Nonstented Stump-closed vs Duct-to-Mucosa Pancreaticojejunostomy After Pancreaticoduodenectomy
Condition: Pancreatic Neoplasms; Biliary Tract Neoplasms; Pancreatitis, Chronic; Duodenal Neoplasms
MeSH terms: Neoplasms; Pancreatic Neoplasms; Biliary Tract Neoplasms; Duodenal Neoplasms; Pancreatitis; Pancreatitis, Chronic
Study type: Interventional
Phase: Phase 3

Summary: 
      Pancreaticojejunostomy is the key procedure of pancreaticoduodenectomy. The aim of our study
      is to investigate a new pancreaticojejunal (PJ) anastomosis procedure named "nonstented
      stump-closed pancreaticojejunostomy" in pancreatoduodenectomy, which could provide a feasible
      option to pancreatic surgeons for patients with pancreaticoduodenectomy.
    

Detailed description: 
      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
    

Intervention name(s): pancreaticojejunostomy
Intervention type(s): Procedure
Intervention description(s): Nonstented stump closed pancreaticojejunostomy:
Close the pancreatic stump with interrupted inverting sutures around the "papillary-like" pancreatic duct.
A small full-thickness enterotomy was penetrated on the jejunal wall for connecting to the "papillary-like" pancreatic duct by placing 4-6 sutures from the "periductal" parenchyma to the whole-layer jejunum hole. After that, interrupted sutures between the front wall of pancreatic stump and the seromuscular jejunum were performed by 4-0 absorbable sutures to complete the anastomosis.
Duct-to-mucosa pancreaticojejunostomy:Two layer anatomosis with "Duct-to-Mucosa" pancreaticojejunostomy is performed by suturing the pancreatic parenchyma to the jejunal seromuscular layer and no stenting tube was used.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pancreaticoduodenectomy; Pancreaticojejunostomy