Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Speech therapy in patients with excessive supragastric belching--a pilot study.

In patients whose main symptom is excessive belching, supragastric belching appears to be the predominant mechanism. This belch pattern is characterized by a rapid influx of air into the oesophagus, immediately followed by rapid air expulsion. The rate at which supragastric belching occurs is influenced by attention and distraction, suggesting a behavioural disorder and speech therapy may be of benefit to these patients. In 17 consecutive patients with excessive belching, concurrent impedance monitoring and high-resolution manometry were performed to ascertain the mechanism of belching. Patients with supragastric belches were referred to a speech therapist, who was familiar with the concept of supragastric belching. Before and after treatment by the speech therapist, patients filled out a VAS scale regarding the severity of their symptoms. In all patients, supragastric belches were identified with impedance monitoring. Eleven patients were referred to a speech therapist, six patients were not able or willing to undergo repetitive treatments. Eleven patients completed treatment by the speech therapist consisting of 10 (8-10) sessions. Overall, the VAS scales showed a significant improvement of the severity of symptoms (P < 0.05). Six of the 11 patients reported a large decrease (>30%) in their symptoms and four patients reported a modest decrease (<30%). In one patient, the VAS scores indicated an increase in symptoms. Speech therapy performed by a well-informed speech pathologist leads to a significant symptom reduction in patients with excessive supragastric belching. This is the first study indicating benefit of a treatment for excessive belching.

Relationship between gastro-oesophageal reflux pattern and severity of mucosal damage.

The aim of the study is to compare the characteristics of reflux episodes in controls and in patients with various degrees of oesophagitis and Barrett's oesophagus. Ambulatory 24-h impedance-pH tracings were analysed from healthy volunteers, patients with non-erosive reflux disease (NERD), patients with grade A oesophagitis, grade B oesophagitis, grade C or D oesophagitis and patients with a short segment (<2 cm) of Barrett's metaplasia. The number of acid and weakly acidic reflux episodes increased from 25.9 +/- 3.9 to 17.9 +/- 1.5 in the controls, 39.9 +/- 6.3 to 33.4 +/- 5.7 in the patients with NERD, 46.6 +/- 6.2 to 40.4 +/- 9.2 in grade A, 68.2 +/- 9.2 to 49.2 +/- 12.3 in grade B, 79.8 +/- 15.6 to 47.4 +/- 4.6 in grade C/D and 75.1 +/- 7.9 to 37.3 +/- 8.5 in the patients with Barrett. The proportion of reflux episodes that is acidic or alkaline was similar all groups. Comparison with normal values revealed that none of the controls, 40% of the patients with NERD, 50% of the patients with grade A, 80% of the patients with grade B and all patients with grade C/D or Barrett's oesophagus had an abnormally high total number of reflux episodes. In the patients with severe oesophagitis a significantly higher percentage of reflux episodes reached the proximal oesophagus (43.8%) compared to the patients with Barrett's oesophagus (19.2%). With increasing degrees of oesophagitis, patients have more reflux episodes but a large overlap between the groups exists making comparison with normal values of limited relevance. In patients with Barrett's oesophagus fewer reflux episodes reach the proximal oesophagus which might explain their low sensitivity to reflux.

Does acute psychological stress increase perception of oesophageal acid?

Gastro-oesophageal reflux disease (GORD) patients often report an increase in their reflux symptoms during stressful situations. The aim of this study was to assess the influence of acute psychological stress on oesophageal acid perception. In 15 healthy volunteers and 10 GORD patients with a positive symptom-reflux association an oesophageal acid perfusion test was performed, once with and once without the presence of an acute psychological stressor (IQ test). The order of the measurements was randomized. The time from onset of the acid infusion to first acid perception, discomfort and pain was noted. Blood pressure was measured to assess the effect of the stress task. In healthy volunteers, the time to first perception (control task: 617 +/- 174 s vs stress task: 561 +/- 162 s), discomfort (control task: 969 +/- 158 s vs stress task: 940 +/- 151 s) or pain (control task: 1393 +/- 122 s vs stress task: 1366 +/- 121 s) did not differ significantly between both measurements. In GORD patients, no significant differences between both measurements were found either in time to first perception (control task: 63 +/- 26 s vs stress task: 43 +/- 15 s), discomfort (control task: 153 +/- 44 s vs stress task: 249 +/- 62 s) or pain (control task: 558 +/- 139 s vs stress task: 633 +/- 118 s). Systolic blood pressure rose significantly during the stress task in both the healthy volunteers (6 +/- 1 mmHg) and the GORD patients (9 +/- 2 mmHg). Neither in the healthy volunteers nor in the GORD patients, the acute psychological stress induced by an IQ test increased oesophageal acid perception. The observed increase in systolic blood pressure shows that the experimental stressors were effective.

Increased swallowing frequency in GORD is likely to be caused by perception of reflux episodes.

Patients with gastro-oesophageal reflux disease (GORD) swallow air more frequently and have more gas-containing reflux episodes than healthy controls. One explanation for this phenomenon may be that GORD patients primarily swallow more frequently and, as a consequence, have more swallow- or transient lower oesophageal sphincter relaxation-associated reflux episodes. Another explanation may be that GORD patients swallow more often in response to perception of reflux episodes. The aim of this study was to differentiate between these two possible mechanisms. In 34 patients with typical reflux symptoms oesophageal 24-h pH-impedance monitoring was performed twice, once off and once on proton pump inhibitor (PPI) therapy. The number of reflux episodes and number of swallows and air swallows was evaluated. The symptom association probability (SAP) was used to distinguish patients with a good relationship between symptoms and reflux episodes (SAP+) from those who had not (SAP-). In both the SAP+ (n = 21) as SAP- patients (n = 13), the acid exposure time decreased during PPI therapy. In the SAP+ patients, the number of swallows decreased on PPI (829 +/- 85 off vs 701 +/- 79 on PPI, P < 0.05), whereas in the SAP- patients, the incidence of swallows (802 +/- 93 off vs 814 +/- 69 on PPI, P = NS) was not influenced by the PPI therapy. PPI therapy reduces the number of swallows in patients with a positive SAP, but not in those with a negative SAP. This finding supports the hypothesis that the increased incidence of swallows in GORD is brought about by responses to perceived reflux events.