Feasibility of resection and plication “RAP” technique for management of medically refractory GERD in patients with altered gastric anatomy

Background and study aims Gastroesophageal reflux disease (GERD) is common, especially in patients after gastric surgery. Medical management of GERD is ineffective in up to 30 % patients and revisional gastric surgery for management of GERD is associated with higher morbidity. We aimed to assess the safety, feasibility, and efficacy of a novel endoscopic resection and plication (RAP) anti-reflux procedure for management of medically refractory GERD in patients with altered gastric anatomy. Patients and methods The RAP procedure involves endoscopic mucosal resection and full-thickness plication over the right posterior-medial axis extending 15 mm above and 20 to 30 mm below the squamocolumnar junction. Adverse events, technical feasibility, GERD health-related quality-of-life (GERD-HRQL) scores, and medication use were prospectively recorded. Results Twenty consecutive patients with previous gastric surgery underwent RAP between September 2018 and August 2020 with a median follow-up of 5.7 months. The median procedure duration was 66 minutes (IQR 53.8–89.5). RAP was technically successful in 19 patients. One patient developed gastric hemorrhage from suture dehiscence, which was managed endoscopically, and four patients developed esophageal stricture requiring endoscopic dilation. Following the RAP procedure, significant improvement in GERD-HRQL score was observed (mean 26.9, 95 %CI 23.36–30.55, P < 0.01). Fourteen of 19 patients reported > 50 % improvement in GERD-HRQL scores. Sixteen of 18 patients reported reduction in requirement for or cessation of antacid therapy. Conclusions Patients with refractory GERD after gastric surgery have limited therapeutic options. We have demonstrated that the RAP procedure is feasible, safe, and clinically effective at short-term follow-up. It provides a potential alternative to revisional surgery in patients with altered gastric anatomy.

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression

Background The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. Methods Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk. Results 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71). Conclusions Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.

530 Case Report of Curling’s Ulcer in Convalescing Burn Patient

Introduction Although stress ulcer disease related to burn injury was noted previously, it was the report of a series of 10 cases by Curling which lent the name to the finding. Occurrence of the disease has been attributed to the stress factors of hemodynamic instability with resultant decrease in defense factors of the gastroduodenal epithelium noted as patients began to survive massive burns. At one time, the incidence was reported as high as 23% of hospitalized burn patients. However, with advances in supportive care and antacid therapy, some have wondered if Curlings ulcers may have become extinct. Methods We report the case of a 21-year-old male admitted after MVC with 53% TBSA burn (32% full-thickness) and multiple blunt trauma injuries. Early in his course he underwent splenectomy, small bowel resection, right hemicolectomy, and ORIF of an unstable lumbar fracture, and below-knee amputation. He underwent staged excision and grafting of burn wounds and had been autografted with exception of about 11%TBSA of the left lower extremity (wound controlled with allograft). On hospital day 38, the patient was noted to have melanotic colostomy output with a concomitant drop in hemoglobin level from 7.6 g/dl to 3.5 g/dl. Results The gastroenterology service was consulted, and they performed upper endoscopy on hospital day 39. A large amount of clotted blood was seen in the stomach, but the source of bleeding was not visualized. Subsequent endoscopy the following day showed an erosion of gastric mucosa in the gastric fundus consistent with ulcer, on which two clips were placed. The patient’s stool was tested for H. pylori antigen and the test was negative. The patient continued on a proton pump inhibitor, non-steroidal anti-inflammatory drugs were held, and his hemoglobin stabilized and melanotic ostomy output resolved. Conclusions Antacid therapy, H2-blockers, and proton pump inhibitors have historically been used in cases of large burns. However, in the care of other critically ill patients the association of this therapy with ventilator associated pneumonias has lead to new scrutiny. In addition, a renewed emphasis on multimodal pain management may be introducing a bias towards an increase in so-called aggressive factors, namely NSAIDS administered over longer periods. Advances in critical care of burn patients have made Curling’s ulcers rare, but not extinct.

Weakly Acidic Bile Is a Risk Factor for Hypopharyngeal Carcinogenesis Evidenced by DNA Damage, Antiapoptotic Function, and Premalignant Dysplastic Lesions In Vivo

Background: There is recent in vivo discovery documenting the carcinogenic effect of bile at strongly acidic pH 3.0 in hypopharynx, while in vitro data demonstrate that weakly acidic bile (pH 5.5) has a similar oncogenic effect. Because esophageal refluxate often occurs at pH > 4.0, here we aim to determine whether weakly acidic bile is also carcinogenic in vivo. Methods: Using 32 wild-type mice C57B16J, we performed topical application of conjugated primary bile acids with or without unconjugated secondary bile acid, deoxycholic acid (DCA), at pH 5.5 and controls, to hypopharyngeal mucosa (HM) twice per day, for 15 weeks. Results: Chronic exposure of HM to weakly acidic bile, promotes premalignant lesions with microinvasion, preceded by significant DNA/RNA oxidative damage, γH2AX (double strand breaks), NF-κB and p53 expression, overexpression of Bcl-2, and elevated Tnf and Il6 mRNAs, compared to controls. Weakly acidic bile, without DCA, upregulates the “oncomirs”, miR-21 and miR-155. The presence of DCA promotes Egfr, Wnt5a, and Rela overexpression, and a significant downregulation of “tumor suppressor” miR-451a. Conclusion: Weakly acidic pH increases the risk of bile-related hypopharyngeal neoplasia. The oncogenic properties of biliary esophageal reflux on the epithelium of the upper aerodigestive tract may not be fully modified when antacid therapy is applied. We believe that due to bile content, alternative therapeutic strategies using specific inhibitors of relevant molecular pathways or receptors may be considered in patients with refractory GERD.

Proton-Pump Inhibitor vs. H2-Receptor Blocker Use and Overall Risk of CKD Progression

Background: The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. Methods: Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR <60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk.Results: 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8,646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P=0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P=0.71).Conclusions: Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.

Antacids and their role in treatment of digestive diseases in pregnant women

Antacids are drugs that can neutralize or buffer the hydrochloric acid of the stomach without affecting its production. History of the clinical use of antacids dates back several centuries. The article discusses the advantages and disadvantages of modern antacids, provides a classification of drugs of this group, considers the mechanisms of their action, explains the term “acid-neutralizing activity”, lists indications for the use of antacids and possible adverse effects of antacid therapy. The results of various foreign and domestic studies on the use of acid-suppressive drugs, including antacids, are presented. Currently, antacids continue to be used for the symptomatic treatment of certain acid-dependent diseases, including gastroesophageal reflux disease (GERD). Due to a number of physiological reasons, GERD often worries pregnant women, most often in the third trimester of pregnancy. The choice of acid-suppressing agents in pregnant women is extremely limited, because the possibility of prescribing any drugs in this category of patients is determined by the safety of the drug, its tolerability, and the absence of teratogenic effects. Features of the mechanism of action of antacids, their favorable pharmacological properties determine the possibility of using modern combined drugs of this group during pregnancy. Relieving heartburn in pregnant women through the use of non-absorbable combined antacids is supported by the FDA, the European guidelines for the treatment of GERD. The article lists antacid drugs registered in the pharmaceutical market, special attention is paid to drugs approved for use during pregnancy.