Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).

The developmental patterns of neurofilament triplet proteins, peptide and amine immunoreactivities were compared in motor (ventral spinal cord), sensory (dorsal spinal cord, dorsal root ganglia, epidermis), and autonomic (intermediolateral cell columns, dermis) regions in the rat and human. In the rat, neurofilament triplet proteins first appeared in motoneurones (embryonic day 13). In the youngest human fetuses studied (6 weeks), immunoreactivity was present throughout the spinal cord. Peptides and amines occurred later. Calcitonin gene-related peptide, galanin, somatostatin, neuropeptide Y and its C-flanking peptide (CPON) were the first to appear localized to motoneurones (embryonic days 15-17 rat; fetal weeks 6-14 human). Numbers of immunoreactive motoneurones decreased toward birth, but immunoreactive fibers increased in the ventral horn with enkephalin, thyrotrophin-releasing hormone, and the monoaminergic markers 5-hydroxytryptamine and tyrosine hydroxylase (all presumably of supraspinal origin) the last to appear perinatally. In the dorsal horn, particularly in the rat, a transient expression of substance P-, somatostatin-, and neuropeptide Y/CPON-immunoreactive cells was detected (embryonic days 15-17). A pronounced increase of calcitonin gene-related peptide-, galanin-, somatostatin- and substance P- immunoreactive fibers was found perinatally in both species. This coincided with an increased detection of cells in the dorsal root ganglia containing these peptides and the earliest appearance of calcitonin gene-related peptide-, somatostatin-, and substance P-immunoreactive fibers in the rat epidermis. Few antigens were localized to the intermediolateral cell columns before embryonic day 20 (rat), fetal week 20 (human), with thyrotrophin-releasing hormone-, 5-hydroxytryptamine-, tyrosine hydroxylase-, and vasoactive intestinal polypeptide-immunoreactive nerves appearing perinatally. In the rat dermis, tyrosine hydroxylase-immunoreactive fibers (sympathetic fibers) and fibers immunoreactive for neuropeptide Y/CPON and vasoactive intestinal polypeptide were detected from postnatal day 1. In conclusion, 1) peptide and amine immunoreactivity develops in motor before sensory or autonomic regions, 2) many peptide-containing cells are transient in fetal life, and 3) central terminals of dorsal root ganglion cells express peptides before terminals in the skin.

The present study examined the relationship between tumour stage, grade, T-lymphocyte subset infiltration and survival in patients who had undergone potentially curative surgery for renal clear-cell cancer (n ¼ 73). Intratumoural CD4 þ T-lymphocyte infiltrate was associated with poor cancer-specific survival, independent of grade, in this cohort. British Journal of Cancer (2003Cancer ( ) 89, 1906Cancer ( -1908 Local and systemic inflammatory responses are regulated through the production of proteins, such as cytokines, by immunologically active cells. In cancer, this mechanism is disturbed by the presence of the tumour and this dysregulation may contribute to the poorer outcome in the cancer patient (Balkwill and Mantovani, 2001).Recent work has suggested that the presence of specific Tlymphocyte subsets has prognostic value in a number of solid tumours. Naito et al (1998) demonstrated that increased numbers of CD8 þ T lymphocytes in the tumour were associated with better survival in patients with colorectal cancer.There has been little work carried out in renal cancer and the results appear to be different from other solid tumours. Kolbeck et al (1992) in a small study reported that increased tumour T-cell infiltration was associated with increased tumour recurrence. More recently, in a larger series, it has been reported that increased numbers of CD8 þ T lymphocytes in the tumour are associated with poor survival in patients with renal cancer (Nakano et al, 2001).The aim of the present study was to examine the relationship between tumour stage, grade, T-lymphocyte subset infiltration and survival in patients who had undergone potentially curative surgery for renal clear-cell cancer. PATIENTS AND METHODS PatientsPatients with histologically proven renal clear-cell cancer that, on the basis of preoperative CT-scan of the abdomen and chest and pathological assessment of the resected tumour, were considered to have undergone potentially curative surgery between July 1997 and December 2000 in the North Glasgow NHS Trust were included in the study. Pathological staging was based on TNM and classified as pII or 4II (Guinan et al, 1997).The study was approved by the local ethical committee. ImmunohistochemistryBlocks from the primary tumour were fixed in 10% buffered formalin and embedded in paraffin wax. One representative block of tumour was selected for each patient. Sections (4 mm) were cut and mounted on slides coated with aminopropyltriethoxysilane. Sections were then immunostained using the peroxidase-based Envision (Dako, Cambridgeshire, UK) technique. The primary antibody for CD4 was mouse monoclonal (Vector, Peterborough, UK) and that for CD8 was mouse monoclonal (Dako, Cambridgeshire, UK). Sections were dewaxed and rehydrated. Endogenous peroxidase was blocked by incubation in 0.3% hydrogen peroxide for 10 min. Antigen retrieval for CD8 was performed by microwaving in 1 mM EDTA buffer, pH 8, for 5 min at full pressure in aplastic pressure cooker in a microwave oven. Antigen retrieval for CD4 was achieved b...

cancer were recruited. The University of California Los Angeles Integrated Staging System (UISS), 'Stage Size Grade Necrosis' (SSIGN) and Kattan scores were constructed. The systemic inflammatory response was assessed by counting white cells, neutrophils, lymphocytes and platelets, and measuring albumin and C-reactive protein (CRP) concentrations. RESULTSOn multivariate analysis of the significant individual covariates, T stage (hazard ratio 2.38, 95% confidence interval 1.06-5.36, P = 0.037), necrosis (3.73, 1.26-11.05, P = 0.018) and CRP (4.31, 1.20-15.49, P = 0.025) were significant independent predictors of relapse-free survival. On multivariate analysis of significant scoring systems and CRP, only UISS (3.50, 1.66-7.40, P = 0.001), SSIGN (2.83, 1.19-6.72, P = 0.018) and CRP (4.14, 1.16-14.73, P = 0.028) were significant independent predictors of relapsefree survival. CONCLUSIONElevated circulating CRP levels appear to be better than other markers of the systemic inflammatory response, and independent of established scoring systems, in predicting relapse-free and cancer-specific survival in patients undergoing potentially curative nephrectomy for renal cancer.

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