Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract

A consecutive series of 1,081 previously untreated patients undergoing 1,119 radical neck dissections (RNDs) for squamous carcinoma of the head and neck was reviewed to study the patterns of nodal metastases. Primary tumors were located in the oral cavity in 501 patients, in the oropharynx in 207 patients, in the hypopharynx in 126 patients, and in the larynx in 247 patients. Lymph node metastases were confirmed histologically in 82% of 776 therapeutic neck dissections, and micrometastases were discovered in 33% of 343 elective RNDs. Lymph node groups in the neck were described by levels (I to V). Predominance of certain levels was seen for each primary site. Levels I, II, and III were at highest risk for metastasis from cancer of the oral cavity, and levels II, III, and IV were at highest risk for metastasis from carcinomas of the oropharynx, hypopharynx, and larynx. Supramohyoid neck dissection (clearing levels I, II, and III) for NO patients with primary squamous cell carcinomas of the oral cavity and anterolateral neck dissection (clearing levels II, III, and IV) for NO patients with primary squamous cell carcinomas of the oropharynx, hypopharynx, and larynx are recommended.     

Simultaneous carcinomas of the esophagus and upper aerodigestive tract

A review of 150 consecutive head and neck cancer patients over a 22-month period revealed a multiple primary cancer rate of 19%, 9% in the head and neck region. Nine patients (6%) had simultaneous esophageal and head and neck cancers. Complete systematic esophagoscopic examinations, in addition to barium swallow radiographic studies, are recommended for all patients with head and neck cancers.     

Progesterone receptors in carcinomas of the upper aerodigestive tract

This study had three major goals: (1) to vigorously verify the presence of progesterone receptors in squamous cell carcinoma of the upper aerodigestive tract (HN-SCC). Antiprogesterone receptor monoclonal antibodies revealed a distinct band at approximately 120 kilodaltons in samples taken from two of four patients with HN-SCC. These results illustrate that progesterone receptor in HN-SCC has the same molecular weight as progesterone receptor in normal human uterus and human breast cancer. Steroid specificity and saturability results support the evidence that it is true progesterone receptors that are measured and not other receptors or sex steroid-binding globulins; (2) to confirm the biochemical function of progesterone receptors in HN-SCC by assessing the binding of progesterone receptor to acceptor sites on chromosomes in the nucleus; and (3) to establish the clinical significance of progesterone receptor measurement. Patients with positive assays were more likely to be free of disease a mean of 6 months after resection. We used logistic regression to account for site of primary disease, grade of tumor, and stage of disease. This logistic regression was significant with a p = 0.014. Patients with a binding index greater than 2 (19 of 73 patients) were 4.34 times more likely to be free of disease than patients with negative assays.     

Trifunctional bispecific antibody-induced tumor cell lysis of squamous cell carcinomas of the upper aerodigestive tract

BACKGROUND: The trifunctional bispecific antibody Removab (tbAB) bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune-cell inducing tumor cell lysis. tbAB-induced tumor cytotoxicity was assessed in an autologous human ex vivo system. METHODS: One hundred forty tumor samples and autologous peripheral blood mononuclear cells from a total of 36 patients with head and neck squamous cell carcinomas (HNSCCs) were incubated on a chicken embryo chorioallantois membrane with Removab. Tumor cells coincubated with cisplatin or cell culture medium served as positive and negative controls. Tumor cell lysis was assessed by acridine orange staining or by fluorescence-activated cell sorting of propidium iodide-marked cells after 24 and 48 hours (T24/T48) coincubation. RESULTS: Coincubation of HNSCC cells with tbAB and autologous peripheral blood mononuclear cells resulted in a 49% +/- 6% decrease of viable cells at T24 (p < .005) and in a decrease of 56% +/- 8% at T48 (p < .005) compared with the control. The tumor cytotoxicity was similar to that of cisplatin (49% +/- 7% decrease at T24 and 49% +/- 8% at T48). CONCLUSION: In an autologous human ex vivo system, the tbAB-induced tumor cell lysis was comparable to that by cisplatin.     

Papillary squamous cell carcinomas of the upper aerodigestive tract: a clinicopathologic and molecular study

BACKGROUND: The limited studies and the small number of published cases of papillary squamous cell carcinoma have precluded accurate assessment of the biologic characteristics of this lesion. METHODS: Thirty-eight of the carcinomas were studied. In-situ hybridization and polymerase chain reaction were performed to detect human papilloma virus (HPV) and p53 expression. RESULTS: HPV was found in 4 of 14 assessable carcinomas by in-situ hybridization and in 5 of 14 by polymerase chain reaction. The most frequently identified HPVs were HPVs in 6/11 and 16/18 patients. In general, a reciprocal relationship was found between p53 and HPV prevalence. The most lethal site for this tumor was the sinonasal tract, whereas patients with papillary squamous cell carcinomas of the larynx had the best outlook. Eleven of 25 (44%) assessable patients died of disease (mean time interval, 2 year). CONCLUSIONS: Papillary squamous cell carcinoma of the upper aerodigestive tract is a distinct variant of squamous cell carcinoma. As such and because of its putative association with HPV, papillary squamous cell carcinoma could be an informative model for defining how viral oncogenes cooperate with other factors in genomic instability, carcinogenesis, and tumor development.     

Photodynamic therapy for early squamous cell cancer of the upper aerodigestive tract

Photodynamic therapy (PDT) is a treatment modality that results in selective destruction of malignant cells by combining a photosensitizing agent (hematoporphyrin derivative), which is taken up by the cells, and a laser light. This therapeutic modality has been effectively used in managing cancers of the skin, bronchi and bladder. In the head and neck area, however, its use has been confined to the palliation of advanced lesions which have proved refractory to conventional therapy. While this is unquestionably a valid role, its true value, therapeutically, may be in the management of early cancers arising in the upper aerodigestive tract. At the University of Cincinnati, PDT has been used on a variety of such early cancers where, for a variety of reasons, conventional therapy was not possible. A preliminary experience with this modality in managing lesions of the larynx, oral cavity and oropharynx has demonstrated that this is a viable alternative.     

Toxicology of upper aerodigestive tract pollutants.

The field of environmental toxicology has become quite important to the study of environmental health in human beings. The stability of the ecosystem in which we live is threatened by the nearly 5 million chemical compounds that have been synthesized worldwide, many of which have real or potentially toxic effects on the environment and on life forms. Four major groups of chemicals--metallic elements, nonmetallic elements, organic compounds and inorganic compounds--have certain agents within them that are known toxins to human beings. Some of these agents have an as yet unknown effect, whereas others have been well characterized. They can be found in the workplace, home, and outdoors, and many are unseen and odorless. In the past, most agents have been described in terms of their carcinogenic potential or major toxic effects on organ systems. It is now likely that the important characterization of some of these agents referrable to the upper aerodigestive tract should be at their receptor sites and identify the very discrete and small effects on these sites and their cumulative effects. The concept of threshold is probably an arbitrary one because to date these discrete effects have not been studied. Susceptibility on an individual basis probably varies from low to high, depending on the patient's immunologic and defense mechanisms and the existence of congenital or acquired risk factors. New attention must be given to more subtle effects on the upper aerodigestive tract (i.e., sinusitis and laryngitis) in view of the potential effects of certain toxic agents on these tissues.     

Selective neck dissections for squamous carcinoma of the upper aerodigestive tract: patterns of regional failure.

BACKGROUND: Surgeons have been using selective neck dissections in the treatment of squamous carcinoma of the upper aerodigestive tract for over 20 years. To date, no data is available that can answer the question "What are the patterns of failure in the neck following a selective neck dissection and is a selective neck dissection a reliable procedure for metastatic disease?" METHODS: To answer this question, the medical records of all patients with squamous carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx treated at The University of Texas M. D. Anderson Cancer Center from January 1, 1985-December 31, 1990, with a selective neck dissection were reviewed. Five hundred seventeen neck dissections were analyzed: suprahyoid (41), supraomohyoid (284), and anterolateral (192). The end point of the study was regional failure and survival. RESULTS: Regional recurrence in patients treated with a suprahyoid dissection was 43% with pathologically positive nodes. The regional recurrence in the patients treated with a supraomohyoid neck dissection was 1.9% with pathologically negative nodes, 35.7% with path N1 without postoperative radiation therapy, and 5.6% with postoperative radiation therapy. The neck staged pathologically N2B failed with and without postoperative radiation, 8.3% and 14%, respectively. Thirteen percent of the anterior/lateral neck dissections failed regionally. If multiple pathologically positive nodes (N2B) were present, the regional failure with postoperative radiation was 30% and 33.3% without postoperative radiation. CONCLUSION: The results of this retrospective study suggest that a selective neck dissection is a satisfactory staging procedure and is a definitive operation if all the nodes are pathologically negative. However, if a node is found to be invaded with cancer, the use of postoperative radiation is advisable.     

Functional anatomy of the lymphatic drainage system of the upper aerodigestive tract and its role in metastasis of squamous cell carcinoma

BACKGROUND: Although there is a significant understanding of the vascular anatomy of the upper aerodigestive tract (UADT), there is less detailed knowledge of the architecture and drainage patterns of the lymphatic system. Detailed knowledge of the lymphatic system is critical for understanding the role of sentinal node identification in the management of different cancers. METHODS: We have combined microscopic techniques with in vivo and in vitro lymphographic studies to survey the architecture and drainage patterns of the lymphatic system of the UADT in 850 organ specimens. RESULTS: These studies show an interaction of superficial and deep lymphatic networks that vary in density but have a constant distribution characterized by predictable patterns of lymph drainage into the regional lymph nodes. CONCLUSIONS: Detailed knowledge of the lymphatic system of the UADT contributes to a better understanding of the patterns of metastatic spread of carcinomas of the UADT and provides a strong rationale for the practice of sentinel node identification in the management of these tumors.     

Preoperative outpatient nutritional support of patients with squamous cancer of the upper aerodigestive tract

In this study, 59 percent of the patients with squamous cancer of the upper aerodigestive tract were considered malnourished by the independent evaluation of a registered dietitian. Malnourished patients tended to present in a more advanced stage of disease, underwent more extensive operative procedures, had more complications, experienced longer hospital stay, and had a higher proportion of irradiated patients compared with patients who were nutritionally healthy. Malnourished patients who received nutritional support preoperatively demonstrated lower complication rates and shorter lengths of hospital stay compared with malnourished patients who underwent similar operative procedures without preoperative nutritional supplementation.     

Surgical treatment of cervical node metastases from squamous carcinoma of the upper aerodigestive tract: evaluation of the evidence for modifications of neck dissection

BACKGROUND: This review article examines the role of the different types of neck dissection in the treatment of squamous carcinoma metastases to the cervical nodes. METHODS: A critical evaluation of the literature on the pathologic basis, oncologic effectiveness, and functional outcome of neck dissection. RESULTS: Pathologic data show preferential metastasis to different lymph node levels, in N0- and N+-staged disease, depending on the primary tumor site. Comparative studies on control of regional metastases suggest that modified radical is no less effective than radical neck dissection, but there is insufficient data to draw firm conclusions on the role of selective neck dissection. Selective and modified radical dissections result in less shoulder disability than radical neck dissection. CONCLUSIONS: Modified radical neck dissection is supported by pathologic and clinical evidence in N1- and 2-staged disease. There may be a role for selective dissection, but there is a need for more information on oncologic outcome. Prospective multicenter systematic data collection on the outcome of neck dissection is a pragmatic alternative to a trial.     

Multicentric squamous-cell carcinoma of the upper aerodigestive tract

In an attempt to define the true frequency of multiple primary squamouscell carcinomas of the upper aerodigestive tract, 3 separate population groups were studied. The results of this investigation confirmed the high incidence of multicentric carcinomas in the upper aerodigestive tract, lung, and esophagus. The clinical significance of this phenomenon is discussed, particularly its effect on patient survival and its possible relationship to local tumor recurrence. The value of routine panendoscopy in the initial assessment is stressed as well as the need for a lifelong follow-up of these patients.     

Targeted sensory restoration to the upper aerodigestive tract with physiologic implications

BACKGROUND: Sensory restoration through sensate flaps placed into critical areas of the upper aerodigestive tract is an attractive reconstructive goal to achieve optimal post-therapy function. The question that has remained unanswered is whether sensory recovery takes place through the newly established neural pathway or through ingrowth of sensory nerves from the periphery of the defect. METHODS: Three patients with squamous cell cancer underwent resection and primary reconstruction of the laryngopharynx with a sensate radial forearm flap. The flaps were designed with a smaller, proximal paddle to serve as a monitor. Reneurotization of the flaps was carried out to the superior laryngeal nerve. RESULTS: All three patients were followed for a minimum of 12 months. Each of these patients reported the development of a cough that resulted from stimulation of the external monitor. This phenomenon was easily duplicated by light stimulation of the monitor, which not only produced the cough but was consistently perceived by the patient as arising from inside their throat. CONCLUSIONS: This series conclusively demonstrates that sensory feedback can be restored in a targeted fashion through neural anastomoses and that a physiologic response that helps in airway protection can be produced through the use of sensate flaps with a strategically selected recipient nerve.     

Role of routine panendoscopy in cancer of the upper aerodigestive tract.

Patients with squamous cell carcinoma of the aerodigestive tract routinely undergo panendoscopy to detect possible synchronous second primary tumors. The aim of our study was to assess the incidence of synchronous and metachronous second primary tumors and to refine the role of panendoscopy. The charts of 358 patients evaluated by means of panendoscopy during work-up of a first primary squamous cell carcinoma of the upper aerodigestive tract were reviewed. The incidence of a second primary tumor was 16.2%, with 6.4% being synchronous and 9.8% being metachronous. In only 3.1% of all patients, a synchronous tumor was clinically silent and only revealed by means of the panendoscopy. The synchronous tumors were mainly in the oral cavity, pharynx, or larynx (61%), whereas the metachronous tumors were most likely in the lung (57%). Despite the low incidence of synchronous second primary tumors, we still recommend panendoscopy for assessment of the primary tumor and as a training field for residents.     

The utility of tolonium chloride rinse in the diagnosis of recurrent or second primary cancers in patients with prior upper aerodigestive tract cancer

BACKGROUND: The clinical utility of tolonium chloride rinse was compared with unaided visual examination alone in the diagnosis of oral carcinoma in patients previously treated for carcinoma of the upper aerodigestive tract. METHODS: A total of 668 patients were enrolled in this multicenter study. At each site, an oral clinical visual examination was completed by one investigator followed by tolonium chloride rinse and examination by a second investigator blinded to the examination findings of the first investigator. If a lesion was considered suspicious (urgent biopsy required at the first visit), the lesion was biopsied after tolonium chloride rinsing. Patients with lesions characterized at the first visit as not suspicious (biopsy not urgent) or that stained with tolonium chloride were asked to return for a second visit. At the second visit, any residual lesion or lesions that retained tolonium chloride were biopsied. RESULTS: A total of 96 biopsies was performed in 81 of the 668 patients (12.1%), of which 30 (31.3%) were diagnosed histologically as carcinoma/carcinoma in situ (CIS) and the remainder as inflammation (31.3%), keratosis (26.6%), dysplasia (21.9%), ulcer (2.1%), other (3.1%), or no abnormality (1.0%). Of the 30 lesions with the diagnosis of carcinoma/CIS, 12 (sensitivity 40.0%) were considered to be clinically suspicious (CS+), whereas 29 (sensitivity 96.7%) retained tolonium chloride (p =.0002). The predictive values of a positive test for clinical examination and tolonium chloride staining were similar (36.4% vs 32.6%; p =.5871), indicating that the greater sensitivity of tolonium chloride was not associated with an excessive number of unnecessary biopsies (false positives). CONCLUSIONS: Tolonium chloride rinse is more sensitive than clinical examination alone in detecting lesions that might be found on biopsy to be carcinoma or CIS. The increased sensitivity is largely attributed to lesions that stain but were not detected clinically on visual examination.     

Association between malignancies of the upper aerodigestive tract and uterine cervix.

Cancers of the cervix and buccal cavity share histologic, epidemiologic, and exposure characteristics. In particular, cigarette smoking and human papillomavirus (HPV) have been cited as etiologic cofactors of both malignancies. Using incidence data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute for the years 1973 through 1984, we evaluated the incidence of second cancers of the buccal cavity following an initial cervical cancer. Standardized incidence ratios (SIR) were uniformly elevated for both white (SIR = 2.0), and black (SIR = 3.5) women. There were also elevated risks for the development of cervical cancer following an initial buccal cavity cancer (SIRs = 3.3 and 2.5, respectively). A similar pattern was evident for laryngeal cancer among white women. HPV transmission could account in part for the paired occurrence of these two anatomically distinct cancer sites. Cigarette smoking could act as a synergistic cofactor in the malignant transformation of viral genome-harboring tissue.     

Toxicity of photodynamic therapy after combined external beam radiotherapy and intraluminal brachytherapy for carcinoma of the upper aerodigestive tract

BACKGROUND AND OBJECTIVE: To describe the toxicity of photodynamic therapy (PDT) in patients with carcinoma of the upper aerodigestive tract who received prior treatment with external beam irradiation and intraluminal brachytherapy (IB). STUDY DESIGN/MATERIALS AND METHODS: Hospital records of PDT patients were reviewed. Three patients who received prior treatment with external beam irradiation and IB were identified. Two patients had esophageal carcinoma treated with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy) followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications: 630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at 1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one light application: 630 nm, 150 J/cm, 200 mW/cm). RESULTS: One patient with esophagus cancer had formation of a tracheoesophageal fistula, which required stent placement. The other esophageal cancer patient developed quadriplegia due to an epidural abscess arising from a fistula with the diseased portion of the esophagus. The lung cancer patient had massive hemoptysis after the procedure and died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary artery. CONCLUSION: Patients with upper aerodigestive tract carcinoma who have received treatment with both external beam irradiation and IB seem to be at higher risk for complications when treated with PDT.