Does type of pancreaticojejunostomy after pancreaticoduodenectomy decrease rate of pancreatic fistula? a randomized, prospective, dual-institution trial

Authors: Berger AC, Howard TJ, Kennedy EP, et alJournal: J American College of Surgeons 2009; 208:738–74Centre: Thomas Jefferson University, Philadelphia, PA; and Indiana University, Indianapolis, IN, USA

BACKGROUND

The pancreatic-enteric anastomosis is the “Achilles heel” of pancreaticoduodenectomy (PD). Leakage or failure of healing, results in pancreatic fistula (PF), an important cause of morbidity following PD. The estimated incidence of this complication is 10% to 25%. There are two widely used methods to accomplish an end to side pancreaticojejunostomy (PJ) after PD: invagination PJ (“dunking” the pancreatic remnant into the jejunum) or duct to mucosa PJ. It has been suggested that the latter is safer, but firm evidence is lacking.

IN SUMMARY Study results

Hard gland Soft gland

Duct to mucosa PJ

Invagination PJ

Duct to mucosa PJ

Invagination PJ

Number 47 49 50 51

Pancreatic fistula rate 17.8% (35 patients) - overall

By gland type (p=0.007)

8.00% 27.00%

By technique (#p=0.06) 11.00% 6.00% 36.00% # 18.00%

There were no substantial differences in overall complications, mortality, and rates of reoperation between the duct to mucosa and the invagination groups.

Major complications Duct to mucosa-25%; invagination-12% (p=0.03)

Interventional radiological procedures

Duct to mucosa-11%; invagination-3% (p=0.03)

PJ = pancreaticojejunostomyAuthors' claim(s): “... considerably fewer fistulas with invagination compared with duct to mucosa pancreaticojejunostomy after pancreaticoduodenectomy. Results confirm increased PF rates in soft as compared with hard glands.”

THE TISSUE REPORT The randomized clinical trial (RCT) is the definitive method of resolving the efficacy of interventions in clinical practice. Quite often, as this study shows, the results are counter-intuitive and run against common wisdom. There is little room for discomfort in the methodology of the study. Considering the well known dictum that pancreaticoduodenectomy should be offered only by centres that can deliver the procedure with mortality rates of 2% or less, any definitive recommendation that reduces risk is a step forward.

The devil is in the details (more on the paper) ...

© Dr Arjun Rajagopalan

EBM-O-METER

Evidence level Overall rating Bias levelsDouble blind RCT

TrashLife's too

short for this

Swiss cheese

Full of holes

SafeHolds water

News-worthy

“Just do it”

Sampling

Randomized controlled trial (RCT) Comparison

Prospective cohort study - not randomized Measurement

Case controlled study Interesting l | Novel l | Feasible l Ethical l | Resource saving lCase series - retrospective

RESEARCH QUESTION

Population

All patients at two university, referral hospitals undergoing pancreaticoduodenectomy (PD).

Indicator variable

A two-layer end to side pancreatic duct to jejunal mucosa anastomosis (duct to mucosa) or a two-layer end to side invagination technique, after stratification into "hard" and "soft" glands.

Outcome variable

Primary: Pancreatic fistula (PF) rate. Secondary: length of hospitalization, percutaneous radiologic intervention rates, reoperation rates, morbidity and 30-day or in-hospital mortality.

Comparison

As described above.

INTERVENTIONAL

2 June 2009DissectionsDissectionsEvidence-based Medicine for Surgeons

SAMPLING Sample type Inclusion criteria Exclusion criteria Final score card

Simple random All patients undergoing pancreatico-duodenectomy

Locally unresectable Inability to locate pancreatic duct Operation other than PD Metastatic disease

Hard+d-m Hard+inv Soft+d-m Soft+inv

Stratified random Target ? ? ?

Cluster Accessible 272

Consecutive Intended 47 49 50 51

Convenience Drop outs 0 0 0 0

Judgmental Study 47 49 50 51

= Reasonable | ? = Arguable | = QuestionableDuration of the study: TJUH: August 2006 to May 2008; IUH: February 2007 to May 2008

With alpha set at 0.05, 95 patients per group (190 total) were needed to have 80% power to detect a difference from 30 to 15%

Sampling bias: Although the study was done in two referral, university hospitals, it is only such centres that can carry out studies of this nature and recruit the required number of patients.

© Dr Arjun Rajagopalan

COMPARISON Randomized Case-control Non-random Historical None

Controls - detailsAllocation details Patients were stratified into two groups: soft (normal) texture (predicted fistula rate of 20% to

40%) and hard (fibrotic) texture (predicted fistula rate of 0% to 10%). Patients were randomized to one of two groups: a two-layer end to side pancreatic duct to jejunal mucosa anastomosis (duct to mucosa) or a two-layer end to side invagination technique. All other aspects of the intraoperative and postoperative management of the patients were not influenced by this study. Prophylactic octreotide was not used in any patient.

(Details of the technique along with excellent, colour illustrations are provided in the original article.)

Comparability Patient demographics, including age and gender,were comparable between the two groups. Intraoperative parameters were not statistically different between the duct to mucosa and the invagination groups. Median estimated blood loss and red blood cell transfusion requirements were similar in the two groups. Diameter of the pancreatic duct was similar for the two groups. 142 patients who underwent PD for malignant disease, and 55 patients had benign or premalignant processes.

Disparity No significant differences.

Comparison bias: Minimal.

MEASUREMENT Measurement error

Device used Device error Observer error

Device suited to task

Y ? N

Rep

etitio

n

Gol

d st

d.

Trai

ning

Prot

ocol

s

Sco

ring

Blin

ding

1.Pancreatic fistula (ISGPF definition) Y N Y N N N N

The International Study Group on Pancreatic Fistulas (ISGPF) defines a pancreatic fistula as “out-put via an operatively placed drain (or a subsequently placed, percutaneous drain) of any measurable volume of drain fluid on or after postoperative day 3, with an amylase content greater than 3 times the upper normal serum value.

Measurement bias: Nothing of note.