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

Methods

Pancreatic surgeons from 9 academic high-volume (~50 PD/yr) pancreas surgery centers in the United States were recruited to contribute patients to this multicenter randomized prospective clinical trial. Patients were randomized to PD with and without the use of routine intraperitoneal drainage. Patients were followed for 90 days and the safety of this approach and spectrum of complications were compared. The trial was originally designed to include patients undergoing PD or distal pancreatectomy. However, the study was stopped because of excess mortality in the patients undergoing PD without drains. Herein, we report the results from patients undergoing PD. Accrual of patients undergoing distal pancreatectomy is currently ongoing and the results with that portion of the study will be reported separately in the future.

It was mandatory that each surgeon offered participation in the study to all patients undergoing PD within their practice during the study period. All patients were enrolled unless they refused the randomization process or refused to comply with follow-up. All patients undergoing PD by participating surgeons during the study period were registered by the study and eligibility criteria were assessed. If a patient was not enrolled, a valid reason was recorded. Comorbid conditions or the indication for resection were not allowed to influence enrollment. Randomization was performed using a computerized randomization system at the coordinating center (Baylor College of Medicine) and occurred before surgery. To ensure an equal distribution among treatment groups of patients with a soft or hard pancreas, randomization was substratified for anticipated diagnosis (Fig. 1).

Figure 1.

Flow chart of participants in the study. DSMB indicates Data Safety Monitoring Board.

The trial was registered at clinicaltrials.gov (NCT01441492). A uniform protocol was submitted to and approved by the institutional review boards and other required regulatory organizations at each subsite, and amendments to the protocol could be initiated only by the coordinating center. The coordinating center trained the research personnel at each subsite before initiating enrollment at that site. All complications of any significant nature were reported immediately by the subsite PI directly to the coordinating center. Operative notes, anesthesia records, hospital notes, discharge summaries, and all other documents were reviewed as supporting documents to validate the information being reported by each subsite. All supporting data were collected from each subsite using a secure, Web-based electronic data capture system. Electronic case report forms (eCRFs) were designed to maximize accurate data collection with "pop-up boxes" to define complications and grading systems. The coordinating center followed quality assurance procedures to ensure the timely and accurate prospective completion of all eCRFs. Subsites forwarded source documents from the medical record to support all data entered. Every source document was reviewed by trained analysts and a surgeon at the coordinating center to confirm that all complications were recorded and graded accurately.

At the time of enrollment, demographics and comorbid conditions were recorded, and subjects filled out a previously validated pancreas-specific quality-of-life questionnaire (FACT-PA),[10] which was repeated 30 days after surgery. Intraoperative data were collected from the operative note and anesthesia record. For subjects assigned to the intraoperative drain group, the specific size, brand, and number of closed-suction drains were at the discretion of the surgeon. The concentration of amylase in a sample of drain fluid was measured and recorded on postoperative day (POD) 3 and at any additional POD desired by the treating surgeon. In the case of multiple drains, the highest concentration of amylase was used. The date the drains were removed was recorded. Drains were left in place until either the amylase concentration was <3× the upper limit of normal serum amylase concentration in the study subsite hospital laboratory and/or the output was 20 mL/d or less for 2 consecutive days.

Particular attention was focused on the use of postoperative imaging, abdominal paracentesis, and percutaneous drainage. If paracentesis was performed or a percutaneous abdominal drain was placed, the fluid was sent for amylase concentration, Gram stain, and culture. Complications were recorded from the discharge summary, hospital daily progress notes and laboratory reports, and outpatient progress notes. Outpatient follow-up visits were required at 30 and 60 days after surgery. All complications occurring within 60 days of surgery were recorded and graded. Subjects were followed for mortality for 90 days because recent reports suggest shorter periods of follow-up result in underreporting.[11] Complications were graded (grades 1–5) in severity using the Common Terminology Criteria for Adverse Events (v4.0), which is a widely accepted standardized classification of adverse events produced by the National Cancer Institute for use in clinical trials.[12]

In addition to the Common Terminology Criteria for Adverse Events grading, postoperative pancreatic fistula was also defined and graded using the 3-tiered definition proposed by the International Study Group on Pancreatic Fistula.[13] Delayed gastric emptying was also defined and graded using the schema proposed by the International Study Group of Pancreatic Surgery.[14] Common Terminology Criteria for Adverse Events grades were used to calculate the average complication severity score for each patient (sum of all complication grades experienced by the patient divided by the number of complications experienced by the patient). Length of hospital stay was calculated from the day of surgery through and including the day of discharge. Readmission was defined as an admission to any hospital for 24 hours or more for any reason within 60 days after surgery. Readmission was not considered as an independent additional complication but was used to grade the severity of the complication that was the reason for readmission.

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