Systematic pelvic and para-aortic lymphadenectomy in advanced ovarian cancer patients with no residual intraperitoneal disease

A comparative non-randomized study was carried out to evaluate the role of systematic pelvic and para-aortic lymphadenectomy (SL) on patients with no residual intraperitoneal disease (NRID) of advanced ovarian cancer (stage IIIC–IV). A total of 142 optimally cytoreduced patients (macroscopic disease absent on peritoneal surface) were divided into two groups: Group A, consisting of 98 patients (53 previously untreated and 45 pretreated at other Institutions), who underwent SL; Group B, consisting of 44 patients (21 previously untreated and 23 pretreated at other Institutions), who did not undergo SL. Each group had statistically equivalent histology, grading, performance status and variety of cytoreductive operations performed. Group A pretreated patients had a greater number of stage III than Group B ( P  = 0.03). Systematic pelvic and para-aortic lymphadenectomy could be carried out with an acceptable morbidity and no mortality. All 142 patients received post-operative chemotherapy including carboplatin. The number of chemotherapy sessions did not differ between the two groups. Comparison of survival revealed that SL significantly improved the survival of previously untreated patients ( P  = 0.02). The survival was significantly different with nodal status ( P  = 0.006). Cox's proportional hazard analysis showed that only systematic lymphadenectomy was a significant covariate. The survival was not significantly different in Group A vs Group B pretreated patients; however, it was significantly different with respect to nodal status ( P <0.001). Cox's proportional hazard analysis showed that only the initial stage of disease was a significant covariate. The results of the present study shows that aggressive surgical cytoreduction with SL could be therapeutic in previously untreated patients with NRID. Currently, an international prospective randomized study is ongoing to clarify definitively the clinical role of SL.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.