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Ablative therapies in oncology surgery Fernando Burdío

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Influence of principal pancreatic duct ligation on the occurrence of neoplastic lesions (PanIN and AFL) in murine pancreatic cancer models

El adenocarcinoma pancreàtic (PDAC) és el tipus de càncer de pàncrees més comú i una de les malalties malignes més devastadores. Tot i l'avenç en la investigació bàsica i aplicada, el pronòstic de l'PDAC no ha millorat en els últims 20 anys requerint-així noves aproximacions per al seu diagnòstic i tractament.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and one of the most devastating. Despite advances in basic and applied research, the prognosis of PDAC has not improved over the past 20 years, necessitating new approaches to diagnosis and treatment. Our studies of normal and genetically modified K-Ras oncogene mice demonstrate that after experimental pancreatic duct ligation (PDL) there is a highly significant reduction in the occurrence of preneoplastic lesions in the pancreas distal to the ligation. This still very preliminary data might suggest that surgery involving the ligation/obstruction of the main pancreatic duct or transpapillary endoscopy in patients with preneoplastic lesions might stop them progressing to PDAC. In fact, several biomedical engineers in our research group (METABLATE, www.metablate.com) are currently designing radiofrequency-assisted electrodes that facilitate the transluminal closure of the major pancreatic duct through endoscopy. This project has interesting synergies that underline its translational significance in the clinical environment.

Other possibly interesting repercussions are the RF transection of the pancreatic neck after cephalic duodenopancreatectomy (CPD) for PDAC of the pancreas head, in certain situations. This technique could reduce the long-term risk of preneoplastic lesions appearing, and even PDAC, in the remains of the pancreas, compared with the conventional way of treating the pancreas after CPD (pancreatic anastomosis).

Figura 1. A. Schematic diagram of the principal pancreatic duct ligation (PDL) surgery. B. Representative pancreases of control mice (i) and after PDL (ii). Histological imaging of post-PDL mice shows atrophy of the distal pancreas (DP) relative to the proximal pancreas (PP). C. Diagram of the technique using a catheter created by our group for endoluminal radiofrequency sealing of the pancreatic duct. 

Important publications:

• Burdío F, Dorcaratto D, Hernandez L, Andaluz A, Moll X, Quesada R, Poves I, Grande L, Cáceres M, Berjano E. Radiofrequency-induced heating versus mechanical stapler for pancreatic stump closure: in vivo comparative study. Int J Hyperthermia. 2016 May;32(3):272-80. doi: 10.3109/02656736.2015.1136845.
• Ewertowska E, Andaluz A, Moll X, Aguilar A, Garcia F, Fondevila D, Quesada R, Trujillo M, Burdío F, Berjano E. Development of a catheter-based technique for endoluminal radiofrequency sealing of pancreatic duct. Int J Hyperthermia. 2019; 36 (1): 677-686. doi: 10.1080/02656736.2019.1627585.
• Quesada R, Burdío F, Iglesias M, Dorcaratto D, Cáceres M, Andaluz A, Poves I, Castiella T, Sánchez P, Berjano E, Grande L. Radiofrequency pancreatic ablation and section of the main pancreatic duct does not lead to necrotizing pancreatitis. Pancreas. 2014 Aug;43(6):931-7. doi: 10.1097/MPA.0000000000000156.
• Dorcaratto D, Burdío F, Fondevila D, Andaluz A, Quesada R, Poves I, Caceres M, Mayol X, Berjano E, Grande L. Radiofrequency is a secure and effective method for pancreatic transection in laparoscopic distal pancreatectomy: results of a randomized, controlled trial in an experimental model. Surg Endosc. 2013 Oct;27(10):3710-9. doi: 10.1007/s00464-013-2952-1.
• Dorcaratto D, Burdío F, Fondevila D, Andaluz A, Poves I, Martinez MA, Quesada R, Berjano E, Grande L. Laparoscopic distal pancreatectomy: feasibility study of radiofrequency-assisted transection in a porcine model. J Laparoendosc Adv Surg Tech A. 2012 Apr;22(3):242-8. doi: 10.1089/lap.2011.0417.
• Andaluz A, Ewertowska E, Moll X, Aguilar A, García F, Fondevila D, Quesada R, Berjano E, Grande L, Burdío F. Endoluminal radiofrequency ablation of the main pancreatic duct is a secure and effective method to produce pancreatic atrophy and to achieve stump closure. Sci Rep. 2019 Apr 11; 9(1):5928. doi: 10.1038/s41598-019-42411-7.
• Quesada R, Andaluz A, Cáceres M, Moll X, Iglesias M, Dorcaratto D, Poves I, Berjano E, Grande L, Burdío F. Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model. Pancreatology. 2016 Jan-Feb;16(1):38-43. doi: 10.1016/j.pan.2015.10.014.