Role of CTC´s Spread During Pancreaticoduodenectomy in Patients With Pancreatic and Periampullary Tumors

Study Overview
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Brief Summary
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This multicentre, prospective and randomized study aims(1:1) to compare the rate of recurrence, metastasis and survival according to the levels of intraoperative circulating tumor cells (CTCs) during cephalic duodenopancreatectomy in patients with pancreatic and periampullary tumors.

Detailed Description
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Cephalic duodenopancreatectomy is the technique indicated for patients with pancreatic head carcinoma and periampullar tumors. There are different technical variants, it is not standardized what is the best option in relation to local recurrence, metastasis and survival. In the study, patients will be randomized into two study groups with pancreatic and periampullary tumors undergoing cephalic pancreatectomy (NT) vs initial approach by superior mesenteric artery (SMA). The measurement of circulating tumor cells (CTCs) allows to assess the degree of cellular dissemination due to surgical manipulation.CTCs will be evaluated during surgery (nº CTCs / mL blood). To do this, a maximum of 4 blood samples from the portal vein will be performed, in each study group according to the following scheme: NT group: basal (at the beginning of surgery), portal vein pancreatic detachment, postresection (NT2) and before closure (NT3). SMA group: basal (at the beginning of surgery), after Kocher maneuver and SMA dissection, postresection, before closure. Subsequently, the quantified levels of CTCs will be correlated with the occurrence of local tumor recurrence, metastasis development and patient patient survival.

Official Title
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Role of Circulating Tumor Cells (CTC´s) Spread During Pancreaticoduodenectomy in Metastasis and Survival Rates in Patients With Pancreatic and Periampullary Tumors

Conditions
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Pancreatic Tumor, Periampullary Carcinoma Resectable, Circulating Tumor Cells, Metastasis

Intervention / Treatment
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* Procedure: No Touch (NT)
* Procedure: Superior Mesenteric Artery First (SMA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients older than 18 years, with adenocarcinomas of the pancreas and potentially resectable periampullary tumors by cephalic duodenopancreatectomy or total duodenopancreatectomy indicated intraoperatively for technical reasons, who voluntarily agree to participate in the study and sign informed consent Exclusion Criteria: Patients in whom liver metastases or peritoneal carcinomatosis are detected during surgery. Patients with neuroendocrine pancreatic tumors or cystic tumors. Patients in whom tumor resection is not finally achieved because it shows intraoperatively that the tumor is locally advanced and unresectable. Patients with macroscopic residual tumor (R2). High-risk patients with severe pathology (ASA IV) according to the American Association of Anesthesiologists. Patients receiving neoadjuvant therapy Patients in whom the intraoperative pathological anatomy indicates borders of pancreatic resection affected

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized (1:1) to 2 study groups according to duodenopancreatectomy surgical approach: No-Touch group (NT) or Artery First group (SMA) in patients with pancreatic and periampullary tumors, to evaluated circulating tumor cells (CTCs) levels during the surgery. Sample size = 86
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No Touch (NT)<br>Pancreatic and Periampullary Tumors resection by no-touch technique | Procedure: No Touch (NT)<br>* Tumor resection by No-touch technique: dissection of hepatic hilum, dissection of superior mesenteric vein (SMV) in caudal aspect of pancreas, section of antrum, pancreatic neck section. Section-ligation of veins of duodenopancreatectomy part of SMV and portal. Then Kocher-uncrossing maneuver of the jejunal loop and final section of the retro-portal (back of the portal vein) blade.<br>|
| Active Comparator: Superior Mesenteric Artery First (SMA)<br>Pancreatic and Periampullary Tumors resection by superior Mesenteric Artery First technique | Procedure: Superior Mesenteric Artery First (SMA)<br>* Tumor resection by SMA technique: Kocher maneuver extends to the left renal vein (LRV). Dissection above the LRV of the SMA (refer to vessel-loop). Then, SMA will be identified on the caudal side of the pancreas (mesenterial root) and progressive dissection until its origin in the aorta artery (previously referenced with vessel loop).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating tumor cells (CTC´s) | Change in the concentration of circulating tumor cells (CTCs) levels (nº CTCs/ mL blood) during the surgery, 4 blood samples will be taken from the portal vein | During the surgery: at the beginning of surgery, immediately after disconnecting the pancreas from the portal vein, just at the moment the pancreatic resection ends and before the skin closed | 
| Local tumor recurrence | Presence (YES or NO) compatible images of local tumor recurrence Valid imaging tests of presence or absence can be checked by: computerized tomography (CT) or magnetic resonance (NMR) | From the day of surgery to 3 years of follow-up | 
| Metastasis | Presence (YES or NO) compatible images of metastasis | From the day of surgery to 3 years of follow-up | 
| Patient survival | Death (YES OR NO): number of patients dying during study | From the day of surgery to 3 years of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | The complications evaluation and their severity will be based on the classification of Dindo-Clavien and the definitions of the International Study Group of Pancreatic Surgery (ISGPS). Pancreatic fistula: Presence (yes or no) and degree (A, B, C) Delayed gastric emptying: Presence (yes or no) and degree (A, B, C) Hemorrhage: Presence (yes or no) and degree (A, B, C) | From the day of surgery up to 6 weeks of follow-up |