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Objective: This study reports the results of treatment for supraglottic laryngeal cancer with nine different treatment modalities with long-term follow-up., Study Design: Retrospective study of 653 patients with supraglottic laryngeal squamous cell cancer treated from April 1955 to January 1999., Methods: The study population included previously untreated patients with cancer of the supraglottic larynx treated with curative intent by one of nine treatment modalities and who were eligible for 5-year follow-up. The treatment modalities included subtotal supraglottic laryngectomy (SSL), SSL with neck dissection (SSL/ND), total laryngectomy (TL), TL/ND, radiation therapy (RT), SSL/RT, SSL/ND/RT, TL/RT, and TL/ND/RT. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine significance., Results: None of the nine treatment modalities produced a survival advantage, either overall or within the stages. Overall disease specific survival (DSS) by treatment modality included SSL 88.9%, SSL/ND 75.8%, TL 83.3%, TL/ND 66.7%, RT 47.2%, SSL/RT 68.9%, SSL/ND/RT 68.1%, TL/RT 59.3%, and TL/ND/RT 46.7%. Improved DSS and cumulative disease specific survival rates were associated with patients under the age of 65 years (P = .0001), early stage disease, N0 disease (P = .0001), clear resection margins (P = .0094), and no recurrence (P = .0001). Posttreatment function showed that 90% of patients were functional in everyday life, 90.7% were eating satisfactorily, 91.4% were breathing naturally, and 83% of SSL patients, 85.7% of RT patients, and 52.8% of TL patients had "good" voices. Laryngeal preservation was accomplished in 86.1% of SSL patients and 72.7% of RT patients (P = .0190)., Conclusions: No treatment modality produced a survival advantage. Because SSL produced the best rate of laryngeal preservation, we recommend its use in treating the primary in eligible patients. The importance of clear resection margins is stressed. Patients with N+ disease should have the neck treated. Patients with N0 disease may be observed safely with no loss of survival advantage. Because of the pattern of recurrence and the high rates of distant metastasis and second primary cancers, follow-up for a period of not less than 8 years is recommended.

Objectives/hypothesis: The best therapeutic approach for the treatment of stage IV glottic carcinoma is controversial., Study Design: A retrospective study., Methods: A retrospective study of Tumor Research Project data was performed using patients with stage IV glottic squamous cell carcinoma treated with curative intent by five different treatment modalities from 1955 to 1998 at Washington University School of Medicine and Barnes-Jewish Hospital (St. Louis, MO)., Results: Ninety-six patients with stage IV glottic carcinoma were treated by five modalities: total laryngectomy (TL) (n = 13), total laryngectomy with neck dissection (TL/ND) (n = 18), radiation therapy alone (RT) (n = 7) (median dose, 69.5 Gy), total laryngectomy combined with radiation therapy (TL/RT) (n = 10), and total laryngectomy and neck dissection combined with radiation therapy (TL/ND/RT) (n = 48). The overall 5-year observed survival (OS) rate was 39%, and the 5-year disease-specific survival (DSS) rate was 45%. The 5-year DSS rates for the individual treatment modalities included the following: TL, 58.3%; TL/ND, 42.9%; RT, 50.0%; TL/RT, 30.0%; and TL/ND/RT, 43.9%. There was no significant difference in DSS for any individual treatment modality (P =.759). The overall locoregional control rate was 69% (66 of 96). The overall recurrence rate was 39% with recurrence at the primary site and in the neck at 19% and 17%, respectively. Recurrence was not related to treatment modality. The 5-year DSS after treatment of locally recurrent cancer (salvage rate) was 30% (3 of 10) and for recurrent neck disease (28 of 67) was 42%. The incidence of delayed regional metastases was 28%; of distant metastasis, 12%; and of second primary cancers, 9%. There was no statistically significant difference in survival between node-negative (N0) necks initially treated (5-y DSS, 31%) versus N0 necks observed and later treated if necessary (5-y DSS, 44%) (P =.685)., Conclusion: The five treatment modalities had statistically similar survival, recurrence, and complication rates. The overall 5-year DSS for patients with stage IV glottic carcinoma was 45%, and the OS was 39%. The cumulative disease-specific survival (CDSS) was 0.4770 with a mean survival of 10.1 years and a median survival of 3.9 years. Patients younger than age 55 years had better survival (DSS) than patients 56 years of age or older (P =.0002). Patients with early T stage had better survival than patients with more advanced T stage (P =.04). Tumor recurrence at the primary site (P =.0001) and in the neck (P =.014) and distant metastasis (P =.0001) had a deleterious effect on survival. Tumor recurrence was not related to treatment modality. Patients with clear margins of resection had a statistically significant improved survival (DSS and CDSS) compared with patients with close or involved margins (P =.0001). Post-treatment quality of life was not significantly related to treatment modality. Patients whose N0 neck was treated with observation and appropriate treatment for subsequent neck disease had statistically similar survival compared with patients whose N0 neck was treated prophylactically at the time of treatment of the primary. A minimum of 7 years of follow-up is recommended for early identification of recurrent disease, second primary tumors, and distant metastasis. None of the standard treatment modalities currently employed has a statistical advantage regarding survival, recurrence, complications, or quality of life.

Background: The best therapeutic approach for the treatment of T3N0M0 (stage III) glottic carcinoma is controversial., Method: A retrospective study of Tumor Research Project data were performed using patients with T3N0M0 glottic squamous cell carcinoma treated with curative intent by seven different treatment modalities from January 1950 to December 1996 at Washington University School of Medicine/Barnes-Jewish Hospital., Results: Two hundred patients with T3N0M0 glottic carcinoma were treated using seven modalities: total laryngectomy (TL, n = 30), TL with neck dissection (TL/ND, n = 40), conservation surgery alone (CS, n = 22), radiation therapy alone (RT, n = 29), TL combined with RT (TL/RT, n = 31), TL and ND combined with RT (TL/ND/RT, n = 36), and CS combined with RT (CS/RT, n = 12). The overall 5-year observed survival rate (OS) was 54% and the 5-year disease-specific survival rate (DSS) was 67%. The 5-year DSS for the individual treatment modalities included TL, 65.4%; TL/ND, 76.5%; CS, 71.4%; RT, 56.5%, TL/RT, 51.9%; TL/ND/RT, 71.4%; and CS/RT, 80%. There was no significant difference in DSS for any individual treatment modality (P =.375). The overall local and regional control rate was 74% (148 of 200). The overall recurrence rate was 37.5% with recurrence at the primary site and in the neck of 19.5% and 11%, respectively. Recurrence was not related to treatment modality. The 5-year DSS after treatment of recurrent cancer (salvage rate) was 35.8%. The incidence of distant metastasis was 11% and for second primary cancers it was 19.5%. There was no statistically significant difference in survival between necks initially treated (72%, 5-y DSS) versus necks observed and later treated if necessary (70%, 5-y DSS) (P =.797)., Conclusions: The seven treatment modalities had statistically similar recurrence, complication, and survival rates. Patients with clear surgical margins have a significant survival advantage compared with patients with close and involved margins. Because postoperative radiation therapy in patients with positive margins did not improve survival, formal re-resection of the site of the positive margin should be considered. In patients whose N0 neck was not treated electively, close follow-up observation with meticulous examinations combined with appropriate treatment for subsequent neck disease resulted in a similar survival rate compared with those patients whose N0 necks were treated initially. Six-year minimum follow-up is recommended for early identification of primary and neck recurrence and for discovering expected second primary cancers. Patients treated with RT and CS had statistically similar rates of survival, maintenance of voice, and acquired permanent tracheal stoma. CS is a valid alternative to RT in treating highly selected patients with T3N0 glottic carcinoma.

A retrospective tumor registry analysis of patients with squamous cell carcinoma (SCC) of the larynx and hypopharynx who were treated with curative intent in the Department of Otolaryngology--Head and Neck Surgery at Washington University School of Medicine and Barnes Hospital between January 1971 and December 1991. In 2,550 patients, the mean age, sex and tumor differentiation did not affect the incidence of distant metastases. The overall incidence of distant metastases was 8.5% (217/2,550 patients) with the following distribution: glottis 4.4%, supraglottis 3.6%, subglottis 14%, aryepiglottic fold 16%, pyriform sinus 17% and posterior hypopharynx 17.6%. The overall 5-year disease-specific survival for distant metastases was 6.4%. Distant metastases were related to advanced local disease (T3 + T4), lymph node metastases at presentation (N+), tumor location (hypopharynx) and locoregional tumor recurrence (p < or = 0.028). A meta-analysis of variables which predispose to a higher incidence of distant metastases indicate that tumor location (hypopharynx > larynx), advanced primary disease (T3 + T4), regional disease (N+), locoregional recurrences, and advanced regional metastases (N2 + N3) are statistically significant., (Copyright 2001 S. Karger AG, Basel)

The third case of liposarcoma of the larynx, this one arising from the preepiglottic space, is presented. The report is unique in so far as the patient previously had been treated for a liposarcoma in another anatomic region. The diagnosis in this case was in doubt until electron microscopic studies were done. Since the histopathology of the laryngeal and the previous liposarcoma were different, the question of metastasis versus multicentricity was raised. Other discussions of liposarcomas over the past three decades have not resolved this aspect of their behavior completely. In this instance, after considering avenues of metastatic spread in conjuction with the histopathology, it would appear that the laryngeal lesion was a second primary and not a metastasis.

The speculation whether juvenile laryngeal papillomatosis may transform into or be associated with epidermoid carcinoma is explored. We document a case of invasive laryngeal carcinoma arising in preexisting juvenile laryngeal papillomatosis. After multiple childhood laryngoscopies and a tracheotomy, a 54-year-old, 30-pack per year smoker, who had never received radiation therapy, developed a florid exophytic transglottic squamous cell carcinoma. Histologically, the invasive epidermoid carcinoma was surrounded by a field of papillomata with varying degrees of atypical changes. After total laryngectomy, isolated papillomata were found in the lower trachea. There were no cervical lymph node metastases. No postoperative radiation therapy was given. Persistent squamous papillomata in the tracheostomy site, the lower trachea, and the posterior pharynx were treated with the CO2 laser. We emphasize the need to maintain a high index of suspicion for malignancy. In addition, we review the problem of benign papillomata in the aerodigestive tract following laryngectomy.

This paper deals with the limitations of conservation surgical therapy for cancer in various sites. The detailed techniques are not included in this paper, but rather its pathophysiological approach to partial surgery. The technique has been reported many times previously.

Four hundred sixty-three patients with glottic carcinoma were treated by surgical techniques with or without preoperative irradiation. Two hundred eighty-one had hemilaryngectomy and 182 total laryngectomy procedures. The overall cure rate for the hemilaryngectomy group was 91 percent and 80 percent for the total laryngectomy group, with an overall cure rate of 87 percent. Our observations support the fact that Stage I glottic carcinoma has slightly better prognosis when treated by hemilaryngectomy. Stage II and III lesions have a significant improvement in cure rate and survival when treated with combined preoperative irradiation and partiall vertical laryngectomy or total laryngectomy than by irradiation alone.

The role of leucine andalanine aminopeptidases is stidued in three different biologic systems: experimental wound healing in the rat, experimental carrageenan induced intraderman granulomas in the rat, and human laryngeal carcinomas. The wound healing experiments indicate that the proliferating granulation tissue has high quantities of aminopeptidases activity which is residing primarily intracellularly in granulocytes, macrophages, mast cells fibroblasts, and new budding vessels. The quantititave levels of tissue aminopeptidases correlate positively with the degree of cellularity of the wound and fibroblastic activity. Some aminopeptidases (isoenzymes) are secreted or released by the fibroblasts in be blood serum. Starch gel electrophoretic analysis demonstrates thses with different concentrations and migration rates. Two are probably released or secreted into the serum, and th third is membranous bound in the cytoplasm (lysosomal). The carrageenan intradermal granuloma demonstrates a different inflammatory reaction which is rich in macrophages and produces a different pattern of aminopeptidases activity. Macrophages produce a high tissue level of aminopeptidase activity which is intracellular bound and not readily leached out into the serum. Gel electrophoresis studies of aminopeptidases produced by the granuloma demonstrate that the tissue bound enzyme is the main component. In addition, there appears to be a mechanism, which is not understood, for specific induction or activation of lysosomal proteolytic and carbohydrase enzymes. This mechanism is dependent on the nature of composition of the injuring agent. Laryngeal carcinomas demonstrate high tissue homogenate levels and normal serum levels of aminopeptidase activities. These enzymes are located in the tumor stroma. They are not directly related to tumor invasiveness but to the degree of stromal proliferation. The tumor stroma behaves as though it were a non-healing wound constantly secreted proteolytic enzymes (aminopeptidases). A major problem that needs to be resolved is to find the operating mechanism by which malignant cells interact with their constantly proliferating fibroblastic stroma.