Trial Information

A Prospective Randomized Clinical Trial of Two Surgical Techniques for Pancreaticojejunostomy in Patients Undergoing Pancreaticoduodenectomy: Nonstented Stump-closed vs Duct-to-Mucosa Pancreaticojejunostomy

Pancreaticoduodenectomy is a standard surgical approach for resectable pancreatic tumors and
periampullary tumors. It is considered a safe procedure resulting from the continuous
improvement in surgical techniques over the years. Although postoperative mortality has
obviously decreased, pancreatic fistula is still a major challenge in pancreatic surgery
and remains the major cause of postoperative morbidity and mortality after
pancreaticoduodenectomy(PD), ranging from 5% to 30%.

Many risks factors have been shown to cause pancreatic fistula(PF) after the operation,
including advanced age, prolonged operation time, intraoperative hemorrhage, BMI, soft
pancreas, size of the main pancreatic duct and texture of the remnant pancreas. Among them,
soft pancreatic texture without a dilated main pancreatic duct is regarded as the most
important risk factor in predicting pancreatic fistula.

The serious consequences of pancreatic fistula result from the pancreatic juice becoming
activated by the bile and intestinal fluid, which will eventually corrupt the PJ anastomosis
and the surrounding normal tissues. The corrosion of the vasculature will lead to lethal
hemorrhage, which is the main cause of mortality after pancreaticoduodenectomy. Furthermore,
pancreatin, together with the bacteria in the alimentary tract, will lead to intra-abdominal
infection and abscess. To reduce the pancreatic fistula rate, several techniques have been
described as alternatives to the conventional PJ anastomosis. Duct-to-mucosa sutures,
binding pancreaticojejunostomy and end-to-side invaginated fashion are widely used in the
current clinical setting. Some non-randomized studies showed that the duct-to-mucosa method
was a relatively safe approach. However, the prospective clinical study found that in
comparison with the conventional end-to-side anastomosis, duct-to-mucosa did not obviously
decrease the incidence of pancreatic fistula as well as other operative complications. The
Peng's binding anastomosis technique might be relatively simple to operate and have shorter
operative time, but as the raw pancreatic surface is exposed to the jejunal lumen directly
after the reconstruction, the activated pancreatic juice might lead to hemorrhage through
vascular corrosion. Moreover, a wide or large pancreatic stump will not fit the size of the
jejunal lumen, which could lead to anastomosis ischemia and leakage. The duct-to-mucosa
method is not affected by the size of pancreatic remnant and the jejunal lumen. The
seromuscular layer of the jejunum covers the pancreatic stump completely and will lower the
incidence of postoperative hemorrhage. It was proved to be superior to invagination
anastomosis in terms of anastomotic patency and function. Unfortunately, in the cases of
small main pancreatic duct or normal soft pancreas, the duct-to-mucosa approach is difficult
to operate and takes more surgery time, while simultaneously increasing the incidence of
postoperative pancreatic fistula(POPF). Therefore, it is difficult to find a single superior
strategy that applies to every case. Selecting an optimal pancreaticojejunal anastomotic
method should be based on the different textures of pancreas and the various sizes of the
main pancreatic duct.

The postoperative pancreatic fistula (POPF), which determines postoperative mortality,
length of hospital stay， is dependent of its definition, and is reported in up to 16% of
patients. The purpose of this study is to determine whether the new anastomosis called
"nonstented stump-closed" pancreaticojejunostomy can reduce the POPF rate and downgrade
compared with the common accepted duct-to-mucosa pancreaticojejunostomy after
pancreaticoduodenectomy. This single-centre, open, randomized controlled trail is conducted
following International Study Group on Pancreatic Fistula (ISGPF) criteria for pancreatic
fistula (PF). The primary endpoint is the POPF rate, and others include overall
postoperative complication rate and their severity reoperation rate and hospital stay.

Objectives:

Through the comparison with classic pancreatic duct-to-mucosa anastomosis, to evaluate
whether "nonstented stump closed" pancreaticojejunal anastomosis can reduce the pancreatic
fistula and other complications incidence; to evaluated the safety and maneuverability.

Patients and methods :all patients diagnosed with periampullar occupations which should be
resected through pancreaticoduodenectomy will be evaluated before surgery, including
CT,Magnetic Resonance(MR), Ultrasound B ,blood biochemical checks and cardiac and thoracical
evaluations. Before the surgery, the patients are divided into two groups by randomization.
After the pancreaticoduodenectomy, the randomization number decided the procedure of the
pancreaticojejunostomy.

Staging investigations will be standard and will include:

pancreatic enhanced CT; magnetic resonance cholangiopancreatography(MRCP); PET-CT if
necessary;

Randomization:

Block randomization will be done using a computer generated sheet. Randomization will be
performed 1 day before the operation.

All surgeries will be performed under general anesthesia with epidural analgesia. The
surgery will be either performed by or under the direct supervision of pancreatic surgeons
with experience in pancreaticojejunostomy surgery. Operative time, blood loss, blood product
replacement and all intraoperative details will be recorded in the proforma. Patients will
be shifted postoperatively to the anesthesia care unit (PCU) for observation and
subsequently to the recovery or high dependency ward once stabilized. Postoperative details
including period of postoperative pancreatic fistula,biliary leakage,postoperative
haemorrhage,postoperative pancreatitis , hospital stay and other complications will be
recorded. Postoperative mortality will be defined as 30-day mortality plus death before
discharge after surgery.

Data management: All collected data will be entered into a statistical software package for
subsequent analysis

Main research variables:

Primary Outcome :

The primary endpoint will be the postoperative pancreatic fistula(POPF) rate.

Secondary Outcome Measures:

postoperative hospital stay time; anastomosis time; reoperation rate; morbidity