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.     

口咽部鳞状细胞癌与性行为和人乳头状瘤病毒感染

高危型人乳头状瘤病毒感染(high risk human papillomavirus, HR HPV)是头颈部鳞状细胞癌发生的一个重要相关因素,特别是原发口咽部、缺少烟酒等危险因素的患者。口咽肿瘤中确认发现HR HPV,以及流行病学病例对照研究明确HR HPV与口咽癌发病风险的关系,已阐明了二者的联系。重点论述口咽癌患者与非口咽癌患者在口腔、喉腔和下咽部位的比较及性行为方式的影响。明确头颈肿瘤的性行为危险因素对未来肿瘤预防是必不可少的,同时以利于理解现有的HPV疫苗对未来头颈肿瘤预防的潜在作用。同时还扩展到性行为作为口咽癌发生的一个危险因素以及其作为HPV暴露标记的作用,强调HR HPV是通过性行为传播到上呼吸消化道,增加HPV相关的口咽癌的发病风险。     

Percutaneous endoscopic gastrostomy in the management of head and neck carcinoma.

In patients undergoing resection of head and neck malignancies, structural and functional deficits commonly preclude adequate oral nutrition and prolong hospital stay. To address this issue, the benefit of routine preoperative placement of percutaneous endoscopic gastrostomy (PEG) was studied in a group of these patients. The postoperative course of 89 patients undergoing primary resection of advanced (stage III and IV) squamous cell carcinomas of the upper aerodigestive tract was examined. The hospital stay was reduced by up to 61% with PEG compared to hospital stay with standard nasogastric tube (NGT) alimentation. The difference was statistically significant for primary sites involving the larynx and pharynx, but not for lesions of the oral cavity. For tongue base tumors, there was a trend toward reduced hospitalization which did not reach statistical significance. The fistulization rate was unchanged. The complication rate for PEG was 5%, and morbidity was less with PEG than with NGT. The authors recommend the preoperative placement of PEGs for all patients with advanced carcinomas of the larynx, hypopharynx, and oropharynx.     

Multiple carcinomas in the upper aerodigestive tract. 1. Oral cavity and oropharynx

BACKGROUND: During the last years an absolute increase of tumour incidence of squamous cell carcinoma as well as an increase in the occurrence of synchronous and metachronous multiple primaries in the upper aerodigestive tract can be observed. This study analyses the so-called "multi-centric cancerization" in patients with primary carcinoma of the oral cavity and the oropharynx. METHODS: During 2 observation periods of 5 years each, from 1985 to 1994, we retrospectively analyzed 235 patients with squamous cell carcinoma of the oral cavity and 232 patients with tumour localisation in the oropharynx. Besides age, sex, tumour localization, TNM-stage and grading, the risk factors tobacco and alcohol were added as causes for the development of multiple primaries. RESULTS: In the primary localisation of the oral cavity synchronous and metachronous double tumours increased from 7% to 17% besides the absolute increase in tumour incidence. In the oropharynx a total increase of second carcinomas from 3% to 20% was found. At the same time a growing abuse of tobacco and alcohol could be observed. CONCLUSIONS: Panendoscopy during pre-therapeutical staging should be obligatory. Regular oncological controls are mandatory, especially for younger patients with smaller tumours and good prognosis, but a high risk of second primaries. In the long run, prevention has to play a decisive role in the fight against second primary tumors of the upper aerodigestive tract. Possible improvements of early diagnosis, genetical examinations, information campaigns as well as research of carcinogenic environmental pollutants are of foremost interest to the clinician.     

Head and neck carcinoma – stage at presentation

A prospective study was performed during a 2-year-period. A total of 127 patients presenting with a squamous cell carcinoma of the head, neck and upper aerodigestive tract were entered into the study. Patients were classified according to the primary site, namely: larynx (n= 44), oropharynx (n= 28), hypopharynx (n= 17) and oral cavity (n= 19) and others (n= 19). Patients were staged according to the UICC TNM classification (1987) and the nature and duration of their symptoms were recorded. Sixty-one per cent of patients were found to be presenting with advanced disease (stages 3 and 4): oropharynx – 71 %; hypopharynx – 77%; oral cavity – 50%; larynx – 34%. No relationship could be established between stage at presentation and duration of symptoms and 53% of patients with advanced disease had been symptomatic for less than 3 months at the time of diagnosis. Only 28% of patients presenting with stage 3 or 4 disease had symptoms for 3 months or longer. Earlier diagnosis will not make a significant impact on the overall prognosis in head and neck cancer.     

Multiple primary malignancies in head and neck cancer

Multiple primary (MP) malignancies were found in 9.7% of 1961 patients with primary head and neck cancer diagnosed at The Johns Hopkins Hospital, Baltimore, during the years 1975 to 1985. The index tumors were divided into six main groups. Out of the 190 MP malignancies, 46.9% were synchronous and 53.1% were metachronous. Seventy-four percent of MP lesions were noted during the first year after diagnosis of the index primary tumor. Patients with an index tumor in the upper aerodigestive tract had a significantly increased risk of developing a second cancer in the head and neck area. This risk was 5.94 for the oral cavity, 6.98 for the pharynx, 3.57 for the larynx, and 7.02 for the esophagus. Patients with an index tumor in the salivary gland or the thyroid gland had, respectively, a 3.59 and a 7.38 higher risk than the general population of developing a second tumor. Efforts aimed at improving the survival of patients with head and neck cancer must incorporate strategies for the prevention, early detection, and treatment of MP neoplasms.     

Basaloid squamous cell carcinoma of oral cavity and oropharynx.

Basaloid squamous cell carcinoma is a variant of squamous cell carcinoma with distinctive histological and immunohistochemical characteristics and aggressive behaviour involving predominantly the upper aerodigestive tract. We describe the clinicopathological findings, along with immunohistochemical investigations, in 5 new cases with carcinoma localized in oral cavity and oropharynx.     

Early detection of premalignant lesions and oral cancer

Cancers of the oral cavity account for approximately 3% of malignancies diagnosed annually in the United States. As with other upper aerodigestive tract cancers, 5-year survival rates for oral cavity cancers decrease with delayed diagnosis. Cancers of the oral cavity are thought to progress from premalignant/precancerous lesions, beginning as hyperplastic tissue and developing into invasive squamous cell carcinoma. Despite the general accessibility of the oral cavity during physical examination, many malignancies are not diagnosed until late stages of disease. To prevent malignant transformation of these oral precursor lesions, multiple screening and detection techniques have been developed to address this problem.     

Role of sensation in swallowing function

OBJECTIVES: Sensation in the oral cavity and laryngopharynx has long been believed to be crucial for normal swallowing. One illustration of this belief has been intense interest in reconstruction after cancer resection using sensate tissue transfer as a means of improving swallowing function. A contrarian view is that mucosal sensation, by itself, is, in fact, relatively unimportant to swallowing function. STUDY DESIGN: A prospective study was designed to test the hypothesis that normal swallow function can occur with anesthesia of the upper aerodigestive tract mucosa. METHODS: Baseline (sensate) swallowing function of 13 healthy adults was assessed via video endoscopic swallow studies (VESS). Each subject was then topically anesthetized with lidocaine applied to the oral cavity, oropharynx, hypopharynx, and larynx. Swallowing was then reassessed via VESS and compared to the baseline examination to look for differences in function. RESULTS: There was little difference in swallowing ability between sensate and anesthetized states, even though all the subjects felt that their swallowing had been profoundly disrupted after lidocaine was applied. The main difference was a small increase in the time from food administration to swallowing. A few experienced trace aspiration, which was instantly eliminated on subsequent swallows with simple coaching. CONCLUSION: Normal swallowing can occur spontaneously or with simple coaching even with complete anesthesia of the upper aerodigestive tract mucosa. Current beliefs about the value of sensate free flaps and the importance of sensation in swallowing in general may need refinement.     

Metachronous second primary tumours in the aerodigestive tract in patients with early stage head and neck squamous cell carcinomas

Early-stage head and neck carcinomas can usually be controlled with the appropriate treatment. In these patients, the long-term prognosis mainly depends on second metachronous malignancies, frequently in the aerodigestive tract. Our study aims to identify risk factors for the appearance of second tumours in this group of patients with early head and neck cancer. Of 949 patients included in the study, 189 (20%) developed a metachronous second primary malignancy, most frequently in the aerodigestive tract. Independent risk factors associated with second tumours were heavy alcohol use and the location of the index tumour in the oropharynx. Compared to non-drinkers, heavy drinkers (>80 g/day) presented a 1.8-times higher risk of a second tumour (CI 95%: 1.01–3.50). Patients with oropharyngeal tumours had a 2.15-higher risk than patients with oral cavity tumours (CI 95%: 1.03–4.47). Recursive partitioning analysis was used to characterise two risk groups for second tumours. The low-risk group included patients over 75 years and patients with low levels of carcinogen use. It comprised 171 patients (18%) with a 5.3% frequency of second tumours. The high-risk group accounted for 80% of the patients ( n =778), and the rate of second neoplasms was 16.3%. Classification of the patients according to the mentioned variables allows us to focus follow-up and prevention efforts on high-risk patients.     

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.     

Statistical survey of multiple primary cancers of the head and neck]

The incidence and factors associated with multiple primary cancer were surveyed and analyzed from April 1978 through December 1990 in our clinic. Fifty-nine cases with multiple primary cancers were selected for study from among 579 cases with malignant head and neck region tumors. The cancers involved the larynx in 17 cases (8.4%), oral cavity in 14 (19.4%), oropharynx in 13 (41.9%), hypopharynx in 7 (8.0%) and nasal cavity or paranasal sinus in 7 (8.0%). Twenty-one cases (35.6%) arose synchronously within one year. From our observations, heavy drinking and smoking were most strongly suspected to be risk factors for induction of malignancy. Most multiple primary cancers in the head and neck region were observed to coexistent in a "so called multicentric zone" consisting of the oral area, pharyngeal area, larynx, esophagus, stomach, and tracheobronchial tree. To avoid overlooking concealed cancer in the multicentric zone, upper gastro-intestinal endoscopy, bronchial endoscopy, chest X-ray and sputum examination should be performed for screening of patients with head and neck malignancies.     

Repair of head and neck defects with thin and double-lined pectoralis flaps

The evolution of nondelayed , single-stage repairs of extensive ablative defects of the upper aerodigestive tract with thin, skin-lined pectoralis myogenous and myocutaneous flaps is described, with particular emphasis on technique and applicability. To date, 15 such modified flap reconstructions of the oral cavity, oropharynx, and pharyngoesophagus have been performed. Other than one instance of flap failure, no significant short- or long-term complications were noted. The functional results of these repairs are equivalent to other, less convenient or technically more difficult methods of reconstruction.     

Incidence of multiple tumors in the upper aerodigestive tract. Routine panendoscopy?

The incidence of multiple squamous cell carcinomas in the upper aerodigestive tract of 589 patients is presented and discussed. Multiple synchronous tumors had been found in 1.83% of patients in 1980-1984. Since the end of 1984 in most cases routine praetherapeutic panendoscopy was performed. 15.6% of these patients with panendoscopy had multiple synchronous primary tumors. The mouth and oropharynx were found to be high risk primary areas and the larynx a low risk area, concerning synchronous tumors in other localizations. The incidence of second primaries in the bronchi and especially in the oesophagus justifies routine praetherapeutic panendoscopy of which our technique is described.     

Lipoid proteinosis of larynx: review of four cases

Lipoid proteinosis is a rare autosomal recessive disorder characterized by intercellular deposition of an amorphous hyaline material. It mainly involves skin and mucosal membranes of upper aerodigestive tract as well as central nervous system, lung, lymph nodes and striated muscles. Etiology and pathogenesis are unknown. Infantile hoarseness is a common presenting feature of the disease due to infiltration of larynx. In two-thirds of the cases, voice changes are present at birth or in early infancy as the first manifestation. We present four patients with lipoid proteinosis involving skin, oropharynx and larynx.     

Mucosal Injuries of the Upper Aerodigestive Tract After Smoking Crack or Freebase Cocaine

The introduction of “crack” and “freebase” cocaine to the United States has resulted in an increased number of patients presenting to emergency rooms with cocaine-related burns of the upper aerodigestive tract. Because symptoms are nonspecific and histories often unreliable, the emergency room physician must keep a high index of suspicion for cocaine use when confronted with these types of patients. We present seven patients who had burns to the upper aerodigestive tract as a result of smoking crack or freebase cocaine. Two of seven patients underwent an emergency tracheotomy, probably because of delayed diagnosis and inadequate early medical intervention. This article reviews the history behind cocaine use, its different modes of administration, potential complications associated with smoking cocaine, diagnostic workup, and treatment options.     

Fluorescence staining of oral and laryngeal cancer after application of 5-aminolevulinic acid

BACKGROUND: Cancer of the oral cavity, oropharynx and larynx are the most common malignancies in the head and neck region. The prognosis for the patients concerned is highly dependent on an early detection and fast surgical treatment. Fluorescence guided examinations may serve as a possible diagnostic tool for better demarcation and delimitation of head and neck cancer. Therefore, the presented study was aimed at the detection of a selective Protoporphyrin IX (PPIX) accumulation in malignant oral, oropharyngeal and laryngeal lesions following topical and systemic application of 5-aminolevulinic acid (5-ALA). PATIENTS: We investigated 193 patients with suspected lesions in the oral cavity and oropharynx (n = 126) as well as in the larynx (n = 67). The patients received a varying dose (rinsing 200 mg, inhalation 30 mg, 2,5 - 25 mg/kg BW by mouth) of 5-ALA in aqueous solution. Both fluorescence pictures and macroscopic findings under white light were recorded using a target integrating, color CCD camera. Fluorescence contrasts between tumor and normal tissue were registered by an optical multichannel analyser. RESULTS: Our results have shown that after topical and systemic application of 5-ALA, PPIX fluorescence could be identified within the mucosa of the oral cavity, oropharynx and the larynx of all patients with a duration of up to 48 hours after systemic application. Malignant lesions usually showed higher intensities of PPIX-fluorescence than surrounding innocuous mucosa. A maximum fluorescence contrast between normal tissue and neoplastic lesions was observed at 1.5 hours after topical application and 3 hours after systemic application. CONCLUSIONS: It will be the aim of further investigations to verify the optimal time of incubation and dosing of systemical 5-ALA application to enhance fluorescence contrasts and set the basis for fluorescence guided resections.     

Muzine auf dem Gebiet der HNO-Heilkunde

BACKGROUND: Mucins are glycoproteins of high-polymer structure. They are an important component of the mucous layer covering the epithelia of the upper aerodigestive tract. Until now there has been little interest with regard to mucins in otorhinolaryngology. METHODS: The present knowledge about mucins of the upper aerodigestive tract is presented. A MEDLINE search was conducted for English- and German-language articles published from 1966 to the present. RESULTS: Thirteen different mucins named MUC 1-13 have been subdivided based on the classification system used by the Human Gene Mapping Committee. Besides mucins, small mucin-associated peptides, called trefoil factor peptides, have attracted much interest. CONCLUSIONS: Classification and attribution of the mucins found in the middle ear, larynx, oropharynx, esophagus, and nasolacrimal ducts has yet to be done. Also, little is known about the distribution of trefoil factor peptides in the upper aerodigestive tract.     

Altered genotoxicity in mucosal cells of head and neck cancer patients due to environmental pollutants

The complexity of carcinogenesis in squamous cell cancer (SCC) of the upper aerodigestive tract requires examining environmental risk factors, including mutagen sensitivities to xenobiotics. Three environmental, occupational, and habitual pollutants – dibutylphthalate (DBP), diisobutylphthalate (DiBP), and N′nitrosodiethylamine (NDELA) – were submitted to genotoxicity testing on mucosal biopsy specimens of tumor and nontumor patients in vitro. The single-cell microgel electrophoresis (Comet) assay was applied to detect DNA strand breaks in human epithelial cells of the pharynx and larynx from nontumor patients, patients with SCC of the oropharynx and patients with SCC of the larynx. Genotoxicity was found for DBP, DiBP, and NDELA in cells derived from nontumor and tumor patients. With respect to phthalates, Olive tail moment (OTM) levels were higher in patients with SCC of the oropharynx and SCC of the larynx (P < 0.01), the latter showing even more pronounced genotoxicity for DiBP. Testing epithelial cells of the patients with either oropharyngeal or laryngeal SCC for NDELA demonstrated results similar to the nontumor patients. Present findings indicate heterogeneous mutagen sensitivities to some but not all xenobiotics. Received: 25 May 1999 / Accepted: 15 October 1999