Prokinetic medication after surgical therapy of reflux patients with disorders of esophageal peristalsis: a randomized clinical study

BACKGROUND: Long-standing gastroesophageal reflux disease (GERD) is frequently associated with impaired esophageal body motility. Partial posterior fundoplication improves esophageal peristalsis. The aim of this prospective randomized study was to investigate whether administration of the prokinetic agent cisapride enhances this effect. METHODS: Forty consecutive GERD patients with impaired esophageal peristalsis entered the study and were randomized in two groups: group 1 with and group 2 without postoperative treatment with cisapride (6 months, 20 mg twice daily). Four patients had to be excluded during the study. Esophageal motility was analyzed preoperatively and 6 months after surgery by measuring contraction amplitudes in the distal two thirds of the esophagus, frequency of simultaneous and interrupted peristaltic waves and total number of defective propagations. RESULTS: In both groups esophageal peristalsis was improved significantly following partial posterior fundoplication (p < 0.05; Wilcoxon Test). However, this effect was significantly more pronounced in patients receiving cisapride medication postoperatively (p < 0.05; Mann-Whitney U test). Lower esophageal sphincter pressure, intra-abdominal sphincter length and the DeMeester reflux score were normalized in both groups following antireflux surgery. CONCLUSIONS: Partial posterior fundoplication combined with postoperative cisapride medication seems to be the therapy of choice in GERD patients with impaired esophageal body motility.     

Gastroesophageal reflux patients' defective antioxidative capacity in the proximal esophageal mucosa before antireflux surgery and also after 4-year follow-up

BACKGROUND: Oxidative stress has a role in the pathogenesis of gastroesophageal reflux disease (GERD). AIM: To investigate the redox balance in proximal esophagus before and 6 and 48 months after antireflux surgery. METHODS: In 20 GERD patients and 9 controls oxidative stress by myeloperoxidase activity (MPO activity) and antioxidative capacity of esophageal mucosa by superoxide dismutase activity (SOD), and glutathione content (GSH) was measured from proximal esophageal samples. RESULTS: In proximal esophagus of GERD patients compared to controls', antioxidative capacity appearing as GSH level was significantly decreased (P < 0.001) at all time points and as SOD levels preoperatively (P < 0.001) and 4 years postoperatively (P = 0.01). MPO activity of patients was significantly lower than controls' preoperatively, and 6 months and 4 years postoperatively (P < 0.05). MPO activity remained lower than that of the distal esophagus at 6 months and 4 years (P < 0.01 for both). CONCLUSIONS: In GERD patients, proximal esophageal mucosal antioxidative defense is defective before and after antireflux surgery. Antireflux surgery seems not to change the level of oxidative stress in proximal esophagus, suggesting that defective mucosal antioxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD.     

Surgery of reflux esophagitis--a renaissance

Gastroesophageal reflux disease (GERD) has a high prevalence of 40% in Western countries. A dysfunction of the lower esophageal sphincter of unknown origin is the main etiology. Less common pathophysiological reasons are disorders of esophageal motility, delayed gastric emptying, gastric acid hypersecretion and bile reflux. As causal surgical therapy for these disorders fundoplication has been developed 50 years ago. This technique uses a wrap of gastric fundus around the distal esophagus as reflux barrier. Because of severe postoperative complications (dysphagia, gas bloat syndrome, gastric ulcer) and recurrence after fundoplication, medical therapy became the treatment of choice with the development of H2-receptor antagonists and proton pump inhibitors in the 1970s. However, after improvement of surgical technique and introduction of laparoscopic fundoplication in 1991 surgery offers a secure and effective causal therapy. Randomized controlled trials proof the superiority of fundoplication versus medical therapy in regard of long term results, recurrence and cost effectiveness as well as the superiority of laparoscopic versus conventional open fundoplication in regard of recovery and cost effectiveness with equal long term results. Therefore, laparoscopic fundoplication by an experienced laparoscopic surgeon is the surgical therapy of choice. However the high prevalence of GERD requires careful selection of patients for surgery. A thorough preoperative evaluation including upper gastrointestinal endoscopy with biopsy, esophageal manometry and 24 h-pH monitoring as well as upper gastrointestinal contrast study is essential. Today the indication for fundoplication is seen in young symptomatic patients, requiring a long-term medical therapy, in hiatal hernia with threatening complications as well as in complications of severe GERD, especially Barrett-esophagus. At present the advantages of total (Nissen) or partial (Toupet) wrap as well as the benefit of dissection of the short gastric vessels for total fundoplication are still unclear, especially concerning long-term results. To answer these technical questions further randomized controlled trials with long-term follow-up have to be performed.     

Primary esophageal motility disorders

Esophageal motility disorders often manifest with chest pain and dysphagia. Achalasia is a disorder of the lower esophageal sphincter and the smooth musculature of the esophageal body. In achalasia the lower esophageal sphincter typically fails to relax with swallowing, and the esophageal body fails to undergo peristalsis. In contrast to spastic disorders of the esophagus, achalasia can be progressive and cause pronounced morbidity. Pseudoachalasia mimics achalasia in terms of symptoms but can be caused by infectious disorders or malignancy. Treatment for achalasia is nonstandardized and includes medical, endoscopic, and surgical options. Spastic disorders of the esophagus, such as diffuse esophageal spasm and nutcracker esophagus, and nonspecific esophageal motility disorder are benign and nonprogressive, with similar findings on esophageal manometry. Although the exact cause remains unknown, these disorders may represent a manifestation of gastroesophageal reflux disease. Treatment of spastic disorders includes medical and surgical approaches and is aimed at symptomatic relief.     

Diagnosis and treatment of esophageal motility disorders

Apart from gastroesophageal reflux disease, achalasia, non-cardiac chest pain and functional dysphagia are the most important manifestations of disturbed esophageal motility. Achalasia is characterized by esophageal aperistalsis and impaired deglutitive relaxation of the lower esophageal sphincter. The morphological correlate is a degeneration of nitrergic neurons in the myenteric plexus. Diagnosis is based on barium esophagram or esophageal manometry with the latter setting the gold standard. Endoscopic exclusion of a tumor at the gastroesophageal junction is mandatory. Appropriate therapeutic interventions are pneumatic dilatation or (laparoscopic myotomy) of lower esophageal sphincter. In patients unfit for these procedures endoscopic injection of botulinum toxin into the lower esophageal sphincter is appropriate. Non-cardiac chest pain may be of esophageal origin. Gastroesophageal reflux, spastic motility disorders and visceral hypersensitivity are arguable underlying mechanisms. The most important diagnostic procedure is 24 h esophageal pH metry correlating symptoms and reflux episodes. Proton pump inhibitors and tricyclic antidepressants serving as visceral analgesics are appropriate therapeutic approaches. Functional dysphagia defines the sensation of impaired passage without mechanical obstruction or a neuromuscular disease with known pathology, e.g. scleroderma. Impaired transit is proven by esophageal scintigraphy or radiogram both using solid boluses. Manometry assesses the underlying mechanisms.     

Laparoscopic fundoplication for gastroesophageal reflux disease (GERD)

Laparoscopic fundoplication became the gold standard in the surgical therapy of GERD. In comparison with open procedures, laparoscopic antireflux surgery has a lower morbidity rate, a better early and late postoperative outcome and is more cost-effective. Antireflux surgery can be performed after a critical evalutation of the patient including gastroscopy, biopsy, 24h-pH-manometry and after a long lasting conservative medical treatment. Indications for antireflux surgery are given by a failed medical treatment, an insufficient compliance, complications of GERD, i.e. stenosis, Barrett-esophagus and atypical reflux symptoms like chronic cough, hoarseness or thoracic pain with presence of a pathological pH-monitoring. Laparoscopic 360 degrees Nissen-fundoplication with crurorrhaphy is our standard procedure, whereas the 270 degrees Toupet technique in our tailored approach is the technique of choice for esophageal motility disorders. Results of antireflux surgery published in literature are discussed and compared with our own ten years experience with 124 cases of laparoscopic fundoplication.     

幽门螺杆菌感染对胃食管反流病患者食管酸暴露及食管动力的影响

目的分析幽门螺杆菌（helicobacterpylor,Hp）感染胃食管反流病（gastroesophagealrefluxdisease,GERD）患者食管远端酸暴露及食管动力变化特点,探讨Hp感染与GERD的关系。方法GERD患者80例,分为Hp阳性组30例,Hp阴性组50例,同期20例慢性浅表性胃炎患者为对照组,对3组进行食管动力学检测和食管24hpH监测。结果Hp阳性组与Hp阴性组DeMeester评分、食管下括约肌压力、24hpH监测各项指标及食管动力学各项指标比较差异均无统计学意义（P〉O．05）;2组DeMeester评分均高于对照组（P〈0．05）,食管下括约肌压力低于对照组（P〈0．05）。结论GERD患者食管下括约肌压力较正常人群低,且存在过量酸反流;Hp感染与GERD发生可能无明显关系。     

Esophageal peristalsis, lower esophageal function, and the methods of their evaluation

Esophageal peristalsis and lower esophageal sphincter(LES) function have an influence on gastroesophageal reflux disease(GERD). Incomplete contraction during primary and secondary peristalsis leads to poor clearance of refluxed gastric acid. Failure of LES function can result in a low basal LES pressure, absent or incomplete LES relaxation after swallowing, or an inadequate increase of LES pressure accompanying gastric activity. In addition, transient LES relaxation(TLESR) has been suggested as an important factor in GERD. Recent studies have indicated that TLESR has a relationship to nitric oxide(NO) and cholecystokinin(CCK).     

Laparoscopic myotomy for oesophageal achalasia--adding an antireflux procedure is not always necessary

Laparoscopy is the access of choice for functional surgery of the gastroesophageal junction, and oesophagocardiomyotomy, as the conventional surgical treatment of achalasia, is one of the favourable indications for laparoscopic surgery. Laparoscopic anterior myotomy technique is highly effective and secure for relieving dysphagia with minimal risk of gastroesophageal reflux. Fifteen patients with the diagnosis of achalasia were treated with laparoscopic anterior face oesophagocardiomyotomy without a concomitant antireflux procedure. There was not any perioperative complication and no procedure was converted to open operation. Oesophageal cineradiography, manometry and 24-h pH monitoring were repeated postoperatively. Manometry showed a significant reduction of the resting tone (48-34.4 to 18-3.2 mmHg), and patients were free of symptoms for reflux and dysphagia at the follow-up between 8 and 96 (median 42) months. Only one patient needed pneumatic dilation, 1 year after the operation for mild dysphagia, and one patient had moderate reflux, which was managed by medication. Thanks to minimal invasive technique of laparoscopic surgery and intraoperative endoscopy, oesophagocardiomyotomy can safely be performed in a length needed without dividing lateral and posterior phrenoesophageal ligamentous attachments. Consequently, adding an antireflux procedure routinely is not necessary. We advocate laparoscopic anterior oesophagocardiomyotomy alone as the first-line treatment for achalasia.     

Gastroesophageal reflux patients' defective antioxidative capacity in the proximal esophageal mucosa before antireflux surgery and also after 4‐year follow‐up

Background. Oxidative stress has a role in the pathogenesis of gastroesophageal reflux disease (GERD).

Aim. To investigate the redox balance in proximal esophagus before and 6 and 48 months after antireflux surgery.

Methods. In 20 GERD patients and 9 controls oxidative stress by myeloperoxidase activity (MPO activity) and antioxidative capacity of esophageal mucosa by superoxide dismutase activity (SOD), and glutathione content (GSH) was measured from proximal esophageal samples.

Results. In proximal esophagus of GERD patients compared to controls', antioxidative capacity appearing as GSH level was significantly decreased (P<0.001) at all time points and as SOD levels preoperatively (P<0.001) and 4 years postoperatively (P = 0.01). MPO activity of patients was significantly lower than controls' preoperatively, and 6 months and 4 years postoperatively (P<0.05). MPO activity remained lower than that of the distal esophagus at 6 months and 4 years (P<0.01 for both).

Conclusions. In GERD patients, proximal esophageal mucosal antioxidative defense is defective before and after antireflux surgery. Antireflux surgery seems not to change the level of oxidative stress in proximal esophagus, suggesting that defective mucosal antioxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD.     

海洛因成瘾者食管运动功能研究

目的海洛因成瘾者常伴腹痛、胸部不适、反酸、反食等症状,是否存在食管运动功能紊乱有待探讨。方法随机抽取海洛因或瘾者41例。按年龄及性别配对41例健康对照组,采用PCPolygrafHR高分辨多通道灌注测压系统对82例研究对象进行食管动力的研究。测量下食管括约肌长度(LESL)、压力(LESP)、松弛率(LESR)、近端收缩压(NSP)、远端收缩村(FSP)等指标,并分析不同的吸毒年限、吸嗜方式、吸嗜量对食管动力的影响。结果海洛因成瘾者LESP、LESR与正常组相比(P<0.05),且病理性蠕动多峰波或双峰波、同步收缩比例则显著高于正常对照组(P<0.05);吸嗜量越大对食管动力损伤越大;肌肉注射、静脉注射海洛因对食管运动功能的损害明显大于香烟、烫吸方式。结论海洛因成瘾者存在食管运动功能紊乱,因此,其中吸嗜量、吸嗜方式与食管动力学指标异常有关系,在戒断康复治疗过程中,必须对此引起足够的重视。     

GERD患者内镜、病理改变与食管测压及pH动态监测之间关系的研究

目前，对GERD（GastoesophagealRefluxDisease，GERD）有不少研究报道，如GERD患者的24h食管pH动态监测、压力测定、内镜和病理等，但对它们之间关系的研究却无系列报道。据称，食管pH动态监测较其它任何临床诊断方法都有更高的敏感性和特异性，被认为是诊断GER的“金标准”。本研究即利用这一“金标准”对GERD患者进行食管PH动态监测及食管压力测定，同时研究其与内铺表现及病理改变之间的关系。1对象与布法1．1研究对象1．1．1正常对照组选择无胃肠肝胆疾病，无食管返流症状、无腹部手术史，心电图、血尿常规、内镇及病理检查…     

Surgical treatment of achalasia in the 21st century

BACKGROUND: Achalasia is a primary motility disorder of the esophagus characterized by poor mid-esophageal motility and failure of the lower esophageal sphincter to properly relax. The optimal treatment of the disease would improve esophageal peristalsis and promote lower esophageal sphincter relaxation. Currently, such therapy is not possible, so treatment of the disorder is aimed at relief of symptoms by disruption of the lower esophageal sphincter. METHODS: Data were collected prospectively on all patients undergoing laparoscopic myotomy and Toupet fundoplication during a 6-year period. RESULTS: Fifty-nine patients with a mean age of 44 years were treated during a 6-year period. Fifty-three patients underwent laparoscopic myotomy with Toupet fundoplication (91%), and four had laparoscopic myotomy without a fundoplication (6%). Fundoplication was not performed in two patients who had a megaesophagus. Two patients required conversion to an open operation. Sixty percent of patients were discharged the day after surgery; the average length of stay for all patients was 2.1 days. Ten percent of patients had minor complications; none required reoperation. Mortality was 0%, and 96% of patients rated their postoperative swallowing ability as excellent or good. CONCLUSION: Surgical myotomy is becoming first-line therapy for all patients with achalasia. A strong working relationship between surgeon and gastroenterologist helps to optimize patient care.     

腹腔镜食管裂孔疝修补术联合不同抗反流术式治疗食管裂孔疝合并胃食管反流病的临床比较

目的探讨并比较腹腔镜食管裂孔疝修补术联合不同抗反流术式治疗食管裂孔疝(HH)合并胃食管反流病(GERD)的效果。方法回顾性分析该院2014年1月-2017年1月行腹腔镜食管裂孔疝修补术联合抗反流术治疗的HH合并GERD患者67例的病例资料。根据抗反流术式的方法分为3组,其中29例采用腹腔镜Nissen胃底折叠术(Nissen组),18例行腹腔镜Toupet胃底折叠术(Toupet组),20例行腹腔镜Dor胃底折叠术(Dor组)。比较3组手术情况及术后恢复情况,术后随访1年,观察手术前后胃镜、高分辨率食管测压及24 h食管pH监测结果,发放GERD-Q症状评分评估患者GERD症状,使用GERD相关生命质量量表(GERD-HROL),记录两组术后并发症发生率、手术失效率及复发率。结果 3组患者手术情况、术后恢复情况及术后第1年胃镜检查情况比较,差异均无统计学意义(P0.05);Toupet组术后1年食管下括约肌(LES)静息呼吸平均值低于Nissen组和Dor组,反流时间、反流次数、无效吞咽高于Nissen组和Dor组,差异均有统计学意义(P 0.05),但Nissen组和Dor组比较,差异无统计学意义(P0.05),3组术后1年LES静息压最小值、24 h pH阻抗监测、DeMeester评分、GERD-Q症状评分和GERD-HROL量表评分比较,差异均无统计学意义(P0.05);3组患者术后并发症发生率、手术无效率及复发率比较,差异均无统计学意义(P0.05)。结论腹腔镜食管裂孔疝修补术联合3种胃底折叠术治疗HH合并GERD均可起到抗反流的效果,但Nissen和Dor手术在改善LES静息呼吸压力值、反流和无效吞咽方面的效果优于Toupet手术。     

GERD and tight junction proteins of the esophageal mucosa

Recent advancement in the research of GERD has revealed that endoscopy negative GERD may not be a milder form of erosive GERD and may have different pathogenesis. We have previously proven that hypersensitivity to the acid of the esophageal mucosa plays an important role in its pathogenesis. Regarding the mechanisms for the esophageal hypersensitivity, we hypothesized that the tight junction proteins of the esophageal mucosa are fully or partially impaired in GERD patients. Accordingly, we immunohistologically studied the expression of various tight junction proteins using the rat reflux esophagitis model. The results demonstrated that the several kinds of tight junction proteins are expressed differently in the various parts of esophagus and their expression altered according to the development of reflux esophagitis.     

Antireflux surgery for symptomatic gastroesophageal reflux: mechanism of action

To determine the effects of Nissen fundoplication upon the symptoms of reflux and the diagnostic tests employed to evaluate reflux and to examine the relationship between gastroesophageal reflux and lower esophageal sphincter pressure before and after fundoplication, 10 patients with symptomatic reflux were studied before and after operation. Clinical evaluation, barium esophagography, endoscopy with mucosal biopsy, esophageal manometry, acid-perfusion and acid-reflux testing, and gastroesophageal scintiscaning were performed on each patient before and after surgery. Following fundoplication, marked symptomatic, radiographic, endoscopic, and histologic improvement was observed. Serial acid-reflux tests at increasing gastroesophageal pressure gradients returned to normal after surgery. Lower-esophageal-sphincter (LES) pressure increased from 8.2 +/- 1.3 to 12.0 +/- 1.5 mm Hg (P less than 0.01). In addition, surgery resulted in a significant decrease in the gastroesophageal reflux index from 17.4 +/- 2.4 to 2.7 +/- 1.1% (P less than 0.001). Surprisingly, the pre- and postoperative resting LES pressures did not correlate significantly with corresponding gastroesophageal reflux indices for individual patients. We conclude that increased LES pressure alone does not explain adequately the functional and clinical improvement which follows fundoplication.     

Prevalence, pathophysiology, and treatment of patients with asthma and gastroesophageal reflux disease

About one third of the US adult population experiences symptoms of gastroesophageal reflux on a monthly basis. Asthma is present in about 5% of the same population. This article reviews and summarizes the literature in the following areas: (1) prevalence of gastroesophageal reflux disease (GERD) in asthmatic patients based on clinical symptoms, endoscopic esophagitis, and 24-hour ambulatory esophageal pH recordings; (2) proposed pathophysiologic mechanisms linking the 2 diseases; and (3) medical and surgical treatment trial results of antireflux therapy for asthmatic patients. Asthmatic patients appear to have an increased prevalence of GERD symptoms and 24-hour esophageal acid exposure. The clinical management of these patients remains controversial. Common management approaches to GERD in asthmatic patients include medical therapy with a proton pump inhibitor and/or antireflux surgery, which improve asthma symptoms in many patients but minimally affect pulmonary function.     

Laparoscopic Nissen fundoplication in a community hospital: patient satisfaction survey

OBJECTIVES: To assess the efficacy of laparoscopic Nissen fundoplication for esophageal reflux in a community hospital. METHODS: One hundred nineteen patients (76%) of 157 patients having laparoscopic fundoplication for symptomatic reflux disease completed a questionnaire. All patients were evaluated with esophagoscopy, esophageal motility, and pH studies. RESULTS: Mean follow-up was 49 months. Ninety-three patients (78%) no longer had heartburn. Seven patients still had daily heart-burn (5.9%). One hundred three patients (86.6%) had no sour regurgitation. Seventy-five patients (63%) had no dysphagia after surgery. Forty-two patients had some dysphagia after surgery (36.8%). Six patients (5.0%) had significant dysphagia. Only 4 patients stated that dysphagia interfered with their quality of life. Twenty-six patients (22.8%) thought that belching and bloating were worse, whereas 42 patients (36.8%) thought that belching and bloating were better after surgery. Antacids, histamine-2 antagonist, and proton pump inhibitors were still being used by 12.6%, 14.3%, and 21.8% of patients, respectively. CONCLUSIONS: Eighty-seven patients were completely satisfied (73.1%), 26 patients somewhat satisfied (22.8%), and 6 patients unsatisfied (5.3%) with surgery. Overall satisfaction with the surgery was 94.7%. One hundred five patients (88.2%) would recommend the surgery to others. Laparoscopic Nissen fundoplication can be effectively done in a community hospital setting.     

Esophageal motility disorders

Esophageal motility disorders consist of a complex array of disturbances in normal esophageal function associated with dysphagia, gastroesophageal reflux, and noncardiac chest pain. A thorough knowledge of normal esophageal anatomy and physiology is important to a full understanding of these motility derangements. Through a complicated interaction of neuromuscular and hormonal influences, the voluntary act of swallowing transforms into an automated sequence of peristaltic waves propelling food and liquids into the stomach in concert with coordinated relaxation of the sphincters. Anatomic and physiologic barriers exist within the esophagus protecting against gastroesophageal reflux and aspiration. With improvements in diagnostic tools such as barium contrast radiography, scintigraphy, pH measurements, and esophageal manometrics with provocative testing, motility disorders have become better defined and understood. Primary motility disorders consist of achalasia, diffuse esophageal spasm (DES), "nutcracker esophagus," hypertensive lower esophageal sphincter, and nonspecific esophageal motility dysfunction (NEMD). A host of secondary and miscellaneous motility disorders also affect the esophagus, including scleroderma and other connective tissue diseases, diabetes mellitus, Chagas' disease, chronic idiopathic intestinal pseudo-obstruction, and neuromuscular disorders of striated muscle. Gastroesophageal reflux disease (GERD) may also be promoted by associated motility disturbances. Treatment modalities include surgical myotomy; dilatation; and pharmacologic manipulations, including use of nitrates, calcium-channel blockers, H2-blockers, and psychotropic drugs where appropriate.     

Hiatal hernia with severe reflux esophagitis: treatment by superselective vagotomy and Nissen fundoplication

Thirty-two patients had surgical treatment for severe reflux esophagitis due to sliding hiatal hernia. A superselective vagotomy was done as an adjunct to a Nissen fundoplication as the antireflux procedure. All patients had severe esophagitis; 16 patients (53%) had dysphagia, nine patients (28%) had esophageal stricture, and all had failed an intensive trial of medical treatment with antireflux measures, antacids, and histamine receptor blockers. Follow-up averaged 14.3 months (3 to 38). Three patients (9%) had significant postoperative esophagitis. The other 29 patients, including those with esophageal stricture, are now asymptomatic. We conclude that the combination of a superselective vagotomy and a Nissen fundoplication is a safe and effective operation for the treatment of severe reflux esophagitis.