Standard Versus Extended Lymphadenectomy in Pancreatoduodenectomy for Patients With Pancreatic Head Adenocarcinoma

Standard Versus Extended Lymphadenectomy in Pancreatoduodenectomy

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.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Pancreatic Ductal
• Intervention / Treatment: Procedure: Extended lymphadenectomy; Procedure: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Junjie Xiong, MD; Phone Number: 86-28-85422474; Email: junjiex2011@126.com
• Study Contact Backup: Name: Xubao Liu, MD; Phone Number: 86-28-85422474; Email: liuxb2011@126.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital
      • Contact: Junjie Xiong, MD; Phone Number: 86-28-85422474; Email: junjiex2011@126.com
      • Sub-Investigator: Hao Zhang, MD
      • Contact: Xubao Liu, MD; Phone Number: 86-28-85422474; Email: liuxb2011@126.com
      • Principal Investigator: Junjie Xiong, MD
      • Principal Investigator: Hongyu Chen, MD
      • Sub-Investigator: Nengwen Ke, MD
      • Sub-Investigator: Chunlu Tan, MD
      • Sub-Investigator: Ming Yang, MD
      • Sub-Investigator: Bole Tian, MD
      • Sub-Investigator: Weiming Hu, MD
      • Sub-Investigator: Kezhou Li, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extended lymphadenectomy; In addition to the standard lymphadenectomy, the nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1) must be dissected. Retroperitoneal lymphatic tissue, nerves and connective tissue range from the hepatic portal down to the beginning part of the inferior mesenteric artery, the right to the right renal hilus, left to the left edge of the abdominal aorta is included.	Procedure: Extended lymphadenectomy; Extended lymphadenectomy with nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1)
Other: Standard lymphadenectomy; Lymph node dissection includes the superior and inferior pyloric nodes (LN5, LN6), anterior and posterior nodes along the common hepatic artery (CHA) (LN8a, 8b), nodes along the common hepatic duct, common bile duct and cystic duct (LN12b1, 12b2, 12c), posterior pancreatoduodenal nodes (LN13a, 13b), nodes along the superior mesenteric artery (SMA) (LN14a, 14b), anterior pancreatoduodenal nodes (LN17a, 17b), but excluding the nerve tissues around common hepatic artery and the superior mesenteric artery.	Procedure: Standard lymphadenectomy; Lymph node dissection includes(LN5, LN6),(LN8a, 8b),(LN12b1, 12b2, 12c),(LN13a, 13b),(LN14a, 14b),(LN17a, 17b)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year overall survival rate	The percentage of patients that are alive at a 5 year	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pancreatic fistula	ISGPS definition	Within 30 days or before discharge
Bile leakage	ISGLS definition	Within 30 days or before discharge
Delayed gastric emptying	ISGPS definition	Within 30 days or before discharge
Post-pancreatectomy haemorrhage	ISGPS definition	Within 30 days or before discharge
Intra-abdominal infection	Presence of fever, signs of peritonitis, high leukocytes count or positive peritoneal drainage fluid culture	Within 30 days or before discharge
Wound infection	Requiring invasive treatment, for example: positive wound exudate culture and requiring continuous re-open drainage or invasive treatment	Within 30 days or before discharge
Postoperative mortality	Death due to any cause before or at postoperative day 30 and 60	Within 30 days or 60 days
Quality of life	EORTC QLQ-C30, according to the scoring manual published by the EORTC Quality of Life group	1 or 3 or 5 year
5-year disease-free survival rate	The percentage of patients alive without recurrence at a 5 year	5 years

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: Royal Liverpool University Hospital
• Investigators: Principal Investigator: Hongyu Chen, MD, West China Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: October 6, 2016
• First Submitted That Met QC Criteria: October 6, 2016
• First Posted (Estimate): October 7, 2016

Study Record Updates

• Last Update Posted (Estimate): October 7, 2016
• Last Update Submitted That Met QC Criteria: October 6, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal
• Other Study ID Numbers: 2015267

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO