A Randomized Prospective Multicenter Trial of Pancreaticoduodenectomy With and Without Routine Intraperitoneal Drainage

George Van Buren II, MD; Mark Bloomston, MD; Steven J. Hughes, MD; Jordan Winter, MD; Stephen W. Behrman, MD; Nicholas J. Zyromski, MD; Charles Vollmer, MD; Vic Velanovich, MD; Taylor Riall, MD; Peter Muscarella, MD; Jose Trevino, MD; Attila Nakeeb, MD; C. Max Schmidt, MD; Kevin Behrns, MD; E. Christopher Ellison, MD; Omar Barakat, MD; Kyle A. Perry, MD; Jeffrey Drebin, MD; Michael House, MD; Sherif Abdel-Misih, MD; Eric J. Silberfein, MD; Steven Goldin, MD; Kimberly Brown, MD; Somala Mohammed, MD; Sally E. Hodges, BS; Amy McElhany, MPH; Mehdi Issazadeh, BS; Eunji Jo, MS; Qianxing Mo, PhD; William E. Fisher, MD

Disclosures

Annals of Surgery. 2014;259(4):605-612. 

In This Article

Results

At the time the study was stopped, 357 patients had been screened and 282 were enrolled from September 15, 2011 to December 6, 2012 (Fig. 1). The most common reason for screen failure was that the patient refused to be randomized. Nine patients had to be withdrawn from the study because the scheduled surgery date after the study was stopped by the Data Safety Monitoring Board. Five patients withdrew their consent before surgery. Three patients had undergone imaging after enrollment, demonstrating metastatic disease. Eighty-six patients underwent distal pancreatectomy and are not included in this analysis because that portion of the study is ongoing. Thirty-nine patients who were randomized and scheduled for PD were not evaluable because they were found to have unresectable disease at the time of exploration, or had an enucleation, or a total pancreatectomy rather than a PD. These patients were excluded from the study and were not followed. There were 3 cases for which the randomization group assignment was inadvertently not followed: 1 patient in the drain group did not have a drain placed and 2 patients in the no-drain group had a drain placed. Each of the 3 surgeons for these cases verified that the protocol deviation was not intentional. With these patients excluded from the analysis (which did not alter the results), there were 137 evaluable patients—68 in the drain group and 69 in the no-drain group. No patients were lost to follow up. The eCRFs had 114 data fields per patient for a total of 15,618 for the study. Data capture was very complete with 15,606 data fields (99.9%) successfully acquired.

There were no significant differences between the 2 cohorts in demographics or comorbidities (Table 1). In addition, there was no significant difference between the 2 cohorts in the indications for surgery, pancreatic duct size, pancreas texture, and operative technique, including the use of a laparoscopic approach, anastomotic technique, vascular resections, additional procedures, operative time, blood loss, or transfusion requirements (Table 2). Among the patients in the group that had drains placed at the time of resection, two-thirds had 2 drains and one-third had 1 drain (Table 2). The drains were removed typically by POD 7. There was no difference between the 2 groups in the utilization of postoperative computed tomography or other abdominal imaging procedures, the need for readmission, or reoperation (Table 2).

PD without routine intraperitoneal drainage was associated with a higher morbidity (Table 3). There was an increase in the number of complications per patient, an increase in the number of patients who had at least 1 grade 2 or more complication, and a higher mean complication severity score. PD without routine intraperitoneal drainage was associated with a higher incidence of gastroparesis, intra-abdominal fluid collection, intra-abdominal abscess, severe (≥grade 2) diarrhea, need for a postoperative percutaneous drain, and a prolonged length of stay. There was no difference between drain and no-drain groups in quality of life when assessed at baseline and at 30 days after surgery (see Supplemental Digital Content Table 1, available at http://links.lww.com/SLA/A521).

The study was stopped early by the Data Safety Monitoring Board because of excess mortality in the patients undergoing PD without routine intraperitoneal drainage. After 90 days of follow-up, there were 8 deaths (12%) in the no-drain group and only 2 deaths (3%) in the drain group (P = 0.097) (Table 4). Among the 10 patients who died, 90% were male, 80% had a soft pancreatic texture, 60% had a pancreatic duct of 3 mm or less, and 80% developed a pancreatic fistula. Two patients (20%) had a combined biliary and pancreatic fistula and 70% developed an intra-abdominal abscess. Five deaths (50%) were associated with intra-abdominal hemorrhage (see Supplemental Digital Content Table 2, available at http://links.lww.com/SLA/A522).

Percutaneous drains were placed in 3 (30%) of the patients who died. Seventy percent of the patients who died were returned to the operating room on average at POD 11 (range: 1–24). One patient who died had a percutaneous drain but was not returned to the operating room. (See Supplemental Digital Content 1, available at http://links.lww.com/SLA/A520, which describes the postoperative course of the 10 patients who died.)

Two deaths, 1 in the drain group and 1 in the no-drain group, were related to recurrent cancer. One patient in the no-drain group had a laparoscopic PD, did not have a documented pancreatic leak, and was discharged on POD 10. However, the patient returned on POD 24 in shock and died from postoperative hemorrhage from the hepatic artery. The remainder of the deaths, 70%, occurred in the setting of a pancreatic fistula associated with sepsis, multisystem organ failure, and/or hemorrhage (Table 4 and Supplemental Digital Content Table 2, available at http://links.lww.com/SLA/A522).

processing....