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Computational analysis of protein tyrosine phosphatases: practical guide to bioinformatics and data resources.

The exponential growth of sequence data has become a challenge to database curators and end-users alike and biologists seeking to utilize the data effectively are faced with numerous analysis methods. Here, with practical examples from our bioinformatics analysis of the protein tyrosine phosphatases (PTPs), we show how computational analysis can be exploited to fuel hypothesis-driven experimental research through the exploration of online databases. We cover the following elements: (i) similarity searches and strategies to collect a non-redundant database of tyrosine-specific PTP domains; (ii) utilization of this database to classify human, fly, and worm PTPs (based on alignments and phylogenetic analysis); (iii) three-dimensional structural analysis to identify conserved regions (structure-function) and non-conserved selectivity-determining regions (substrate specificity); and (iv) genomic analysis, including mapping of exon structure, identification of pseudogenes, and exploration of disease databases. We discuss the importance of manual curation, illustrating examples in which pseudogenes give rise to predicted proteins in GenBank and note that domain servers, such as PFAM and SMART, erroneously include dual-specificity and lipid phosphatases in their collection of tyrosine-specific PTPs. To capitalize on our annotated set of 402 PTP domains (from 47 species and five phyla), we identify sequence conservation across taxonomic categories and explore structure-function relationships among tandem domain receptor-like PTPs. We define three Src homology 2 domain-containing PTP genes in stingray, zebrafish, and fugu and speculate on their evolutionary relationship with human pseudogenes. Our annotated sequences, along with a web service for phylogenetic classification of PTP domains, are available online (http://ptp.cshl.edu and http://science.novonordisk.com/ptp).

Amino Acid Sequence↗

Severe exacerbations of COPD patients: the role of pulmonary infections.

Infection is usually considered the main cause of acute exacerbation in chronic obstructive pulmonary disease (COPD). However, uncertainty persists concerning the exact role of bacterial and viral infection in this setting because of the confusing and conflicting data on the role of tracheobronchial microflora and the usefulness of antibiotics in treating this disease. Most COPD patients have evidence of lower respiratory tract chronic bacterial colonization during remission periods as well as during acute exacerbations. This is evidenced by using microbiological analysis of secretions, which reflect all the respiratory tract (sputum), the lower respiratory tract (transtracheal aspiration), or the distal respiratory tract (protected specimen brush). Potentially pathogenic organisms can be recovered from the respiratory tract secretions of virtually all patients with COPD at some time during the course of their disease. Absence of difference in isolation of potentially pathogenic organisms between remission periods and acute exacerbations suggests that bacterial infection is probably not the predominant cause of acute exacerbations in COPD. In contrast, data indicate that the association between viral infections and acute exacerbations is clearer than that with bacteria, affecting probably more than 20% of cases. The role of antibiotic therapy in acute exacerbations of COPD remains controversial. (1) Clearly, antibiotic therapy is urgently required in COPD patients with pneumonia. (2) Review of the conflicting results of studies evaluating the role of antibiotic therapy for preventing acute exacerbations suggests that there is no clear-cut rationale for prophylactic treatment of infection for all patients with COPD; it seems, however, that such treatment may be of some use in highly selected patients, such as those with many exacerbations in the winter. (3) Similarly, data are conflicting concerning the curative use of antibiotic therapy, with some studies suggesting acceleration of recovery, prevention of acute deterioration, and longer period of freedom from recurrent exacerbations; conversely many patients recover from exacerbations without resorting to an antibiotic. Unfortunately, no clear data identify patients who could benefit from antibiotic treatment, probably justifying most clinicians' choice to treat acute exacerbations as infectious events.

Acute Disease↗

Locus-specific databases: from ethical principles to practice.

Locus-specific databases (LSDBs) play an essential role in clinical care and research. They differ from traditional genetic databases in that they propose to place the mutations of "anonymized" patients directly on the World Wide Web. The proliferation of ethical guidelines and legal requirements affects the rapid and free transmission of clinical data, which is vital for both the daily management of patients and research into better diagnostics and treatment. This paper proposes a review of ethical principles endorsed by international instruments that are of particular relevance to LSDBs. It aims to translate them into 12 proposed practical guidelines that LSDB curators can use in collecting data for clinical research. Perhaps these guideposts will serve as a first step toward translating principles into practice.

Databases, Nucleic Acid↗

ParPEST: a pipeline for EST data analysis based on parallel computing.

BACKGROUND: Expressed Sequence Tags (ESTs) are short and error-prone DNA sequences generated from the 5' and 3' ends of randomly selected cDNA clones. They provide an important resource for comparative and functional genomic studies and, moreover, represent a reliable information for the annotation of genomic sequences. Because of the advances in biotechnologies, ESTs are daily determined in the form of large datasets. Therefore, suitable and efficient bioinformatic approaches are necessary to organize data related information content for further investigations. RESULTS: We implemented ParPEST (Parallel Processing of ESTs), a pipeline based on parallel computing for EST analysis. The results are organized in a suitable data warehouse to provide a starting point to mine expressed sequence datasets. The collected information is useful for investigations on data quality and on data information content, enriched also by a preliminary functional annotation. CONCLUSION: The pipeline presented here has been developed to perform an exhaustive and reliable analysis on EST data and to provide a curated set of information based on a relational database. Moreover, it is designed to reduce execution time of the specific steps required for a complete analysis using distributed processes and parallelized software. It is conceived to run on low requiring hardware components, to fulfill increasing demand, typical of the data used, and scalability at affordable costs.

Algorithms↗

Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences.

We report here a genome-wide analysis of alternative splicing in 2 million human expressed sequence tags (ESTs), to identify splice forms that are up-regulated in tumors relative to normal tissues. We found strong evidence (P < 0.01) of cancer-specific splice variants in 316 human genes. In total, 78% of the cancer-specific splice forms we detected are confirmed by human-curated mRNA sequences, indicating that our results are not due to random mis-splicing in tumors; 73% of the genes showed the same cancer-specific splicing changes in tissue-matched tumor versus normal datasets, indicating that the vast majority of these changes are associated with tumorigenesis, not tissue specificity. We have confirmed our EST results in an independent set of experimental data provided by human-curated mRNAs (P-value 10(-5.7)). Moreover, the majority of the genes we detected have functions associated with cancer (P-value 0.0007), suggesting that their altered splicing may play a functional role in cancer. Analysis of the types of cancer-specific splicing shifts suggests that many of these shifts act by disrupting a tumor suppressor function. Sur prisingly, our data show that for a large number (190 in this study) of cancer-associated genes cloned originally from tumors, there exists a previously uncharacterized splice form of the gene that appears to be predominant in normal tissue.

Alternative Splicing↗

cpnDB: a chaperonin sequence database.

Type I chaperonins are molecular chaperones present in virtually all bacteria, some archaea and the plastids and mitochondria of eukaryotes. Sequences of cpn60 genes, encoding 60-kDa chaperonin protein subunits (CPN60, also known as GroEL or HSP60), are useful for phylogenetic studies and as targets for detection and identification of organisms. Conveniently, a 549-567-bp segment of the cpn60 coding region can be amplified with universal PCR primers. Here, we introduce cpnDB, a curated collection of cpn60 sequence data collected from public databases or generated by a network of collaborators exploiting the cpn60 target in clinical, phylogenetic, and microbial ecology studies. The growing database currently contains approximately 2000 records covering over 240 genera of bacteria, eukaryotes, and archaea. The database also contains over 60 sequences for the archaeal Type II chaperonin (thermosome, a homolog of eukaryotic cytoplasmic chaperonin) from 19 archaeal genera. As the largest curated collection of sequences available for a protein-encoding gene, cpnDB provides a resource for researchers interested in exploiting the power of cpn60 as a diagnostic or as a target for phylogenetic or microbial ecology studies, as well as those interested in broader subjects such as lateral gene transfer and codon usage. We built cpnDB from open source tools and it is available at http://cpndb.cbr.nrc.ca.

Animals↗

Adenocarcinoma of the Esophagogastric Junction in China according to Siewert's classification.

BACKGROUND: There had never been a clear definition of the cancer of cardia before Siewert's classification, which was proposed in 1996 and approved in 1997 at the second International Gastric Cancer Congress in Munich. On the basis of the classification, this study aims to research into the clinicopathological characteristics and surgical modes of adenocarcinoma of the esophagogastric junction in China. METHODS: The study reviewed the data of the distal esophageal cancer, the cancer of cardia and the proximal gastric cancer at the First Hospital of Xi'an Jiaotong University from January 1995 to December 1999. Surgical patients were defined and classified according to Siewert's classification, and 203 patients were up to the classification. Then the study compared and analyzed the clinicopathological characteristics and the survival rates of the three types of the tumor. RESULTS: Among the 203 patients, there were 29 patients with adenocarcinoma of the distal esophagus (Type I); 80 patients with true carcinoma of cardia (Type II); and 94 patients with subcardial carcinoma (Type III). Obvious differences were found in the clinicopathological characteristics of the three types, but no significant difference of the 5-year survival rates was found among the three types of patients with curative resection. CONCLUSION: On the data, the distribution of the three types of tumor was found to be different from that reported in Western countries and in Japan; and the three types of patients who had undergone curative resection were found to have similar 5-year survival rates.

Adenocarcinoma↗

Introduction to resources in molecular genetics.

Perhaps no other discipline has experienced as dramatic an information explosion in recent years as has the field of molecular genetics. While the flood of scholarly publications stemming from this research has been extensively indexed in MEDLINE, a number of new databases have been developed that provide direct access to the primary sequence data as well as to curated, reference information. A select group of these databases, including NCBI's GenBank, LocusLink, RefSeq, OMIM, and Genes and Disease, is examined. Following a brief description of each database, a proposed instructional program for their integration into an undergraduate genetics course at the University of Vermont is described.

Data Display↗

Poxvirus Bioinformatics Resource Center: a comprehensive Poxviridae informational and analytical resource.

The Poxvirus Bioinformatics Resource Center (PBRC) has been established to provide informational and analytical resources to the scientific community to aid research directed at providing a better understanding of the Poxviridae family of viruses. The PBRC was specifically established as the result of the concern that variola virus, the causative agent of smallpox, as well as related viruses, might be utilized as biological weapons. In addition, the PBRC supports research on poxviruses that might be considered new and emerging infectious agents such as monkeypox virus. The PBRC consists of a relational database and web application that supports the data storage, annotation, analysis and information exchange goals of the project. The current release consists of over 35 complete genomic sequences of various genera, species and strains of viruses from the Poxviridae family. Sequence and annotation information for these viruses has been obtained from sequences publicly available from GenBank as well as sequences not yet deposited in GenBank that have been obtained from ongoing sequencing projects. In addition to sequence data, the PBRC provides comprehensive annotation and curation of virus genes; analytical tools to aid in the understanding of the available sequence data, including tools for the comparative analysis of different virus isolates; and visualization tools to help better display the results of various analyses. The PBRC represents the initial development of what will become a more comprehensive Viral Bioinformatics Resource Center for Biodefense that will be one of the National Institute of Allergy and Infectious Diseases' 'Bioinformatics Resource Centers for Biodefense and Emerging or Re-Emerging Infectious Diseases'. The PBRC website is available at http://www.poxvirus.org.

Computational Biology↗

The UMD-p53 database: new mutations and analysis tools.

The tumor suppressor gene TP53 (p53) is the most extensively studied gene involved in human cancers. More than 1,400 publications have reported mutations of this gene in 150 cancer types for a total of 14,971 mutations. To exploit this huge bulk of data, specific analytic tools were highly warranted. We therefore developed a locus-specific database software called UMD-p53. This database compiles all somatic and germline mutations as well as polymorphisms of the TP53 gene which have been reported in the published literature since 1989, or unpublished data submitted to the database curators. The database is available at www.umd.necker.fr or at http://p53.curie.fr/. In this paper, we describe recent developments of the UMD-p53 database. These developments include new fields and routines. For example, the analysis of putative acceptor or donor splice sites is now automated and gives new insight for the causal role of "silent mutations." Other routines have also been created such as the prescreening module, the UV module, and the cancer distribution module. These new improvements will help users not only for molecular epidemiology and pharmacogenetic studies but also for patient-based studies. To achieve theses purposes we have designed a procedure to check and validate data in order to reach the highest quality data.

Databases, Genetic↗

The Mouse Genome Database (MGD): from genes to mice--a community resource for mouse biology.

The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.

Animals↗

CERTOMICS: trusted single-cell multiomics pipeline for high-resolution profiling of adoptive cellular immunotherapies.

SUMMARY: Adoptive cellular immunontherapies, such as chimeric antigen receptor (CAR) T cell therapy, have transformed cancer treatment, yet challenges such as resistance, relapse, and high costs limit their efficacy and accessibility. A comprehensive understanding of cellular heterogeneity and molecular profiles is essential to improve these therapies. Advanced single-cell multiomics technologies have the power to analyze the complex interactions between CAR-engineered cells, immune cells, and tumor cells. However, standardized single-cell multiomics computational pipelines specifically tailored to CAR-engineered cell products are lacking. Due to the synthetic nature of CAR transgenes, additional steps for reliable identification and characterization of CAR-positive cells are required but not included in existing data-processing workflows. To address this, we present CERTOMICS, a Nextflow-based, CAR-aware pipeline offering enhanced CERTainty in immunophenotyping and data interpretation, tailored for single-cell multiOMICSprofiling of adoptive cellular immunotherapies. The pipeline standardizes processing 10x Genomics single-cell multiomics data and integrates CAR-specific identification and quality control. Additionally, a curated repository of CAR construct sequences and annotation data is provided, serving as an extensible resource to support the analysis and development of CAR T cell therapies. AVAILABILITY AND IMPLEMENTATION: Detailed documentation of this pipeline, along with a resource on latest FDA-approved CAR therapies is available on our website: https://fraunhofer-izi.github.io/Living-Drugs-Wiki/. The data underlying this article are available on GitHub at https://github.com/fraunhofer-izi/CERTOMICS. The code is also published on Zenodo at https://doi.org/10.5281/zenodo.18709693.

Multiomics↗

Utility of screening procedures for detecting recurrence of disease after complete response in patients with small cell lung carcinoma.

BACKGROUND: Studies evaluating the efficacy of routine follow-up testing in detecting disease recurrence in treated lung carcinoma patients are lacking. METHODS: To investigate this subject, the authors studied 115 patients who had previously been entered on North Central Cancer Treatment Group (NCCTG) small cell lung carcinoma clinical trials, had achieved a complete response after chemotherapy/radiotherapy treatment, and subsequently developed disease progression. The authors included 58 patients with limited stage and 57 patients with extensive stage disease. Follow-up testing on these clinical trials was scheduled at 4-month intervals in the first year and every 6 months thereafter. At each visit, testing included a clinical history, physical examination, chest X-ray, chemistry group, and hematology group. Patients' records were evaluated to determine the first test(s) to identify disease recurrence, whether the recurrence was diagnosed at the time of routine follow-up or between scheduled follow-up evaluations, the sites of recurrence, and patient outcome. RESULTS: Recurrences occurred in 56 patients (49%) in the first follow-up year, 51 (44%) in the second year, and 8 (7%) after 2 years. Recurrences were signaled by clinical histories in 71% of patients, by physical examinations in 10%, chest X-rays in 12%, and abnormal chemistry testing in 6%. Although 41% of recurrences were detected at scheduled clinical visits, 59% of patients had disease recurrence signaled by symptoms that prompted interval visits between scheduled appointments. At last follow-up, all the patients in this study had died (median survival, 115 days [range, 1-793 days] after diagnosis of recurrence), supporting the lack of curative therapy for patients with recurrent small cell lung carcinoma. CONCLUSIONS: These data, demonstrating that clinical histories and physical examinations are the most fruitful means of detecting evidence of recurrent lung carcinoma, are consistent with data regarding the follow-up of other curatively treated cancers, such as breast carcinoma and melanoma. Chest X-rays in asymptomatic patients detect recurrences in a small proportion of patients, whereas routine blood tests appear to be of little value.

Carcinoma, Small Cell↗

Human immunodeficiency virus reverse transcriptase and protease sequence database.

The HIV RT and Protease Sequence Database is an online relational database that catalogs evolutionary and drug-related human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease sequence variation (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protease sequences including International Collaboration database submissions (e.g., GenBank) and sequences published in journal articles. Sequences are linked to data about the source of the sequence sample and the antiretroviral drug treatment history of the individual from whom the isolate was obtained. The database is curated and sequences are annotated with data from >230 literature references. Users can retrieve additional data and view alignments of sequence sets meeting specific criteria (e.g., treatment history, subtype, presence of a particular mutation). A gene-specific sequence analysis program, new user-defined queries and nearly 2000 additional sequences were added in 1999.

Databases, Factual↗

Human Immunodeficiency Virus Reverse Transcriptase and Protease Sequence Database.

The HIV RT and Protease Sequence Database is an on-line relational database that catalogues evolutionary and drug-related human immunodeficiency virus reverse transcriptase (RT) and protease sequence variation (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protease sequences including International Collaboration database submissions (e.g., GenBank) and sequences published in journal articles. Sequences are linked to data about the source of the sequence sample and the anti-HIV drug treatment history of the individual from whom the isolate was obtained. The database is curated and sequences are annotated with data from 180 literature references. Users can retrieve additional data and view alignments of sequences sets meeting specific criteria (e.g., treatment history, subtype, presence of a particular mutation).

Anti-HIV Agents↗

Resection of synchronous liver metastases from colorectal cancer.

Whereas resection for metachronous liver metastases from colorectal cancer is considered to be a potentially curative approach, little is known about the prognosis after resection of synchronous liver metastases. In the past, these patients usually underwent only palliative therapy. Therefore, we have analyzed the data of 36 patients who underwent curative hepatic resection of synchronous liver metastases from colorectal carcinomas from 1977 to 1987 at the Department of Surgery, Hannover Medical School. In 19 patients, liver resection was combined with colonic resection; in the other 17 patients, hepatic resection was performed after a median interval of 2 months following resection of the primary tumor. No operative mortality was observed in either of the approaches. The median survival time was 28 months for all patients with a median recurrence-free interval of 13.5 months. Overall 5-year survival probability for all patients was 20%. There were no significant differences observed between immediate or delayed liver resection (median survival 18 months versus 31 months). Survival rates were not different after resection of solitary versus multiple liver metastases (26 versus 28 months). Twenty-one of the 36 patients had a recurrence of their liver metastases. In 7 of them, curative liver resection could be performed again. These 7 patients had a significantly improved survival (p less than 0.05) compared to the residual 14 patients. It is concluded that patients with synchronous liver metastases from colorectal cancer may profit from resection of the primary tumor and liver metastases. Timing of liver resection--immediate versus delayed--obviously has no impact on survival rates.

Adult↗

Radical cystectomy for elderly patients with bladder carcinoma: an updated experience with 404 patients.

BACKGROUND: The authors evaluated the experiences at their institution with radical cystectomy and urinary diversion performed on elderly bladder carcinoma patients to determine whether age had an impact on the clinical or functional results for this group of patients. METHODS: Between August 1971 and December 1996, 404 patients age 70 years or older (median age, 74 years) underwent radical cystectomy and urinary diversion for invasive bladder carcinoma: 352 (87%) were ages 70-79 years and 52 (13%) were age 80 years or older. Data analyzed included the following: perioperative mortality; early (within 90 days after surgery) and late (more than 90 days after surgery) postoperative complications, related and unrelated to the urinary diversion; length of hospital stay; pathologic staging; and clinical outcome. These data were then compared with those for 762 patients younger than 70 years (median age, 61 years) who underwent the same procedure during the same time period. RESULTS: The overall mortality rate for patients age 70 years or older was 2.8% (3.2% for those ages 70-79 years, 0% for those age 80 years or older), compared with 2% for patients younger than 70 years. The early complication rate for patients age 70 years or older was 32%, compared with 25% for patients younger than 70 years. Patients age 80 years or older had a similar early complication rate of 29%. Late postoperative complications occurred in 12.4% of patients age 70 years or older, compared with 22.8% of patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 3-year and 5-year overall survival rates for patients age 70 years or older were 60% and 53%, respectively, compared with 68% and 63%, respectively, for patients younger than 70 years (P=0.001). There was no statistical difference between the groups when rates of disease recurrence were compared (P=0.3627). The 5-year recurrence rate for patients age 70 years or older was 35%, compared with a 5-year recurrence rate of 31% for patients younger than 70 years. CONCLUSIONS: These data suggest that an aggressive, curative, radical surgical approach and urinary diversion may be a viable treatment strategy for properly selected elderly patients who are in generally good health and require definitive therapy for invasive bladder carcinoma.

Aged↗

Stage I (T1 N0 M0) squamous cell carcinoma of the laryngeal glottis: therapeutic results and voice preservation.

BACKGROUND: The therapeutic outcomes for voice preservation in Stage I (T1 N0 M0) glottic carcinoma, treated with conservation surgery, radiation therapy, and endoscopic resection, are controversial. METHODS: A retrospective tumor registry retrieval of data on patients treated with curative intent at Washington University Medical Center-Barnes Hospital between January 1971 and December 1990 for the surgical group, January 1971 to December 1985 for the low-dose radiation group, and January 1986 to January 1995 for the high-dose radiation group, was performed. RESULTS: The 659 patients with Stage I (T1 N0 M0) glottic carcinoma treated with curative intent were subdivided into four groups: (1) 90 patients received low-dose radiation (mean dose 58 Gy, range 55-65 Gy, daily fractionation 1.5-1.8 Gy); (2) 104 patients received high-dose radiation (mean dose 66.5 Gy, range 65-70 Gy, daily fractionation 2-2.25 Gy); (3) 404 patients underwent conservation surgery; and (4) 61 patients had endoscopic resection. T1A (85%) and T1B (15%) disease was equally distributed among the groups. The anterior commissure was involved in 38 patients in the radiation therapy groups and 56 patients in the surgical groups. The overall local control was 89%. The overall local salvage was 84%. The overall unaided laryngeal voice preservation was 90%. The overall 5-year disease specific and actuarial survival rates were 95% and 81%, respectively. Prevalence of 2% regional metastases, 1.2% distant metastases, and 14% second primary malignancies were documented. The cure rate was 69% for regional metastases, 13% for distant metastases, and 44% for second primary malignancies. There were 5 complication deaths (0.1%), and 38 (6%) patients died of intercurrent disease. The use and dose of tobacco products was significantly increased in patients who died of intercurrent disease (p = 0.004) or developed second primary malignancies (p = 0.024). No significant difference was observed among the four therapeutic groups in the 5-year cause-specific survival rate (p, 0.68). Actuarial survival was significantly decreased in the low-dose radiation therapy group as compared with the other three therapeutic groups (p = 0.04). Initial local control was poorer for the endoscopic (77%) and low-dose radiation (78%) groups as compared with the high-dose radiation (89%) and conservation surgery (92%) groups (p = 0.02) but significant differences were not found for ultimate local control following salvage treatment. Unaided laryngeal voice preservation was similar for high-dose radiation (89%), conservation surgery (93%) and endoscopic resection (90%), but significantly poorer for low-dose radiation (80%; p = 0.02). T1B disease (N = 94) had similar local control and voice preservation with conservation surgery (87%) and high-dose radiation (88%) but lower results with low-dose radiation and endoscopic resections (67% unaided laryngeal voice preservation; p = 0.02). CONCLUSION: (1)The four therapeutic groups achieved similar rates of disease specific survival and ultimate local control. (2) Low-dose radiation was associated with significantly lower overall actuarial survival and unaided laryngeal voice preservation. (3) Endoscopic resection was associated with a significantly lower initial local control rate, but following salvage therapy achieved equivalent results to the other treatment methods. (4) Patients with (T1 N0 M0) glottic carcinoma had similar survival, local control, and unaided laryngeal voice preservation rates with high-dose radiation, conservation surgery, and endoscopic resections, but not with low-dose radiation therapy. (c) 1999 John Wiley & Sons, Inc. Head Neck 21: 707-717, 1999.

Adult↗