Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck.

BACKGROUND: The current study presents mature results from a Phase III randomized trial comparing radiation therapy and concurrent chemoradiotherapy in patients with resectable American Joint Committee on Cancer Stage III and IV disease. METHODS: One hundred patients were randomized to receive either radiation therapy alone (Arm A) (at a dose of between 66-72 grays [Gy] at 1.8-2 Gy per day) and the identical radiation therapy with concurrent chemotherapy (Arm B) (5-fluorouracil, 1000 mg/m(2)/day, and cisplatin, 20 mg/m(2)/day, both given as continuous intravenous infusions over 4 days beginning on Days 1 and 22 of the radiation therapy). Primary site resection was planned for patients with residual or recurrent local disease. Cervical lymph node dissection was performed for regional persistent disease or recurrence, or if N2-3 disease was present at the time of presentation. RESULTS: After completing all therapy including surgery, 82% of the patients in Arm A and 98% of the patients in Arm B had been rendered disease free (P = 0.02). At a median follow-up of 5 years (range, 3-8 years), the 5-year Kaplan-Meier projections for overall survival for Arm A versus Arm B were 48% versus 50% (P = 0.55). Kaplan-Meier projections for the recurrence free interval were 51% versus 62% (P = 0.04), projections for a distant metastasis free interval were 75% versus 84% (P = 0. 09), projections for overall survival with primary site preservation were 34% versus 42% (P = 0.004), and projections for local control without surgical resection were 45% versus 77% (P < 0.001). Salvage surgery proved to be successful in 63% and 73%, respectively, of the Arm A and Arm B patients with primary site failure. Unrelated death while free of disease occurred in 22% and 32%, respectively, of Arm A and Arm B patients (P = 0.26). CONCLUSIONS: The addition of concurrent chemotherapy to definitive radiation in patients with resectable Stage III and IV squamous cell carcinoma of the head and neck improves the likelihood of disease clearance, a recurrence free interval, and primary site preservation. However, overall survival does not appear to be improved, reflecting both effective surgical salvage after local recurrence and competing causes of death.

Diagnosis of papillary carcinoma in a thyroglossal duct cyst by fine-needle aspiration biopsy.

The incidence of papillary thyroid carcinoma arising in a thyroglossal duct cyst is rare and occurs in about 1 % of thyroglossal duct cysts. Only 17 such cases diagnosed with fine-needle aspiration biopsy have been previously reported in the English-language literature, with a diagnostic rate of 53%. In this article, the cytologic features of the current case are emphasized and those of the previous reported cases are briefly reviewed. Diagnostic pitfalls of papillary carcinoma arising in thyroglossal duct cysts diagnosed by fine-needle aspiration biopsy are also discussed.

Plasmacytomas of the head and neck.

Plasmacytomas are rare tumors that often appear in the head and neck region and are characterized by a monoclonal proliferation of plasma cells. On both clinical presentation and pathologic examination these tumors may be confused with more common tumors of the head and neck. The purpose of this article is to review our experience with these rare neoplasms, with emphasis on clinical, pathologic, and therapeutic features. On retrospective chart review, we identified 20 patients with the diagnosis of plasmacytoma of the head and neck region at the Cleveland Clinic Foundation between 1976 and 1993. Records were reviewed with regard to initial symptoms, location of the neoplasm, diagnostic evaluation, treatment modalities, and survival. Of the 20 cases we identified, the tumor arose in the sinonasal/nasopharyngeal region in 11 (55%). Two cases (10%) represented medullary plasmacytomas, arising in the clavicle and presenting as supraclavicular masses. The mean follow-up was 60.2 months (range 6 to 131 months). In 15 of the 20 cases, immunohistochemistry staining for immunoglobulin light chain production was conducted. One of the two cases (50%) classified as medullary plasmacytoma demonstrated conversion to multiple myeloma, whereas only 2 of 18 cases of extramedullary plasmacytoma (11%) converted to multiple myeloma. The primary modality of treatment was radiation therapy with typical doses of 4500 to 6000 cGy. Kaplan-Meier survival estimates demonstrated 95% survival at 1 year, 82% survival at 5 years, and 10-year estimated survival of 72%. Plasmacytomas of the head and neck region are rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiologic and pathologic studies including immunohistochemistry. Despite the typical presentation as a locally destructive tumor, plasmacytomas are highly radiosensitive, and 70% to 80% survival may be obtained with the use of radiotherapy. Patients with plasmacytomas require long-term follow-up to detect conversion to multiple myeloma.

Vagal paraganglioma: a review of 46 patients treated during a 20-year period.

BACKGROUND: Vagal paragangliomas (VPs) arise from paraganglia associated with the vagus nerve. Approximately 200 cases have been reported in the medical literature. Because of their rarity, most information regarding these tumors has arisen from case reports and small clinical series. OBJECTIVE: To detail the clinicopathologic features of 46 patients with VP with an emphasis on the role of a multidisciplinary skull base team in both the successful extirpation and rehabilitation. DESIGN: Retrospective review of 46 patients with VP managed by a single skull base team. SETTING: An academic tertiary medical center. RESULTS: Forty-six patients were treated over a 20-year period (1978-1998). Ten (22%) demonstrated intracranial extension. There was a history of familial paragangliomas in 9 (20%) of the patients. The incidence of multicentric paragangliomas was 78% in patients with familial paragangliomas vs 23% in patients with nonfamilial paragangliomas. Management of this group of 46 patients consisted of surgery (n = 40), radiation therapy (n = 4), and observation (n = 2). The operative approach consisted of a transcervical excision often combined with a transtemporal or lateral skull base approach as dictated by the tumor extent. Postoperative cranial nerve deficits were common, and, as such, aggressive rehabilitation was a vital component in the management of these tumors. CONCLUSIONS: The management of VP and its associated cranial nerve deficits remains a difficult clinical problem. Options for treatment include surgical resection, radiation therapy, and, in selected cases, observation. Surgical extirpation requires a multidisciplinary skull base team to achieve complete tumor resection. Radiation therapy is reserved for elderly patients and patients at risk for bilateral cranial nerve deficits. Rehabilitation of cranial nerve deficits is an integral part of the management of VP.

Comparison of surgical complications after organ-preservation therapy in patients with stage III or IV squamous cell head and neck cancer.

OBJECTIVE: To determine the incidence of minor and major complications in patients with squamous cell carcinoma of the upper aerodigestive tract who require surgical salvage or planned neck dissection after an initial treatment regimen with radiotherapy or concurrent chemoradiotherapy for organ preservation. DESIGN: The medical records of 100 patients treated in a phase 3 trial comparing radiotherapy alone with concurrent chemoradiotherapy for stage III and IV head and neck squamous cell carcinoma were reviewed. Fifty-four patients underwent 59 surgical procedures. Twenty-nine planned neck dissections were performed for persistent neck disease or initial stage N2 or greater. For persistent or recurrent disease at the primary site, 30 salvage operations were performed. SETTING: Academic tertiary care referral center. RESULTS: Complications occurred in 15 (46%) of the 33 procedures in the radiation-only group and 12 (46%) of the 26 procedures in the chemoradiotherapy group. Major complications occurred in 4 (12%) of the procedures in the radiation-only group and 3 (12%) of the procedures in the chemoradiotherapy group. The incidence of minor complications was 33% and 35% in the radiation-only and chemoradiotherapy groups, respectively. The major complication rate for salvage operations did not differ between the radiation-only and chemoradiotherapy groups (16% and 27%, respectively; P=.79 by chi2 test). The incidence of major complications in planned neck dissections was 7% of the radiation-only group and 0% of the chemoradiotherapy group. CONCLUSIONS: After radiation or concurrent chemoradiotherapy, surgery can be performed with an acceptable rate of major complications. Adding chemotherapy did not increase the incidence of surgical complications. These results differ from other reports in the literature.

Extranodal lymphomas of the head and neck. A 20-year experience.

BACKGROUND: Extranodal non-Hodgkin lymphoma (NHL) of the head and neck is a relatively uncommon disease. Over the last 3 decades, a variety of systems, including the Rappaport, Luke-Collins, and Working Formulation classifications, have been used to classify extranodal NHLs of the head and neck. Most studies have included a relatively small number of patients, used different modalities of therapy, and did not include all head and neck sites. These limitations make comparisons between different studies and drawing any conclusions difficult. OBJECTIVES: To describe in a uniform fashion a relatively large number of patients with extranodal NHL of the head and neck treated at the same institution, using only the most current classification system and to describe the clinical features, behavior, and outcome of this relatively uncommon, but potentially curable disease. DESIGN: A retrospective study of 98 patients with extranodal NHL of the head and neck. All patients were reclassified according to the Working Formulation system (regardless of the time of diagnosis) in order to uniformly define the clinical course of this disease in the head and neck. SETTING: A tertiary care referral center. RESULTS AND CONCLUSIONS: The sinonasal tract was the most commonly involved site (25%). If the nasopharynx (16%), tonsil (12%), and base of tongue (8%) are grouped together, this combined site (Waldeyer ring) becomes the most common site of disease (36%). Patients with tonsillar lymphoma had a 20% incidence of associated gastrointestinal involvement. Approximately 50% of the patients had associated nodal disease, and only 20% had systemic or B symptoms. Three fourths of the patients had stage I or II disease, and approximately two thirds had intermediate-grade lymphoma. Radiation therapy was the primary modality of therapy for localized disease (stages I and II), especially for low-grade lymphomas. Combination chemotherapy with or without radiation was used for more advanced disease and for intermediate- and high-grade lymphomas. Surgery was limited to establishing the diagnosis. Two thirds of the patients had a remission after initial therapy. Two thirds of these patients had no further relapse. Three fourths of the patients with relapse after initial remission died of their disease. The overall and disease-free survival rates for all patients were 60% and 50%, respectively. Outcome of therapy was related to stage and histologic grade. Patients with lymphomas of high histopathologic grade and recurrent and recurrent and disseminated disease had the poorest prognosis.

Management of the neck in a randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer.

BACKGROUND: Treating the neck after organ-preservation treatment with radiotherapy or chemoradiotherapy can be problematic. METHODS: To develop management guidelines, we reviewed the results of a 100-patient phase-3 trial that had compared outcome after radiotherapy alone with outcome after chemoradiotherapy for head and neck cancer. Patients were randomly assigned to receive radiotherapy alone or concurrent chemoradiotherapy. After completing therapy, patients were reassessed, and surgery was recommended for persistent disease at the primary site or neck and for all patients with stage N2-3 neck nodes regardless of clinical response. RESULTS: Of the 47 patients with stage NO-1, 43 had a complete response (CR); of the 18 N1 patients, all but 4 had a CR. One of these 4, as well as 5 others among the NO-1 patients, underwent neck dissection (n = 6). No disease was found on pathologic examination, and no patient had neck recurrence. Of the remaining 41 N0-1 patients, 3 had disease progression and received no further therapy. Of the 38 others, 4 had neck recurrence, with 3 recurring at the primary site. Of the 53 with stage N2-3, 23 had less than a complete response (

A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results.

BACKGROUND: A phase III randomized comparison of radiotherapy alone versus combination chemotherapy and concurrent continuous-course radiotherapy was performed at the Cleveland Clinic Foundation. METHODS: Between March 1990 and June 1995, 100 patients with resectable stage III and IV squamous cell head and neck cancer were randomized to either Arm A: radiotherapy alone, 68-72 Gy at 1.8-2.0 Gy per day; or to Arm B: the identical radiotherapy with concurrent chemotherapy. Chemotherapy consisted of 5-fluorouracil, 1000 mg/m2/day, and cisplatin 20 mg/m2/ day, both given as continuous intravenous infusions over 4 days beginning on day 1 and day 22 of the radiotherapy. At 50-55 Gy, patients were clinically reassessed. If a response was evident, radiotherapy was completed. In non-responding patients, however, radiotherapy was terminated and surgery recommended. After completion of all treatment, salvage surgery was performed, if possible, for any residual primary or nodal disease or for any subsequent locoregional recurrence. RESULTS: Except for an overrepresentation of T1 patients on Arm A, the treatment arms were equivalent. Toxicity was greater in the patients on Arm B with a higher incidence of grade III and IV neutropenia, thrombocytopenia, cutaneous reaction, and mucositis. Feeding tubes were also required more often, and weight loss was greater on the chemotherapy arm. No toxic deaths occurred. With a median follow-up of 36 months, the Kaplan-Meier 3-year projections of relapse-free survival are 52% for Arm A and 67% for Arm B (p = .03), and the likelihood of developing hematogenous metastases is 21% for Arm A and 10% for Arm B (p = .04). Although overall survival is not significantly different, overall survival with successful primary site preservation was 35% for Arm A and 57% for Arm B (p = .02). This difference remains statistically significant in the subsets of patients with laryngeal and hypopharyngeal primaries but not in patients with oropharyngeal primaries. CONCLUSIONS: Continuous-course radiotherapy and concurrent combination chemotherapy is an intensive, toxic but tolerable treatment regimen, which, when compared with radio therapy alone, can produce an improvement in relapse-free survival, a decrease in distant metastases, and an improvement in overall survival with successful primary site preservation.

Cost accounting: toward a measure of truth.

With the reimbursement systems for home care changing and evolving, home care agencies need to be careful in choosing a cost accounting system. There is the traditional system that focuses on compliance, or the cost accounting information system, which caters to the needs of management decision making. Which system is appropriate, and when?

Secondary tracheoesophageal puncture: factors predictive of voice quality and prosthesis use.

OBJECTIVE: To identify factors predicting prosthesis use and final speech quality in patients undergoing secondary tracheoesophageal puncture (TEP) for voice restoration alter laryngectomy. METHODS: We undertook a retrospective study of 168 patients who underwent secondary TEP at the Cleveland Clinic between June 1980 and October 1993. Factors examined were: patient demographics, extent of initial surgery, method of pharyngeal preparation, history of irradiation, insufflation test results, pharyngeal stricture, and concurrent medical conditions. Univariate and multivariate statistical analyses were performed to identify predictive factors. RESULTS: At last evaluation, 73.8% (124) of the patients were still using the prosthesis. Quality of speech was the only predictor of prosthesis use (p < .001). Phonation on the first day was achieved in 90% (151) of patients. Speech result improved significantly over the first 6 months (p < .001). Univariate analysis found that the need for reconstruction at laryngectomy (p = .04), the presence of pharyngeal stricture (p = .001), and continued prosthetic use (p < .001) were associated with the speech result. There was no significant advantage to the lack of approximation of the pharyngeal constrictors (p = .31). Stepwise logistic regression showed that only the absence of pharyngeal stricture was associated with a better-quality voice (p = .001). CONCLUSION: Tracheoesophageal puncture is a reliable method for restoring voice after laryngectomy. Prosthesis use decreases with time, and good voice quality is the only predictor of continued prosthesis use. In this series the absence of pharyngeal stricture was the only significant predictor of good to excellent speech.

The use of fibrin glue in the healing of skin flaps.

PURPOSE: To determine whether the use of fibrin glue has an impact on wound drainage created in an animal model. MATERIALS AND METHODS: Fibrin glue was prepared from single-donation autologous phlebotomy before surgery. Bilateral skin flaps were raised over the parotid gland in 10 rabbits. After exposure of the parotid, fibrin glue was applied on one side using an atomizer. The opposite side was treated with normal saline. Self-suction drains were placed under each flap and the wounds closed. Drainage was recorded daily for 7 days. RESULTS: Drainage differed significantly (P = .001) between the two sides on the first postoperative day and subsequent days. The average drainage on the fibrin-glue-treated side was 2.1 mL on the first day and 0.5 mL on subsequent days. On the nontreated side, the average output was 13.4 mL on the first day and 4.6 mL on subsequent days. CONCLUSIONS: This preliminary animal investigation showed that fibrin glue treatment decreased wound drainage. It is hoped that this concept may be applied to commonly performed head and neck procedures in which large flaps are elevated and large potential spaces are created. By decreasing the amount of drainage, fibrin glue has the potential to improve coaptation of flaps and minimize potential for seroma and hematoma formation. In some cases, the use of closed suction drains may be shortened and possibly eliminated, with shorter length of hospitalization.

Magnetic resonance imaging and the management of parapharyngeal space tumors.

OBJECTIVE: The purpose of this study was to evaluate our experience with the diagnosis and management of tumors of the parapharyngeal space (PPS), with particular emphasis on the evolving role of magnetic resonance imaging (MRI). METHODS: A case series review of 51 patients with parapharyngeal tumors who underwent surgical excision between 1980 and 1992 were analyzed with regard to presenting signs and symptoms, histologic diagnosis, imaging technique (computed tomography [CT] versus MRI), surgical approach, and outcome. RESULTS: Fifty-one patients underwent surgical excision of a parapharyngeal tumor of which the vast majority (78%) were benign neoplasms. Compared with benign neoplasms, the malignant tumors were much more likely to be associated with pain, trismus, and a cranial nerve deficit. MRI was able to locate the tumor in 20 of 21 patients (95%), while CT was able to localize the tumor in 32 of 38 patients (84%). CONCLUSIONS: MRI, because of its superior soft-tissue resolution and ability to provide imaging in multiple planes, is the imaging modality of choice to diagnose neoplasms of the parapharyngeal space. Because most of these tumors are benign, MRI allows the surgeon to select the surgical approach with the least morbidity.

Overview of the rectus abdominis myocutaneous flap in head and neck reconstruction.

The functional and aesthetic consequences of ablative head and neck oncologic surgery pose a significant challenge to the reconstructive surgeon. With the advent of microvascular free tissue transfer the reconstructive capabilities of the surgeon have been greatly expanded. The rectus abdominis musculocutaneous free flap has assumed an important role in contemporary head and neck reconstruction because of its ease of dissection, length and size of the vascular pedicle, convenience of harvest in the supine position, reliability and versatility, and low donor site morbidity.

An overview of treatment options for lower airway obstruction.

Effectively treating airway stenosis is a challenging problem for the otolaryngologist-head and neck surgeon. A number of options are available. The most effective management requires an approach that is flexible and individualized for each patient. This article outlines the available options and highlights the indications, techniques, results, and potential complications of each.

Adenomatous lesions of the temporal bone immunohistochemical analysis and theories of histogenesis.

Adenomatous lesions of the temporal bone represent a diverse group of neoplasms. At least three histopathologic patterns have been described: glandular; ribbon-like, or "festooning;" and aggressive papillary. Combinations of glandular and ribbon-like histologies in the same lesion are not uncommon. The glandular and ribbon-like histologies have been associated with carcinoid tumors, and the aggressive papillary tumor has been considered a separate entity. Recently, the endolymphatic sac has been proposed as the site of origin of the aggressive papillary lesions. Previous reports have described neuroendocrine properties with characteristics embracing the three histologic types. The authors postulate that the neural crest is the site of origin of this unusual group of neoplasms. Immunohistochemical analysis on the pathologic specimens of patients with adenomatous lesions of the temporal bone was performed to test this hypothesis. From 1975 to 1992 seven patients were treated at the Cleveland Clinic Foundation with a diagnosis of middle ear adenoma. A panel of special stains for neuroectodermal markers, including synaptophysin, chromogranin, neuron specific enolase, calcitonin, and serotonin was used on the paraffin-embedded formalin-fixed specimens. Three lesions were also evaluated by electron microscopy, all demonstrating dense core, intracytoplasmic granules. Three ribbon-like tumors were positive for synaptophysin and chromogranin, and two of these were positive for serotonin. One glandular tumor was positive for synaptophysin, and an aggressive papillary tumor was positive for synaptophysin and neuron specific enolase. An additional papillary tumor was referred following a third recurrence without accompanying immunohistochemical data. Cholesteatoma-like material was identified with a few glandular cells interspersed, all negative by immunohistochemical evaluation. The seventh specimen, initially diagnosed as papillary adenoma on light microscopy, was not studied by the aforementioned stains, and was later identified as a papilloma of sinonasal origin. The neural crest gives rise to pluripotential stem cells with widespread anatomic distribution, including the temporal bone. Because immunomarkers used in this study are specific for neuroectodermal differentiation, results suggest that temporal bone adenomas have neuroendocrine characteristics and could be derived from the specialized neuroectoderm of the neural crest.

Tension pneumocephalus following craniofacial resection.

BACKGROUND: The craniofacial approach is a reliable method for excising tumors involving the anterior skull base. Advances in technique have minimized complications. Although cerebrospinal fluid leaks and meningitis are well-known complications, tension pneumocephalus is not well described. We review two cases and discuss the pathophysiology, clinical manifestations, radiographic features, and treatment of tension pneumocephalus. METHODS: Case study. We reviewed the records of all patients who underwent anterior craniofacial resection at our institution, a tertiary care center, from 1976 to 1993. Among 45 patients identified, 2 had tension pneumocephalus. RESULTS: Neurologic deterioration after anterior craniofacial resection occurred in both patients in the immediate postoperative period. Both patients had extradural intracranial air under pressure and were diagnosed with tension pneumocephalus. In one patient, this was treated by needle aspiration followed by catheter drainage, and the second patient was treated with needle aspiration followed by airway diversion. The first patient recovered fully and was discharged on postoperative day 14; the second patient's mental status did not return to the preoperative level, and he was discharged on postoperative day 23 to a rehabilitative facility. Approximately 3 months later, his level of mentation returned to baseline. CONCLUSIONS: Tension pneumocephalus is a potentially devastating complication that may occur after craniofacial resection. It requires prompt recognition and treatment to minimize morbidity.

Undifferentiated nasopharyngeal carcinoma presenting as a parotid mass.

BACKGROUND: Nasopharyngeal carcinoma has a variety of presentations. However, in more than 50% of cases it may present with serous otitis or cervical metastases. Although the metastases usually occur in the neck, the lymphatic network of the parotid may also serve as a site for the metastatic deposits. We present a case in which the initial manifestation of nasopharyngeal carcinoma of the lymphoepithelioma type was a parotid mass. METHODS: Case study. RESULTS: A patient who was initially seen with an isolated parotid mass was found to have an undifferentiated carcinoma of the lymphoepithelial type. Further evaluation identified an occult nasopharyngeal carcinoma, and the patient underwent radiotherapy. CONCLUSIONS: A diagnosis of a malignant lymphoepithelial lesion of the parotid gland or undifferentiated carcinoma of the lymphoepithelial type mandates a search for an occult primary nasopharyngeal tumor.

The AO system for primary mandibular reconstruction.

We reviewed the records of 27 patients who underwent primary mandibular reconstruction with AO plates to investigate the outcome and complications of this procedure. Immediate soft-tissue flap coverage was required in 26 patients. Early complications were seen in 44% of the patients, with the highest incidence after irradiation (P = 0.02). Late complications were mostly related to tumor recurrence (12). Late complications not associated with recurrence were persistent pain (2), minor infections (3), plate exposure (3), and plate fracture (1). Good to excellent cosmetic results were obtained in all but 1 patient. Full mastication was not possible for any of our patients, and therefore function was not fully restored. Speech and deglutition were mostly influenced by the amount of soft-tissue resection. Mean follow-up was 20 months (range 3 to 52). At last evaluation, 12 patients were alive and free of disease, and 15 were dead of disease or other causes. Our results show that primary mandibular reconstruction with rigid plates is a safe, effective, and reliable technique to restore mandibular continuity and cosmesis. For lateral defects, this method is a viable alternative to free vascularized osseocutaneous flaps.

Cricoarytenoid arthritis and ankylosing spondylitis.

A variety of systemic diseases may manifest with laryngeal symptoms. Cricoarytenoid arthritis with or without limitation of vocal fold motion is an example. It has been described in up to 25% of rheumatoid patients. Ankylosing spondylitis is classified among the seronegative spondylarthritides. Besides its systemic features, rare reports of cricoarytenoid involvement have been published. Six previous cases reported have been characterized by a long history of ankylosing spondylitis before the cricoarytenoid joint involvement occurred. We describe only the seventh case of cricoarytenoid arthritis secondary to ankylosing spondylitis and the first patient (to our knowledge) to present with bilateral vocal fold fixation as the initial presenting symptom.