Ulcer Margin Research Articles

P0005 Transcriptomic analysis reveals molecular differences between intestinal tuberculosis and ileal Crohn's Disease

Abstract Background Intestinal tuberculosis (ITB) and ileal Crohn's disease (iCD) are common chronic granulomatous diseases of the intestine, exhibiting similarities in clinical and histopathological features, which makes differential diagnosis challenging. We aim to explore the transcriptomic signature of ITB and iCD and identify potential biomarkers for differential diagnosis. Methods We prospectively enrolled seven iCD patients, seven ITB patients, and nine healthy donors. All participants underwent laboratory tests and colonoscopies. Biopsy samples from the ulcer margins of the ileocecal region were collected for bulk transcriptome analysis. Differentially expressed genes (DEGs; P-value<0.05, fold change>2) were selected for further analysis. Results Patients with ITB and iCD showed no statistical differences in routine blood tests, inflammatory markers, or nutritional indicators. Transcriptome analysis revealed 2,690 and 1,849 differentially expressed genes (DEGs) in ITB and iCD, respectively, compared to healthy controls. KEGG pathway enrichment analysis of DEGs that changed commonly or specifically in two diseases revealed shared activation of the IL-17 signaling pathway and upregulation of cytokine-cytokine receptor interactions in the iCD and ITB groups. Distinct changes in the iCD group included upregulation of virus-related responses, neuroactive ligand-receptor interaction, efferocytosis, and downregulation of bile secretion and cholesterol metabolism. In contrast, the ITB group showed activation of chemokine signaling and complement-related pathways and downregulation of tyrosine and retinol metabolism pathways. Further comparison of inflammatory cytokines, chemokines, and extracellular matrix (ECM) related genes among the three groups revealed that ITB patients exhibited a more robust pro-inflammatory response and more pronounced ECM remodeling than iCD patients. To identify diagnostic markers for ITB and iCD, we analyzed the DEGs that changed specifically in iCD or ITB, selecting the top 20 genes with the most tremendous fold changes. We found that genes such as CCL17, PDZK1, PLA2G12B, PRRX1, and ZNF488 showed significant differences in expression between the iCD and ITB groups. Receiver Operating Characteristic (ROC) Curve analysis demonstrated strong predictive value for these five genes in distinguishing ITB from iCD patients, with AUC values of 0.8214, 0.8367, 0.8750, 0.8571, and 0.9643, respectively. Conclusion Our study advances the molecular understanding of ITB and iCD, emphasizing distinct transcriptomic responses in the mucosal tissues of these conditions. Notably, five genes—PRRX1, PDZK1, PLA2G12B, ZNF488, and CCL17—exhibited strong diagnostic potential for distinguishing ITB from iCD.

Transcriptional responses consistent with perturbation in dermo-epidermal homeostasis in septic sole ulceration

The aim of this study was to evaluate transcriptional changes in sole epidermis and dermis of bovine claws with septic sole ulceration of the lateral claw. Assessment included changes in transcripts orchestrating epidermal homeostatic processes including epidermal proliferation, differentiation, inflammation, and cell signaling. Sole epidermis and dermis was removed from region 4 of lesion-bearing lateral and lesion-free medial claws of pelvic limbs in multiparous, lactating Holstein cows. Control sole epidermis and dermis was obtained from region 4 of lateral claws of normal pelvic limbs. Transcript abundances were evaluated by real-time QPCR and relative expression analyzed by ANOVA. Relative to normal lateral claws, sole epidermis and dermis in ulcer-bearing claws exhibited downregulation of genes associated with growth factors, growth factor receptors, activator protein 1 (AP-1) and proto-oncogene (CMYC) transcription components, cell cycle elements, lateral cell-to-cell signaling elements and structures of early and late keratinocyte differentiation. These changes were accompanied by upregulation of pro-inflammatory transcripts interleukin 1 α (IL1A), interleukin1 β (IL1B), interleukin 1 receptor 1 (IL1R1), inducible nitric oxide synthase (NOS2), the inflammasome components NOD like receptor protein 3 (NLRP3), pyrin and caspase recruitment domain (PYCARD), and caspase-1 interleukin converting enzyme (CASPASE), the matrix metalloproteinases (MMP2 and MMP9), and anti-inflammatory genes interleukin 1 receptor antagonist (IL1RN) and interleukin1 receptor 2 (IL1R2). Transcript abundance varied across epidermis and dermis from the ulcer center, margin and epidermis and dermis adjacent to the lesion. Sole epidermis and dermis of lesion-free medial claws exhibited changes paralleling those in the adjacent lateral claws in an environment lacking inflammatory transcripts and downregulated IL1A, interleukin 18 (IL18), tumor necrosis factor α (TNFA) and NOS2. These data imply perturbations in signal pathways driving epidermal proliferation and differentiation are associated with, but not inevitably linked to epidermis and dermis inflammation. Further work is warranted to better define the role of crushing tissue injury, sepsis, metalloproteinase activity, and inflammation in sole ulceration.

Physiological healing of chronic gastric ulcer is not impaired by the hydrogen sulphide (H2S)-releasing derivative of acetylsalicylic acid (ATB-340): functional and proteomic approaches.

Gastric ulcers affect approx. 10% of population. Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA) predispose to or impair the physiologically complex healing ofpre-existing ulcers. Since H2S is an endogenous cytoprotective molecule, we hypothesized that new H2S-releasing ASA-derivative (ATB-340) could overcome pathological impact of NSAIDs on GI regeneration.Clinically translational gastric ulcers were induced in Wistar rats using state-of-the-art microsurgical model employing serosal application of acetic acid. This was followed by 9 days long i.g. daily treatment with vehicle, ATB-340 (6-24mg/kg) or equimolar ASA doses (4-14mg/kg). Ulcer area was assessed macro- and microscopically. Prostaglandin (PG)E2 levels,indicating pharmacological activity of NSAIDsand 8-hydroxyguanozine content,reflecting nucleic acids oxidation in serum/gastric mucosa, were determined by ELISA. Qualitative and/or quantitative pathway-specific alterations at the ulcer margin were evaluated using real-time PCR and mass spectrometry-based proteomics.ASA, unlike ATB-340, dose-dependently delayed/impaired gastric tissue recovery, deregulating 310 proteins at the ulcer margin, including Ras signalling, wound healing or apoptosis regulators. ATB-340 maintained NSAIDs-specific cyclooxygenase-inhibiting capacity on systemic and GI level but in time-dependent manner. High dose of ATB-340 (24mg/kg daily), but not ASA, decreased nucleic acids oxidation and upregulated anti-oxidative/anti-inflammatory heme oxygenase-1, 24-dehydrocholesterol reductase or suppressor of cytokine signalling (SOCS3) at the ulcer margin.Thus, ASA impairs the physiological healing of pre-existing gastric ulcers, inducing the extensive molecularly functional and proteomic alterations at the wound margin. H2S-releasing ATB-340 maintains the target activity of NSAIDs with limited impact on gastric PGE2 signalling and physiological GI regeneration, enhancing anti-inflammatory and anti-oxidative response, andproviding the pharmacological advantage.

P342 Role of the Number and Location of Endoscopic Biopsies on the Detection of Granuloma in Patients with Isolated Intestinal Tuberculosis

Abstract Background Detecting granulomas is valuable for the diagnosis of isolated intestinal tuberculosis (ITB). However, how to perform an effective endoscopic biopsy remains unclear. We aimed to explore the impact of the number and location of endoscopic biopsies on granuloma detection in patients with isolated ITB. Methods A prospective analysis was conducted in 50 patients with confirmed isolated ITB who underwent predetermined endoscopic biopsy and pathological tests. 50 patients with isolated ITB were included for analysis. The diagnosis was confirmed based on microbiological, endoscopic, and histopathological evidences. For each patient, eight endoscopic biopsy specimens were obtained from either ulcer bases (n=4) or ulcer margins (n=4). After fixation, the specimens were serially sectioned into 8 slices on average. The slices were then stained and examined by an experienced gastrointestinal pathologist who were blinded to the patient information. Results The detection rates of granulomas from 2, 4, 6, and 8 biopsy specimens were 10, 28, 50, and 82%, respectively (5/50 vs 14/50 vs 25/50 vs 41/50, P<0.00001). When 4 biopsy specimens were used, the granuloma detection rate with specimens from the ulcer base was significantly higher than that from the ulcer margin (41/50 vs 14/50, P<0.0001). 34% (17/50) of the patients had necrotising-confluent granuloma, and 12% (6/50) had confluent (>400 um) granuloma. In total, 205 granulomas were identified in 41 patients. Multi-granulomas were detected on 49 slices while mono-granulomas on were detected on 72 slices. 62.9% (129/205) of granulomas were detected in the ulcer base, 27.8% (57/205) in the lamina propria, and 9.3% (19/205) in the submucosa. Conclusion Using more than 8 or 4 biopsy specimens from the ulcer base improved the detection rate (over 50%) of necrotising or confluent granulomas for ITB. To improve the accuracy of diagnosis, clinicians should obtain ≥4 pieces of endoscopic biopsy from the ulcer base and conduct a deep biopsy into the lamina propria. Nevertheless, the integration of clinical characteristics and anti-TB responses is still required for suspected patients with undetected granulomas.

Clinical characteristics of Martorell hypertensive ischaemic leg ulcer

Objective: We sought to characterise the clinical picture of Martorell hypertensive ischaemic leg ulcer (HYTILU) by describing the ulcer borders with three clinical features: ‘the red lipstick sign’; purple border; and livedo racemosa. We also aimed to characterise comorbidities and determinants of healing time. Method: A single-centre, retrospective cohort study was conducted between 2015–2020. We scrutinised ulcer photographs for relevant clinical signs. Data on comorbidities, medication and ulcer treatments, as well as method of diagnosis and healing time, were collected from patients' electronic medical records. Results: In total, 38 female patients and 31 male patients (mean age 73 years) were assessed, with a mean follow-up time of 174 days. The ‘red lipstick-like’ margin covered 0–50% of the ulcer margin in 56.5% of the ulcers, and 51–100% of the ulcer margin in 43.5% of the ulcers. Purple border or livedo racemosa was observed in 70.5% of the ulcers. All patients had hypertension and 52.2% of patients had type 2 diabetes. A heavy cardiovascular disease burden and frequent concomitant vascular pathologies were found. Infections requiring systemic antibiotics, ulcer size and duration of symptoms before diagnosis were strongly associated with healing time. We also found that use of systemic corticosteroids and severity of hypertension (measured by the number of antihypertensive medications used) delayed healing. Conclusion: Our data suggest that ‘the red lipstick sign’ could be a novel diagnostic feature in HYTILUs alongside purple border, livedo racemosa and necrotic/fibrinous ulcer bed. The results also elucidated HYTILU comorbidities, and showed that infections and delay in diagnosis impeded healing.

Management of perforated peripheral ulcerative keratitis (PUK-Mooren’s ulcer) with iris prolapse study in two cases

Aim: The aim of this study was to describe the management of two cases of perforated peripheral ulcerative keratitis (PUK-Mooren’s ulcer) with iris prolapse by using dried sclero-corneal patch graft and subsequently replacing donor sclero-corneal patch graft. Methods: After sectoral conjunctival resection, ulcer margin excision, and prolapsed iris excision, preserved dried sclero-corneal tissue is fashioned, and patch grafting is done as an emergency. After getting the donor sclerocorneal rim, it was again fashioned (matching the size and removal of Descemet’s membrane) and replaced the dried scleral patch graft followed by a bandage contact lens. Results: Eleven to 16 months after their initial evaluation, these patients still had some useful vision and selfsatisfaction. Conclusion: A dried sclera-corneal patch graft could be a satisfactory option in the temporary management of perforated PUK with iris prolapse until donor tissue is available. This patch graft prevents hypotony, posterior synechiae, and secondary glaucoma.

S2797 Closing the Gap: First Report of Endoscopic Suture Closure of Malignant Gastric Hemorrhage

Introduction: Gastrointestinal bleeding secondary to luminal malignancy is typically difficult to manage with conventional endoscopic therapies. Endoscopic suturing devices have become increasing popular for the management of various resection defects, inadvertent perforations, and bariatric endosurgery. Limited recent data suggests that this technology is effective for refractory bleeding from benign peptic ulcer disease. Herein we describe a case of the successful endoscopic closure of a bleeding malignant gastric ulcer using endoscopic suturing. Case Description/Methods: A 60-year-old male with a past history of primary thrombocytopenia, and recent diagnosis of signet ring gastric adenocarcinoma/linitis plastica (T2, N2, M0) on FLOT chemotherapy (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) presented with hematemesis and acute on chronic anemia. Physician examination was notable for tachycardia and hypotension. Laboratory evaluation was notable for a hemoglobin of 7.8 g/dL from 15.0 g/dL four days prior. The patient was intubated and urgent upper endoscopy in the intensive care unit was performed which showed active oozing and bleeding from a cratered gastric ulcer (previously biopsy proven adenocarcinoma) on the proximal lesser curvature measuring approximately 20 mm in size (A). Diffuse thickening of gastric folds consistent with linitis plastica was also seen. Initial attempts with bipolar cautery and epinephrine injection were unable to achieve hemostasis. An endoscopic suturing system was employed to place a suture in a figure of eight fashion and cinched at end with closure of the ulcer bed (B). The ulcer bed was not visible after suturing and hemostasis was achieved (C). Repeat upper endoscopy after two weeks for nasojejunal feeding tube placement did not show presence of ulcer and any recurrent bleeding. Patient is being clinically optimized to resume chemotherapy. Discussion: To our knowledge, we describe herein the first case of successful use of endoscopic suturing for closure of a bleeding malignant gastric ulcer. We hypothesize that the thickened gastric folds secondary to the histologic nature of linitis plastica allowed for adequate tissue purchase at the margins of the bleeding gastric ulcer which would typically be precluded in malignant tissue due to its friable nature.Figure 1.: A: Endoscopic image of gastric adenocarcinoma and associated cratered ulcer with oozing hemorrhage. B: Endoscopic image of suture device during closure. C: Endoscopic image of successful approximating edges of ulcer after endoscopic suturing without evidence of bleeding.

647. A CASE OF ACUTE GASTRIC TUBE ULCER BLEEDING SAVED BY EMERGENCY SURGERY

Abstract Gastric tube ulcer is recognized as one of the complications after esophageal cancer surgery. When a ulcer bleeds, or penetrates to the pericardial space, or perforates, it often follows a fatal course due to its anatomical position and the complexity of surgical treatment. We report a case of persistent bleeding from a gastric tube ulcer after esophageal cancer operation, which was unable to treat endoscopically. The case was a 67-year-old man. Thoracoscopic subtotal esophagectomy and posterior mediastinal route subtotal gastric reconstruction were performed for middle thoracic esophageal cancer. His fifth-year regular endoscopy revealed a gastric tube ulcer. As a cause of myalgia, the patient was prescribed NSAIDs every day by a nearby doctor. Initially, no bleeding was observed, and discontinuance of NSAIDs and conservative treatment with PPI was continued. However, five months later, sudden hematemesis was observed at night, and he was transferred to a nearby doctor. Emergency endoscopy revealed gastric tube ulcer bleeding. And he was transferred to our hospital in an emergency. However, two days later, hematemesis and persistent ulcer hemorrhage were observed. Due to the difficulty of cauterizing to heartbeat, emergency surgery was performed. The first attempt was made to approach by a posterior mediastinal route, but it was difficult to confirm the ulcer and it was difficult to control bleeding without compression. Adding the thoracotomy, the ulcer was confirmed under direct vision. An ulcer defect was about 5 cm, bleeding was from the ulcer margin. Barbed suture closure and the omental patch were performed. The postoperative course was uneventful and discharged from the hospital 21 days after the operation. We experienced a rare case of acute hemorrhagic gastric tube ulcer that was difficult to treat conservatively and was saved by emergency surgery. After reconstruction of esophageal cancer, there are complicated situations such as the route of the elevated gastric tube, the position of the ulcer, and the risk of perforation to the pericardial space. Prompt and accurate medical care is required.

Morphological features of complicated gastroduodenal ulcers

The objective of the study was to evaluate structural changes in the margin of gastroduodenal ulcers complicated by perforation, bleeding or penetration in terms of the features of ulcer healing.Methods and materials. Histological and IHC studies were performed on 25 patients of the main group with perforated gastroduodenal ulcers and 23 patients of the control group with chronic recurrent ulcers complicated by bleeding and penetration. Histological sections were stained with hematoxylin and eosin, and Van Gieson's picrofuchsin. Immunohistochemical reactions were performed with antibodies to Ki-67, CD68, CD138, and CD34.Results. On macroscopic evaluation, a clear even margin of the perforation was noted. Histological examination with the background of acute dyscirculatory changes clearly shows a zone of necrosis and a weakly expressed layer of granulation tissue, which in majority of the cases was practically absent. The margin of a perforated ulcer consists of a minimally presented, clearly delimited zone of tissue detritus and a practically unchanged muscle layer. Plasma cells dominated in the cell infiltrate, and the index of proliferative activity in the epithelium of the ulcer margins was about 45 %, distributed fairly evenly.Conclusions. Perforated ulcers can be considered as a special group of ulcers with the most pronounced changes of infiltration by plasmatic cells and eosinophils, edema and acute dyscirculatory changes, uniform and fairly high proliferative activity of the epithelium. Changes in the margins of the perforated ulcer allow for complete regeneration without excessive scarring with precise suturing of the perforation.

Identification and phylogenic analysis of Leishmania species among patients and reservoir hosts based on N-acetylglucosamine-1-phosphate transferase gene in Central Iran.

Leishmaniosis, a vector-born disease that infects humans and other vertebrates, is the result of infection with Leishmania species belong to the family Trypanosomatidae. The present study was performed to determine the status of cutaneous leishmaniosis in Isfahan province. Samples were taken from the margin of skin ulcers of patients with suspected CL referred to the medical health centers in Isfahan province. Also, ear and snout samples were taken from the rodents. In total, 85 parasitologically positive samples were subjected to the PCR-RFLP method based on the nagt gene for identification of Leishmania species, also 11 samples were subjected to sequencing and phylogenetic analysis. For all positive samples, a 1450-1460 bp band of the nagt gene was amplified in PCR method. The digestion pattern of ACC1 enzyme in 79 of patients indicated L. major and in one sample was similar to L. tropica. Four rodent reservoirs distingue as L. major and one sample as L. turanica. Phylogenetic analysis confirmed the species identification and three haplotypes were reported. The results of the current study showed that L. major is the predominant species of Leishmania parasites in Isfahan province and the main reservoir of CL is Rhombomys opimus. Also, the nagt gene is a useful and practical marker for determining different species of Leishmania parasites as well as their phylogenetic analysis.

Isolated Fungating Axillary Lymph Node Metastasis in Anal Canal Carcinoma – A Rare Case Report

Anal canal cancer is the least common malignancy of the gastrointestinal tract. Main risk factors include infection with human papillomavirus strains, immunosuppression, multiple sexual partners, and receptive anal intercourse. We present a rare case of anal canal carcinoma with fungating right axillary lymph node metastasis. A 65-year-old farmer had presented to the surgical department with complaints of bleeding per rectum and ulceration around the anus for 6 months. He also gives a history of fecal incontinence and right axillary swelling. On examination, there was an ulcer around the anus circumferentially with everted edges and indurated base. There were multiple enlarged bilateral inguinal lymph nodes and fungating right axillary lymph node. Magnetic resonance imaging of the pelvis revealed features suggestive of neoplastic etiology of anal canal. Biopsy of ulcer margin and axillary lymph node was suggestive of squamous cell carcinoma. Positron emission tomography/computed tomography (PET/CT) of the whole body revealed no other site metastatic foci. The patient underwent diversion sigmoid colostomy and was started on chemoradiation (Nigro regimen). The patient had very good response to the regimen, and follow-up PET/CT scan showed no active uptake in the tumor foci.

Small intestinal mucosa-associated lymphoid tissue lymphoma with deep ulcer and severe stenosis: A case report.

IntroductionAlthough eosinophils are commonly present on the mucosa of the gastrointestinal tract, various pathological conditions may cause a secondary increase in eosinophil quantity.Presentation of caseA 78-year-old man was referred to our hospital due to abdominal pain. Examinations revealed an ulcerative lesion with white moss in the terminal ileum and severe stenosis on the oral and anal sides. Tissue biopsies obtained from the ulcer margins showed a predominance of chronic inflammatory cells and abundant eosinophils in addition to lymphocytes/plasma cells. Secondary causes of tissue eosinophilia were suspected; however, the diagnosis could not be confirmed because of atypical endoscopic findings. Partial resection of the ileum was performed for therapeutic and diagnostic purposes. Histopathology of the resected specimen identified a lymphoepithelial lesion with an invasive tendency. While CD20 staining was positive, MUM-1 and Bcl-6 staining were negative. Based on these findings, the lesion was diagnosed as a small intestinal mucosa-associated lymphoid tissue lymphoma (Lugano staging, stage II1).DiscussionHypereosinophilia in this lesion was suggested to be secondary to chronic inflammation due to tumor growth or impaired transit.ConclusionThere is a type of gastrointestinal MALT lymphoma showing an invasive tendency. In such cases, it may demonstrate atypical findings and hypereosinophilia in gastrointestinal tissues.

Microbiological Profile and Antibiotic Sensitivity Pattern of Bacteria in Diabetic Foot Ulcers in a Tertiary Care Hospital

Introduction: Diabetic foot is any foot pathology due to diabetes or sequelae of diabetes mellitus. This study was conducted to identify the common microorganisms isolated from diabetic foot and to analyse the antibiotic susceptibility pattern of bacteria isolated from diabetic foot. Materials and Method: The study was a hospital based cross-sectional study where 146 foot ulcer samples (who had type 2 diabetes) were analysed. Swabs were collected from the edge and margins of ulcers, and organisms were identified by gram staining culture and biochemical reactions. Result:Out of 146 patients, 69 specimens showed growth of organisms. Total 84 aerobic organisms were isolated and out of them, 64 cases showed bacterial growth, in which 84 bacteria were isolated, which represented an average of 1.28 organisms per case. Among these organisms, 62 gram-negative and 22 gram-positive organisms were isolated. E. coli was the most common gram-negative isolate (23.81%), followed by Pseudomonas aeruginosa (21.4%), and Klebsiella pneumonia(8.33%), while among gram-positive bacteria, S. aureus was the most common isolate (22.6%). Conclusion: Incidence of growth was 47.2% in which E. coli (23.8%) was the most common isolate. Gram-negative bacteria were more common than gram-positive bacteria. Diabetic foot infections are polymicrobial in nature.

H. pylori and peptic ulcer perforation: prevalence of infection and role in surgical outcome

Background: Perforated peptic ulcer is one of the most common surgical emergencies. Despite a definite association of H. pylori with peptic ulcer disease, its association with peptic ulcer perforation is still doubtful. The aim of the present study was to know the prevalence of H. pylori infection and its role in surgical outcome of patients.Methods: This prospective observational study was carried out at a tertiary care hospital of north India for a period of two years and included 136 consecutive patients of perforated peptic ulcer who underwent emergency laparotomy. H. pylori infection was tested on ulcer margin biopsy using rapid urease test kit and confirmed on histopathological examination.Results: 136 consecutive patients of perforated peptic ulcer were included in this study with mean age of 42.43 years and sex ratio of 11.4:1. H. pylori infection was present in fifty four percent (54%) of patients. There was no relationship of H. pylori infection with morbidity and mortality of patients.Conclusions: H. pylori infection should be assessed at the time of primary surgical management on biopsy specimen using rapid urease test and confirmed on histopathological examination. All positive patients should be subjected to H. pylori eradication therapy.

Microbiological evaluation of resection margins of the infected diabetic foot ulcer

To evaluate the impact of surgical debridement on the microbiology of resection margins of an infected diabetic foot ulcer and to compare the use of marginal sampling as a guide for antimicrobial therapy. Forty consecutive participants were studied. Tissue samples from infected diabetic foot ulcers were obtained at first contact by podiatrists. After surgical debridement to macroscopically healthy tissue, multiple samples were obtained from the margins of the residuum and also from excised non-viable tissue. Debridement was done by a single surgeon. Bacterial species were classified according to pathogenic potential a priori into Red Group-Definite pathogen causing infection, Yellow Group-Likely to be causing infection if present in more than one specimen and Green Group -Commensals, not causing infection. There was a relative reduction of 49% (p=0.002) in bacteria in the most pathogenic (red) group, and 59% (p=0.002) in the yellow group in podiatry samples compared with resection specimen. Positive cultures from margins of the residuum were observed in 75% of cases. There was a relative reduction of 67% (p=0.0001) in bacteria in the red and 48% (p=0.06) in the yellow group in marginal samples from the residuum compared with podiatry samples. After surgical debridement to healthy tissue, positive cultures from marginal tissue samples provided vital information on the presence of pathogenic bacteria. This allowed antibiotics to be individualised post-surgical debridement.

A simple way to manage a chronic ulcer at the cranioplasty titanium implant exposure site by dermal autograft and platelet-rich plasma

Abstract Rationale: Titanium implant exposure is not a rare complication after cranioplasty. Usually, we apply a free flap or local flap for reconstruction. Patient concerns: A 56-year-old male with a medical history of gout, hepatitis and chronic renal disease presented with an ulcer and implant exposure after titanium cranioplasty. The flap around the ulcer was too thin to perform local flap reconstruction. Free flap surgery was rejected by the patient. Diagnoses: The ulcer with implant exposure had little exudate without malodor. The underlying wound had epithelial ingrowth and was 1.5 cm × 0.5 cm in size over the left parietal region of the head. The wound culture was staphylococcus lugdunensis-positive. Interventions: Oral antibiotics and biofilm decontamination were used to manage peri-implantitis for 6 weeks. Dermal autografts were harvested with a thickness of 0.020 inches. A 2 mm wide area of de-epithelization was created around the ulcer margin. Platelet-rich plasma was locally injected into the periwound skin. Outcomes: The patient was followed up by telephone at 9 months postoperatively, and the scar condition was stable without recurrent ulcers. Lessons: Dermal autografts with platelet-rich plasma may serve as an alternative method when a local flap is not feasible and the wound defect is smaller than 1 cm2.

S2232 Gastrointestinal Histoplasmosis Masquerading as Crohn’s Disease in the Immunocompetent Adult

INTRODUCTION: A misdiagnosis of gastrointestinal histoplasmosis (GIH) as Crohn’s disease can be catastrophic. Endoscopic data for GIH false negative biopsy rates are not well-established in the literature. CASE DESCRIPTION/METHODS: A 38-year-old female from Ecuador presented to the gastroenterology clinic with abdominal pain, weight loss, and chronic diarrhea. She denied pulmonary symptoms, fever or recent travel for several years. Her past medical and surgical history were significant for treated hepatitis C and C-section. Physical exam revealed a diffuse and mildly tender abdomen. Outpatient colonoscopic exam reported multiple ulcers. Biopsies at ulcer margins revealed non-necrotizing granulomas. Special tests were negative for CMV, TB and fungal organisms. HIV and C. difficile were ruled out. Presumed Crohn’s disease was diagnosed. Mesalamine 1 gm QID and Prednisone 60mg taper were started. At follow up, the patient was admitted to the hospital with worsening diarrhea, abdominal pain and fever. CT abdomen/pelvis showed diffuse enterocolitis. Vancomycin and meropenem were initiated and steroids discontinued. She developed hematochezia requiring multiple blood transfusions. A flexible sigmoidoscopy found severe inflammation extending from the rectum to the sigmoid (Figure 1). A total abdominal colectomy with ileostomy for fulminant and refractory disease was performed. GMS staining revealed a vast number of yeast consistent with histoplasmosis (Figure 2). Amphotericin B followed by itraconazole was started with serial antigen monitoring. The patient’s symptoms resolved and she was discharged with an extended itraconazole regimen. DISCUSSION: This case highlights the unique challenges in GIH. The organism may persist within granulomas for years. Reactivation of latent GIH has been described in the literature and would explain our patient’s disease course. Her initial symptoms could be explained by underlying Crohn’s disease or spontaneous progression of histoplasmosis. Perhaps the greatest challenge was the initial interpretation of the negative GMS stain leading to a significant diagnostic dilemma. Histology with GMS staining may help reveal the organism, and is considered a rapid and reliable diagnostic test. However, sensitivity data is not well established. Previous case series have demonstrated a false negative rate of 11% in an AIDS population. The sensitivity data in immunocompetent hosts is not known. Importantly, a misdiagnosis will lead to treatment error and a potential fatal outcome.Figure 1.: Severe colitis and large sigmoid ulcer with proximal stricture.Figure 2.: GMS stain after total colectomy showing ovoid yeast cells consistent with histoplasma organisms.

S2133 Amyloidosis-Associated Gastric Ulceration and Submucosal Hematoma

INTRODUCTION: A 77-year-old woman with a history of atrial fibrillation treated with apixaban presented to the hospital after a presyncopal event and hematemesis. Endoscopic evaluation revealed a large submucosal hematoma, which was initially suspicious for an isolated gastric varix, and 2 large gastric ulcers which biopsy later identified as amyloidosis. CASE DESCRIPTION/METHODS: A 77-year-old woman with a history of atrial fibrillation treated with apixaban presented to the hospital after a presyncopal event. Approximately 12 hours after admission, she was noted to have frank hematemesis, requiring IV fluids, blood, and plasma transfusion. EGD demonstrated copious clotted blood in the gastric fundus and a submucosal lesion which appeared to be an isolated varix in the gastric body. The patient was then transferred to a tertiary care center to be evaluated for endoscopic cyanoacrylate therapy. Upon arrival, she was noted to have intermittent episodes of bradycardia, but otherwise remained stable. She experienced no additional episodes of GI bleeding. Repeat EGD demonstrated 2 large, clean-based gastric ulcers with beefy-red margins. Biopsy later identified these as amyloidosis. No interventions were performed on the gastric lesion initially thought to be a gastric varix. This lesion was likely a submucosal hematoma. The patient was discharged to home in stable condition on twice-daily proton-pump inhibitor therapy. DISCUSSION: Amyloidosis is characterized by the pathologic deposition of proteins throughout the body. Within the GI tract, this deposition increases the frailty of blood vessels, hinders intrinsic peristalsis and decreases the compliance of the gut wall, and may present with varying degrees of upper and lower GI bleeding. Cardiac conduction abnormalities are also associated with amyloidosis. The cornerstone of treatment for acquired amyloidosis is the treatment of the underlying disorder causing elevated amyloid precursors. Uniquely, amyloidosis is also associated with submucosal hematoma. The patient in this case presented with massive upper GI bleeding due to amyloid-induced ulcers, and bleeding from these ulcers was exacerbated by apixaban use. Two unique findings suggesting amyloidosis were unexplained bradycardia and a prominent gastric submucosal hematoma (initially thought to be a gastric varix), both of which are highly associated with amyloidosis. Although the patient was discharged in stable condition, she remains at high risk of morbidity and mortality from this systemic disease.Figure 1.: Large gastric body ulcer with prominent beefy-red margins. Biopsies from ulcer margins showed amyloidosis.Figure 2.: Two large amyloidosis-associated gastric ulcers on opposing walls of the gastric body.Figure 3.: This amyloidosis-associated submucosal hematoma was initially mistaken for a gastric varix.

Role of metaplasia during gastric regeneration.

Spasmolytic polypeptide/trefoil factor 2 (TFF2)-expressing metaplasia (SPEM) is a mucous-secreting reparative lineage that emerges at the ulcer margin in response to gastric injury. Under conditions of chronic inflammation with parietal cell loss, SPEM has been found to emerge and evolve into neoplasia. Cluster-of-differentiation gene 44 (CD44) is known to coordinate normal and metaplastic epithelial cell proliferation. In particular, CD44 variant isoform 9 (CD44v9) associates with the cystine-glutamate transporter xCT, stabilizes the protein, and provides defense against reactive oxygen species (ROS). xCT stabilization by CD44v9 leads to defense against ROS by cystine uptake, glutathione (GSH) synthesis, and maintenance of the redox balance within the intracellular environment. Furthermore, p38 signaling is a known downstream ROS target, leading to diminished cell proliferation and migration, two vital processes of gastric epithelial repair. CD44v9 emerges during repair of the gastric epithelium after injury, where it is coexpressed with other markers of SPEM. The regulatory mechanisms for the emergence of CD44v9 and the role of CD44v9 during the process of gastric epithelial regeneration are largely unknown. Inflammation and M2 macrophage infiltration have recently been demonstrated to play key roles in the induction of SPEM after injury. The following review proposes new insights into the functional role of metaplasia in the process of gastric regeneration in response to ulceration. Our insights are extrapolated from documented studies reporting oxyntic atrophy and SPEM development and our current unpublished findings using the acetic acid-induced gastric injury model.

Risk factors of lymph node metastasis after non-curative endoscopic resection of undifferentiated-type early gastric cancer.

This study aimed to investigate risk factors for lymph node (LN) or distant metastasis after non-curative endoscopic resection (ER) of undifferentiated-type early gastric cancer (EGC). Of 1124 patients who underwent ER for undifferentiated-type gastric cancer at 18 tertiary hospitals across six geographic areas in Korea between 2005 and 2014, 634 with non-curative ER beyond the expanded criteria were retrospectively enrolled. According to the treatment after ER, patients were divided into additional surgery (n = 270) and follow-up (n = 364) groups. The median follow-up duration was 59months for recurrence and 84months for mortality. LN metastasis was found in 6.7% (18/270) of patients at surgery. Ulcer [odds ratio (OR) 3.83; 95% confidence interval (CI) 1.21-12.13; p = 0.022] and submucosal invasion (OR 10.35; 95% CI 1.35-79.48; p = 0.025) were independent risk factors. In the follow-up group, seven patients (1.9%) developed LN or distant recurrence. Ulcer [hazard ratio (HR) 7.60; 95% CI 1.39-35.74; p = 0.018], LVI (HR 6.80; 95% CI 1.07-42.99; p = 0.042), and positive vertical margin (HR 6.71; 95% CI 1.28-35.19; p = 0.024) were independent risk factors. In the overall cohort, LN metastasis rates were 9.6% in patients with two or more risk factors and 1.2% in those with no or one risk factor. LVI, ulcer, submucosal invasion, and positive vertical margin are independently associated with LN or distant metastasis after non-curative ER of undifferentiated-type EGC. Surgical resection is strongly recommended for patients with two or more risk factors.