Jörgen Wenner

Endoscopic surveillance of columnar-lined esophagus - Frequency of intestinal metaplasia detection and impact of antireflux surgery

ObjectiveTo quantify the occurrence of intestinal metaplasia in columnar-lined esophagus (CLE) during endoscopic surveillance and to evaluate the impact of antireflux surgery on the development of intestinal metaplasia. Summary Background DataThe malignant potential in segments of CLE is mainly restricted to those containing intestinal metaplasia. Patients with segments of CLE in which no intestinal metaplasia can be detected are rarely enrolled in a surveillance program but may still be at increased risk of developing esophageal adenocarcinoma because intestinal metaplasia may be missed or may develop with time. MethodsThe occurrence of intestinal metaplasia on biopsy samples was determined on repeated endoscopies in 177 patients enrolled in a surveillance program for CLE. The incidence of intestinal metaplasia in patients with no evidence of intestinal metaplasia on the two first endoscopies was evaluated on the subsequent endoscopies and compared in patients with medically and surgically treated gastroesophageal reflux disease. ResultsIntestinal metaplasia was found in 53% of the patients (94/177) on their first surveillance endoscopy and was more prevalent in long segments of CLE. The prevalence of intestinal metaplasia increased markedly with increasing number of surveillance endoscopies. Intestinal metaplasia tended to be detected early in patients with long segments of CLE; in patients with shorter segments, intestinal metaplasia was also detected late in the course of endoscopic surveillance. Patients with surgically treated reflux disease were 10.3 times less likely to develop intestinal metaplasia compared with a group receiving standard medical therapy. ConclusionBiopsy samples from a single endoscopy, despite an adequate biopsy protocol, are insufficient to rule out the presence of intestinal metaplasia. Patients in whom biopsy specimens from a segment of CLE show no intestinal metaplasia have a significant risk of having undetected intestinal metaplasia or of developing intestinal metaplasia with time. Sampling error is probably the reason for the absence of intestinal metaplasia in segments of CLE longer than 4 cm, whereas development of intestinal metaplasia is common in patients with shorter segments of CLE. Antireflux surgery protects against the development of intestinal metaplasia, possibly by better control of reflux of gastric contents.

Metaplastic columnar mucosa in the cervical esophagus after esophagectomy

ObjectiveTo evaluate the pathogenesis of metaplastic processes within the esophagus using a human model in which the exact duration of reflux was known. Summary Background DataThe pathogenesis of Barrett’s esophagus (BE) is incompletely understood. Patients undergoing esophagectomy and gastric tube reconstruction represent a good model for studying the pathophysiology of columnar cell metaplasia of the human esophagus because the cervical esophagus is rarely or never exposed to gastric contents before the surgical procedure. MethodsThirty-two patients underwent manometry, simultaneous 24-hour pH and bilirubin monitoring, and endoscopy with biopsy 3 to 10.4 years after esophagectomy. The presence of columnar mucosa in the cervical esophagus was confirmed on histologic examination. The findings on endoscopy and histology were related to clinical data and the results of pH and bilirubin monitoring 1 cm proximal to the esophagogastrostomy. ResultsFifteen (46.9%) of the 32 patients had metaplastic columnar mucosa within their cervical esophagus. Metaplasia was significantly more common in patients with a preoperative diagnosis of BE. The length of metaplastic mucosa correlated significantly with the degree of esophageal acid exposure, but the presence of abnormal bilirubin exposure was unrelated to the presence of metaplasia. The prevalence of metaplasia did not change with increasing time. Intestinal metaplasia was found within the columnar-lined segment in three patients 8.5, 9.5, and 10.4 years after esophagectomy. All patients with intestinal metaplasia had abnormal exposure of both acid and bilirubin, but the presence of combined reflux was not significantly higher in these patients compared with patients with nonintestinalized segments of columnar mucosa. ConclusionsEsophageal columnar metaplasia is a common complication after gastric pull-up esophagectomy. Metaplasia is more likely to develop in patients with previous BE than other patients. Metaplasia develops in response to squamous epithelial injury in predisposed individuals.

Barrett Esophagus: Risk Factors for Progression to Dysplasia and Adenocarcinoma

Objective:To evaluate risk factors for dysplasia and adenocarcinoma development in nondysplastic Barrett mucosa. Summary Background Data:The risk for patients with Barrett esophagus to develop esophageal adenocarcinoma is low, and most patients undergoing surveillance will not develop malignancy. Identification of risk factors may allow for more rational surveillance programs in which patients are stratified according to their individual risk of progressing to dysplasia and invasive adenocarcinoma. Methods:The development of dysplasia and esophageal adenocarcinoma was studied during long-term endoscopic and histologic surveillance in 140 patients with Barrett esophagus free from dysplasia. Risk factors for progression to dysplasia and adenocarcinoma were evaluated. Results:Median follow-up was 5.8 years. Forty-four patients (31.4%) developed low-grade dysplasia and 7 patients (5%) developed high-grade dysplasia or esophageal adenocarcinoma. Dysplasia development was significantly less common after antireflux surgery compared with conventional medical therapy. Low-grade dysplasia (relative risk = 5.5; 95% confidence interval, 1.1–28.6) and long duration of reflux symptoms (relative risk = 1.3; 95% confidence interval, 1.2–1.7) were independently associated with an increased risk of developing high-grade dysplasia or esophageal adenocarcinoma. Conclusions:Successful antireflux surgery protects the Barrett mucosa from developing high-grade dysplasia and esophageal adenocarcinoma, possibly by better control of reflux of gastric contents. Low-grade dysplasia is the only clinically useful risk factor that permits stratification of the surveillance intervals according to the risk of the individual patient.

Heller's esophagomyotomy with or without a 360 degrees floppy Nissen fundoplication for achalasia. Long-term results from a prospective randomized study.

Hellers esophagomyotomy relieves dysphagia but does not restore esophageal peristalsis. The myotomy may induce reflux and the addition of a 360 degrees fundoplication may be hazardous with regard to the remaining aperistaltic esophagus. The aim of this prospectively randomized clinical trial was to compare the outcome for patients with uncomplicated achalasia who underwent an anterior Hellers esophagomyotomy (H group) with or without an additional floppy Nissen fundoplication (H + N group). Between 1984 and 1995, 20 patients were prospectively randomized to one or other of the performed operations, 10 patients per group. Esophagitis including Barretts esophagus (n = 2) was seen under medical treatment, in 6 of 9 in the H group but none in the H + N group. No patient in the H + N group required postoperative continuous acid-reducing drugs. Twenty-four-hour esophageal pH-studies in median 3.4 years after surgery showed pathological reflux expressed as a percentage of time below pH 4 of 13.1% in the H group compared to 0.15% (P < 0.001) in H + N group. One patient with recurrent dysphagia in the H + N group later had an esophagectomy. The remaining patients reported significant improvement of dysphagia without symptoms of reflux at 8.0 years follow-up. Hellers esophagomyotomy eliminates dysphagia, but can induce advanced reflux that requires medical treatment. The addition of a 360 degrees fundoplication eliminates reflux without adding dysphagia in the majority of patients and can be recommended for most patients with uncomplicated achalasia.

Randomized clinical trial of laparoscopic versus open fundoplication for gastro-oesophageal reflux

The aim of this study was to compare the long‐term results of laparoscopic and open antireflux surgery in a randomized clinical trial by investigating subjective and objective outcomes.

Wireless Esophageal pH Monitoring Is Better Tolerated than the Catheter-Based Technique: Results from a Randomized Cross-Over Trial.

OBJECTIVES:Esophageal pH monitoring using a wireless pH capsule has been suggested to generate less adverse symptoms resulting in improved patient acceptance compared with the catheter-based method although evidence to support this assumption is lacking. The aim of this study was to evaluate and compare the subjective experience of patients undergoing both techniques for esophageal pH monitoring.METHODS:Using a randomized study design, patients referred for esophageal pH testing underwent both wireless and traditional catheter-based 24-h pH recording with a 7-day interval. The wireless pH capsule was placed during endoscopy and followed by 48-h pH recording. All patients answered a questionnaire, including a 10-cm visual analog scale (VAS), which described the perceived severity of symptoms and the degree of interference with normal daily activities during the pH tests.RESULTS:Thirty-one patients, 16 women and 15 men, were included in the analysis. The severity of all adverse symptoms associated with the wireless technique was significantly lower compared with the catheter-based technique (median VAS 2.1 vs 5.1, P < 0.001). Wireless pH recording was associated with less interference with off-work activities and normal daily life, median VAS 0.6 and 0.7 compared with 5.0 and 5.7, respectively, for the catheter-based technique (P < 0.0001). Patients actively working during both tests reported less interference with normal work during the capsule-based test than during the catheter-based pH test (median VAS 0.3 vs 6.8, P = 0.005). Twenty-seven patients (87%) stated that, if they had to undergo esophageal pH monitoring again, they preferred the wireless test over the catheter-based pH test (P < 0.0001).CONCLUSIONS:This randomized study showed that a significant majority of patients undergoing esophageal pH monitoring preferred the wireless pH capsule over the traditional catheter-based technique because of less adverse symptoms and less interference with normal daily life.

Wireless oesophageal pH monitoring: Feasibility, safety and normal values in healthy subjects.

Objective A new wireless technique for oesophageal pH monitoring has recently been introduced (Bravo®). To implement this technique in clinical practice, values of normal oesophageal acid exposure need to be defined in a large age- and gender-matched healthy population. The aims of this study were to investigate the feasibility and safety of the wireless technique and to establish normal values for oesophageal acid exposure. Material and methods Fifty-seven asymptomatic subjects underwent upper gastrointestinal endoscopy with transoral placement of a radio-transmitting capsule 6 cm above the squamocolumnar junction. Oesophageal acid exposure was monitored via a portable receiver during 48 h. Results Seven men were excluded from the study: capsule dysfunction in 1 and oesophagitis in 6. Fifty subjects (25 M, 25 F, median age 42 years) were included in the study. The radio-transmitting capsule was successfully attached to the oesophageal mucosa in all cases and there were no complications. During pH monitoring 2 capsules were prematurely detached after 32 and 36 h, respectively. The median percentage time with oesophageal pH of less than 4 was 0.7% on day 1 and 1.0% on day 2 (p=0.033) and the 95th percentile for the 48-h recordings was 4.4%. Conclusions Ambulatory pH monitoring using the Bravo® system is feasible and appears to be safe. This is the first study to establish normal values for oesophageal acid exposure in a large age- and gender-matched healthy population and offers a basis for the use of the wireless technique in clinical practice.

Short-term outcome after laparoscopic and open 360 degrees fundoplication - A prospective randomized clinical trial

Background: Despite the lack of randomized trials supporting the laparoscopic approach, laparoscopic antireflux surgery has gained widespread acceptance during the last decade. The aim of this study was to compare the short-term symptomatic and objective outcome after laparoscopic and open 360° fundoplication in a prospective randomized clinical trial. Methods: Sixty patients with GERD were randomized to undergo either laparoscopic (LF) or open 360° fundoplication (OF). Endoscopy, esophageal manometry, 24-h pH monitoring, clinical symptom evaluation, and symptom scoring according to a validated questionnaire (the Gastrointestinal Symptom Rating Scale [GSRS]) was performed preoperatively and 6 months after surgery. Results: Five patients randomized to the laparoscopic group were converted to open surgery. Esophageal acid exposure was restored to normal in all patients. Lower esophageal sphincter length and resting pressure were significantly increased after both laparoscopic and open fundoplication (p <0.001); there were no differences between the groups. No significant differences were seen in symptomatic outcome, although there was a trend toward a higher rate of mild dysphagia (p = 0.051) after laparoscopic surgery. GSRS revealed a decrease in reflux score (p <0.001) and abdominal pain score (p <0.001) postoperatively. There were no significant differences in GSRS scores between the two groups. Conclusion: Laparoscopic 360° fundoplication is as effective in treating reflux disease as open fundoplication. Six months postoperatively, no significant differences were seen in symptomatic or objective outcome. Long-term evaluation is needed.

Impact of Proton Pump Inhibitors on Benign Anastomotic Stricture Formations After Esophagectomy and Gastric Tube Reconstruction: Results From a Randomized Clinical Trial.

Objective:The primary aim of this study was to evaluate if the use of proton pump inhibitors (PPIs) reduced the prevalence of benign anastomotic strictures after uncomplicated esophagectomies with gastric tube reconstruction and circular stapled anastomoses. Summary Background Data:Benign anastomotic strictures are associated with anastomotic leaks or conduit ischemia. Also patients without those complications develop benign anastomotic strictures. We hypothesize that patients without postoperative anastomotic complications may develop benign anastomotic strictures due to exposure of acid gastric tube contents to the anastomotic area, and that the formation of such strictures may be reduced by prophylactic use of PPIs. Methods:Eighty patients without preoperative chemo- or radiotherapy, without clinical or radiological signs of anastomotic leaks were included in this clinical trial. The patients were randomized to b.i.d. PPIs or no treatment for 1 year. Benign anastomotic strictures were defined as anastomotic narrowing not allowing a standard diagnostic endoscope to pass without dilatation. The study was registered in the EudraCT database (2009-009997-28) for clinical trials. Results:Seventy-nine patients were evaluated. Benign anastomotic strictures developed in 5/39 (13%) patients in the PPI group and in 18/40 (45%) in the control group (RR 5.6, 95% CI: 2.0–15.9, P = 0.001). The use of a narrower 25 mm cartridge as compared to a wider 28 or 31 mm cartridge significantly increased stricture formations (RR 2.9, 95% CI: 1.1–7.6, P = 0.025). Conclusions:Prophylactic PPI treatment reduced the prevalence of benign anastomotic strictures following esophagectomy with gastric tube reconstruction and circular stapled anastomoses. Larger sized circular staple cartridges additionally reduced the stricture prevalence.

Acid Reflux Immediately Above the Squamocolumnar Junction and in the Distal Esophagus: Simultaneous pH Monitoring Using the Wireless Capsule pH System.

OBJECTIVES:The pattern of reflux in the most distal esophagus of asymptomatic individuals is largely unknown. Using a wireless technique we compared the degree and the pattern of acid reflux just above the squamocolumnar junction (SCJ) with that measured at the conventional level for pH monitoring.METHODS:Fifty-three asymptomatic volunteers underwent endoscopy with transoral placement of two pH recording capsules, one immediately above and one 6 cm above the SCJ. Ambulatory pH monitoring was performed during 48 h.RESULTS:Three subjects were excluded as the distal capsule was inadvertently placed with the pH electrode below the SCJ. The median percent time with pH < 4 and the median number of reflux episodes were significantly higher immediately above the SCJ compared with that found more proximally (1.6% vs 0.9% and 67 vs 26, p < 0.0001). Of all acid reflux events, 69% were isolated episodes immediately above the SCJ. Only 26% of reflux episodes detected at the SCJ extended to the more proximal pH electrode. Reflux events occurring just above the SCJ were more acidic. The number of reflux events with a minimum pH below 2 or 3 was significantly higher at the SCJ compared with that recorded by the upper capsule (16% and 44% vs 6% and 34%, p < 0.0001).CONCLUSIONS:Conventional pH monitoring substantially underestimates the degree of acid exposure in the most distal esophagus. In healthy subjects, acid exposure immediately above the SCJ was considerably higher and was characterized by shorter reflux episodes that had a lower minimum pH compared with that measured at the traditional level for pH monitoring.