Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival

We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCR

Polyinosinic polycytidylic acid prevents efficient antigen expression after mRNA electroporation of clinical grade dendritic cells.

Contains fulltext : 79503.pdf (publisher's version ) (Closed access)Tumor-derived peptides are used frequently as antigen (Ag) source in dendritic cell (DC) therapy in cancer patients. An alternative is to load DC with tumor-associated Ag (TAA)-encoding RNA. RNA-loading obviates prior knowledge of CTL and Th epitopes in the Ag. Multiple epitopes for many HLA alleles (both MHC class I and class II) are encoded by the RNA and loading is independent of the patient's HLA make-up. Herein, we determined the optimal conditions for mRNA-electroporation of monocyte-derived DC for clinical application in relation to different maturation cocktails. The data demonstrate that TAA carcinoembryonic antigen, gp100 and tyrosinase are expressed already 30 min after electroporation with the encoding mRNA. Moreover, gp100-specific CTL are activated by gp100 mRNA-electroporated DC. Importantly, we show here that the presence of polyinosinic-polycytidylic acid [poly(I:C)] in the maturation cocktail prevents effective protein expression of the electroporated mRNA as well as subsequent CTL recognition. This effect of poly(I:C) correlates with the induction of IFN-induced genes and innate anti-viral effector molecules in DC. Together these data show that electroporation of mature DC with TAA-encoding mRNA is attractive for use in DC vaccination protocols in cancer patients, but protein expression should be tested for each maturation cocktail