Aerodigestive Tract Malignancies Research Articles

Esophageal cytology in the follow‐up of patients with treated upper aerodigestive tract malignancies

Esophageal cytology in the follow‐up of patients with treated upper aerodigestive tract malignancies

Esophageal cytology in the follow-up of patients with treated upper aerodigestive tract malignancies

Patients with an history of carcinoma of the upper aerodigestive tract are at high risk for recurrence or the development of new tumors in this region. In the majority of follow-up protocols, these patients undergo radiologic and endoscopic evaluation as a means of surveillance for the early detection of recurrence. The brush biopsy-capsule technique represents a noninvasive and inexpensive screening device for this patient population. In the current study, the authors retrospectively assessed the sensitivity, specificity, and predictive value of esophageal brush-capsule cytology for the detection of malignant lesions of the upper aerodigestive tract in this high risk patient population. Cytologic specimens from 334 patients with previously treated upper aerodigestive malignancies were available for review. The cytologic, endoscopic, and clinical follow-up of each case were studied over a follow-up period of 3 years. Gold standard was the clinical follow-up for the negative cases (who were not submitted to biopsy) and biopsy for the positive cases. Sensitivity, specificity, and predictive value were calculated. Using cytology 33 malignancies were detected in 25 patients during a 3-year follow-up period. The test was found to have a sensitivity of 88.7% and a specificity of 90.7%. In 66% of cases the malignancies were located in the oropharynx; the others were located in the esophagus. In 70% of cases the malignancies were detected at an early stage. Esophageal brush-capsule cytology is a simple noninvasive technique that has been proven to be useful in the early detection of metachronous and recurrent neoplasms in the follow-up of patients with previously treated carcinomas of the ear, nose, and throat.

Effects of Ethanol Treatment on Proliferation and Differentiation in a Head and Neck Squamous Cell Carcinoma Cell Line

Introduction: Epidemiologic studies have provided evidence that chronic ethanol consumption is an independent risk factor in upper aerodigestive tract cancer, but the underlying mechanisms are largely unknown. Method: To examine ethanol effects on mucosal keratinocytes in vitro, we used a squamous cell carcinoma of the head and neck (SCCHN) cell line as a model and, to exclude line specific effects, two other cell lines. The influence of ethanol on proliferation (using [3H]thymidine uptake/cell number), cell cycle distribution, cytokeratin pattern, and growth factor receptor expression (using FACS analyses) was investigated. Result: Ethanol increased in a dose dependent manner (tested range 10-3M to 10-10 M) the [3H]thymidine uptake and cell number, with unaltered viability (>95%) in all concentrations. In ail tested cell lines, addition of 10-3 M ethanol caused: (a) a significant increase of cells in the S-phase of the cell cycle; (b) a shift of cytokeratin pattern that suggested inhibition of differentiation; and (c) significant upregulation of EGF, IL-4, and PDGF receptors. Conclusions: Our results demonstrated an increased proliferation and reduced differentiation induced by ethanol in mucosa derived neoplastic cells, which may enhance further growth of neoplastic cells. These effects may also be involved in the carcinogenesis of upper aerodigestive tract malignancies.

Effects of Ethanol Treatment on Proliferation and Differentiation in a Head and Neck Squamous Cell Carcinoma Cell Line

Epidemiologic studies have provided evidence that chronic ethanol consumption is an independent risk factor in upper aerodigestive tract cancer, but the underlying mechanisms are largely unknown. To examine ethanol effects on mucosal keratinocytes in vitro, we used a squamous cell carcinoma of the head and neck (SCCHN) cell line as a model and, to exclude line specific effects, two other cell lines. The influence of ethanol on proliferation (using [3H]thymidine uptake/cell number), cell cycle distribution, cytokeratin pattern, and growth factor receptor expression (using FACS analyses) was investigated. Ethanol increased in a dose dependent manner (tested range 10(-3) M to 10(-10) M) the [3H]thymidine uptake and cell number, with unaltered viability (>95%) in all concentrations. In all tested cell lines, addition of 10(-3) M ethanol caused: (a) a significant increase of cells in the S-phase of the cell cycle; (b) a shift of cytokeratin pattern that suggested inhibition of differentiation; and (c) significant upregulation of EGF, IL-4, and PDGF receptors. Our results demonstrated an increased proliferation and reduced differentiation induced by ethanol in mucosa derived neoplastic cells, which may enhance further growth of neoplastic cells. These effects may also be involved in the carcinogenesis of upper aerodigestive tract malignancies.

Surgical outcomes in head and neck cancer patients 80 years of age and older.

Elderly patients over 80 years of age represent a growing population, some of whom have complex medical problems that are compounded by the presence of upper aerodigestive tract cancer. Forty-three patients, aged 80 years and older, who were initially seen with head and neck squamous cell carcinoma from 1986 to 1992 at a tertiary-care center were compared with 79 similar patients, aged 65 years or younger, in a retrospective, case-control study. Median overall survival for the patients over 80 years of age was significantly lower than that for the controls (p = .001). However, their overall survival was similar to the actuarial survival for the general octogenarian population. Advanced age also adversely affected local control (p < .001) and disease-specific survival (p = .041). Although the older age group had a higher frequency of morbid preoperative conditions, there were no significant differences in perioperative or postoperative complications between the two groups. Careful preoperative staging and evaluation of associated medical illnesses, as well as skillful perioperative and postoperative management, are essential for reducing operative morbidity and mortality in the octogenarian patient. Successful outcome depends upon appropriate surgical management, treatment of concurrent illnesses, and minimization of postoperative complications. Individualized surgical management of the elderly head and neck cancer patient is effective, well tolerated, and clinically indicated for upper aerodigestive tract malignancies.

Oral and Upper Aero-Digestive Tract Malignancy: A Review of a Five-Year Experience

(25%) and 179 males (69.4%). In 12 cases (4.7%), sex was not specified. The most affected age group was between 41-50 years (24.5%), and the least affected were those above 91 years and below 11 years ( Table 1). The most common malignancy was squamous cell carcinoma (50.7%), followed by basal cell carcinoma (15.9%). Metastatic carcinoma constituted about 13.2%, nonHodgkin’s lymphoma 10.8%, including Burkitt’s lymphoma (1.2%), and adenocarcinoma was 2.3%. 5 The lowest incidence was mucoepidermoid, verrucous carcinoma, and melanoma, accounting for 1.2%. This was followed by Hodgkin’s (0.8%) and adenoid cystic carcinoma (0.5%). There were three cases of anaplastic carcinoma (1.2%). Rhabdosarcoma and neuroblastoma constituted 0.8%. (Table 2). Lymph nodes were the most affected site, with malignancy comprising 20.2%. The skin of the head and neck was the second most common site (19.3%), followed by the nasopharynx (15.9%), buccal mucosa (9.7%), tongue (8.9%), neck (6.9%), and larynx and salivary glands (3.9% each) ( Tables 3 and 4). The least involved sites were the minor salivary glands and gingiva. The sternocleidomastoid was involved with rhabdosarcoma in one case.

Surgical outcomes in head and neck cancer patients 80 years of age and older

Background Elderly patients over 80 years of age represent a growing population, some of whom have complex medical problems that are compounded by the presence of upper aerodigestive tract cancer. Methods Forty-three patients, aged 80 years and older, who were initially seen with head and neck squamous cell carcinoma from 1986 to 1992 at a tertiary-care center were compared with 79 similar patients, aged 65 years or younger, in a retrospective, case-control study. Results Median overall survival for the patients over 80 years of age was significantly lower than that for the controls (p = .001). However, their overall survival was similar to the actuarial survival for the general octogenarian population. Advanced age also adversely affected local control (p < .001) and disease-specific survival (p = .041). Although the older age group had a higher frequency of morbid preoperative conditions, there were no significant differences in perioperative or postoperative complications between the two groups. Conclusions Careful preoperative staging and evaluation of associated medical illnesses, as well as skillful perioperative and postoperative management, are essential for reducing operative morbidity and mortality in the octogenarian patient. Successful outcome depends upon appropriate surgical management, treatment of concurrent illnesses, and minimization of postoperative complications. Individualized surgical management of the elderly head and neck cancer patient is effective, well tolerated, and clinically indicated for upper aerodigestive tract malignancies. © 1998 John Wiley & Sons, Inc. Head Neck 20:216–223, 1998.

Head and neck cancer screening among 4611 tobacco users older than forty years.

We implemented screening for squamous cell carcinomas of the oral cavity, pharynx, and larynx with symptom assessment and systematic inspection of the oral mucosa by primary care practitioners at health care sites serving inner-city residents of Boston; 4611 tobacco users older than 40 years were screened, and 313 with specific criteria were referred to otolaryngology for diagnostic evaluations. In these screened patients, the prevalence of oral mucosal lesions was almost 13% and prevalence of persistent hoarseness was more than 11%. Although the identification of these cancers was rare (nearly 3%), abnormal findings were seen in more than 70% of referred patients. These clinical and histologic diagnoses are described. We have documented the range of pathologic conditions in high-risk patients screened for upper aerodigestive tract malignancy.

Head and neck cancer screening among 4611 tobacco users older than forty years

We implemented screening for squamous cell carcinomas of the oral cavity, pharynx, and larynx with symptom assessment and systematic inspection of the oral mucosa by primary care practitioners at health care sites serving inner-city residents of Boston; 4611 tobacco users older than 40 years were screened, and 313 with specific criteria were referred to otolaryngology for diagnostic evaluations. In these screened patients, the prevalence of oral mucosal lesions was almost 13% and prevalence of persistent hoarseness was more than 11%. Although the identification of these cancers was rare (nearly 3%), abnormal findings were seen in more than 70% of referred patients. These clinical and histologic diagnoses are described. We have documented the range of pathologic conditions in high-risk patients screened for upper aerodigestive tract malignancy. (Otolaryngol Head Neck Surg 1997;116:201-8.)

Surgical management of cervical lymph node metastases.

Surgical management of regional metastases from upper aerodigestive tract malignancies has shifted from the traditional radical resection to more conservative procedures that are tailored to the extent of nodal disease and to the location of the primary tumor. When the primary tumor is treated surgically, a selective neck dissection is now performed routinely in the patient with a clinically negative neck who has a significant risk of developing regional disease. Future directions of research should emphasize clinicopathologic and molecular predictors of occult metastases in the N0 neck to allow selective, therapeutic, and cost-effective treatment of the cervical lymphatics.

The natural history of globus pharyngeus.

While globus pharyngeus is a common disorder, accounting for 3% to 4% of new otolaryngology outpatient referrals, few long-term follow-up studies have been conducted on patients with this condition. The authors of this study followed 74 patients with a diagnosis of globus pharyngeus for an average of 7 years, 7 months (range: 7 years to 8 years, 10 months). During the follow-up period, 55% of patients were asymptomatic and 45% of patients had persistent symptoms. An in-depth analysis of features at clinical presentation failed to reveal any reliable prognostic indicators. A number of patients developed other conditions during the follow-up period, but no patient developed upper aerodigestive tract malignancy. This study represents the longest follow-up of globus patients to date and, to the authors' knowledge, is the first to address the issue of malignancy in globus.

Human papillomavirus in laryngeal and hypopharyngeal carcinomas. Relationship to survival.

To determine the relationship between human papillomavirus (HPV) DNA detection in upper aerodigestive tract malignancies and patient outcome. Archival paraffin-embedded specimens from 78 previously untreated patients with squamous carcinomas of the larynx and hypopharynx were pathologically verified and analyzed by polymerase chain reaction for detection of HPV DNA. Charts were independently reviewed and coded until final analysis. The University of Texas M. D. Anderson Cancer Center, Houston, a tertiary cancer referral center. DNA was successfully extracted from 65 archival patient samples (83%). The mean (+/- SEM) duration of follow-up for these patients was 42 +/- 21 months. Thirty specimens (46%) exhibited detectable HPV DNA. Detection of HPV was significantly related to decreased survival, independent of disease stage. Log rank testing revealed that HPV detection, pathologic vascular invasion, and nodal status were the most significant predictors of death of disease. Laryngeal and hypopharyngeal carcinomas with detectable HPV may represent a biologically distinct subset of tumors that carry a poorer prognosis than do cancers with no detectable HPV.

Radiotherapy for carcinoma-in-situ of the glottic larynx

Purpose : To describe the long-term results of radiotherapy as treatment for carcinoma-in-situ of the glottic larynx. Methods and Materials : Twenty-nine patients with a histologic diagnosis of carcinoma-in-situ (CIS) of the true vocal cord were treated in the Department of Radiation Oncology at Stanford University Medical Center over a 32-year period from 1958–1990. Twenty patients were treated at the time of initial diagnosis following biopsy only (12) or vocal cord stripping (8) and the remainder were referred for treatment of recurrent CIS following one or more prior surgical procedures. Treatment was delivered with megavoltage equipment to a total dose of 53–66.5 Gy (mean 62 Gy) in 180–250 cGy fractions. The mean follow-up time is 10 years, with a range of 2–27 years. Results : Two patients relapsed locally. One patient had recurrent CIS 5 months after radiotherapy and was salvaged with vocal cord stripping. The other developed microinvasive squamous cell carcinoma and underwent total laryngectomy. The actuarial freedom from local relapse and overall survival at 10 years are 92% and 64%, respectively. No local failures occurred more than 5 years after treatment. Late complications from radiotherapy were rare, and voice quality was good-to-excellent in 90% of patients. The actuarial risk of a second aerodigestive tract malignancy is 11% at 10 years. Conclusion : Radiation therapy is an effective and safe treatment modality for carcinoma-in-situ of the glottic larynx. Long-term local control is achieved in approximately 90% of patients with 75% having normal voice.

The incidence of second primary tumors in long-term survivors of small-cell lung cancer.

A review of 446 patients who were enrolled consecutively in small-cell lung cancer (SCLC) protocols was performed to identify in long-term survivors the frequency of new primary tumors and their clinical impact. Forty-seven patients (10.5%) were identified to be free of disease at 2 years. Second primary tumors (SPTs) were diagnosed in 14 patients. The overall risk for developing an SPT was 10.3% per person-year. Actuarial risk at 8 years was 50.3% for an SPT. In this review, SCLC showed one of the highest incidences of SPTs reported in aerodigestive tract malignancies. A long-term survivor was more likely to have an SPT than a relapse of SCLC. Consequently, the odds of death from an SPT compared with that from a relapse increased sharply from 1:13 within 4 years from diagnosis to 8:1 afterwards. Long-term survivors of SCLC would be excellent candidates for chemoprevention trials.

Surgical complications in cancers of the upper aerodigestive tract

The present paper studies the post-operative complications encountered in 300 patients of various upper aerodigestive tract malignancies who were surgically treated. The complications encountered included wound sepsis with or without a fistula, aspiration penumonitis, chylous leak, meningitis, secondary haemorrhage, pleural injury, tracheal tear and tetany. Advanced disease, salvage surgery following radiation failure and positive resected margins were found to adversely affect the complication rate. Ways and means to prevent and treat the above complications are also discussed.

The Role of Endoscopy in Evaluating Head and Neck Cancer Patients: Conclusion of a Multi-institutional Prospective Study

At the annual meeting of the American Academy of Otolaryngology–Head and Neck Surgery in Washington, DC, on September 26, 1988, Nancy Snyderman, MD, University of Arkansas, Little Rock, presented a combined study, for eight institutions, that investigated the diagnostic role of panendoscopic examination. This was a prospective study begun in 1985 that included 569 patients who presented with upper aerodigestive tract malignancies and, as part of their preoperative evaluation, underwent panendoscopic examinations. Synchronous tumors were defined as a second tumor that appeared at the same time as the index tumor, whereas metachronous tumors were those that appeared within 6 months. Synchronous tumors were found in 7.9% of cases. Metachronous tumors were found in 10% of cases. The most common sites for the second primary tumor were other locations in the head and neck and in the lung. Of the head and neck primary tumors, the most common second site was

Mandibulotomy in the irradiated patient.

Though the "mandibular swing," as an approach to certain upper aerodigestive tract malignancies, has been gaining popularity in recent years, there has been little reported as to the feasibility of this procedure in subjects who have received radical preoperative radiotherapy. We have recently reported the results of 23 such patients, and we now present an update. The results presented are of a retrospective analysis of 44 patients, 50% of whom received radical preoperative radiotherapy to fields including the osteotomy site. As in the previous study, there were no statistically significant differences between the complication rates in the irradiated and nonirradiated patient populations. All the patients were orally rehabilitated.

Changing trends in the management of squamous carcinoma of the tongue

An analysis of 412 patients with primary squamous carcinoma of the tongue seen from 1969 through 1978 reveals that the age and clinical stage of patients with tongue cancer have remained constant when compared with previous reports from our hospital. The proportion of female patients has increased, and we are seeing more patients with tumors located in the base of the tongue. Treatment methods are changing. Mandible-sparing procedures were used more often, and significantly more patients received primary and adjuvant radiotherapy in the early study period. At the same time, there were fewer composite neck, tongue, and jaw resections and fewer laryngectomies, although more patients had elective treatment of the neck. The overall determinate cure rate has not changed since the 1957 through 1963 period. Age, sex, and adjuvant radiotherapy did not seem to affect survival. When patients with oral tongue primary lesions were compared with those with tumors in the base of the tongue, the prognosis seemed to be better in those with oral primary lesions when the patient had stage I or II disease. Finally, patients with tongue cancer have at least a 1 in 5 chance of development of a second aerodigestive tract malignancy and require lifelong scrutiny. Although current therapy results in lower morbidity, the proportions of patients with stage III and IV tumors remain high, and the cure rates remain disappointingly stable.