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.

Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer.

PURPOSE: To compare two published schedules of cisplatin plus fluorouracil (5-FU) infusion and radiation as either sequential or concomitant treatment for toxicity and efficacy in patients with unresectable head and neck cancer. PATIENTS AND METHODS: This was a randomized trial between cisplatin 100 mg/m2 over 15 minutes on day 1 plus 5-FU 1.0 g/m2 by continuous infusion on days 1 to 5, repeated every 3 weeks for three cycles, followed by 70 Gy of radiation in 7 to 8 weeks, versus cisplatin 60 mg/m2 over 15 minutes on day 1 plus 5-FU 800 mg/m2 by continuous infusion on days 1 to 5 plus radiation 2 Gy on days 1 to 5, repeated every other week for seven cycles. Unresectable head and neck squamous cancer patients not previously treated with radiation or chemotherapy and with a performance status of 0 to 2 were stratified by tumor (T) and node (N) groupings and performance status and randomized. RESULTS: Two hundred fifteen patients were entered and 214 analyzed, 107 on each arm. After all treatment, overall response rates were different (P = .003), with similar complete response rates, but more partial responses and fewer patients with no change or progression with concomitant treatment. Cox regression analysis for progression-free survival identified concomitant treatment (P = .003), Radiation Therapy Oncology Group (RTOG) stage III grouping (P < .0001), performance status (P = .0002), concomitant treatment (P = .003), and treating institution (P = .006) as significant. The sequential and concomitant treatments showed similar distant failure patterns (10% and 7%, respectively), but divergent regional failure rates (55% and 39%). Severe and worse toxic events were similar between the treatment programs, but radiation-induced mucositis combined with cisplatin-induced water-losing nephropathy, in the concomitant arm only, demanded more supportive care. Survival duration was similar between the treatment arms, but significantly more patients in the sequential arm died of their cancer (P = .011). CONCLUSION: Concomitant treatment offered improved disease control, predominantly of regional disease, but benefit was dependent on the experience of the treating institution. Translation of this benefit into improved survival is not yet evident, with an excess of deaths from other causes in the concomitant arm.

Combined simultaneous cisplatin/fluorouracil chemotherapy and split course radiation in head and neck cancer.

Fifty-three patients with stage III (eight patients, 15%), stage IV (36 patients, 68%), or recurrent disease (nine patients, 17%) entered a study of simultaneous cisplatin, 60 mg/m2 day 1, fluorouracil (5-FU) infusion, 800 mg/m2 days 1 to 5, and radiation, 2 Gy days 1 to 5, every other week for a total of seven cycles (70 Gy in 13 weeks). Patient acceptance was high, with only two patients (4%) refusing to complete therapy. The median actual dose delivered was 88% of the planned dose for cisplatin, 78% for 5-FU, and 70 Gy for radiation. Weight loss of 10% or more and severe mucositis were the most common side effects (53% and 48% incidence, respectively). All patients were followed at least 1 year (median, 51 months). While the complete response rate (55%) seemed no better than that reported in other series, freedom of progression of regional disease (73%), and the survival of all patients (median, 37 months) were substantially improved. Only 33% of partial responders have failed regionally, while 15% of complete responders have failed regionally (P greater than .10), which indicates that clinical assessment of response was unreliable. Stage, the presence of N3 disease, and delivery of less than the median actual dose received of 5-FU (but not cisplatin) were significantly associated with failure. This regimen is feasible and tolerable in this difficult patient population. It generally requires no special forced feeding techniques. Survival results from this limited institution study appear better than those using sequential multimodality therapies. With such favorable regional control, this approach may offer an alternative in the future to radical surgery and radiation in resectable disease. More definitive evaluation seems warranted.

Continued malignant cell proliferation in head and neck tumors during cytotoxic therapy.

The effect of cytotoxic therapy on the proliferation of squamous cell carcinoma of the head and neck in vivo in patients was evaluated before and 15-35 days after the start of therapy. To accomplish this, iododeoxyuridine was administered at t = 0, and bromodeoxyuridine was administered 15-35 days later during treatment with a tumor biopsy obtained for study immediately after each pyrimidine infusion. Monoclonal antibodies specific for the halogenated pyrimidines were used to identify cells that were in the S-phase at the time of the infusions. Eleven patients were studied prior to treatment. Of those, the intratreatment biopsy of eight patients contained tumor tissue. In the other three patients, tumor tissue was not present in the second biopsy. Continued precursor incorporation into DNA-synthesizing cells during treatment was detected in six of eight tumor specimens. In two tumor specimens, an increase in the percentage of S-phase cells was noted, in two specimens tumor cells synthesizing DNA were not detected, and in four specimens the percentage of S-phase tumor cells was lower than that in the pretherapy specimen. Patients in whom there were no S-phase cells detected during treatment or in whom no tumor was detected in the second biopsy had a favorable treatment outcome in comparison to those patients in whom continued tumor proliferation during treatment was detected. The number of cells in S-phase prior to the initiation of treatment was not predictive of whether or not proliferation would continue during cytotoxic therapy. Evidence for reentry of kinetically quiescent cells into the cycle during treatment was noted. Additionally, cytotoxic therapy altered the proliferation pattern of normal-appearing mucosa as well. The results of this study demonstrate that tumor cell proliferation does continue in some squamous cell carcinoma of the head and neck during intensive cytotoxic therapy.

Cyclin D1 expression in squamous cell carcinomas of the head and neck and in oral mucosa in relation to proliferation and apoptosis.

Deregulation of expression of the cell cycle regulator cyclin D1 (cD1) may be responsible for rapid proliferation of squamous cell carcinoma of the head and neck (SCCHN). We have studied the expression of cD1 in 46 SCCHNs using immunohistochemistry. Before biopsy, the patients received an in vivo infusion of iododeoxyuridine (IdUrd) for cell proliferation assessment. Additionally, the level of apoptosis was estimated using in situ end labeling (ISEL). Among 33 tumors, the proportion of cD1(+) cells varied from 0.5 to 51.3% (19.9 +/- 2.2%). Thirteen tumors did not express cD1. The fraction of S-phase (IdUrd-positive) cells was 26.3 +/- 1.8% in cD1(+) versus 20.0 +/- 2.4% in cD1(-) tumors (P = 0.06). The percentages of cD1(+) cells and of S-phase cells were not correlated (P = 0.37). Apoptosis was detected by ISEL in 15 of 33 tumors studied. ISEL-positive tumors contained a significantly higher proportion of cD1(+) cells (14.9 +/- 2.6%) than cD1(-) ones (7.9 +/- 2.8%; P = 0.03). There was a positive correlation between the percentage of cD1(+) cells and the degree of ISEL (r = 0.54; P < 0.001). In noninvolved oral mucosa, cD1(+) cells were located primarily in the suprabasal layers (29.3 +/- 3.8% versus 1.2 +/- 0. 2% in the basal layer). Only 23 of 44 mucosal specimens contained cD1(+) cells. All cD1(-) samples were proliferatively active and contained IdUrd-labeled cells. The percentage of cD1(+) cells in the oral epithelium from nontumor controls (uvula samples) was significantly higher than in the SCCHN group in both basal (2.4 +/- 0.4%; P = 0.008) and suprabasal (42.7 +/- 3.3%; P = 0.005) layers. Additionally, whereas in uvuli, cD1(+) cells were distributed evenly along the epithelial lining, in SCCHN samples the regions showing cD1 expression alternated with areas in which cD1 expression was undetectable. These data indicate that cD1 expression in SCCHN varies among tumors and is not correlated with cell proliferation. In noninvolved oral mucosa, cD1 expression differs from that in truly normal epithelium obtained from nontumor patients. A correlation between cD1 expression and the extent of ISEL positivity suggests a possible involvement of cD1 expression in the apoptotic pathways.

Cell kinetics of head and neck cancers.

We measured the tumor cell proliferative rate in 26 patients with head and neck cancer, 22 of which were squamous cell carcinomas (SCCs). Patients received sequential infusions of iododeoxyuridine and bromodeoxyuridine, after which the tumor was biopsied and studied. The percentage of labeled cells [labeling index (LI)] in well-differentiated SCCs was 20.4 +/- 2.7% (mean +/- SE) and 23.8 +/- 2.1% in moderately differentiated SCCs (P = 0.135). The LIs of two poorly differentiated SCCs were 39.4 and 55.9%. The LI was 2.5% in a high-grade lymphoepithelioma and 24.8% in a malignant lymphoma. In one well-differentiated and one poorly differentiated mucoepidermoid tumor, the LIs were 3.0% and 29.1%, respectively. S-phase duration time measurements ranged from 5.1-21.5 h (12.8 +/- 1.5). The calculated potential doubling times ranged from 18.8-84.5 h (47.3 +/- 6.7). The duration of G2 was between 90 and 180 min. To track the fate of labeled cells, in four patients a repeat biopsy was obtained 7-14 days after the iododeoxyuridine/bromodeoxyuridine infusion. These patients did not receive treatment between the biopsies. Due to the dilution of the label, most labeled cells in the second biopsy demonstrated a "fragmented" pattern resulting from repeated cell divisions. In two patients, however, 25% of cells in the second biopsy had undiluted label, suggesting that these cells had not divided after incorporating iododeoxyuridine/bromodeoxyuridine. On Day 7 labeled cells migrated to keratinized parts of tumors and to necrotic foci. Thus, the arrest of cell cycle transition, tumor cell differentiation, and cell death may be major routes of tumor cell loss from the proliferative compartment. This may explain the difference between very short potential doubling times and the actual rate of tumor growth.

In vivo labelling with halogenated pyrimidines of squamous cell carcinomas and adjacent non-involved mucosa of head and neck region.

The frequency and distribution of labelled cells were studied immunohistochemically in 37 squamous cell carcinomas (SCC) of head and neck after in vivo infusion of IdUrd and BrdUrd. Tumours were classified according to their labelling patterns. Low and moderate grade SCC consisted of tumour islands separated by interstitial tissue. In some tumours labelled cells only appeared near the basal layer while in others proliferative cells were evenly distributed within the neoplastic island. In anaplastic carcinomas labelled cells were distributed either randomly or around blood vessels (cord structures). While the basal layer in adjacent normal epithelium contained very few labelled cells (LI = 1.6 +/- 0.2%), the LI of basal cells in tumour islands were much higher than the average LI of the tumour (47.2 +/- 2.8% and 23.8 +/- 1.6%, respectively). In patients who had received cytotoxic therapy up to two months before the biopsy, the LI in the basal layer of normal epithelium was 19.0 +/- 3.5%. In sequential biopsies obtained 1-2 weeks after the infusion of IdUrd and BrdUrd some labelled tumour cells were found in necrotic foci and in pearl structures. Additionally, in six tumours, we found areas of cells labelled with IdUrd alone, even though the IdUrd infusion had been followed by a BrdUrd infusion 1 h later. This is in agreement with the phenomenon of intermittent tumour blood flow described earlier in experimental tumours.

Treatment of advanced head and neck cancer with concomitant radiation and chemotherapy.

Forty-four patients with predominantly inoperable or recurrent head and neck cancers were treated with combined chemotherapy (CT) and radiation therapy (RT) in a Phase I/II study. CT and RT were combined in a concomitant fashion to take advantage of radiosensitizing properties of the chemotherapeutic agents. Each treatment cycle consisted of cisplatin 60 mg/M2 on day 1, 5-FU infusion at a dose of 800 mg/M2 per day continuously for 5 days and RT at 200 cGy per day, days 1 through 5. The treatment cycle was repeated every 2 weeks for 7 cycles in patients treated curatively and for 2 to 6 cycles in patients treated palliatively due to prior radiation therapy or the presence of metastatic disease. Regional control was achieved in 98% of the patients. Regional control has persisted in 87% of the patients treated curatively with a minimum follow-up of 24 months. Distant failure occurred in 23% of this group. Actuarial survival of 2 years for the curative group is 66%. Concomitant combination of radiation with radiation potentiating chemotherapeutic agents shows promise of increase in local control.

Treatment of carcinoma of the hypopharynx.

In a review of 80 patients with hypopharyngeal squamous-cell carcinoma, 43 patients were found to have had lesions arising in the pyriform sinus, 34 had lesions arising on the postcollateral wall of the hypopharynx, and 3 had lesions in the postcricoid area. Therapeutic modalities included radical radiation therapy in 56 patients, radiation plus surgery in 13 patients, and planned combined therapy in 11 patients. The five-year determinate survival rate of all the patients was 20%. Patients with posterolateral wall tumors had a 23% rate of cure, but those with pyriform sinus tumors had only a 13% rate of cure. The five-year determinant survival rate was 12.5% for patients undergoing radical radiation therapy, 15.4% for those undergoing unplanned radiation and surgery (salvage therapy), and 55.6% for those with planned combined therapy. Over 40% of the patients had a recurrence of their disease; an additional 20% developed distant metastatic spread which usually occurred within the first year. The type of therapy did not alter the rate of recurrence but did affect the rate of distant metastatic spread, with planned combined therapy greatly improving control of the primary lesion. This study suggests that, even with advanced disease, the most effective therapy for hypopharyngeal carcinoma is planned combined radiation therapy and surgery.

Incidence and type of otopathology associated with congenital palatopharyngeal incompetence.

Based upon the known association of cleft palate and middle ear disease, a study was undertaken to determine the incidence and type of middle ear pathology associated with velar anomalies exclusive of cleft palate which may produce congenital palatal pharyngeal incompetence. The range of velar anomalies encountered was subdivided into congenital palatal incompetence Type 1 (clinically manifested by one or more of a triad of visible palatal anomalies including submucous deficiency of the hard palate, bifid uvula, and a diastasis of velar musculature) and congenital palatal incompetence Type 2 (no visible velar anomalies but radiographic anomalies of the velopharyngeal region such as short or thin velum and/or enlarged nasopharyngeal dimensions consequent to vertebral and skull base anomalies). Middle ear disease was assessed separately in CPI Types 1 and 2 in order to differentiate the effects upon middle ear function between overt and occult velar anomalies. Middle ear disease was more frequent in CPI Type 1 than in CPI Type 2. The predominant otopathologic finding was serous otitis media, paralleling the type associated with cleft palate. Tympanic membrane atrophy, tympanosclerosis and tympanic membrane perforation, often considered sequelae of chronic serous otitis media, were noted infrequently. This investigation supports the concept that middle ear disease frequently occurs with congenital palatal incompetence as it does with cleft palate.

Transnasal microsurgical correction of choanal atresia.

Experience with the transnasal microsurgical correction of bilateral congenital choanal atresia is presented. Four case reports are presented to illustrate the advantages of this surgical approach utilizing standard otosurgical instruments and supplemental fiberoptic nasopharyngeal visualization.

Safety and tolerability of the implantable recurrent laryngeal nerve stimulator.

The recurrent laryngeal nerve (RLN) stimulator has been implanted on a limited basis since 1988 for control of spasmodic dysphonia. A similar vagus nerve stimulator has been implanted in a larger series of patients to control epilepsy. The safety and tolerability of these two stimulators were evaluated. In 113 patients implanted with the vagus nerve stimulator, the complication rate was 0.9%. All patients were monitored for vital signs, electrocardiographic changes, and adverse effects. The absence of changes in vital signs and electrocardiograms during vagal stimulation establishes the safety of this treatment. Since placement of the electrode around the vagus nerve is an easier surgical technique than placement deep to the RLN, it seems reasonable to change the technique to implant the stimulator on the vagus in patients with spasmodic dysphonia.

Evaluation of a new laser-resistant fabric and copper foil-wrapped endotracheal tube.

The risk of an endotracheal tube's combustion during laser airway surgery necessitates the use of special anesthetic techniques and equipment to prevent this complication. This study was designed to evaluate the Laser-Trach(TM), a new laser-resistant rubber endotracheal tube for use during laser airway surgery. The Laser-Trach endotracheal tubes that were evaluated were size 6.0 mm internal diameter (ID) red rubber endotracheal tubes which had been commercially wrapped by Kendall-Sheridan (Mansfield, Mass.) with copper foil tape and overwrapped with fabric. The fabric layer was saturated with water prior to our tests, as recommended by the manufacturer. The Laser-Trach endotracheal tubes were compared with plain (bare) size 6.0 mm ID Rusch red rubber endotracheal tubes. The tubes under study were positioned horizontally on wet towels in air and had 5 L x min(-1) of oxygen flowing through them. They were subjected to continuous laser radiation at 40 W from either a CO2 or an Nd-YAG laser. The Nd-YAG laser was propagated via a 600-micron fiber bundle. Each laser was directed perpendicularly at the shaft of the endotracheal tube being studied, and its output was continued until a blowtorch fire occurred or 60 seconds had elapsed. Sixty seconds of CO2 laser fire did not ignite any of the eight Laser-Trach endotracheal tubes tested. However, blowtorch ignition of all eight bare rubber tubes tested occurred after 0.87 +/- 0.21 (mean +/- SD) seconds of CO2 laser fire. Nd-YAG laser contact with the Laser-Trach endotracheal tubes caused the perforation and blowtorch ignition of all eight tubes tested after 18.79 +/- 7.83 seconds. This was a significantly (P<.05) longer time than the 5.45 +/- 4.75 seconds required for the blowtorch ignition of all eight plain rubber endotracheal tubes tested with the Nd-YAG laser. Our results show that under the conditions of this study, the shafts of the Kendall-Sheridan Laser-Trach endotracheal tubes were resistant to the C02 laser. However, this endotracheal tube is not recommended for use with the Nd-YAG laser.

Severity of sleep apnea as a predictor of successful treatment by palatopharyngoplasty.

As awareness and understanding of obstructive sleep apnea has increased so has the number of treatments for this disorder. Options include surgical procedures: tracheostomy, palatopharyngoplasty (PPP), and mandibular advancement. Other treatments are medication, nasal CPAP, Tongue Retaining Device, and a position alarm. With these numerous choices available, it is important that reliable indicators be developed to guide treatment choice. And although PPP surgery is a one-time intervention with possibility of permanent correction, reports of percentages of successful treatment have varied widely from 85% to 0%. This has led us to investigate predictors of successful treatment. Twenty-two patients treated with PPP following their diagnosis by standard clinical polysomnography were restudied an average of 8 weeks later. When 11 successful cases were compared to 11 unsuccessful cases, successes were found to be initially more severely apneic (mean AI = 90.55 versus 49.45). Palatopharyngoplasty appears to be most appropriate for the sleep apnea patient whose apnea index is 70 or above and less effective for milder cases.

Obstructive sleep apnea: variations in surgical management.

Forty patients with obstructive sleep apnea (OSA) were either treated by submucous resection, alone or by palatopharyngoplasty (PPP). Before surgery, each patient underwent a thorough sleep evaluation for the diagnosis of OSA. Of the 23 patients treated by submucous resection alone, eight had more than a 50% reduction in their apnea index and were considered successfully treated. Of the remaining 15, ten received a supplemental tongue retaining device (TRD). Five of the ten were markedly improved. The overall success rate in this group was 57%. Of the 17 patients treated by submucous resection and PPP, ten were treated successfully. Six of the remaining seven patients were subsequently treated with a TRD, which was successful in four. The overall success rate in this group was 82%.

Bupivacaine for postoperative analgesia following endoscopic sinus surgery.

This prospective study was conducted to examine pain after endoscopic sinus surgery (ESS). The hypothesis was that a long-acting anesthetic agent would result in patients experiencing less pain in the 24-hour postoperative period and therefore needing fewer oral analgesics. We randomized 100 patients undergoing ESS to receive either lidocaine (1% or 2%) with epinephrine or bupivacaine (0.25% or 0.5%) with epinephrine as an anesthetic and for a sphenopalatine block. Postoperative pain was assessed with a standard numeric pain assessment scale at baseline and at 2, 6, and 24 hours after surgery. The use of analgesics during this period was also documented. We compared the results between patients receiving bupivacaine and those receiving lidocaine, as well as between patients who required nasal packing and those who did not. We discovered that in general, pain after ESS was less severe than expected. We further found that the type of anesthetic used did not significantly affect postoperative pain; pain score changes and use of analgesics were similar between the two anesthesia groups. Postoperative pain was also similar between the "packing" and "no packing" groups. Although patients receiving packing had consistently lower increases in pain (and in fact many patients in this group had decreases in pain from baseline), none of the differences between group means was statistically significant.

A review of revision functional endoscopic sinus surgery.

For some patients, traditional or functional endoscopic sinus surgery (FESS) fails to relieve persistent or recurrent sinus disease. This subset of patients may require revision surgery. The objective of this study was to define and evaluate which features of sinus disease and prior treatment were characteristic of patients requiring revision FESS. Within a series of 295 consecutive FESS procedures, 43 patients who had prior sinus surgery and required revision FESS were studied and followed for a mean 14.1-month period. The characteristics of 13 patients with persistent disease following revision FESS and the potential technical risks and complications encountered were also evaluated. This study concludes that revision FESS is a safe technique that was effective in 69.8% of the patients, and that certain factors may predict a poor surgical outcome.

The effect of blood on laser-resistant endotracheal tube combustion.

The protection afforded against CO2 laser-induced combustion by five different types of tracheal tubes or protective foil wraps was evaluated. They were compared before and after the application of human blood to their external surfaces. The tracheal tubes tested were polyvinylchloride (PVC) tubes wrapped with Venture copper (Cu) foil tape, 3M aluminum (Al) foil tape, and the Laser-Guard protective coating. The Xomed Laser Shield II and Mallinckrodt Laser-Flex tracheal tubes were also tested. A CO2 laser set to 38 W in the continuous mode was directed at the shaft of the tracheal tube under study, which had 5 L/min of oxygen flowing through it. The laser was actuated for 90 seconds or until combustion or melting occurred. The copper foil-wrapped and aluminum foil-wrapped PVC tracheal tubes were unaffected by 90 seconds of laser fire in five trials with each type of tape. However, the application of blood to the foil wrapped PVC tracheal tube shafts resulted in combustion in 3 of 5 copper foil-wrapped tubes and melting of the underlying tracheal tube shaft in 3 of 5 aluminum foil-wrapped PVC tracheal tubes. Blood did not affect the protection afforded by the Laser-Guard coating when it was applied to the shafts of PVC tracheal tubes. Similarly, the Xomed Laser Shield II tracheal tube's shaft offered good protection from the laser both before and after application of blood. Combustion occurred in 1 of 4 Mallinckrodt Laser Flex tracheal tubes studied prior to the application of blood. The application of blood resulted in almost immediate combustion in all 4 Mallinckrodt Laser Flex tracheal tubes tested. The presence of blood on the surface of metallic foil-wrapped or special tracheal tubes may make laser-induced combustion more likely during airway surgery. However, the Laser-Guard protective coating and the Xomed Laser-Shield II tracheal tube provide good protection even when covered with blood.

DentaScan: a new diagnostic method for evaluating mandibular and maxillary pathology.

Although computerized tomography (CT) is valuable for evaluating head and neck pathology, it can be suboptimal when evaluating the presence or extent of mandibular and maxillary involvement by tumor, infection, or other pathology. The presence of dental restoration artifact, CT gantry positioning problems, and the inability to obtain cross-sectional images will diminish the accuracy of standard CT images. A program, termed either DentaScan or multiplanar reformation (CT/MPR), eliminates these problems by processing axial CT scan information to obtain true cross-sectional images and panoramic views of the mandible and maxilla. In this study, DentaScan imagery was used in 26 patients whose mandibles or maxillas were affected by tumor, osteomyelitis, or other pathology. CT scanning with multiplanar reformation proved useful in the precise location, assessment, monitoring, and treatment of various pathologies of the mandible and maxilla. Selected case studies illustrate the therapeutic implications and advantages of this new imaging technique.

Nucleolar organizer regions in squamous cell carcinoma of the head and neck.

Nucleolar organizer regions are collections of nucleolar proteins associated with ribosomal genes that can be visualized in histologic sections using a silver colloid stain, thus the term silver-staining nucleolar organizer region (AgNOR). In some tissues, the number of AgNORs per nucleus correlates with cellular proliferation and, independently, with malignant change. AgNORs were studied in 66 paraffin-embedded head and neck squamous cell carcinomas and in 12 samples of normal tonsillar squamous epithelium. Carcinomas had a significantly higher mean AgNOR count than the benign epithelium (P less than .0001). Among carcinomas, mean AgNOR count increased with stage of the disease (P less than .001), but there was no significant correlation with histologic grade or DNA ploidy as determined by flow cytometry. These data suggest that AgNOR count should be evaluated as a possible aid in differentiating benign from malignant squamous epithelial proliferations in the head and neck, and also possibly as a prognostic marker in these carcinomas.