Manuel Pera

Deterioration of esophageal motility with age : A manometric study of 79 healthy subjects

OBJECTIVES:Data are limited on the effect of age on esophageal function. We evaluated whether aging influences the motor activity of the esophagus.METHODS:Standard esophageal manometry was performed in 79 healthy, nonpaid volunteers of both sexes, 18–73 yr of age. Lower (LES) and upper esophageal sphincter (UES) characteristics and the properties of esophageal peristaltic waves were assessed by age groups: ≤25 yr, 26–35 yr, 36–45 yr, 46–55 yr, 56–65 yr, and >65 yr.RESULTS:Age correlated inversely with LES pressure and length, UES pressure and length, and peristaltic wave amplitude and velocity, and correlated directly with the proportion of simultaneous contractions. Age was inversely correlated with the upper limits of normality (95th percentiles) of LES pressure (r =−0.943, p= 0.005), UES pressure (r =−0.943, p= 0.005), middle and lower peristaltic wave amplitude (r =−0.947, p= 0.004, and r =−0.844, p= 0.035, respectively), upper/middle peristaltic progression speed (r =−0.943, p= 0.005), and the proportion of simultaneous contractions (r = 0.926, p= 0.008), but not with the lower normal limits (5th percentiles) of these variables. Gender did not affect esophageal motility variables. The 95th percentiles of LES pressure differed by 20 mm Hg, those of lower peristaltic amplitude by 82 mm Hg, and those of percent simultaneous contractions by a factor of 2, between the younger and the older age groups.CONCLUSIONS:The results suggest that normal esophageal motility deteriorates with advancing age. Thus, age-related normality limits of esophageal pressures should be considered before establishing the manometric diagnosis of hypercontractile esophageal motility disorders.

Trends in Incidence and Prevalence of Specialized Intestinal Metaplasia, Barrett’s Esophagus, and Adenocarcinoma of the Gastroesophageal Junction

Most available information on the epidemiology of Barrett’s esophagus (BE) relates to patients with long segments (> 3 cm) of specialized intestinal metaplasia (SIM). Its prevalence is 3% in patients undergoing endoscopy for reflux symptoms and 1% in those undergoing endoscopy for any clinical indication. The latter prevalence is similar to the 1% found in autopsy series. A “silent majority” with BE remain unrecognized in the general population. BE is more common in men, and the prevalence rises with age. Recent endoscopic series document a rise in the diagnosis of endoscopically apparent short segments (< 3 cm) of BE (SSBE). The prevalence of SSBE in both unselected and reflux patients is 8% to 12%. Specialized intestinal metaplasia at the cardia, below a normal-appearing squamocolumnar junction, has been reported to vary from 6% to 25% in patients presenting for upper endoscopy. Unlike patients with long segment Barrett’s esophagus (LSBE), the role of gastroesophageal reflux disease in the pathogenesis of SSBE and SIM of the cardia is controversial. Recent data suggest that the etiology of SIM of the cardia might be secondary to Helicobacter pylori infection, although the role of other environmental factors cannot be ruled out. The incidence of adenocarcinoma of the esophagus and esophagogastric juction (EGJ) has been increasing over the past 15 years in Western countries. Surgical series and population-based studies show that by 1994 adenocarcinomas of the esophagus accounted for half of all esophageal cancer among white men. LSBE and SSBE predispose to the development of adenocarcinoma of the esophagus and EGJ. The role of SIM of the cardia as a precursor lesion for EGJ adenocarcinoma is still unclear. The prevalences of dysplasia in LSBE and SSBE are around 6% and 8%, respectively. The incidence of adenocarcinoma in patients with LSBE is about 1 in 100 patient-years. Cancer risk for SSBE and SIM at the cardia is unknown. Smoking and obesity increase the risk for esophageal and EGJ adenocarcinomas.

Laparoscopic sleeve gastrectomy and laparoscopic gastric bypass are equally effective for reduction of cardiovascular risk in severely obese patients at one year of follow-up.

BACKGROUND Very few studies have compared laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) outcomes or analyzed improvement in cardiovascular risk (CVR) after bariatric surgery. None of the studies considered the Mediterranean population. Our primary objective was to compare the 10-year estimated CVR reduction achieved by LRYGB and LSG in Spanish subjects with severe obesity. The secondary objectives were to compare the techniques in terms of weight loss and co-morbidity improvement. The study was performed at a university hospital in Barcelona, Spain. METHODS A 12-month prospective cohort study of 140 consecutive patients (95 LRYGB and 45 LSG) compared the 2 surgical intervention groups to study the percentage of excess weight loss, resolution and improvement/resolution of co-morbidities, and effect on CVR using both the Framingham risk score (FRS) and the Registre Gironí del Cor (REGICOR) model. RESULTS At 12 months, the overall CVR decreased from 6.6% to 3.4% using the FRS and from 3.7% to 1.9% using the REGICOR score. Neither model found a difference between the 2 surgical intervention groups in decreased postoperative CVR risk, with a FRS of 3.4% ± 2.2% for LRYGB versus 3.3% ± 2.1% for LSG (P = .872) and a REGICOR score of 1.9% ± 1.5% versus 1.8% ± 1.6%, respectively (P = .813). No differences were observed in the percentage of excess weight loss or the resolution of type 2 diabetes mellitus and hypertension. The hypercholesterolemia improvement/resolution rate was lower in the LSG group than in the LRYGB group. CONCLUSION Bariatric surgery reduces the estimated CVR by one half at 1 year after surgery. Except for the less-improved cholesterol metabolism, LSG, a restrictive technique, proved to be equally as effective at 1 year of follow-up as LRYGB.

Frequent overexpression of Aurora Kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions

Upper gastrointestinal adenocarcinomas are a common cause of cancer‐related deaths. In this study, the authors investigated the prevalence and biological significance of Aurora Kinase A (AURKA) overexpression in upper gastrointestinal adenocarcinomas.

Recent changes in the epidemiology of esophageal cancer

One of the most notable changes in the epidemiology of esophageal cancer is the increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction (EGJ) in the United States and western countries over the past two decades. Incidence rates of squamous cell carcinoma (SCC) of the esophagus have been steady or declining along recent years in these geographical areas. In this review we update information about the three main risk factors for SCC of the esophagus and discuss recent trends in incidence of esophageal adenocarcinomas as well as the role of different risk factors possibly associated with this epidemiological change.

Proliferative Activity in Barrett’s Esophagus Before and After Antireflux Surgery

ObjectiveTo assess proliferation in the columnar-lined esophageal mucosa before and after antireflux surgery. Summary Background DataIntestinal metaplasia persists in Barrett’s mucosa after reflux control. It remains at risk for uncontrolled cellular proliferation and adenocarcinoma formation. MethodsForty-five patients with Barrett’s esophagus had a mean follow-up of 4 years after a Collis-Nissen gastroplasty. Proliferative activity was assayed immunohistochemically for Ki-67 expression in 73 preoperative and 176 postoperative biopsies. Correlation with manometric and 24-hour pH results was obtained. ResultsThe Collis-Nissen gastroplasty restored the median lower esophageal sphincter gradient from 5.5 mmHg before surgery to 14.5 mmHg at 24 months and 12.9 mmHg at 48 months after surgery. The median esophageal acid exposure was reduced from 8% to 1% and 1% of recording time, respectively. The median Ki-67 labeling index increased from 28.5% before surgery to 36.1% at 12 to 23 months. It returned to preoperative level (26.9%) at 24 to 47 months. After surgery, abnormal intraesophageal acid exposure was documented in 12 patients but could not be correlated with sphincter pressure. After surgery, the pattern of proliferation in patients with acid exposure less than 4% in their esophagus showed significant differences when compared with the proliferation pattern of patients where abnormal intraesophageal acid exposure was recorded. New present dysplasia was observed only in patients with abnormal acid exposure. ConclusionsIn Barrett’s mucosa, from preoperative values, proliferation peaked early after surgery and then decreased to preoperative levels. Despite sphincter restoration and global reflux control, abnormal esophageal acid exposure persisted in 12 patients. Patients with abnormal esophageal acid exposure displayed more proliferation and more dysplasia.

Epithelial cell hyperproliferation after biliopancreatic reflux into the esophagus of rats

BACKGROUND Chronic reflux of duodenal contents into the esophagus of rats produces severe esophagitis and exerts a co-carcinogenic effect on the proliferating cells by enhancing the formation of nitrosamine-induced esophageal carcinomas. We investigated the effect of the different components of the duodenal reflux on the epithelial cell proliferation of the lower esophagus. METHODS Sprague-Dawley rats underwent three surgical reflux models (biliopancreatic, pancreatic, and biliary) and a sham operation. Animals were sacrificed at 72 hours, 6 weeks, and 9 weeks after the operation. Histology and cell proliferation, determined by ornithine decarboxylase activity, polyamine (putrescine, spermidine, spermine) levels, and proliferating cell nuclear antigen labeling index of the basal and suprabasal layers, were studied in the distal esophagus. RESULTS Both biliopancreatic and pancreatic reflux induced severe esophagitis starting on week 6. Suprabasal proliferating cell nuclear antigen labeling index significantly increased throughout the 9 weeks of the study in the biliopancreatic and pancreatic reflux groups, although this increase was earlier in the former group. Ornithine decarboxylase activity and polyamine levels were significantly increased in the biliopancreatic and pancreatic groups on week 6, decreasing on week 9. CONCLUSIONS Increased esophageal cell proliferation after both biliopancreatic and pancreatic reflux into the lower esophagus may therefore be one mechanism by which duodenal-content reflux stimulates esophageal carcinogenesis in experimental animals.

Experimental Barrett's esophagus and the origin of intestinal metaplasia.

Many questions remain unanswered regarding the pathogenesis and the cell origin of Barretts esophagus. Recent studies suggest that progenitor cell populations, which are presumed to reside at the basal layer in the squamous epithelium and at the esophageal glands duct epithelium, may differentiate into a glandular phenotype leading to the development of columnar epithelium in the distal esophagus. Other studies also support the hypothesis that cardiac epithelium may precede the occurrence of specialized intestinal metaplasia. It remains unclear whether cardiac-type epithelium in Barretts esophagus arises from squamous epithelium or from migration of native cardiac epithelium at the EGJ into the distal esophagus. Experimental animal models of chronic reflux esophagitis, although with some shortcomings when researchers extrapolate the study data to the human situation, have provided interesting insights into possible mechanisms associated with the occurrence of Barretts esophagus. A better understanding of the molecular mechanisms regulating the development of Barretts esophagus is necessary for developing new strategies directed toward prevention and treatment of this metaplastic condition with a potential risk for malignant transformation.

Long-term Control of Gastroesophageal Reflux Disease Symptoms After Laparoscopic Nissen-Rosetti Fundoplication

Laparoscopic fundoplication is the gold standard surgical treatment for gastroesophageal reflux disease, although some patients develop recurrence or collateral symptoms related to surgery. The aims of this study were to describe the long-term symptoms control in patients undergoing laparoscopic fundoplication, to analyze the patterns of failure and to correlate postoperative symptoms with anatomic and physiologic findings. Extensive preoperative and postoperative work-up including symptom questionnaire, barium meal, endoscopy, manometry, and 24-hour pH-metry were performed in 130 consecutive patients undergoing laparoscopic fundoplication. Mean follow-up was 52 months. After laparoscopic fundoplication, 117 patients (90%) were asymptomatic with Visick grade I and II symptoms reported by 124 patients (95%). On evaluation, 119 (92%) patients were satisfied and willing to repeat surgery. Two failure patterns, anatomic abnormalities (wrap migration into the chest or down onto the stomach with or without repair disruption) and functional (incompetence of antireflux mechanism), were reported in 17 patients. Reflux can be controlled in up to 90% of patients with gastroesophageal reflux disease with relatively few complications and a high degree of patient satisfaction. The most common cause of recurrent symptoms is an anatomic failure of the fundoplication.

Uncut collis-nissen gastroplasty: early functional results

BACKGROUND This study reviewed the short-term results of the uncut Collis-Nissen gastroplasty. METHODS From 1990 through 1993, 27 consecutive patients (16 men, 11 women) underwent an uncut Collis-Nissen gastroplasty. Mean age was 59 years (range, 30 to 75 years). Three patients had a previous failed antireflux procedure. Indications for operation were gastroesophageal reflux disease resistant to medical treatment in 18 patients and symptomatic hiatal hernia in 9 patients. Fourteen patients had Barretts esophagus and 4 had a peptic stricture. Complete esophageal function testing including barium swallow, endoscopy, manometry, and 24-hour pH recording was performed in 26 of 27 patients preoperatively and postoperatively. RESULTS Five patients (19%) had complications, which included atelectasis in 2, cardiac dysrhythmia in 2, and prolonged ileus in 1. There were no operative deaths. Follow-up was complete in all patients and ranged from 8 to 45 months (mean, 22 months). Subjectively, symptoms of reflux were resolved in all patients. Six patients complain of slow esophageal emptying and 3 have occasional episodes of dysphagia. None required postoperative dilation. Ulcers and erosions healed in all 26 patients who underwent endoscopy but recurred in 2 at 21 and 36 months postoperatively. Mean lower esophageal sphincter gradient increased from 8.3 mm Hg preoperatively to 14.6 mm Hg (p = 0.0001). Total percent of acid exposure decreased from 8.0% preoperatively to 1.7% (p = 0.003). CONCLUSIONS We conclude that the uncut Collis-Nissen procedure provides acceptable short-term control of gastroesophageal reflux disease.