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Indian Hills Cherokee Section, United States

Rustagi T.,Section of Digestive Diseases | Corbett F.S.,Florida Digestive Health Specialists | Mashimo H.,Harvard University
Gastrointestinal Endoscopy | Year: 2015

Background Chronic radiation proctopathy (CRP) is a common sequela occurring even many years after pelvic radiation. Current ablative therapies for bleeding ectatic vessels have the potential for deep tissue injury leading to ulcerations, perforation, and fistulas. Radiofrequency ablation (RFA) therapy avoids deep tissue injury and is a promising treatment for CRP. Objective To assess the long-term safety and efficacy of RFA for the treatment of CRP. Design Multicenter, retrospective analysis of a prospectively collected database. Setting Veterans Affairs Boston Healthcare System, Massachusetts; Sarasota Memorial Hospital and Suncoast Endoscopy of Sarasota, Florida. Patients A total of 39 consecutive patients with CRP. Interventions Endoscopic RFA of CRP. Main Outcome Measurements The primary endpoint of the study was complete resolution of rectal bleeding. Secondary endpoints included visually scored improvement of CRP on endoscopic follow-up by using a rectal telangiectasia density (RTD) grading score, improvement in hemoglobin level, and adverse events related to the procedure. Results A total of 39 male patients (mean [± standard deviation {SD}] age 72.9 ± 6.6 years) were included in the study. The mean number of RFA sessions was 1.49 (median 1, interquartile range [IQR] 1-2, range 1-4), with a mean interval of 18 weeks between sessions. Rectal bleeding stopped completely in all patients during the mean follow-up of 28 months (range 7-53 months). A significant improvement occurred in the mean (± SD) hemoglobin level from 11.8 ± 2 to 13.5 ± 1.6 g % (P <.0001). Endoscopic severity also improved significantly with an improvement in the median RTD score from 3 (IQR 2-3) to 0 (IQR 0-1) (P <.0001). Treatment with RFA led to discontinuation of blood transfusion and iron therapy in 92% and 82% patients, respectively. Limitations Retrospective analysis, lack of control group. Conclusion RFA therapy led to complete resolution of rectal bleeding in all treated CRP patients, with improvement in clinical and endoscopic indices without any major adverse events. Further controlled studies are needed to establish RFA as the endoscopic therapy of choice for treatment of CRP. © 2015 American Society for Gastrointestinal Endoscopy. Source


Tandon P.,Yale University | Inayat I.,Yale University | Tal M.,Yale University | Spector M.,Yale University | And 3 more authors.
Clinical Gastroenterology and Hepatology | Year: 2010

Background & Aims: The reduction of portal pressure in patients with early compensated cirrhosis may be more responsive to drugs increasing intrahepatic vasodilatation than those reducing portal venous inflow. The phosphodiesterase-5 (PDE-V) inhibitor sildenafil can potentially reduce portal pressure by decreasing intrahepatic resistance, but its systemic vasodilatory effects may be deleterious. The aim of this study was to evaluate the effect of sildenafil on systemic and portal hemodynamics in an open-label pilot study. Methods: Twelve patients with compensated cirrhosis and baseline hepatic venous pressure gradient (HVPG) >5 mm Hg received 25 mg of oral sildenafil. Mean arterial pressure (MAP), heart rate (HR), and HVPG were repeated after 30 and 60 minutes in 9/12 patients at 90 minutes (after an additional 25 mg of sildenafil). HVPG tracings were read by 3 blinded observers. Results: All 12 patients were Child A with median MAP of 92 mm Hg (interquartile range, 83-94) and HVPG 10.4 mm Hg (interquartile range, 6.6-13.0). While MAP decreased significantly at all time points, sildenafil had no effect on HVPG. Conclusions: As shown with other vasodilators in compensated cirrhotic patients, sildenafil at therapeutic doses for erectile dysfunction reduces MAP without reducing portal pressure. The search should continue for specific intrahepatic vasodilators. © 2010 AGA Institute. Source


Kupec J.T.,Section of Digestive Diseases
The West Virginia medical journal | Year: 2011

Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous, neurological and intestinal complications due to the mutation of the neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors (GISTs) are relatively rare primary tumors of the stomach and small intestine. Patients with NF1 are prone to developing GISTs. We present a case of recurrent gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1. A 42 year-old male with NF1 presented with significant GI bleeding; endoscopies failed to identify the source. Multiple lesions involving the small bowel were seen on laparotomy; he underwent reparative small bowel resection. Pathology showed a well circumscribed spindle cell proliferation with minimal atypia and rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations in exons 9, 11, 13 and 17 were negative. Up to 25% of patients with NF1 develop GISTs with non-specific presentations; however they may be a source of significant GI bleeding. The pathology, course and molecular composition of these tumors are different from sporadic GISTs. In NF1, GISTs are usually multiple, located in the small bowel (as opposed to the stomach as in sporadic cases) and occur at a younger age. Their clinical scenario is not unlike other hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1-associated GISTs almost uniformly do not exhibit gain-of-function activation of KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of the NF1 gene) and are not likely to respond to imatinib. Multiple means of localizing GISTs exist and capsule endoscopy should be recommended to all NF1 patients as it provides a non-invasive approach to localizing the tumors for further surgical management. Source


Slivka A.,Hepatology and Nutrition | Gan I.,Digestive Disease Institute | Jamidar P.,Section of Digestive Diseases | Costamagna G.,Policlinico Policlinico Universitario Agostino Gemelli | And 4 more authors.
Gastrointestinal Endoscopy | Year: 2015

Background Characterization of indeterminate biliary strictures remains problematic. Tissue sampling is the criterion standard for confirming malignancy but has low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) showed excellent sensitivity in a registry; however, it has not been validated in a prospective study. Objective To prospectively validate pCLE in real time during ERCP for indeterminate biliary strictures. Design Prospective, international, multicenter study. Setting Six academic centers. Patients A total of 136 patients with indeterminate biliary strictures. Interventions Investigators provided a presumptive diagnosis based on the patient history, ERCP impression, and pCLE during the procedure before and after tissue sampling results were available. A presumptive diagnosis also was made separately by a blinded investigator during ERCP and after tissue sampling to estimate care without pCLE. Follow-up was at least 6 months. Main Outcome Measurements Accuracy, sensitivity, and specificity during ERCP alone, ERCP with pCLE, and ERCP with pCLE and tissue sampling. Results A total of 112 patients were evaluated (71 with malignant lesions). Tissue sampling alone was 56% sensitive, 100% specific, and 72% (95% confidence interval [CI], 63%-80%) accurate. pCLE with ERCP was 89% sensitive, 71% specific, and 82% (95% CI, 74%-89%) accurate. After tissue sampling returned, strictures could be characterized with 88% (95% CI, 81%-94%) accuracy. Limitations No randomization of care maps. pCLE not blinded. Conclusion pCLE provided a more accurate and sensitive diagnosis of cholangiocarcinoma compared with tissue sampling alone. Incorporation of pCLE into the diagnostic armamentarium of patients with indeterminate biliary strictures may allow for a more accurate assessment, potentially reducing delays in diagnosis and costly repeat testing. (Clinical trial registration number: NCT01392274.) © 2015 American Society for Gastrointestinal Endoscopy. Source


Hoque R.,Yale University | Sohail M.A.,Yale University | Salhanick S.,Beth Israel Deaconess Medical Center | Malik A.F.,Yale University | And 3 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2012

Inflammation contributes to liver injury in acetaminophen (APAP) hepatotoxicity in mice and is triggered by stimulation of immune cells. The purinergic receptor P2X7 is upstream of the nod-like receptor family, pryin domain containing-3 (NLRP3) inflammasome in immune cells and is activated by ATP and NAD that serve as damage-associated molecular patterns. APAP hepatotoxicity was assessed in mice genetically deficient in P2X7, the key inflammatory receptor for nucleotides (P2X7-/-), and in wild-type mice. P2X7-/- mice had significantly decreased APAP-induced liver necrosis. In addition, APAP-poisoned mice were treated with the specific P2X7 antagonist A438079 or etheno-NAD, a competitive antagonist of NAD. Pre- or posttreatment with A438079 significantly decreased APAP-induced necrosis and hemorrhage in APAP liver injury in wild-type but not P2X7-/- mice. Pretreatment with etheno-NAD also significantly decreased APAP-induced necrosis and hemorrhage in APAP liver injury. In addition, APAP toxicity in mice lacking the plasma membrane ecto-NTPDase CD39 (CD39-/-) that metabolizes ATP was examined in parallel with the use of soluble apyrase to deplete extracellular ATP in wild-type mice. CD39-/- mice had increased APAP-induced hemorrhage and mortality, whereas apyrase also decreased APAP-induced mortality. Kupffer cells were treated with extracellular ATP to assess P2X7-dependent inflammasome activation. P2X7 was required for ATP-stimulated IL-1β release. In conclusion, P2X7 and exposure to the ligands ATP and NAD are required for manifestations of APAP-induced hepatotoxicity. © 2012 the American Physiological Society. Source

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