Relapse in resected lung cancer revisited: does intensified follow up really matter? A prospective study

<p>Abstract</p> <p>Background</p> <p>beside the well known predominance of distant vs. loco-regional relapse, several aspects of the relapse pattern still have not been fully elucidated.</p> <p>Methods</p> <p>prospective, controlled study on 88 patients operated for non-small cell lung cancer (NSCLC) in a 15 months period. Stage IIIA existed in 35(39.8%) patients, whilst stages IB, IIA and IIB existed in 10.2%, 4.5% and 45.5% patients respectively. Inclusion criteria: stage I-IIIA, complete resection, systematic lymphadenectomy with at least 6 lymph node groups examined, no neoadjuvant therapy, exact data of all aspects of relapse, exact data about the outcome of the treatment.</p> <p>Results</p> <p>postoperative lung cancer relapse occurred in 50(56.8%) patients. Locoregional, distant and both types of relapse occurred in 26%, 70% and 4% patients respectively. Postoperative cancer relapse occurred in 27/35(77.1%) pts. in the stage IIIA and in 21/40(52.55) pts in the stage IIB. In none of four pts. in the stage IIA cancer relapse occurred, unlike 22.22% pts. with relapse in the stage IB. The mean disease free interval in the analysed group was 34.38 ± 3.26 months.</p> <p>The mean local relapse free and distant relapse free intervals were 55 ± 3.32 and 41.62 ± 3.47 months respectively Among 30 pts. with the relapse onset inside the first 12 month after the lung resection, in 20(66.6%) pts. either T3 tumours or N2 lesions existed. In patients with N0, N1 and N2 lesions, cancer relapse occurred in 30%, 55.6% and 70.8% patients respectively</p> <p>Radiographic aspect T stage, N stage and extent of resection were found as significant in terms of survival. Related to the relapse occurrence, although radiographic aspect and extent of resection followed the same trend as in the survival analysis, only T stage and N stage were found as significant in the same sense as for survival. On multivariate, only T and N stage were found as significant in terms of survival.</p> <p>Specific oncological treatment of relapse was possible in 27/50(54%) patients.</p> <p>Conclusion</p> <p>the intensified follow up did not increase either the proportion of patients detected with asymptomatic relapse or the number of patients with specific oncological treatment of relapse.</p

Diversity across Major and Candidate Genes in European Local Pig Breeds

In the frame of the European TREASURE* project, the genetic characterization of 20 local pig breeds is being performed with genetic and genomic tools. The objectives are the study of genetic diversity in these populations and the identification of useful markers for authentication, traceability, conservation and breeding programs. In first place, a candidate gene approach has been applied and the most relevant genes and mutations associated with pig productive, meat quality, reproductive and disease resistance traits have been prioritized and analyzed. Two OpenArray® chips of 32 and 16 SNPs were designed and genotyped in 48 animals from each one of 20 breeds included in the project (Alentejana, Apulo Calabrese, Basque, Bísaro, Black Majorcan, Black Sicilian, Black Slavonian, Casertana, Cinta Senese, Gascon, Iberian, Krskopolje, Lithuanian indigenous wattle, Mangalitsa, Mora Romagnola, Moravka, Old Lithuanian White, Sarda, Schwäbisch Hällisches, Turopolje). Forty SNPs located in 34 genes were successfully genotyped (MC1R, TYRP1, NR6A, PCK1, RYR1, IGF2, MC4R, PHKG1, SCD, GBP5, TAS2R39, TAS2R4, MUC4, ESR1, CYP2E1, LEP, CAST, MTTP, CYB5A, FTO, PPARGC1A, CAPN1, PPARD, CTSL, LEPR, PRKAG3, ACACA, KIT, ACSL4, ADIPOQ, FASN, AHR, FUT1, MSTN). Results provide relevant information regarding genetic diversity and segregation of SNPs responsible for specific production and quality traits. Coat color and morphological trait-genes, showing low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for breeding programs. For instance, we observed predominance of unfavorable alleles for disease resistance and boar taint genes in most breeds, and segregation of many genes involved in meat quality, fatness and growth. These results joint with ongoing genomic assays, will provide essential information regarding genetic diversity, structure, selective signatures and biological processes responsible for specific production and quality traits

Diversity across Major and Candidate Genes in European Local Pig Breeds

In the frame of the European TREASURE* project, the genetic characterization of 20 local pig breeds is being performed with genetic and genomic tools. The objectives are the study of genetic diversity in these populations and the identification of useful markers for authentication, traceability, conservation and breeding programs. In first place, a candidate gene approach has been applied and the most relevant genes and mutations associated with pig productive, meat quality, reproductive and disease resistance traits have been prioritized and analyzed. Two OpenArray® chips of 32 and 16 SNPs were designed and genotyped in 48 animals from each one of 20 breeds included in the project (Alentejana, Apulo Calabrese, Basque, Bísaro, Black Majorcan, Black Sicilian, Black Slavonian, Casertana, Cinta Senese, Gascon, Iberian, Krskopolje, Lithuanian indigenous wattle, Mangalitsa, Mora Romagnola, Moravka, Old Lithuanian White, Sarda, Schwäbisch Hällisches, Turopolje). Forty SNPs located in 34 genes were successfully genotyped (MC1R, TYRP1, NR6A, PCK1, RYR1, IGF2, MC4R, PHKG1, SCD, GBP5, TAS2R39, TAS2R4, MUC4, ESR1, CYP2E1, LEP, CAST, MTTP, CYB5A, FTO, PPARGC1A, CAPN1, PPARD, CTSL, LEPR, PRKAG3, ACACA, KIT, ACSL4, ADIPOQ, FASN, AHR, FUT1, MSTN). Results provide relevant information regarding genetic diversity and segregation of SNPs responsible for specific production and quality traits. Coat color and morphological trait-genes, showing low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for breeding programs. For instance, we observed predominance of unfavorable alleles for disease resistance and boar taint genes in most breeds, and segregation of many genes involved in meat quality, fatness and growth. These results joint with ongoing genomic assays, will provide essential information regarding genetic diversity, structure, selective signatures and biological processes responsible for specific production and quality traits

Genome‐wide detection of copy number variants in European autochthonous and commercial pig breeds by whole‐genome sequencing of DNA pools identified breed‐characterising copy number states

In this study, we identified copy number variants (CNVs) in 19 European autochthonous pig breeds and in two commercial breeds (Italian Large White and Italian Duroc) that represent important genetic resources for this species. The genome of 725 pigs was sequenced using a breed‐specific DNA pooling approach (30–35 animals per pool) obtaining an average depth per pool of 42×. This approach maximised CNV discovery as well as the related copy number states characterising, on average, the analysed breeds. By mining more than 17.5 billion reads, we identified a total of 9592 CNVs (~683 CNVs per breed) and 3710 CNV regions (CNVRs; 1.15% of the reference pig genome), with an average of 77 CNVRs per breed that were considered as private. A few CNVRs were analysed in more detail, together with other information derived from sequencing data. For example, the CNVR encompassing the KIT gene was associated with coat colour phenotypes in the analysed breeds, confirming the role of the multiple copies in determining breed‐specific coat colours. The CNVR covering the MSRB3 gene was associated with ear size in most breeds. The CNVRs affecting the ELOVL6 and ZNF622 genes were private features observed in the Lithuanian Indigenous Wattle and in the Turopolje pig breeds respectively. Overall, the genome variability unravelled here can explain part of the genetic diversity among breeds and might contribute to explain their origin, history and adaptation to a variety of production systems.info:eu-repo/semantics/acceptedVersio

Dominance and parent-of-origin effects of coding and non-coding alleles at the acylCoA-diacylglycerol-acyltransferase (DGAT1) gene on milk production traits in German Holstein cows

<p>Abstract</p> <p>Background</p> <p>Substantial gene substitution effects on milk production traits have formerly been reported for alleles at the K232A and the promoter VNTR loci in the bovine acylCoA-diacylglycerol-acyltransferase 1 (<it>DGAT1</it>) gene by using data sets including sires with accumulated phenotypic observations of daughters (breeding values, daughter yield deviations). However, these data sets prevented analyses with respect to dominance or parent-of-origin effects, although an increasing number of reports in the literature outlined the relevance of non-additive gene effects on quantitative traits.</p> <p>Results</p> <p>Based on a data set comprising German Holstein cows with direct trait measurements, we first confirmed the previously reported association of <it>DGAT1 </it>promoter VNTR alleles with milk production traits. We detected a dominant mode of effects for the <it>DGAT1 </it>K232A and promoter VNTR alleles. Namely, the contrasts between the effects of heterozygous individuals at the <it>DGAT1 </it>loci differed significantly from the midpoint between the effects for the two homozygous genotypes for several milk production traits, thus indicating the presence of dominance. Furthermore, we identified differences in the magnitude of effects between paternally and maternally inherited <it>DGAT1 </it>promoter VNTR – K232A haplotypes indicating parent-of-origin effects on milk production traits.</p> <p>Conclusion</p> <p>Non-additive effects like those identified at the bovine <it>DGAT1 </it>locus have to be accounted for in more specific QTL detection models as well as in marker assisted selection schemes. The <it>DGAT1 </it>alleles in cattle will be a useful model for further investigations on the biological background of non-additive effects in mammals due to the magnitude and consistency of their effects on milk production traits.</p

Diversity across major and candidate genes in European local pig breeds

The aim of this work was to analyse the distribution of causal and candidate mutations associated to relevant productive traits in twenty local European pig breeds. Also, the potential of the SNP panel employed for elucidating the genetic structure and relationships among breeds was evaluated. Most relevant genes and mutations associated with pig morphological, productive, meat quality, reproductive and disease resistance traits were prioritized and analyzed in a maximum of 47 blood samples from each of the breeds (Alentejana, Apulo-Calabrese, Basque, Bísara, Majorcan Black, Black Slavonian (Crna slavonska), Casertana, Cinta Senese, Gascon, Iberian, Krskopolje (Krskopoljski), Lithuanian indigenous wattle, Lithuanian White Old Type, Mora Romagnola, Moravka, Nero Siciliano, Sarda, Schwa-bisch-Hallisches Schwein (Swabian Hall pig), Swallow-Bellied Mangalitsa and Turopolje). We successfully analyzed allelic variation in 39 polymorphisms, located in 33 candidate genes. Results provide relevant information regarding genetic diversity and segregation of SNPs associated to production and quality traits. Coat color and morphological trait-genes that show low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for association studies as well as breeding programs. For instance, we observed predominance of alleles that might be unfavorable for disease resistance and boar taint in most breeds and segregation of many alleles involved in meat quality, fatness and growth traits. Overall, these findings provide a detailed catalogue of segregating candidate SNPs in 20 European local pig breeds that may be useful for traceability purposes, for association studies and for breeding schemes. Population genetic analyses based on these candidate genes are able to uncover some clues regarding the hidden genetic substructure of these populations, as the extreme genetic closeness between Iberian and Alentejana breeds and an uneven admixture of the breeds studied. The results are in agreement with available knowledge regarding breed history and management, although largest panels of neutral markers should be employed to get a deeper understanding of the population’s structure and relationships

Whole-genome sequencing of European autochthonous and commercial pig breeds allows the detection of signatures of selection for adaptation of genetic resources to different breeding and production systems

Background: Natural and artificial directional selection in cosmopolitan and autochthonous pig breeds and wild boars have shaped their genomes and resulted in a reservoir of animal genetic diversity. Signatures of selection are the result of these selection events that have contributed to the adaptation of breeds to different environments and production systems. In this study, we analysed the genome variability of 19 European autochthonous pig breeds (Alentejana, Bísara, Majorcan Black, Basque, Gascon, Apulo-Calabrese, Casertana, Cinta Senese, Mora Romagnola, Nero Siciliano, Sarda, Krškopolje pig, Black Slavonian, Turopolje, Moravka, Swallow-Bellied Mangalitsa, Schwäbisch-Hällisches Schwein, Lithuanian indigenous wattle and Lithuanian White old type) from nine countries, three European commercial breeds (Italian Large White, Italian Landrace and Italian Duroc), and European wild boars, by mining wholegenome sequencing data obtained by using a DNA-pool sequencing approach. Signatures of selection were identified by using a single-breed approach with two statistics [within-breed pooled heterozygosity (HP) and fixation index (FST)] and group-based FST approaches, which compare groups of breeds defined according to external traits and use/specialization/type. Results: We detected more than 22 million single nucleotide polymorphisms (SNPs) across the 23 compared populations and identified 359 chromosome regions showing signatures of selection. These regions harbour genes that are already known or new genes that are under selection and relevant for the domestication process in this species, and that affect several morphological and physiological traits (e.g. coat colours and patterns, body size, number of vertebrae and teats, ear size and conformation, reproductive traits, growth and fat deposition traits). Wild boar related signatures of selection were detected across all the genome of several autochthonous breeds, which suggests that crossbreeding (accidental or deliberate) occurred with wild boars. Conclusions: Our findings provide a catalogue of genetic variants of many European pig populations and identify genome regions that can explain, at least in part, the phenotypic diversity of these genetic resources

Runs of homozygosity provide a genome landscape picture of inbreeding and genetic history of European autochthonous and commercial pig breeds

ROHs are long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROHs and their length are indicators of the level and origin of inbreeding. Frequent common ROHs within the same population define ROH islands and indicate hotspots of selection. In this work, we investigated ROHs in a total of 1131 pigs from 20 European local pig breeds and in three cosmopolitan breeds, genotyped with the GGP Porcine HD Genomic Profiler. plink software was used to identify ROHs. Size classes and genomic inbreeding parameters were evaluated. ROH islands were defined by evaluating different thresholds of homozygous SNP frequency. A functional overview of breed-specific ROH islands was obtained via over-representation analyses of GO biological processes. Mora Romagnola and Turopolje breeds had the largest proportions of genome covered with ROH (~1003 and ~955&nbsp;Mb respectively), whereas Nero Siciliano and Sarda breeds had the lowest proportions (~207 and 247&nbsp;Mb respectively). The highest proportion of long ROH (&gt;16&nbsp;Mb) was in Apulo-Calabrese, Mora Romagnola and Casertana. The largest number of ROH islands was identified in the Italian Landrace (n = 32), Cinta Senese (n = 26) and Lithuanian White Old Type (n = 22) breeds. Several ROH islands were in regions encompassing genes known to affect morphological traits. Comparative ROH structure analysis among breeds indicated the similar genetic structure of local breeds across Europe. This study contributed to understanding of the genetic history of the investigated pig breeds and provided information to manage these pig genetic resources

Predicting survival after pulmonary metastasectomy for colorectal cancer: previous liver metastases matter

BACKGROUND: Few patients with lung metastases from colorectal cancer (CRC) are candidates for surgical therapy with a curative intent, and it is currently impossible to identify those who may benefit the most from thoracotomy. The aim of this study was to determine the impact of various parameters on survival after pulmonary metastasectomy for CRC. METHODS: We performed a retrospective analysis of 40 consecutive patients (median age 63.5 [range 33-82] years) who underwent resection of pulmonary metastases from CRC in our institution from 1996 to 2009. RESULTS: Median follow-up was 33 (range 4-139) months. Twenty-four (60%) patients did not have previous liver metastases before undergoing lung surgery. Median disease-free interval between primary colorectal tumor and development of lung metastases was 32.5 months. 3- and 5-year overall survival after thoracotomy was 70.1% and 43.4%, respectively. In multivariate analysis, the following parameters were correlated with tumor recurrence after thoracotomy; a history of previous liver metastases (HR = 3.8, 95%CI 1.4-9.8); and lung surgery other than wedge resection (HR = 3.0, 95%CI 1.1-7.8). Prior resection of liver metastases was also correlated with an increased risk of death (HR = 5.1, 95% CI 1.1-24.8, p = 0.04). Median survival after thoracotomy was 87 (range 34-139) months in the group of patients without liver metastases versus 40 (range 28-51) months in patients who had undergone prior hepatectomy (p = 0.09). CONCLUSION: The main parameter associated with poor outcome after lung resection of CRC metastases is a history of liver metastases