bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21–q22 in soft tissue sarcomas
Authors: Forus Anne , Weghuis Daniël Olde , Smeets Dominique , Fodstad Øystein , Myklebost Ola , van Kessel Ad Geurts
Published: February 2007

Comparative genomic hybridization (CGH) was recently developed as a tool to survey entire genomes for variations in DNA sequence copy numbers. We have applied this technique to detect and map amplified regions in 54 soft tissue sarcomas. Aberrations were detected by visual analysis of hybridizations or contrast‐enhanced digital images, followed by quantitative digital ratio imaging of the aberrant chromosomes. Several tumors showed increased DNA sequence copy number at 12q14, as expected. However, CGH analysis detected amplification of 12q14 also in some tumors where neither MDM2 nor CDK4 was amplified, suggesting that another as yet unknown gene(s) may drive amplification of this region in sarcomas. Furthermore, a novel recurring amplicon was detected at 1q21‐q22. DNA amplifications coinciding with this segment were as frequent as those observed for 12q14, indicating that 1q21‐q22‐linked gene(s) may also play an important role in the development and/or progression of human soft tissue sarcomas.
Comparative genomic hybridization analysis of human sarcomas: II. Identification of novel amplicons at 6p and 17p in osteosarcomas
Authors: Forus Anne , Weghuis Daniël Olde , Smeets Dominique , Fodstad Øystein , Myklebost Ola , van Kessel Ad Geurts
Published: February 2007

Using comparative genomic hybridization (CGH), we have identified and mapped regions of DNA amplification in primary and metastatic osteosarcomas. Samples were obtained from four patients and ten independent xenografts. Sixty‐four percent of the tumors showed increased DNA‐sequence copy numbers, affecting 23 different chromosomal sites. Most of these regions were not previously associated with the development and/or progression of these tumors. Amplicons originating from 1q21–q23, 6p, 8q23‐qter, and 17p11‐p12 were observed most frequently. The 6p and 17p11–p12 amplicons seem to be specific for osteosarcomas, indicating that these regions may harbor genes relevant for the development of these tumors.
Identification of two distinct regions of deletion at 6q in gastric carcinoma
Authors: Queimado Lurdes , Seruca Raquel , Costa‐Pereira Altamiro , Castedo Sérgio
Published: February 2007

Loss of heterozygosity (LOH) affecting the long arm of chromosome 6 has been found repeatedly in human cancers. Recently, our group reported that del(6)(q21‐22→qter) was the most consistent structural cytogenetic abnormality in gastric carcinomas. To determine more precisely the deleted region, we studied 51 tumors with 9 polymorphic markers on this chromosome arm. LOH of one or more markers was found in 39% of the tumors. LOH at region 6q22.3 was detected in 50% of informative tumors and at 6q26‐q27 in 37% of informative tumors. By comparative analysis of LOH regions, we identified two separate regions of overlapped deletions at 6q, one between 6q16.3‐q21 and 6q22.3‐q23.1, another distal to 6q23‐q24. A comparison of clinicopathologic features of gastric carcinomas with and without LOH at 6q revealed statistically significant or suggestive differences between LOH and young age of the patients and proximal location of the tumors. The two informative early gastric carcinomas both showed LOH at 6q. The occurrence of LOH at 6q was similar in all histological types. We conclude that two distinct regions at 6q appear to be involved in the early stages of gastric carcinogenesis.
Balanced translocation in a neuroblastoma patient disrupts a cluster of small nuclear RNA UI and tRNA genes in chromosomal band Ip36
Authors: van der Drift Pauline , Chan Alvin , Laureys Geneviève , van Roy Nadine , Sickmann Grace , den Dunnen Johan , Westerveld Andries , Speleman Frank , Versteeg Rogier
Published: February 2007

Chromosomal band Ip36 probably harbours several neuroblastoma suppressor genes. A neuroblastoma patient has been described with a constitutional balanced translocation, t(1;17)(p36;q12‐21). Cytogenetically, no loss of chromosomal material was visible. The Ip36 translocation breakpoint could therefore have inactivated one allele of a tumour suppressor gene, thus predisposing the patient to develop neuroblastoma. We localized this breakpoint by pulsed field gel electrophoresis, analysis of yeast artificial chromosomes, and fluorescence in situ hybridization. Here we report that the breakpoint is within a large cluster of small nuclear RNA U1 (RNU1) and some tRNA genes (TRE, TRN) on chromosomal band 1p36. The size of this cluster is over two megabases and it contains many other locally repeated sequences. Polyadenylated transcripts were identified for some of these sequences. In addition, the cluster is the target for integration of an adenovirus 5/SV40 hybrid virus. The translocation breakpoint maps distal of this viral integration site and proximal of marker PND.
Fluorescence in situ hybridization analysis of whole‐arm 7;12 translocations in hematologic malignancies
Authors: Johansson Bertil , Arheden Kristina , Höglund Mattias , Othzén Annika , Békássy Albert N. , Turesson Ingemar , Heim Sverre , Mitelman Felix
Published: February 2007

Cytogenetic analysis of one case of acute myeloid leukemia (AML), one of acute lymphoblastic leukemia (ALL), one of refractory anemia with excess of blasts (RAEB), and one of acute mixed lineage leukemia (AMLL) with unbalanced 7;12 translocations mapped the breakpoints to the centromeres on both chromosomes. The rearrangements were interpreted as the whole‐arm translocations der(7;12)(q10;q10) in the AML and ALL and der(7;12)(p10;q10) in the RAEB and AMLL. However, further analysis by metaphase and/or interphase fluorescence in situ hybridization (FISH) showed centric fusion only in the AML and ALL. In the RAEB and AMLL, centromeric material from chromosome 7 but not from 12 was present in the derivative chromosome. Whereas the t(7;12) resulted in loss of 12p in all four cases, the corresponding chromosome 7 imbalances differed—monosomy for 7q in the RAEB and AMLL and monosomy for 7p in the AML and ALL. Six hematologic neoplasms with unbalanced whole‐arm or near‐centromeric 7;12 translocations and seven dic(7;12) with juxtacentromeric breakpoints have been reported previously: 2 AML, 1 RAEB in transformation, and 10 ALL. All karyotypically informative cases had loss of 12p material. All but one of the cases with combined 7p and 12p deletion were ALL, whereas all cases with 7q and 12p loss showed myeloid differentiation. No particular clinical, morphologic, or immunophenotypic features seem to characterize ALLs with t(7;12). AMLs with an unbalanced t(7;12), often together with 5q deletions, might be associated with previous genotoxic exposure and poor prognosis.
Mitochondrial ATP synthase α‐subunit gene amplified in a retinoblastoma cell line maps to chromosome 18
Authors: Bie Wenjun , Squire Jeremy A. , Fraser Murray , Paterson Malcolm C. , Godbout Roseline
Published: February 2007

The human retinoblastoma cell line Y79 has multiple copies of the MYCN gene and the DEAD box gene DDX1. Both genes have been mapped to chromosome band 2p24. A third gene, encoding the α‐subunit of mitochondrial ATP synthase (ATPSA), is also amplified in Y79. Here we report that there are at least four human mitochondrial ATPSA‐related genes located on four different chromosomes. The ATPSA gene that is amplified in Y79 originates from chromosome 18. In Y79, the amplified copies of both the ATPSA and the MYCN genes are located on a homogeneously staining region (HSR) at chromosome band 1p34.
TP53 mutations and breast cancer prognosis: Particularly poor survival rates for cases with mutations in the zinc‐binding domains
Authors: Børresen Anne‐Lise , Andersen Tone Ikdahl , Eyfjörd Jorunn E. , Cornelis Renee S. , Thorlacius Steinunn , Borg Åke , Johansson Ulla , Theillet Charles , Scherneck Siegfried , Hartman Susanne , Cornelisse Cees J. , Hovig Eivind , Devilee Peter
Published: February 2007

Acquired mutations in TP53 as well as immunohistochemically detectable protein expression have been implicated as prognostic factors for breast cancer. We have evaluated the relationship between mutations detected in 119 breast tumours and various clinicohistopathological indices, stratifying the mutations according to the functional domains as defined by the recent elucidation of the crystal structure of the protein. Patients with missense mutations located in regions encoding parts of the protein involved in zinc‐binding had significantly decreased disease‐free and overall survival relative to patients whose tumours had mutations in other domains. These results indicate that these biochemically defined domains also have biological relevance in terms of breast cancer disease course, and suggest that some mutations in TP53, more than others, can contribute to the development of clinically more aggressive and perhaps treatment resistant breast tumours. When confirmed, this will be of potential importance in predicting the clinical behaviour of breast cancer and its responsiveness to therapy.
Complex MLL rearrangement in a patient with T‐cell acute lymphoblastic leukemia
Authors: Chervinsky David S. , Sait Sheila N. J. , Nowak Norma J. , Shows Thomas B. , Aplan Peter D.
Published: February 2007

MLL (also known as ALL‐1, HTRX, or HRX) gene translocations are among the most common chromosomal abnormalities recognized in both B‐lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, MLL gene rearrangements are uncommon in T‐cell ALL. We recently detected an MLL gene rearrangement in a patient with typical T‐cell ALL (CD2+, CD4+, CD5+, CD7+, CD8+, HLA DR−) and an apparently normal karyotype (46.XX). The rearrangement was cloned and characterized; a DNA fragment distal to the breakpoint was mapped by fluorescence in situ hybridization (FISH) to 19p13, indicating that the leukemic blasts had undergone a cytogenetically undetected rearrangement involving chromosomes 11 and 19. A reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay demonstrated an in‐frame fusion mRNA between the amino terminus of MLL and the carboxy terminus of ENL (also known as MLLT1 or LTG19), a gene that has been mapped to 19p13. In addition, MLL sequences distal (telomeric) to the breakpoint were deleted from the genome, which precludes the formation of a reciprocal ENL/MLL fusion protein. These findings suggest that an MLL/ENL fusion protein (and not a reciprocal ENL/MLL fusion) was likely to be pathogenic in this patient, and they reinforce previous studies showing that leukemic blasts with apparently normal karyotype may harbor MLL rearrangements. Additionally, this report provides the first conclusive evidence of an MLL/ENL gene fusion characterized at a molecular level in a patient with T‐cell ALL.
Chromosomes in gliomatosis cerebri
Authors: Hecht Barbara K. , Turc‐Carel Claude , Chatel Marcel , Lonjon Michel , Roche Jean Luc , Gioanni Janine , Hecht Frederick , Gaudray Patrick
Published: February 2007

Gliomatosis cerebri is a rare brain tumor which histologically resembles a diffuse cerebral astrocytoma. It can simultaneously infiltrate multiple sites in the cerebrum, cerebellum, brainstem, and spinal cord. This remarkable diffuseness has led to the idea that gliomatosis cerebri does not derive from a solitary focus but must arise from a broad field of glial cells. We studied the chromosomes from gliomatosis cerebri in a 12‐year‐old boy by conventional cytogenetics and fluorescence in situ hybridization (FISH). Aside from normal cells, we found a majority of cells with the karyotype 44,XY,del(6)(q25),del(14)(q21), der(15;21)(q10;q10),add(18)(q22),del(19)(p12),add(20)(p13), ‐21. A smaller proportion of cells had 88 chromosomes with a doubling of this abnormal karyotype. These findings are consistent with a clonal neoplasm stemming from a single cell. The chromosome changes we observed, with the possible exception of the chromosome 6 deletion, did not resemble those frequently found in astrocytomas. Gliomatosis cerebri may therefore belong to a separate category of brain tumors.
Identification of amplified DNA sequences in breast cancer and their organization within homogeneously staining regions
Authors: Muleris Martine , Almeida Anna , Gerbault‐Seureau Michèle , Malfoy Bernard , Dutrillaux Bernard
Published: February 2007

A modified comparative genomic hybridization (mCGH) technique was used to identify and map amplified DNA sequences in six homogeneously staining regions (hsr) from three primary breast carcinomas. Five different chromosomal regions and bands were identified as sites of amplification: 8p1, 17q21.1, 17q23 (two cases), 19q13.3, and 20q13.3. The mCGH site located on 17q21.1 was demonstrated to correspond to a 50–100‐fold amplification of ERBB2. Further in situ hybridization experiments were used to confirm the mCGH results and to characterize the organization of the amplified sequences within the hsr. In five of six instances, two or more chromosomal regions were found amplified in the same hsr. In the tumor with the less modified karyotype, the two hsr comprised DNA sequences from three different chromosomes and showed different patterns of amplification. In the tumor with the most rearranged karyotype, the hsr‐carrying chromosomes were formed by the translocation and amplification of sequences from three or four different chromosomal sites. This illustrates the complexity of the amplification process in breast cancers.
Alterations of CDKN2 (p16) in non‐small cell lung cancer
Authors: Vos Sven De , Miller Carl W. , Takeuchi Seisho , Gombart Adrian F. , Cho Steve K. , Koeffler H. Phillip
Published: February 2007

The cyclin‐dependent kinase inhibitor known as p16 (CDK41, CDKN2, INK4A, MTS1) has been proposed as a tumor suppressor gene on chromosome segment 9p21. We have evaluated CDKN2 alterations in 34 non‐small cell lung cancers (NSCLCs) with matched normal tissue controls and in 9 NSCLC cell lines by Southern blotting, single‐strand conformation polymorphism (SSCP) with the polymerase chain reaction, and direct sequencing. In addition, loss of heterozygosity at chromosome segment 9p21, with the use of the microsatellite marker D9S171, was studied in these samples. Whereas CDKN2 was either deleted or mutated in NSCLC cell lines at a high frequency (6/9, 67%), alterations were much less frequent (7/34, 21%) in primary tumor samples. Only one sample contained a point mutation in exon 1 of CDKN2. In addition, two samples had homozygous deletions of CDKN2 in exon 1; one had a homozygous and three a hemizygous deletion of exon 2. Possibly normal tissue contaminating our tumor samples may have masked homozygous deletions in these cases. Four patient samples had LOH in the region of CDKN2 on chromosome segment 9p21; two of these samples had potentially inactivating alterations of CDKN2; one sample had a mutation of CDKN2, and the other had a homozygous deletion of exon 1. In summary, inactivation of CDKN2 is implicated in the development of about 20% of NSCLC, but the possibility of another tumor suppressor gene on chromosome segment 9p21 important in lung cancer cannot be eliminated.
Allelic imbalance study of 16q in human primary breast carcinomas using microsatellite markers
Authors: Dorion‐Bonnet F. , Mautalen S. , Hostein I. , Longy M.
Published: February 2007

The high incidence of allelic imbalance on the long arm of chromosome 16 in breast cancer suggests its involvement in the development and progression of the tumor. Several loss of heterozygosity (LOH) studies have led to the assignment of commonly deleted regions on 16q where tumor suppressor genes may be located. The most recurrent LOH regions have been 16q22.1 and 16q22.4‐qter. The aim of this study was to gain further insight into the occurrence of one or multiple “smallest regions of overlap” on 16q in a new series of breast carcinomas. Hence, a detailed allelic imbalance map was constructed for 46 sporadic breast carcinomas, using 11 polymorphic microsatellite markers located on chromosome 16. Allelic imbalance of one or more markers on 16q was shown by 30 of the 46 tumors (65%). Among these 30 carcinomas, LOH on the long arm of chromosome 16 was detected at all informative loci in 19 (41%); 13 of them showed allelic imbalance on the long but not on the short arm, with the occurrence of variable “breakpoints” in the pericentromeric region. The partial allelic imbalance in 11 tumors involved either the 16q22.1‐qter LOH region or interstitial LOH regions. A commonly deleted region was found between D16S421 and D16S289 on 16q22.1 in 29 of the 30 tumors. The present data argue in favor of an important involvement of a tumor suppressor gene mapping to 16q22.1 in the genesis or progression of breast cancer.
Molecular mapping of the putative gonadoblastoma locus on the Y chromosome
Authors: Salo Pia , Kääriäinen Helena , Petrovic Vida , Peltomäki Päivi , Page David C. , de la Chapelle Albert
Published: February 2007

Based on the high incidence of gonadoblastoma in females with XY gonadal dysgenesis or 45,X/46,XY mosaicism, the existence of a susceptibility locus on the Y chromosome (GBY) has been postulated. We attempted to map GBY by making use of a recently developed dense map of Y‐chromosomal sequence‐tagged sites (STSs). In two female patients with gonadoblastoma, small marker chromosomes contained portions of the Y chromosome, and a single region of overlap could be defined extending from probe pDP97 in interval 4B, which contains the centromere, to marker sY182 in interval 5E of the proximal long arm. This interval is contained in a YAC contig that comprises approximately 4 Mb of DNA. Our findings confirm the previous localization of GBY and greatly refine it. The localization of GBY overlaps with the region to which a putative growth determinant, GCY, was recently assigned.
Spontaneous length variation in microsatellite dna from human T‐cell clones
Authors: Hackman Peter , Gabbani Gigliola , Österholm Anne‐May , Hellgren Dennis , Lambert Bo
Published: February 2007

Recently, much interest has been focused on instability of microsatellite DNA sequences such as di‐ and tri‐nucleotide repeats in human cancers. Certain tumors show an increased frequency of mutation leading to repeat length variation at microsatellite loci, and it is thought that such instability may be a marker for the transformed phenotype. However, the spontaneous frequency by which repetitive DNA such as CA‐repeats undergoes size changes in normal human somatic cells is not known. Therefore, it is not possible to decide if there is an increase in the frequency of microsatellite mutation in specific tumors or if the change observed simply reflects the frequency of microsatellite mutation in the cell population from which the tumor originates. To investigate this we have established panels of T‐tymphocyte clones from 28 healthy males and determined the spontaneous length variations at three CA‐repeat markers that are often used to investigate satellite instability: D2S123, D9S180, and D10S197. We found 3 T‐cell clones with altered microsatellite size in a total of 178. This corresponds to a background frequency of 3 somatic microsatellite mutations in 1,028 alleles studied, i.e., 2.9 × 10−3. This frequency is comparable to that found in many tumors of the breast, brain, ovary, and skin but is considerably lower than the frequency of microsatellite mutation in tumors related to hereditary non‐polyposis colorectal cancer.
AF6gene on chromosome band 6q27 maps distal to the minimal region of deletion in epithelial ovarian cancer
Authors: Saha Vaskar , Lillington Debra M. , Shelling Andrew N. , Chaplin Tracy , Yaspo Marie‐Laure , Ganesan Trivadi S. , Young Bryan D.
Published: February 2007

Chromosome 6 has been shown to contain at band q27 a minimal region of deletion associated with epithelial ovarian cancers andAF6, a gene disrupted in acute myeloid leukemia with t(6;11)(q27;q23). Using rapid amplification of cDNA ends by polymerase chain reaction, the breakpoint inAF6was confirmed and a cDNA clone identified. This clone was used as a probe to screen a chromosome 6 cosmid library, and a single cosmid C‐109F0645 was isolated. By fluorescence in situ hybridization, C‐109F0465 was found to map distal to the critically deleted region associated with ovarian malignancies.AF6is therefore distinct from and lies telomeric to this region.
Massive cytogenetic heterogeneity in a pancreatic carcinoma: Fifty‐four karyotypically unrelated clones
Authors: Gorunova Ludmila , Johansson Bertil , Dawiskiba Sigmund , Andrén‐Sandberg Åke , Jin Yuesheng , Mandahl Nils , Heim Sverre , Mitelman Felix
Published: February 2007

Chromosome analysis after short‐term culture revealed remarkable cytogenetic heterogeneity in a pancreatic carcinoma. The patient had no prior history of radio‐ or chemotherapy. A total of 54 aberrant, near‐diploid, karyotypically unrelated clones were identified, three of which displayed clonal evolution. The abnormalities were unbalanced in 30% of the clones. From one to eight karyotypic anomalies per clone were found. Numerical changes were rare, whereas structural aberrations were numerous and diverse and included deletions, duplication, insertions, inversions, translocations, ring formation, and telomeric associations. All chromosomes except No. 15 were involved in structural rearrangements, chromosomes 1, 6, 7, 8, 11, and 12 being the most frequently affected. A similarly massive cytogenetic polyclonality has never been reported previously. Although the spectrum of epithelial neoplasms characterized by karyotypically unrelated clones is increasing, the pathogenetic role of this type of cytogenetic intratumor heterogeneity remains unknown.
Analysis of the wilms tumor suppressor gene WT1 in endometrial carcinoma
Authors: Rackley Raymond , Casey Graham , Zhao Xiao‐Ian , Miller David W. , Williams Bryan R. G. , Coppes Max J.
Published: February 2007

This study reports on the evaluation of the Wilms tumor suppressor gene WT1 in 14 endometrial carcinomas. Despite the fact that several endometrial carcinomas were shown to express WT1, we were unable to demonstrate mutations in the MT1 zinc finger region, suggesting that WT1 does not play a prominent role in the etiology of this malignancy.
Asynchrony of the early maturation of white matter bundles in healthy infants: Quantitative landmarks revealed noninvasively by diffusion tensor imaging
Authors: Dubois Jessica , Dehaene‐Lambertz Ghislaine , Perrin Muriel , Mangin Jean‐François , Cointepas Yann , Duchesnay Edouard , Le Bihan Denis , Hertz‐Pannier Lucie
Published: February 2007

Normal cognitive development in infants follows a well‐known temporal sequence, which is assumed to be correlated with the structural maturation of underlying functional networks. Postmortem studies and, more recently, structural MR imaging studies have described qualitatively the heterogeneous spatiotemporal progression of white matter myelination. However, in vivo quantification of the maturation phases of fiber bundles is still lacking. We used noninvasive diffusion tensor MR imaging and tractography in twenty‐three 1–4‐month‐old healthy infants to quantify the early maturation of the main cerebral fascicles. A specific maturation model, based on the respective roles of different maturational processes on the diffusion phenomena, was designed to highlight asynchronous maturation across bundles by evaluating the time‐course of mean diffusivity and anisotropy changes over the considered developmental period. Using an original approach, a progression of maturation in four relative stages was determined in each tract by estimating the maturation state and speed, from the diffusion indices over the infants group compared with an adults group on one hand, and in each tract compared with the average over bundles on the other hand. Results were coherent with, and extended previous findings in 8 of 11 bundles, showing the anterior limb of the internal capsule and cingulum as the most immature, followed by the optic radiations, arcuate and inferior longitudinal fascicles, then the spinothalamic tract and fornix, and finally the corticospinal tract as the most mature bundle. Thus, this approach provides new quantitative landmarks for further noninvasive research on brain‐behavior relationships during normal and abnormal development. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Hand sensory–motor cortical network assessed by functional source separation
Authors: Porcaro Camillo , Barbati Giulia , Zappasodi Filippo , Rossini Paolo M. , Tecchio Franca
Published: February 2007

The functional source separation procedure (FSS) was applied to identify the activities of the primary sensorimotor areas (SM1) devoted to hand control. FSS adds a functional constraint to the cost function of the basic independent component analysis, and obtains source activity all along different processing states. Magnetoencephalographic signals from the left SM1 were recorded in 14 healthy subjects during a simple sensorimotor paradigm—galvanic right median nerve stimuli intermingled with submaximal isometric thumb opposition. Two functional sources related to the sensory flow in the primary cortex were extracted requiring maximal responsiveness to the nerve stimulation at around 20 and 30 ms (S1a, S1b). Maximal cortico‐muscular coherence was required for the extraction of the motor source (M1). Sources were multiplied by the Euclidean norm of their corresponding weight vectors, allowing amplitude comparisons among sources in a fixed position. In all subjects, S1a, S1b, M1 were successfully obtained, positioned consistently with the SM1 organization, and behaved as physiologically expected during the movement and processing of the sensory stimuli. The M1 source reacted to the nerve stimulation with higher intensity at latencies around 30 ms than around 20 ms. The FSS method was demonstrated to be able to obtain the dynamics of different primary cortical network activities, two devoted mainly to sensory inflow, and the other to the motor control of the contralateral hand. It was possible to observe each source both during pure sensory processing and during motor tasks. In all conditions, a direct comparison of source intensities can be achieved. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Twice‐a‐day radiotherapy for T3 squamous cell carcinoma of the glottic larynx
Authors: Parsons James T. , Mendenhall William M. , Mancuso Anthony A. , Cassisi Nicholas J. , Stringer Scott P. , Million Rodney R.
Published: February 2007

Between March 1978 and April 1986, 21 previously untreated patients with T3 squamous cell carcinoma of the true vocal cord received radical courses of twice‐a‐day radiotherapy (120 cGy twice daily) to total doses of 7,440–7,680 cGy. The rate of local control at the primary site was 67% after radiotherapy. The ultimate control rate after salvage surgery was 83%. Five‐year absolute and cause‐specific survival rates were 59% and 81%, respectively. It is concluded that radiotherapy is a rational approach for many patients with T3 glottic cancer.
Management of laryngeal radionecrosis: Animal and clinical experience
Authors: Oppenheimer Randy W. , Krespi Yosef P. , Einhorn Robert K.
Published: February 2007

Radiation necrosis of the laryngeal cartilages is an uncommon complication of radiotheapy for laryngeal carcinoma. It is a devastating process for which there is no one acceptable treatment. Medical management offers only temporary, symptomatic relief, which further necessitates surgical treatment. Surgical management may start with a tracheotomy; however, it often ends with a total laryngectomy. Physiologically, the necrotic cartilages are the source of the problem. It is a general surgical principle that nonviable tissue must be excised to promote healing. Therefore, if the affected laryngeal cartilages were removed, the larynx should heal. Total or near total removal of the thyroid and cricoid cartilages with preservation of the endolaryngeal soft tissues has not been reported in the literature. Theoretically, if the entire cartilaginous framework is removed, there would be no structural support for the airway. We have found using animal models, that submucosal resection of the laryngeal cartilages, leaving the perichondrium and endolaryngeal soft tissues intact can result in a competent airway. Animal and clinical experience will be presented.
Operative treatment of substernal goiters
Authors: Shaha Ashok R. , Alfonso Antonio E. , Jaffe Bernard M.
Published: February 2007

This report describes the operative experience in 72 patients with substernal goiters treated over the past 5.5 years. Even though the incidence of multinodular goiter has decreased in the United States due to the routine use of iodized salt, we continue to see a large number of patients with massive goiters, predominantly from Carribean Islands. The diagnosis of substernal goiter was made on clinical examination augmented by such radiologic studies, as chest x‐ray, barium esophagograms, airway films, and CT scans. Computed tomographic (CT) scanning was particularly helpful in evaluating the extent of substernal extension. Confirmation of the extent of disease was made at the time of operation. Ninety percent of the patients had tracheal deviation and 85% were symptomatic from airway compression. Esophageal compression was noted in 60% of the patients. All patients had a long history of goiter with recent onset of pressure symptoms. Flow‐volume‐loop studies were performed in 44% of the patients and were useful in the evaluation of pressure symptoms. However, the decision for operation was made primarily based on clinical evaluation of signs and symptoms. Sixteen patients in this group were admitted with acute airway distress requiring airway intubation or semi‐emergency decompression. Only 1 patient required mediastinal splitting, while all others were operated by the cervical approach. The decision as to the extent of thyroidectomy was made at the time of operation. Drains were routinely used because of the large dead space. One patient developed a hematoma in the recovery room and required re‐exploration. There were no instances of recurrent laryngeal nerve palsies or of hypoparathyroidism. Two patients required tracheostomy, 1 because of poor pulmonary reserve and the other because of tracheomalacia. Even with considerable tracheal compression, tracheomalacia was noted in only 1 patient. All the patients were treated with thyroxine postoperatively. Sixty patients had benign diagnosis on pathologic examination; 12 had malignancies. Our data suggest that patients with substernal goiters should be treated operatively, especially if there are pressure symptoms or signs of tracheal compression. Using the cervical approach, 98% of the goiters can be removed easily with minimal morbidity.
Vocal rehabilitation of tracheoesophageal speech failures
Authors: Baugh Reginald F. , Lewin Jan S. , Baker Shan R.
Published: February 2007

Twenty‐three tracheoesophageal speech failures were prospectively evaluated by clinical parameters and transnasal air insufflation at 3 L per minute. The results of testing allow an accurate indication of the etiology of the speech failure. Pharyngoesophageal spasm accounted for 79% of the failures; hypopharyngeal strictures for 26%. One patient was found to have both pharyngoesophageal spasm and a hypopharyngeal stricture. A modified air insufflation test result greater than 20 mm Hg reliably identified all tracheoesophageal speech failures prior to tracheoesophageal puncture. Clinical parameters were not helpful in identifying speech failures. Successful treatment of the specific etiology of the failure resulted in a reduction of the measured intraesophageal pressures. Ninety‐one percent of the tracheoesophageal speech failures were successfully rehabilitated and achieved fluent tracheoesophageal speech. Successful rehabilitation was associated with long‐term tracheoesophageal speech use.
Response to chemotherapy as justification for modification of the therapeutic strategy for pharyngolaryngeal carcinomas
Authors: Demard François , Chauvel Pierre , Santini José , Vallicioni Jacques , Thyss Antoine , Schneider Maurice
Published: February 2007

From September 1983 to September 1987, 238 patients with squamous cell carcinoma of the upper aerodigestive tract were given 3 cycles of chemotherapy [cisplatinum (cis‐DDP), 100 mg/m2 on day 1; 5‐fluorouracil (5‐FU), 1,000 mg/m2 on days 2‐6] before any local treatment. Eighty‐one of these patients had pharyngolaryngeal cancer. Of the 45 of 50 laryngeal cancers and 26 of 31 hypopharyngeal cancers suitable for evaluation, complete responses (CR) were obtained in 51.1% and 53.8%, respectively. These response rates led to changes in the postchemotherapy protocols. For CRs, mutilating surgical protocols were replaced by definitive radiotherapy: one local recurrence has been observed among the 9 laryngeal cancers, and 3 of 10 hypopharyngeal cancer patients, who had an initial indication of total laryngectomy or total pharyngolaryngectomy replaced by radiotherapy. In the group of CR, survival rates at 2 years were 93% and 69%, respectively, for the larynx and hypopharynx vs 65.6% and 40% for non‐CR patients. The possibility of conservative treatment sparing vocal function with a high degree of reliability would in itself appear to be justification for induction chemotherapy in pharyngolaryngeal cancers, even though its long‐term effects remain controversial.
Postoperative radiotherapy for oral cavity cancers: Impact of anatomic subsite on treatment outcome
Authors: Zelefsky Michael J. , Harrison Louis B. , Fass Daniel E. , Armstrong John , Spiro Ronald H. , Shah Jatin P. , Strong Elliot W.
Published: February 2007

We have retrospectively reviewed the treatment results of postoperative radiotherapy (RT) for advanced oral cavity cancers. The purpose of this study was to determine the impact of anatomic subsite on the results of treatment. Between 1975 and 1985, 51 patients with squamous cell carcinoma of the oral tongue (OT = 29 patients) and floor of mouth (FOM = 22 patients) were treated with combined surgery plus RT. All had an indication(s) for RT including advanced primary disease (T3 or T4) (29 patients), close or positive margins (34 patients), and multiple positive neck nodes and/or extracapsular extension (41 patients). With a median follow‐up of 6 years, the 5‐year actuarial local control rate was 74% and the rate of distant metastasis (DM) was 34%. Despite the similar T stage, margin status and median RT dose, the 5‐year actuarial local failure rate was 38% for OT vs. 11% for FOM (ρ = 0.03). Furthermore, the median survival after recurrence was 9 months for OT and 40 months for FOM (ρ = 0.02). At 5 years the determinate survival for both sites was (55%), and the likelihood of developing a second malignancy was 31%. The likelihood of developing DM was 50% for FOM (NO‐N1 = 3 of 12, N2‐N3 = 8 of 10) and 21% for OT (NO‐N1 = 4 of 21, N2‐N3 = 1 of 8). This study highlights significant differences between FOM and OT cancers in response to combined surgery and RT. Future strategies should be directed at the enhancement of local control for OT and better systemic therapy for those with advanced N‐stage FOM. Second primary cancers were an even greater threat to survival than anticipated.
Esthesioneuroblastoma: Is there a role for elective neck treatment?
Authors: Beitler Jonathan J. , Fass Daniel E. , Brenner Harry A. , Huvos Andrew , Harrison Louis B. , Leibel Steven A. , Fuks Zvi
Published: February 2007

A retrospective review of the Memorial Sloan Kettering Cancer Center experience (MSKCC) with esthesioneuroblastoma was performed. From 1975 to 1985 14 cases were identified. Overall 5‐ and 10‐year survival was 86% and 70%, respectively. Four local failures were observed and 4 neck failures were observed. A review of the literature since 1966 revealed an unexpectedly high incidence of neck failure, and of the 21 of 110 patients with neck failures that were identified through the literature, there were 6 subsequent deaths.
Oral cavity reconstruction: An objective assessment of function
Authors: Haribhakti Vijay V. , Kavarana Naozer M. , Tibrewala Anil N.
Published: February 2007

The prime objective of oral cavity reconstruction is restoration of function, which must be carefully studied while evaluating the success of any reconstructive endeavour. We devised a unique comprehensive test series for the purpose that is suitable for use in routine follow‐ups, and capable of providing objective documentation. Functional assessment included evaluation of general health, food intake, oral competence, mastication, speech, swallowing, tongue mobility, and shoulder–neck function. Fifty patients who had had surgery were analyzed and their functional scores compared with those of 10 normal volunteers. The extent of mandibular resection and the magnitude of soft tissue excision significantly affected overall scores of function. Oral competence, as reflected by the water holding test (WHT), was uniformly impaired in the 50 patients, and in dentate individuals, the quality of bolus provided good correlation with all other functional scores. Among reconstructive modalities employed here, the bi‐paddled pectoralis major flap produced the best overall scores.
Dynamic radiographic imaging following total laryngectomy
Authors: Muller‐Miny Heribert , Eisele David W. , Jones Bronwyn
Published: February 2007

Cinepharyngoesophograms of the pharynx were obtained in 51 patients after total laryngectomy for squamous cell carcinoma. The radiological findings were correlated with operative reports and follow‐up findings in 47 patients. Postoperative anatomic changes were well‐demonstrated radiographically. A spectrum of radiographic findings were observed and included narrowing at the superior surgical closure site in 52% and pseudodiverticula in 47% of all patients. Cricopharyngeal prominence was observed in 15%, fistulae in 10%, and pharyngeal pouches in 6% of all cases. Increased retropharyngeal soft tissue thickness was not found to be indicative of tumor recurrence. We conclude that cineradiography is a useful method for demonstrating both functional and structural changes following laryngectomy for carcinoma.
Squamous cell carcinoma of the oral cavity derived from a skin graft: A case report
Authors: Sa'do Banna , Nakamura Norifumi , Higuchi Yoshinori , Ozeki Satoru , Harada Hidemitsu , Tashiro Hideo
Published: February 2007

A case of oral cancer that had derived from a 19‐year skin graft on the left buccal mucosa is reported. The patient had had three previous operations due to squamous cell carcinoma, erosion, and squamous cell carcinoma of the left buccal mucosa, respectively. In the last two operations, skin was transplanted, and the present cancer is believed to have derived from the latter one. The tumor was resected, and a new skin was grafted. In situ hybridization of human papilloma virus (HPV) was carried out; the HPV 16 DNA could not be detected in the specimen. Eight months later, a cervical lymph node metastasis was detected; thus, a radical neck dissection was performed. © 1994 John Wiley & Sons, Inc.
Relationship between vocal cord paralysis and benign thyroid disease
Authors: Collazo‐Clavell Maria L. , Gharib Hossein , Maragos Nicolas E.
Published: February 2007

Background. Vocal cord paralysis is generally associated with advanced thyroid malignancy. It may also be present in the setting of benign thyroid disease. This association may be incidental as well as causal.

Methods. Retrospective review of cases with concurrent diagnosis of vocal cord paralysis and benign thyroid disease.

Results. Eight cases found, all with documented vocal cord paralysis, by laryngoscopy. Four patients had nodular thyroid disease, but in two it was contralateral to the recurrent laryngeal nerve paralysis. The remaining patients had goiters of various sizes. Six patients were euthyroid, two on thyroid hormone replacement. Two patients were thyrotoxic: one had Graves' disease and the other had subacute thyroiditis.

Conclusions. Vocal cord paralysis can be the result of benign thyroid disease by such mechanisms as compression, stretching, or inflammation. Malignant thyroid disease should always be ruled out in structural thyroid abnormalities. Vocal cord paralysis can also be an incidental finding unrelated to thyroid abnormality. © 1995 Jons Wiley & Sons, Inc.
Low‐dose radiotherapy for multicystic benign lymphoepithelial lesions of the parotid gland in HIV‐positive patients: Long‐term results
Authors: Beitler Jonathan J. , Vikram Bhadrasain , Silver Carl E. , Rubin John S. , Bello Jacqueline A. , Mitnick Robin J. , Gejerman Glen , Davis Lawrence W.
Published: February 2007

Background. Multicystic benign lymphoepithelial lesions of the parotid gland (BLL) seen in patients with human immunodeficiency virus (HIV) can produce considerable cosmetic deformity as well as physical discomfort. We previously reported our preliminary results with low‐dose radiotherapy in this disease, and all 8 patients were satisfied with the initial improvement in their appearance. We now report the long‐term follow‐up of those patients and additional patients.

Methods. Twelve HIV‐positive patients with BLL were treated with 8–10 Gy of external radiation using 2‐Gy daily fractions. Objective responses and subjective duration of patient‐defined cosmetic control were recorded.

Results. All 12 patients (100%) had at least a 50% decrease in the size of their parotid masses. Five of 12 (42%) had a complete response and 7 (58%) had a partial response. Persisting complete response was achieved in only 1 patient, however, with relapse in the other 11 patients. Cosmetic palliation, as judged by the patients, was achieved for a median of 9.5 months. Eight patients were subsequently retreated with doses of 6–16 Gy (median and mode: 10 Gy). None (0%) of the 8 patients retreated achieved local control.

Conclusions. Very low‐dose radiation (8–10 Gy) provides reliable but temporary cosmetic palliation for BLL. Retreatment was unsatisfactory, and we are now investigating higher initial doses of radiation to prolong palliation and eliminate recurrences. © 1995 Jons Wiley & Sons, Inc.
Composite mucochondral flap for repair of cerebrospinal fluid leaks
Authors: Friedman Michael , Venkatesan T. K. , Caldarelli David D.
Published: February 2007

Background. Cerebrospinal fluid leaks from defects in the anterior cranial fossa present a difficult management problem. Particularly when the defects are large, conventional techniques may not be sufficient to close them. We describe a new technique for treating such CSF leaks using a composite mucochondral flap from the nasal septum.

Methods. We treated five patients with the composite mucochondral flap. All patients were women aged 29–60 years. Two patients had an encephalocele, one had an esthesioneuroblastoma, and one had adenocarcinoma; one leak was spontaneous.

Results. The CSF leak was successfully closed in all five patients. No patients have experienced recurrence; the longest follow‐up has been 39 months. The donor site on the septum healed without complication in all patients.

Conclusions. The composite flap is useful for repairing large defects or after radiotherapy or trauma. The advantage of skeletal support to counter the pressure exerted by CSF seems clear.
Simulation of the soil wetting shape under porous pipe sub‐irrigation using dimensional analysis
Authors: Qiaosheng Shu , Zuoxin Liu , Zhenying Wang , Haijun Liang
Published: February 2007

Based on the discharge characteristics test for a porous pipe used widely in greenhouse sub‐irrigation in west Liaoning Province, China, Time Domain Reflectometry (TDR) was applied to monitor the process of soil water movement during sub‐irrigation. A model to determine the soil wetting shape was developed using a dimensional analysis method. Statistical analysis revealed that this model has a high accuracy in simulating the wetted soil shape, demonstrating that there was no significant difference between predicted and observed soil wetted width under different depths. It showed that one simple model could also be used to simulate the shape of the wetting area under a porous pipe sub‐irrigation system, which was expected to provide aids for deciding depth and intervals of pipes and designing a sub‐irrigation scheme. Copyright © 2007 John Wiley & Sons, Ltd.
Modification of sericin‐free silk fibers for ligament tissue engineering application
Authors: Liu Haifeng , Ge Zigang , Wang Yue , Toh Siew Lok , Sutthikhum Vallaya , Goh James C. H.
Published: February 2007

Biomedical application of silk requires the removal of sericin that is the gumming material of native silk fibers. This is because sericin can elicit an adverse immune response after implantation in the human body. However, the removal of sericin causes the silk fiber to fray and weakens its structural property, making it very difficult to knit or braid them into a scaffold for ligament tissue engineering applications. The aim of this study was to replace sericin with gelatin using NDGA as a cross‐linking agent to biomimic the natural structure of native silk fibers. The physical properties and biocompatibility of the modified and native silk fibers were compared by in vitro and in vivo models. The mechanical and swelling properties of sericin‐free silk fibers were greatly increased after modification with gelatin. Both modified and native silk fibers were shown to be nontoxic by in vitro cytotoxicity tests. The in vivo study demonstrated that the modified silk fibers, after 4 weeks' subcutaneous implantation in rats, caused little or no inflammatory reaction as compared with native silk fibers. The superior mechanical properties and lower inflammatory potential of modified silk fibers make them a promising candidate for ligament tissue engineering applications. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Long‐term variations in mechanical properties and in vivo degradability of CPC/PLGA composite
Authors: Dagang Guo , Haoliang Sun , Kewei Xu , Yong Han
Published: February 2007

A new type of bone cement composite was successfully achieved by mixing degradable biosecure polylactic‐co‐glycolic acid (PLGA) fibers with high initial strength calcium phosphate cement (CPC). Its higher initial strength was mainly responsible for the in situ reinforcing effect of residual tetra‐calcium phosphate monoxide (r‐TTCP) particles reported in our previous work. So this bone cement composite containing fibers and the controlling group could be termed as CPC/PLGA composite and pure CPC or fiber‐free group, respectively. In this study, we had investigated mechanical properties and microstructures of the CPC/PLGA composite immersed in 0.9% saline solution for different time and its in vivo degradation behaviors after implanting in rabbit muscle and femur bone, respectively. Results showed that the incorporation of the degradable fibers not only greatly increased the initial toughness and flexural strength of the CPC/PLGA composite but also significantly improved its later osteo‐conduction as well as degradation rate. The rabbit muscle implant tests showed that the weight loss ratio of the CPC/PLGA composite increased by 41.03% as compared to the pure CPC. And the rabbit femur implant tests showed that the composite exhibits outstanding biocompatibility and bioactivity and more excellent osteoconduction and degradability than the pure CPC. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007