Second primary carcinomas in the upper aerodigestive tract in different locations and age groups

BACKGROUND: Second primary tumors are of great importance for diagnostics, therapy and prognosis in patients suffering from squamous cell carcinomas of the upper aerodigestive tract. The clinical observation of an increase of second primaries was the reason for analyzing all patients with head and neck cancer treated for a certain period of time at our institution. METHODS: The hospital charts of 576 patients treated for squamous cell carcinoma of the oral cavity, the oropharynx, the hypopharynx and larynx treated from 1993 till 1996 at the Department of Otolaryngology, Head and Neck Surgery of the University of Würzburg were reviewed retrospectively. RESULTS: 10.1% of all patients developed a second primary tumor. The rate was highest for patients with carcinoma of the oral cavity (17.5%), followed by tumors of the hypo- and oropharynx (11.7% and 11.5%) and the larynx (6.4%). Besides the location, younger age was detected as a risk factor for the formation of second malignancies. The latency between first and second primary tumor was 2.9 years in average. 31% of the second primaries were detected synchronous, 39% metachronous. CONCLUSION: The results demonstrate that younger patients and patients with carcinomas of the upper digestive tract need a consequent follow-up. The development of second primaries even years after the first malignoma demonstrates the necessity of lifelong follow-up and oncological care.     

Multiple primaries of the upper aerodigestive tract, esophagus, and lung

The existence of multiple primary tumors of the upper aerodigestive tract, esophagus, and lung (UADT-E-L) is related with a common etiopathogenic factor (alcohol-tobacco association). In a review of 43 patients, 6.75% with a UADT-E-L tumor developed another neoplasm, 3.25% at the same site. Nine percent (8.59%) of the tumors were synchronic and 10.85% were metachronic. The most frequent association was larynx-lung. Another neoplasm was detected by physical examination and/or radiology in 44.18% of cases, with a time lapse of less than 3 years in 50%. The most frequent treatment was surgery with/without complementary radiotherapy. The most common stage was T1-T2 (62.06%) and N0-N1 (68.96%). The survival rate was 31% at 2 years and 25% at 3 years.     

Nocardiosis of the upper aerodigestive tract

Nocardia asteroides is the major cause of nocardiosis in the respiratory tract. The primary site of infection is the lung, with the upper aerodigestive tract being a rare region for localized disease to occur. We describe a case of a nocardial vallecular cyst and discuss the diagnosis and management of this unusual infection.     

Basaloid-squamous carcinomas of the upper aerodigestive tracts

Basaloid-squamous carcinoma is a new addition to the lexicon of variants of squamous cell carcinoma. The carcinoma is distinctive histologically, is biologically high grade, and manifests a predilection for the base of tongue, hypopharynx, and supraglottic larynx.     

Amyloidosis of the upper aerodigestive tract

OBJECTIVES/HYPOTHESIS: To delineate the clinical and pathologic characteristics of upper aerodigestive tract amyloidosis with particular attention to laryngeal amyloidosis. STUDY DESIGN: Retrospective chart review of patients with amyloidosis of Thomas Jefferson University and its affiliated hospitals. MATERIAL AND METHODS: The charts of 16 patients with upper aerodigestive tract amyloidosis identified from the databases of the Thomas Jefferson University pathology department were reviewed and included in the study. RESULTS: Sixteen patients (9 male and 7 female, with an average age of 49.8 years) with upper aerodigestive tract amyloidosis were identified. The most common site of amyloid involvement was the larynx. Consequently, patients most commonly presented with hoarseness (14 of 16). All patients underwent surgical removal of the amyloid deposits. Fourteen patients had primary localized amyloidosis. Two experienced systemic involvement. Seven of the 16 patients developed recurrences requiring further treatment. CONCLUSIONS: Amyloidosis of the upper aerodigestive tract generally behaves as a benign, localized condition treatable by surgical resection. Regular follow-up with laryngoscopy is indicated for early diagnosis of recurrence, and multiple surgical procedures may be required to control symptoms.     

Caustic ingestion injuries of the upper aerodigestive tract.

Few reports have described in detail the injuries that occur to the oral cavity, pharynx, and larynx following caustic ingestion. The role of dynamic radiographic studies to delineate the extent of damage has been minimized. In-depth radiographic analysis of such cases has not, to our knowledge, been previously reported. In order to examine the injuries and functional abnormalities of these sites following caustic ingestion, the records of The Johns Hopkins Swallowing Center were reviewed. Five patients were identified as having significant upper aerodigestive tract caustic injuries. All patients had dysphagia, epiglottis injuries, and incomplete laryngeal protection with aspiration. Four of five had sustained some degree of esophageal stenosis. Also noted were pharyngeal muscle dysfunction, nasopharyngeal regurgitation, tongue fixation, and hypopharyngeal stenosis. Roentgenographic findings are described and illustrated. The multidisciplinary approach to the management and rehabilitation of these patients is discussed.     

Extensive upper aerodigestive tract anomalies in 'VACTERL' Association.

Extensive upper aerodigestive tract anomalies are rare in newborns. When they occur, they are often accompanied by other congenital malformations. We present a case of a newborn who presented to the Montreal (Quebec) Children's Hospital with severe tracheoesophageal abnormalities, as part of vertebral, anal, cardiac, tracheal, esophageal, renal, and limb anomalies (VACTERL) association. In spite of surgical intervention, the patient finally succumbed to other congenital abnormalities. Management of infants with such conditions usually involve complex reconstructive efforts, while prognoses remain poor due to other congenital defects and cardiopulmonary complications.     

Multiple synchronous and metachronous cancers of the upper aerodigestive tract: a nine-year study

This retrospective study was based on 9,089 patients and includes 855 cases (9.4%) of multiple primary cancers treated between 1975 and 1983. Three hundred fifty (42.1%) of these multiple cancers were considered synchronous, while 480 (57.9%) were classified as metachronous. Fifty percent of the metachronous cancers occurred within 31 months after the first primary; the mean time between the first primary and the second primary was 45 months. Approximately 22% of second primaries were found more than 5 years after the initial tumor. Five-year survival rates were higher in metachronous cancers (55%) than in synchronous cancers (18%). Survival rates varied according to the treatment. In 49.4% of synchronous tumors the treatment had to be modified because of the presence of two cancers. In these patients, 5-year survival rates were as low as 8%. In synchronous cancers that required no modification of the treatment, the prognosis was better and the survival rate was 28%. The preferential anatomical location of the second synchronous and metachronous cancers is discussed for first primaries situated in the oral cavity (103 cases), the oropharynx (120 cases), the hypopharynx (92 cases), and the larynx (87 cases). Second primaries in the esophagus were mostly synchronous cancers while, in the lung, second cancers were more frequently metachronous tumors.     

Condylomatous lesions of the upper aerodigestive tract

Condyloma acuminatum is one of four types of common human verrucous lesions that are of viral etiology. Also known as "moist wart," condyloma acuminatum is most often seen on the mucosal surfaces of the anogenital area. However, occurrences in the mucosal lined areas of the head and neck region are quite rare. Since 1901, 30 cases of condylomatous lesions have been reported in the upper aerodigestive tract, occurring mainly in the various regions of the oral cavity. Eighteen of the cases were confirmed by histopathologic documentation, while the remainder were anecdotal. We have recently encountered six new cases of condyloma acuminatum, verified by histologic examination. One occurred on the tongue, another in the tonsillar fossa, one in the hypopharynx and three on the vocal cords. We present these cases and review the previously reported cases. In addition, we will discuss the differential diagnosis of these lesions, and their importance to the practicing otolaryngologist.     

Predictive factors of nodal metastases in oral cavity and oropharynx carcinomas.

OBJECTIVE: To estimate the value of tumor (T)-related parameters (singly or in association) in predicting the presence of occult metastases in oral cavity and oropharynx carcinomas. STUDY DESIGN: We considered tumor size (T size), Broders' grading of histologic differentiation (G), invasive cell grading (ICG), and thickness. For every single factor, we evaluated the correlation between the parameter and occult metastases in N0 neck disease, the correlation between the parameter and metastases independently from node (N) class, and the relation between the parameter and extracapsular spread. On the basis of previous results, we gave a score to each parameter that showed higher significativity the sum of which we called global score (GS). We compared the predictivity of metastasis of the GS to that of the single parameters to obtain a more efficacious index. METHODS: Sixty-one patients with carcinomas of the oral cavity and oropharynx who underwent surgery on T and N were examined. RESULTS: Our preliminary results have highlighted a significant correlation between G, ICG, and the presence of occult metastases. No correlation between T size and metastases was highlighted. The GS obtained from G and ICG turned out to be highly significant. A strong correlation was found between the ICG score and extracapsular spread: a high risk of extracapsular spread was found in patients with an ICG score > or =13. CONCLUSION: We perform elective neck dissection in T1-T2 N0 neck disease with ICG > or =13 and GS1 > or =9.     

Analysis of T-cell receptor expressing lymphocytes infiltrating squamous cell carcinomas of the upper aerodigestive tract

T-lymphocytes expressing T -cell receptors (TCRs) of the / type have been suggested to play an important role in mucosal defense against infection and neoplastic transformation. In this study, an immunohistochemical investigation was performed on the distribution of / and / TCRs among tumor-infiltrating lymphocytes. Thirteen patients with squamous cell carcinomas of the upper aerodigestive tract were studied, using monoclonal antibodies and an avidin-biotin-peroxidase technique. Most of the T-cells had an / TCR. Only 1.6% of the T-cells within the cancer tissue and 1.2% of the T-cells in the parenchyma adjacent to the cancer tissue expressed /gd TCRs. These results are consistent with the results of similar studies in bronchial and breast carcinomas. Biopsies from normal oral mucosa in nine healthy individuals showed that 1.3% of the T -cells within the epithelium and 1.0% of those in the lamina propria adjacent to the epithelium expressed / TCRs. Quantitatively the results do not support the theory that / T-cells play an important role in the immunological response against cancer tissue in the mucosa of the upper aerodigestive tract. The functional role of these cells in the mucosa and in response to carcinomas is, however, still uncertain.     

Site and incidence of multiple cancers in patients with squamous cell carcinomas of the upper aerodigestive tract

The etiology of multiple primary cancers has not been clearly elucidated, although some pathogenic factors are known. The studies reported here include 796 patients who, between January 1970 and March 1989, presented with a carcinoma of the upper aerodigestive system. The charts of 687 patients were analyzed retrospectively; 109 patients were studied prospectively by systematic pretherapeutic panendoscopy. Multiple primary cancers were found in 76 cases (9.5%), 33 patients had synchronous cancers, and 43 had metachronous cancers. In the prospective study, the incidence of multiple cancers was higher (13.7%) than in the retrospective group (8.8%). Synchronous primaries were more frequent in the prospective study (8.2%) than in the retrospective analysis (3.4%). Second primaries were mostly found in the esophagus, the hypopharynx, the buccal cavity, and the lung. The authors also examined whether the anatomic location of the second primary cancer can be related to the site of the first. The five-year survival rate among patients with synchronous cancers (18%) was lower than among patients with metachronous cancers (41%). The prognosis for synchronous cancers deteriorates if the planned treatment has to be modified following the discovery of a second primary. Systematic pretherapeutic panendoscopy should be used to help detect early asymptomatic second primaries which might be missed during clinical examination.     

Oral hygiene and dental status in patients with squamous cell cancers of the upper aerodigestive tract

Dental status and oral hygiene were investigated in a case-control study of 100 patients suffering from head and neck cancer and 214 age- and sex-matched controls. The dental status and paradontal status are poor in cancer patients. The number of decayed or missing teeth was significantly higher in our patients compared with controls. Furthermore, in the tumour group the rate of moderate or severe gingivitis and the presence of extensive tartar were significantly higher. These findings are mainly due to poor oral hygiene. Few of the cancer patients ever brushed their teeth, and the number of dental check-ups was significantly lower than in control subjects. Poor oral hygiene is predominantly an expression of self-neglect due to chronic alcohol consumption, which was present in nearly all of our patients. Furthermore, it seems to be related to an unsatisfactory health education in the lower social strata, to which most of cancer patients belong.     

Biochemoprevention for dysplastic lesions of the upper aerodigestive tract.

OBJECTIVES: To evaluate the efficacy and secondarily the toxic effects of biochemopreventive therapy (high-dose isotretinoin [13-cis-retinoic acid], alpha-tocopherol, and interferon alfa) in the reversal of advanced premalignant lesions of the upper aerodigestive tract and to correlate the therapeutic events with modulation of biomarkers. DESIGN: Prospective, nonrandomized chemoprevention trial. SETTING: Tertiary cancer care referral center and ambulatory care. PARTICIPANTS: Thirty-six patients with advanced premalignant lesions of the upper aerodigestive tract, without cancer during the 2 years before the intervention, with evaluable lesions, and without retinoid therapy for 3 months before the trial. INTERVENTION: Administration of oral isotretinoin (100 mg/m2 per day), oral alpha-tocopherol (1200 IU/d), and subcutaneous interferon alfa (3 megaunits per square meter twice weekly) for 12 months, with serial biopsies and clinical examination at 0, 6, 12, and 18 months from study start. MAIN OUTCOME MEASURES: Clinical and histologic responses to the intervention. RESULTS: Of the 36 patients, evaluation was possible in 30 for response at 6 months and in 21 at 12 months. At 6 months, there were 10 pathologic complete responses and 7 partial responses; at 12 months, 7 complete and 3 partial responses. A striking difference in response was observed in favor of laryngeal lesions (9/19 [47%] complete response rate at 6 months and 7/14 [50%] at 12 months vs 1/11 [9%] and 0/7 [0%], respectively, for oral lesions). Toxic effects were acceptable and did not exceed grade 3. CONCLUSION: Biochemoprevention is a promising biologic approach for laryngeal dysplasia and needs to be investigated further.     

Extraesophageal reflux and upper aerodigestive tract diseases

Reflux disease can cause multiple disorders not only of the esophagus but also of the upper aerodigestive tract. In the last decade, an association between reflux disease and multiple head and neck diseases was described, including those of the larynx and pharynx as well as those of the nose, the sinuses and the middle ear. The present article summarizes these different diseases and possible pathomechanisms are explained. In particular, there is a need to differentiate between the classical gastroesophageal reflux disease (GERD) and the extraesophageal manifestation of the reflux disease, called extraesophageal reflux (EER). Both diseases are characterized by different symptoms and can cause different disorders. To differentiate between GERD and EER, double-probe pH monitoring is mandatory. At last, some aspects of reflux therapy are explained.     

Simultaneous squamous cell carcinomas of the oral cavity and oropharynx

INTRODUCTION: Squamous cell carcinoma of the oral cavity is often a single localization, but the discovery of another or several associated lesions is not exceptional. The goal of our study was a retrospective analysis of patients having 2 simultaneous squamous cell carcinomas of the upper aerodigestive tract (UADT), i.e. diagnosed during the same panendoscopy by excluding the esophagus and the lung. PATIENTS AND METHODS: Between 1995 and 2001, 1,129 patients were treated for squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx in the Bordeaux Maxillo-facial Surgery Unit. 1% of these patients presented 2 simultaneous squamous cell carcinomas of UADT. RESULTS: Our series was divided in 9 men (75%) and 3 women (25%) with an average age of 61.3 years (48-86). At the end of the study 2 patients were lost to follow-up, 3 patients were alive without recurrence, and 1 patient was alive with recurrence. The average follow-up time was 17.6 months. DISCUSSION: A review of the literature gave an incidence of simultaneous squamous cell carcinomas of UADT varying from 1.3 to 12.8% according to authors. Thus, any patient having squamous cell carcinoma of the UADT must be considered as having an important potential risk to present another simultaneous cancer and to benefit from a systematic panendoscopy. In spite of an early diagnosis, the prognostic of these lesions remains bad.