Subbaramiah Sridhar

ACG practice guidelines: Esophageal reflux testing

Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented.

Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis

Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis Guadalupe Garcia-Tsao, M.D.,1 Arun J. Sanyal, M.D.,2 Norman D. Grace, M.D., FACG,3 William D. Carey, M.D., MACG,4 the Practice Guidelines Committee of the American Association for the Study of Liver Diseases and the Practice Parameters Committee of the American College of Gastroenterology 1Section of Digestive Diseases, Yale University School of Medicine and VA-CT Healthcare System, New Haven, Connecticut; 2Division of Gastroenterology, Virginia Commonwealth University Medical Center, Richmond, Virginia; 3Division of Gastroenterology, Brigham and Women’s Hospital, Boston, Massachusetts; 4The Cleveland Clinic, Cleveland, Ohio

Eosinophilic ascites, an unusual presentation of eosinophilic gastroenteritis: A case report and review

Eosinophilic ascites (EA) is a rare disorder of unknown etiology that has been reported in both adult and pediatric patients. It is a part of the syndrome of eosinophilic gastroenteritis, which is characterized by eosinophilic infiltration of any or all layers of the gut wall and may involve any segment of the gastrointestinal tract. Peripheral eosinophilia may or may not be present. We report a case of EA that developed post partum.

Type 2 cGMP-dependent protein kinase regulates homeostasis by blocking c-Jun N-terminal kinase in the colon epithelium

Analysis of knockout animals indicates that 3′,5′cyclic guanosine monophosphate (cGMP) has an important role in gut homeostasis but the signaling mechanism is not known. The goals of this study were to test whether increasing cGMP could affect colon homeostasis and determine the mechanism. We increased cGMP in the gut of Prkg2+/+ and Prkg2−/− mice by treating with the PDE5 inhibitor Vardenafil (IP). Proliferation, differentiation and apoptosis in the colon mucosa were then quantitated. Vardenafil (Vard) treatment increased cGMP in colon mucosa of all mice, but reduced proliferation and apoptosis, and increased differentiation only in Prkg2+/+ mice. Vard and cGMP treatment also increased dual specificity protein phosphatase 10 (DUSP10) expression and reduced phospho-c-Jun N-terminal kinase (JNK) levels in the colon mucosa of Prkg2+/+ but not Prkg2−/− mice. Treatment of Prkg2−/− mice with the JNK inhibitor SP600125 reversed the defective homeostasis observed in these animals. Activation of protein kinase G2 (PKG2) in goblet-like LS174T cells increased DUSP10 expression and reduced JNK activity. PKG2 also increased goblet cell-specific MUC2 expression in LS174T cells, and this process was blocked by DUSP10-specific siRNA. The ability of cGMP signaling to inhibit JNK-induced apoptosis in vivo was demonstrated using dextran sodium sulfate (DSS) to stress the colon epithelium. Vard was a potent inhibitor of DSS-induced epithelial apoptosis, and significantly blocked pathological endpoints in this model of experimental colitis. In conclusion, Vard treatment activates cGMP signaling in the colon epithelium. Increased PKG2 activity alters homeostasis by suppressing proliferation and apoptosis while promoting differentiation. The PKG2-dependent mechanism was shown to involve increased DUSP10 and subsequent inhibition of JNK activity.

Lubiprostone induced ischemic colitis.

Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

Risk of Gastrointestinal Bleeding with Dabigatran: A Head-to-Head Comparative Study with Rivaroxaban

Introduction: The risk of gastrointestinal (GI) bleeding of dabigatran and rivaroxaban is relatively unexplored. The aim of our study was to compare this risk in both drugs. Methods: We examined the medical records of patients on either dabigatran or rivaroxaban from October 2010 to April 2013 in two hospitals. Results: A total of 374 patients (147 rivaroxaban vs. 227 dabigatran) were identified. GI bleeding occurred in 5.3% in the dabigatran when compared to 4.8% in the rivaroxaban group (p = 0.8215). Multivariate analysis showed that the odds of GI bleeding while on dabigatran for ≤40 days when compared to ≥40 days was 8.3 (p < 0.0001). In the rivaroxaban group, patients who were on the drug for ≤40 days had a higher incidence of bleeding when compared to those >40 days (OR = 2.8, p = 0.023). Concomitant use of antiplatelets (single or dual) or non-steroidal anti-inflammatory drugs was not associated with increased bleeding in the dabigatran group; however, the use of dual antiplatelet agents with rivaroxaban was associated with an increased risk of GI bleeding (OR = 7.4, p = 0.0378). Prior GI bleeding had a higher risk of bleeding in the rivaroxaban group (OR = 15.5, p = 0.0002). Conclusion: Dabigatran was not associated with a higher incidence of GI bleeding. Both drugs had a higher bleeding risk in the first 40 days.

Management of thrombocytopenia in advanced liver disease.

Thrombocytopenia (defined as a platelet count <150×10(9)) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×10(9) to 75×10(9)) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease.

Lubiprostone used with polyethylene glycol in diabetic patients enhances colonoscopy preparation quality.

AIM To assess the additive effect of lubiprostone on the quality of colon preparation in diabetics given single-dosed polyethylene glycol electrolyte (PEG) for colonoscopy. METHODS This was an investigator-initiated, single-center, single-blinded prospective trial comparing the efficacy of L + PEG to PEG alone on colon preparation quality in diabetics undergoing screening colonoscopy. The study was approved by our institutions IRB. The PEG was given as a single-dose to address patient-compliance concerns voiced by our IRB with split-dosing. All patients received only clear liquids the day prior to colonoscopy. Experimental group (Grp L) received PEG + 1 dose L 2 h prior to and 2 h after PEG completion. Control group (Grp C) received only PEG the evening prior to the colonoscopy. Patients were randomly assigned to one of the 2 groups. The endoscopist was blinded to which colon prep was given and all colonoscopies were complete. Upon colonoscopy completion, the endoscopist rated the colon prep-quality by a validated 5-point Likert scale (1-excellent to 5-inadequate). RESULTS Sixty patients were enrolled in the study; 30 Grp L and 30 Grp C. Overall, patients were excluded due to study non-completion in 12 (41%) Grp L and 5 (17%) Grp C, P = 0.04. Average colon preparation score Grp L = 2.47 and Grp C = 3.00, P = 0.09. Although this was not statistically significant, there was a trend towards improved colon prep in Grp L. Statistical significance may have been achieved if completion rates had been similar between both study groups. CONCLUSION Use of 2-L capsules with PEG resulted in a trend towards improved colon prep over PEG alone in diabetic patients when given as a single-dose regimen.

Ischemic colitis: A forgotten entity. Results of a retrospective study in 118 patients

The aim of our study was to document our 6‐year experiences in identifing the clinical characteristics, laboratory findings, risk factors and the outcomes of patients with ischemic colitis (IC) in a community hospital setting.

Sildenafil suppresses inflammation-driven colorectal cancer in mice

Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis and has been implicated in the suppression of colitis and colon cancer. In this study, we investigated the cGMP-elevating ability of the phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent disease in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against dextran-sulfate sodium (DSS)-induced barrier dysfunction. In mice treated with AOM/DSS, oral administration of sildenafil throughout the disease course reduced polyp multiplicity by 50% compared with untreated controls. Polyps that did form in sildenafil treated mice were less proliferative and more differentiated compared with polyps from untreated mice, but apoptosis was unaffected. Polyps in sildenafil treated mice were also less inflamed; they exhibited reduced myeloid-cell infiltration and reduced expression of iNOS, IFNγ, and IL6 compared with untreated controls. Most of the protection conferred by sildenafil was during the initiation stage of carcinogenesis (38% reduction in multiplicity). Administration of sildenafil during the later promotion stages did not affect multiplicity but had a similar effect on the polyp phenotype, including increased mucus production, and reduced proliferation and inflammation. In summary, the results demonstrate that oral administration of sildenafil suppresses polyp formation and inflammation in mice treated with AOM/DSS. This validation of PDE5 as a target highlights the potential therapeutic value of PDE5 inhibitors for the prevention of colitis-driven colon cancer in humans. Cancer Prev Res; 10(7); 377–88. ©2017 AACR. See related editorial by Piazza, p. 373.