This study was conducted as a phase III randomized, controlled, trial at a university hospital in Sweden. Patients diagnosed with pancreatic or periamullary cancer and scheduled to undergo pancreaticoduodencectomy ad modum Whipple with a panceraticogastrostomy and roux-en-y loop were included. Inclusion criteria were: understand and speak Swedish, no diagnosed neurological injuries or diseases affecting the ability to swallow or gastric function, no ongoing treatment for mental disease, no ongoing abuse of alcohol or other drugs, no previously known allergies to the contents of chewing gum. Primary outcomes were time to flatus/stool and secondary outcomes were length of hospital stay and start of clear liquids and fluid diet. Primary and secondary outcomes were assessed though patient records.
Procedure
Participants were included on the day of admission, which was the day prior to surgery. Randomization to the two groups (1:1) was done when patients returned from the intensive care unit (ICU) to the ward. This procedure was chosen in order to avoid perioperative drop-outs due to inoperable tumors. A personnel from an independent institution not involved in the study administered pre-coded numbered, identical opaque envelopes to assign to the groups. A computer generated random table was used. The treatment group received chewing gum and standard care. Controls received standard care and sips of glucose, in total 3.6 g/day in a 12-ml mixture per day, the same amount of glucose per day as the treatment group received via the chewing gum. The chewing gum used was Chiza™, a natural organic gum whose main ingredients are latex, glucose and natural flavors (lime or spearmint). Patients started to chew after they returned from the ICU the day after surgery. Chewing gum was administered every fourth hour (08.00-12.00, 12.00-16.00 and 16.00-20.00). During each four-hour period, patients chewed two pieces of gum for 30 minutes. Chewing gum was used during the whole hospital stay. The time to the first postoperative flatulence and defecation was recorded, in addition to standard clinical data, by the first and the second authors.
Patients were monitored postoperatively at the ICU for 24 hours before returning to the surgical ward. All patients received a nasogastric tube perioperatively with cautious suction, which was kept for seven days. All patients received continuous thoracic epidural infusion of Bupivacain 1 mg/ml, Fentanyl 2 mg/ml and Adrenaline 2 mg/ml as an analgesic combined with intravenous paracetamol four times a day; all patients received a proton pump inhibitor (PPI) during the entire hospital stay and somastostatin for seven days postoperatively. When the nasogastric tube was removed, patients were allowed to start drinking a limited amount of clear liquids and later liquid foods (e.g. soups) and easily digested foods (e.g. fish). During fasting, patients received parenteral nutrition of glucose and Smofkabiven™ based on individual needs. Blood glucose levels were tested every fourth to sixth hour during the first postoperative week. When fluids could be tolerated, the epidural analgesia was converted to orally administered analgesia (Oxycodone and Paracetamol) until discharge based on the individual needs of the patient.
A standardized care plan focusing on rehabilitation, patient education, psychosocial needs and monitoring signs and symptoms was used in the postoperative nursing care to ensure equal and evidence based care.
Statistics
Statistical power was calculated on the basis of results of the study by Add-El-Maeboud et al. [6] in which the mean value of time to the first flatulence was 17.9 h in the treatment group and 24.4 h in the control group. With a power of 80% and a level of significance of 0.05, 18 patients were needed in each group. As the variables were not normally distributed, comparisons between the groups were analyzed with non-parametric tests, the Mann Whitney U test and Chi 2 test. The statistically significant p value was set at <0.05.
Due to a radical change in postoperative care as well as surgical technique, adopting the ERAS protocol for pancreaticoduodenectomy [14], the study was terminated in advance as this change in care procedures differed extensively from the previous strategies, e.g. removal of the nasogastric tube much earlier in the postoperative phase and not using parenteral nutrition support as patients were allowed to start oral intake much earlier.