Clinical Study A Reappraisal of Chemotherapy-Induced Liver Injury in Colorectal Liver Metastases before the Era of Antiangiogenics

Background and Aims. Chemotherapy of colorectal liver metastases can induce hepatotoxicity in noncancerous liver. We describe these lesions and assess risk factors and impacts on postresection morbidity and mortality in naive patients to chemotherapy before the era of bevacizumab. Methods. Noncancerous liver tissue lesions were analysed according to tumour, chemotherapy, surgery, and patient characteristics. Results. Fifty patients aged 62 ± 9.3 years were included between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative hyperplasia (NRH), 2 (4%) steatosis >30%, zero steatohepatitis, and 16 (32%) surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, = 0.04), especially LV5FU2 ( = 0.02). SD was associated with oxaliplatin (54.5% versus 23.5%, = 0.05) and low body mass index ( = 0.003). NRH was associated with oxaliplatin ( = 0.03) and extensive resection ( = 0.04). No impact on mortality and morbidity was observed, apart postoperative elevation of bilirubin levels in case of PSF ( = 0.03), longer hospitalization in case of surgical hepatitis ( = 0.03), and greater blood loss in case of portal fibrosis ( = 0.03). Conclusions. Chemotherapy of colorectal liver metastases induces sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related to 5FU, without any impact on postoperative mortality

The use of chemical actinometry for the evaluation of the light absorption efficiency in scattering photopolymerizable miniemulsions

International audienc

Stability of folic acid under several parameters

International audienceFolic acid is a small molecule, also known as vitamin B-9. It is an essential compound involved in important biochemical processes. It is widely used as a vector for targeted treatment and diagnosis especially in cancer therapeutics. Nevertheless, not many authors address the problem of folic acid degradation. Several researchers reported their observations concerning its denaturation, but they generally only took into account one parameter (pH, temperature, light or O-2 etc.). In this review, we will focus on five main parameters (assessed individually or in conjunction with one or several others) that have to be taken into account to avoid the degradation of folic acid: light, temperature, concentration, oxygen and pH, which are the most cited in the literature. Scrupulous bibliographic research enabled us to determine two additional degradation factors that are the influence of singlet oxygen and electron beam on folic acid stability, which are not considered as among the prime factors. Although these two factors are not commonly present as compared to the others, singlet oxygen and electron beams intervene in new therapeutic technologies and must be taken in consideration for further applications such photodynamic or X-rays therapies

Somatostatin receptor scintigraphy screening in advanced hepatocarcinoma: A multi-center French study.

International audienceBACKGROUND: Somatostatin receptor scintigraphy (SRS) has been reported for receptor (SSTR) screening in advanced hepatocarcinoma (aHC) prior to somatostatin analogue treatment. AIMS: To evaluate SSTR screening with SRS in aHC patients. RESULTS: Seventy aHC patients (63 men) aged 65 +/- 11 y were included, with alcohol, viral or other causes cirrhosis in 35 (50%), 23 (33%), 12 (17%) cases respectively. CLIP score was 2.7 +/- 1.7, with more than three nodules in 37 (53%) cases. Largest nodule measured 7.6 +/- 4.5 cm. Median alpha-fetoprotein was 574 UI/mL. SRS was positive in 25/70 (35.7%) livers and 7/17 (41.2%) metastatic sites. Positive SRS patients differed from others for tumor size (9.2 +/- 4 vs. 6.7 +/- 4.6 cm, p = 0.03), prothrombin time (PT) (75.2 +/- 15.2 vs. 61.9 +/- 19%, p = 0.005), albumin (34.1 +/- 5.9 vs. 30.5 +/- 7.2 g/L, p = 0.04) and Child-Pugh (6.7 +/- 1.8 vs. 7.7 +/- 2.3, p = 0.04). After multivariate analysis, only PT was associated with positive SRS (p = 0.028). Immunohistochemistry was positive for SSTR2s in 6/7 tumors (SRS uptake in 5/6 cases). METHODS: SRS was performed prior treatment, with images at 4, 24 and 48 h. For seven tumors, SSTR2 subtype was detected immunohistochemically. CONCLUSIONS: In advanced hepatocarcinoma, we report SRS uptake in 35.7% of livers and 41.2% of metastatic sites. SRS value in screening patients for somatostatin analogue treatment remains to be assessed

The orphan GPR50 receptor promotes constitutive TGFβ receptor signaling and protects against cancer development

Transforming growth factor-β (TGFβ) regulates many cellular processes. Here the authors show that the orphan G-protein coupled receptor GPR50 can activate the TGFβ receptor I, in the absence of TGFβ, by stabilizing its active conformation and show antitumor activity in a mouse model of breast cancer