Effect of time interval between surgery and preoperative chemoradiotherapy with 5-fluorouracil or 5-fluorouracil and oxaliplatin on outcomes in rectal cancer.

BACKGROUND AND OBJECTIVES: Preoperative chemoradiotherapy for locally advanced rectal cancer is now considered "standard of care." However, the optimal time interval for resection after neoadjuvant therapy is unknown. METHODS: Between 11/90 and 11/04, 107 patients with rectal adenocarcinoma underwent preoperative chemo/RT at the University of Pennsylvania. Fifty-six percent had LAR and 40% had APR. Chemotherapy consisted of 5-FU/oxaliplatin in 28% and 5-FU in 72% of patients. All patients received preoperative RT. RESULTS: A longer time interval between chemo/RT and surgery was associated with tumor downstaging (OR 1.24, P = 0.02). A longer time interval was not associated with: nodal downstaging (OR 1.00, P = 0.98); pathologic complete response (PCR) (OR 0.97, P = 0.80); likelihood of performing an LAR (OR 0.90, P = 0.47); improved disease free survival (DFS), local control, or distant control (HR 1.05, P = 0.49; HR 1.14, P = 0.22; HR 1.06, P = 0.52, respectively). The PCR rate was 34.5% in the 5-FU/oxaliplatin/radiation group, and 13.7% in the 5-FU/radiation group. If patients with microscopic CR were excluded, then the PCR rate for 5FU/OX was 21.4% and for 5-FU was 12.2%. CONCLUSIONS: Time interval between surgery and chemo/RT appeared to have little effect on PCR or LAR rates. Patients receiving 5 FU/oxaliplatin/RT had a high PCR rate. A prospective randomized trial to test superiority of 5 FU/oxaliplatin is warranted.

Expression of proneural and neurogenic genes in the embryonic mammalian vestibular system.

One of the most striking aspects of all auditory and vestibular sensory epithelia is the mosaic pattern of hair cells and supporting cells. The factors that are required for the development of this mosaic have not been determined, however the results of recent studies have demonstrated that components of the neurogenic (Notch) signaling pathway are expressed in the developing inner ears of a number of different vertebrate species. To examine whether this signaling pathway may play a similar role in the development of the hair cell mosaic in the mammalian vestibular system, the expression patterns of proneural (Math1) and neurogenic (Notch1, Jagged2, HES5) genes were examined in the developing mouse inner ear. Results indicate that Notch1 is initially expressed throughout the developing inner ear and becomes restricted to non-sensory cells within the developing sensory epithelia. In contrast, initial expression of Math1 and Jagged2 is localized to the developing sensory epithelia and ultimately becomes restricted to hair cells. Interestingly, transcripts for HES5, a target of Notch activation, are expressed in the developing cristae but not in the saccule or utricle. These results are consistent with the hypothesis that formation of the hair cell mosaic is regulated through the neurogenic pathway. However the differential expression of HES5 within the ear indicates that the downstream targets of Notch1 activation are not consistent across all of the sensory epithelia and suggests that the effects of activation of Notch1 in the saccule and utricle must be regulated through alternate target genes.