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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Standard Versus Extended Lymphadenectomy in Pancreatoduodenectomy

Conditions
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Carcinoma, Pancreatic Ductal

Intervention / Treatment
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* Procedure: Extended lymphadenectomy
* Procedure: Standard lymphadenectomy


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Extended lymphadenectomy<br>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<br>* Extended lymphadenectomy with nerve tissues around CHA and the SMA and nodes around the celiac trunk and SMA (No.16a2, 16b1)<br>|
| Other: Standard lymphadenectomy<br>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<br>* Lymph node dissection includes(LN5, LN6),(LN8a, 8b),(LN12b1, 12b2, 12c),(LN13a, 13b),(LN14a, 14b),(LN17a, 17b)<br>|

What is the study measuring?
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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 |