[18F]FDG-PET/CT and long-term responses to everolimus in advanced neuroendocrine neoplasia.

PURPOSE: This study aims to identify in patients with neuroendocrine neoplasia (NEN) the potential correlation between FDG-PET findings and responses to everolimus therapy to identify predictors of long-term efficacy. METHODS: Retrospective analysis of patients with sporadic, advanced, progressive NEN treated with everolimus was performed based on the available data on FDG-PET patients obtained before commencing therapy. Data are expressed as the median (25-75th IQR). Risk factor analysis and survival analysis were performed by logistic regression and Cox proportional hazard regression and the determination of Kaplan-Meier curves, as appropriate. RESULTS: Sixty-six patients were evaluated (NET G1 19.7%, NET G2 75.7%, and NET G3 4.6%), including 45.4% with positive FDG-PET findings. Overall, disease stabilization and a partial response were achieved for 71.2% and 6% of patients, respectively. A long-term response (> 24 months) was observed in 33% of patients. Ki67 was the only predictor of tumor progression (p = 0.03). No significant difference in clinical outcomes was observed between patients with positive or negative FDG-PET findings (median PFS was 24 months and 18 months, respectively, p = 0.337; the disease control rate was 83.3% and 70%, respectively, p = 0.245). CONCLUSIONS: Everolimus is a valid therapeutic option for advanced, progressive, well-differentiated NEN, even in patients with positive FDG-PET findings.

Genotype-phenotype correlations in 5-fluorouracil metabolism: a candidate DPYD haplotype to improve toxicity prediction.

5-Fluorouracil is among the most widely used anticancer drug, but a fraction of treated patients develop severe toxicity, with potentially lethal injuries. The predictive power of the available pretreatment assays, used to identify patients at risk of severe toxicity, needs improvements. This study aimed to correlate a phenotypic marker of 5-fluorouracil metabolism (the individual degradation rate of 5-fluorouracil-5-FUDR) with 15 functional polymorphisms in the dihydropyrimidine dehydrogenase gene (DPYD). Single SNP (single-nucleotide polymorphism) analysis revealed that the SNPs rs1801160, rs1801265, rs2297595 and rs3918290 (splice site variant IVS14+1G>A) were significantly associated with a decreased value of 5-FUDR, and the rs3918290 causing the larger decrease. Multi-SNP analysis showed that a three-SNP haplotype (Hap7) involving rs1801160, rs1801265 and rs2297595 causes a marked decrease in 5-FUDR, comparable to that caused by the splice site variant rs3918290, which is the main pharmacogenetic marker associated with severe fluorouracil toxicity. The similar effect played by Hap7 and by the splice site variant rs3918290 upon individual 5-FUDR suggests that Hap7 could also represent a similar determinant of fluorouracil toxicity. Haplotype assessment could improve the predictive value of DPYD genetic markers aimed at the pre-emptive identification of patients at risk of severe 5-fluorouracil toxicity.The Pharmacogenomics Journal advance online publication, 28 July 2015; doi:10.1038/tpj.2015.56.

The importance of lymph node retrieval and lymph node ratio following preoperative chemoradiation of rectal cancer.

AIM: Preoperative chemoradiation (CRT) for rectal cancer decreases the number of examined lymph nodes (NELN) found in the resected specimen. However, the prognostic role of lymph node evaluation including overall numbers and the lymph node ratio (LNR) in patients having preoperative CRT have not yet been defined. The study has assessed the influence of CRT on the NELN and on lymph node number and LNR on the survival of patients with rectal cancer. METHOD: Between 2003 and 2011, 508 patients with nonmetastatic rectal cancer underwent mesorectal excision. Of these 123 (24.2%) received preoperative CRT. Univariate and multivariate analysis was performed to define the role of NELN and LNR as prognostic indicators of survival. RESULTS: Neoadjuvant CRT significantly reduced the NELN (P < 0.0001). Disease-free survival (DFS) and overall survival (OS) of patients with fewer or more than 12 nodes retrieved did not differ statistically. Node-negative patients with six or fewer lymph nodes were significantly associated with a poor DFS and OS on univariate analysis (P = 0.03 and P = 0.03). LNR significantly influenced the DFS and OS on multivariate analysis [DFS, P = 0.0473, hazard ratio (HR) 2.4980, 95% confidence interval (CI) 1.2631-9.4097; OS, P = 0.0419, HR 1.1820, 95% CI 1.1812-10,710]. CONCLUSION: The cut-off of 12 lymph nodes does not influence survival and should not be considered for cancer-specific prediction of patients having neoadjuvant CRT. In contrast LNR is an independent prognostic predictor of DFS and OS in such patients.

[Carcinoid of Meckel's diverticulum: presentation of a clinical case]. / Carcinoide del diverticolo del Meckel: presentazione di un caso clinico.

Clinical findings and surgical treatment of a 68 years old man with carcinoid tumor of Meckel's diverticulum are reported. Carcinoids in Meckel's diverticula are rare tumors, commonly discovered incidentally during surgical procedures for different indications. Symptoms are frequently expression of a metastatic disease. Specific diagnostic and therapeutic tools are discussed.