piperidines and Esophageal-Diseases

Severe gastroesophageal reflux disease is usually a chronic problem with periods of relapse, but effective medical and surgical therapies are available. Two recently introduced agents, omeprazole (Prilosec) and cisapride (Propulsid), represent advances in medical therapy; the safety of long-term, continuous omeprazole therapy is under investigation. Used by surgeons with sufficient experience, the new laparoscopic approach offers potential advantages over conventional anti-reflux surgery in suitable candidates. The decision of whether to recommend long-term medical therapy or surgery must be individualized. Medical therapy may be the best choice in elderly patients and poor surgical candidates, in patients whose symptoms are well controlled with omeprazole and who accept its benefit-risk profile, and when a highly experienced anti-reflux surgeon is not available. Surgery may be appropriate (assuming a skilled surgeon is available) in patients who are young, have trouble taking medication, need multiple agents to control symptoms, and need continuous omeprazole therapy but are unwilling to accept the theoretical risk of gastric carcinoid tumors that accompanies it.

Topics: Antacids; Anti-Ulcer Agents; Cisapride; Drug Therapy, Combination; Esophageal Diseases; Esophagogastric Junction; Fundoplication; Gastroesophageal Reflux; Hernia, Hiatal; Histamine H2 Antagonists; Humans; Laparoscopy; Life Style; Long-Term Care; Omeprazole; Peristalsis; Piperidines; Risk-Taking; Severity of Illness Index

The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH < 4.0, p < 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p < 0.01), upright reflux (p < 0.05), supine reflux (p < 0.001), and postprandial reflux (p < 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p < 0.01), supine reflux (p < 0.05), and postprandial reflux (p < 0.05). Cisapride also reduced both the number (p<0.01) and duration (p<0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.

Topics: Adult; Aged; Anti-Ulcer Agents; Cisapride; Double-Blind Method; Drug Therapy, Combination; Esophageal Diseases; Esophagitis, Peptic; Esophagogastric Junction; Female; Gastric Acid; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Monitoring, Physiologic; Muscle Contraction; Muscle, Smooth; Piperidines; Ranitidine; Time Factors

A 26-year-old man was admitted to our institution for ulcerative colitis treatment. He used mesalamine, steroid, immunomodulators, and anti-TNFα anti-body, but it was difficult to maintain remission. We started induction therapy with tofacitinib (TOF) 10 mg twice daily. He maintained clinical remission but had chest pain 44 days after the start of TOF. Esophagogastroduodenoscopy showed multiple ulcers from middle to lower esophagus. Although rare, TOF induced esophageal ulcers were considered based on his clinical course and endoscopic findings.

Topics: Adult; Colitis, Ulcerative; Esophageal Diseases; Esophagoscopy; Esophagus; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Ulcer

Protein glycosylation plays an important role in various biological processes, such as modification of protein function, regulation of protein-protein interactions, and control of turnover rates of proteins. Moreover, glycans have been considered as potential biomarkers for many mammalian diseases and development of aberrant glycosylation profiles is an important indicator of the pathology of a disease or cancer. Hence, quantitation is an important aspect of a comprehensive glycomics study. Although numerous MS-based quantitation strategies have been developed in the past several decades, some issues affecting sensitivity and accuracy of quantitation still exist, and the development of more effective quantitation strategies is still required. Aminoxy tandem mass tag (aminoxyTMT) reagents are recently commercialized isobaric tags which enable relative quantitation of up to six different glycan samples simultaneously. In this study, liquid chromatography and mass spectrometry conditions have been optimized to achieve reliable LC-MS/MS quantitative glycomic analysis using aminoxyTMT reagents. Samples were resuspended in 0.2 M sodium chloride solution to promote the formation of sodium adduct precursor ions, which leads to higher MS/MS reporter ion yields. This method was first evaluated with glycans from model glycoproteins and pooled human blood serum samples. The observed variation of reporter ion ratios was generally less than 10% relative to the theoretical ratio. Even for the highly complex minor N-glycans, the variation was still below 15%. This strategy was further applied to the glycomic profiling of N-glycans released from blood serum samples of patients with different esophageal diseases. Our results demonstrate the benefits of utilizing aminoxyTMT reagents for reliable quantitation of biological glycomic samples.

Topics: Biomarkers; Cell Line, Tumor; Chromatography, Liquid; Esophageal Diseases; Fetuins; Glycomics; Glycoproteins; Humans; Oximes; Piperidines; Polysaccharides; Ribonucleases; Tandem Mass Spectrometry

Crizotinib was the first clinically available inhibitor of the tyrosine kinase ALK, and next-generation ALK inhibitors, such as alectinib, are now under development. Although crizotinib is generally well tolerated, severe esophageal injury has been reported as a rare but serious adverse event of crizotinib therapy. We now describe the successful treatment with alectinib of a patient who developed crizotinib-induced esophageal ulceration.

Topics: Carbazoles; Carcinoma, Non-Small-Cell Lung; Crizotinib; Endoscopes; Esophageal Diseases; Female; Humans; Lung Neoplasms; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Tomography, X-Ray Computed; Treatment Outcome; Ulcer

Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation.. Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight.. The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy.. Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.

Topics: Angiogenesis Inhibitors; Animals; Cicatrix; Disease Models, Animal; Dissection; Drug Therapy, Combination; Esophageal Diseases; Esophageal Stenosis; Esophagoscopy; Follow-Up Studies; Injections; Intestinal Mucosa; Mitomycin; Nucleic Acid Synthesis Inhibitors; Piperidines; Quinazolinones; Swine; Transforming Growth Factor beta3; Wound Healing

Long-term follow-up examination with esophagogastroduodenoscopy was performed on seven patients who had undergone successful delayed anastomosis for isolated esophageal atresia. The follow-up period ranged from 1.2 to 11.3 years (mean, 5.3). All patients had undergone fundoplication because of symptomatic gastroesophageal reflux (GER). Three anastomotic strictures had to be resected. At the time of the last follow-up examination, the subjective results were excellent for five patients and good for two. The last endoscopy showed macroscopic esophagitis in three and normal mucosa in four. The fundoplication was partly disrupted in two patients. In three patients the fundoplication was competent but partly intrathoracic. Histological examination showed moderate esophagitis in one, mild esophagitis in one, and normal mucosa in five patients; however, four patients were on continuous medication for esophagitis. In conclusion, the subjective results of patients with isolated esophageal atresia treated with esophageal anastomosis are good. However, long-term complications caused by GER are common in these patients. Therefore, active search and treatment of reflux is necessary for these patients.

Topics: Anastomosis, Surgical; Anti-Ulcer Agents; Cisapride; Constriction, Pathologic; Endoscopy, Digestive System; Esophageal Atresia; Esophageal Diseases; Esophagitis; Follow-Up Studies; Fundoplication; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Infant; Piperidines; Postoperative Complications; Sucralfate

An intraluminal balloon was used to study the peristaltic reflex, which is mediated by the intrinsic nerves of the oesophagus. Serial balloon distension was performed in nine asymptomatic volunteers and 133 patients with oesophageal symptoms. Eight of the volunteers had a normal response with proximal stimulation and distal inhibition of motility. Only 42 patients (31.6 per cent) had a normal response. The commonest abnormal response (39.1 per cent) was some form of failure of the distal inhibitory reflex. Other patterns of abnormality were an unresponsive oesophagus (15.8 per cent) with no motility change during balloon inflation, or spasm (13.5 per cent) proximal to the balloon. These alterations of secondary peristaltic activity suggest that there are abnormalities of the intrinsic (enteric) nerves of the oesophagus. Different abnormalities were found in patients with similar symptoms. Awareness of this difference might allow a more rational approach to treatment. This hypothesis was tested in a small pilot study treating functional dysphagia with cisapride. Three of nine patients had marked symptomatic improvement within 4 weeks and all three had an unresponsive oesophagus. The remaining six patients, who had failure of distal inhibition or a normal response, did not improve.

Topics: Adult; Aged; Catheterization; Cisapride; Deglutition Disorders; Esophageal Diseases; Esophagus; Female; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Peristalsis; Piperidines; Reflex, Abnormal; Serotonin Receptor Agonists

Topics: Adolescent; Adult; Aged; Biliary Tract Diseases; Deglutition Disorders; Esophageal Diseases; Female; Humans; Male; Middle Aged; Muscles; Piperidines