted to evaluate for acute gastrointestinal bleeding. She underwent EGD with findings of LA Grade A esophagitis as well as extrinsic compression on the stomach with overlying erythema and granularity of the mucosa in the gastric body. Multiple biopsies were taken and were pathologically shown to contain focal atypical glands suggestive of metastatic ovarian carcinoma. The atypical cells were located near the base of the biopsy, coursing through the muscularis mucosae with an infiltrative configuration. Immunophenotyping showed AE1/3, CK7, and PAX8 positivity and CK20 negativity, consistent with a tumor of Muellerian origin. Her bleeding resolved with PPI therapy and she was restarted on palliative chemotherapy. Discussion: Although rare, ovarian metastases to the stomach need to be on the differential diagnosis in the proper setting. This likely occurs through malignant ovarian cells being disseminated throughout the abdominal cavity by peritoneal fluid. Luminal tumor invasion begins at the serosa and progresses inward to the mucosa as shown by the pathology in our case. Diagnosis is made by endoscopy and biopsy. Immunohistochemical staining can be used in cases where it is difficult to differentiate ovarian from gastrointestinal origin, as serous ovarian carcinomas are often CK7 positive and CK20 negative, whereas gastrointestinal carcinomas tend to be CK7 negative and CK20 positive.

Slow Overmethylation of Housekeeping Genes in the Body Mucosa Is Associated with the Risk for Gastric Cancer

Helicobacter pylori infection increases age-related diverse overmethylation in gene-control regions, which increases the risk of gastric cancer. The H. pylori-associated overmethylation changes subsequently disappear when gastric atrophy and cancer develop. To identify cancer-risk epigenotypes, we traced dynamic methylation changes in the background mucosa of the stomach depending on the extent of gastric atrophy. Paired biopsy specimens were obtained from the noncancerous antrum and body mucosa of 102 patients with cancer and 114 H. pylori-positive and 112 H. pylori-negative controls. The grade of gastric atrophy was evaluated using the endoscopic atrophic border score. The methylation-variable sites at the CpG-island margins and near the transcriptional start sites lacking CpG islands were semiquantitatively analyzed by radioisotope-labeling methylation-specific PCR. We selected eight housekeeping genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR retroelements (MMP2, CDKN2A, RUNX2, and RUNX3) and eight stomach-specific genes (TFF2, PGC, ATP4B, TFF1, TFF3, GHRL, PGA, and ATP4A). Analysis of age-related methylation in the H. pylori-positive controls revealed slow overmethylation in the body and in the LTR-adjacent genes. A high-frequency overmethylation defined based on the slowly overmethylated genes was frequently observed in the body of patients with gastric cancer with open-type atrophy (OR, 12.7; 95% confidence interval, 3.2-49.8). The rapidly changing methylation of Alu-adjacent genes was barely increased in the antrum of patients with gastric cancer. Among diverse methylation changes associated with H. pylori infection, an increase in slowly changing methylation could serve as a cancer-risk marker.

PTU-164 Evidence Of Two Aetiologies Of Gastroesophageal Junctional Cancers Based On Gastric Parietal Cell Density

IntroductionSerum pepsinogen I:II ratio, a surrogate marker of atrophic gastritis, suggests that some adenocarcinomas at the gastroesophageal junction (GOJ) develop on a background of atrophic gastritis, similar to non-cardia gastric...

Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known. To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis. Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration. This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.