Jatin P. Shah

Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract

A consecutive series of 1,081 previously untreated patients undergoing 1,119 radical neck dissections (RNDs) for squamous carcinoma of the head and neck was reviewed to study the patterns of nodal metastases. Primary tumors were located in the oral cavity in 501 patients, in the oropharynx in 207 patients, in the hypopharynx in 126 patients, and in the larynx in 247 patients. Lymph node metastases were confirmed histologically in 82% of 776 therapeutic neck dissections, and micrometastases were discovered in 33% of 343 elective RNDs. Lymph node groups in the neck were described by levels (I to V). Predominance of certain levels was seen for each primary site. Levels I, II, and III were at highest risk for metastasis from cancer of the oral cavity, and levels II, III, and IV were at highest risk for metastasis from carcinomas of the oropharynx, hypopharynx, and larynx. Supramohyoid neck dissection (clearing levels I, II, and III) for NO patients with primary squamous cell carcinomas of the oral cavity and anterolateral neck dissection (clearing levels II, III, and IV) for NO patients with primary squamous cell carcinomas of the oropharynx, hypopharynx, and larynx are recommended.

Estimating Risk of Recurrence in Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System

BACKGROUND A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. METHODS This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. RESULTS Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediate-risk, and 68% of the high-risk patients (p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. CONCLUSIONS Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.

The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity

A retrospective review of the records of 501 previously untreated patients from January 1, 1965 through December 31, 1986 with squamous cell carcinoma of the oral cavity was undertaken to ascertain the prevalence of ipsilateral neck node metastases (NM) by neck level. The 501 patients underwent 516 radical neck dissections. Patients were grouped by clinical neck status at the time of neck dissection: elective dissection (ED) in the NO neck, immediate therapeutic dissection (ITD) in the N+ neck, and subsequent therapeutic dissection (STD) in the neck observed which converted clinically to N+. Pathologically identified NM occurred 34% of the time in ED, 69% in ITD and 90% in STD. The sensitivity, specificity, and overall accuracy of the clinical exam was 70%, 65%, and 68%, respectively. Detailed analysis was performed for each group based on the primary site. This revealed a prevalence of NM in level IV of 3% (five of 167) for ED versus 17% (49/ 296) for ITD + STD (P < 0.001). Tongue, retromolar trigone, and cheek did not have NM in level V in any group. The prevalence of NM in level V for floor of mouth or gum primaries was < 1% (one of 109) in ED versus 6% (ten of 167) in ITD + STD (P < 0.03). These data support the trend toward selective limited neck dissection in both NO and N+ patients. Further, they provide the foundation for planning of future prospective trials to assess the efficacy of modifications in the extent of neck dissection.

Initial Results from a Prospective Cohort Study of 5583 Cases of Thyroid Carcinoma Treated in the United States during 1996 An American College of Surgeons Commission on Cancer Patient Care Evaluation Study

The American College of Surgeons Commission on Cancer (CoC) has conducted national Patient Care Evaluation (PCE) studies since 1976.

Current concepts in management of oral cancer--surgery.

Oral cancer is the sixth most common cancer worldwide, with a high prevalence in South Asia. Tobacco and alcohol consumption remain the most dominant etiologic factors, however HPV has been recently implicated in oral cancer. Surgery is the most well established mode of initial definitive treatment for a majority of oral cancers. The factors that affect choice of treatment are related to the tumor and the patient. Primary site, location, size, proximity to bone, and depth of infiltration are factors which influence a particular surgical approach. Tumors that approach or involve the mandible require specific understanding of the mechanism of bone involvement. This facilitates the employment of mandible sparing approaches such as marginal mandibulectomy and mandibulotomy. Reconstruction of major surgical defects in the oral cavity requires use of a free flap. The radial forearm free flap provides excellent soft tissue and lining for soft tissue defects in the oral cavity. The fibula free flap remains the choice for mandibular reconstruction. Over the course of the past thirty years there has been improvement in the overall survival of patients with oral carcinoma largely due to the improved understanding of the biology of local progression, early identification and treatment of metastatic lymph nodes in the neck, and employment of adjuvant post-operative radiotherapy or chemoradiotherapy. The role of surgery in primary squamous cell carcinomas in other sites in the head and neck has evolved with integration of multidisciplinary treatment approaches employing chemotherapy and radiotherapy either sequentially or concurrently. Thus, larynx preservation with concurrent chemoradiotherapy has become the standard of care for locally advanced carcinomas of the larynx or pharynx requiring total laryngectomy. On the other hand, for early staged tumors of the larynx and pharynx, transoral laser microsurgery has become an effective means of local control of these lesions. Advances in skull base surgery have significantly improved the survivorship of patients with malignant tumors of the paranasal sinuses approaching or involving the skull base. Surgery thus remains the mainstay of management of a majority of neoplasms arising in the head and neck area. Similarly, the role of the surgeon is essential throughout the life history of a patient with a malignant neoplasm in the head and neck area, from initial diagnosis through definitive treatment, post-treatment surveillance, management of complications, rehabilitation of the sequelae of treatment, and finally for palliation of symptoms.

Prognostic factors in differentiated carcinoma of the thyroid gland.

A retrospective review of a consecutive series of 931 previously untreated patients with differentiated thyroid carcinoma treated over a 50-year period was undertaken to analyze prognostic factors. Data pertaining to demographic status, clinical, operative, and pathologic findings, and survival were analyzed. Univariate statistical analysis was performed based on the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed to assess the independent effect of these variables using the Cox model. There were 630 female and 301 male patients, with an average age of 43 years. A total of 532 patients were younger than 45 years. Seven hundred thirty-one patients had either pure or mixed papillary carcinoma, and 200 had follicular carcinoma. In 153 patients, lesions were larger than 4 cm. Extrathyroidal extension was noted in 71 patients. Multifocal lesions were present in 159 patients. Regional lymph node metastasis was present on admission in 451 patients, and distant metastases were noted on presentation in 45 patients. Determinate survival for all patients was 87% at 10 years. Favorable prognostic factors using univariate analysis included female gender, multifocal primary tumors, and regional lymph node metastases. Adverse prognostic factors included age over 45 years, follicular histology, extrathyroidal extension, tumor size exceeding 4 cm, and the presence of distant metastases. On multivariate analysis, the only factors that affected the prognosis were patient age, histology, tumor size, extrathyroidal extension, and distant metastases. These observations support findings of reports from the Mayo Clinic and Lahey Clinic regarding the significance of prognostic factors for differentiated carcinoma of the thyroid gland.

Head and Neck Cancers

Recent evidence suggests that dysregulated translation and its control significantly contribute to the etiology and pathogenesis of the head and neck cancers, specifically to that of squamous cell carcinoma (HNSCC). eIF4E is one of the most studied components of the translation machinery implicated in the development and progression of HNSCC. It appears that dysregulation of eIF4E levels and activity, namely by the PI3K/AKT/mTOR pathway, plays an important role in the etiology and pathogenesis of HNSCC and correlates with clinical outcomes. In this chapter, we will discuss the role of eIF4E and some other translation factors as they relate to the biology and treatment of HNSCC.

Primary mucosal malignant melanoma of the head and neck

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.

Factors associated with complications in microvascular reconstruction of head and neck defects.

The use of microvascular free tissue transfer has allowed the reconstruction of increasingly complex defects in higher risk patients after head and neck cancer resections. However, the combination of these factors also gives rise to a higher risk for the development of complications. This study was performed to establish the pretreatment factors associated with complication development after microvascular free tissue transfer for the reconstruction of defects resulting from head and neck cancer ablations, with particular attention to the role of comorbid conditions. A retrospective cohort study was conducted including 200 consecutive microvascular free tissue transfers performed for the reconstruction of surgical defects in the head and neck region at a single tertiary care institution. Comorbidity severity was assessed using the Charlson comorbidity index, a novel approach to comorbid staging in this setting. The flap survival rate was 98 percent. Complications developed in 56 cases (28 percent), with multiple complications occurring in 21 of these cases (10.5 percent). Univariate analysis revealed that prior radiation treatment (p = 0.03), anesthesia time over 10 hours (0.05), and advanced Charlson comorbidity grade (0.002) were associated with an increased risk for the development of complications. However, only the presence of advanced Charlson grade proved significant after multivariate analysis (odds ratio 3.9; 95 percent CI = 1.5 to 10.1). In addition, increasing Charlson grade (p = 0.003) and age over 70 years (p = 0.04) correlated with increasing complication severity. Systemic complications occurred in 28 patients (14 percent), with advanced Charlson grade being the only significant factor associated with the development of complications after controlling for confounding factors (odds ratio 3.8; 95 percent CI = 1.5 to 9.7). In patients over 70 years of age, increasing operative time also impacted on the development of systemic complications (p = 0.002), especially in patients with advanced Charlson grades (0.01). Recipient site complications occurred in 30 patients (15 percent), with history of prior radiation therapy being the only factor associated with increased risk by multivariate analysis (odds ratio 2.5; 95 percent CI = 1.1 to 5.7). No factors predicted the development of donor-site complications, which occurred in 11 cases (5.5 percent). The median hospital stay for the entire population was 16 days. The development of complications increased the median hospital stay by 7.5 days (p < 0.001). The effect of the development of complication on hospital stay remained significant even after controlling for the effects of confounding variables (relative risk = 9.87; 95 percent CI = 5.9 to 19.9). Microvascular surgery is a highly successful and relatively safe method for the reconstruction of large head and neck defects. The Charlson comorbidity index grading may be useful for identifying patients at increased risk for the development of complications after microvascular reconstruction, allowing for improved perioperative planning. In addition, patients with prior radiation exposure have a significantly higher risk for developing complications at the recipient site. Although advanced age is not associated with an increased risk for complications, older patients may be more sensitive to the effects of prolonged anesthesia and are likely to develop more severe complications.

Diagnostic and Prognostic Value of [18F]Fluorodeoxyglucose Positron Emission Tomography for Recurrent Head and Neck Squamous Cell Carcinoma

PURPOSE: Patients with recurrent head and neck squamous cell carcinoma (HNSCC) present a diagnostic and therapeutic challenge. We evaluated the diagnostic accuracy and prognostic value of [18F]fluorodeoxyglucose positron emission tomography (PET) in this patient population. PATIENTS AND METHODS: We performed a retrospective review of 143 patients with previously treated HNSCC who underwent 181 PET scans at our institution from May 1996 through April 2001 to detect recurrent disease. Disease recurrence within 6 months was used as the gold standard for assessing true disease status at PET. RESULTS: With equivocal sites considered positive, the sensitivity and specificity of PET for detecting recurrence overall were 96% and 72%, respectively. PET was highly sensitive and specific at regional and distant sites. At local sites, sensitivity was high, but specificity was lower because of false-positive findings. One fifth of all false-positive PET scans occurred at sites of known inflammation or infection. The a...