Oesogastric and pancreatic adenocarcinomas are poor-prognosis cancers. Incidence of pancreatic cancer drastically increases to such an extent that it will become the second cause of cancer's mortality by 2030. A major challenge is to optimize the therapies for localized setting, when oxaliplatin-based chemotherapy is the standard, before and after surgical excision. Because in 50% of cases oxaliplatin triggers a grade 2-3 sinusoidal obstruction syndrome (SOS) which increases post-operative morbidity, decreases histological response to chemotherapy, increases tumor recurrence, and aggravates the risk of chemotherapy-induced peripheral neuropathy (CIPN).
There is an urgent need to better understand the biological processes involved in SOS, in order to prevent and treat it without stopping or reducing oxaliplatin administration.
The biological link between oxaliplatin and SOS has not been described, but recent murine experiments argue for HMGB1 to be the mediator released after exposure to oxaliplatin and inducing SOS, and thereafter CIPN. To date, no biomarker is established between murine and patient analyses, and the release of HMGB1 after oxaliplatin treatment and its effect on hepatic parenchyma is not described in patients. Investigators hypothesized is that HMGB1 would also been increased in patients after oxaliplatin treatment, and correlated to the development of SOS and CIPN. If confirmed, personalized treatment will be possible to target this pathway.
Therefore, investigators propose to dynamically explore this hypothesis in localized oesogastric and pancreatic cancer patients who will be routinely managed by an initial laparoscopy and post-oxaliplatin surgical excision.
ECOG WHO Performance status = 0 or 1
Signed and dated informed consent
Patients with histological diagnosis of oesogastric or pancreatic adenocarcinoma
Resectable tumors
Histology other than adenocarcinoma
Metastatic disease
History of previous treatment with oxaliplatine
History of systemic chemotherapy administration within 5 years prior to inclusion,
Single group
assess the serum HMGB1 concentrations before and after an oxaliplatin-based chemotherapy
Biological/Vaccineassess the serum HMGB1 concentrations
Serum HMGB1 concentrations
Assess Serum HMGB1 concentrations in two groups of patients : with grade 0 or 1 SOS and with grade ≥2 SOS, at two timepoints: before exploratory laparoscopy and before surgical excision to determinate the effect of HMGB1 on SOS development
variation of serum HMGBI concentration (ng/ml)
mesurated the serum HMGB1 concentration (ng/ml) at several time of treatment of the patient then comparated these assess the dynamic variation of serum HMGB1 concentrations after oxaliplatin-based chemotherapy in oesogastric and pancreatic cancer patients with grade 0 or 1 SOS and with grade ≥2 SOS
variation of serum RAGE (receptor of HMGBI) concentration
mesurated the serum RAGE concentration (ng/ml) at several time of treatment of the patient then comparated these assess the dynamic variation of serum HMGB1 concentrations after oxaliplatin-based chemotherapy in oesogastric and pancreatic cancer patients with grade 0 or 1 SOS and with grade ≥2 SOS
sinusoidal obstruction syndrome (SOS) diagnosis
compare SOS histology diagnosis (absent, mild, moderate, severe) with no invasive biological scores "APRI and FIB4"which use ASAT (U/L), ALAT(U/L), plaquettes (G/L) and the age (years) of the patient
sinusoidal obstruction syndrome (SOS) diagnosis
compare SOS histology diagnosis (absent, mild, moderate, severe)) with splenic's volumetric measured by radiological's assessment
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