La technique d'une DPC pour adénocarcinome a évolué ces dernières années tant au niveau sécurité qu'au niveau carcinologique mais cela n'a pas suffit à faire progresser la survie. On peut se demander si la modification de la technique chirurgicale pourrait avoir un impact significatif sur la survie.A) Nous avons recherché, sur 23 pièces de DPC encrées, la présence de la mutation K-ras au niveau de la marge veineuse affirmée R0 en analyse histologique : 13 spécimens (groupe kras+) exprimaient une mutation K-ras au sein de la marge veineuse versus 10 spécimens (groupe kras-) ne l'exprimant pas. Les tumeurs des 2 groupes étaient comparables (taille, envahissement ganglionnaire, engainement périnerveux…). La survie globale à 1 an et 3 ans des groupes kras- versus kras+ étaient de 80% versus 84,6% et 16,7% versus 0% (p=0,03), respectivement. Les médianes de survie des groupes kras- versus kras+ étaient de 24 mois versus 16 mois (p=0,04), respectivement.B) Nous avons comparé, après appariement, 19 patients ayant eu une DPC avec résection « par excès » de la veine porte (groupe VP) avec 19 patients ayant eu une DPC sans résection de la veine porte (groupe contrôle). Les survies médianes et à 3 ans du groupe VP versus groupe contrôle étaient 42 mois versus 22 mois (p=0,04) et 60% versus 31% (p=0,03), respectivement.En conclusion, notre travail a montré qu'au-delà de la marge déterminée par le chirurgien pendant la chirurgie, de celle de l'anatomopathologiste déterminée par l'analyse microscopique, il existait une marge génique. La résection systématique de la veine porte semblait bénéfique car elle permettait sans doute de passer au-delà de cette marge génique. / Pancreticoduodenectomy (PD) for adenocarcinoma was safer during the last decades but did not improve survival. We sought to determine if technical changes during PD could improve survival.A) In a first study, we determine the presence of K-ras mutation in the venous margin of 23 PD's specimens. Thirteen specimens had K-ras mutation (kras+ group) and 10 specimens did not (kras- group). Except K-ras mutation status, tumors of the 2 groups were not different when comparing major histological findings (margin status, lymph node invasion, perineural invasion…). Overall 1- and 3-years survival of patients of kras- group versus kras+ group were 80% versus 84,6% and 16,7% versus 0% (p=0,03), respectively. Median survival of patients of kras- group versus kras+ group were 24 months versus 16 months (p=0,04), respectively.B) In a second study, we compared 19 patients with “excessive” portal vein resection during PD (PV group) with 19 matched patients who underwent PD without venous resection (control group). Median survival of patients of PV group versus control group were 42 months versus 22 months (p=0,04), respectively.In conclusion, we showed that the « genic margin » concept was consistent. Systematic portal vein resection could avoid positive genic margin and might be benefic for patient who underwent PD for resecable adenocarcinoma.

Colorectal cancer (CRC) is the third most widespread and fourth most fatal malignancy disease. The CRC from a primary site can spread to other tissues, forming secondary tumours. CRC can metastasise to the liver through the effect of K-Ras and Pten mutation (Mt.) (Abbas et al. 2020). This study aimed to assess the hypothesis that the Ran inhibitor mebendazole MBZ reduces cell invasion and metastasis of CRC. I have investigated MBZ effect on the CRC isogenic human cell lines with specific mutations (HCT-116 K-Ras, DLD-1 K-Ras and Pten deletion and wild type HCT-116 and DKO-3. I used qRT-PCR and western blotting to identify expression levels of various genes and signalling molecules after treatment with 0.5 mM MBZ. In addition, several assays were performed to investigate MBZ effect on biological properties of the cells such as proliferation, migration, invasion, and colony formation. MBZ downregulated Ran and induced apoptosis through inhibition of Bcl-2 expression as well as inducing caspase -3, -7, -9 and PARP cleavage. Moreover, MBZ showed an effect on immune response by down regulating C5a, IL-1ß and IL-1α analysed at mRNA level. When treated with MBZ, the migration, invasion and colony formation abilities of HCT-116 K-Ras Mt., DLD-1 K-Ras Mt. and HCT-116 Pten-/- were significantly reduced compared to a control treated cell line. This was also the case with wild type cell lines such as HCT-116 and DKO-3. Furthermore, signalling molecules such as p- Erk 1/2 and p- Akt were upregulated after MBZ treatment and exert inhibition on Akt 1/2/3 and VEGFR1/2 mRNA levels. In conclusion; MBZ which is a Ran inhibitor, has significantly reduced proliferation, colony formation, and migration in colorectal cell lines with K-Ras and Pten gene deletion compared to wild type cells in a dose-dependent manner. This work paves the way to clinical validation of MBZ as a combination therapy for reducing the invasion of CRC cells.