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Biomedical subjects

Ashok R Shaha

Publications and source records attributed to Ashok R Shaha.

At least 19 recordsLinked to original sources
PubMed2003

Current management of mucosal melanoma of the head and neck.

While mucosal-based melanomas of the head and neck region are uncommon lesions, when they do arise they usually follow an inexorably aggressive course. Experience with these tumors is, necessarily, limited; as such, well-worked out treatment protocols for the treatment of such lesions are in short supply. It appears as though mucosal melanomas (MuMs) develop more frequently in the nasal cavity and paranasal sinus region, and less often in the oral cavity. It seems that the incidence of nodal metastasis is significantly lower for sinonasal MuMs than it is for MuMs of the oral cavity; this observation may influence decisions about performing neck dissection as a function of location of the primary MuM. At present, surgical excision remains the mainstay of treatment; however, anatomical complexities within the region can hamper attempts at complete excision. Radiotherapy has not traditionally been relied on for routine treatment of MuM, although some recent reports have challenged this view. Chemotherapy is, at present, employed principally in the treatment of disseminated disease and for palliation. As a diagnostic matter, MuM belongs to the class of tumors that, on light microscopy, may with some regularity be confused with other malignancies (including sarcomas, plasmacytomas, and carcinomas); as a consequence, this is a diagnosis which is often best confirmed by way of ancillary testing via immunohistochemical studies. A better grasp of the best means of treating MuM will likely come only when large referral centers are able to pool their experiences with these uncommon yet virulent malignancies.

Head and Neck Neoplasms↗
PubMed2003

Prognostic indicators of outcomes in patients with distant metastases from differentiated thyroid carcinoma.

BACKGROUND: Distant metastasis is uncommon in differentiated thyroid cancer and the prognosis is unclear. This study aims to evaluate outcomes and to define independent variables that are associated with tumor-related mortality in patients with distant metastasis from thyroid carcinoma. STUDY DESIGN: A retrospective review of the thyroid cancer research database identified 336 patients with distant metastasis from differentiated thyroid carcinoma treated at a single institution between 1941 and 2000. After excluding patients with local or regional recurrence, distant disease was either the first site of recurrence or was detected at the time of diagnosis of the primary tumor in 242 patients (72%). Patient, tumor, and treatment-related factors were analyzed for their relation to disease-specific survival (DSS) using multivariate Cox regression and the log-rank test. RESULTS: Median survival was 4.1 years and 10-year DSS was 26%. Distant disease was synchronous with the primary diagnosis in 97 of 242 (40%) patients. The site of metastasis was lung only in 103 (43%) patients, bone only in 80 (33%), other sites in 14 (6%), and more than one organ system in 45 (19%). Multivariate analysis identified age 45 years or more, symptoms, site other than lung only or bone only, and no radioactive iodine treatment for the metastasis as predictors of poor outcome with 13%, 11%, 16%, and 12% 10-year DSS, respectively. This compares with age less than 45 years, asymptomatic presentation, metastasis only in the lung or bone, and radioactive iodine treatment with 10-year DSS rates of 58%, 45%, 32%, and 33%, respectively (all p < 0.0001). Radioactive iodine treatment was more often given in patients who were less than 45 years of age, asymptomatic, and with metastasis only in the lung or bone only (p = 0.03, 0.11, 0.01). CONCLUSIONS: Longterm survival is possible in patients with distant metastasis from differentiated thyroid cancer. This retrospective study found that age of 45 years or more, site other than lung only or bone only, and symptoms at the time of diagnosis are associated with poorer outcomes.

Adenocarcinoma, Follicular↗
PubMed2003

Management of sarcomas of the head and neck in adults.

Sarcomas account for less than 1% of all malignant neoplasms occurring in the head and neck in adults. These tumors exhibit variable growth and degrees of aggressiveness which are primarily dependent on histologic grade. The pattern of growth demonstrated by sarcomas is generally by local advancement with high-grade tumor exhibiting extensive involvement of adjacent visceral and neurovascular structures. Regional metastasis is uncommon. Etiologic considerations include the tumorigenic effects of prior external beam radiotherapy and the development of second malignancies in the form of sarcomas. The clinical presentation of these neoplasms is variable and dependent on subsite of involvement as well as the aggressiveness of tumor growth. Histologic diagnosis is frequently challenging, often requiring the aid of immunohistochemical staining techniques. Treatment is predominantly surgical, utilizing wide local excision where en-bloc resection is feasible. Radiotherapy, by means of external beam or implant, plays an important adjunctive role in management, especially for tumors where en-bloc resection with margin control is not possible. Chemotherapy regimens are available for soft tissue neoplasms and osteosarcoma and are primarily designed to improve local control. Survival is predicted on the incidence of local recurrence and risk of distant metastasis, both of which are influenced by tumor grade. Low-grade tumors exhibit improved survival over that of less differentiated tumors.

Head and Neck Neoplasms↗
PubMed2003

Current philosophy on the management of cancer of the base of the tongue.

Cancer of the base of the tongue is a challenging disease for the head and neck surgeon, radiation oncologist and medical oncologist. However, over the last 10-15 years, improved treatment strategies have evolved which offer patients high probability of loco-regional control, survival, and good quality of life. The ability to offer patients good oncologic and functional outcomes serves as a paradigm for the successful application of multidisciplinary care, and the emphasis on quality of life in head and neck cancer treatment. This review provides an overview of the treatment options that exist, their advantages and disadvantages, and hopefully provides proper guidelines for the current management of this challenging disease.

Combined Modality Therapy↗
PubMed2003

Current management of tonsillar cancer.

Traditionally, risk factors for the development of tonsil cancer include the use of alcohol and/or tobacco, however a significant proportion of new cases develop in young patients without these risk factors. Recent investigation suggests that human papilloma virus (HPV) may serve as an etiology in such cases and represent a unique risk factor in a sub-set of patients. Irrespective of the etiology, in the majority of cases early carcinoma of the tonsil can effectively be treated using single modality therapy. While local-regional control and survival are similar following surgery or radiotherapy, primary surgery can be accomplished with minimal functional morbidity while reserving radiation for recurrent disease. In contrast, surgical salvage following external beam radiotherapy can be technically challenging and is often associated with a significant increase in surgical complications and functional morbidity. In contrast to early tonsillar disease, advanced tonsil cancer represents a clinical challenge that requires multimodality therapy. While advanced lesions are often treated with a combination of radiation, chemotherapy, and surgical ablation, management of the neck and distant metastases continues to present a therapeutic dilemma.

Carcinoma↗
PubMed2003

Sentinel lymph node biopsy in head and neck cancer.

In the past decade, the technique of sentinel lymph node biopsy (SLNB) has been applied to a vast array of primary neoplasms, ranging from head and neck melanoma to vulvar carcinoma. At present, experience with SLNB is greatest in patients with melanoma and breast cancer. In view of the well known complications associated with cervical node dissection, it has been suspected for some time that cervical SLNB, if successful, might reduce the morbidity associated with the definitive care of patients with head and neck cancers. This report assesses the current status of SLNB in the treatment of head and neck cancers; while formal investigations of the efficacy of this technique are recommended, SLNB has not yet been demonstrated to possess the same level of utility seen in SLNB in melanoma and breast cancer patients. As a consequence, the application of SLNB to head and neck cancers remains an experimental technique--one which has not yet acquired the status of the standard of patient care.

Carcinoma, Squamous Cell↗
PubMed2003

Management of cancer of the retromolar trigone.

Treatment of cancer of the retromolar trigone (RMT) is controversial. While early lesions may be managed with single-modality, more advanced lesions may invade the mandible, pterygoid musculature, and the adjacent mucosa of the tonsillar pillar and soft palate, therefore making therapeutic decisions more complicated. Treatment options traditionally include surgical resection, external beam irradiation, and combined modality therapy. The choice of therapy is dependent on the extent of the tumor, nodal metastasis, and the medical status of the patient and comorbid conditions. The following review outlines the current issues relevant to the diagnosis and therapy of patients with RMT malignancy.

Humans↗
PubMed2003

Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis.

We studied 45 patients with typical and 8 with atypical parathyroid adenomas as well as 20 with parathyroid carcinomas. Clinical, pathological, and molecular analyses were conducted on all adenomas. Clinical data were analyzed for 20, histopathologic slides for 16, and tissue specimens for 8 patients with carcinoma. Molecular expression profiles were investigated by immunohistochemistry (IHC) for Ki-67, p53, mdm2, p21, Bcl-2, cyclin D1, and p27 on paraffin-embedded tissues arrayed on tissue microarrays. Trabecular growth and vascular, capsular, and soft-tissue invasion were characteristic of parathyroid carcinomas but not of typical adenomas. No adenomas recurred. Seventy-four percent of carcinomas recurred, most in the neck. Seventy-nine percent of patients with such illness died of disease after an indolent, multiply recurrent course responsive to repeated resections; the 5-year survival rate was 50%. High Ki-67 proliferative index was seen in 2% of adenomas and 25% of carcinomas, whereas p27 expression was present in 80% of adenomas and 18% of carcinomas. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), was observed in 76%, 29%, and 0% of typical and atypical adenomas and carcinomas, respectively. The complexity of molecular phenotypes increased with tumor aggressiveness. Parathyroid carcinoma is an aggressive disease with a propensity for multiple recurrences. It is characterized by capsular, vascular, and soft-tissue invasion. Recurrence portends poor outcome. Molecular markers, Ki-67 and p27, may distinguish parathyroid carcinoma from adenoma. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), appears to be unique to nonmalignant parathyroid tumors, and multimarker phenotypes are more complex in carcinomas.

Adenoma↗
PubMed2003

The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the oral tongue.

PURPOSE: Amplification at chromosome 3q26.3 is a common and crucial event in head and neck squamous cell carcinoma (HNSCC), impacting significantly on tumor progression and clinical outcome. Two novel oncogenes, namely squamous cell carcinoma (SCC)-related oncogene (SCCRO) and PIK3CA (gene encoding phosphatidylinositol-3 kinase catalytic alpha-polypeptide), have been identified as targets of 3q26.3 amplification. This study aimed to delineate the role of SCCRO and PIK3CA in the pathogenesis of oral tongue SCC. EXPERIMENTAL DESIGN: The association between gene copy number for SCCRO and PIK3CA measured by fluorescence in situ hybridization and level of mRNA expression quantitated by real-time reverse transcription-PCR was assessed in a panel of human HNSCC cell lines. In addition, gene expression in 49 consecutive primary SCCs of the oral tongue was determined and correlated with clinicopathological characteristics and outcome. RESULTS: The mRNA level of SCCRO and PIK3CA was significantly correlated to the gene copy number in nine HNSCC cell lines. In addition, the expression level of SCCRO and PIK3CA was significantly greater in malignant tissues compared with those in histologically normal mucosae (2.17- and 2.46-fold, respectively; P < 0.001). Matched tumor normal control analysis revealed that 24.5 and 69.4% of patients expressed high levels of SCCRO and PIK3CA, respectively. Univariate analyses demonstrated that SCCRO overexpression correlated with nodal metastases (P = 0.05) and advanced stage (P = 0.02), whereas PIK3CA overexpression was associated with vascular invasion (P = 0.04). Only SCCRO overexpression was associated with disease-specific (P = 0.04) and overall survival (P = 0.02). Furthermore, SCCRO overexpression remained an independent predictor for cervical nodal metastasis on multivariate regression analysis (chi(2) likelihood ratio = 4.38; P = 0.04). CONCLUSIONS: Although both SCCRO and PIK3CA may play a role in the pathogenesis of oral tongue SCC through amplification at 3q26, SCCRO appears to be a significant predictor of regional metastasis and may be a marker for tumor aggressiveness and clinical outcome.

Adult↗
PubMed2002

Chromosomal aberrations in patients with head and neck squamous cell carcinoma do not vary based on severity of tobacco/alcohol exposure.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) have been causally associated with tobacco and alcohol exposure. However, 10-15% of HNSCC develop in absence of significant carcinogen exposure. Several lines of evidence suggest that the genetic composition of HNSCC varies based on the extent of tobacco/alcohol exposure, however, no genome wide measures have been applied to address this issue. We used comparative genomic hybridization (CGH) to screen for the genetic aberrations in 71 patients with head and neck squamous cell carcinoma and stratified the findings by the status of tobacco/alcohol exposure. RESULTS: Although the median number of abnormalities (9), gains (6) and losses (2) per case and the overall pattern of abnormalities did not vary significantly by the extent of tobacco/alcohol exposure, individual abnormalities segregating these patients were identified. Gain of 1p (p = 0.03) and 3q amplification (p = 0.05) was significantly more common in patients with a history of tobacco/alcohol exposure. CONCLUSIONS: This data suggests that the overall accumulated chromosomal aberrations in head and neck squamous cell carcinoma are not significantly influenced by the severity of tobacco/alcohol exposure with limited exceptions.

Adult↗
PubMed2002

Improved outcomes in patients with osteogenic sarcoma of the head and neck.

BACKGROUND: The current study reviews the authors' recent institutional experience in the treatment of osteosarcoma of the head and neck (OSHN). METHODS: The clinical records of 44 patients who were treated between 1981 and 1998 for OSHN were reviewed retrospectively. Archived histologic material was reviewed and data were analyzed to identify factors predictive of disease control and survival. Outcomes were compared with a previously reported historic cohort treated at the study institution. RESULTS: Patients ranged in age from 6 to 64 years (median, 31 years). The mandible was the primary site in 18 patients (41%), the maxilla in 20 patients (45%), and the skull in 6 patients (14%). Surgery was employed in all 44 patients, neoadjuvant chemotherapy was administered in 30 patients (68%), and postoperative radiation therapy was given to 7 patients (16%). The surgical excision margins were positive in 13 patients (30%). High-grade lesions were reported in 50% patients and low-grade lesions were noted in 18% of patients (grade was not assessable in 32%). Histologic response was "unfavorable" in 22 of 30 patients (73%) who were treated with neoadjuvant chemotherapy. The 3-year overall, disease-specific, and recurrence-free survival rates were approximately 81%, 81%, and 73%, respectively (median follow-up of 41 months). Positive surgical margins were found to be the only significant predictor of worse disease-specific survival. Compared with the historical cohort, the current experience demonstrated an obvious improvement in the 5-year local control (35% vs. 78%), distant metastases (37% vs. 13%), and overall survival (23% vs. 70%). CONCLUSIONS: Negative surgical margins were found to be the only significant predictor of overall and disease-specific survival. The results of the current study represent a considerable improvement over the authors' previously published experience and compare favorably with the results reported in the literature.

Adolescent↗
PubMed2002

Sentinel lymph node biopsy for cutaneous head and neck melanomas.

OBJECTIVE: To report the results of sentinel lymph node biopsy (SLNB) for cutaneous head and neck melanomas (CMHNs). DESIGN: Consecutive series followed for a median of 20 months. SETTING: Tertiary cancer care center. PATIENTS: Fifty-six individuals with clinically node-negative CMHN, median Breslow thickness, 2.6 mm (range, 0.2-20.0 mm). INTERVENTIONS: Preoperative technetium 99m sulfur colloid lymphoscintigraphy (PLSG) followed within 4 hours by intraoperative handheld gamma probe localization (IHGP). Intraoperative injection of 1% isosulfan blue dye (IBD) was used in 48 patients. Immediate completion nodal dissection was performed for metastatic SLNs on intraoperative frozen section analysis and monitoring for negative SLNs. MAIN OUTCOME MEASURES: Rate of SLN identification, SLN and non-SLN positivity, same-basin recurrence, and disease-specific and recurrence-free survival. RESULTS: Combination of IHGP and IBD improved SLN identification to 96% from 93% for IHGP and 73% for IBD alone. Four patients had a positive SLN on frozen section analysis. A negative SLNB correctly predicted regional nodal control in 47 of 48 patients but missed 1 of 5 patients who had regional lymphatic disease. All 4 patients who failed SLNB remain alive and free of recurrent disease. Two-year Kaplan-Meier disease-specific and relapse-free survival was 91% and 88%, respectively. Two-year disease-specific survival was 93% for SLN-negative patients and 50% for SLN-positive patients (P=.20). CONCLUSIONS: Combining PLSG with IHGP and IBD improves the success rate of SLNB. Although SLNB is a reliable indicator of the status of the draining lymphatic basins in CMHN, patients with negative SLNs must be observed for longer periods to understand the true implications of the procedure.

Adolescent↗
PubMed2002

Primary mucosal malignant melanoma of the head and neck.

INTRODUCTION: The relative rarity of mucosal melanomas of the head and neck (MMHN) has made analysis of treatment approaches difficult. Advances in diagnostic techniques and treatment interventions have had obvious impact on outcomes in cutaneous melanoma, but the effects on outcome in MMHN remain undefined. This study aims to assess the outcome and identify clinical and histologic prognostic indicators in a recent cohort of patients with MMHN treated at a single institution. METHODS: The clinical records of 59 patients with the diagnosis of MMHN treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1978 and 1998 were retrospectively reviewed. Pathologic material on each of these patients was prospectively reviewed by at least two pathologists (MP, KB, or AH) for confirmation of diagnosis and assessment of histologic variables. Survival was calculated by the Kaplan-Meier method. Clinical (patient demographics, tumor characteristics, and treatment) and histologic data (tumor thickness, melanosis, melanoma in situ, vascular invasion, and multifocality) were analyzed for impact on outcome by both univariate and multivariate analyses. RESULTS: Thirty-five patients (59%) had sinonasal tumors (SNMM), whereas 24 (41%) had oral (ORMM) tumors. Forty-seven patients (79.6%) were staged as stage I, 8 (13.6%) as stage II, and 4 (6.8%) were classified as stage III. Regional lymphatic metastases at presentation were more frequent in ORMM compared with SNMM (25% vs 6%, p =.05). Surgery was used in all patients. Adjuvant radiation therapy was used more frequently in the SNMM group compared with the ORMM group (40% vs 17%, p =.04). The rates of local failure for ORMM and SNMM were 51% and 50%, nodal failure rates were 42% and 20%, and distant failure rates were 67% and 40%, respectively (p = NS). With a median follow-up of 20 months, the 5-year disease-specific survival rate was 44% (40% for ORMM vs 47% for SNMM, p = NS). Significant prognostic factors for disease-specific survival on univariate analysis included advanced clinical stage at presentation, tumor thickness greater than 5 mm, presence of vascular invasion, and development of nodal and distant metastases. On multivariate analysis, however, regional nodal failure lost significance. CONCLUSIONS: Clinical stage at presentation, tumor thickness greater than 5 mm, vascular invasion on histologic studies, and development of distant failure are the only independent predictors of outcome in MMHN.

Adult↗
PubMed2002

Prediction of survival in patients with head and neck cancer using the histoculture drug response assay.

BACKGROUND: Chemoresponse is a significant outcome predictor in patients with head and neck cancer, regardless of the treatment modality used. The histoculture drug response assay (HDRA) has been shown to be a reliable method for in vitro chemoresponse assessment. In this study, we have correlated the HDRA assessment with survival in patients with head and neck squamous cell carcinoma (HNSCC). METHOD: Tumor specimens from 41 of 42 patients undergoing treatment for HNSCC were successfully evaluated by the HDRA. Tumor tissue was histocultured on Gelfoam sponges gel in 24-well plates, followed by treatment with cisplatin (15 microg/mL) or 5-fluorouracil (40 microg/mL) in triplicate. A control group received no drug treatment. After completion of drug treatment, the relative cell survival in the tumors was determined using the MTT assay. The inhibition rate (IR) for each drug was calculated relative to the control for each case, and sensitivity was defined as a tumor IR of greater than 30%. Treatment was based on established protocols for the location and stage of the tumor and included surgery, radiation, and/or chemotherapy. Survival comparisons were performed using the generalized Wilcoxon test for the comparison of Kaplan-Meier survival curves. RESULTS: Resistance to 5-fluorouracil was present in 13 cases (32%), to cisplatinum in 13 cases (32%), and to both agents in 11 cases (27%). The 2-year cause-specific survival was significantly greater for patients sensitive to 5-fluorouracil (85% vs 64%; p =.04), cisplatinum (86% vs 64%; p =.05), or both agents (85% vs 63%; p =.01). The association between HDRA assessment of chemoresponse and clinical outcome remained significant even after controlling for the effects of TNM stage and the presence of recurrent cancer at presentation by multivariate analysis. CONCLUSIONS: Chemosensitivity determined by the HDRA seems to be a strong predictor of survival in patients with advanced HNSCC and should be considered further.

Antimetabolites, Antineoplastic↗
PubMed2002

Management of well-differentiated thyroid carcinoma presenting within a thyroglossal duct cyst.

BACKGROUND AND OBJECTIVE: Well-differentiated thyroid carcinoma (WDTC) is diagnosed in approximately 1.5% of thyroglossal duct cysts (TGDC). No clear consensus exists regarding further management after adequate excision of the cyst, especially the role of total thyroidectomy and postoperative radioactive iodine therapy. The current review was undertaken in an attempt to clarify these issues. METHODS: Demographic, clinical, tumor, treatment, pathology, and outcome data on 57 eligible patients reported in recent literature were pooled together with 5 patients treated at our institution for this analysis. RESULTS: A Sistrunk operation was performed for resection of the thyroglossal duct cyst in the majority (90%) of patients. Histologic examination of the tumor in the cyst revealed that papillary carcinoma was the most frequent (92%) histologic type. A total thyroidectomy was performed consequent to the diagnosis of thyroglossal duct cyst carcinoma in approximately half of the 62 patients. A malignant tumor was reported in 27% of the thyroidectomy specimens. Postoperative radioactive iodine therapy was administered in 16 (26%) patients. With a median follow-up of 71 months (range 1-456 months), the 5- and 10-year Kaplan-Meier overall survival was 100 and 95.6%, respectively. There were no disease-related deaths reported in any of the patients. Univariate analysis revealed that the only significant predictor of overall survival was the extent of primary surgery for the thyroglossal cyst. The addition of total thyroidectomy to Sistrunk operation did not have a significant impact on outcome (P = 0.1). Patients treated with postoperative radioactive iodine (RAI) fared significantly worse than those that did not need RAI, which may be explained by the fact that this modality would generally be used in patients with higher risk tumors. CONCLUSIONS: The Sistrunk operation is adequate for most patients with incidentally diagnosed TGDC carcinoma in the presence of a clinically and radiologically normal thyroid gland. Results of adequate excision using the Sistrunk operation are excellent and the concept of risk-groups should be used to identify patients, who would benefit from more aggressive treatment.

Adolescent↗