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In this article we evaluate two factors that may be responsible for the reported increased mortality rate in metachronous cancers: prior radiation therapy and stage at presentation. A select group of 358 patients was split into three groups: no prior cancer (group 1), prior cancer treated with radiation therapy (group 2), and prior cancer treated with surgery alone (group 3). We compared survival among the three groups according to stage (T1 or T2 vs. T3 or T4) using the Lifetest procedure. Survival in patients with advanced (T3 or T4) cancers was uniformly poor, and survival in patients with low-staged (T1 or T2) cancers was disproportionately poor only for patients in group 2. Metachronous cancers are not necessarily more lethal, except when the cancer arises within prior irradiated tissue. Initial treatment decisions for patients with primary cancers must always provide for the contingency of a metachronous cancer, and the judicious use of radiation therapy is essential. (Otolaryngol Head Neck Surg 1998;119:619-23.)

The authors have investigated whether genetic abnormalities in two genes, loss of heterozygosity (LOH) of p53 and amplification of the cyclin D1 gene, correlate with clinical outcome in 56 matched pairs of blood and tumor from patients with squamous cell carcinoma of the head and neck (SCCHN). Frequency of p53 LOH was 47.4%, of cyclin D1 amplification 33.9%, and of both abnormalities together 23.7%. p53 LOH was associated with T4 (P = 0.003) and stage IV (P = 0.015) tumors. Cyclin D1 amplification was associated with recurrences and/or metachronous tumors (P = 0.007). The total number of p53 and cyclin D1 abnormalities (scored as zero, one, and two) show a pattern that seems to be additive; the increase in the number of these abnormalities is associated with a proportional increase in the frequency of T4, stage IV, presence of recurrences and/or metachronous tumors, and possibly a proportional decrease in the disease-free interval in the sample. The association of the markers with recurrences and/or metachronous tumors persists if the tumor stage effect is mathematically removed. The combined analysis of the p53 and cyclin D1 abnormalities seems to be more informative than either of them individually and may have predictive value in SCCHN.

We implemented screening for squamous cell carcinomas of the oral cavity, pharynx, and larynx with symptom assessment and systematic inspection of the oral mucosa by primary care practitioners at health care sites serving inner-city residents of Boston; 4611 tobacco users older than 40 years were screened, and 313 with specific criteria were referred to otolaryngology for diagnostic evaluations. In these screened patients, the prevalence of oral mucosal lesions was almost 13% and prevalence of persistent hoarseness was more than 11%. Although the identification of these cancers was rare (nearly 3%), abnormal findings were seen in more than 70% of referred patients. These clinical and histologic diagnoses are described. We have documented the range of pathologic conditions in high-risk patients screened for upper aerodigestive tract malignancy.

Introduction: Cancer in the tongue base, which is adjacent to or invading the lingual epiglottis, requires resection of part or all of the larynx to assure adequate surgical margin. Based on whole mount laryngeal sections, a tongue base-partial supraglottic laryngectomy procedure was designed for tumors adjacent to or minimally invading the lingual epiglottis. Methods: A group of five patients with carcinoma of the tongue base adjacent to or minimally invading the lingual epiglottis was identified. This technique requires excision of the epiglottis, hyoepiglottic ligament, and pre-epiglottic space with the lesion. The structural physiological integrity of the false vocal cords with or without the hyoid bone is preserved. Results: Clear tumor margins were obtained in all five patients. In three patients who required up to 50% resection of the tongue base, decannulation and resumption of a full oral diet was achieved. Two patients with more extensive lesions required 70% resection of the tongue base. Both patients underwent completion laryngectomy months later because of persistent aspiration. Conclusion: This preliminary report suggest that partial supraglottic laryngectomy may be used with acceptable functional results in patients with limited tongue base lesions.

A system for multidisciplinary data collection for metastatic neck disease is discussed. Information from 87 neck dissections and 3218 lymph nodes is reported to illustrate the strength of the model. Clinical (endoscopic) assessment under general anesthesia, surgical assessment during the neck dissection, and radiographic (computed tomographic scan) assessment were compared with the pathological evaluation. All disciplines stratified the necks by region and node size. This model provides an effective stratagem for multi-institutional studies.

The tendency of epiglottic cancer to invade the preepiglottic space and the significance of this invasion was evaluated in 36 surgical specimens of epiglottic carcinoma originally staged T1 or T2. None of the 9 lesions originating above the hyoepiglottic ligament invaded the preepiglottic space. Twenty-four of the 27 (89%) lesions originating below the hyoepiglottic ligament showed invasion of the preepiglottic space and were clinically understaged. Of the 3 infrahyoid lesions showing no invasion of the preepiglottic space, 1 was a verrucous carcinoma and another was a mucoepidermoid carcinoma arising on the petiole. All other lesions were squamous cell carcinoma. In 12 of the 24 patients (50%) with preepiglottic space invasion, cervical node metastasis was present despite the preoperative staging of T1 or T2.

Transoral surgery in the supraglottic larynx is facilitated by the use of a new instrument, an adjustable supraglottiscope. Conventional adjustable laryngoscopes are not designed for supraglottic surgery and are therefore difficult to use in this area. The adjustable supraglottiscope: (1) provides wide exposure of the supraglottis and much of the lower pharynx, (2) allows instruments to be introduced from the side (between the blades), (3) allows for true suspension, and (4) retracts the endotracheal tube out of the way. These factors provide greater visualization and control of the surgical field and thus improve hemostasis and precision. The adjustable supraglottiscope has been used successfully in a variety of clinical situations. Transoral supraglottic surgery now takes considerably less time and is done with much greater ease. The adjustable supraglottiscope is a valuable instrument in our armamentarium and extends our versatility for endoscopic management of lesions of the supraglottic larynx and lower pharynx.

Screening programs show promise in increasing the rate of early detection of head and neck cancers in high-risk populations. Prout et al (Otolaryngol Head Neck Surg 1997;116:201-8) examined the usefulness of a large-scale screening program for head and neck cancer in an inner city population by primary care physicians. Symptom assessment was based on the American Cancer Society's "Seven Warning Signs for Cancer," (Cancer manual. 8th ed. Boston: American Cancer Society, Massachusetts Division; 1990. p. 40-64) 4 of which are relevant to the head and neck. However, these signs may be insufficient for detection of early head and neck cancer. We analyzed these and other typical symptoms to determine their role in early detection. Coincident medical problems, tobacco abuse, and alcohol abuse were also analyzed. Our findings indicate that no symptom or symptom complex is strongly correlated with early head and neck cancer for any subsite except the glottis. Symptom duration is an unreliable indicator of the duration of disease. However, patients under medical supervision are more likely to have their cancers detected early, supporting the value of surveillance by the primary care physician. The absence of definite early warning signs for most head and neck cancers suggests the need to develop essential screening criteria. Defining the population that is at high risk for head and neck cancer and subjecting it to an aggressive screening protocol is essential.

This simple, inexpensive device for submucosal true vocal fold saline infusion into Reinke's space improves the diagnosis and treatment of small vocal cord lesions and is a useful addition to our microlaryngoscopy instrumentation.

Since 1977, we have used induction chemotherapy (CT) plus radiation therapy (RT) with curative intent in 35 advanced head and neck cancer (Ca) patients who otherwise would have required total laryngectomy. Fourteen patients had advanced Ca of the larynx or supraglottic larynx (SGL); 21 patients had Ca of the hypopharynx. In six patients the Ca was Stage III; in 26 patients it was Stage IV. Three patients had Stage II disease--2 with cancer of the pyriform sinus and one patient with Stage II SGL Ca who refused surgery. Chemotherapy consisted of platinum (P) + bleomycin in 18 patients until 1982, then P + fluorouracil in the next 17 patients. Total response rate was 77%--complete (CR) in 26% and partial (PR) in 51%. There were two toxic deaths. Surgery was limited to tracheostomy in 4 patients prior to CT and to radical neck dissection after CT in 4 others. Two patients required salvage laryngectomy at 11 and 31 months, respectively. One patient underwent partial laryngectomy with voice preservation. Thirty-two patients were evaluable for overall response after RT. Final disease-free status was achieved in 20/34. One long-term survivor was lost to follow-up (44 months) and 8 patients remained alive at 13+ to 109+ months. Median failure-free survival for all patients was no less than 24 months. Not counting 4 early deaths free of disease, 2-year local control using only chemotherapy plus radiation was 52% (16:31). Overall, 33 of 35 patients retained their voices. Sixteen patients (46%) have survived 2 years or longer. Survival of patients who achieved CR after induction chemotherapy was 48 months versus 14 months for those with less than a CR (p = 0.001). Patients with a hypopharyngeal primary had only a 33% 2-year local control rate with chemotherapy and radiation and a median survival of only 12 months versus 77% control and a minimum 39-month survival for those whose tumor arose in the larynx (p = 0.009). Induction chemotherapy plus radiation therapy is an effective strategy which can produce a high rate of larynx preservation, local control, and long-term survival in patients with advanced cancer of the larynx. Patients with hypopharyngeal primaries have a lesser rate of long-term survival and local control, despite similar overall response rates.

This case represents a peripheral nerve sheath tumor as a cause of nasal obstruction. Nerve sheath tumors are relatively uncommon; however, most otolaryngologists will encounter them. These tumors develop from cranial and spinal nerve roots and from peripheral nerves. In total, approximately 25% to 44% of nerve sheath tumors occur in the head and neck region. Although the most important are cranial nerve tumors--the majority being acoustic neuromas arising from the vestibular nerve--they may also develop in the nasal cavity.

An initial endoscopic surgical approach to early supraglottic cancer provides the surgeon with the ability to accurately stage these lesions, avoiding possible undertreatment while allowing for a valuable treatment option for those supraglottic cancers with histologically incontrovertibly superficial disease. Early invasion of the preepiglottic and paraglottic spaces can be determined accurately without altering or delaying any treatment option (open surgical excision, radiotherapy, or chemotherapy). The tendency of supraglottic cancers to transgress the natural foramina of the epiglottis is well established, and the concern about this depth of invasion is reflected by the 1977 revised staging criteria, which required assessment of the preepiglottic space (PES). Along with the microscope and the carbon dioxide laser, the adjustable supraglottiscope facilitates the determination of PES invasion and facilitates en bloc excision of superficial supraglottic cancers. The resulting morbidity typically is no different from that with routine direct endoscopy and biopsy.

Endoscopic epiglottectomy (epiglottidectomy) may be performed with relative ease and minimal morbidity by using standard microlaryngoscopy techniques and the CO2 laser. Depending on the indications, the removal may be partial or complete. Indications for 51 epiglottectomies included treatment of supraglottic airway obstruction--30 cases; discovery of benign or malignant neoplasm (diagnosis and staging)--20 cases; treatment of malignant neoplasm--7 cases; glottic visualization--4 cases; and treatment of chronic inflammatory conditions--1 case. It is not unusual for a patient to have more than one indication for this procedure. Some epiglottic cancers invade the pre-epiglottic space. This crucial information may not be detectable by MRI or CT scanning techniques. Laser epiglottectomy provides a method to explore and perform a biopsy of the pre-epiglottic space and thereby stage these lesions accurately. There are no significant problems with postoperative alimentation, airway, or voice. Any form of primary or adjuvant therapy can be started without delay.

• We carried out a prospective, double-blind study at three institutions, comparing esophagography with esophagoscopy for the detection of simultaneous cancer of the esophagus in patients with other squamous cell cancers of the head and neck. The goal was to determine whether esophagography and esophagoscopy are necessary for the examination of patients before treatment. One hundred eighty-two patients were studied; both examinations were done in 148 patients. Twenty-one patients could not undergo esophagoscopy; esophagography was inadequate in 9 patients; 4 patients could have neither examination. Concordance was noted between the two procedures in 86.5% of patients. Sixty-five percent were normal, and 21.5% were abnormal. One esophageal cancer was found in this series that was diagnosed by both methods. Our data suggest that esophagoscopy and esophagography may be complementary in evaluating squamous cell carcinoma of the head and neck in patients before treatment. Esophagography alone was useful in patients in whom esophagoscopy could not be performed. ( Arch Otolaryngol Head Neck Surg . 1990;116:917-919)

Transoral excision of supraglottic and hypopharynx cancer as a single modality is effective when lesions are selected for small size and endoscopic accessibility. Excisional biopsy with clear margins of larger supraglottic tumors in combination with postoperative radiotherapy provides an excellent treatment alternative for selected lesions in patients who are not candidates for open surgery. In this preliminary report, 45 cases using this minimally invasive approach are reviewed outlining oncologic rationale and functional advantages. A large bore tubed laryngoscope or the adjustable bivalve supraglottiscope was used along with a carbon dioxide laser in all cases. In 22 of the 45 patients (mostly TI), local en bloc excision of the primary cancer was performed as sole treatment on selected lesions of the supraglottis and hypopharynx. There were no local recurrences, however, 1 patient developed a neck recurrence and was salvaged by neck dissection. Twenty-three of the 45 patients had more extensive primaries (mostly T2, T3) and N0 necks. Transoral excisional biopsy was followed by full-course radiation therapy to the primary site and both necks. All 23 were followed a minimum of 2 years, and the median follow-up period was 58 months. Clear margins were obtained in 16 of 23, and there were no recurrences in the larynx. Two of 16 did fail in the neck and died despite neck dissection. Seven of 23 patients had positive margins and, despite full-course radiotherapy to the primary site and both necks, 5 of 7 failed locally or regionally. Two of the 7 died of their disease despite open salvage surgery. Therefore, 4 of 23 patients who underwent transoral excision of larger lesions followed by full-course radiotherapy died of recurrent cancer.

ORGANIC voice disorders are common, and their management is usually simple. Most people have experienced hoarseness with an upper-respiratory infection and know that treatment requires only time an...

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.

The carbon dioxide laser has been found to be a useful surgical adjuvant in our efforts to treat carcinoma and benign tumors of the head and neck. It has been of help in establishing the proper staging, in diagnosing recurrence after radiation therapy, in re-establishing the airway blocked by tumor, and in reducing tumor mass prior to definitive therapy. It provides a simple method of excision for curative therapy. All of this is accomplished with minimal morbidity. Most patients can return home on the first postoperative day. They can eat, have a serviceable voice, and require no tracheotomy or analgesics, all of which provide a significant cost benefit.

Congenital choanal atresia frequently demands immediate recognition in the newborn, and provision of a nasal airway as soon as possible. A variety of techniques are available to correct this problem, but none is entirely satisfactory. Transpalatal procedures are associated with significant morbidity in the newborn, and transnasal microsurgical procedures are less predictable when a thick bony plate is present in the choanal obstruction. Transnasal resection with the CO2 laser has been carried out in seven patients (ten sides), whose ages ranged from 16 hours to 14 years. From this early experience, it appears that the procedure is entirely feasible and convenient. It seems to have significant advantages over conventional microsurgical techniques. Eight out of ten choanae have remained patent for four months or more. A lumen keeper is needed during the immediate postoperative period for at least two to three weeks. The procedure is associated with minimal morbidity.

Biopsy specimens of “normal” mucous membrane of patients susceptible to the effects of the carcinogens of tobacco revealed morphologic abnormalities on electron microscopic examination that were consistent with the concept that carcinogenesis is a multistep process of sequential neoplastic development extending over a long period of time. Such changes in the upper aerodigestive tract are probably tobacco induced and may be reversible if tobacco exposure is eliminated. Use of the electron microscope can provide the clinician with an accurate assay of the severity of mucosal alterations induced by tobacco. The ability to detect such morphologic abnormalities should provide another deterrant to smoking and a useful tool in the further study of these phenomena.

Orbital pseudotumor is believed to be a nonspecific, acute or chronic inflammatory process involving the intraorbital soft tissue. Orbital pseudotumor may masquerade as sinusitis with orbital complications or as a severe upper respiratory tract infection. Five cases are presented to illustrate the difficulties in diagnosis when initial symptoms relate to the upper respiratory system rather than to an isolated orbital mass. In these cases, orbital ultrasound and computed tomograms were helpful in making the diagnosis. Treatment consisted of systemic corticosteroids in four of the five patients. Recognition of early symptoms and findings, along with earlier involvement with the ophthalmologist, will make a more effective treatment regimen possible.

Endoscopic treatment of early carcinoma of the larynx is curative, the cure rates in our experience being equal to those achieved by radiation therapy and by laryngofissure. It is highly cost effective in terms of money and of patient out-of-work time. It can be used repeatedly and does not interfere with future treatments. It is our method of choice.

Partial endoscopic excision of obstructing laryngeal carcinoma with the CO2 laser is an alternative to emergency tracheotomy or emergency laryngectomy whenever the airway control can be initially ensured by endotracheal intubation. The practical advantages of this approach are elimination of the septic complications of tracheotomy, the opportunity for planned preoperative chemotherapy or radiation therapy, and better nutritional and psychologic preparation of the patient for surgery.

Keratosis, atypia, carcinoma in situ, and microinvasive cancer occurring as white or red patches on the vocal cords are part of the diathesis of cancer of the aerodigestive tract and represented a sequential continuum. Excisional biopsy is the preferred treatment for identification and potential cure of the lesion. If the margins of excision are inadequate, further treatment options are either reexcision or radiotherapy. Radiotherapy should be used only when the need for voice conservation prevails. Cessation of smoking does not remove the potential for progression of the disease, therefore, all patients must be followed indefinitely. Excisional biopsy of keratosis, carcinoma in situ, and microinvasive cancer of the larynx offers an excellent prognosis for voice preservation and survival.

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 less than .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.

The CO2 laser has been found to be a useful adjunct in our efforts to treat laryngeal carcinoma. Utilized endoscopically, it has been of help in establishing the proper staging, in diagnosing recurrence after radiation therapy, in reestablishing airways blocked with tumor, in debulking tumor mass prior to radiation and/or chemotherapy, and as a primary mode of excisional therapy, all accomplished with minimal morbidity. Most patients may return home the first postoperative day, eating, with serviceable voice, and requiring no tracheotomy or analgesics, all of which provide a significant cost benefit.

1. 1. Carcinoma of the palatine arch is part of a regional diathesis of carcinoma of the mucosa of the upper aerodigestive tract and this concept has a definite influence on the choice of treatment. 2. 2. Surgery has an important role in the management of both the primary tumors and the regional metastatic nodes. 3. 3. Radiation therapy is indispensible in the management of carcinoma of the tonsillar crypts, stage IV tumors of the palatine arch, and primary tumors of the palatine arch with certain specific extensions. 4. 4. Comprehensive management of carcinoma of the palatine arch requires careful evaluation of each patient and his disease, vigorous application of the chosen method of treatment by either the surgeon or the radiotherapist, and continuous follow-up study and supportive treatment for the rest of the patient's life.

Gould: We will start with some general observations about phonosurgery. Hirano: Whenever you treat the vocal fold, it is very impor tant to unders tand its funct ional anatomy as a vibrator or sound generator. The vocal fold is not uniform but rather a layered structure. At the surface there is a very thin capsule, which is called epithelium. Under the epithelium there is a lamina propria of the mucosa, which consists of three layers. This structure differs from animal to animal, and no animal has been found that has the same structure as a human adult. Most superficially, there is a layer that is very loose and pliable. This layer is called Reinke's space, and it is most important in vibration. If something is stiff in this layer, it alters and produces deterioration in normal vibration. Under this top layer are two deeper layers, which still belong to lamina propria, an intermediate and a deep layer. These two layers together are called the vocal ligament. The human adult is the only animal that has a vocal ligament. Human infants do not have vocal ligaments. The main body of the vocal fold consists of muscular tissue called the vocalis muscle. This is part of the thyroarytenoid muscle. Proceeding from Reinke's space to the vocalis muscle, the tissue gets gradually stiffer. When surgery is performed on the vocal fold, it is very important to maintain as much as possible of this normal structure. Sometimes some of the

Transoral excisional biopsy has been used in the evaluation and management of 103 T1 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. Excisional biopsy with positive margins and larger T1 tumors establishes the absolute need for radiotherapy. Excisional biopsy is ideal for the diagnosis and management of verrucous carcinoma and spindle cell carcinoma. Recurrent/residual squamous cell carcinoma after radiotherapy should be explored by excisional biopsy which may be curative or will establish the need for partial or total laryngectomy. The appropriate use of excisional biopsy in the selective management of early T1 glottic cancers requires attention to detail by the surgeon and the pathologist and sound clinical judgment.

The sequence of histological change induced by CO2 laser irradiation was discussed in terms of two factors: the physiomechanical factor and the physiochemical factor. At sufficiently high heat energy levels, the immediate findings are characterized by crater formation resulting from rapid vaporization of the water and ejection of the solid component. In the immediate vicinity of the crater edge, the maximum tissue temperature rise is 65 degrees C above the 32 degrees C ambient tissue temperature and it decreases to the primary tissue temperature within a distance of 2 mm. The healing process of CO2 laser induced lesions proceeds with minimal delay. The lymphatic and vascular channels are occluded in the marginal area of coagulation resulting in a marked hemostatic effect. This sealing effect increases the margin of safety in preventing possible dissemination of tumor cells. By selecting the appropriate power, time, and focus cone angle, precise destruction of preselected areas of tissue can be achieved with an extraordinary hemostatic effect without damaging the underlying tissue. These advantages are especially helpful in function-preserving surgery.

Medical management of organic laryngeal disorders always involves evaluation and advice; it frequently includes reassurance and sometimes voice therapy. Occasionally medication is also necessary.

The carbon dioxide and neodymium:yttrium aluminum garnet lasers have well documented but characteristically different biological effects, yet little is known about their cumulative, synergistic, or paradoxical effects when used sequentially on living tissue. Using a Merrimack ML 880 laser, a series of superimposed CO2 and Nd:YAG lesions in various combinations were produced on the undersurface of dog tongues. Therapeutic time and power settings were chosen and the number of applications varied, with suitable controls. Observations and measurements were made on acute, healing, and healed lesions. All lesions were excised and submitted for routine hematoxylin and eosin histology. Acute lesions were also assessed for cell viability using rhodamine 123 as a supravital marker. The results show that, even though all the lesions eventually heal, the actual cell damage produced by the Nd:YAG laser is much more than is suggested by the size of the acute lesion. This cell damage can be reduced by the surface carbonization produced by initial application of the CO2 laser. Higher surface temperatures are reached in this combination with less fibrosis and scarring than equal energy counterparts where the Nd:YAG laser was applied first. The knowledge of these synergistic effects can be used to advantage in the clinical setting. The rhodamine 123 technique also appears to be a valid measure of acute thermal tissue injury.

Six patients with advanced squamous cell cancers of the head and neck, with serum IgA greater than or equal to 400 mg/dl and IgE less than or equal to 1000 IU/ml, underwent a trial of six 2-liter plasma exchanges over a 2-3-week period. Disease progressed in patients 1, 2, and 4, who died on days 44, 72, and 159. The tumor in patients 3 and 6 regressed significantly, repeatedly in patient 3 over each of four courses of apheresis. Tumor recurred in both patients after cessation of treatment, and they died at days 420 and 79. Patient 5, with inoperable disease, received full-dose radiotherapy immediately following the course of apheresis, and showed complete response in the primary lesion and a major response in the extensive lymph node metastases, dying on day 421 of apparently unrelated causes. Serum IgE in the three patients experiencing tumor regression rose paradoxically during plasmapheresis. Only patient 3 had an elevated level of soluble E-receptor suppressor factor prepheresis; the serum of patient 6 was lymphocytotoxic prepheresis but this activity decreased or disappeared during each of the exchanges studied. Controlled trials are now indicated.

Twenty-one male patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with an induction regimen of bleomycin 15 mg/m2 I.V. bolus followed by a continuous 24-hour I.V. infusion at a dose of 15 mg/m2/day for 7 days. One week following induction therapy, patients were reevaluated for response and then received definitive therapy with surgery and/or radiation therapy. The chemotherapy yielded a major response rate of 33% (one CR, six PR). Toxic manifestations of this regimen were mild, consisting of fever, alopecia, rash, and mucositis. There was no pulmonary toxicity detected. The response rate obtained with bleomycin infusion is inferior to the combination of cis-platinum with a bleomycin infusion as induction therapy in previously untreated patients with squamous cell carcinoma of the head and neck.

Eleven patients with unresectable or marginally resectable (stage III and IV) cancer of the head and neck were treated according to protocol with preoperative chemotherapy, surgical resection, and postoperative radiotherapy. Chemotherapy consisted of a combination of cis-diamminedichloroplatinum (II) (cis-DDP), 120 mg/M2, and bleomycin, 15 mg/M2, given sequentially during a three week treatment period. Seven patients initially had unresectable lesions which became amenable to surgical resection after chemotherapy. All eleven patients had approximately a 25 to 100 per cent reduction in tumor size. Histopathologic examination after chemotherapy showed a marked tendency towards cellular differentiation and keratin formation. Tumor necrosis was conspicuous by its absence. These histologic changes appear to be different from those seen after the use of other chemotherapeutic agents and radiotherapy. The histopathologic results closely resemble those found after the administration of bleomycin alone, although considerably accentuated.

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: 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); the type of definitive local treatment (those patients who received surgery and radiotherapy were at lower risk of pure local failure); TN Stage (patients with T4N3 or T3N3 tumor were at higher risk of both local and distant failure); and 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.

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.

Recurrent squamous papillomas of the upper respiratory tract were examined by light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Surface of the cells is irregular and is covered by numerous stout microvilli. These are shorter and broader than those of cells of the uninvolved mucosa. The villi often seem umbilicated at the apex; the remainder of them, however, are rounded. The epithelium participating in the formation of papillomas shows some maturation of the cells but this does not progress normally. The predominating area is the thickened spinous layer representing the bulk of the lesion. The basal layer shows mildly increased activity but the basement membrane is intact. The cells often are very closely packed but in some areas, more particularly in the deep layer, they are loosely arranged. The intercellular space contains a moderately electron-dense finely fibrillar material. No abnormal mitoses are found. The neighboring univolved epithelium often shows increased growth activity and some inflammation. The larygneal papillomas propably represent an overgrowth of epithelium which may develop following hindered desquamation caused and/or heralded by a chronic inflammatory condition probably of viral origin and may be preceded by epithelial metaplasia and hyperplasia.

Forty-one patients with unresectable Stage IV head and neck squamous cell carcinoma were treated with combined modality therapy (CM) consisting of induction chemotherapy followed by surgery and/or radiotherapy (RT). Treatment and survival results are reported and compared to results obtained in treating 41 historic controls with RT alone. No patient had distant metastases. Patients in the CM group received cis-platinum (DDP) 120 mg/m/sup 2/ on days 1 and 22 with prehydration and mannitol diuresis and bleomycin 15 ..mu../m/sup 2/ as a continuous infusion between days 3-9 started after a 15 ..mu../m/sup 2/ IV push. Patients underwent reendoscopy two weeks after completing chemotherapy to evaluate response. Subsequent surgery and/or radiotherapy were administered depending on tumor resectability after chemotherapy. Induction chemotherapy with DDP and bleomycn infusion followed by surgery and/or radiotherapy appears to be associated with a higher CR rate and prolonged survival compared to RT alone. (JMT)

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.

A CO2 laser rigid bronchoscope system has been used to palliate symptoms of a malignancy obstructing the tracheobronchial airway. Fifty-nine endoscopic laser operations (34 patients) were done between 1975 and 1981. Severe dyspnea and obstructive atelectasis were the most common indications for treatment. Contraindications for treatment included extrinsic tracheobronchial compression, widespread distant metastases, rapidly progressing tumors, and highly vascular neoplasms. There were nine primary tracheal malignancies, five metastases from distant sites, and 20 primary lung cancers with tracheobronchial obstructions. Most patients were previously treated with one or more standard modalities (radiation therapy, surgery, and chemotherapy). Removal of airway obstruction was occasionally indicated prior to radiation therapy to facilitate treatment. There were seven instances of complications in this group of patients and one mortality. Most patients (23 of 34) have died from their malignancy. The best palliation was achieved in proximal (tracheal and main stem bronchial), slower growing tumors.

Recurrent respiratory papillomatosis is most common in childhood but it affects all age groups; it represents a diathesis of the aerodigestive tract so that lesions may develop at various sites — the nares, lips, pharynx, nasopharynx, larynx, tracheobronchial tree, and the lungs. Ablation of all visible papillomas with the surgical laser achieved remissions in approximately one-third of patients for one year or more; since relapses may occasionally occur 2 to 20 years later, cure can never be assumed. At the present time, management is directed towards total ablation of all visible papilloma consistent with preservation of the airway and voice; reduction of the tumor burden to minimal proportions is thought to allow the maximum opportunity for remission. As the host-papilloma relationship is unraveled, it may be possible in the future to provoke an immune response so that remissions can be predicted and produced consistently.