Clinical trial NCT02928081: Standard Versus Extended Lymphadenectomy in Pancreatoduodenectomy for Patients With Pancreatic Head Adenocarcinoma
Official title: Standard Versus Extended Lymphadenectomy in Pancreatoduodenectomy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Carcinoma, Pancreatic Ductal
Lead sponsor: West China Hospital
Sponsor class: OTHER
Collaborators: name: Royal Liverpool University Hospital
First posted: 2016-10-07
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to determine whether the performance of extended lymphadenectomy in association with pancreatoduodenectomy improves the long-term survival in patients with pancreatic head ductal adenocarcinoma.Half of participants will receive pancreatoduodenectomy with extended lymphadenectomy,while the other half will receive pancreatoduodenectomy with standard lymphadenectomy.

Detailed description: Pancreatic cancer is a common malignant disease of the digestive system, and its incidence has been steadily increasing recently. Currently, the only potential curative treatment for pancreatic cancer is radical surgery. However, due to the peculiarity of the anatomical location of pancreas (in the retroperitoneum, surrounded by peripheral nerves and blood vessels) and its biological characteristics (neurotropic, highly malignant, and with probable skip metastasis), it is difficult to achieve R0 resection in patients with pancreatic cancer. High postoperative recurrence and distant metastasis rate are key factors in reducing long-term survival of patients with pancreatic cancer. The radical surgery modalities for pancreatoduodenectomy to achieve R0 resection involve extended lymphadenectomy, multivisceral resections, with or without simultaneous vein removals. Currently, the lymphadenectomy extent and approaches used to achieve R0 status are diverse. In 2014, the International Study Group for Pancreatic Surgery (ISGPS) reached a consensus to strive to resect lymph nodes (LNs) 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b in standard lymphadenectomy for pancreatoduodenectomy. However, no consensus was reached on dissection of LN 16 due to variation in the literature and different expert opinions. On the current evidence, benefit of extended lymph node dissection seems to be outweighed by the risks. But deficiencies exist in the design of previous RCTs, such as insufficient sample size, lack of certain critical data for statistical analysis, inclusion of other pathological types of pancreatic neoplasms and variable retroperitoneal lymph node resection and nerve plexus dissection . Therefore, the power of evidence was low. Most studies report a high frequency of lymph node metastasis to LNs 13, 14, 17, 12 and 16 in pancreatic cancer, and tendency to metastasis from LNs 13, 14 to LN 16. In a lot of case reports, only nodal station 16a2 and 16b1 were positive in LN 16.

This study is performed to confirm whether pancreatoduodenectomy with extended lymphadenectomy could improve survival. Subjects undergoing surgery will be randomized to pancreatoduodenectomy with extended lymphadenectomy including nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1) versus standard pancreatoduodenectomy. Subjects will be followed every three months for survivorship or death. The primary endpoint of 5-year overall or disease-free survival survival will be determined at five year post surgery.

Eligibility criteria: Inclusion Criteria:

* Subject was diagnosed with pancreatic ductal adenocarcinoma supported by pathological and radiological examination preoperatively
* Subject with absence of vascular invasion and metastasis
* Subject with absence of prior history of cancer

Exclusion Criteria:

* Subject was diagnosed that other pancreatic tumour types (neuroendocrine tumors, intraductal papillary mucinous neoplasm, serous cystadenoma, mucinous cystadenocarcinoma, solid pseudopapillary neoplasm and pancreatitis)
* Subject was found with liver, omental, mesenteric or peritoneal metastasis intraoperatively
* Subject with presence of other significant diseases (e.g., coronary heart disease)

Primary outcomes:
measure: 5-year overall survival rate
timeFrame: 5 years
Secondary outcomes:
measure: Postoperative pancreatic fistula
timeFrame: Within 30 days or before discharge
measure: Bile leakage
timeFrame: Within 30 days or before discharge
measure: Delayed gastric emptying
timeFrame: Within 30 days or before discharge
measure: Post-pancreatectomy haemorrhage
timeFrame: Within 30 days or before discharge
measure: Intra-abdominal infection
timeFrame: Within 30 days or before discharge
measure: Wound infection
timeFrame: Within 30 days or before discharge
measure: Postoperative mortality
timeFrame: Within 30 days or 60 days
measure: Quality of life
timeFrame: 1 or 3 or 5 year
measure: 5-year disease-free survival rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Hongyu Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xiong J, Szatmary P, Huang W, de la Iglesia-Garcia D, Nunes QM, Xia Q, Hu W, Sutton R, Liu X, Raraty MG. Enhanced Recovery After Surgery Program in Patients Undergoing Pancreaticoduodenectomy: A PRISMA-Compliant Systematic Review and Meta-Analysis. Medicine (Baltimore). 2016 May;95(18):e3497. doi: 10.1097/MD.0000000000003497.
citation: Xiong JJ, Tan CL, Szatmary P, Huang W, Ke NW, Hu WM, Nunes QM, Sutton R, Liu XB. Meta-analysis of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Br J Surg. 2014 Sep;101(10):1196-208. doi: 10.1002/bjs.9553. Epub 2014 Jul 16.
citation: Chen Y, Ke N, Tan C, Zhang H, Wang X, Mai G, Liu X. Continuous versus interrupted suture techniques of pancreaticojejunostomy after pancreaticoduodenectomy. J Surg Res. 2015 Feb;193(2):590-7. doi: 10.1016/j.jss.2014.07.066. Epub 2014 Aug 5.
citation: Chen Y, Tan C, Mai G, Ke N, Liu X. Resection of pancreatic tumors involving the anterior surface of the superior mesenteric/portal veins axis: an alternative procedure to pancreaticoduodenectomy with vein resection. J Am Coll Surg. 2013 Oct;217(4):e21-8. doi: 10.1016/j.jamcollsurg.2013.07.383. No abstract available.
citation: Chen Y, Wang X, Ke N, Mai G, Liu X. Inferior mesenteric vein serves as an alternative guide for transection of the pancreatic body during pancreaticoduodenectomy with concomitant vascular resection: a comparative study evaluating perioperative outcomes. Eur J Med Res. 2014 Aug 21;19(1):42. doi: 10.1186/s40001-014-0042-z.
citation: Nimura Y, Nagino M, Takao S, Takada T, Miyazaki K, Kawarada Y, Miyagawa S, Yamaguchi A, Ishiyama S, Takeda Y, Sakoda K, Kinoshita T, Yasui K, Shimada H, Katoh H. Standard versus extended lymphadenectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas: long-term results of a Japanese multicenter randomized controlled trial. J Hepatobiliary Pancreat Sci. 2012 May;19(3):230-41. doi: 10.1007/s00534-011-0466-6.
citation: Jang JY, Kang MJ, Heo JS, Choi SH, Choi DW, Park SJ, Han SS, Yoon DS, Yu HC, Kang KJ, Kim SG, Kim SW. A prospective randomized controlled study comparing outcomes of standard resection and extended resection, including dissection of the nerve plexus and various lymph nodes, in patients with pancreatic head cancer. Ann Surg. 2014 Apr;259(4):656-64. doi: 10.1097/SLA.0000000000000384.
citation: Wang Z, Ke N, Wang X, Wang X, Chen Y, Chen H, Liu J, He D, Tian B, Li A, Hu W, Li K, Liu X. Optimal extent of lymphadenectomy for radical surgery of pancreatic head adenocarcinoma: 2-year survival rate results of single-center, prospective, randomized controlled study. Medicine (Baltimore). 2021 Sep 3;100(35):e26918. doi: 10.1097/MD.0000000000026918.