Serial Endoscopy Research Articles

GPR15 in colon cancer development and anti-tumor immune responses

IntroductionThe chemoattractant receptor, G protein-coupled receptor 15 (GPR15), promotes colon homing of T cells in health and colitis. GPR15 function in colon cancer is largely unexplored, motivating our current studies.MethodsIn human study, immune cells were isolated from tumor tissues and healthy surgical tumor margins (STM), and their proportions as well as expression of GPR15 was analyzed by flow cytometry. In mouse studies, colon cancer was induced in GPR15-deficient (KO) and GPR15-suficient (Het) mice using azoxymethane (AOM) and dextran sulfate sodium (DSS) solution in drinking water. Serial endoscopy was performed in mice to monitor and visualize the distal region of colon. Mice were euthanized 10 weeks after the initial DSS administration, and the colon length and the number of polyps were recorded. Next, we identified the effects of GPR15L on established tumors in the MC38-colorectal cancer (CRC) mouse model. Immune cells were isolated from the mice colons or tumors and assessed by flow cytometry.ResultsOur analysis of human CRC tissue revealed a significant reduction in GPR15+ immune cell frequencies in tumors compared to ‘tumor-free’ surgical margins. Similarly, our data analysis using The Cancer Genome Atlas (TCGA) indicated that lower GPR15 expression is associated with poor survival in human colon cancer. In the AOM/DSS colitis-associated colon cancer model, we observed increased colonic polyps and lower survival in Gpr15+-KO compared to Gpr15-Het mice. Analysis of immune cell infiltrates in the colonic polyps showed significantly decreased CD8+ T cells and increased IL-17+ CD4+ and IL-17+ CD8+ T cells in Gpr15-KO than in Het mice. Consistent with a protective role of GPR15, administration of GPR15L to established tumors in the MC38-CRC model increased CD45+ cell infiltration, enhanced TNFa expression on CD4+ and CD8+ T cells at the tumor site and dramatically reduced tumor burden.DiscussionOur findings highlight an important, unidentified role of the GPR15-GPR15L axis in promoting a tumor-suppressive immune microenvironment and unveils a novel, colon-specific therapeutic target for CRC.

Intratympanic Administration of Dieckol Prevents Ototoxic Hearing Loss.

Objective. Systemic administration of dieckol reportedly ameliorates acute hearing loss. In this study, dieckol was delivered to the inner ear by the intratympanic route. The functional and anatomic effects and safety of dieckol were assessed using the rat ototoxicity model. Materials and methods. Dieckol in a high-molecular-weight hyaluronic acid vehicle (dieckol+vehicle group) or vehicle without dieckol (vehicle-only group) were randomly delivered into 12 ears intratympanically. Ototoxic hearing loss was induced by intravenous administration of cisplatin, gentamicin, and furosemide. The hearing threshold and surviving outer hair cells (OHC) were enumerated. Biocompatibility was assessed by serial endoscopy of the tympanic membrane (TM), and the histology of the TM and the base of bulla (BB) mucosa was quantitatively assessed. Results. The hearing threshold was significantly better (difference of 20 dB SPL) in the dieckol+vehicle group than in the vehicle-only group. The number of surviving OHCs was significantly greater in the dieckol+vehicle group than in the vehicle-only group. There were no signs of inflammation or infection in the ear. The thickness of the TM and the BB mucosa did not differ between the two groups. Conclusion. Intratympanic local delivery of dieckol may be a safe and effective method to prevent ototoxic hearing loss.

Serial evaluation of segmental esophageal reconstruction using a polyurethane scaffold in a pig model

BackgroundMany esophageal pathologies are clinically treated by resection and reconstruction of the esophagus. Surgical esophagectomy remains a morbid procedure and despite minimally invasive advances, has changed little in decades. Novel approaches to esophageal segmental resection and reconstruction are an unmet need.MethodsCircumferential thoracic esophageal transection was performed in both male and female pigs and the defects reconstructed using 5 or 10 cm polyurethane (PU) tubular grafts and stented. A subset were treated with stent only. Animals were survived to 14, 30, 60, and 399 days. Tissues were evaluated histologically, and via non-invasive serial endoscopy and contrast swallowing studies in long-term animals.ResultsLuminal patency was achieved in all animals with no clinical evidence of leak. In short-term animals, there was healing noted in all cases with a variably sized region of ulceration remaining at the most central part of the repaired tube (between the proximal and distal anastomosis). In four long-term animals following stent removal, two resumed normal diet and thrived, while two animals were euthanized prior to the proposed endpoint because of stricture formation and inability to tolerate a normal diet. Re-epithelialization was observed in all groups, and more complete over time.ConclusionsThe PU scaffold provides a matrix across which formation of new tissue can occur. The mechanisms through which this happens remain unclear, but likely a combination of fibrosis and tissue contraction, in conjunction with new tissue formation.

Gastric subepithelial tumor: long-term natural history and risk factors for progression.

Subepithelial tumors are often detected incidentally during upper gastrointestinal endoscopy. However, their natural history and clinical management have yet to be clearly established. The aim of this study was to evaluate the natural history and risk factors for progression of gastric SETs. The study retrospectively reviewed the medical records of patients who were diagnosed with gastric SET using upper gastrointestinal endoscopy between January 2005 and December 2017. Tumor progression was defined by a ≥ 25% increase in diameter. Among 3237 patients, 1859 underwent serial upper gastrointestinal endoscopy for more than six months. Endoscopic ultrasonography was further performed in 733 (39.43%) patients. Resection was performed in 73 (3.93%) patients. Tumor progressed in 138 (7.42%) patients over a mean follow-up period of 59.41months (range, 5-215months). In progressed tumors, the mean initial size was 15.01mm (range, 2-50mm) and the mean size increment was 12.86mm (range, 3-50mm). Large initial tumor size (OR: 1.03, 95% CI: 1.01-1.05), surface ulcer or erosion (OR: 2.47, 95% CI: 1.21-5.06), lobulated shape (OR: 3.76, 95% CI: 2.00-7.06), and middle-third location (OR: 1.65, 95% CI: 1.08-2.52) were significant risk factors for tumor progression. Large SETs had higher rates of progression and tended to grow faster than smaller tumors (r = 0.44, p < 0.001). The majority of gastric SETs did not increase in size during the long-term follow-up. Serial endoscopy may be sufficient as a follow-up tool for small SETs with intact overlying mucosa without lobulated shape.

Receipt of Serial Endoscopy Procedures Prior to Esophageal Adenocarcinoma Diagnosis Is Associated with Better Survival.

The poor prognosis of esophageal adenocarcinoma (EAC) has focused efforts on early detection by serial endoscopic surveillance of Barrett's esophagus (BE). Previously, we reported that receipt of endoscopy before EAC diagnosis was associated with improved survival. We aimed to refine our previous analysis, assessing surveillance as measured by performance of serial endoscopy before EAC diagnosis and evaluating its association with stage and survival. A retrospective cohort study was performed using the Surveillance, Epidemiology and End Results-Medicare database. Patients aged ≥ 70years with EAC diagnosed during 1998-2009 were identified. Diagnosis with BE and receipt of ≥ 2 upper endoscopic procedures within 5years before cancer diagnosis were identified. We compared a reference group not receiving serial endoscopy to 3 patterns based on ≥ 2 endoscopy dates relative to a timepoint 2years before cancer diagnosis: "remote," "recent," and "sustained." Among 5532 patients, 28% (n = 1,575) had localized stage. Thirteen percent (n = 703) received ≥ 2 endoscopic procedures before cancer diagnosis: 224, 298, and 181 in the "recent," "remote," and "sustained" groups. Serial endoscopy and prior BE were associated with localized stage ("sustained" group OR 2.95, 95% confidence interval [CI] 2.07, 4.19; prior BE OR 2.68, 95% CI 2.03, 3.56). Serial endoscopy was associated with improved survival even with adjustment for lead time bias ("sustained" group HR 0.45, 95% CI 0.37, 0.55) and length time bias. Sustained endoscopy was associated with earlier stage and improved survival. These results support the role of sustained surveillance in early detection of EAC.

Jejunal Necrosis after Embolization with Ethylene Vinyl Alcohol Copolymer

A 61-year-old man with a left lung allograft for idiopathic pulmonary fibrosis presented with pneumonia, sepsis, and a hemoglobin level of 5.8 g/dL. The early hospital course included episodic maroon-colored stools without source identification on serial endoscopy.

Magnetic cholecysto-duodenal anastomosis

Introduction There is a growing interest in minimally invasive endoscopic gallbladder drainage therapies. Unlike stenting, a technology based on magnetic compression could theoretically produce a durable drainage anastomosis without residual foreign material. This study aimed to evaluate the safety and technical feasibility of a cholecysto-duodenal magnetic compression anastomosis. Material and methods We performed a survival study of two Yorkshire pigs. Duodenal magnets were deployed endoscopically; reciprocal gallbladder magnets were placed laparoscopically, and the magnets were coupled. Pigs underwent serial endoscopy documenting magnet expulsion and evolution of cholecysto-duodenal anastomosis creation. Necropsies and histological evaluation were performed. Primary endpoints were technical success and safety. Secondary endpoints included anastomosis integrity, patency, and histologic characteristics. Results Magnets were successfully delivered and coupled. Patent, leak-free anastomoses formed by day 4. Magnets were expelled by day 10. All anastomoses were widely patent at one month (mean diameter 15 mm). Necropsy showed the absence of adhesions affecting the anastomosis. Histology showed complete re-epithelialization without inflammation or foreign body reaction. Conclusions Magnetic cholecysto-duodenal anastomosis for gallbladder drainage appears safe and feasible in the animal model. The anastomoses are patent, leak-free, and without inflammation from the presence of foreign material. Technical modifications for magnet delivery under endoscopic ultrasound (EUS) guidance are currently underway.

Gastroesophageal reflux disease after peroral endoscopic myotomy: Short-term, medium-term, and long-term resultsGastroesophageal reflux disease after peroral endoscopic myotomy (POEM)

Introduction and aimsAchalasia is characterized by incomplete relaxation of the lower esophageal sphincter and esophageal aperistalsis. The efficacy of peroral endoscopic myotomy (POEM) is similar to that of the Heller myotomy, with an apparently greater prevalence of gastroesophageal reflux disease. Our aim was to determine the presence of GERD in a post-POEM cohort of Mexican patients with achalasia and follow-up of at least 12 months. Materials and methodsA retrospective cohort study was conducted on post-POEM patients with a minimum of 12 months of follow-up, within the time frame of 2012 to 2017. Pregnant patients were excluded. Serial endoscopy, pH study, and GERDQ application were performed. Univariate and bivariate data analyses were carried out and statistical significance was set at a P<0.05. ResultsSixty-eight patients had post-POEM follow-up for 12 months. Of those patients, follow-up continued to 24 months for 58, 36 months for 47, 48 months for 39, and 60 months for 25. Mean patient age was 47.8±14.3 years, 57.3% of the patients were women, 77.9% were treatment-naïve, and 54.4% had type II achalasia. The pH study, endoscopy, and questionnaire were positive in 73, 28, and 18% at 3 months; 48, 35, and 13% at 6 months, and 55, 30, and 15% at 12 months, respectively. Once the proton pump inhibitor was begun, the percentages decreased to 5, 2, and 6% at 24 months; 6, 2, and 8% at 36 months; 4,1, and 6% at 48 months; and 3, 1, and 4% at 60 months, respectively. There was no relation between the efficacy of POEM and the presence or intensity of GERD. There were no secondary complications due to gastroesophageal reflux. ConclusionsThe post-POEM prevalence of GERD was 50% in the short term (12 months), with no evidence of complications at the medium term or long term (60 months). Gastroesophageal reflux was adequately controlled through proton pump inhibitors administration in over 95% of the cases.

Gastroesophageal reflux disease after peroral endoscopic myotomy: Short-term, medium-term, and long-term results.

Achalasia is characterized by incomplete relaxation of the lower esophageal sphincter and esophageal aperistalsis. The efficacy of peroral endoscopic myotomy (POEM) is similar to that of the Heller myotomy, with an apparently greater prevalence of gastroesophageal reflux disease. Our aim was to determine the presence of GERD in a post-POEM cohort of Mexican patients with achalasia and follow-up of at least 12 months. A retrospective cohort study was conducted on post-POEM patients with a minimum of 12 months of follow-up, within the time frame of 2012 to 2017. Pregnant patients were excluded. Serial endoscopy, pH study, and GERDQ application were performed. Univariate and bivariate data analyses were carried out and statistical significance was set at a P<0.05. Sixty-eight patients had post-POEM follow-up for 12 months. Of those patients, follow-up continued to 24 months for 58, 36 months for 47, 48 months for 39, and 60 months for 25. Mean patient age was 47.8±14.3 years, 57.3% of the patients were women, 77.9% were treatment-naïve, and 54.4% had type II achalasia. The pH study, endoscopy, and questionnaire were positive in 73, 28, and 18% at 3 months; 48, 35, and 13% at 6 months, and 55, 30, and 15% at 12 months, respectively. Once the proton pump inhibitor was begun, the percentages decreased to 5, 2, and 6% at 24 months; 6, 2, and 8% at 36 months; 4,1, and 6% at 48 months; and 3, 1, and 4% at 60 months, respectively. There was no relation between the efficacy of POEM and the presence or intensity of GERD. There were no secondary complications due to gastroesophageal reflux. The post-POEM prevalence of GERD was 50% in the short term (12 months), with no evidence of complications at the medium term or long term (60 months). Gastroesophageal reflux was adequately controlled through proton pump inhibitors administration in over 95% of the cases.

Upper Gastrointestinal Crohn’s Disease: Literature Review and Case Presentation

Upper gastrointestinal tract predominant Crohn's Disease (CD) remains an elusive clinical entity, manifesting limited or vague symptomatology, eluding clinical suspicion, and delaying subsequent diagnostic evaluation. As a result, it has not been widely described and there is a lack of clear recommendations for diagnosis or management. Standard IBD evaluation including serologic testing, imaging, and endoscopy may initially not be fruitful. Furthermore, endoscopic evaluation may be grossly normal in patients without long standing-disease. We describe an 18-year-old male who presented with only unexplained, persistent iron-deficiency anemia. Extensive outpatient testing including multiple endoscopic evaluations with standard biopsies was unfruitful. Ultimately, a positive fecal calprotectin prompted enteroscopy with endoscopic mucosal resection (EMR) in an effort to obtain a larger, deeper tissue specimen. Grossly cobblestoned mucosa along with histopathology revealing focal crypt abscesses, chronic inflammation in the lamina propria, and superficial foveolar epithelial regenerative changes were consistent with CD. This patient's case illustrates the need for a high degree of suspicion for CD in patients with unexplained or persistent iron deficiency anemias. Persistent investigation yielded an elevation in fecal calprotectin suggesting underlying gastrointestinal inflammation and prompted advanced endoscopic evaluation with EMR. Waxing and waning tissue findings are characteristic of CD and pose a unique challenge in patients with upper gastrointestinal predominant pathology. As such, diligent workup including laboratory evaluation, imaging, and serial endoscopy is critical to establish pathology and dictate subsequent management in IBD, especially upper gastrointestinal tract predominant CD.

Endoluminal Vacuum for Spontaneous Esophageal Perforation

Endoscopic endoluminal vacuum therapy is a technique that has been used traditionally for the management of surgical anastomotic leakages and perforations in the esophagus and colon. We present a case of the use of this technique in a spontaneous esophageal perforation of unknown etiology. After review of the available literature, in this video, we demonstrate the use of this technique in a novel therapy of spontaneous esophageal perforations. Patient is a 64 year old man without a significant past medical history who developed retrosternal chest pain and was found to have a spontaneous esophageal perforation that resulted in a walled off mediastinal cavity upon initial endoscopic evaluation. The cavity was filled with debris content and extensive irrigation and lavage was performed with hydrogen peroxide for further examination. To help facilitate healing, the decision was made to place an endoluminal wound vacuum. An endoluminal sponge was sutured onto a sixteen french nasogastric tube which was facilitated down the upper intestinal tract endoscopically and placed in the cavity. External suction was attached and placed at 125 mmHG on continuous suction. After 4 days, the patient had a repeat endoscopy that showed improvement in the cavity size and notable healing. A hard object was identified which was thought to be the source of the original perforation, however it was unclear the identity of this object. The sponge was downsized and replaced. A week later, the patient had a third endoscopy which demonstrated a significantly smaller cavity with healthy granulation tissue. At this time, the patient had wanted to facilitate discharge so we decided to place a fully covered esophageal stent. The patient clinically progressed well and had been tolerating a regular diet prior to discharge. Patient had a follow up endoscopy for removal of the stent and the mediastinal cavity was no longer visualized. A small outpouching remained which was closed with one hemostatic clip. The patient had been seen for follow up with stable PO tolerance and no further complications. This case helped to highlight a new therapy with a pre-existing technique for spontaneous esophageal perforations. With serial endoscopy and downsizing of the endoluminal sponge, we recognize that perforations have the ability to heal quickly and safely. This technique can be a tool to help patients avoid invasive measures to treat esophageal perforations with good endoscopic and clinical outcome. Watch the video: https://goo.gl/Nu1HDC

The evolution and outcome of surveillance of Barrett's oesophagus over four decades in a UK District General Hospital.

We present the long-term outcome of Barrett's oesophagus (BO) at a District General Hospital set against the increasing numbers of patients with gastro-oesophageal reflux disease (GORD). Data were collected prospectively over 37 years. Comparison of GORD without Barrett's (NoBO) versus BO was performed from 1/1/1977 to 31/12/2001 when the NoBO database closed and outcomes of all cases of BO diagnosed until 31/12/2011 and followed up until 31/12/2013 have been reported. During the period 1977-2001 the number of GORD NoBO cases was 11 610, and that of BO cases was 764 (6.2% of all GORD); total number of BO cases in 1977-2011 was 1468. NoBO patients were younger than BO patients: 52.2 versus 61.6 years. There was a male predominance in both groups: NoBO 55% and BO 62% (P<0.0001). The prevalence of oesophageal adenocarcinoma (OAC) was 87/1468 (5.9%) BO cases. Its incidence was 54/1381 (3.9%); the mean interval between the diagnosis of BO and incident OAC was 9 years (range 13 months-25.4 years); there was one OAC per 192 patient-years of follow-up (0.52% per year). Mortality was significantly lower in 37 patients under endoscopic surveillance at the time OAC was diagnosed (51 vs. 88% P=0.0141) partly because of older age and comorbidity of the other 17, in whom serial endoscopy was contraindicated. A proportional hazards model to allow for age estimated that the hazard rate ratio was lower in the surveillance group; however, this difference did not reach statistical significance (0.64, 95% confidence interval 0.30-1.48, P=0.08). Excluding prevalent cancers from both groups, mortality in BO was double that in NoBO (47 vs. 24%). These 37 years of observation suggest, but do not confirm, that endoscopic surveillance may reduce the risk of death from OAC. Modern technology is likely to yield better results, but larger prospective studies are needed to confirm the benefits.

PTU-145 The Rotherham Barrett’s Oesophagus Surveillance Programme. The Final Outcome after 37 Years

Introduction We present the long-term outcome of Barrett’s oesophagus (BO) observed over 37 years at a District General Hospital. We comment on the risk of developing oesophageal adenocarcinoma (OAC), its outcome, and on the value of endoscopic surveillance. Methods The study includes all patients diagnosed with BO from 1.1.1977 to 31.12.2011 and followed-up until 31.12.2013 (37 years). Patients with prevalent OAC were excluded from analysis. Data were prospectively collected and updated at every visit and all deaths recorded. Patients were followed-up by surveillance endoscopy or if contraindicated by age or co-morbidity then by clinic visit or telephone survey, with urgent endoscopy reserved for recurrence of symptoms for all patients. To compare outcome we divided OAC patients according to their method of follow-up at the time OAC was diagnosed. To adjust for the confounding factor of age when creating survival estimates we applied a Cox proportional hazards regression which included gender, age, and age squared (for there is evidence that the relationship with age and survival is not linear). Results Total numbers: 1977–2011 n = 1381. BO numbers steadily increased but plateaued towards the end of the study. BO diagnosis was confirmed by histology in 88%. Outcome: In a total FU of 10366 patient-years (mean 7.5y range 0–36y), 54/1381 (3.9%) developed OAC (mean interval 9 years, SD 5.5, range 13 months–25.4 years). Thus 1 OAC developed per 192 patient-years of FU i.e. 0.52% per year. Mortality: Deaths from all causes were 417/1381 (30.2%). Surveillance and survival: Mortality was significantly lower in the 37 patients under endoscopic surveillance at the time OAC was diagnosed (51% vs 88% p = 0.0141) due in part to the older age and co-morbidity of the other 17 in whom serial endoscopy was contraindicated (mean age 67y vs 75y p = 0.002, respectively). However, after adjusting for age there was no significant difference in mortality between the two groups (p = 0.08). Importantly though, the estimated hazard rate ratio was lower in the surveillance group (0.64, 95% CI 0.30 to 1.48). Conclusion Reduction of risk: The risk of dying from OAC was reduced by about one-third in those under endoscopic surveillance at the time OAC was diagnosed. Identifying such a reduction of risk is a very useful indicator of the value of surveillance. Numbers and implications: This substantial long-term study was still not large enough to show a significant reduction in death once adjusted for confounding factors. Our results stress the need for individual centres to contribute to data warehouses such as national registries. We now have clear evidence that BO surveillance confers benefit. With today’s technology which offers a wider scope of both palliative and curative treatments, and a continued systematic and disciplined approach, we have reason to expect that endoscopic surveillance will give even better results in the future. Disclosure of Interest None Declared

Definitive Concurrent Chemotherapy and High Dose (60-70Gy) Radiation Therapy for Esophageal Cancer

Based on the results of the intergroup-0123/RTOG 94-05 trial that demonstrated no benefit of dose escalation over 50.4 Gy in definitive chemoradiation therapy (CRT) for esophageal carcinoma, 50.4 Gy appears to be accepted as a standard dose. Radiobiologically, however, higher radiation doses, if safely delivered, could lead to better local control. We have used combination of standard FP (5-fluorouracil [5-FU] and cisplatin) chemotherapy and radiation with doses >60 Gy in the treatment of non-metastatic esophageal cancer. We report clinical outcome of the treatment protocol. Between 2002 and 2014, 78 patients with stage I-III or IV (M1 LYM) esophageal cancer were treated with CRT. Median age of the patients was 68 years (range: 46 to 84); 66 were men and 12 were women. Histology was squamous cell carcinoma in 96%. Patients were divided into 4 groups according to the stage and operability; Group 1: stage I patients (n = 10); Group 2: stage II-III operable patients (n = 16); Group 3: stage II-III (non-T4) inoperable patients (n = 19); and Group 4: stage III-IV (T4/M1 LYM) patients (n = 33). Chemotherapy protocols were either cisplatin (70 mg/m2) plus 5-FU (700 mg/m2 x 4 days) administered every 4 weeks or low-dose daily cisplatin (10 mg/m2) and 5-FU (175 mg/m2). Radiation was given by 10-MV X rays with a daily fraction of 1.8-2 Gy. Treatment volume included primary tumor plus regional lymph nodes. A total dose between 60 and 70 Gy was chosen depending on the treatment volume. Median radiation dose was 64 Gy (range: 14-70 Gy; 4 patients could not complete planned treatment). Failure was confirmed by pathology or findings of progressive disease on serial endoscopy and/or imaging studies. Overall survival (OS) and local control (LC) rates were calculated by the Kaplan-Meier method. Toxicities were evaluated by the Common Terminology Criteria for Adverse Events version 4.0. For all 78 patients, the 3-year LC and OS rates were 62% and 26%, respectively; they were 100% and 100%, respectively, in Group 1, and 76% and 40%, respectively, in Group 2. The 2-year LC and OS were 63% and 15%, respectively, in Group 3, and 62% and 16%, respectively, in Group 4. Overall response rate was 76% (complete response in 28 and partial response in 31). Grade 3 or higher acute toxicities, mainly hematological, were observed in 45% of the patients and 10% experienced grade 3-4 late toxicities. CRT with standard FP and 60-70 Gy of radiation appears to be tolerable for patients with esophageal cancer. Although outcome of this treatment in inoperable patients is not satisfactory, the 3-year LC of 100% for stage I patients and 76% for stage II-III operable patients appear promising. Further investigation is warranted to clarify the optimal radiation dose in CRT for esophageal cancer.

Risk of progression for incidental small subepithelial tumors in the upper gastrointestinal tract.

Subepithelial tumor is a relatively common finding in upper gastrointestinal endoscopy. This study aimed to evaluate the natural course of incidentally detected small subepithelial tumors in the upper gastrointestinal tract and to analyze risk factors for increase in the size of such tumors. Medical records of 1684 patients with subepithelial tumors in the upper gastrointestinal tract incidentally detected between 2004 and 2013 were retrospectively reviewed. If serial follow-up endoscopy showed significant size increase, endoscopic or surgical resection was recommended because of possibility of malignant change. 954 participants with subepithelial tumors underwent serial upper gastrointestinal endoscopy for a period > 6 months. Initial mean size of subepithelial tumors was 8.7 mm (range 1 - 35 mm). During a mean follow-up of 47.3 months (range 6 - 118 months), lesion size was unchanged in 920 participants (96.4 %), and in 34 participants (3.6 %) lesions had increased at least 25 % in diameter (mean increment 6.2 mm, range 2 - 15 mm). Subepithelial tumors with overlying mucosal changes (hyperemia, erosion, or ulcer) had a significantly higher risk of increasing in size (odds ratio [OR] = 3.61, 95 % confidence interval [95 %CI] 1.06 - 12.28). Growth rates (size increment per year) for enlarging lesions were significantly correlated with initial size (r = 0.44, P = 0.009). Most incidentally detected small subepithelial tumors in the upper gastrointestinal tract showed no size change during follow-up. Thus, regular follow-up with serial endoscopy may be sufficient for small subepithelial tumors (< 2 cm) with intact overlying mucosa.

Endoscopy and FACS analysis in classic and humanized murine models of GVHD (HUM1P.316)

Abstract It is perplexing that standard murine GVHD model endpoints of weight loss (WL) and composite clinical changes (CCC) often fail to respond to standard forms of therapy (tacrolimus and anti-p40 monoclonal antibody). To improve on the translatability of GVHD models we evaluated serial endoscopy as a means to directly assess injury and serial blood counts to predict onset of severe disease. Two models were used. CD3+ cells were magnetically depleted from bone marrow harvested from male Balb/c mice. Varying numbers of (depleted) bone marrow and splenocytes were then injected IV into lethally irradiated (8Gy) C57Bl/6 hosts. Serial endoscopy performed after GVHD onset (~2 weeks post transfer) demonstrated changes which strongly correlated with WL and CCC (R2=-0.84 and 0.79). Next we induced GVHD in a humanized model by the adoptive transfer of human PBMCs into severely immunocompromised mice (NSG). Serial blood draws demonstrated a strong correlation between peripheral blood human T cell (PBTC) numbers and WL and CCC (R2=-0.85 and 0.67 on day 42) suggesting that assessment of PBTC numbers may be applicable to the evaluation of therapies directly targeting these cell types. Day 7 human PBTC counts predicted final WL and CCC scores with high correlation (R2=-0.86 and 0.90) indicating that this metric can be used to stratify animals into groups prior to the onset of observable disease and treatment.

Incremental change in acute esophageal necrosis: report of two cases

Acute esophageal necrosis, also called "black esophagus" because of its characteristic appearance on endoscopy, is a life-threatening disease; however, its temporal evolution on endoscopy is not well understood. We describe the serial changes in acute esophageal necrosis in two patients, who underwent four upper endoscopic examinations each. Serial endoscopy demonstrated progressive necrosis extending from the lower esophagus proximally to involve the middle or upper thoracic esophagus in both patients. The first patient was treated with transhiatal esophagectomy, followed by esophageal reconstruction, and medical control of repeated duodenal ulcer bleeding. The second patient died of esophageal perforation, as a complication of Sengstaken-Blakemore tube stent placement to control esophageal bleeding. We report these cases to demonstrate the importance of early detection and prompt surgical treatment of acute esophageal necrosis.

Extra-hepatic portal venous obstruction: the Scottish experience

Introduction/background Extra-hepatic portal vein obstruction (EHPVO) is a significant cause of portal hypertension and gastrointestinal (GI) haemorrhage in children. Population based data on this rare condition is limited. Opinion is divided on the most appropriate management strategy with regards to serial therapeutic endoscopy versus the relatively new Meso-Rex shunt surgery. Aims (1) To identify all cases of EHPVO in Scotland and describe the early presentation and diagnostic work up. (2) To study the long term outcome of this condition in the era of the Meso-Rex shunt. Methods Multicentre collaborative study with retrospective longitudinal collection of data based on case note review. Information collected included demographic data, mode of presentation and endoscopic and radiological findings. Results Thirteen patients were identified (8 male, 5 female). One was lost but the remaining twelve were followed up for a mean of 9.5 years (range 1-18 years). This represented 114 years of cumulative follow up. 6/13 (46%) presented with significant GI bleeds under the age of 5. 10/13 (77%) had significant perinatal factors that may have contributed to the origin of portal venous thrombosis. 8/13 (62%) had at least one abnormality on the thrombophilia screen. There were 25 episodes of GI bleeding that required hospitalisation and 20% of these episodes required blood transfusion. 7/13 (54%) have either already had a Meso-Rex shunt or are currently being considered for this surgery. Interestingly, none of the patients who had extended treatment with propranolol have proceeded to a shunt procedure. Ultrasound scanning was successful in making the diagnosis in the majority but often needed to be repeated before this was confirmed. Conclusion The diagnosis of EHPVO requires a high index of suspicion. Unexplained gastrointestinal bleeding, particularly in the very young child should alert the clinician to the possibility of EHPVO. Perinatal risk factors may contribute to the origin of this rare disease highlighting the importance of a high standard of care in the neonatal period. Early consideration of the Meso-Rex shunt eliminates the need for therapeutic endoscopy and may result in reducing the risk of GI bleeds. Further collaborative study investigating this rare condition will help refine current practice.

Sa1647 Clinical and Endoscopic Characteristics of Gastric Tumors Diagnosed in Serial Screening Endoscopy

Sa1647 Clinical and Endoscopic Characteristics of Gastric Tumors Diagnosed in Serial Screening Endoscopy Hyoun Woo Kang*, Hyoung Jung Na, Jae Hak Kim, Jun Kyu Lee, Yun Jeong Lim, Moon Soo Koh, Jin Ho Lee, Eo-Jin Kim Internal Medicine, Dongguk University College of Medicine, Goyang, Republic of Korea; Pathology, Dongguk University College of Medicine, Goyang, Republic of Korea Background: Although biennial upper endoscopy is recommended for screening gastric cancer in Korea, there has been little study on the characteristics of clinical and endoscopic characteristics of gastric tumors diagnosed in screening endoscopy. Material and Methods: We retrospectively reviewed clinical and endoscopic characteristics of gastric cancer or adenoma cases which were diagnosed as during serial screening endoscopy and in which prediagnostic endoscopy was negative from October 2005 to July 2011 at our hospital. Clinical characteristics including mean follow up periods and endoscopic characteristics including location, pathology and prediagnostic endoscopic findings were analyzed. Results: A total of 56 lesions with a histologic diagnosis of gastric epithelial neoplasms (31 early gastric cancers, 4 advanced gastric cancers and 21 gastric adenomas) were included. All cases were consecutively treated with endoscopic submucosal dissection or operation. Mean interval between two endoscopies was 688 day (1501775 day), so we divided into less than 2 years group (n 33) and more than 2 years groups (n 20) by interval between 2 serial examinations. The locations of tumors were antrum 31, body 23 and cardia 2. The initial endoscopic findings were normal 3, gastritis 5, erosion 7, ulcer 7, atrophy 23, and intestinal metaplasia 11. The initial pathologic findings were Helicobacter pylori colonization 68.4% (13/19), neutrophils 52.6 % (10/19), mononuclear cells 84.2% (16/19), atrophy 94.7% (18/19), and intestinal metaplasia 68.8%(11/19). Among 53 cases(except 3 cases due to follow up loss), 3 patients were not cured because of metastasis at the time of diagnosis or recurrence during follow up period. In less than 2 years group, all patients were cured, but in more than 2 years group, 2 patients had distant metastasis at the time of diagnosis and 1 patient had recurrence during follow up period. It showed the statistical difference (p 0.022). Conclusions: In conclusions, findings of atrophy during screening upper endoscopy, especially in location of antrum, should necessitate precautious follow up endoscopy. Screening endoscopy for cancer detection may be done within every 2 years.

A Rare Case of Jejunal Dieulafoyʼs Lesion in a 21-Year-Old Male

Purpose: Dieulafoy's lesion is a rare and potentially life threatening cause of gastrointestinal bleeding occurring in only 2% of all gastrointestinal bleeds in adults. The most common site is the proximal third of the stomach within 6cm of the gastro-esophageal junction. Other sites include the duodenum, colon, jejunum and esophagus, with the duodenum being the most common extra-gastric site. Mortality rates for these lesions approached 80% prior to the era of endoscopy, however, rates have decreased significantly to less than 10% with use of newly available treatment options. A 21-year-old male presented with complaint of blood in his stools. He had no significant past medical history. Two days prior, he had eaten at a Chinese restaurant. Later, he had 3 heavy bowel movements and noticed fresh blood mixed with his stool. He denied any medication use, smoking or any other substance abuse. His father was diagnosed at 58 years of age with colon cancer. Physical exam revealed a hemodynamically stable, obese male. A rectal exam revealed gross blood. His hemoglobin level was 11.4. An initial CT scan of abdomen was negative for any significant findings. The patient had 3 bloody bowel movements over the next 12 hours and became hemodynamically unstable. He was aggressively resuscitated with fluids and transfused with packed red blood cells. An emergency endoscopy and sigmoidoscopy did not reveal any source of bleeding. A mesenteric angiogram was performed revealing a site of extravasation in left mid-abdomen from a jejunal branch. Embolization was performed. Additional foci of extravasation were located in jejunal branches of superior mesenteric artery where embolization could not be performed due to inaccessibility. Following angiogram, he underwent exploratory laparotomy in which 22cm of jejunum was resected and ‘jejunal polyp' was found. The ‘jejunal polyp' was found to be a dieulafoy's lesion on pathologic examination. The current report of jejunal dieulafoy's lesion is one of less than two dozen appearing in the literature. Before considering this rare diagnosis, upper and lower GI bleeds must be ruled out. Periodic or serial endoscopy and colonoscopy may be needed due to intermittent nature of bleeding. Following this, a tagged red blood cell scan as well as an angiogram may be performed in case of an active bleed. Dieulafoy's lesion must be considered as a part of differential diagnosis and must be acted upon promptly given its life threatening nature. However, this should only be done after an upper or lower GI source is excluded.