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Biomedical subjects

Randal S Weber

Publications and source records attributed to Randal S Weber.

At least 19 recordsLinked to original sources
PubMed2007

Radiation-induced xerostomia.

BACKGROUND: Radiation-induced xerostomia is a frequent and usually permanent side effect of radiation therapy for head and neck cancer. We summarize recent developments in the prevention and treatment of radiation-induced xerostomia. METHODS: The Medline database was searched for articles published within the past 10 years on the prevention and treatment of postirradiation xerostomia. Proceedings of recent important national meetings and government Web registries of clinical trials and therapeutic agents were also consulted. Priority was given to randomized controlled trials but, because of the scarcity of such trials, small open trials were included in this review. No other predetermined selection criteria were used, although articles exploring the effects of xerostomia and its treatment on quality of life were considered of special interest. RESULTS: A variety of preventive approaches for postirradiation xerostomia exist, involving more conformal radiation delivery technology, radioprotective agents, and even preirradiation surgical techniques. Therapeutic interventions include supportive care, saliva supplementation, and the use of pro-cholinergic salivary secretagogues. CONCLUSIONS: Radiation-induced xerostomia constitutes a significant morbidity after orofacial irradiation. Careful preventive techniques, meticulous supportive care, and new preventive and therapeutic agents may prove useful in combination.

Animals↗
PubMed2006

Implications of methylation patterns of cancer genes in salivary gland tumors.

PURPOSE: We investigated the methylation status and protein expression of four tumor suppressor genes to determine their role in salivary gland tumorigenesis. EXPERIMENTAL DESIGN: We performed methylation-specific PCR and protein analyses of 29 normal salivary glands, 23 benign, and 79 malignant salivary gland neoplasms to determine the pattern and potential diagnostic and/or biological role of the RASSF1, RARbeta2, DAPK, and MGMT tumor suppressor gene methylation in these tumors. RESULTS: No methylation was detected in the normal tissues. Methylation occurred in 9 of 23 (39.1%) benign tumors; 3 (25.0%) pleomorphic adenomas and 6 (66.7%) Warthin's tumors at the MGMT, DAPK, or RASSF1 genes. Methylation occurred in 33 of 79 (41.8%) malignant tumors; 8 (30.8%) adenoid cystic carcinomas, 6 (33.3%) mucoepidermoid carcinomas, 6 (42.9%) acinic cell carcinomas, and 13 (62.0%) salivary duct carcinomas. RASSF1 and RARbeta2 represented 75.8% of methylation events occurring most frequently in salivary duct and acinic cell carcinomas. Overall, we found no significant correlation between protein expression and methylation status of individual genes, but observed low or absent protein expression in several methylated tumors. Significant correlations were found between methylation and aggressive malignant phenotypes (P = 0.0004) and age (P = 0.05). CONCLUSIONS: (a) Benign and malignant salivary tumors differed in the frequency and pattern of gene methylation; (b) high-grade carcinomas were significantly methylated compared with low-grade phenotypes; (c) RASSF1 and RARbeta2 were highly methylated in malignant tumors and can be targeted for therapy; and (d) methylation pattern may serve as a diagnostic and biological marker in assessing these tumors.

Adolescent↗
PubMed2006

4-Nitroquinoline-1-oxide-induced mutagen sensitivity and risk of nonmelanoma skin cancer: a case-control analysis.

The UV radiation-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) is thought to induce squamous cell carcinoma (SCC) similar to those induced by UV radiation in animals. Therefore, we tested the hypothesis that cellular sensitivity to 4-NQO is associated with risk of developing skin cancer in a case-control study of 191 patients with nonmelanoma skin cancer (NMSC; 81 SCC and 110 basal cell carcinoma (BCC)) and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 microM for 24 hours and scored for chromatid breaks in 50 well-spread metaphases. We found that the mean frequency of chromatid breaks per cell (b/c) was significantly higher in the cases (mean+/-SD, 0.46+/-0.43 for SCC and 0.43+/-0.38 for BCC) than in the controls (0.25+/-0.25; P<0.001 for both comparisons) and were associated with more-than-twofold increased risk for both SCC and BCC after adjustment for known risk factors. Therefore, our findings support the notion that sensitivity to 4-NQO reflects susceptibility to UV-induced NMSC. However, there is a lack of correlation between UVB-induced b/c and 4-NQO-induced b/c in this study population. Therefore, these findings need to be verified by additional studies.

4-Nitroquinoline-1-oxide↗
PubMed2006

Technetium Tc 99m sestamibi sensitivity in oxyphil cell-dominant parathyroid adenomas.

OBJECTIVE: A subset of parathyroid adenomas contains a relative overabundance of oxyphil cells that are capable of greater technetium Tc 99m sestamibi tracer uptake and retention than other cell types. We examined whether the presence of oxyphil cells augments the sensitivity of technetium Tc 99m sestamibi preoperative localization and whether the histologic findings of a lesion could be predicted based on the adenoma mass and serum calcium and parathyroid hormone levels. DESIGN: Retrospective, single-blinded comparison of technetium Tc 99m sensitivity rates, lesion mass, and preoperative serum calcium and parathyroid hormone values of patients with chief and mixed cell-dominant adenomas and those with oxyphil-dominant parathyroid adenomas. SETTING: Tertiary care university hospital. PATIENTS: Sixty-three patients diagnosed as having a parathyroid adenoma. INTERVENTION: All patients underwent resection of a parathyroid adenoma following a preoperative technetium Tc 99m sestamibi localization study and serum calcium and parathyroid hormone level analysis. MAIN OUTCOME MEASURE: Technetium Tc 99m sensitivity rate. RESULTS: The overall technetium Tc 99m sestamibi sensitivity rate was 76.2%. The sensitivity within the chief and mixed cell-dominant (n = 52) and oxyphil cell-dominant groups (n = 11) were 71.2% and 100%, respectively (P = .04). There was no correlation between histologic findings of the lesion and its size or serum calcium and parathyroid hormone levels. CONCLUSIONS: Oxyphil cell predominance within an adenoma augments technetium Tc 99m sestamibi scan sensitivity in a statistically significant manner. The use of technetium Tc 99m sestamibi preoperative localization may therefore be differentially greater in patients with these types of lesions.

Chi-Square Distribution↗
PubMed2006

Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: is it necessary for all?

In the absence of large-scale randomized trials evaluating dissection versus observation of the involved neck after neoadjuvant chemoradiotherapy, there is a need to collect data that will either support or ultimately refute a role for planned posttreatment neck dissection. A significant percentage of patients with extensive (N2 or N3) neck disease who demonstrate a complete response to chemoradiation therapy may harbor residual occult metastases, and identification of this subset of patients remains a clinical challenge. Because surgical salvage rates are greatly diminished when occult nodal disease becomes clinically manifest, planned posttreatment neck dissection is advocated but may not be necessary in all patients. The role of positron emission tomography chemoradiotherapy (PET-CT) in this scenario remains unproven but holds promise in being able to identify which patients may be harboring residual disease in the neck after chemoradiotherapy. The implementation of as yet unidentified molecular tumor markers in combination with PET-CT may ultimately prove to be effective in identifying patients who will best benefit from posttherapy neck dissection. Correlation of imaging results and pathologic node status will be important in determining the accuracy and, therefore, the value of this imaging modality for predicting the presence or absence of residual disease.

Carcinoma, Squamous Cell↗
PubMed2006

Isolated cervical esophageal reconstruction for rare esophageal tumors.

BACKGROUND: Isolated defects in the cervical esophagus in patients who have not undergone total laryngectomy are uncommon. We report 2 cases of rare esophageal tumors requiring reconstruction of the cervical esophagus after tumor resection. METHODS AND RESULTS: The patients were a 51-year-old woman with an esophageal granular cell tumor and a 54-year-old woman with an esophageal schwannoma. Both defects were reconstructed with a radial forearm flap. A small subclinical leak developed in 1 patient and healed spontaneously within 2 weeks. At 1 year and 2 years of follow-up, both patients were consuming a normal diet and had normal voices. CONCLUSIONS: A thin and well-vascularized flap such as the radial forearm flap is essential for reconstructing an isolated cervical esophageal defect so as to maximize functional outcome.

Cervicoplasty↗
PubMed2006

Importance of patient examination to clinical quality assurance in head and neck radiation oncology.

BACKGROUND: When quality assurance programs in clinical radiation oncology focus mainly on the technical aspects of treatment, they tend to underplay questions of therapeutic process and outcome. We determined the value of clinical peer review in radiation therapy for head and neck cancer that involved head and neck examination. METHODS: Data were collected prospectively on 134 consecutive patients with preliminary radiation therapy (RT) plans. Peer review was performed that included head and neck examination and imaging review to confirm target localization. RESULTS: Peer review led to changes in treatment plans for 66% of patients. Most changes were minor, but 11% of changes were major and thought to be of a magnitude that could potentially affect therapeutic outcome or normal tissue toxicity. Most changes involved target delineation based on physical findings CONCLUSIONS: Peer review of radiation target localization in RT plans led to changes that could potentially affect rates of cancer control or complication in about 10% of patients. We suggest that the accuracy of head and neck radiation oncology treatment plans might be increased by co-examination by another head and neck cancer specialist, typically a radiation oncologist or head and neck surgeon, to confirm RT target volumes.

Clinical Competence↗
PubMed2006

Preliminary investigation of symptom distress in the head and neck patient population: validation of a measurement instrument.

OBJECTIVE: Observations indicate that the acute toxicity of chemoradiation for squamous cell carcinoma (SCC) of the head and neck is not the same as that which occurs with radiation therapy alone. Thus, the specific aim of this pilot study was to estimate the reliability and validity of a modified version of a symptom distress scale used to assess the qualitative difference in symptom distress between the 2 populations. METHODS: Over a period of 4 months a consecutive sample of 56 patients with head and neck cancer were recruited from the Department of Radiation Oncology to take part in our pilot study. The Cancer Disease and Treatment Concern Scale (CDTCS) was modified by adding 15 additional items and called the Head and Neck Distress Scale (HNDS). All dimensions were interrogated with at least four questions and a domain score was generated. In addition, the Head and Neck Radiotherapy Questionnaire (HNRQ), an established 22-item multidimensional questionnaire was also administered by interview after completion of the HNDS. RESULTS: Fifty-six patients, 32 chemoradiation patients (mean age 64 years) completed the HNDS, taking 8 to 10 minutes to complete. The HNDS scores correlated well with the HNRQ scores (r = 0.835), demonstrating an acceptable level of content and concurrent validity. There was a significant difference in the overall HNDS scores between the chemoradiation group and the radiation therapy group (ANOVA, P = 0.001). CONCLUSION: The HNDS is a valid measure of acute symptom distress and appears able to discriminate between the chemoradiation and radiation alone patients. There is considerable variation in symptoms that cause these patients distress.

Adult↗
PubMed2006

Intensity-modulated radiation therapy and xerostomia.

Conformal radiation with intensity-modulated radiation therapy, IMRT, is a radiation technique that potentially can minimize the dose to salivary glands and thereby decrease the incidence of xerostomia. Precise target determination and delineation is most important when using salivary gland-sparing techniques of IMRT. The reduction of xerostomia may be achieved by sparing the salivary glands on the noninvolved oral cavity and keeping the mean parotid gland dose of < 26-30 Gy if the treatment of disease is not compromised and parotid function preservation is desired.

Head and Neck Neoplasms↗
PubMed2005

In vitro sensitivity to ultraviolet B light and skin cancer risk: a case-control analysis.

BACKGROUND: Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established. METHODS: We assessed in vitro UVB-induced chromatid breaks in a hospital-based case-control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher (P = .001 and P < .001, respectively), but that in CMM case patients (mean = 0.30 breaks per cell, 95% CI = 0.28 to 0.33) was not (P = .22). A frequency of chromatid breaks per cell above the median of control subjects was associated with nearly threefold increased risks for BCC (OR = 2.78, 95% CI = 1.79 to 4.30) and SCC (OR = 2.62, 95% CI = 1.50 to 4.60), but not with an increased risk of CMM. A dose-response relationship was evident between mutagen sensitivity and risk for both BCC (Ptrend < .001) and SCC (Ptrend < .001). Multiplicative interactions between mutagen sensitivity and sun exposure variables on risk, particularly for sunburn in BCC and hair color, tanning ability, and family history of skin cancer in SCC, were seen for NMSC but not CMM. CONCLUSIONS: UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM.

Adult↗