Search

Purpose: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor., Patients and Methods: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM)., Results: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis., Conclusions: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Objective: To analyze the outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) in octogenarian patients., Methods: The RESURGE (REnal SUrgery in the Eldely) multi-institutional database was queried to identify patients ≥80 years old who had undergone a PN or RN for a renal tumor. Multivariable binary logistic regression estimated the association between type of surgery and occurrence of complications. Multivariable Cox regression model assessed the association between type of surgery and All-Causes Mortality., Results: The study analyzed 585 patients (median age 83 years, IQR 81-84), 364 of whom (62.2%) underwent RN and 221 (37.8%) PN. Patients undergoing RN were older (P = .0084), had larger tumor size (P < .0001) and higher clinical stage (P < .001). At multivariable analysis for complications, the only significant difference was found for lower risk of major postoperative complications for laparoscopic RN compared to open RN (OR: 0.42; P = .04). The rate of significant (>25%) decrease of eGFR in PN and RN was 18% versus 59% at 1 month, and 23% versus 65% at 6 months (P < .0001). After a median follow-up time of 39 months, 161 patients (31%) died, of whom 105 (20%) due to renal cancer., Conclusion: In this patient population both RN and PN carry a non-negligible risk of complications. When surgical removal is indicated, PN should be preferred, whenever technically feasible, as it can offer better preservation of renal function, without increasing the risk of complications. Moreover, a minimally invasive approach should be pursued, as it can translate into lower surgical morbidity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In Plasmodium falciparum, resistance to chloroquine (CQ) is conferred by a K to T mutation at amino acid position 76 (K76T) in the P. falciparum CQ transporter (PfCRT). To date, at least 15 pfcrt genotypes, which are represented by combinations of five amino acids at positions 72-76, have been described in field isolates from various endemic regions. To identify novel mutant pfcrt genotypes and to reveal the genetic relatedness of pfcrt genotypes, a large-scale survey over a wide geographic area was performed., Methods: Sequences for exon 2 in pfcrt, including known polymorphic sites at amino acid positions 72, 74, 75 and 76, were obtained from 256 P. falciparum isolates collected from eight endemic countries in Asia (Bangladesh, Cambodia, Lao P.D.R., the Philippines and Thailand), Melanesia (Papua New Guinea and Vanuatu) and Africa (Ghana). A haplotype network was constructed based on six microsatellite markers located -29 kb to 24 kb from pfcrt in order to examine the genetic relatedness among mutant pfcrt genotypes., Results: In addition to wild type (CVMNK at positions 72-76), four mutant pfcrt were identified; CVIET, CVIDT, SVMNT and CVMNT (mutated amino acids underlined). Haplotype network revealed that there were only three mutant pfcrt lineages, originating in Indochina, Philippines and Melanesia. Importantly, the Indochina lineage contained two mutant pfcrt genotypes, CVIET (n = 95) and CVIDT (n = 14), indicating that CVIDT shares a common origin with CVIET. Similarly, one major haplotype in the Melanesian lineage contained two pfcrt genotypes; SVMNT (n = 71) and CVMNT (n = 3). In Africa, all mutant pfcrt genotypes were the CVIET of the Indochina lineage, probably resulting from the intercontinental migration of CQ resistance from Southeast Asia., Conclusions: The number of CQ-mutant lineages observed in this study was identical to that found in previous studies. This supports the hypothesis that the emergence of novel CQ resistance is rare. However, in the mutant pfcrt genotypes, amino acid changes at positions 72, 74 and 75 appear to have recently been generated at least several times, producing distinct pfcrt mutant genotypes. The occurrence of new mutations flanking K76T may yield stronger resistance to CQ and/or a higher fitness than the original pfcrt mutant.

Worldwide spread of Plasmodium falciparum drug resistance to conventional antimalarials, chloroquine and sulfadoxine/pyrimethamine, has been imposing a serious public health problem in many endemic regions. Recent discovery of drug resistance-associated genes, pfcrt, pfmdr1, dhfr, and dhps, and applications of microsatellite markers flanking the genes have revealed the evolution of parasite resistance to these antimalarials and the geographical spread of drug resistance. Here, we review our recent knowledge of the evolution and spread of parasite resistance to chloroquine and sulfadoxine/pyrimethamine. In both antimalarials, resistance appears to be largely explained by the invasion of limited resistant lineages to many endemic regions. However, multiple, indigenous evolutionary origins of resistant lineages have also been demonstrated. Further molecular evolutionary and population genetic approaches will greatly facilitate our understanding of the evolution and spread of parasite drug resistance, and will contribute to developing strategies for better control of malaria.

The organization and allelic recombination of the merozoite surface protein-1 gene of Plasmodium vivax (PvMsp-1), the most widely prevalent human malaria parasite, were evaluated in complete nucleotide sequences of 40 isolates from various geographic areas. Alignment of 31 distinct alleles revealed the mosaic organization of PvMsp-1, consisting of seven interallele conserved blocks flanked by six variable blocks. The variable blocks showed extensive variation in repeats and nonrepeat unique sequences. Numerous recombination sites were distributed throughout PvMsp-1, in both conserved blocks and variable block unique sequences, and the distribution was not uniform. Heterozygosity of PvMsp-1 alleles was higher in Asia (0.953 +/- 0.009) than in Brazil (0.813 +/- 0.047). No identical alleles were shared between Asia and Brazil, whereas all but one variable block nonrepeat sequence found in Brazil occurred in Asia. These observations suggest that P. vivax populations in Asia are ancestral to Brazilian populations, and that PvMsp-1 has heterogeneity in frequency of allelic recombination events. Recurrent origins of new PvMsp-1 alleles by repeated recombination events were supported by a rapid decline in linkage disequilibrium between pairs of synonymous sites with increasing nucleotide distance, with little linkage disequilibrium at a distance of over 3 kb in a P. vivax population from Thailand, evidence for an effectively high recombination rate of the parasite. Meanwhile, highly reduced nucleotide diversity was noted in a region encoding the 19-kDa C-terminal epidermal growth factor-like domain of merozoite surface protein-1, a vaccine candidate.