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

Carcinoma, Pancreatic Ductal Clinical Trial

Official title:

Standard Versus Extended Lymphadenectomy in Pancreatoduodenectomy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02928081
• Other study ID #: 2015267
• Status: Recruiting
• Phase: N/A
• First received: October 6, 2016
• Last updated: October 6, 2016
• Start date: January 2016
• Est. completion date: April 2021

Study information

• Verified date: October 2016
• Source: West China Hospital
• Contact: Xubao Liu, MD
• Phone: 86-28-85422474
• Email: liuxb2011[@]126.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: April 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Pancreatic Ductal

Intervention

Procedure:
• Extended lymphadenectomy
Extended lymphadenectomy with nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1)
• Standard lymphadenectomy
Lymph node dissection includes(LN5, LN6),(LN8a, 8b),(LN12b1, 12b2, 12c),(LN13a, 13b),(LN14a, 14b),(LN17a, 17b)

Locations

Country	Name	City	State
China	West China Hospital	Chengdu	Sichuan

Sponsors (2)

Lead Sponsor	Collaborator
West China Hospital	Royal Liverpool University Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

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. — View 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. — View 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. E — View 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 v — View 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 adenocar — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-year overall survival rate	The percentage of patients that are alive at a 5 year	5 years	No
Secondary	Postoperative pancreatic fistula	ISGPS definition	Within 30 days or before discharge	Yes
Secondary	Bile leakage	ISGLS definition	Within 30 days or before discharge	Yes
Secondary	Delayed gastric emptying	ISGPS definition	Within 30 days or before discharge	Yes
Secondary	Post-pancreatectomy haemorrhage	ISGPS definition	Within 30 days or before discharge	Yes
Secondary	Intra-abdominal infection	Presence of fever, signs of peritonitis, high leukocytes count or positive peritoneal drainage fluid culture	Within 30 days or before discharge	Yes
Secondary	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	Yes
Secondary	Postoperative mortality	Death due to any cause before or at postoperative day 30 and 60	Within 30 days or 60 days	Yes
Secondary	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	No
Secondary	5-year disease-free survival rate	The percentage of patients alive without recurrence at a 5 year	5 years	No