One- and ten-year outcome of laparoscopic anterior 120° versus total fundoplication: a double-blind, randomized multicenter study.

BACKGROUND: Nissen fundoplication is an effective treatment for gastroesophageal reflux disease (GERD) but can cause adverse effects like flatulence and dysphagia. The aim was to compare laparoscopic anterior 120° fundoplication (APF) to total fundoplication (Nissen) concerning flatulence and other adverse effects, in a randomized blinded study. METHODS: Seventy-two patients were randomized to APF (n = 36) or Nissen (n = 36). Gastroscopy, 24-h pH monitoring and evaluation for symptoms and quality of life using questionnaires (GSRS, PGWB and 7-graded Likert scales) were performed preoperatively, at 1 and 10 years postoperatively. Patients and the researchers were blinded to operative method. RESULTS: When entering the study, most patients had mild-moderate reflux disease according to the symptom score, the 24-h pH measurements, and frequency and grade of esophagitis. At 1-year (n = 68) flatulence, dysphagia, heartburn and acid regurgitation did not differ between groups. More patients could belch (p = 0.005), and pH monitoring showed a higher time with pH < 4 in the APF group (p = 0.006). At 10 years (n = 61), the APF group reported less dysphagia (p < 0.001), more heartburn (p = 0.019) and more patients could belch (p = 0.012) and vomit (p < 0.001) compared to the Nissen. No difference remained at 10 years in pH monitoring (n = 23) between groups. Symptoms of heartburn and acid regurgitation were less than preoperatively in both groups (p < 0.001). No revisional operations were performed. CONCLUSIONS: Both procedures offer good long-term control of reflux symptom, with modest post-fundoplication symptoms. Anterior 120° fundoplication results in less dysphagia, better ability to belch and vomit than total fundoplication at 10-year follow-up. The results suggest that APF could be an alternative to Nissen fundoplication in the surgical treatment of mild-moderate GERD.

Structured diagnostic and treatment approach versus the usual primary care approach in patients with gastroesophageal reflux disease: a cluster-randomized multicenter study.

GOALS: To compare the clinical outcomes of gastroesophageal reflux disease (GERD) patients treated with an implemented new structured pathway (NSP) or according to existing local clinical practices [old clinical pathway (OCP)]. BACKGROUND: GERD is a major challenge at the primary care level. STUDY: Primary care centers (n=24) were cluster randomized to handle patients suffering from symptoms suggestive of GERD according to the NSP (n=97) or the OCP (n=134). In the NSP, the GerdQ questionnaire score was used both for diagnosis and management including treatment. We used validated questionnaires to evaluate disease symptoms, quality of life, and costs at inclusion and at follow-up 2 to 6 months later. RESULTS: On the basis of the Reflux Disease Questionnaire, 56% of the patients treated with the NSP reported total symptom relief at the follow-up compared with 33% in the OCP group (P=0.0013). The reflux symptoms after treatment affected daily activities to a lesser extent in the patients in the NSP group compared with the OCP group (10% vs. 13%, respectively, P=0.01). The utility score of the EuroQoL-5D questionnaire improved more in the NSP group than in the OCP group (0.05 vs. 0.02, respectively, P<0.001). The patients in the NSP group had an approximately 50% lower average total cost for GERD-related health care resources compared with the OCP group [301 Swedish Kronor (SEK) vs. 588 SEK, respectively, NS]. CONCLUSIONS: The management of GERD patients in primary care centers using a structured clinical pathway and the results of the GerdQ improves the clinical outcome compared with prevailing local routines (NCT00842387).

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.

Is the course of gastroesophageal reflux disease progressive? A 21-year follow-up.

OBJECTIVE. We re-evaluated a cohort of patients referred for reflux symptoms and objectively diagnosed with pathological reflux, with the purpose of clarifying the course of conservatively treated gastroesophageal reflux disease (GERD). MATERIAL AND METHODS. All consecutive patients with GERD diagnosed between 1984 and 1988 showing pathologic 24-h pH-metry in the interval 3.8-10% and without any previous surgery in the gastroesophageal tract were assessed for further follow-up. A total of 40 evaluable patients were followed in the years 2007-08 with endoscopy, manometry, 24-h pH-metry, Helicobacter pylori assessment and the self-administered questionnaires the GERD Impact Scale, the Reflux Disease Questionnaire, the Quality of Life in Reflux and Dyspepsia and the Medical Outcome Study Short Form-36 Health Survey. Baseline data from the 1980s were retrieved and compared with the evaluations conducted at follow-up. RESULTS. At follow-up 20.7 years (range 18.8-23.5 years) after referral, the study population showed more use of acid suppressants (p = 0.007) and increasing prevalences of esophagitis (p = 0.001) and Barrett's esophagus (p = 0.002). Esophagitis was seen in 16/40 patients (40%) at baseline and in 29/40 (72.5%) at follow-up. No significant deterioration was seen at follow-up in manometry data and in most pH data. Patients with esophagitis (ERD) were less likely to have a positive H. pylori test (hazard ratio 0.054; p = 0.002) than non-erosive (NERD) patients. Symptom evaluations showed significantly lower quality of life in the ERD group. CONCLUSIONS. After 20 years a considerable part of the cohort still experienced symptoms of reflux and showed endoscopic progression, although no significant deteriorations were seen in manometry data and in most pH-metry data. H. pylori infection was inversely associated with erosive esophagitis and this supports the hypothesis that H. pylori colonization is a protective factor against GERD.

Wireless pH recording immediately above the squamocolumnar junction improves the diagnostic performance of esophageal pH studies.

BACKGROUND AND AIMS: The optimal position for pH electrode placement in the diagnosis of gastroesophageal reflux disease (GERD) is unknown. The aim of this study was to evaluate the discriminatory power of targeted pH recording immediately above the squamocolumnar junction (SCJ) and to compare the results with those obtained by simultaneous recording at the conventional level for pH monitoring. SUBJECTS AND METHODS: Sixty-two patients with typical reflux symptoms and 49 asymptomatic volunteers underwent 48-h simultaneous wireless pH monitoring with two endoscopically placed pH recording capsules, one immediately above the SCJ and one at the traditional position, 6 cm above the SCJ. The diagnostic accuracy, sensitivity, and specificity of pH monitoring at the two levels were analyzed using receiver operating characteristics (ROC) curves. RESULTS: Of the 62 patients (39 men and 23 women, median age 48 yrs), 32 patients had erosive esophagitis and 30 had no endoscopic evidence of mucosal injury. Analysis of the area under the ROC curve (AUC) indicated that the total percent time with pH<4 for the entire 48-h period was the parameter that best distinguished GERD patients from controls. pH monitoring performed directly above the SCJ significantly increased the number of patients correctly classified with GERD compared to standard electrode placement. With a predefined test specificity of 90%, pH monitoring immediately above the SCJ increased the sensitivity of the test from 63% to 86% in all patients, from 78% to 97% in patients with esophagitis and from 47% to 73% in patients with no esophagitis. CONCLUSIONS: Compared to standard electrode placement, wireless pH recording immediately above the SCJ improved the diagnostic performance of esophageal pH monitoring in patients with GERD.

The Reflux Disease Questionnaire: a measure for assessment of treatment response in clinical trials.

BACKGROUND: Critical needs for treatment trials in gastroesophageal reflux disease (GERD) include assessing response to treatment, evaluating symptom severity, and translation of symptom questionnaires into multiple languages. We evaluated the previously validated Reflux Disease Questionnaire (RDQ) for internal consistency, reliability, responsiveness to change during treatment and the concordance between RDQ and specialty physician assessment of symptom severity, after translation into Swedish and Norwegian. METHODS: Performance of the RDQ after translation into Swedish and Norwegian was evaluated in 439 patients with presumed GERD in a randomized, double-blind trial of active treatment with a proton pump inhibitor. RESULTS: The responsiveness was excellent across three RDQ indicators. Mean change scores in patients on active treatment were large, also reflected in effect sizes that ranged from a low of 1.05 (dyspepsia) to a high of 2.05 (heartburn) and standardized response means 0.99 (dyspepsia) and 1.52 (heartburn). A good positive correlation between physician severity ratings and RDQ scale scores was seen. The internal consistency reliability using alpha coefficients of the scales, regardless of language, ranged from 0.67 to 0.89. CONCLUSION: The results provide strong evidence that the RDQ is amenable to translation and represents a viable instrument for assessing response to treatment, and symptom severity.

Two different surgical approaches in the treatment of adenocarcinoma at the gastroesophageal junction.

BACKGROUND: Adenocarcinoma at the gastroesophageal junction may be regarded as of esophageal or of gastric origin, and tumor removal may follow the principles of esophagectomy or extended gastrectomy. We determined the impact of this strategy on our patients with tumors at this site. METHODS: Baseline patient and tumor characteristics were collected, and tumors were categorized according to Siewert's classification (I, II, or III) of gastroesophageal junction tumors. Totally, 133 patients were operated on between 1990 and 2001. Ninety-six patients with type I (n = 67), II (n = 26), and III (n = 3) tumors underwent esophagectomy and gastric tube reconstruction, and 37 patients with type I (n = 5), II (n = 26), and III (n = 6) tumors underwent extended gastrectomy and long Roux-en-Y reconstructions. RESULTS: After adjusting for the independently significant impact factors-tumor stage, tumor dissection (R0-R2), and length of tumor free resection margins-we did not find any specific survival benefit associated with either of the two evaluated surgical approaches for tumor resection and reconstruction. The EORTC quality of life forms revealed good results as indicated by the functional scales and the symptom scales. CONCLUSIONS: Provided that adequate tumor dissection is performed, patients with adenocarcinoma at the gastroesophageal junction can be resected and reconstructed using the principles for esophagectomy or extended gastrectomy.

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.

Optimal thresholds and discriminatory power of 48-h wireless esophageal pH monitoring in the diagnosisof GERD.

BACKGROUND: The discriminative power of 48-h wireless esophageal pH monitoring in the diagnosis of gastroesophageal reflux disease has not been clearly demonstrated, and the cutoff level for esophageal acid exposure generating the optimal sensitivity and specificity is unknown. SUBJECTS AND Patients with typical reflux symptoms and a distinct response to acid suppressive medication METHODS: underwent upper GI endoscopy followed by 48-h wireless esophageal pH studies with the pH electrode placed 6 cm above the squamocolumnar junction. The results were compared to those obtained in 55 healthy controls. Sensitivity, specificity, and thresholds for esophageal acid exposure were analyzed using receiver operating characteristic (ROC) curves. RESULTS: The patient population consisted of 64 patients, 25 women and 39 men, with a median age of 48 yr. Analysis of the area under the ROC curve showed that, for all patients as well as for subgroups of patients with (N = 33) and without (N = 31) esophagitis, the total percent time with pH <4 for the 48-h study period was the best parameter to discriminate patients from controls. Analysis of acid exposure for day 1, day 2, or using the day with the highest acid exposure did not improve the diagnostic accuracy. A test specificity in the range of 90-95% resulted in a cutoff level of 3.6-4.4% of the total time with pH <4 for the 48-h period. This threshold generated a test sensitivity of 59-64% in all patients, 76-79% for patients with esophagitis and 42-48% in patients with no esophagitis. CONCLUSIONS: The total percentage of time that esophageal pH was less than 4 for the entire 48-h study period was the parameter that best discriminated patients with typical reflux symptoms from healthy controls, and to achieve a specificity of 90-95% a cutoff level of 4% is recommended. The low sensitivity of wireless pH recording in patients without erosive esophagitis substantially reduces the clinical value of the test.

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.

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. MATERIALS 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.

Patients' experiences of illness, operation and outcome with reference to gastro-oesophageal reflux disease.

BACKGROUND: Describing the illness-story from a patient perspective could increase understanding of living with a chronic disease for health professionals and others, facilitate decision-making about treatment and enhance information about the outcome from a patient perspective. AIM: To illuminate patients' illness experiences of having a gastro-oesophageal reflux disease (GORD), going through surgery and the outcome. METHODS: Twelve patients were interviewed 5 years after having had the operation; six patients had had fundoplication via laparoscopy and six via open surgery. Each patient was asked to talk openly about their experiences, thoughts, feelings and consequences of living with the illness, going through surgery and the period from surgery to the day of interview. A qualitative content analysis was performed concerning the context of the data and its meaning. FINDINGS: Three central categories were identified and nine subcategories: living with GORD- symptoms of the disease affecting daily living, taking medicines, work, family and social life; concerns related to surgery- decision-making about the operation, influence by physicians; life after the operation- outcomes and consequences, side-effects and complications of the operation, sick leave, information and sharing experiences with future patients. All patients were free from symptoms of the illness after surgery independent of type of surgery, but side-effects from surgical treatment varied individually. Interviewees would have liked information concerning side-effects after surgery from previous patients. CONCLUSIONS: This study contributes to knowledge about patients' long-term suffering, their control of symptoms and how they have tried to cure themselves, but also about their concerns about surgery and the importance of surgical treatment to their quality of life. They wanted information about treatment, outcome and consequences, not only from a health care perspective but also from previous patients having had the same treatment.

Cervical or thoracic anastomosis after esophageal resection and gastric tube reconstruction: a prospective randomized trial comparing sutured neck anastomosis with stapled intrathoracic anastomosis.

OBJECTIVE: The purpose of the study was to compare in prospective randomized fashion a manually sutured esophagogastric anastomosis in the neck and a stapled in the chest after esophageal resection and gastric tube reconstruction. SUMMARY BACKGROUND DATA: Despite the fact that all reconstructions after esophagectomy will result in a cervical or a thoracic anastomosis, controversy still exists as to the optimal site for the anastomosis. In uncontrolled studies, both neck and chest anastomoses have been advocated. The only reported randomized study is difficult to evaluate because of varying routes of the substitute and different anastomotic techniques within the groups. The reported high failure rate of stapled anastomoses in the neck and the fact that most surgeons prefer to suture cervical anastomoses made us choose this technique for anastomosis in the neck. Our routine and the preference of most surgeons to staple high thoracic anastomoses became decisive for type of thoracic anastomoses. METHODS: Between May 9, 1990 and February 5, 1996, 83 patients undergoing esophageal resection were prospectively randomized to receive an esophagogastric anastomosis in the neck (41 patients) or an esophagogastric anastomosis in the chest (42 patients). To evaluate selection bias, patients undergoing esophageal resection during the same period but not randomized (n = 29) were also followed and compared with those in the study (n = 83). Objective measurements of anastomotic level and diameter were assessed with an endoscope and balloon catheter 3, 6, and 12 months after surgery. The long-term survival rates were compared with the log-rank test. RESULTS: Two patients (1.8%) died in hospital, and the remaining 110 patients were followed until death or for a minimum of 60 months. The genuine 5-year survival rate was 29% for chest anastomoses and 30% for neck anastomoses. The overall leakage rate was 1.8% (2 cases of 112) with no relation to mortality or anastomotic method. All patients in the randomized group had tumor-free proximal and distal resection lines, but 1 patient in the nonrandomized group had tumor infiltrates in the proximal resection margin. At 3, 6, and 12 months after operation, there was no difference in anastomotic diameter between the esophagogastric anastomosis in the neck and in the thorax (P = 0.771), and both increased with time (P = 0.004, ANOVA repeated measures). Body weight development was the same in the two groups. With similar results in randomized and nonrandomized patients, study bias was eliminated. CONCLUSIONS: When performed in a standardized way, neck and chest anastomoses after esophageal resection are equally safe. The additional esophageal resection of 5 cm in the neck group did not increase tumor removal and survival; on the other hand, it did not adversely influence morbidity, anastomotic diameter, or eating as reflected by body weight development.