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Biomedical subjects

G B Snow

Publications and source records attributed to G B Snow.

At least 91 records · Page 5Linked to original sources

Results of the surgical management and histopathological evaluation of 88 parotid gland Warthin's tumours.

With the introduction of parotidectomy after identification of the facial nerve the recurrence rates for benign tumours has declined rapidly. Subsequently, attention was focused on other sequelae of parotid surgery. To reduce the specific surgical morbidity, several modifications of parotidectomy have been implemented. This study compares the results of the different surgical techniques with regard to the histopathological findings and recurrence rate for Warthin's tumour of the parotid gland. Eighty-eight primary surgical parotid procedures were performed on 85 patients for a Warthin's tumour. The surgical procedures included 52 'partial' superficial parotidectomies, 22 'standard' superficial parotidectomies, 12 partial superficial/deep lobe parotidectomies, and two 'selective' deep lobe parotidectomies. No patient developed a recurrence or experienced permanent facial nerve paresis/paralysis, the median follow-up being 93 months. Histopathological examination revealed a multifocal origin in 23% (20/88) of the surgical specimens. Partial parotidectomy is an effective treatment for Warthin's tumour. There is no need for extended follow-up.

Adenolymphoma↗

Biologic implications of genetic changes in head and neck squamous cell carcinogenesis.

Cytogenetic techniques for the analysis of genetic changes common in head and neck squamous cell carcinogenesis show complex patterns of chromosomal deletions, translocations, and amplifications. Powerful molecular biologic techniques have recently made possible the investigation of these abnormalities at the DNA level. Tumour suppressor gene loss and oncogene activation can now be recognized in tumours. Multiple genetic loci are implicated in the carcinogenesis process, while much evidence points to the existence of yet to be recognized tumour suppressor genes. An overview of the genetic changes commonly seen in head and neck squamous cell carcinogenesis and the possible implications of these are presented.

Carcinoma, Squamous Cell↗

Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia.

With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology.

Adult↗

Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients.

PURPOSE: To evaluate the possible value of chemotherapy in the treatment of craniofacial osteosarcoma (CFOS). DESIGN: In a systematic review, data of 201 patients (age, 36.6 +/- 19.0 years [mean +/- SD]) from 20 uncontrolled series on CFOS indexed in Medline and Excerpta Medica between 1974 and 1994 were pooled; 180 patients had undergone surgery. Various chemotherapy regimens had been given to 71 patients. Radiotherapy was used in 69 patients. All patients had data for overall survival, and 182 had data for disease-free survival analysis. Cumulative survival distributions were estimated by the product-limit method, and a multiple regression analysis was performed. RESULTS: Patients' overall and disease-free survival rates were significantly improved by treatment with chemotherapy. This was confirmed for patients with complete surgical removal, as well as for those with incomplete removal of tumor. In a proportional hazards model, complete surgical removal and chemotherapy were independent significant factors for overall and disease-free survival. The effect of radiotherapy was insignificant. No prognostic factors could be identified among age groups, sex, and subsites. CONCLUSION: Evidence exists that chemotherapy improves survival in CFOS. We advocate the adoption of the chemotherapy protocols used for OS of the long bones for CFOS.

Adult↗

A simple and reliable technique for culturing of human oral keratinocytes and fibroblasts.

Cultures of non-malignant oral cells are needed for many applications in the field of oral biology. We describe an efficient and rapid method for the culture of both keratinocytes and fibroblasts isolated from oral tissue, uvulas from patients undergoing reconstructive surgery and non-cancerous tissue from oral cancer patients. High cell yields with a high purity could be obtained. The technique is described in detail with respect to isolation of the cell types, the best way to propagate for over 5 passages and to measure cell proliferation in a colorimetric assay. Culture was successful in over 80% of cases for keratinocytes and over 63% for fibroblasts. Problems encountered were the risk of microbiological infection, the size of the specimen and the type of culture medium used. The potential applications of these primary cell cultures are mentioned.

Carcinoma, Squamous Cell↗

Surgical management of 246 previously untreated pleomorphic adenomas of the parotid gland.

BACKGROUND: Recent modifications of surgical technique may have influenced outcome following parotidectomy. This retrospective study compares the results of the different surgical methods with regard to recurrence rate and the effects on morbidity between 1974 and 1994. METHODS: A total of 246 primary surgical parotid procedures were performed on 245 patients for pleomorphic adenoma. These included 131 'partial' superficial parotidectomies, 61 'total' superficial parotidectomies, 30 partial superficial/deep lobe parotidectomies, eight total parotidectomies, and 16 'selective' deep lobe parotidectomies. In the recent past, the posterior branch of the greater auricular nerve was preserved in the majority of patients. Eleven patients received postoperative radiotherapy. Median follow-up was 95 months. Fourteen patients died without recurrent tumour. RESULTS: Two patients (0.8 per cent) developed local recurrence, both after total parotidectomy for a deep lobe tumour. No patient experienced permanent facial nerve palsy. The incidence of gustatory sweating for partial superficial parotidectomy was 6.9 per cent (nine of 131) compared with 13.1 per cent (eight of 61) for total superficial parotidectomy. CONCLUSION: Partial parotidectomy is an effective treatment for the majority of pleomorphic adenomas; local recurrence is rare and morbidity is low. Prolonged follow-up is unnecessary.

Adenoma, Pleomorphic↗

Monoclonal antibody U36, a suitable candidate for clinical immunotherapy of squamous-cell carcinoma, recognizes a CD44 isoform.

At present, tumor-targeting with monoclonal antibodies (MAbs) is among the most promising novel adjuvant-therapy modalities for the treatment of patients with minimal residual disease of head-and-neck squamous-cell carcinoma (HNSCC). For this purpose we developed MAb U36, recognizing a 200-kDa antigen expressed on the outer cell surface of squamous-cell carcinomas and their normal counterparts. Clinical radioimmunoscintigraphy (RIS) and biodistribution studies have shown that the MAb-U36-defined antigen is a suitable target molecule for antibody-based therapy of head-and-neck cancer. In the present study we further characterized the antigen by cDNA cloning. The cDNA was isolated by expression cloning in COS-7 cells. Sequence analysis and database searching revealed that the MAb-U36-defined antigen is identical to the squamous-cell-specific CD44 splice variant epican. The epitope recognized by MAb U36 was mapped by screening overlapping synthetic peptides of the epican-specific region encoded by exon 7-11 (v3-v7), and appeared to be located in the v6 domain. The applicability of MAb U36 for targeting human tumors of various origin expressing the CD44v6 domain is discussed.

Amino Acid Sequence↗

DNA-damage processing in blood lymphocytes of head-and-neck-squamous-cell-carcinoma patients is dependent on tumor site.

It has been reported that an intrinsic susceptibility to cancer is related to the way an individual responds to DNA-damaging agents. The aim of this study was to evaluate whether, in addition to bleomycin-induced chromosomal instability, radiation-induced initial DNA damage and subsequent repair is associated with the development of head-and-neck squamous-cell carcinoma. In this study, 2 assays were performed to measure DNA damage in human peripheral-blood lymphocytes. One was a chromosomal aberration assay which determines sensitivity to chromatid breaks induced by bleomycin, the other an elegant immunochemical assay which measures the level of radiation-induced strand breaks as well as subsequent repair. Age, smoking and alcohol-drinking behavior did not influence the number of chromatid breaks, initial DNA damage or repair capacity. As has been found in previous studies, the mean number of chromatid breaks per cell was significantly different between patients (n = 18) and control persons (n = 19), whereas the amount of initial DNA damage was not. No correlation was found between the outcome of the 2 assays in the subject groups. In contrast to laryngeal-carcinoma patients, oral-cavity-carcinoma patients showed significantly slower repair capacity than controls. Our hypothesis is that the way DNA damage is processed by the patients determines at which site cancer develops in the head and neck area.

Adult↗

[Development and results of surgical treatment of pleomorphic adenoma of the parotid gland in 245 patients, 1974-1994].

OBJECTIVE: To describe the results of parotidectomy for pleomorphic adenoma of the parotid gland in 245 patients, 1974-1994. DESIGN: Descriptive. SETTING: Academic Medical Hospital, Free University, Amsterdam, the Netherlands. METHOD: Of all patients follow-up data were obtained by yearly physical diagnostic examination during 10 years, and by a questionnaire (1995) from the general practitioners involved. RESULTS: In the period 1974-1994, 246 primary surgical parotid procedures were performed on 245 patients for pleomorphic adenoma. The surgical procedures included: 131 'partial' and 61 'complete' superficial parotidectomies, 30 partial superficial/ deep lobe parotidectomies, 8 total parotidectomies, and 16 'selective' deep lobe parotidectomies. Eleven patients received postoperative radiotherapy for different reasons. The median follow-up was 95 months. Fourteen patients died without recurrent tumour. Two patients (0.8%) developed a local recurrence, both after total parotidectomy for a deep lobe tumour. None of the patients experienced permanent facial nerve paresis or paralysis. The incidence of auriculotemporal sweating for partial superficial parotidectomy proved to be 6.9% (9/I31) as compared with 13.1% (8/61) for complete superficial parotidectomy. In the later years, in the majority of patients, the posterior branch of the greater auricular nerve was preserved. CONCLUSION: In the hands of the experienced head and neck surgeon partial parotidectomy is an effective treatment for the great majority of pleomorphic adenomas: local recurrence is rare, while in general morbidity is minimal. Rarely there is a need for prolonged follow-up.

Adenoma, Pleomorphic↗

Genetic susceptibility to head and neck squamous cell carcinoma.

BACKGROUND: In addition to influences of exposure to carcinogenic compounds, the development of cancer may depend on an individual intrinsic cancer susceptibility. Biomarkers for cancer susceptibility can be powerful additions to epidemiologic analyses. PURPOSE: This multicenter, case-control analysis combines previously published data and new data to substantiate the value of mutagen sensitivity as a biomarker of susceptibility to head and neck squamous cell carcinoma and, more importantly, to gain insight into the interaction between susceptibility and exposure to carcinogens. METHODS: Mutagen sensitivity (mean number of chromatid breaks per cell of cultured lymphocytes treated with bleomycin in the late S-G2 phase of the cell cycle) was determined in 313 patients with head and neck cancer and in 334 control subjects at two major U.S. medical institutions and one European institution, yielding a unique study population. The ages of the case and control subjects, as well as their history of use of tobacco and alcohol, were also recorded. The relationships between variables were analyzed by use of Student's t tests, Spearman's rank correlations, and multiple linear regression. For estimation of cancer risk, crude odds rations (ORs) were measured and multiple logistic regression was performed. All P values were based on two-sided tests. RESULTS: There were no differences across institutions in the distribution of mutagen sensitivity (Kruskal-Wallis test) for both case subjects and control subjects. Values for case subjects were consistently and significantly (P<.0001) higher than values for control subjects in the overall analyses. Age and tobacco or alcohol use did not influence the outcome in terms of mutagen-sensitivity values for either the case or the control subjects. A mean number of breaks per cell dichotomized at 1.0 was found to be the best predictor of a hypersensitive phenotype. For nonsensitive, heavy smokers, the OR was 11.5 (95% confidence interval [CI] = 5.0-26.6). This risk increased dramatically in mutagen-hypersensitive, heavy smokers to 44.5 (95% CI = 17.4-114.0). Multiple logistic regression analysis confirmed these results, and a significant trend was found (P<.01) for the dose-dependent increase in cancer risk by smoking. The consumption of alcohol potentiated the effects of smoking, resulting in an OR of 57.5 (95% CI = 17.5-188.0) in hypersensitive persons. CONCLUSIONS: Mutagen sensitivity was found to be a biomarker of cancer susceptibility. This study underscores the importance of utilizing both susceptibility markers and the exposure data for the identification of persons at high risk of developing cancer. IMPLICATIONS: More accurate risk estimation can define susceptible subgroups who might be targeted for intensive behavioral interventions, surveillance through screening, and enrollment in chemoprevention programs.

Adult↗

Potential early markers of carcinogenesis in the mucosa of the head and neck using exfoliative cytology.

Patients with head and neck squamous cell carcinoma (HNSCC) who are thought to be cured are at high risk of development of a secondary primary tumour in the mucosa of the upper aerodigestive tract and the lungs. This phenomenon is in agreement with the concept of 'field cancerization', which implies that the whole mucosa is potentially condemned to the development of neoplasia. The hypothesis advanced in this study was that early markers of carcinogenesis should therefore be present in all cells of the mucosa of patients with HNSCC. The expression of cytokeratin 16, cytokeratin 19, and histo-blood group antigen H (ABH), type 2 chain was analysed by means of immunocytochemistry on exfoliated cells taken from six sites of the upper aerodigestive tract of the 'healthy' mucosa of previously untreated HNSCC patients (n = 25) and controls (n = 10). Statistically significant differences were found in the mucosal expression of these markers between patients and controls. Since no overlap in ABH type 2 chain expression existed between patients and controls and the expression between sites in a given individual was highly correlated, this marker was considered the most promising of those tested. These data suggest that cytokeratin 16, cytokeratin 19, and ABH type 2 chain are markers of field cancerization in easily available exfoliated cells, which may be applied to monitor and/or predict the occurrence of second primary tumours.

ABO Blood-Group System↗

Age-dependence of human papillomavirus DNA presence in oral squamous cell carcinomas.

The aetiology of oral cancer is thought to be multifactorial. Apart from the two known major risk factors (tobacco and alcohol), a viral aetiology has been proposed, with special reference to human papillomavirus (HPV). 35 cases of oral squamous cell carcinoma (OSCC), seen at the Departments of Oral & Maxillofacial Surgery and Oral Pathology and Otolaryngology of the Free University of Amsterdam, were analysed as well as 12 biopsies of clinically and histologically normal gingival mucosa collected from healthy individuals after tooth extractions, using the polymerase chain reaction (PCR) and two different sets of primers that are able to detect a broad spectrum of HPV types. An overall HPV positivity of 54.3% in OSCC was found, the majority of positive cases (78.9%) harbouring HPV type 16. In contrast, no positivity for HPV was detected in the clinically normal oral mucosal samples analysed. Furthermore, a significant association between HPV presence and age was found: patients older than 60 years showed a lower prevalence of the virus (29.4%) compared with patients below this age (77.8%) (P < 0.05). The results from the present study suggest an association between HPV and OSCC, particularly in patients under the seventh decade.

Adult↗

Influence of the antioxidant N-acetylcysteine and its metabolites on damage induced by bleomycin in PM2 bacteriophage DNA.

Bleomycin is considered to be a useful model compound for studying environmental carcinogenesis, due to its broad spectrum of DNA damaging properties. In addition, bleomycin is a useful antitumor drug because of its cytotoxic properties. To investigate the influence of the antioxidant N-acetylcysteine and its metabolites glutathione and cysteine on bleomycin-induced DNA damage and more importantly to gain insight into the biological relevance of such damage, PM2 DNA was exposed to Cu(2+)-bleomycin in the presence and absence of the thiols N-acetylcysteine, glutathione and cysteine. It was found that the presence of these thiols led to a considerable enhancement of bleomycin-induced single- and double-strand breaks and a concomitant decrease in the biological activity of PM2 DNA in a dose-dependent way. A similar observation was made when ascorbic acid was used. Bleomycin showed no DNA damaging activity when PM2 DNA was pretreated with the strong Fe ion chelator desferal and its activity was strongly inhibited by the addition of Cu2+ ions or under hypoxic (N2) conditions. Cu(2+)-bleomycin under our conditions is not active by itself, but most probably after binding to DNA exchanges Cu2+ for Fe3+ bound to DNA. Fe(3+)-bleomycin is then reduced to Fe(2+)-bleomycin, a process potentiated by the added antioxidants, and subsequently activated by O2. The contribution to biological inactivation of bleomycin alone or in the presence of ascorbic acid is only approximately 15%. The contribution to lethality in the presence of thiols is higher. These results indicate that ascorbic acid only enhances the DNA damaging properties of bleomycin, whereas the thiol compounds in addition influence the type of DNA damage. The remainder of the biological inactivation is probably caused by double damage, such as single-strand breaks with closely opposed alkali-labile sites or base damage.

Acetylcysteine↗

The incidence of micrometastases in neck dissection specimens obtained from elective neck dissections.

Although modern imaging techniques become more accurate for the assessment of lymph node metastases in the neck as criteria and technology evolve, micrometastases remain occult with any technique. Even the routine histopathological examination of neck dissection specimens is unable to detect all micrometastases. Because knowledge on the incidence of micrometastases in the clinically NO neck might be of importance for decision making regarding elective treatment, a retrospective study on 96 elective neck dissections was conducted. Meticulous histopathological examination of the neck dissection specimens yielded 3092 lymph nodes of which 67 (2.2%) were tumor-positive. Twenty-six of these 67 lymph node metastases were micrometastases. Of the 36 tumor-positive neck dissection specimens, 21 contained micrometastases. In 9 tumor-positive specimens only micrometastases were found. This high incidence of micrometastases has important implications for the diagnostic work-up, the treatment, and histopathological examination of the NO neck.

Carcinoma, Squamous Cell↗

Primary non-Hodgkin's lymphoma of the salivary glands. An analysis of 22 cases.

Twenty-two patients with primary non-Hodgkin's lymphoma (P-NHL) of the salivary glands have been studied with reference to age, sex, clinical symptoms, location of primary tumor, histological subtype, grade of malignancy according to the Working Formulation, stage of disease, treatment and follow up. The clinical features corresponded with previously reported data on salivary gland lymphomas. The most frequent histological diagnosis was MALT lymphoma. Most patients had a localised low-grade lymphoma. Overall survival was influenced by grade of malignancy according to the Working Formulation.

Adult↗