Demonstration of immunoglobulin in tumor and marginal tissues of squamous cell carcinomas of the head and neck.

Immunofluorescence (IF) techniques on cryostatcut sections of tumor tissues demonstrated that immunoglobulin was associated with cells of squamous cell carcinomas of the head and neck. The immunoglobulin was found consistently to be of the IgG class; IgM and IgA were detected also but in only one tumor sample each. The C3 component of complement was also in most tumor tissues. The immunoglobulin could be removed from the tissues by being washed with low pH glycine buffer but not with pH 7 buffer, indicating that the immunoglobulin may be in antibody-antigen complexes. All the tissues obtained from the histologically normal margins of the surgical specimens were also positive for the presence of bound immunoglobulin, whereas head and neck epithelial tissues from tumor-free control patients were negative in the IF assays. Preliminary experiments showed that IgG from patients' diluted serum and the IgG fraction isolated from patients' serum would bind to glycine buffer-eluted tumor tissue.

Culture of squamous head and neck cancer on 3T3 fibroblasts following isokinetic velocity sedimentation.

Growth in culture of squamous head and neck cancer is hampered by microbial contamination, low plating efficiency, and cellular heterogeneity within tumors. Furthermore, clumps of cells must be removed if plating efficiency is to be accurately determined. Isokinetic velocity sedimentation was applied to 44 primary tumor specimens in an effort to minimize these problems. Seven fractions were evaluated for cell number, clump number, cell viability, clonogenic growth, plating efficiency, and microbial overgrowth. Unseparated specimens were simultaneously cultured. Microbial growth was significantly associated with the highest gradient fraction. Clumps were significantly associated with the lowest gradient fraction. Colony formation was significantly associated with middle gradient isokinetic velocity sedimentation, although seven specimens grew only when fractionated, suggesting the possibility of inhibitor cells within the tumor specimen.

A randomized trial of adjuvant chemotherapy in head and neck cancer.

Ninety-five patients with squamous cell carcinoma of the head and neck were entered into a randomized study testing a two-week course of induction chemotherapy with methotrexate and leucovorin given prior to regional therapy. In addition, following regional therapy, patients randomized to chemotherapy were to receive similar methotrexate courses every three months for one year. Poor tolerance to this regimen after radiation and surgery led to a change in the chemotherapy following regional therapy to a combination of Adriamycin (Adria Laboratories, Columbus, Ohio) and cisplatin every three weeks for four cycles after the first 35 patients had been entered. Nine cases were ineligible and four lacked any follow-up data, leaving 82 analyzable cases. Using Cox regression analysis, no differences in the percentage of patients achieving disease control, the relapse-free survival, or the overall survival were identified between any treatment group. As has been described in many pilot studies of induction chemotherapy of head and neck cancer, chemotherapy responders had a more favorable disease-free survival than chemotherapy nonresponders in the total group of patients receiving adjuvant chemotherapy. However, correcting for imbalances in the expected three year disease-free survival of these patients, based on their disease site and stage, erased this difference, indicating tumor response to this regimen of chemotherapy is not an independent factor affecting disease outcome. The division of patients into arbitrary prognostic categories based on the expected outcome for each specific tumor site and stage proved to be a useful method for balancing treatment groups, given the multiple site-stage combinations within the upper aerodigestive tract. The defined prognostic categories were the single most sensitive predictors of relapse-free and overall survival.

Electron microscopy in the diagnosis of head and neck tumors.

Six patients with malignant head and neck tumors are shown to have required electron microscopy for accurate diagnosis. In all of these tumors, there were ultrastructural features of cytodifferentiation that were not discernible by light microscopy, such as neurosecretory granules, desmosomes, cytoplasmic processes, tonofibrils, and myofilaments. Electron microscopy is helpful in the differential diagnosis of tumors in general, but its effectiveness is particularly apparent in small-cell "undifferentiated" tumors such as neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, undifferentiated squamous-cell carcinoma of the lymphoepithelioma type, and malignant lymphoma. It has also been helpful in the identification of amelanotic melanoma and spindle-cell carcinoma.

Advanced supraglottic carcinoma: a comparative study of sequential treatment policies.

Data from 131 consecutive patients with operable stage III or IV (American Joint Committee) supraglottic carcinoma were analyzed. Based on existing treatment policies at the time of presentation, patients received either preoperative radiation therapy (RT) (48 patients), surgery alone (42 patients), or postoperative RT (41 patients). Preoperative RT dose levels were either 2,000 rad in five fractions (33 patients) or 5,000 rad in 25 fractions (15 patients). Postoperative RT dosages were 5,000 to 6,000 rad in 6 to 6 1/2 weeks. Surgical procedures included either subtotal or total laryngectomy and radical neck dissection. Tumor control was achieved in 21 of 42 patients (50%) treated with surgery alone, 23 of 48 patients (48%) treated with preoperative RT, and 29 of 41 patients (71%) treated with postoperative RT (P = 0.005). The actuarial, recurrence-free survival at 5 years was 36% and 35%, respectively, in the surgery alone or preoperative RT groups as compared to 55% in postoperatively irradiated patients. The authors conclude that advanced but resectable supraglottic carcinomas may be best treated with surgery followed by RT, rather than with surgery alone or with combined preoperative RT and surgery.

Indications for and techniques of tracheotomy.

Although the operation has been practiced for centuries, the modern technique of tracheotomy was introduced and popularized in the beginning of the 20th century. The initial indication for tracheotomy was limited to impending airway obstruction resulting from trauma, but current indications are broader. Tracheotomy is one of four methods available to intubate the trachea and is associated with physiologic changes that are dependent on the duration of tracheotomy. Although surgical in nature, it is employed to relieve or prevent airway obstruction and to offer ventilatory support. Tracheotomy may be performed as an elective or an emergency procedure. Ideally, it is done in a controlled situation. However, when performed in an emergency setting, variations of the procedure, such as minitracheotomy or cricothyroidotomy, may be temporarily substituted. Preferably, tracheotomy is performed in an operating room; however, it may be carried out successfully in an intensive care unit as well.

Measuring musical abilities of autistic children.

Three normal children with reported musical ability and three autistic children were tested for the ability to imitate individual tones and series of tones delivered by voice, piano, and synthesizer. Accuracy of imitation was judged by two independent observers on the basis of pitch, rhythm, and duration. The autistic children overall performed as well as or better than the age-matched normal children. These results are discussed and their implications for future neurological and clinical research are considered.

Fluorescein kinetics in perilymph and blood: a fluorophotometric study.

A modified slit lamp fluorophotometer was used to determine fluorescein concentration changes in the perilymph, cerebrospinal fluid and blood of chinchillas after intravenous injection of 0.2 ml of fluorescein sodium. This new technique provides a means of determining quantitative changes of fluorescein concentration in the perilymph without the need to withdraw fluid samples through the round window membrane of cochlear wall. Fluorescein was observed to enter the perilymph between 1 and 2 minutes after injection, and it reached its peak concentration in the mean time of 23 minutes. The mean peak concentration was 4.20 X 10-6 g/ml. Both increasing and decreasing fluorescein concentration changes in the perilymph followed an exponential time course. Although the observations of cerebrospinal fluid fluorescence were thought to represent a composite of the fluorescence of the cerebrospinal fluid itself and the underlying brain stem blood vessels, the peak fluorescence did not exceed that observed in the perilymph. These observations support the view that most of the perilymph is produced in the cochlea by ultrafiltration from the cochlear blood vessels. The slit lamp fluorophotometer appears to be a satisfactory means of recording fluorescein concentration changes in the perilymph without disturbing the cochlear physiology by penetrating the labyrinth to obtain fluid samples.

Lung cancer after head and neck cancer: role of chest radiography.

OBJECTIVE: To examine whether screening chest radiographs lead to significantly longer life span in patients found to have pulmonary lesions than in those in whom lung cancer was detected after symptoms developed. STUDY DESIGN: A retrospective study. MATERIAL AND METHODS: Charts of 1,086 patients with squamous cell cancer of the head and neck treated for cure from January 1, 1974, to December 31, 1998, were analyzed. RESULTS: Pulmonary cancer developed in 62 patients. In 41 patients pulmonary malignancy was found because of patient symptoms. In 21 patients lung cancer was detected by routine annual chest radiography. Seventy-five percent of lung cancers were detected within 3 years of initial treatment of the head and neck cancer. CONCLUSION: Chest radiography is a poor screening tool, because it failed to find pulmonary lesions in more than 65% (41/62) of patients who were later found to have pulmonary cancer. Survival rate did not differ between patients in whom pulmonary cancer was found by screening chest radiography and those in whom symptoms prompted evaluation (P = .48). Using current treatment protocols, routine yearly chest radiography did not improve survival in patients with head and neck cancer. However, there maybe new therapeutic regimens under investigation that would benefit these patients if their lung cancers were found in early stages of disease. Future directives must include the establishment of an effective follow-up protocol for the early detection of lung malignancies in these patients.

Otospongiosis (otosclerosis): polytomographic and histologic correlation.

The Temporal Bone Laboratory of Northwestern University Medical School has three sets of temporal bones from patients who had antemortem polytomographic examinations resulting in a diagnosis of otospongiotic involvement of the cochlea. One of these cases was thought to have been an example of pure cochlear otospongiosis. The other two cases were patients with clinical (stapedial) otospongiosis, and their polytomograms were interpreted as unilateral otospongiosis with involvement of the basal turn of the cochlea. In the first set of temporal bones, no otospongiosis was present. In the other two sets, the otospongiotic lesion did not involve the cochlea, and a contralateral otospongiotic lesion was present that had not been seen on the polytomograms. Caution must be exercised in the interpretation of subtle polytomographic changes noted in the cochlear capsule and restraint used in the X-ray diagnosis of pure cochlear otospongiosis until there is evidence of correlation with pathological material.

Pharyngeal reconstruction after laryngectomy.

A method of pharyngeal reconstruction following laryngectomy is described. In 44 successive laryngectomies using this technique, no postoperative pharyngocutaneous fistulas occurred. Ten of the patients had received full courses of radiation therapy prior to the surgical procedure and had recurrent carcinomas. Other reports have noted that laryngectomy following full courses of "unplanned preoperative" radiation therapy is usually associated with a high incidence of postoperative pharyngeal fistula. The pharyngeal fistula problem, and the pharyngeal repair that was used in our series, are discussed. The pharynx was closed carefully in three layers with fine, absorbable sutures, and a submucosal inverting technique was used for the important mucous membrane closure. Tube feedings were used for two weeks after surgery. A high incidence of pharyngocutaneous fistula after laryngectomy in the irradiated patient can be prevented.

Temporal bone histopathology of Paget's disease with sensorineural hearing loss and narrowing of the internal auditory canal.

A temporal bone report is presented of a patient with progressive sensorineural hearing loss and advanced Paget's disease involving the skull. The histopathology reveals Pagetic bone invading the internal auditory canal and compressing the cochlear division of the VIIIth cranial nerve resulting in severe neural degeneration. There are no other histopathologic abnormalities present in the cochlea to explain the hearing loss. A low-frequency conductive hearing loss was also present, but no histopathologic correlate could be identified.

Fluorescein angiography of the tympanic membrane.

Little is known about the dynamic vasculature of the tympanic membrane, despite the fact that it is within easy view of the otolaryngologist. An understanding of its blood supply dynamics may lead to a better understanding of the tympanic membrane's physiological properties and response to surgery. Also, certain patterns of blood flow may correlate with disease entities and be of diagnostic value. Currently, we have done 30 fluorescein angiograms of the tympanic membrane. The fluorescein angiograms from a normal ear and from ears with several types of ear pathology are described.

The submandibular triangle in squamous cell carcinoma of the larynx and hypopharynx.

A 15-year retrospective analysis was carried out at the University of Illinois College of Medicine, Chicago, reviewing the tumor staging and pathology data of 239 patients treated for carcinoma of the larynx and hypopharynx requiring laryngectomy alone, laryngectomy with neck dissection, or laryngopharyngectomy and neck dissection. Surgery was the primary treatment modality in 205 of the 239 cases, with the remaining 34 having surgery to treat radiation therapy failure. Primary tumors were located within the supraglottic region, the glottic region and, less commonly, the pyriform sinus. Ninety-five of the 239 patients either presented with or developed nodal metastases following initial treatment. Of these, only two had tumors within the lymph nodes of the submandibular triangle. This data corroborates impressions that tumors of the larynx and hypopharynx rarely metastasize to the submandibular triangle and that sparing this area during neck dissection for lesions of the larynx would seem justified.

Lymphoepithelioma of the nasopharynx.

There is uncertainty as to whether the clinical behavior of nasopharyngeal lymphoepithelioma differs from that of squamous cell carcinoma of the nasopharynx. To determine if significant differences existed, we have studied 39 patients with nasopharyngeal lymphoepithelioma and compared their data with 50 nasopharyngeal squamous cell carcinoma patients. In contrast to squamous cell carcinoma, lymphoepithelioma occurred at a younger age, presented as smaller primary tumors, and manifested more extensive cervical lymph node involvement. When analyzed by T stage, N stage, or overall stage groups, the 5-year actuarial survivals were better in the lymphoepithelioa patients. Late tumor recurrences (beyond 4 years) were seen in the lymphoepithelioma patients, whereas all of the recurrences in the squamous cell carcinoma group occurred within 4 years. Tumor recurrences were more common in the cervical lymph nodes in the lymphoepithelioma group and in the primary site of the squamous cell carcinoma group.

Heterotopic salivary tissue in the neck.

Six cases of heterotopic salivary gland tissue in the anterolateral neck are presented with a review of their clinical and histopathologic characteristics. Neoplastic transformation, fistulization, and isolated rests represent a spectrum of these uncommon lesions. The embryologic derivation of salivary tissue and close association with the branchial apparatus are discussed. The significance of salivary carcinoma presenting in the neck is reinterpreted in light of the embryogenesis of these heterotopias.

Human laryngeal reinnervation: the Northwestern experience.

Recent publications have reported impressive success with laryngeal reinnervation utilizing a nerve-muscle pedicle. This innovative surgical procedure is claimed to be useful for unilateral and bilateral vocal cord paralysis. Although the surgical results reported by Tucker have been good, they have lacked corroboration from other centers. We have performed six laryngeal reinnervation procedures at Northwestern University Medical School. Four patients presented with bilateral vocal cord paralysis and two patients with unilateral paralysis. All six operations were successful in restoring vocal cord function. The technique, problems, and results are discussed. Our experience supports the initial reports of success with this new operation.

Squamous cell carcinoma of the soft palate.

Thirty-eight patients with squamous cell carcinoma of the soft palate treated between 1960 and 1975 were reviewed. Males in the seventh decade predominated. All symptomatic patients complained of sore throat and/or odynophagia. Seventy-eight percent were symptomatic less than three months. Approximately equal numbers of patients presented with T1, T2, and T3 tumors. Twenty-seven percent had cervical metastases when initially seen. The majority (89%) of patients were treated with radiation initially and the remainder (11%) received radiation therapy at the time of postsurgical recurrence with an absolute five year survival of 33%. Patients less than 60 years of age and those with small primary tumors and no neck metastases demonstrated better survival. Radiation therapy to the primary tumor and neck appears to be the preferred modality of initial treatment.

Postoperative radiotherapy for persistent tumor at the surgical margin in head and neck cancers.

Seventy-two patients with a carcinoma of the head and neck, who were treated with surgery and postoperative irradiation, were reviewed to determine the local recurrence rates and survival in patients with inadequate surgical margins. Tumor recurrence rate was 31% for patients with microscopic tumors at resection margins and 50% for those with macroscopic tumor. Actuarial 3-year survival for these patients was 71% and 43%, respectively. All 4 patients who were irradiated later than 6 weeks after surgery developed recurrent malignancy despite the resection margins being free of tumor. Excluding these patients the 3-year survival for R0 patients was similar to that of R1 patients. It is concluded that postoperative irradiation is effective in patients with tumor at the surgical margins. It is suggested that the time interval between surgery and radiation therapy be limited to less than 6 weeks. Radiation dose prescriptions for various clinical situations are discussed.

Tracheal reconstruction using an epithelial equivalent.

The application of a rapidly vascularized epithelial equivalent that inhibits wound contraction would have great potential in the prevention and repair of tracheal stenosis. An animal model was developed to simulate the effects of circumferential tracheal injury and an autologous epithelial equivalent was created from a fibroblast-collagen matrix and subsequently implanted in the traumatized site in an attempt to prevent stenosis. Postinjury physiologic and histologic evaluation revealed near-normal mucosal flow analysis in the treated sites and an area of less than 20% stenosis versus 95+% in controls. This study's findings indicate that tracheal stenosis can be limited by the use of an epithelial equivalent.