Samuel A. Giday

Safety Analysis of a Hemostatic Powder in a Porcine Model of Acute Severe Gastric Bleeding

BackgroundNon-variceal upper gastrointestinal (UGI) bleeding is a common condition that requires prompt lifesaving therapy and traditional endoscopic treatments require high technical proficiency to perform.AimsThis study was conducted to identify any local or systemic histopathologic effects of a hemostatic powder in a porcine model of active, severe, non-variceal UGI hemorrhage.MethodsThis prospective, non-blinded animal study was performed in accordance with Good Laboratory Practice and Animal Care and Use Guidelines. Six animals underwent gastrotomy and creation of a looped vascular bundle, which was placed into the stomach lumen. The transplanted vascular bundle was punctured with an endoscopic needle–knife to create Forrest grade Ia or Ib bleeding. The hemostatic powder was then applied until hemostasis was achieved.ResultsInitial hemostasis was achieved in all animals. Results of pre- and post-treatment coagulation studies were similar. All animals survived at least 9xa0days post-procedure. The hemostatic powder was not found in any local, regional, or systemic tissues. Gross and histologic analysis of systemic organs showed no infarct, particulate, or embolic effects. No gross or microscopic necropsy findings were treatment-related.ConclusionsThe hemostatic powder achieved initial hemostasis (even in animals with spurting arterial bleeding) with no bowel obstruction or unintended luminal effects, no local or regional particulate effects, no systemic embolic effects, and no systemic coagulopathic effects.

M1105 Performance Characteristics of Suspected Blood Indicator Feature in Capsule Endoscopy According to Indication for Study

Background & Aims: The suspected blood indicator (SBI) feature of wireless capsule endoscopy (WCE) was developed for rapid screening of intestinal lesions with bleeding potential. Our aim was to assess the accuracy and performance characteristics of the SBI according to the indications for study in a large cohort of patients. Methods: We reviewed collected data on all WCE studies performed at Johns Hopkins Hospital from January 2006 to June 2007. Study indications were as follows: anemia of unknown origin (n 53), obscure gastrointestinal bleeding (n 112), suspected Crohn’s disease (n 122), and other (n 4). Concordant and discordant findings between gastroenterologists’ readings and SBI were recorded for each patient. Results: A total of 221 lesions with bleeding potential was detected. The overall sensitivity, specificity, positive predictive value, and negative predictive value for the SBI were 56.4%, 33.5%, 24.0%, and 67.3%, respectively. For actively bleeding lesions, the SBI sensitivity and positive predictive value were only 58.3% and 70%, respectively. The sensitivity was highest (64%) in patients undergoing WCE for suspected Crohn’s disease, with a negative predictive value of 80.4%. The sensitivity was only 58.3% and 41.3%, respectively, in studies performed for obscure gastrointestinal bleeding and anemia. Conclusions: Performance characteristics of the currently available SBI feature in WCE are suboptimal and insufficient to screen for lesions with bleeding potential. Even in patients with active intestinal bleeding, the sensitivity of SBI was less than 60%, which is lower than previously reported. However, in patients with suspected Crohn’s disease, the high sensitivity and negative predictive value of SBI may make it a useful tool for the detection of large areas of abnormal mucosa.

Natural orifice translumenal endoscopic surgery for anterior spinal procedures.

Background. NOTES techniques allow transesophageal access to the mediastinum. The aim of this study was to assess the feasibility of transesophageal biopsy of thoracic vertebrae. Methods. Nonsurvival experiments on four 50-kg porcine animals were performed. Transesophageal access to the mediastinum was attained using submucosal tunneling technique. Results. The posterior mediastinum was successfully accessed and navigated in all animals. Vertebral bodies and intervertebral spaces were easily approached while avoiding damage to adjacent vessels. Bone biopsy was successfully performed without complications, but the hardness of bone tissue resulted in small and fragmented samples. Conclusions. Peroral transesophageal access into the posterior mediastinum and thoracic vertebral bone biopsy was feasible and safe. The proximity of the esophagus to the vertebral column provides close and direct access to the thoracic spine and opens up new ground for the performance of multilevel anterior spine procedures using NOTES techniques.

Histopathological features of liver biopsy in sickle cell patients with iron overload and hepatitis C

Objective: To evaluate the effects of HCV mfectinn on hepatic pathology m sickle cell patients with Iron overload. Patients and Methods: Between 1992 and 2002, twenty of 44 sickle cell patients with territni level more than 1000 ng/dl agreed to have hver biopsy at Howard University Hospital (50% men, 50% women, median age 37 years). All the patients had multiple transfusmns in the past (more than 40 units) The majority of the patients (90%) had Hemoglobin SS and 10% had Hemoglobin SC. None of the patients had iron chelation therapy prior to biopsy. Liver biopsy results and clinical reemds were retrospectively reviewed. A blinded pathologist performed the histopathologic assessments of liver biopsies. Histology including hepatic iron content was graded. Results: Hemosidemsis was present in all of the biopsy specimens. Fourteen (70%) had 4 + iron depositions in bepatocyles, one patient had 3 + , one patient had 2 + and three patients had only 1 + hepatic iron deposition. One patient had pigment granules in hepatocytes but no iron stain was performed. Advanced cirrhosis was noted in three patients, recipient cirrhosis in one patient and bridging fibrosis in three patients Patchy sinusoidal fibrosis was obser`,ed in eight patients. All the patients with advanced and incipient cirrhoses had anti HCV antibodies, whereas only two patients with patchy sinusoidal fibrosis were HCV positive. Only one patient with HCV infection had no evidence of fibrosis All patients with HCV refection had 4 + hepatic iron whereas only 61% of patmnts without HCV refection had 4 + -iron deposition, considering that all received simi lar number of transfusions. Conclusion: Our data indicates that patients with sickle cell disease who have hepatitis C virus infection are at an increased risk of developing severe hepatic iron overload and advanced cirrhosis.

T1376 Location and Size Predict Invasiveness of Pancreatic Serous Cystic Neoplasms

subunit of the chromatin-modifying complex of proteins often known as Polycomb group (PcG). EzH2 is abnormally elevated in several cancers High levels of EzH2 correlate strongly with high-grade malignancies that are invasive, poorly differentiated and of advanced stage at presentation. Recently, miR-101 has been shown to interact with EzH2 mRNA and inhibit protein translation. Though recent reports demonstrate significant down regulation of miR101 in several solid tumors suggesting that it might serve as a solid tumor signature, its role in pancreatic cancer in targeting EzH2 is not understood. Methods: PANC-1 and MiaPaca-2 cell lines were transfected with miR-101 expression plasmid (miR-101 sequence is as follows: 5 UAC AGU ACU GUG AUA ACU GAA G 3) using effectene (Qiagen Inc., Valencia, CA). Standard protocols were followed for western blot analysis of EzH2 levels after miR-101 plasmid transfection. Triplicate growth curves were generated using Cell Counting Kit-8 (CCK-8, Dojindo, Gaithersburg, MD). Standard protocols were followed for colony formation assays, apoptosis and cell cycle phase determination. Eight week-old CB17/ICr-SCID mice were injected with 3 million PANC-1 cells subcutaneously that were transfected with miR-101 plasmid. Results: Transfection of miR-101 resulted in more than 80% knockdown of the EzH2 protein in both the cell lines. Furthermore, we show that the down regulation of miR-101 in turn increases the expression of EzH2. Significant reduction in cell proliferation, colony formation was observed in response to miR101 expression. MiR101 transfected cells showed marked reduction in palpable tumor generation by PANC1 cells, indicating its anti-oncogenic activity of In Vivo. Conclusion: MiR-101 inhibits cell proliferation, colony formation and ability of PANC-1 cells to generate palpable tumors. We conclude that miR-101 may be a potent tumor suppressor in pancreatic adeno-carcinoma by virtue of its repression of EZH2.

M1394 How Common is Crohn's Pancreatitis? A 14 Year Autopsy Review

G A A b st ra ct s pancreatic EUS TCB with or without additional FNA (n=37) by 5 endosonographers in our group. All specimens were interpreted by dedicated GI pathologists blinded to the clinical data. All complications were prospectively tracked and logged in the database. Results: AIP patients undergoing EUS TCB (38 male, 10 female; mean age 59.7 years (range 18-87)) had a mean of 2.9 TCBs (range 1-7) per patient. AIP was histologically diagnosed on EUS TCB in 35 (73%) patients; the diagnostic sensitivity varied among the 5 endosonographers from 33% to 90%. Non-diagnostic cases were found to have chronic pancreatitis (n=8), nonspecific histology (n=2), and failed tissue acquisition (n=3). EUS FNA (mean 3.4 passes, range 1-7 passes) failed to establish or suggest the diagnosis in any patient (n=37). Complications of EUS TCB included mild transient abdominal pain (n=3) and self-limited intraprocedural bleeding (n=1). No patient required hospitalization or therapeutic intervention. The diagnosis of AIP was strongly suspected prior to EUS in 14 patients as a result of their clinical, laboratory, and imaging findings. For 22 patients the diagnosis was considered preEUS as part of a broader differential, and in 12 patients the EUS appearance alone led to the initial suspicion of AIP. Serum IgG4 was ≥1x ULN in 42%, and ≥2xULN in only 23% of patients. None of the patients with EUS TCB diagnosis of AIP underwent surgery. In the patients with false negative EUS TCB, diagnosis was made by HISORt criteria. Over a mean follow-up of 2.6 years no false negative diagnoses of pancreatic cancer were identified. Conclusions: In a large cohort with AIP undergoing EUS TCB we show that pancreatic biopsy is safe and provides sufficientmaterial to definitively diagnose AIPwith high sensitivity. EUS TCB obviates the need for surgical intervention in this medically treatable disease.