A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps.

Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of CYP2C19 genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of CYP2C19 prior to prescribing PPIs. There are strong data to support the influence of CYP2C19 genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on H. pylori and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.

Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores.

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S-metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.001). The natural log of CLo was lower with an AS of 1 (7.6 ± 0.4 mL/minute) vs. 2-2.25 (8.3 ± 0.6 mL/minute; P = 0.012), similar between an AS of 1 and 1.25-1.5 (7.8 ± 0.5 mL/minute; P = 0.702), and lower with an AS of 1.25-1.5 vs. 2-2.25 (P = 0.03). There was also a greater reduction in heart rate with metoprolol among study participants with AS of 1 (-10.8 ± 5.5) vs. 2-2.25 (-7.1 ± 5.6; P < 0.001) and no significant difference between those with an AS of 1 and 1.25-1.5 (-9.2 ± 4.7; P = 0.095). These data highlight linear trends among CYP2D6 AS and metoprolol PK and PD, but inconsistencies with the phenotypes assigned by AS based on the current standards. Overall, this case study with metoprolol suggests that utilizing CYP2D6 AS, instead of collapsing AS into phenotype categories, may be the most precise approach for utilizing CYP2D6 pharmacogenomics in clinical practice.

Pilot Study: Neurocognitive Disorders and Colonoscopy in Older Adults.

In a preoperative anesthesia setting with integrated neuropsychology for individuals >64 years of age, we completed a pilot study examining the association between neurocognitive disorders with frequency of missed colonoscopies and quality of bowel preparation (prep). Gastroenterologists completed the Boston Bowel Preparation Scale (BBPS) for each patient. Of 47 older adults seen in our service, 68% met criteria for neurocognitive disorders. All individuals failing to attend the colonoscopy procedure had met criteria for major neurocognitive disorder. Poor bowel prep was also identified in 100% of individuals with major neurocognitive disorder and 28% of individuals with mild neurocognitive disorder. Our pilot data suggest that, in high-risk individuals, the presence of neurocognitive disorders is risk factors for missed appointments and inadequate bowel prep. These pilot data provide reference statistics for future intervention protocols.

Endoscopic Dilation of Refractory Postlaryngectomy Strictures: A Case Series and Literature Review.

BACKGROUND: Endoscopic dilation of postlaryngectomy strictures (PLS) is safe and effective; however, PLS are often refractory and require serial dilations. Long-term outcomes of dilation in patients with refractory PLS are not well reported. MATERIALS AND METHODS: Seven patients with dysphagia and refractory PLS underwent serial endoscopic dilation therapy during a 4.5-year period. Dilation characteristics, technical success, clinical success, and diet advancement (as assessed by Diet/GT scale) were measured. Results. All strictures were complex, and there were no reported complications. The median number of dilations per patient was 12 (range 7 to 48). The average interval in between dilations was six weeks. Technical success was achieved in 6/7 patients, and clinical success was achieved in 2/7 patients. 6/7 patients had advancements in Diet/GT scores. CONCLUSIONS: Dilation of refractory PLS is safe and effective and frequently requires the use of a retrograde approach, fluoroscopic guidance, and/or lumen patency strings. Serial dilations are required to maintain luminal patency, relieve dysphagia, and advance oral diet. The definition of clinical success of dilation in these patients should avoid the use of a specific time interval between dilations to characterize success.

Endoscopic Dilation of Bariatric RNY Anastomotic Strictures: a Systematic Review and Meta-analysis.

Gastrojejunostomy anastomotic strictures are a complication of Roux-en-Y gastric bypass surgery without an established treatment guideline. A systematic review and meta-analysis were performed to determine the safety and efficacy of endoscopic dilation in their management. PubMed, Web of Science, and Cochrane Central (1994-2017) were searched. Data was analyzed with random effects meta-analysis and mixed effects meta-regression. Twenty-one observational studies (896 patients) were included. The stricture rate for laparoscopic patients was 6% (95% CI, 5-9%). Only 38% (95% CI, 30-47%) required greater than one dilation. Symptom improvement occurred in 97% (95% CI, 94-98%). The complication rate was 4% (95% CI, 3-6%). Endoscopic dilation of GJA strictures is safe, effective, and sustaining. This study can guide endoscopists in the treatment of a common bariatric surgical complication.

Upper Gastrointestinal Conditions: Nonmalignant Conditions of the Esophagus.

Eosinophilic esophagitis (EE) is an allergic disorder of the esophagus. This diagnosis requires the presence of specific symptoms and a significantly elevated number of eosinophils in the esophageal lining as determined by endoscopic biopsies. Symptoms tend to be nonspecific among patients younger than 15 years. Among adults, dysphagia is the most common symptom. Comanagement with a gastroenterology subspecialist is essential, particularly for EE patients with a stricture. EE is commonly misdiagnosed as gastroesophageal reflux disease (GERD). The diagnosis of GERD is established by symptom response (eg, postprandial heartburn, regurgitation) to acid suppression, such as administration of a once-daily proton pump inhibitor. Red flag signs and symptoms for esophageal cancer include dysphagia, weight loss, and unexplained anemia. Risk factors include tobacco use, obesity, a long history of heartburn, and a family history of esophageal cancer. Most experts agree that the presence of risk factor(s) signals the need for screening with an upper endoscopy. An abnormal or pathologic pH study result for a patient with negative endoscopy results indicates the presence of nonerosive reflux disease.

Upper Gastrointestinal Conditions: Gallbladder Conditions.

Asymptomatic patients with gallstones typically do not require treatment. Surgical intervention is indicated in most symptomatic patients with gallstones. For patients with uncomplicated cholecystitis, laparoscopic cholecystectomy performed within 24 hours of admission is associated with significantly decreased morbidity, hospital length of stay, and cost. Most gallbladder polyps are found incidentally during ultrasonography. Patients with gallbladder polyps are at increased risk of malignant transformation if they are older than 50 years; the gallbladder wall is thickened; or the polyp is adenomatous, solitary, larger than 10 mm, sessile in appearance, or has a rapid increase in size. It is crucial but sometimes difficult to differentiate between benign and malignant polyps using transabdominal ultrasonography. Cholecystectomy is recommended for all patients with a polyp larger than 1 cm.

Upper Gastrointestinal Conditions: Pancreatitis.

The most common etiologies of acute pancreatitis are gallstones (particularly 5 mm or smaller) and alcohol consumption. The serum amylase level may be normal in up to one-fifth of patients with acute pancreatitis; therefore, this level by itself is not a reliable diagnostic factor. The serum lipase level has a higher positive predictive value and specificity compared with the amylase level. Acute biliary pancreatitis with evidence of cholangitis represents an emergency indication for endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy within 24 hours of presentation. Early aggressive fluid rehydration with lactated Ringer solution and close monitoring within the first 12 to 24 hours may decrease risk of progression to systemic inflammatory response syndrome, prevent serious complications, improve morbidity, and decrease mortality from pancreatitis. Early enteral feeding reduces length of hospital stay, rate of infectious complications, and risks of morbidity and mortality. During a first hospitalization, laparoscopic cholecystectomy is recommended for patients with gallstone pancreatitis. Without cholecystectomy, approximately 20% to 30% of patients are readmitted within the next 90 days with a biliary condition or acute pancreatitis, sometimes severe. Early diagnosis and intervention in patients with chronic pancreatitis may prevent irreversible pancreatic damage.

Upper Gastrointestinal Conditions: Nonmalignant Conditions of the Stomach.

Functional dyspepsia can be categorized into two syndromes: postprandial distress syndrome and epigastric pain syndrome. Helicobacter pyloriinfection is one of the most common chronic infections worldwide. Acute H pylori infection causes dyspepsia, and chronic infection can cause peptic ulcer disease. H pylori also is one of the causative agents in gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. The incidence of H pylori infection varies among different ethnic populations and geographic locations. Screening for and eradication of H pylori infection in healthy asymptomatic high-risk individuals has reduced the incidence of gastric cancer significantly. H pylori eradication is the first-line treatment in patients with low-grade mucosa-associated lymphoid tissue lymphoma and may be curative. The monoclonal fecal antigen test and urea breath test identify active infection, confirm eradication, and have high negative and positive predictive values regardless of H pylori prevalence. Decreasing outpatient usage of antibiotics decreases H pylori resistance. The American Society for Gastrointestinal Endoscopy recommends screening for premalignant lesions in the stomach only in patients with a family history or from a high-risk ethnic group. Gastroparesis is a debilitating condition that requires care from a multidisciplinary team that can offer different management modalities.

Symptom predictability in gastroesophageal reflux disease and role of proton pump inhibitor test.

There are problems with the definition, assessment, and measurement of gastroesophageal reflux disease (GERD). The Reflux Disease Questionnaire and the GERD questionnaire are patient-reported outcome (PRO) measures for use in a primary care setting, which are easy to use and are validated. There is no widely accepted definition of a proton pump inhibitor test and performance of the test in the clinical setting is not standardized. The use of the PRO measures in primary care with predetermined cutoff values may help to reduce the cost of diagnosing GERD and increasing rates of response for evaluated patients to acid suppression.

Endoscopic lumen restoration for obstructive aphagia: outcomes of a 25-year experience.

BACKGROUND: After chemoradiation therapy for head/neck cancer, some patients develop strictures that progress to complete pharyngoesophageal occlusion. Total lumen occlusion is less often due to other conditions. Enteral access (enterostomy tube) and good nutritional status tend to minimize the significance of dysphagia and therefore may mask recognition of impending complete lumen occlusion. OBJECTIVE: Review outcomes of a 25-year experience with endoscopic lumen restoration (ELR) in 30 patients. DESIGN: Retrospective, case review study. SETTING: Two tertiary-care referral centers. PATIENTS: This study involved 30 consecutive patients referred for obstructive aphagia due to complete lumen occlusion, primarily after chemoradiation therapy for head/neck cancer. INTERVENTION: Antegrade and retrograde endoscopy with tri-plane fluoroscopy for penetrating the occluded segment, serial retrograde and antegrade dilations, plus swallowing rehabilitation therapy. MAIN OUTCOME MEASUREMENTS: Restoration of lumen patency, swallowing function, and removal of enteral feeding tube. RESULTS: ELR was successful in 30 patients in 31 of 33 attempts (93%). Return to soft to regular diet was achieved in 15 of 30 patients (50%), and fluids to pureed food with partial percutaneous endoscopic gastrostomy nutrition was achieved in 5 of 30 patients (17%). Ten of 30 patients (33%) were considered unsafe for oral feeding because of oropharyngeal neuromotor deficits. Complications occurred in 5 of 30 patients (17%), with no prolonged sequelae, deaths, or surgery, but two stents were placed for anastomotic fistulas. The median duration of follow-up was 22.75 months. LIMITATIONS: Retrospective, case review study. CONCLUSION: ELR by using tri-plane fluoroscopic guidance with antegrade and retrograde endoscopy and serial dilations allows lumen restoration and swallowing to some degree in a majority of patients. Engagement of a core team of specialists can provide optimal restoration of swallowing function.