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Scott T Kelley

Publications and source records attributed to Scott T Kelley.

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Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities.

The assessment of microbial diversity and distribution is a major concern in environmental microbiology. There are two general approaches for measuring community diversity: quantitative measures, which use the abundance of each taxon, and qualitative measures, which use only the presence/absence of data. Quantitative measures are ideally suited to revealing community differences that are due to changes in relative taxon abundance (e.g., when a particular set of taxa flourish because a limiting nutrient source becomes abundant). Qualitative measures are most informative when communities differ primarily by what can live in them (e.g., at high temperatures), in part because abundance information can obscure significant patterns of variation in which taxa are present. We illustrate these principles using two 16S rRNA-based surveys of microbial populations and two phylogenetic measures of community beta diversity: unweighted UniFrac, a qualitative measure, and weighted UniFrac, a new quantitative measure, which we have added to the UniFrac website (http://bmf.colorado.edu/unifrac). These studies considered the relative influences of mineral chemistry, temperature, and geography on microbial community composition in acidic thermal springs in Yellowstone National Park and the influences of obesity and kinship on microbial community composition in the mouse gut. We show that applying qualitative and quantitative measures to the same data set can lead to dramatically different conclusions about the main factors that structure microbial diversity and can provide insight into the nature of community differences. We also demonstrate that both weighted and unweighted UniFrac measurements are robust to the methods used to build the underlying phylogeny.

Animals↗

Effects of abiotic factors on the phylogenetic diversity of bacterial communities in acidic thermal springs.

Acidic thermal springs offer ideal environments for studying processes underlying extremophile microbial diversity. We used a carefully designed comparative analysis of acidic thermal springs in Yellowstone National Park to determine how abiotic factors (chemistry and temperature) shape acidophile microbial communities. Small-subunit rRNA gene sequences were PCR amplified, cloned, and sequenced, by using evolutionarily conserved bacterium-specific primers, directly from environmental DNA extracted from Amphitheater Springs and Roaring Mountain sediment samples. Energy-dispersive X-ray spectroscopy, X-ray diffraction, and colorimetric assays were used to analyze sediment chemistry, while an optical emission spectrometer was used to evaluate water chemistry and electronic probes were used to measure the pH, temperature, and E(h) of the spring waters. Phylogenetic-statistical analyses found exceptionally strong correlations between bacterial community composition and sediment mineral chemistry, followed by weaker but significant correlations with temperature gradients. For example, sulfur-rich sediment samples contained a high diversity of uncultured organisms related to Hydrogenobaculum spp., while iron-rich sediments were dominated by uncultured organisms related to a diverse array of gram-positive iron oxidizers. A detailed analysis of redox chemistry indicated that the available energy sources and electron acceptors were sufficient to support the metabolic potential of Hydrogenobaculum spp. and iron oxidizers, respectively. Principal-component analysis found that two factors explained 95% of the genetic diversity, with most of the variance attributable to mineral chemistry and a smaller fraction attributable to temperature.

Bacteria↗

Phylogenetic diversity of Pasteurellaceae and horizontal gene transfer of leukotoxin in wild and domestic sheep.

Wild and domestic animal populations are known to be sources and reservoirs of emerging diseases. There is also a growing recognition that horizontal genetic transfer (HGT) plays an important role in bacterial pathogenesis. We used molecular phylogenetic methods to assess diversity and cross-transmission rates of Pasteurellaceae bacteria in populations of bighorn sheep, Dall's sheep, domestic sheep and domestic goats. Members of the Pasteurellaceae cause an array of deadly illnesses including bacterial pneumonia known as "pasteurellosis", a particularly devastating disease for bighorn sheep. A phylogenetic analysis of a combined dataset of two RNA genes (16S ribosomal RNA and RNAse P RNA) revealed remarkable evolutionary diversity among Pasteurella trehalosi and Mannheimia (Pasteurella) haemolytica bacteria isolated from sheep and goats. Several phylotypes appeared to associate with particular host species, though we found numerous instances of apparent cross-transmission among species and populations. Statistical analyses revealed that host species, geographic locale and biovariant classification, but not virulence, correlated strongly with Pasteurellaceae phylogeny. Sheep host species correlated with P. trehalosi isolates phylogeny (PTP test; P=0.002), but not with the phylogeny of M. haemolytica isolates, suggesting that P. trehalosi bacteria may be more host specific. With regards to populations within species, we also discovered a strong correlation between geographic locale and isolate phylogeny in the Rocky Mountain bighorn sheep (PTP test; P=0.001). We also investigated the potential for HGT of the leukotoxin A (lktA) gene, which produces a toxin that plays an integral role in causing disease. Comparative analysis of the combined RNA gene phylogeny and the lktA phylogenies revealed considerable incongruence between the phylogenies, suggestive of HGT. Furthermore, we found identical lktA alleles in unrelated bacterial species, some of which had been isolated from sheep in distantly removed populations. For example, lktA sequences from P. trehalosi isolated from remote Alaskan Dall's sheep were 100% identical over a 900-nucleotide stretch to sequences determined from M. haemolytica isolated from domestic sheep in the UK. This extremely high degree of sequence similarity of lktA sequences among distinct bacterial species suggests that HGT has played a role in the evolution of lktA in wild hosts.

Alleles↗

Phylogenetic analysis of general bacterial porins: a phylogenomic case study.

Bacterial porin proteins allow for the selective movement of hydrophilic solutes through the outer membrane of Gram-negative bacteria. The purpose of this study was to clarify the evolutionary relationships among the Type 1 general bacterial porins (GBPs), a porin protein subfamily that includes outer membrane proteins ompC and ompF among others. Specifically, we investigated the potential utility of phylogenetic analysis for refining poorly annotated or mis-annotated protein sequences in databases, and for characterizing new functionally distinct groups of porin proteins. Preliminary phylogenetic analysis of sequences obtained from GenBank indicated that many of these sequences were incompletely or even incorrectly annotated. Using a well-curated set of porins classified via comparative genomics, we applied recently developed bayesian phylogenetic methods for protein sequence analysis to determine the relationships among the Type 1 GBPs. Our analysis found that the major GBP classes (ompC, phoE, nmpC and ompN) formed strongly supported monophyletic groups, with the exception of ompF, which split into two distinct clades. The relationships of the GBP groups to one another had less statistical support, except for the relationships of ompC and ompN sequences, which were strongly supported as sister groups. A phylogenetic analysis comparing the relationships of the GenBank GBP sequences to the correctly annotated set of GBPs identified a large number of previously unclassified and mis-annotated GBPs. Given these promising results, we developed a tree-parsing algorithm for automated phylogenetic annotation and tested it with GenBank sequences. Our algorithm was able to automatically classify 30 unidentified and 15 mis-annotated GBPs out of 78 sequences. Altogether, our results support the potential for phylogenomics to increase the accuracy of sequence annotations.

Algorithms↗

Somatostatin receptor profiling in hepatic metastases from small intestinal and pancreatic neuroendocrine neoplasms: immunohistochemical approach with potential clinical utility.

BACKGROUND: The expression of somatostatin receptors (SSTRs) on endocrine tumor (ET) cells forms the basis for somatostatin analog treatment of patients with SSTR-positive, hormonally active ETs. In patients with SSTR-negative ETs, the clinical response is generally absent or suboptimal, while nonfunctioning ETs with SSTR positivity show a variable response to such therapy. METHODS: We retrospectively studied SSTR subtype expression in hepatic metastases from 14 adult patients with primary endocrine carcinomas (ECAs) of the small intestine and pancreas and compared SSTR subtype expression among the primary and metastatic ECAs. Polyclonal antibodies against the 5 SSTR subtypes were used on formalin-fixed, paraffin sections from each primary and metastatic ECA. Both qualitative and semiquantitative evaluation of the stained ECA sections was carried out. RESULTS: Eleven (61%) of 18 hepatic metastases from small intestinal and pancreatic ECAs were positive for SSTR-1, 15 (83%) for SSTR-2, 13 (72%) for SSTR-3, 10 (56%) for SSTR-4, and 15 (83%) for SSTR-5. Among 11 hepatic ECA metastases from small intestinal ECAs (carcinoids), 7 (63%) expressed SSTR-1, 9 (81%) expressed SSTR-2, 8 (72%) expressed SSTR-3, 6 (54%) expressed SSTR-4, and 10 (91%) expressed SSTR-5. Of 7 hepatic ECA metastases from pancreatic ECAs, 4 expressed SSTR-1, 6 expressed SSTR-2, and 5 expressed SSTR-3 and SSTR-5 each. We also observed the immunohistochemical evidence of heterogeneity of expression of various SSTR subtypes in the primary enteropancreatic ECAs and their hepatic metastases. CONCLUSIONS: SSTR subtype expression needs to be correlated to somatostatin analog therapy. Immunohistochemical profiling of various SSTR subtypes as a part of routine surgical pathologic analysis of enteropancreatic ETs may become a useful predictor of responsiveness of ETs to various SSTR analogs.

Adult↗

Microbial diversity in bighorn sheep revealed by culture-independent methods.

We investigated the effectiveness of culture-independent molecular methods for determining host-associated microbial diversity in bighorn sheep (Ovis canadensis). Results from bacterial culture attempts have been the primary source of information on host-associated bacteria, but studies have shown that culture-based results significantly underestimate bacterial diversity in biological samples. To test the effectiveness of culture-independent methods, we extracted DNA from nasal and oropharyngeal swab samples collected from bighorn sheep in four different populations. From these samples, we amplified, cloned, and sequenced small subunit (16S) ribosomal DNA (rDNA) to identify the scope of microbial diversity in bighorn respiratory tracts. Phylogenetic analysis of these rDNA gene sequences revealed organismal diversity an order of magnitude higher than was determined by culture methods. Pasteurellaceae bacteria were the most diverse phylogenetic group in live bighorn sheep, and members of bacterial genera often associated with respiratory disease were found in all the samples. Culture-independent methods were also able to directly detect leukotoxin (lktA) gene sequences in swab and lung tissue samples. Overall, our results show the power of culture-independent molecular methods for identifying microbial diversity in bighorn sheep and the potential for these methods to detect the presence of virulence genes in biological samples.

Animals↗

Structural implications of novel diversity in eucaryal RNase P RNA.

Previous eucaryotic RNase P RNA secondary structural models have been based on limited diversity, representing only two of the approximately 30 phylogenetic kingdoms of the domain Eucarya. To elucidate a more generally applicable structure, we used biochemical, bioinformatic, and molecular approaches to obtain RNase P RNA sequences from diverse organisms including representatives of six additional kingdoms of eucaryotes. Novel sequences were from acanthamoeba (Acathamoeba castellanii, Balamuthia mandrillaris, Filamoeba nolandi), animals (Caenorhabditis elegans, Drosophila melanogaster), alveolates (Theileria annulata, Babesia bovis), conosids (Dictyostelium discoideum, Physarum polycephalum), trichomonads (Trichomonas vaginalis), microsporidia (Encephalitozoon cuniculi), and diplomonads (Giardia intestinalis). An improved alignment of eucaryal RNase P RNA sequences was assembled and used for statistical and comparative structural analysis. The analysis identifies a conserved core structure of eucaryal RNase P RNA that has been maintained throughout evolution and indicates that covariation in size occurs between some structural elements of the RNA. Eucaryal RNase P RNA contains regions of highly variable length and structure reminiscent of expansion segments found in rRNA. The eucaryal RNA has been remodeled through evolution as a simplified version of the structure found in bacterial and archaeal RNase P RNAs.

Acanthamoeba castellanii↗

Dedifferentiation precedes invasion in the progression from Barrett's metaplasia to esophageal adenocarcinoma.

PURPOSE: Adenocarcinoma arises in Barrett's esophagus by progression from metaplasia to cancer through grades of dysplasia. Our aim in this exploratory study was to characterize the broad changes in gene expression that underlie this histologic progression to cancer and assess the potential for using these gene expression changes as a marker predictive of malignant progression in Barrett's epithelium. EXPERIMENTAL DESIGN: Microarray analysis was used to obtain individual gene expression profiles from endoscopic biopsies of nine esophageal adenocarcinomas and the Barrett's epithelia from which three of the cancers had arisen. Pooled samples from the Barrett's epithelia of six patients without cancer or dysplasia served as a reference. RESULTS: Barrett's epithelia from which cancer had arisen differed from the reference Barrett's epithelia primarily by underexpression of genes, many of which function in governing cell differentiation. These changes in gene expression were found even in those specimens of Barrett's epithelia from which cancer had arisen that lacked dysplasia. Each cancer differed from the Barrett's epithelium from which it had arisen primarily by an overexpression of genes, many of which were associated with tissue remodeling and invasiveness. Cancers without identifiable Barrett's epithelium differed from cancers that had arisen from a Barrett's epithelium by having an even greater number of these overexpressed genes. CONCLUSIONS: Histologic progression from Barrett's epithelium to cancer is associated with a gradient of increasing changes in gene expression characterized by an early loss of gene function governing differentiation that begins before histologic change; gain in function of genes related to remodeling and invasiveness follows later. This correlation of histologic progression with increasing changes in gene expression suggests that gene expression changes in biopsies taken from Barrett's epithelium potentially could serve as a marker for neoplastic progression that could be used to predict risk for developing cancer.

Adenocarcinoma↗

Molecular identification of potential pathogens in water and air of a hospital therapy pool.

Indoor warm-water therapy pool workers in a Midwestern regional hospital were diagnosed with non-tuberculosis pulmonary hypersensitive pneumonitis and Mycobacterium avium infections. In response, we conducted a multiseason survey of microorganisms present in this therapy pool water, in biofilms associated with the pool containment walls, and in air immediately above the pool. The survey used culture, microscopy, and culture-independent molecular phylogenetic analyses. Although outfitted with a state-of-the-art UV-peroxide disinfection system, the numbers of bacteria in the therapy pool water were relatively high compared with the potable water used to fill the pool. Regardless of the source, direct microscopic counts of microbes were routinely approximately 1,000 times greater than conventional plate counts. Analysis of clone libraries of small subunit rRNA genes from environmental DNA provided phylogenetic diversity estimates of the microorganisms collected in and above the pool. A survey of >1,300 rRNA genes yielded a total of 628 unique sequences, the most common of which was nearly identical to that of M. avium strains. The high proportion of clones with different Mycobacterium spp. rRNA genes suggested that such organisms comprised a significant fraction of microbes in the pool water (to >30%) and preferentially partition into aerosols (to >80%) relative to other waterborne bacteria present. The results of the study strongly validate aerosol partitioning as a mechanism for disease transfer in these environments. The results also show that culture protocols currently used by public health facilities and agencies are seriously inadequate for the detection and enumeration of potential pathogens.

Air Microbiology↗

Isolation by distance, web service.

BACKGROUND: The population genetic pattern known as "isolation by distance" results from spatially limited gene flow and is a commonly observed phenomenon in natural populations. However, few software programs exist for estimating the degree of isolation by distance among populations, and they tend not to be user-friendly. RESULTS: We have created Isolation by Distance Web Service (IBDWS) a user-friendly web interface for determining patterns of isolation by distance. Using this site, population geneticists can perform a variety of powerful statistical tests including Mantel tests, Reduced Major Axis (RMA) regression analysis, as well as calculate FST between all pairs of populations and perform basic summary statistics (e.g., heterozygosity). All statistical results, including publication-quality scatter plots in Postscript format, are returned rapidly to the user and can be easily downloaded. CONCLUSION: IBDWS population genetics analysis software is hosted at http://phage.sdsu.edu/~jensen/ and documentation is available at http://www.bio.sdsu.edu/pub/andy/IBD.html. The source code has been made available on Source Forge at http://sourceforge.net/projects/ibdws/.

Computer Graphics↗

Tumor response to neoadjuvant chemoradiation therapy for rectal adenocarcinoma is mediated by p53-dependent and caspase 8-dependent apoptotic pathways.

BACKGROUND: We tested the hypothesis that rectal tumors are most responsive to neoadjuvant therapy if they possess p53 and/or caspase 8 activity. PATIENTS AND METHODS: Fifty patients diagnosed with biopsy-proven rectal cancer underwent neoadjuvant chemoradiation therapy consisting of 5-fluorouracil (300 mg/m(2) daily) and radiation (4,500 cGy). Endorectal ultrasonography was performed before and after neoadjuvant therapy along with digital rectal examination and/or sigmoidoscopy for staging purposes and to evaluate response to therapy. All patients underwent resection with specimens submitted for gross and microscopic review. Pretreatment biopsy specimens were subjected to immunohistochemical staining for mutated p53 and caspase 8 bioactivity. RESULTS: The study population consisted of 32 men and 18 women. There were 17 complete responses (CRs; 34%), 17 partial responses (PRs; 34%), and 16 cases of no response (NR; 32%). There were 10 stage I tumors (20%), 22 stage II tumors (44%), and 18 stage III tumors (36%) in the cohort at the time of initial diagnosis. p53 protein staining (ie, mutated p53) was positive in 31 tumors (62%; CR, n = 8; PR, n = 11; NR, n = 12); caspase 8 positivity was apparent in 30 specimens (60%; CR, n = 13; PR, n = 13; NR, n = 4). In terms of pretreatment predictions, we scored 3 separate levels of response (CR, 3; PR, 2; NR, 1) and compared them with the expected responses (ie, p53 positivity and caspase 8 negativity should yield NR, whereas all other combinations should yield responses). Wilcoxon 2-sample tests yielded a 1-sided P value of 0.007. CONCLUSION: The present study highlights a possible mechanism for tumor response to neoadjuvant manipulation, namely that dual mechanisms for apoptotic cell death are working in concert to cause tumor regression; one is p53 transcription-dependent, and the other is p53 transcription-independent.

Adenocarcinoma↗

New perspective on uncultured bacterial phylogenetic division OP11.

Organisms belonging to the OP11 candidate phylogenetic division of Bacteria have been detected only in rRNA-based sequence surveys of environmental samples. Preliminary studies indicated that such organisms represented by the sequences are abundant and widespread in nature and highly diverse phylogenetically. In order to document more thoroughly the phylogenetic breadth and environmental distribution of this diverse group of organisms, we conducted further molecular analyses on environmental DNAs. Using PCR techniques and primers directed toward each of the five described subdivisions of OP11, we surveyed 17 environmental DNAs and analyzed rRNA gene sequences in 27 clonal libraries from 14 environments. Ninety-nine new and unique sequences were determined completely, and approximately 200 additional clones were subjected to partial sequencing. Extensive phylogenetic comparisons of the new sequences to those representing other bacterial divisions further resolved the phylogeny of the bacterial candidate division OP11 and identified two new candidate bacterial divisions, OP11-derived 1 (OD1) and Sulphur River 1 (SR1). The widespread environmental distribution of representatives of the bacterial divisions OD1, OP11, and SR1 suggests potentially conspicuous biogeochemical roles for these organisms in their respective environments. The information on environmental distribution offers clues for attempts to culture landmark representatives of these novel bacterial divisions, and the sequences are specific molecular signatures that provide for their identification in other contexts.

Bacteria↗

Molecular analysis of shower curtain biofilm microbes.

Households provide environments that encourage the formation of microbial communities, often as biofilms. Such biofilms constitute potential reservoirs for pathogens, particularly for immune-compromised individuals. One household environment that potentially accumulates microbial biofilms is that provided by vinyl shower curtains. Over time, vinyl shower curtains accumulate films, commonly referred to as "soap scum," which microscopy reveals are constituted of lush microbial biofilms. To determine the kinds of microbes that constitute shower curtain biofilms and thereby to identify potential opportunistic pathogens, we conducted an analysis of rRNA genes obtained by PCR from four vinyl shower curtains from different households. Each of the shower curtain communities was highly complex. No sequence was identical to one in the databases, and no identical sequences were encountered in the different communities. However, the sequences generally represented similar phylogenetic kinds of organisms. Particularly abundant sequences represented members of the alpha-group of proteobacteria, mainly Sphingomonas spp. and Methylobacterium spp. Both of these genera are known to include opportunistic pathogens, and several of the sequences obtained from the environmental DNA samples were closely related to known pathogens. Such organisms have also been linked to biofilm formation associated with water reservoirs and conduits. In addition, the study detected many other kinds of organisms at lower abundances. These results show that shower curtains are a potential source of opportunistic pathogens associated with biofilms. Frequent cleaning or disposal of shower curtains is indicated, particularly in households with immune-compromised individuals.

Base Sequence↗

The genetic core of the universal ancestor.

Molecular analysis of conserved sequences in the ribosomal RNAs of modern organisms reveals a three-domain phylogeny that converges in a universal ancestor for all life. We used the Clusters of Orthologous Groups database and information from published genomes to search for other universally conserved genes that have the same phylogenetic pattern as ribosomal RNA, and therefore constitute the ancestral genetic core of cells. Our analyses identified a small set of genes that can be traced back to the universal ancestor and have coevolved since that time. As indicated by earlier studies, almost all of these genes are involved with the transfer of genetic information, and most of them directly interact with the ribosome. Other universal genes have either undergone lateral transfer in the past, or have diverged so much in sequence that their distant past could not be resolved. The nature of the conserved genes suggests innovations that may have been essential to the divergence of the three domains of life. The analysis also identified several genes of unknown function with phylogenies that track with the ribosomal RNA genes. The products of these genes are likely to play fundamental roles in cellular processes.

Animals↗

Acidosis plus melphalan induces nitric oxide-mediated tumor regression in an isolated limb perfusion human melanoma xenograft model.

BACKGROUND: Isolated limb perfusion (ILP) with melphalan is an accepted treatment for intransit melanoma of the extremities. Using an ILP human melanoma xenograft model, we tested the hypothesis that acidosis augments the antitumor effect of melphalan and that nitric oxide (NO) induction mediates tumor regression. METHODS: NIH1286 human melanoma tumor bearing athymic nude rats underwent a 10-minute ILP. Group C was perfused at physiologic pH without acid or melphalan, group M received melphalan at physiologic pH (7.2), group A received 0.2 N of HCl at pH 6.8, and group A/M received melphalan and HCl at pH 6.8. Groups 1400W + A and 1400W + A/M were injected with 1400W, a specific inhibitor of inducible NO synthase, 1 hour pre-ILP. Tumor response was followed for up to 60 days in all survival experiments. In 4 to 6 animals from groups C, M, A, and A/M, tumor NO was measured pre- and post-ILP, and tumor and thigh muscle from 2 additional animals in each group were collected at 20 minutes and 24 hours post-ILP and processed for terminal deoxynucleotidyl transferase dUTP nick end labeling staining. RESULTS: Maximum mean reduction in tumor size after ILP in the different groups was as follows: C = 0%, M = 55%, A = 99.6% (3 of 4 complete responses), A/M = 100% (all complete responses), 1400W + A = 0%, and 1400W + A/M = 25%. Median tumor NO was 0.87 +/- 0.74 (SD) micromol/L before ILP and increased significantly (Mann-Whitney rank sum test, P <.001) after ILP (C = +6.9%, n = 4; M = +7.5%, n = 5; A = +66.0%, n = 6; A/M = +35.9%, n = 6). Also, minimal apoptotic cell death was seen in C and M, whereas A and A/M showed evidence of widespread apoptosis. CONCLUSIONS: Acidosis enhances the antitumor effect of melphalan. NO induction appears to play a role in tumor regression.

Acidosis↗

Neoadjuvant chemoradiotherapy is not associated with a higher complication rate vs. surgery alone in patients undergoing esophagectomy.

Recent studies have claimed a higher rate of perioperative complications related to the use of neoadjuvant chemoradiotherapy in the treatment of esophageal cancer. We tested the hypothesis that neoadjuvant chemoradiotherapy has no significant effect on the perioperative complication rate. Data on 155 patients with esophageal carcinoma treated between 1996 and 2001 were collected in a prospective database. This included 61 patients (40%) treated with neoadjuvant chemoradiotherapy (group I) and 94 patients (60%) who underwent esophagectomy alone (group II). Neoadjuvant therapy consisted of two courses of cisplatinum and continuous-infusion 5-fluorouracil with radiation followed by esophagectomy. Ivor-Lewis esophagectomy was performed in 146 (94%) and a transhiatal resection in nine (6%). The two groups (I vs. II) were comparable in terms of age (61.3+/-11 years vs. 64.8+/-11 years), diagnosis (adenocarcinoma: 82% vs. 83%; squamous cell carcinoma:11% vs. 16%), and stage (stage 0 to I: 39% vs. 38%; stage II: 25% vs. 34%; stage III: 30% vs. 24%; and stage IV: 6% vs. 4%). The neoadjuvant group had 23 complete responses, 11 partial responses, and 27 nonresponses. There were 39 complications (25.1%) for the cohort, which included three deaths (1.9%) and four anastomotic leaks (2.6%) demonstrated by Gastrografin swallow (1 in group I vs. 3 in group II. Only one leak required reoperation (group II); all others responded to conservative treatment. Group I had 14 complications (22.9%) vs. 25 (26.5%) in group II (P=NS). Groups were comparable with respect to the rate of pulmonary events (4.9% vs. 6.3%), arrhythmias (6.5% vs. 8.5%), and stricture formation (6.5% vs. 7.4%). Neoadjuvant chemoradiotherapy in patients with esophageal cancer was not associated with increased perioperative morbidity or mortality. Complete response to chemoradiotherapy also did not affect the complication rate (26% vs. 22%).

Adenocarcinoma↗