Stanley M. Shapshay

Detection of preinvasive cancer cells

More than 85% of all cancers originate in the epithelium that lines the internal surfaces of organs throughout the body. Although these are readily treatable provided they are diagnosed in one of the preinvasive stages, early lesions are often almost impossible to detect. Here we present a new optical-probe technique based on light-scattering spectroscopy that is able to detect precancerous and early cancerous changes in cell-rich epithelia.

Predictive Factors of Success or Failure in the Endoscopic Management of Laryngeal and Tracheal Stenosis

Stenosis of the larynx and/or trachea presents perplexing problems. No one technique has proved totally satisfactory in the management of all varieties of stenosis. Recent reports have described the successful use of the CO2 laser in the endoscopic management of stenosis of the larynx and trachea. Failures of this technique need emphasis to assure appropriate selection of therapeutic method. Retrospectively, 49 cases of laryngeal stenosis, 6 cases of tracheal stenosis and 5 cases of combined laryngeal and tracheal stenosis were studied (total 60 patients) following treatment at the Boston University Affiliated Hospitals. Follow-up ranged from 1 to 8 years. Multiple procedures were required in 35 laryngeal patients. Of the laryngeal patients 39 were successfully managed (average number of procedures in successful cases 2.18). Of 11 tracheal patients with combined laryngeal and tracheal procedures, 3 were successfully managed (average number of procedures in successful cases 6). Failures in laryngeal stenosis included four patients in whom an adequate airway was not established though voice was present while maintaining tracheostomies. Thirteen patients failing endoscopic management required open surgery with good result. Factors associated with poor result or failure include circumferential scarring with cicatricial contracture, scarring wider than 1 cm in vertical dimension, tracheomalacia and loss of cartilage, previous history of severe bacterial infection associated with tracheostomy, and posterior laryngeal inlet scarring with arytenoid fixation. In these circumstances, multiple procedures, more extensive alternative open surgical techniques, or maintenance of tracheostomy were necessary. In successful cases only three or fewer procedures on average were required. The factors associated with failure or success of endoscopic methods in the management of laryngotracheal stenosis, including use of the CO2 laser and soft Silastic stents, are analyzed.

Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications.

The management of laryngeal and tracheal stenosis continues to challenge us, despite advances in surgical techniques and better understanding of the wound healing process. Injury to the airway mucosa is the inciting event, regardless of the cause of the stenosis. Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. Topical application of mitomycin-C (0.4 mg/mL) was used as an adjuvant treatment in the endoscopic laser management of laryngeal and tracheal stenosis in 15 patients. Fourteen patients (93%) have shown improvement of their airway and resolution of their preoperative symptoms. After a mean follow-up of 18 months, no complication was noted with regard to the application of mitomycin-C. This study gives promising findings on the efficacy and safety of mitomycin-C as an adjuvant treatment in the management of selected cases of laryngeal and tracheal stenosis.

Induction chemotherapy in advanced squamous head and neck carcinoma with high-dose cis-platinum and bleomycin infusion.

Forty patients with advanced head and neck cancer were treated with combined Cis‐platinum‐Bleomycin chemotherapy. Cis‐diammine dichloroplatinum (DDP) 120 mg/m2 iv was given after prehydration, with mannitol diuresis on Day 1. On Day 3, an initial loading dose of Bleomycin 15 mg/m2 was given by rapid iv push followed by continuous 24 hour intravenous infusion of Bleomycin 15 mg/m2 Day 3 through Day 10. DDP 120 mg/m2 iv was administered again on Day 22. The patients were evaluated for tumor response and resectability between Day 29 to Day 35. Of 39 patients who were evaluable, there were 8 complete responses or CR (20%) and 22 partial responses or PR (56%), for a major response rate of 76%. Nineteen patients had surgery (14 patients whose lesions were initially inoperable and 5 patients who were initially operable). Chemotherapy toxicity in 40 patients included alopecia (40), vomiting (39), mucositis (11), skin rash (10), fever (17), weight loss of more than 5 lbs. (25), WBC less than 3,000 (2), platelets less than 100,000 (1), peak serum creatinine of 2 mg% (3), severe‐hearing loss (1), hypersensitivity reaction (2). Surgical complication in 19 patients were pharyngocutaneous fistulae (2), wound dehiscence (1), meningitis and brain abscess (1). There was one death secondary to nephrotoxicity. This particular combination chemotherapy when given as initial treatment, appears very effective in reduction of tumor bulk. Long‐term follow‐up and randomization is necessary to determine effect upon survival.

Endoscopic Treatment of Subglottic and Tracheal Stenosis by Radial Laser Incision and Dilation

Five patients with severe fibrous subglottic and tracheal stenosis were treated by endoscopic radial laser incision and dilation using both carbon dioxide and neodymium:yttrium aluminum garnet lasers. Good results were noted without complications in all patients in a follow-up period of at least 1 year. Careful selection of patients, excluding those with tracheal collapse or tracheomalacia, and preservation of tracheal epithelium with minimal heat and mechanical trauma are considered essential for good results.

Excisional biopsy in the selective management of T1glottic cancer: A three‐year follow‐up study

Transoral excisional biopsy has been used in the evaluation and management of 103 Tl glottic cancers. A 3‐year follow‐up on these patients indicates that excisional biopsy unequivocally established the diagnosis and stage of the disease and that it is adequate treatment for micro and mini squamous cell cancers of the glottis in which the margins of excision are clear.

Patterns of relapse in locally advanced head and neck cancer patients who achieved complete remission after combined modality therapy

Relapse patterns in patients with locally advanced head and neck cancer who achieved complete remission were evaluated. After combined modality therapy with induction chemotherapy followed by surgery and/or radiotherapy, 71 of 103 patients were clinically free of disease. The 5‐year recurrence rate was estimated at 51%, with a 39% local and 26% distant failure rate by 5 years. The factors significantly affecting the relapse patterns were: (1) the site of the primary tumor (those with oral cavity lesions were more likely to fail locally, whereas hypopharynx patients had a higher risk of distant metastases); (2) the type of definitive local treatment (those patients who received surgery and radiotherapy were at lower risk of pure local failure); (3) TN Stage (patients with T4N3 or T3N3 tumor were at higher risk of both local and distant failure); and (4) time to response and presence of oropharyngeal lesions (patients who had a longer period from diagnosis to final complete response [CR] and patients with oropharyngeal primaries were at higher risk for simultaneous local and distant failure). Type of chemotherapy, patient age, tumor differentiation, and response to induction chemotherapy did not significantly influence the patterns of relapse. A combined modality approach with induction chemotherapy, surgery, and/or radiotherapy does not seem to reduce the incidence of distant metastases significantly.

Autofluorescence characteristics of oral mucosa

The fluorescence characteristics of tissues depend upon their biochemical composition and histomorphological architecture, both of which undergo a change during malignant transformation. These changes are detectable as an alteration in the fluorescence spectral profile of the tissues.

A prospective randomized trial of methotrexate versus cisplatin in the treatment of recurrent squamous cell carcinoma of the head and neck

A prospective randomized study was conducted to determine the relative effectiveness, toxicity and tolerance of methotrexate (MTX) versus cisplatin (DDP) in patients with recurrent head and neck squamous cell carcinoma. Forty‐four patients were randomized to receive either MTX, 40 mg escalated to 60 mg/m2 IV push weekly, or DDP, 50 mg/m2 6 hour infusion days 1 and 8 every 4 weeks. All patients had objectively measurable disease and a performance status greater than 60% (Karnofsky scale). All had been treated with surgery and/or radiotherapy. No patients had prior chemotherapy. Prior treatment, performance status, and site of primary disease were comparable in both groups. Complete and partial objective responses were achieved in 23.5% of the MTX group and 28.6% of the DDP group (P = 0.51). Median duration of response was 84 days in the MTX group and 92 days in the DDP group. Median survival of patients was 6.1 months with MTX and 6.3 months with DDP. Mucositis was noted in 38% of patients in the MTX group (P = 0.001) compared to none in the DDP group. Vomiting occurred in 87% of patients in the DDP group (P < .0001) compared to 10% of patients in the MTX group. This study demonstrates that in the treatment of recurrent head and neck squamous cell carcinoma, MTX and DDP are equally effective, although MTX appears to be better tolerated. Cancer 52:206‐210, 1983.

Idiopathic Subglottic Stenosis Revisited

Idiopathic subglottic stenosis (ISS) is a rare inflammatory process of unknown cause, usually limited to the subglottic region and the first 2 tracheal rings. We performed a retrospective analysis of our experience with a series of patients with this condition. The study involved retrospective review of the records of patients with ISS. A series of criteria that included patient clinical history, laboratory tests, flexible nasolaryngoscopic examination, and biopsies were used to establish a diagnosis. Symptoms, treatment, and outcome were examined. A total of 16 patients were identified; 14 were female (87.5%), and 2 were male. The mean follow-up time was 75.5 months. Fourteen patients required surgical treatment for respiratory compromise. Nine of these cases have been controlled effectively with endoscopic laser techniques. Endoscopic management failed in 5 patients, and 2 patients underwent laryngotracheal resection and reconstruction. Mitomycin-C was used in 6 patients as an adjuvant to endoscopic laser surgery. Patients in whom endoscopic treatment failed were noted to have thicker (>1 cm) and more complex stenoses. The diagnosis of ISS is a diagnosis of exclusion. A complete workup of the patient must be performed to rule out other causes of stenosis. Endoscopic laser surgery is a valid initial approach for thinner, noncomplicated lesions. Patients with thicker, complex lesions in whom endoscopic treatment fails are best managed with laryngotracheal resection and reconstruction. However, adjuvant use of mitomycin-C may prove beneficial in the treatment of these patients. Estrogen may play a role in the pathogenesis of ISS by altering the wound healing response.