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Symbiosis is increasingly recognized as a dynamic relationship, with the net outcome falling along a continuum from mutualism to parasitism. A key example of this comes from a recently discovered microsporidian symbiont ofDaphnia,the net impact of which was found to vary from negative to positive. We investigated the taxonomic position of this microsporidian and the morphology of infected hosts, as well as the virulence, ecology and host range of the symbiont; we also provide information about its culturing methods. The genetic data indicates that the microsporidian symbiont belongs toOrdospora pajunii, a newly described microsporidian parasite ofDaphnia. We show thatO. pajuniiinfection damages the gut, causing infected epithelial cells to lose microvilli and then rupture. The prevalence of this microsporidian can be high (up to 100% in the lab and 77% of adults in the field). Its overall virulence seems low in most cases, but some genotypes suffer reduced survival and reproduction. Susceptibility and virulence are strongly host-genotype dependent. We found that North AmericanO. pajuniiare able to infect multipleDaphniaspecies, including the European speciesD. longispina, as well as the genusCeriodaphnia. We propose theDaphnia-O. pajuniisymbiosis as a valuable system for studying the mechanisms of context-dependent shifts between mutualism and parasitism, as well as for understanding how symbionts might alter host interactions with resources.ImportanceThe net outcome of symbiosis can shift between parasitism and mutualism, but the mechanisms underlying such changes remain cryptic. A full understanding of what drives shifts of symbiotic relationships will require comprehensive knowledge of the biology and ecology of the symbionts. However, we have few systems in which this is possible, especially for cases where something that is typically a parasite becomes a mutualist. Recently, a microsporidian symbiont ofDaphniawas found to shift from parasitism towards mutualism, but little was known about this symbiont (including its species identity). Here, we describe this endosymbiont ofDaphnia, identifying it as the microsporidiumOrdospora pajunii. We described its phylogeny, morphology, virulence and ecology, enabling future study of this interaction as a model for shifts along the mutualism-parasitism continuum.

10 p.-6 fig., Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia–Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation., This research was supported by the NSF awards DEB-1456588 to D.H. and DEB-1442113 to A.R., the Department of Energy award 0000238431 to D.H., the GENOBIOREF (BIO2017-86559-R) project of the Spanish Ministry of Science and Innovation (cofinanced by FEDER funds) to F.J.R.-D., S.C., and A.T.M., grant PID2019-103901GB-I00 of the Spanish Ministry of Science and Innovation to P.F., and the NIH award R56AI146096 to A.R. J.L.S. and A.R. were supported by the HHMI and the Burroughs Wellcome Fund. The work (proposal: 10.46936/10.25585/60001048) conducted by the US Department of Energy JGI (https://ror.org/04xm1d337), a DOE Office of Science User Facility, was supported by the Office of Science of the US Department of Energy operated under contract no. DE-AC02-05CH11231.

Species of the phylum Blastocladiomycota, early diverging zoosporic (flagellated) lineages of fungi, are vastly understudied. This phylum includes the genusCoelomomyceswhich consists of more than 80 fungal species that are obligate parasites of arthropods. KnownCoelomomycesspecies lack a complete asexual life cycle, instead surviving through an obligate heteroecious alternation of generations life cycle. Despite their global distribution and interesting life cycle, little is known about the genomics of anyCoelomomycesspecies. To address this, we generated three draft-level genomes and annotations forC. lativittatusrepresenting its haploid meiospore, orange gamete, and amber gamete life stages. These draft genome assemblies ranged in size from 5002 to 5799 contigs with a total length of 19.8-22.8 Mb and a mean of 7416 protein-coding genes. We then demonstrated the utility of these genomes by combining the draft annotations as a reference for analysis ofC. lativittatustranscriptomes. We analyzed transcriptomes from across host-associated life stages including infection of larva and excised mature sporangia from the mosquito,Anopheles quadrimaculatus. We identified differentially expressed genes and enriched GO terms both across and within life stages and used these to make hypotheses aboutC. lativittatusbiology. Generally, we found theC. lativittatustranscriptome to be a complex and dynamic expression landscape; GO terms related to metabolism and transport processes were enriched during infection and terms related to dispersal were enriched during sporulation. We further identified five HMG box genes inC. lativittatus, three belonging to clades with mating type (MAT) loci from other fungi,as well as four ortholog expansions inC. lativittatuscompared to other fungi. TheC. lativittatusgenomes and transcriptomes reported here are a valuable resource and may be leveraged toward furthering understanding of the biology of these and other early diverging fungal lineages.

Members of the fungal genusArmillariaare necrotrophic pathogens with efficient plant biomass-degrading strategies. The genus includes some of the largest terrestrial organisms on Earth, spreading underground and causing tremendous losses in diverse ecosystems. Despite their global importance, the mechanism by whichArmillariaevolved pathogenicity in a clade of dominantly non-pathogenic wood-degraders (Agaricales) remains elusive. Here, using new genomic data, we show thatArmillariaspecies, in addition to widespread gene duplications andde novogene origins, appear to have at least 775 genes that were acquired via 101 horizontal gene transfer (HGT) events, primarily from Ascomycota. Functional and expression data suggest that HGT might have affected plant biomass-degrading and virulence abilities ofArmillaria, two pivotal traits in their lifestyle. We further assayed gene expression during root and cambium colonization, and report putative virulence factors, extensive regulation of horizontally acquired and wood-decay related genes as well as novel pathogenicity-induced small secreted proteins (PiSSPs). Two PiSSPs induced necrosis in live plants, suggesting they are potential virulence effectors conserved acrossArmillaria. Overall, this study details how evolution knitted together horizontally and vertically inherited genes in complex adaptive traits, such as plant biomass degradation and pathogenicity, paving the way for development of infection models for one of the most influential pathogens of temperate forest ecosystems.

The brown rot fungus Fomitopsis pinicola efficiently depolymerizes wood cellulose via the combined activities of oxidative and hydrolytic enzymes. Mass spectrometric analyses of culture filtrates identified specific proteins, many of which were differentially regulated in response to substrate composition.

The halotolerant and osmotolerant yeast Zygosaccharomyces rouxii can produce multiple volatile compounds and has the ability to grow on lignocellulosic hydrolysates. We report the annotated genome sequence of Z. rouxii NRRL Y-64007 to support its development as a platform organism for biofuel and bioproduct production.

Fungi survive in diverse ecological niches by secreting proteins and other molecules into the environment to acquire food and interact with various biotic and abiotic stressors. Fungal secretome content is, therefore, believed to be tightly linked to fungal ecologies. We sampled 132 genomes from the early-diverging terrestrial fungal lineage zygomycetes (Mucoromycota and Zoopagomycota) and characterized their secretome composition. Our analyses revealed that phylogeny played an important role in shaping the secretome composition of zygomycete fungi with trophic mode contributing a smaller amount. Reconstruction of the evolution of secreted digestive enzymes revealed lineage-specific expansions, indicating that Mucoromycota and Zoopagomycota followed different trajectories early in their evolutionary history. We identified the presence of multiple pathogenicity-related proteins in the lineages known as saprotrophs, suggesting that either the ecologies of these fungi are incompletely known, and/or that these pathogenicity-related proteins have important functions associated with saprotrophic ecologies, both of which invite further investigation.

238 Background: Appendiceal neuroendocrine tumors (ANETs) are well known for their benign and slow progression; nonetheless, the presence of lymph node metastasis has been described in up to 50% of all cases. The risk of metastasis is mainly associated with tumor size, and the role of other pathological features remains unclear. Hence, this study was designed to assess the pathologic features of ANETs associated with an increased risk of lymph node metastasis. Methods: Patients ≥18yrs of age with ANETs were identified in the National Cancer Database (NCDB) from 2004 to 2017. Groups were defined based on lymph node status as N(-) (all examined nodes were negative) and N(+) (one or more examined nodes were positive). Multivariable models using demographics and oncological features were used to identify factors independently associated with nodal metastasis (N+). Marginal effects, specifically for tumors

Background Neoadjuvant treatment is important for improving the rate of R0 surgical resection and overall survival outcome in treating patients with pancreatic ductal adenocarcinoma (PDAC). However, the true efficacy of radiotherapy (RT) for neoadjuvant treatment of PDAC is uncertain. This retrospective study evaluated the treatment outcome of neoadjuvant RT in the treatment of PDAC. Methods Collected from the National Cancer Database, information on patients with PDAC who underwent neoadjuvant chemotherapy (NAC) and pancreatectomy between 2010 to 2016 was used in this study. Short- and long-term outcomes were compared between patients who received neoadjuvant chemoradiotherapy (NACRT) and NAC. Results The study included 6936 patients, of whom 3185 received NACRT and 3751 NAC. The groups showed no difference in overall survival (NACRT 16.1 months versus NAC 17.4 months; P = 0.054). NACRT is associated with more frequent margin negative resection (86.1 versus 80.0 per cent; P < 0.001) but a more unfavourable 90-day mortality than NAC (6.4 versus 3.6 per cent; P < 0.001). The odds of 90-day mortality were higher in the radiotherapy group (odds ratio 1.81; P < 0.001), even after adjusting for significant covariates. Patients who received NACRT received single-agent chemotherapy more often than those who received NAC (31.5 versus 10.7 per cent; P < 0.001). Conclusion This study failed to show a survival benefit for NACRT over NAC alone, despite its association with negative margin resection. The significantly higher mortality in NACRT warrants further investigation into its efficacy in the treatment of pancreatic cancer.

The Tremellomycetes are a species-rich group within the basidiomycete fungi; however, most analyses of this group to date have focused on pathogenic Cryptococcus species within the order Tremellales. Recent genome-assisted studies of other Tremellomycetes have identified interesting features with respect to biotechnological applications as well as the evolution of genes involved in mating and sexual development. Here, we report genome sequences of two strains of Filobasidium floriforme, a species from the order Filobasidiales, which branches basally to the Tremellales, Trichosporonales, and Holtermanniales. The assembled genomes of strains CBS6241 and CBS6242 are 27.4 Mb and 26.4 Mb in size, respectively, with 8314 and 7695 predicted protein-coding genes. Overall sequence identity at nucleic acid level between the strains is 97%. Among the predicted genes are pheromone precursor and pheromone receptor genes as well as two genes encoding homedomain (HD) transcription factors, which are predicted to be part of the mating type (MAT) locus. Sequence analysis indicates that CBS6241 and CBS6242 carry different alleles for both the pheromone/receptor genes as well as the HD transcription factors. Orthology inference identified 1482 orthogroups exclusively found in F. floriforme, some of which were involved in carbohydrate transport and metabolism. Subsequent CAZyme repertoire characterization identified 267 and 247 enzymes for CBS6241 and CBS6242, respectively, the second highest number of CAZymes among the analyzed Tremellomycete species. In addition, F. floriforme contains five CAZymes absent in other species and several plant-cell-wall degrading CAZymes with the highest copy number in Tremellomycota, indicating the biotechnological potential of this species.

SUMMARYIn this study, we aim to identify genomic traits of the transitions to the ectomycorrhizal ecology within the Boletales, one of the most diverse lineages of symbiotrophic fungi.We sequenced the genomes and compared the gene repertoires of symbiotrophic Boletales species to their saprotrophic brown-rot relatives. We also reconstructed gene duplication/loss histories along a time-calibrated phylogeny.We showed that the rate of gene duplication is constant along the backbone of Boletales phylogeny with large loss events in lineages leading to several families. The rate of gene family expansion sharply increased in the late Miocene and mostly took place in Boletaceae.Most of the ectomycorrhizal Boletales are characterized by a large genome size due to transposable element (TE) expansions and a reduction in the diversity of plant cell wall degrading enzymes (PCWDEs) compared to their brown-rot relatives. However, several species in the Boletaceae, Paxillaceae and Boletinellaceae have kept a substantial set of endoglucanases and LPMOs acting on cellulose/hemicellulose and fungal polysaccharides suggesting that they may partly decompose organic matter by a combined activity of oxidative and hydrolytic enzymes.The present study provides novel insights on our understanding of the mechanisms that influence the evolutionary diversification of boletes and symbiosis evolution.

International audience; - We aimed to identify genomic traits of transitions to ectomycorrhizal ecology within the Boletales by comparing the genomes of 21 symbiotrophic species with their saprotrophic brown-rot relatives.- Gene duplication rate is constant along the backbone of Boletales phylogeny with large loss events in several lineages, while gene family expansion sharply increased in the late Miocene, mostly in the Boletaceae.- Ectomycorrhizal Boletales have a reduced set of plant cell-wall-degrading enzymes (PCWDEs) compared with their brown-rot relatives. However, the various lineages retain distinct sets of PCWDEs, suggesting that, over their evolutionary history, symbiotic Boletales have become functionally diverse. A smaller PCWDE repertoire was found in Sclerodermatineae. The gene repertoire of several lignocellulose oxidoreductases (e.g. laccases) is similar in brown-rot and ectomycorrhizal species, suggesting that symbiotic Boletales are capable of mild lignocellulose decomposition. Transposable element (TE) proliferation contributed to the higher evolutionary rate of genes encoding effector-like small secreted proteins, proteases, and lipases. On the other hand, we showed that the loss of secreted CAZymes was not related to TE activity but to DNA decay.- This study provides novel insights on our understanding of the mechanisms influencing the evolutionary diversification of symbiotic boletes.

Fungi that decay wood have characteristic associations with certain tree species, but the mechanistic bases for these associations are poorly understood. We studied substrate-specific gene expression and RNA editing in six species of wood-decaying fungi from the 'Antrodia clade' (Polyporales, Agaricomycetes) on three different wood substrates (pine, spruce, and aspen) in submerged cultures. We identified dozens to hundreds of substrate-biased genes (i.e., genes that are significantly upregulated in one substrate relative to the other two substrates) in each species, and these biased genes are correlated with their host ranges. Evolution of substrate-biased genes is associated with gene family expansion, gain and loss of genes, and variation in cis- and trans- regulatory elements, rather than changes in protein coding sequences. We also demonstrated widespread RNA editing events in the Antrodia clade, which differ from those observed in the Ascomycota in their distribution, substitution types, and the genomic environment. Moreover, we found that substrates could affect editing positions and frequency, including editing events occurring in mRNA transcribed from wood-decay-related genes. This work shows the extent to which gene expression and RNA editing differ among species and substrates, and provides clues into mechanisms by which wood-decaying fungi may adapt to different hosts.

Global, large-scale surveys of phylogenetically diverse plant and lichen hosts have revealed an extremely high richness of endophytes in the Xylariales, one of the largest clades of filamentous fungi and a significant source of novel secondary metabolites (SMs). Endophytes may produce host protective antimicrobial or insecticidal SMs, as well as compounds that facilitate symbiotic establishment through suppression or degradation of host immune response, but the ecological roles of most SMs are unknown. Here we characterized metabolic gene clusters in 96 genomes of endophytes and closely related saprotrophs and pathogens in two clades of Xylariales (Xylariaceae s.l. and Hypoxylaceae). Hundreds of genes appear horizontally transferred to xylarialean fungi from distantly related fungi and bacteria, including numerous genes in secondary metabolite gene clusters (SMGCs). Although all xylarialean genomes contain hyperabundant SMGCs, we show that increased gene duplications, horizontal gene transfers (HGTs), and SMGC content in Xylariaceae s.l. taxa are linked to greater phylogenetic host breadth, larger biogeographic distributions, and increased capacity for lignocellulose decomposition compared to Hypoxylaceae taxa. Overall, our results suggest that xylarialean endophytes capable of dual ecological modes (symbiotic and saprotrophic) experience greater selection to diversify SMGCs to both increase competitiveness within microbial communities and facilitate diverse symbiotic interactions.

17 p.-7 fig., Because they comprise some of the most efficient wood-decayers, Polyporales fungi impact carbon cycling in forest environment. Despite continuous discoveries on the enzymatic machinery involved in wood decomposition, the vision on their evolutionary adaptation to wood decay and genome diversity remains incomplete., We combined the genome sequence information from 50 Polyporales species, including 26 newly sequenced genomes and sought for genomic and functional adaptations to wood decay through the analysis of genome composition and transcriptome responses to different carbon sources.The genomes of Polyporales from different phylogenetic clades showed poor conservation in macrosynteny, indicative of genome rearrangements. We observed different gene family expansion/contraction histories for plant cell wall degrading enzymes in core polyporoids and phlebioids and captured expansions for genes involved in signaling and regulation in the lineages of white rotters. Furthermore, we identified conserved cupredoxins, thaumatin-like proteins and Lytic Polysaccharide Monooxygenases with a yet uncharacterized appended module as new candidate players in wood decomposition.Given the current need for enzymatic toolkits dedicated to the transformation of renewable carbon sources, the observed genomic diversity among Polyporales strengthens the relevance of mining Polyporales biodiversity to understand the molecular mechanisms of wood decay., This work was supported by the U.S. Department of Energy Joint Genome Institute, a Department of Energy Office of Science User Facility (grant # DE-AC02-05CH11231, DESC0019427 to I.V.G. and B.M.); Institut Carnot 3BCAR, the French National Research Institute for Agriculture, Food and Environment, The Region Provence Alpes Côte d’Azur and the Groupement de Recherche Génomique Environnementale to H.H.; the Laboratory of Excellence ARBRE (grant # ANR-11-LABX-0002-01 to F.M.); the Region Lorraine and the European Regional Development Fund to F.M.; the Hungarian Academy of Sciences’ Momentum Program (grant # LP2019-13/2019 to L.G.N.); the Spanish Ministry of Economy, Industry and Competitiveness (grant # BIO2017-86559-R to A.T.M.); the Consejo Superior de Investigaciones Científicas (grant # PIE-201620E081 to A.T.M.); the Agencia Estatal de Investigación, the European Regional Development Fund and the Ministry of Science, Innovation and Universities (grant # RTI2018-093683-B-I00 to L.D.E. and M.J.M.) and the Czech Science Foundation (grant# 17-20110S to P.B. and M.Š.).

Adjuvant chemotherapy and/or chemoradiation [chemo(radiation)] is considered the standard of care for resected patients with pancreatic adenocarcinoma. However, invasive carcinoma arising from an intraductal papillary mucinous neoplasm (IPMN) seems to have different biologic behavior and prognosis. Retrospective data suggest a survival benefit of adjuvant chemo(radiation) for resected invasive IPMNs with metastatic nodal disease; however, it is unclear whether this remains valid for node-negative patients.To compare the outcome of patients with invasive IPMNs who received adjuvant chemo(radiation) with that of those treated with surgery alone, we queried the National Cancer Database regarding data of patients who underwent pancreatic resection for invasive IPMN between 2006 and 2015. A propensity score analysis was conducted to balance covariates between treatment groups.For the study, 492 patients were eligible, of whom 267 (54.3%) received adjuvant chemo(radiation). Estimated 1- and 3-year overall survival rates were 88.9% and 73.5% versus 93.2% and 72.8% for patients who did or did not receive adjuvant chemo(radiation), respectively. Among patients with negative nodal stage, there was no difference in overall survival between patients who received versus patients who did not receive adjuvant chemo(radiation) (P = 0.973). In contrast, among patients with positive nodal disease, those who received adjuvant chemo(radiation) had significantly better OS compared with those who did not (P = 0.001).In patients with resected invasive IPMNs, adjuvant chemo(radiation) was associated with significantly improved overall survival only in presence of nodal metastases. This finding can help clinicians to select adjuvant treatment in a patient-tailored fashion.

To identify objective preoperative prognostic factors that are able to predict long-term survival of patients affected by PDAC.In the modern era of improved systemic chemotherapy for PDAC, tumor biology, and response to chemotherapy are essential in defining prognosis and an improved approach is needed for classifying resectability beyond purely anatomic features.We queried the National Cancer Database regarding patients diagnosed with PDAC from 2010 to 2016. Cox proportional hazard models were used to select preoperative baseline factors significantly associated with survival; final models for overall survival (OS) were internally validated and formed the basis of the nomogram.A total of 7849 patients with PDAC were included with a median follow-up of 19 months. On multivariable analysis, factors significantly associated with OS included carbohydrate antigen 19-9, neoadjuvant treatment, tumor size, age, facility type, Charlson/Deyo score, primary site, and sex; T4 stage was not independently associated with OS. The cumulative score was used to classify patients into 3 groups: good, intermediate, and poor prognosis, respectively. The strength of our model was validated by a highly significant randomization test, Log-rank test, and simple hazard ratio; the concordance index was 0.59.This new PDAC nomogram, based solely on preoperative variables, could be a useful tool to patients and counseling physicians in selecting therapy. This model suggests a new concept of resectability that is meant to reflect the biology of the tumor, thus partially overcoming existing definitions, that are mainly based on tumor anatomic features.

The use of the laparoscope in biliary tract surgery continues to play a major role in improving the operative management of patients with biliary diseases. Laparascopic cholecystectomy has been safely performed as a day-case procedure and has lowered the morbidity of cholecystectomy in the setting of acute cholecystitis. Laparoscopic common bile duct exploration allows cholecystectomy and the removal of common bile duct stones to be performed during the same procedure, thereby decreasing hospital stay. Several new noninvasive modalities have been recently developed to image the biliary tract. In addition, laparoscopic ultrasound has led to rapid intraoperative imaging of the extrahepatic biliary tree. The long-term results of laparoscopic bile duct injuries have been better defined during the past several years. Finally, the role of surgical resection for gallbladder cancer detected during or after laparoscopic cholecystectomy has recently been evaluated.

Summary: We present 3D-SURFER, a web-based tool designed to facilitate high-throughput comparison and characterization of proteins based on their surface shape. As each protein is effectively represented by a vector of 3D Zernike descriptors, comparison times for a query protein against the entire PDB take, on an average, only a couple of seconds. The web interface has been designed to be as interactive as possible with displays showing animated protein rotations, CATH codes and structural alignments using the CE program. In addition, geometrically interesting local features of the protein surface, such as pockets that often correspond to ligand binding sites as well as protrusions and flat regions can also be identified and visualized. Availability: 3D-SURFER is a web application that can be freely accessed from: http://dragon.bio.purdue.edu/3d-surfer Contact: dkihara@purdue.edu Supplementary information: Supplementary data are available at Bioinformatics online.

The etiology of lung tumors arising in nonsmokers remains unclear. Although mutations in the K-ras and p53 genes have been reported to be significantly higher in smoking-related lung carcinomas, in the present study we performed a more comprehensive analysis in search of additional genetic changes between lung adenocarcinoma from tobacco- and non-tobacco-exposed patients. We selected a matched cohort of 18 lifetime nonsmoking and 27 smoking patients diagnosed with primary adenocarcinoma of the lung and searched for chromosomal alterations in each tumor by testing normal and tumor tissue with 54 highly polymorphic microsatellite markers located on 28 different chromosomal arms. Allelic losses or gains at chromosomal arms 3p (37 versus 6%), 6q (46 versus 12%), 9p (65 versus 22%), 16p (28 versus 0%), 17p (45 versus 11%), and 19p (58 versus 16%) were present significantly more often in adenocarcinomas from smokers than from nonsmokers. Chromosomal arms showing allelic imbalance in lung tumors from nonsmokers were rare but occurred more often at 19q (22%), 12p (22%), and 9p (22%). The FAL (fractional allelic loss or gain) is defined as the percentage of chromosomal arm losses/gains among the total informative chromosomal arms. Tumors from smokers harbored higher levels of FAL (13 (48%) of 27 showed FALor = 0.3) compared with the lung tumors from the nonsmoker patients (2 (11%) of 18 showed FALor = 0.3; P = 0.02; odds ratio, 0.13; 95% confidence interval, 0.01-0.79). Our data demonstrate that widespread chromosomal abnormalities are frequent in lung adenocarcinoma from smokers, whereas these abnormalities are infrequent in such tumors arising in nonsmokers. These observations support the notion that lung cancers in nonsmokers arise through genetic alterations distinct from the common events observed in tumors from smokers.

The safe performance of a right hepatic lobectomy requires adequate exposure of the hepatic veins and of the suprahepatic vena cava. An extended subcostal or midline incision is commonly used to provide exposure for this operation. The technique for an extended subcostal incision that uses the natural hinge mechanism of the rib cage to provide exposure to the right upper quadrant is described. This approach provides adequate exposure during a difficult hepatectomy, avoiding the need for a thoracotomy or sternotomy.