Search PubMed⌕ Search

Biomedical subjects

G B Snow

Publications and source records attributed to G B Snow.

At least 55 records · Page 3Linked to original sources
PubMed1999

Outcome of observing the N0 neck using ultrasonographic-guided cytology for follow-up.

OBJECTIVE: To assess the outcome of patients who underwent transoral tumor excision and a wait-and-see policy for the NO neck, using ultrasonographic-guided fine-needle aspiration cytology (US-FNAC) of the neck for both selecting patients for neck treatment or observation and for follow-up. DESIGN: Retrospective outcome analysis of a patient cohort without palpable or US-FNAC detectable nodal metastases undergoing transoral tumor excisions. Patients were followed up for 1 to 4 years using palpation and US-FNAC. SETTING: Academic center. PATIENTS: A consecutive sample of 77 patients mainly with oral carcinomas. Excluded were patients who had neck dissections, radiotherapy, or no US-FNAC during follow-up. INTERVENTION: Transoral tumor excision. Neck dissection with radiotherapy for regional failure. OUTCOME MEASURE: The recurrence rate in the neck, without failure at the primary site and the salvage rate of these neck recurrences were the most important measures. Treatment delay and histopathologic findings were assessed as well. RESULTS: Fourteen patients (18%) had occult lymph node metastases and neck failures. Of the 14 neck failures, 9 were detected within 7 months of which 6 were not palpable. Ten (71%) of these 14 patients were successfully salvaged, and 4 died of uncontrolled disease. Three of the 4 patients also had distant metastases. CONCLUSIONS: The low recurrence rate (18%) can be attributed to the initial US-FNAC. The high salvage rate (71%) indicates that strict US-FNAC follow-up enables early detection of recurrence in the neck. A wait-and-see policy thus seems warranted, provided regular US-FNAC examinations during follow-up can be guaranteed.

Adult↗
PubMed1999

Plasma retinoid levels in head and neck cancer patients: a comparison with healthy controls and the effect of retinyl palmitate treatment.

Vitamin A and related compounds, also known as retinoids are thought to play a role in the development of head and neck cancer. We measured levels of the major retinoids, retinol, all-trans retinoic acid, 13-cis retinoic acid and 13-cis-4-oxo retinoic acid in plasma of head and neck cancer patients in comparison with controls without cancer. No differences were found between plasma levels of these retinoids between 25 head and neck cancer patients and 21 controls. Mean baseline levels for the patients were 2458. 6.0, 6.4 and 8.6 nM for retinol, all-trans retinoic acid, 13-cis retinoic acid and 13-cis-4-oxo retinoic acid, respectively. In addition, we selected 10 patients from the chemoprevention trial Euroscan and measured the effect on retinoid levels of 300,000 I.U. daily retinyl palmitate intake during 1 month. Medication caused significant elevations in retinol levels (1.2 fold), all-trans retinoic acid (2.2 fold) and its metabolites 13-cis retinoic acid (5.8 fold) and 13-cis-4-oxo retinoic acid (8.9 fold). Because of its high increase in levels, 13-cis-4-oxo retinoic acid seems a good candidate to serve as a suitable marker to monitor patient compliance in future chemo-prevention trials involving retinoids. No relations were found between the occurrence of side-effects of retinyl palmitate and retinoid levels during treatment. However, the two patients who developed side-effects had the highest pre-treatment levels of 13-cis retinoic acid and 13-cis-4-oxo retinoic acid, suggesting that retinoid toxicity is associated with relatively high basal retinoid metabolism.

Anticarcinogenic Agents↗
PubMed1999

A comparison of bleomycin-induced damage in lymphocytes and primary oral fibroblasts and keratinocytes in 30 subjects.

The number of chromatid breaks in peripheral blood lymphocytes (PBL) after exposure to bleomycin in the S/G2 phase of the cell cycle (in the literature referred to as 'mutagen sensitivity') is associated with an increased risk of environmentally related cancers, including oral cancer. The aim of this study was to elucidate whether mutagen sensitivity measured in lymphocytes actually reflects chromosomal instability of normal cells in the areas in which tumors develop. Therefore, bleomycin-induced chromosomal damage in and growth inhibition of cultured oral fibroblasts and oral keratinocytes from 30 persons were compared with the standard mutagen sensitivity score in PBL. A correlation was found for the percentage of aberrant metaphases between PBL and oral fibroblasts but not for the number of breaks per cell. These data do not allow a conclusion to be drawn on the use of fibroblasts to study cancer risk. Within the fibroblasts it was found that a high number of breaks per cell was associated with less growth inhibition, indicative of damage-resistant growth. Oral keratinocytes were extremely sensitive to bleomycin, as indicated by a strong cell cycle block which resulted in a mitotic index too low to determine chromosomal breaks. Moreover, in the cell proliferation assay keratinocytes were found to be 100 times more sensitive as compared with fibroblasts. There was no correlation between bleomycin sensitivity of keratinocytes compared with fibroblasts from a single patient as measured by growth inhibition. This may be due to the strong influence of alcohol consumption by the subjects, which was found to increase the sensitivity of keratinocytes but not of PBL and fibroblasts. In conclusion, oral fibroblasts but not keratinocytes can be used to measure sensitivity for chromatid breaks. The apparent influence of environmental factors on keratinocytes makes them a useful source to study exposure characteristics but limits their application for the determination of genetic factors.

Adult↗
PubMed1999

Mutagen sensitivity in common cutaneous malignant melanoma and dysplastic naevus syndrome.

Sunlight (ultraviolet radiation) has been identified as the major environmental risk factor for the development of cutaneous malignant melanoma and dysplastic naevi. This is, however, not sufficient to explain all melanoma cases. In recent years much emphasis has been given to genetic susceptibility to melanoma. A biomarker of susceptibility to environmentally related cancer is mutagen sensitivity. This is measured as the number of chromatid breaks in lymphocytes which are exposed to bleomycin in the G2 phase of the cell cycle. It has been described that patients with common melanoma show an increased mutagen sensitivity compared with controls. In the present study mutagen sensitivity was measured in 10 dysplastic naevus syndrome patients and compared with that in 11 patients with common melanoma. We found similar results for common melanoma patients as have been reported earlier: a relatively high mean breaks per cell value (0.93 +/- 0.31). In contrast, melanoma patients with dysplastic naevi showed a significantly (P<0.01) lower mutagen sensitivity value (0.46 +/- 0.34). This phenomenon was even more pronounced when only hereditary dysplastic naevi patients (one or more family members with dysplastic naevi) were considered (n = 5; 0.24 +/- 0.05). These results suggest a difference in the initiation of the carcinogenic process in melanoma with a dysplastic naevus as a precursor and melanoma without dysplastic naevi.

Adolescent↗
PubMed1999

Sensitive detection of squamous cells in bone marrow and blood of head and neck cancer patients by E48 reverse transcriptase-polymerase chain reaction.

In previous studies, we described the selective reactivity of monoclonal antibody E48 with normal squamous and transitional epithelia and their malignant counterparts and the capacity of monoclonal antibody E48 for selective tumor targeting in head and neck cancer patients. Cloning of the E48 encoding cDNA and elucidation of the gene structure enabled the selection of an intron-spanning primer set for the detection of circulating tumor cells in blood and bone marrow of head and neck cancer patients. Extensive optimizations led to a reproducible reverse transcriptase-PCR assay with an internal standard for RNA quality control and an external standard for sensitivity control. In reconstruction experiments, we were able to reach a reproducible sensitivity of one single tumor cell per 7 ml of blood (2 x 10(7) nucleated cells). When applying this method to patient material, we were able to detect positive signal in 35% of the bone marrow samples (0 of 2 stage II, 0 of 4 stage III, 4 of 11 stage IV, and 4 of 6 recurrences) and 10% of the blood samples (2 of 21) of patients with squamous cell carcinoma of the head and neck. The specificity of the method was demonstrated on 29 blood and bone marrow samples of noncancer controls, which were all negative. Our study shows the feasibility of E48 reverse transcriptase-PCR for the detection of squamous cells in nonsquamous tissues.

Adult↗
PubMed1999

Sonographically guided aspiration cytology of neck nodes for selection of treatment and follow-up in patients with N0 head and neck cancer.

BACKGROUND AND PURPOSE: The management of the clinically negative neck (NO) remains controversial because the incidence of occult metastases is high and the prognostic difference between elective treatment and a "wait and see" approach remains unclear. This study was undertaken to assess the role of sonographically guided aspiration cytology for the selection of the initial-management strategy for the neck and for the early detection of neck metastases during follow-up of patients with NO. METHODS: Seventy-seven clinically and cytologically confirmed NO patients, who underwent a transoral tumor excision and no neck treatment, were followed up for 1 to 4 years by both palpation and sonographically guided aspiration cytology. RESULTS: Fourteen patients (18%) had recurrent neck tumor; 10 (71%) of these necks were salvaged. Of the 14 neck failures, six were detected before being palpable and nine were detected within 7 months. Eleven of the 19 aspirated tumor-positive nodes had a minimal diameter smaller than 1 cm, and all four patients who eventually died had lymph node metastases larger than 14 mm. CONCLUSION: With sonographically guided aspiration cytology, the risk of missing occult metastases was 18%, which is less than expected after palpation only. Sonographically guided aspiration cytology is an effective technique for following up on the status of the neck after transoral tumor excision, and should be used at frequent intervals if no elective neck treatment is performed.

Adult↗
PubMed1999

Evaluation of soluble CD44v6 as a potential serum marker for head and neck squamous cell carcinoma.

In recent years, the measurement of soluble CD44 levels in the circulation of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the detection of human cancer. The high CD44v6 expression in head and neck squamous cell carcinoma (HNSCC) would enable the use of soluble CD44v6 proteins present in the circulation of HNSCC patients as a marker of disease. In the present study, we determined CD44v6 plasma levels using a domain-specific ELISA in healthy volunteers, non-cancer patients, and HNSCC patients before and after surgical removal of the tumor. A difference between the CD44v6 plasma levels of HNSCC patients and controls could not be observed. Moreover, surgical removal of the tumor did not result in a reduction of the CD44v6 plasma level in the HNSCC patients. In addition, the spectrum of soluble v6-containing CD44 proteins present in the plasma of HNSCC patients and controls was determined by immunoprecipitation experiments, but again, tumor-related isoforms could not be distinguished in patient samples. Additional experiments to unravel the biological source of these circulating proteins indicated surprisingly that the v6-containing proteins present in the circulation of healthy individuals are only released in part, if at all, by activated lymphocytes or other nucleated blood cells. Most circulating CD44v6 proteins seem to be derived from the normal epithelial cell compartments, including breast cells, colon cells, and squamous cells. Taken together, these data do not support the use of soluble CD44v6 as a tumor marker in HNSCC or any other tumor type that has developed from tissues producing soluble isoforms.

Antibodies, Monoclonal↗
PubMed1998

Perspectives of combined radioimmunotherapy and anti-EGFR antibody therapy for the treatment of residual head and neck cancer.

Rhenium-186 based radioimmunotherapy (RIT) may have potential for the treatment of minimal residual disease in patients with squamous cell carcinoma of head and neck (HNSCC). In an effort to enhance the efficacy of RIT, we evaluated the combination of RIT and anti-epidermal growth factor receptor (EGFR) therapy in nude mice bearing established HNSCC s.c. xenografts. For this purpose we used the EGFR-blocking monoclonal antibody (MAb) 425. Treatment of HNSCC-bearing mice with the combination of a single administration of 200 microCi 186Re-labeled MAb U36 as well as 1.1 mg unlabeled MAb 425 showed an enhanced efficacy in comparison to the single treatments. When 500 microCi 186Re-labeled MAb U36 were administered, all tumors eventually regressed completely. The combination of this RIT treatment with multiple injections of MAb 425 significantly increased the rate of tumor regression. Although RIT with 186Re-labeled MAbs appears to be very efficient on HNSCC xenografts, the combination with anti-EGFR MAb 425 may enhance the efficacy.

Animals↗
PubMed1998

p53 expression above the basal cell layer in oral mucosa is an early event of malignant transformation and has predictive value for developing oral squamous cell carcinoma.

Epithelial dysplasia is usually used to establish the prognosis of oral premalignant lesions. Its assessment, however, is subjective and does not always correctly predict the outcome of the lesions in terms of malignant transformation. Early molecular alteration(s) that dictate the development of cancer should be identified and used to evaluate oral premalignant lesions. In this context, alterations in the expression of p53 were investigated. Thirty-five oral premalignant lesions and 11 carcinomas that developed from them in a period of 16 years were investigated for p53 expression by immunohistochemistry. Normal oral mucosa from healthy individuals and oral benign lesions were used as controls. In benign lesions and normal mucosa, p53 staining, when present, was confined to the basal cell layer. Seven out of 35 (20 per cent) premalignant lesions showed p53 expression clearly above the basal cell layer and six of these (86 per cent) developed carcinomas. Suprabasal p53 expression was found in three lesions with no or mild dysplasia that developed carcinomas. All carcinomas derived from premalignant lesions with p53 suprabasal expression showed p53 expression in neoplastic cells. The combined use of histological parameters (presence of moderate or severe dysplasia) with p53 expression patterns (p53 staining above the basal cell layer) showed the highest sensitivity for the detection of lesions that progressed to carcinoma (91 per cent). When used individually, the p53 expression pattern showed higher specificity than assessment of dysplasia (96 per cent vs. 54 per cent) and higher positive predictive value (86 per cent vs. 44 per cent) for correct prediction of the malignant transformation of the lesions. The results suggest that clear expression of p53 above the basal cell layer is an early event in oral carcinogenesis and an indicator of a developing carcinoma, even preceding morphological tissue alterations. However, since immunohistochemistry cannot always detect changes in p53 expression in lesions preceding carcinoma, p53 immunohistochemical analysis is strongly recommended in conjunction with histological parameters, to increase the sensitivity of detection of cases that will progress to carcinoma.

Adult↗
PubMed1998

Parotid gland tumors: histologic reevaluation and reclassification of 478 cases.

BACKGROUND: The histologic classification of epithelial salivary gland tumors may present difficulties due to their great morphologic diversity. METHODS: In this study, 478 parotid gland tumors were reevaluated and reclassified according to the 1991 WHO histologic classification of salivary gland tumors. RESULTS: In 56 cases, the original diagnosis was changed, either within the benign or the malignant tumor group. In six cases (1.3%), the original diagnosis was changed from benign to malignant or vice versa. CONCLUSIONS: During the mean follow-up period of 10.3 years, no events occurred supporting or rejecting the proposed change in diagnosis in these six patients. With regard to the three cases in which an original malignant diagnosis was made, the possibility of an overdiagnosis, and therefore an overtreatment, remains.

Female↗
PubMed1998

The impact of tumour volume and other characteristics on uptake of radiolabelled monoclonal antibodies in tumour tissue of head and neck cancer patients.

Radioimmunotherapy (RIT) seems to be a realistic option for eradication of minimal residual squamous cell carcinoma of the head and neck (HNSCC), although uptake levels of radiolabelled monoclonal antibodies (MAbs) in tumour tissue vary strongly. The aim of this study was to obtain greater insight into the factors influencing the accumulation of MAbs in HNSCC. Twenty-seven HNSCC patients were injected with radiolabelled MAb E48 or U36 and underwent surgery 2 days after injection. Radioactivity was measured in tumour biopsies taken from the surgical specimen. Uptake levels were correlated with various patient, tumour and MAb characteristics, including age, sex, site, TNM stage, volume as assesssed by computed tomography or magnetic resonance imaging, degree of differentiation, antigen expression of the tumour, the particular MAb that had been injected and the MAb dose. A stepwise regression multivariate analysis showed that tumour volume is the most significant prognostic factor (P=0. 01) for MAb uptake. In conclusion, a significantly higher MAb uptake is found in small tumours as compared to larger tumours. Therefore, RIT may be particularly effective in head and neck cancer patients when used in an adjuvant setting.

Aged↗
PubMed1998

Assessment of tumour invasion into the mandible: the value of different imaging techniques.

In oral carcinomas close to the mandible, tumour invasion of the mandible is important in selecting segmental or marginal resection. Imaging may play a role in assessing tumour invasion. This study compares the accuracy of panoramic X-ray, CT and MR imaging in assessing invasion of the mandible in 29 patients. At histopathology, 6 patients had mandible erosion, 12 had invasion and 11 had an intact mandible. Magnetic resonance imaging had the highest sensitivity (94%), but a low specificity (73%), with 3 of 11 intact mandibles interpreted as positive. Furthermore, MR often overestimated the extent of tumour invasion. On the other hand, CT and panoramic X-ray had a lower sensitivity (64 and 63%, respectively) and a higher specificity (89 and 90%, respectively). Computed tomography (using 5-mm sections) and panoramic X-ray had a similar accuracy, and negative findings do not exclude invasion. Magnetic resonance imaging was the most sensitive technique but had more false positives and frequently overestimated the extent of tumour invasion. Because none of the radiological techniques are accurate enough, clinical examination seems at present to remain the most important modality in deciding between segmental and marginal resection. Tumour invasion at CT or panoramic X-ray is a strong argument for a segmental resection.

Adult↗
PubMed1998

Management of benign lymphoepithelial lesions of the parotid gland in human immunodeficiency virus-positive patients.

The diagnosis and radiotherapeutic treatment of these HIV-associated benign lymphoepithelial lesions in the parotid gland are discussed. As an example of these lesions, a case is presented involving a 43-year-old HIV-infected man with a 2-year history of enlargements in both parotid glands. After evaluation by computer tomography and cytology, the diagnosis of benign lymphoepithelial lesions was made. Treatment by low-dose radiotherapy (15 Gy) caused regression of both lesions. The lesion on the left regressed completely, but the one on the right side responded only partially. A second course of high-dose radiotherapy (24 Gy) to the right lesion caused regression to a cosmetically acceptable size.

Adult↗
PubMed1998

Diagnostic evaluation of the neck.

Modern imaging for neck node metastases has increased our ability to predict the presence of palpably occult metastases and predict the resectability of large metastases. The accuracy of CT scans, MR imaging, but especially US-FNAC, has increased to such an extent that clinical consequences are being attached to negative radiologic findings in a clinically N0 neck. As not all palpably occult metastases can be detected, especially when they are micrometers, follow-up should be strict, with use of US-FNAC in the neck observed instead of treated electively.

Head and Neck Neoplasms↗
PubMed1998

Differences in immune status between well-nourished and malnourished head and neck cancer patients.

Malnutrition is reported to occur in approximately 30% of head and neck cancer patients. Also, impaired immunocompetence is described as a common phenomenon in this patient group. The purpose of this study was to assess the possible relationship between malnutrition and some prognostically important immune parameters in head and neck cancer patients. Thirty-two malnourished (recent weight loss >/= 10%) and 34 well-nourished patients undergoing curative treatment for advanced head and neck cancer were studied prospectively, and six parameters of their immune status (leucocytes, lymphocytes, lymphocyte phenotyping, monocytes, HLA-DR expression on monocytes and serum interleukin-10) were determined on the day of panendoscopy. Reference values for monocytes, HLA-DR expression and interleukin-10 were obtained from 43 healthy controls. Although the number of monocytes was elevated in both patient groups, the HLA-DR expression on these monocytes was significantly lower in the malnourished than in the well-nourished and control groups. Tumor stage, tumor localization, recurrence after initial radiotherapy, age and gender were not correlated to HLA-DR expression. No relationships emerged between nutritional status and lymphocyte subsets. Malnourished head and neck cancer patients show a significantly lower HLA-DR expression on monocytes than well-nourished ones and healthy controls. According to the literature this would imply an increased risk for postoperative complications. Indeed, postoperative complications occur more frequently in malnourished than in well-nourished patients.

Adult↗
PubMed1998

Synthesis and evaluation of 99mTc/99Tc-MAG3-biotin conjugates for antibody pretargeting strategies.

Four 99mTc-MAG3-biotin conjugates were synthesized to determine their potential use in antibody pretargeting strategies for radioimmunoscintigraphy (RIS). To use these 99mTc-MAG3-biotin conjugates as model compounds for 186Re-MAG3-biotin conjugates for radioimmunotherapy (RIT), nanomolar amounts of 99Tc were added as carrier to 99mTc. The biotin derivatives used for the preparation of the conjugates-biocytin, biotin hydrazide, biotinyl-piperazine, and biotinyl-diaminosuccinic acid-differed at the site that is regarded to be susceptible to hydrolysis by biotinidase present in human plasma. All four conjugates were produced with high radiochemical purity, were stable in PBS, and demonstrated full binding capacity to streptavidin. The 99mTc/99Tc-MAG3-labeled biotinyl-piperazine and biotinyl-diaminosuccinic acid conjugates were stable in mouse as well as human plasma, whereas the corresponding biocytin and biotin hydrazide conjugates were rapidly degraded. The biodistribution in nude mice at 30 min after injection was similar for all conjugates, and a rapid blood clearance and high intestinal excretion were both observed. It is concluded that the metabolic routing of a conjugate containing biotin and MAG3 is dominated by these two moieties. For this reason, MAG3-biotin conjugates do not seem suited for pretargeted RIT, for which quantitative and fast renal excretion is a prerequisite to minimize radiation toxicity. However, in a pretargeted RIS approach the 99mTc-MAG3-biotin conjugates might have potential.

Animals↗
PubMed1998

Malignant epithelial parotid gland tumours: analysis and results in 65 previously untreated patients.

BACKGROUND: Optimal management of malignant epithelial parotid tumours requires knowledge of the available therapeutic modalities and the different biological characteristics. The aim of the study was to review the characteristics of patients at presentation, histological classification, disease-free and overall survival rates, and the results of the applied treatment policy regarding the facial nerve and neck. METHODS: Between 1974 and 1995 a total of 65 patients was treated with curative intent for a previously untreated malignant epithelial parotid gland tumour. All patients underwent some type of parotidectomy, 20 of whom had an en bloc radical neck dissection. In selected cases the facial nerve or its branches were peeled off the tumour thus violating the objective of tumour-free margins and relying heavily on the efficacy of postoperative radiotherapy. In total 51 patients received postoperative radiotherapy. None of the patients was lost to follow-up. RESULTS: There were 12 locoregional failures (18 per cent). In only one of these 12 patients was salvage therapy successful; the remaining 11 patients died from the tumour. All but one of the eight patients with distant metastasis only died from the tumour. The estimated 5- and 10-year disease-free rates were 68 and 59 per cent respectively. The corresponding survival rates were 75 per cent and 67 per cent. A significant relationship could be observed between tumour stage and survival. The presence of lymph node metastases proved to be the strongest single prognostic factor. CONCLUSION: In selected cases a conservative approach towards the facial nerve is justified.

Adolescent↗