Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis.

BACKGROUND: The current study was performed to report the long-term results of a trial comparing concurrent chemotherapy and radiotherapy (CCRT) with surgery and adjuvant radiotherapy (RT) in patients with stage III/IV nonmetastatic head and neck squamous cell carcinoma. METHODS: Patients with stage III/IV resectable head and neck squamous cell carcinoma were randomized to surgery followed by RT or CCRT. The trial was halted prematurely due to poor accrual. Human papillomavirus status was tested on archival material using polymerase chain reaction sequencing. RESULTS: Of the total of 119 patients, 60 patients were randomized to primary surgery (S arm) and 59 patients were randomized to CCRT (C arm). Human papillomavirus status was tested in 75 patients, and only 3 were found to be positive. The median follow-up for surviving patients was 13 years. Analysis of the entire cohort demonstrated no statistically significant difference in overall survival and disease-specific survival (DSS): 5-year rates were 45% versus 35% for overall survival (P = .262) and 56% versus 46% for DSS (P = .637) for the S arm and C arm, respectively. Analysis by subsites indicated that this difference favoring the S arm was mainly driven by survival data among patients with cancers of the oral cavity and maxillary sinus. For patients with oral cavity cancer, survival was significantly better in those who underwent primary surgery compared with CCRT; the 5-year DSS rate was 68% versus 12% for the S arm and C arm, respectively (P = .038). For patients with cancers of the maxillary sinus, the 5-year DSS rate was 71% for patients on the S arm and 0% for patients on the C arm (P = .05). CONCLUSIONS: These long-term results demonstrate a significant advantage for primary surgery in patients with cancers of the oral cavity or maxillary sinus, providing strong support for primary surgery as the main modality of treatment for these subsites. In other subsites, CCRT and surgery with adjuvant RT were found to demonstrate similar efficacy for survival in patients with advanced resectable tumors.

Recurrent giant fibrovascular polyp of the esophagus.

Giant fibrovascular polyps of the esophagus and hypopharynx are rare benign esophageal tumors. They arise most commonly in the upper esophagus and may, rarely, originate in the hypopharynx. They can vary significantly in size. Even though they are benign, they may be lethal due to either bleeding or, rarely, asphyxiation if a large polyp is regurgitated. Patients commonly present with dysphagia or hematemesis. The polyps may not be well visualized on endoscopy and imaging plays a vital role in aiding diagnosis as well as providing important information for pre-operative planning, such as the location of the pedicle, the vascularity of the polyp and the tissue elements of the mass. They can also be recurrent in rare cases, especially if the resection margins of the base are involved. We review the recent literature and report a case of a 61-year-old man with a recurrent giant esophageal fibrovascular polyp with illustrative contrast barium swallow, CT and intra-operative images, who required several surgeries via a combination of endoscopic, trans-oral, trans-cervical, trans-thoracic and trans-abdominal approaches.

Indirect MR lymphangiography of the head and neck using conventional gadolinium contrast: a pilot study in humans.

PURPOSE: To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites. METHODS AND MATERIALS: We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence. RESULTS: The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sites that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer. CONCLUSIONS: We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases.

Advanced-staged tonsillar squamous carcinoma: organ preservation versus surgical management of the primary site.

BACKGROUND: Our aim was to review our experience in the management of advanced tonsillar squamous cell carcinoma (SCC) and to compare treatment outcomes between patients treated with and without surgery to the primary site. METHODS: The records of 74 patients with advanced-stage tonsillar SCC were reviewed. The median age at diagnosis was 58 years. Thirty-eight patients received definitive surgery to the primary site, and 36 were treated with an organ-preservation approach (OP) using radiotherapy +/- chemotherapy. RESULTS: No significant difference in overall survival (OS) or freedom from relapse (FFR) by treatment was found. T classification and N status were significant independent predictors on multivariate analysis for OS and FFR. Major late toxicity was noted in 10 patients in the surgical group and nine in the OP group. CONCLUSION: Patients treated with OP and primary surgery had comparable OS and FFR. T classification and N status were significant independent predictors for tumor relapse and survival. On the basis of these results, we favor organ-preservation therapy for patients with advanced-stage tonsillar SCC.

Long-term results of 100 consecutive comprehensive neck dissections: implications for selective neck dissections.

OBJECTIVE: The optimal surgical procedure for the neck in patients with squamous head and neck cancers is controversial. Selective neck dissections have replaced modified radical neck dissections as the procedure of choice for the clinically negative (N0) neck and are now being considered for patients with early-stage neck disease. We report the long-term local recurrence rates in 100 consecutive patients undergoing a radical or modified radical neck dissection for clinically positive (N+) and N0 neck disease and review comprehensively the literature reporting and comparing regional control rates for both neck dissection types. PATIENTS: The clinical records of 100 consecutive patients who underwent a comprehensive neck dissection (levels I-V) for squamous head and neck cancers with a minimum of a 2-year follow-up were retrospectively reviewed for primary site of disease, clinical and pathologic neck status, histopathologic grade, neck dissection type, and the site and time of recurrence. RESULTS: Complete data were available for 97 patients on whom 99 neck dissections were performed. Three patients died from unknown causes. Seventy-six patients with N+ disease underwent a therapeutic neck dissection, while 24 patients with clinically N0 disease underwent an elective dissection. The overall neck recurrence rate in patients with controlled primary disease was 7%. The neck or regional failure rate for patients completing the recommended adjuvant radiotherapy was 4%. Six (25%) of 24 patients with clinically N0 disease had occult metastases. The recurrence rate for this group was 4%. CONCLUSION: Further study is needed to determine the optimal surgical management of the N0 and limited N+ neck.

Laryngeal embryonal rhabdomyosarcoma: a case of cervical metastases 13 years after treatment and a 25-year review of existing literature.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, the majority of which are of the embryonal rhabdomyosarcoma (ER) variety. Present day treatment protocols involve a combination of aggressive surgery, chemotherapy, and radiation therapy. Embryonal rhabdomyosarcoma of the larynx is rare and unlike ER of other regions exhibits excellent response to multimodality treatment without the need for extensive surgery. We report a case of cervical metastases in a 29-year-old man 13 years after treatment of his laryngeal ER. To our knowledge, this is the first reported case of late neck metastases in ER of the larynx and the second reported case of delayed presentation of recurrent disease. A 25-year review of all published reports of ER of the larynx was conducted that highlights the move toward organ preservation with the multimodality treatment protocols. Embryonal rhabdomyosarcoma of the larynx is highly responsive to combination chemoradiotherapy, allowing for excellent cure rates without the need for extensive surgery. Late relapses warrant long-term follow-up.

Postoperative endocrine function in patients with surgically treated thyrotoxicosis.

BACKGROUND: Endocrine function after surgery for thyrotoxicosis is difficult to predict. The operative morbidity and long-term thyroid function of patients surgically treated for thyrotoxicosis is presented, and factors postulated to affect long-term function are correlated with outcome. METHODS: The clinical records of 289 consecutive patients who underwent surgery for thyrotoxicosis were reviewed. Indications for surgery, intraoperative findings, postoperative complications, and endocrine status 1, 2, and 5 years after surgery were analyzed. Sex, age, duration of medical treatment, weight of thyroid removed and preserved, and antimicrosomal/antithyroglobulin antibody status were correlated with outcome 5 years after surgery. RESULTS: The incidence of permanent recurrent laryngeal nerve injury and hypocalcemia were 0.7% and 1.7%. The cumulative hypothyroid and hyperthyroid rates for the first, second, and fifth postoperative years were 13.8% and 3.5%, 14.5% and 4.8%, and 15.6% and 8.0%. All the prognostic variables analyzed did not achieve a significant correlation with outcome at 5 years by univariate and multivariate age- and sex-adjusted relative risk. CONCLUSIONS: Failure from hypothyroidism develops early; recurrent hyperthyroidism increases with the number of years of follow-up. Patients undergoing subtotal thyroidectomy warrant long-term follow-up because of the inability to accurately predict postoperative function with consistently reliable prognostic factors.

Detection of neoplasms in the oral cavity by digitized endoscopic imaging of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.

Studies of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) fluorescence have shown a sensitivity of 95-100% for oral cancer diagnosis, but the specificity is only about 50-60%. To improve the diagnostic specificity, a 5-ALA mediated digitized fluorescence endoscopic imaging system was built in this study to enable the on-line image acquisition, analysis and fluorescence quantification for the early detection of neoplasms in the oral cavity. PPIX fluorescence endoscopy and fluorescence image quantification were performed on 16 patients with known or suspected premalignant or malignant lesions in the oral cavity. Preliminary data from the head and neck clinical trials show that the red-to-blue intensity ratio of malignant tissue is larger than that of benign tissue. By applying the intensity ratio as a diagnostic algorithm, both high specificity and sensitivity can be achieved for discriminating malignant tissue from benign tissue, and the capability of classifying different histopathological stages of oral lesions has also been demonstrated. It was found that the red fluorescence intensity distribution in the lesion area could also be obtained to better understand the situation of PPIX accumulations in the tissues. Our initial results indicate that the digitized endoscopic imaging system combined with the fluorescence image quantification method and the ratio diagnostic algorithm developed in this study has the potential to significantly improve the non-invasive diagnosis of early oral neoplasms in vivo.

Detection of squamous cell carcinomas and pre-cancerous lesions in the oral cavity by quantification of 5-aminolevulinic acid induced fluorescence endoscopic images.

BACKGROUND AND OBJECTIVES: Studies of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence have shown a sensitivity of 95-100% for oral cancer diagnosis, but the specificity is only about 50-60%. Here, we explore the applicability of quantifying PPIX fluorescence images to improve the diagnostic specificity and detect early oral lesions. STUDY DESIGN/MATERIALS AND METHODS: PPIX Fluorescence endoscopy and imaging were performed on 28 patients with a known or suspected premalignant or malignant oral cavity lesion. A total of 70 biopsies were taken from the tissue sites imaged for histological analysis. The red-to-blue and red-to-green intensity ratios were calculated from the fluorescence images to correlate with histology. RESULTS: Suspicious lesions display bright reddish fluorescence, while normal mucosas exhibit blue color background in the fluorescence images. The red-to-blue and red-to-green intensity ratios of malignant tissues are larger than those of benign tissues. Combining the two ratio diagnostic algorithms yields a sensitivity and specificity of 95% and 97%, respectively, exceeding each diagnostic algorithm alone for discriminating malignant tissue from benign tissue. CONCLUSIONS: Quantifying PPIX fluorescence endoscopic images combined with the ratio diagnostic algorithms developed in this study has the potential to significantly improve the noninvasive diagnosis of oral cavity lesions in vivo.