Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy.

AIMS: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is an increasingly used therapeutic strategy for advanced rectal cancer, but risk stratification and final outcomes remain suboptimal. Recently, the oncogenic role of the fibroblast growth factor/fibroblast growth factor receptor (FGFR) signalling pathway has been recognised; however, its clinical significance in rectal cancer has not been elucidated. In this study, we identify and validate targetable drivers associated with the FGFR signalling pathway in rectal cancer patients treated with CCRT. METHODS: Using a published transcriptome of rectal cancers, we found FGFR2 gene significantly predicted response to CCRT. The expression levels of FGFR2, using immunohistochemistry assays, were further evaluated in 172 rectal cancer specimens that had not received any treatment. Expression levels of FGFR2 were statistically correlated with major clinicopathological features and clinical survival in this valid cohort. RESULTS: High expression of FGFR2 was significantly related to advanced pretreatment tumour (p=0.022) and nodal status (p=0.026), post-treatment tumour (p<0.001) and nodal status (p=0.004), and inferior tumour regression grade (p<0.001). In survival analyses, high expression of FGFR2 was significantly associated with shorter local recurrence-free survival (p=0.0001), metastasis-free survival (MeFS; p=0.0003) and disease-specific survival (DSS; p<0.0001). Notably, high expression of FGFR2 was independently predictive of worse outcomes for MeFS (p=0.002, HR=5.387) and DSS (p=0.004, HR=4.997). CONCLUSIONS: High expression of FGFR2 is correlated with advanced tumour stage, poor therapeutic response and worse survival in rectal cancer patients receiving neoadjuvant CCRT. These findings indicate that FGFR2 is a prognostic factor for treating rectal cancer.

Diabetes mellitus impairs the response to intra-arterial chemotherapy in hepatocellular carcinoma.

Diabetes mellitus is associated with a poorer outcome in patients with hepatocellular carcinoma. The impact of diabetes mellitus on the treatment of hepatocellular carcinoma, especially chemotherapy, is uncertain. Intra-arterial chemotherapy is one of the therapeutic options of unrespectable hepatocellular carcinoma. To clarify this point, we analyze the therapeutic effect of intra-arterial chemotherapy in unrespectable hepatocellular carcinoma patients with or without diabetes mellitus. Fifty-two patients with advanced hepatocellular carcinoma underwent intra-arterial chemotherapy with cisplatin and fluorouracil. Tumor response was assessed by computed tomography. An in vitro hepatocellular carcinoma cell line, Hep G2, was evaluated for the cytotoxic effect of cisplatin and fluorouracil in different concentrations of insulin and glucose mimicking diabetic conditions. Fifty-two patients were included, 14 had diabetes and 38 were non-diabetics. Non-diabetic patients had a lower rate of progressive disease (16% vs. 43%, P=0.039). The median time to progression was significantly longer in non-diabetics compared with the diabetic counterpart (a median of 206 days vs. 88 days, P=0.02). In the hepatocellular carcinoma cell line, Hep G2, insulin rather than glucose was more important for promoting cell proliferation and enhancing the drug resistance of cisplatin or fluorouracil. Our study showed that intra-arterial chemotherapy for unrespectable hepatocellular carcinoma was less effective in diabetic patients than the non-diabetic counterpart in terms of the progression-free rate and time to disease progression survival.

Hepatic artery infusion catheter implantation without embolization of the gastroduodenal artery in cases of retrograde blood flow.

Between January 2007 and January 2008, a port/catheter system for hepatic arterial infusion chemotherapy was implanted in seven patients with retrograde blood flow in the gastroduodenal artery (GDA). The GDA was not coil-embolized when the catheter tip was positioned in the right gastroepiploic artery. In all cases, implantation of the port/catheter system was successful, and there were no complications. Interventionalists can economize on expensive microcoils by using this simple and time-saving method.