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Biomedical subjects

Thom R Loree

Publications and source records attributed to Thom R Loree.

At least 19 recordsLinked to original sources

Chemoprevention of head and neck cancer with aspirin: a case-control study.

OBJECTIVE: To evaluate the chemopreventive potential of aspirin against head and neck cancer. DESIGN: Hospital-based case-control study. SETTING: National Cancer Institute-designated comprehensive cancer center. Patients Individuals who received medical services at the Roswell Park Cancer Institute, Buffalo, NY, between 1982 and 1998 and who completed a comprehensive epidemiologic questionnaire. MAIN OUTCOME MEASURE: Aspirin use among 529 patients with head and neck cancer and 529 hospital-based control subjects matched by age, sex, and smoking status. RESULTS: Aspirin use was associated with a 25% reduction in the risk of head and neck cancer (adjusted odds ratio, 0.75; 95% confidence interval, 0.58-0.96). Consistent risk reductions were also noted in association with frequent and prolonged aspirin use. Further, a consistently decreasing trend in risk was noted with increasing duration of aspirin use (P(trend) = .005). Risk reduction was observed across all 5 primary tumor sites, with cancers of the oral cavity and oropharynx exhibiting greater risk reduction. When analyzed by smoking and alcohol exposure levels, participants moderately exposed to either showed a statistically significant 33% risk reduction (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.91), whereas participants exposed to both heavy smoking and alcohol use did not benefit from the protective effect of aspirin. The reduction in risk was relatively more significant in women. CONCLUSIONS: Aspirin use is associated with reduced risk of head and neck cancer. This effect is more pronounced in individuals with low to moderate exposure to cigarette smoke or alcohol consumption.

Alcohol Drinking↗

Intraparotid sentinel lymph node biopsy for head and neck melanoma.

OBJECTIVE: The objective of this retrospective clinical review was to assess the safety and accuracy of intraparotid sentinel node biopsy in patients with melanoma. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Twenty-eight patients with cutaneous melanoma of the head and neck undergoing sentinel lymph node (SLN) biopsy in which the radionuclide localized to the parotid gland on preoperative lymphoscintigraphy were studied. METHODS: All patients underwent wide local excision of the tumor and intraparotid sentinel node biopsy using intraoperative gamma probe localization. RESULTS: There were 25 men and 3 women ranging in age from 34 to 81 years. The primary site was on the auricle in 14 patients: temple, 4; forehead, 5; cheek, 3; and on the neck in 2 patients, respectively. The mean Breslow thickness was 2.3 mm (range, 0.9-7.0 mm). In 27 of 28 patients, an intraparotid SLN was identified. In one patient, final pathology did not reveal lymphoid tissue despite a high count in the parotid tissue excised. Median number of SLN per patient was two. Six patients had microscopic metastases in the SLN. In two of these patients, additional microscopic lymph node metastases were found in the neck after subsequent formal lymphadenectomy. The pathologic staging for the group (n = 14) was: stage 1B, 4; 2A, 4; stage 2B, 3; and stage 3B, 3 patients, respectively. All patients are alive and without evidence of disease (mean follow up, 31 months). There were no surgical complications, specifically no patient experienced temporary or permanent facial paralysis. CONCLUSION: Intraparotid SLN biopsy for staging cutaneous head and neck melanoma is a reliable, accurate, and safe procedure.

Adult↗

Advanced soft palate cancer: the clinical importance of the parapharyngeal space.

OBJECTIVE: To identify the incidence of parapharyngeal space (PPS) recurrences and how they impact survival in advanced-stage soft-palate carcinoma patients. STUDY DESIGN AND SETTING: One hundred thirty-seven patients' charts were reviewed from 1971 to 1996. Inclusion criteria were patients who received a per-oral resection, discontinuous neck dissection, and postoperative adjuvant radiation therapy; 15 patients met criteria for inclusion. The incidence of PPS recurrences, regional failure, and survival were endpoints that were analyzed. RESULTS: There were no local failures in our study. Regional failures excluding the PPS (levels I-V) were 27%, and 40% occurred within the PPS. Cervical adenopathy was associated with 83% of the PPS recurrences. Median survival for PPS recurrences was 26 months, compared with 67 months for levels I-V recurrences (n = ns). CONCLUSIONS: The incidence of PPS recurrences is substantial in advanced-stage soft-palate cancer. PPS recurrences negatively impact survival; without effective salvage techniques for these recurrences or effective adjuvant therapy, poor patient outcomes can be expected.

Adult↗

Molecular prognosticators and genomic instability in papillary thyroid cancer.

OBJECTIVES/HYPOTHESIS: Tumor progression has been attributed to the accumulation of DNA damage concurrent with selection of advantageous mutations; this DNA damage may result from failure to maintain genomic integrity or from susceptibility to carcinogens. Glutathione S-transferases (GSTs), enzymes that metabolize many carcinogens, may play a role in preserving genome integrity. The objectives of this study are to assess the relationship of GST genotypes with prognosis, clinicopathologic parameters, and genomic instability in papillary thyroid cancer. STUDY DESIGN: Prospective analysis. METHODS: GSTM1 and GSTT1 genotypes of 35 matched normal and papillary thyroid cancer specimens were determined by polymerase chain reaction (PCR) using primers specific for the coding sequences of each gene. Genomic instability was measured by intersimple sequence repeat PCR for each tumor/normal pair and compared with the GAMES prognostic scoring system and clinicopathologic parameters including age, extrathyroidal extension, tumor grade, size, stage metastasis, sex, and smoking history. RESULTS: GSTM1 and GSTT1 null genotypes were found in the normal tissues of 46% and 45%, respectively. No gene losses were detected in the tumor specimens. A significant association between the GSTM1 null genotype and increased risk of recurrence and death was observed. Elevated GII correlated with smoking and tumor stage but not with GST genotype. CONCLUSION: The association of GSTM1 null genotype with intermediate and high risk GAMES categories suggests that GSTM1 provides some protection against disease progression. However, this protection does not confer resistance to disease onset. GST genotyping may be a useful adjunct prognosticator with GAMES.

Adolescent↗

Thyroid carcinoma.

Explore the source record for details and available documents.

Biomarkers, Tumor↗

Parathyroid carcinoma: a multicenter review of clinicopathologic features and treatment outcomes.

We conducted a retrospective study of 13 patients with parathyroid carcinoma to assess their clinical characteristics and surgical outcomes. Study parameters included patient demographics, survival, treatment response, and recurrence. We found that all patients who had undergone local tumor excision developed a recurrence, compared with only 33% of those available for follow-up after en bloc tumor resection. Based on these findings, we recommend en bloc tumor resection as the initial treatment of choice for patients diagnosed with parathyroid carcinoma.

Adult↗

Development of head and neck squamous cell carcinoma is associated with altered cytokine responsiveness.

Growth of head and neck squamous cell carcinoma (HNSCC) is generally associated with an inflammatory component. It is hypothesized that these tumor cells develop mechanisms to evade the growth inhibitory effects of cytokines that are present in the tumor microenvironment. This study determined the changes in responsiveness to inflammatory cytokines that accompany the transition of normal to transformed epithelial cells. Paired primary cultures of normal epithelial cells (NEC) and SCC cells were established from 16 patients. Receptor-mediated activation of signal transducer and activator of transcription and extracellular signal-regulated kinase pathways in response to cytokine treatments was identified by immunoblot analysis. Thymidine incorporation determined the impact of the cytokines on DNA synthesis. HNNEC and HNSCC displayed a prominent signaling in response to oncostatin M, interleukin-6, IFN-gamma, and epidermal growth factor. Untreated HNSCC showed an elevated level of phosphorylated signal transducer and activator of transcription 3 and extracellular signal-regulated kinase (P < 0.001) compared with HNNEC, suggesting constitutively activated pathways. Moreover, HNSCC cells phosphorylated significantly more signal transducer and activator of transcription 1 in response to oncostatin M (P = 0.002) and IFN-gamma (P = 0.018) treatments. DNA synthesis of SCC cells was less inhibited by cytokines produced by endotoxin-stimulated macrophages (P = 0.016) than that of NEC. Low-dose oncostatin M slightly enhanced proliferation of SCC, whereas that of NEC was suppressed (P = 0.016). This study identified significant alterations in signal transduction pathways engaged by cytokines and which are associated with loss of growth inhibition of HNSCC. Increased signal transducer and activator of transcription phosphorylation, along with constitutively phosphorylated extracellular signal-regulated kinase in HNSCC, suggest that these pathways as molecular markers are important in the malignant transformation process and are potential targets for treatment.

Aged↗

Hypotensive endovascular test occlusion of the carotid artery in head and neck cancer.

OBJECT: To evaluate the reliability of balloon test occlusion with hypotensive challenge (BTO and HC) as a predictor of neurological complications before internal carotid artery (ICA) sacrifice in patients with advanced head and neck cancer, the authors retrospectively reviewed the medical records of patients presenting to their institutions between 1992 and 1997 in whom this preoperative assessment was performed. METHODS: Eleven patents who were candidates for extended comprehensive neck dissection (ECND) and potential ICA sacrifice were included in the study. Eight patients tolerated the test and underwent endovascular occlusion or surgical ligation of the ICA before ECND (four patients), preservation of the ICA at the time of surgery (three patients), or palliative therapy (one patient). Of three patients in whom BTO and HC failed, one patient received palliative treatment only; the other two underwent ECND with preservation of the ICA. In the group of patients who passed the test and underwent ICA occlusion or ligation before ECND, fatal thromboembolic stroke occurred within 24 hours of permanent balloon occlusion in one patient, resulting in a combined neurological morbidity/mortality rate of 25% in this subset of patients and an overall complication rate of 9% in this series. CONCLUSIONS: The authors found that BTO and HC offers a simple and reliable method of preoperative risk assessment when ICA resection is planned for regional control of disease in advanced head and neck cancer. This management option, however, is associated with a potential for neurological complication that must be weighed against the natural course of the disease and the risks and benefits of other treatment modalities.

Adult↗

Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction.

BACKGROUND: In thyroid tumors, the coexistence of well- and poorly differentiated tumor types has led to the hypothesis that poorly differentiated thyroid tumors develop from well-differentiated thyroid tumors. By evaluating the genomic instability of histologically distinct but coexisting tumor foci, this study aimed to develop an improved understanding of thyroid tumorigenesis and tumor evolution. DESIGN: Laser capture microdissection (LCM) was carried out on archival formalin-fixed, paraffin-embedded sections from a tumor containing foci of classic papillary thyroid cancer and anaplastic thyroid cancer. DNA was extracted from each microdissected tumor focus. In addition, cryopreserved bulk normal and neoplastic thyroid tissue underwent DNA extraction. All DNA samples were subsequently evaluated for genomic instability by means of inter-simple sequence repeat polymerase chain reaction. RESULTS: The LCM DNA from each archival paraffin-embedded tumor focus demonstrated unique patterns of banding as compared with the cryopreserved tumor and normal tissue DNA. Thus, intratumoral variability in genomic instability was observed. Comparison of inter-simple sequence repeat polymerase chain reaction patterns of LCM DNA from adjacent foci of papillary and anaplastic tumors showed conserved genome alterations. CONCLUSIONS: At the genome level, thyroid tumors may be highly heterogeneous. The intratumoral histologic heterogeneity observed in thyroid neoplasms reflects genetically heterogeneous underlying tumor cell populations that are demonstrated by the observed differences in their rates and extents of genomic instability. The conserved genomic alterations in the microdissected papillary and anaplastic foci suggest intratumoral evolution, with transformation of a preexisting papillary tumor to anaplastic carcinoma.

Aged↗

Anaplastic transformation of thyroid cancer: review of clinical, pathologic, and molecular evidence provides new insights into disease biology and future therapy.

BACKGROUND: Anaplastic thyroid cancer ranks among the most lethal of all human malignancies. Its rarity and rapidly fatal course have made it a difficult cancer to both study and treat. Unfortunately, there has been little progress in the management and control of this malignancy. Anaplastic transformation, or the intratumoral evolution of anaplastic carcinoma from pre-existing differentiated thyroid cancer, has become a well-accepted process, despite a limited understanding of its underlying mechanisms. METHODS: It is through review of the literature that an understanding of the aggressive disease biology can be developed. The aim of this review is to evaluate the relevant clinical, pathologic, and molecular studies to develop an insight into the mechanisms that underlie the intratumoral molecular evolution of anaplastic thyroid carcinoma. RESULTS/CONCLUSION: It is based on an understanding of this process that effective treatments for this aggressive malignancy are currently being developed.

Carcinoma↗

Papillary thyroid cancer: high inter-(simple sequence repeat) genomic instability in a typically indolent cancer.

OBJECTIVES: The object of this study is to measure genomic instability in papillary thyroid cancer and correlate these measurements with known clinical prognosticators such as patient age, tumor size, histologic subtype, and three commonly used thyroid risk assessment indices. A secondary objective of this study was to use the measurements of genomic instability to estimate the number of mutational events present in the papillary thyroid cancer genome. METHODS: Inter-simple sequence repeat polymerase chain reaction (ISSR-PCR) is a rapid and reproducible technique for quantitation of genomic instability, or the degree of genome alteration, in solid tumors. This includes quantitation of amplifications, deletions, translocations, and insertions. Twenty-eight papillary carcinomas were evaluated by ISSR-PCR. RESULTS: Evaluation of 28 papillary carcinomas by ISSR-PCR demonstrated a wide range of genomic instability. Of the panel of clinicopathologic factors examined, only patient age was significantly associated with genomic instability. The mean genomic instability index value was greatest in the youngest age group, which was significantly different from the median value measured in the oldest age group (3.7, 2.5, respectively, p =.05). The mean value in the intermediate age group fell between the younger and older groups (3.1). By use of ISSR-PCR, we have calculated 15,000 individual genomic events as having occurred in each papillary tumor cell. CONCLUSIONS: Despite its generally indolent biologic behavior, papillary thyroid cancer exhibits a high degree of genomic instability comparable to that seen in colorectal cancer. These results suggest that elevated genomic instability, as measured by ISSR-PCR, may not be sufficient to enable thyroid tumor progression to less indolent disease and that this process is severely constrained by some additional essential factor such as the differentiated state of the tissue or the need to bring into play an additional form of genomic destabilization.

Adolescent↗

Current concepts in the management of a second malignancy of the lung in patients with head and neck cancer.

Simultaneous, synchronous, and metachronous presentation of lung malignancies when treating head and neck squamous cell cancers is one of the most difficult challenges in head and neck surgery. However, good (> 40%) 5-year survival can be obtained when proper screening techniques, patient selection, and therapy are combined. Because of the complexity of the head and neck resection and reconstruction and the multiple surgical and medical services used to diagnose and treat this clinical entity, a comprehensive review of the current literature is provided. The clinically pertinent meanings of simultaneous, synchronous, and metachronous second malignancy of the lung are presented. A review of the current literature is presented that divides second lung malignancy into two groups: second primary and metastasis. The incidence of a second lung malignancy is identified. The tools used in the screening of high-risk patients and the role of the new diagnostic studies such as positron emission tomography and positron emission tomography CT scans are reviewed. Finally, the current literature on patient selection and surgical therapy is used to put forth a clinical pathway followed at the authors' institution for the treatment of these patients.

Carcinoma, Squamous Cell↗

Squamous cell carcinoma of the head and neck in nonsmokers and nondrinkers: an analysis of clinicopathologic characteristics and treatment outcomes.

BACKGROUND: The objective of this study was to describe the clinicopathologic manifestations of disease and outcomes of treatment among individuals without a history of smoking tobacco or consuming alcohol who develop head and neck cancer. METHODS: Of 1648 invasive head and neck cancer cases treated between 1970 and 2001 at Roswell Park Cancer Institute, 40 patients were identified as never having smoked tobacco or consumed alcohol during their lifetime. These cases were reviewed to gather data on multiple clinicopathologic variables. RESULTS: Mean age at presentation of nonsmoker/nondrinker head and neck cancer patients was 60 years (range, 27 to 90 years), and 78% (n = 31) of the patients were women. The distributions of tumor sites were 75.0% oral cavity (n = 30), 20.0% oropharynx (n = 8), and 5.0% larynx (n = 2). Sixteen patients (40%) experienced a recurrence of disease during the follow-up period, and 10 patients (25.0%) developed a second primary tumor a median of 6 years after their initial diagnosis. CONCLUSIONS: The nonsmoker/nondrinker head and neck cancer patient tends to be elderly and female, have oral cavity primary tumors, and be predisposed to second primary tumor development.

Adult↗

A logical and stepwise operative approach to radical neck dissection.

A thorough understanding of the anatomy of the neck is essential to avoid injury to vital structures when performing radical neck dissection. The complicated anatomical relations of the various nerves, vessels, and muscles within the confined area of the neck can often be daunting. We outline strategic anatomical landmarks and their relationships to important nerves, arteries, veins, and lymphatics to simplify the complicated and formidable anatomy of the neck. We also delineate key maneuvers that, when combined with the anatomical landmarks, offer a stepwise and logical approach to performing radical neck dissection that confers improved safety.

Humans↗

Genomic instability measurement in the diagnosis of thyroid neoplasms.

BACKGROUND: Clinically palpable thyroid nodules are present in approximately 10% of the population, although only 5% to 7% of these nodules harbor malignancy. Fine-needle aspiration has become one of the central tools in the diagnostic armamentarium of the surgeon/endocrinologist. There is, however, up to a 30% indeterminate diagnostic rate associated with this technique, resulting in unnecessary surgical interventions for patients harboring benign disease. A second issue of clinical importance is the unreliability of predicting outcomes based either on histologic findings alone or in combination with clinical staging. To address these diagnostic and clinical shortcomings, we have used measurement of genomic instability as a diagnostic and prognostic indicator for thyroid neoplasms. METHODS: Genomic instability of thyroid tissue samples was determined by inter-(simple sequence repeat) PCR, microsatellite instability analysis, and fluorescence in situ hybridization (FISH) on thyroid neoplasms from 22 patients. RESULTS: Inter-(simple sequence repeat) PCR detected genomic instability with an index range 0% to 1.9% (mean, 0.56%) in patients with benign disease, whereas in patients with malignant histologic findings the values ranged from 0% to 6.6% (mean, 2.9%). This difference between benign and malignant values was statistically significant (p =.004). There was no demonstrable microsatellite instability or loss of heterozygosity for six markers examined in this group. Losses of chromosomes 17 and X in benign disease and gains of chromosomes 7, 12, 17, and X in Hurthle cell carcinoma were observed, although not at a significant rate. CONCLUSIONS: Genomic instability as measured by inter-(simple sequence repeat) PCR was significantly higher for malignant diseases compared with benign thyroid tissues, but no such association was seen with aneuploidy or microsatellite instability.

Adolescent↗