William J. Richtsmeier

Hyperfractionated Irradiation with or without Concurrent Chemotherapy for Locally Advanced Head and Neck Cancer

BACKGROUND Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.

The versatile midface degloving approach

The exposure obtained using the degloving approach is superb and the absence of resultant facial scar or deformity provides a dramatic new addition to the otolaryngologists surgical repertoire. The advantages of the degloving technique in exposure of the midface, nasal cavities, paranasal sinuses, nasopharynx, skull base, and clivus have led to its increasing importance in the otolaryngology literature. Within 2 years of the techniques introduction in our department, it had been used 48 times for a wide variety of problems, including inverting papilloma, juvenile angiofibroma, chordoma and selected cases of fungal disease of the sinuses.

Endoscopic Staple‐Assisted Esophagodiverticulostomy for Zenker's Diverticulum

We have used a new technique, endoscopic staple‐assisted esophagodiverticulostomy (ESED), for the treatment of Zenkers diverticulum. This technique is a modification of the endoscopic approach first described by Mosher 1 in 1917 and popularized by Dohlman and Mattsson 2 in which the common wall between the esophagus and diverticulum was divided without mucosal closure. ESED differs in that an endosurgical stapler is used to create an esophagodiverticulostomy by dividing the common wall between the esophagus and diverticulum, with the mucosal and muscular edges sealed by the staples. We have performed this procedure in six patients, with no perioperative morbidity in any patient. All patients resumed oral intake on either the first or second postoperative day, with no evidence of fistula formation or mediastinitis. Hospital stay has averaged 2 days (range, 1 to 3 days). Patient follow‐up after ESED averages 6 months and is available for five of the six patients treated. There has been complete resolution of pretreatment symptoms in these five patients, with resumption of regular diet between postoperative day 3 and day 14 (average, day 9). Our results demonstrate that ESED is a safe and effective treatment for Zenkers diverticulum. This endoscopic approach offers a number of advantages over previously used treatments for Zenkers diverticulum, including reduced morbidity, rapid convalescence, short hospitalization, brief operative time, and predictable resolution of symptoms.

A Submucosal True Vocal Fold Infusion Needle

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

Estrogen and progesterone receptors in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) often requires transfusion and has major ill-effects. The recent literature reports successful high-dose estrogen treatment of epistaxis caused by HHT. To investigate this, biopsy specimens taken from areas clinically involved with telangiectasia in four patients were evaluated for estrogen- and progesterone-binding receptors. Specimens from two women (ages 34 and 38) were positive for both estrogen and progesterone receptors in ranges observed in breast carcinoma specimens. Specimens from two men (ages 34 and 78) were positive only for progesterone receptors at lower but clearly detectable levels of activity. Nasal mucosa specimens from control patients −2 male and 4 female – yielded no detectable levels of estrogen or progesterone receptors. Because of the side effects of high-dose estrogen (especially in males), we have initiated systemic progesterone therapy with both megestrol acetate and medroxyprogesterone acetate. Marked diminution in epistaxis incidence and severity was observed in three patients after initial systemic progesterone treatment. All treated patients have been maintained with good epistaxis control for over 1 year.

Utility of immediate on-site cytopathological procurement and evaluation in fine needle aspiration biopsy of head and neck masses

The utility of on‐site microscopic evaluation of fine needle aspirates (FNAs) of the head and neck was assessed by comparing the diagnostic yield in 336 specimens obtained with immediate on‐site cytopathological procurement and evaluation to that achieved in 548 cases performed without immediate on‐site evaluation. Three hundred six (91%) of 336 immediate evaluation specimens were adequate for cytopathologic diagnosis, compared to 391 (71%) of 548 specimens not evaluated immediately (P < .001, chi‐squared test). The higher satisfactory rate in immediate evaluation cases was related primarily to 1. immediate reaspiration of the masses until sufficient cytopathologic material was obtained for diagnosis; and 2. optimal specimen preparation.

Myotomy length determinants in endoscopic staple-assisted esophagodiverticulostomy for small Zenker's diverticula

A small Zenkers pouch is a major challenge for endoscopic staple-assisted esophagodiverticulostomy (ESED). This study tested the stapler dimensions so as to identify limitations they impose on ESED. Combining ESED with additional endoscopic suturing could extend the incision and consequently the myotomy. Zenkers diverticulum residual pouch measurements were performed with a previously reported latex glove model and in patients undergoing surgery. Two stapler designs were compared by measuring the residual pouch length for both the stock and modified staplers. One other stapler model cannot be modified without damaging the mechanism. The Endostitch was used to place an additional suture at the apex of the staple line, allowing cutting between the staples while leaving a closed distal incision. All three staplers suitable for ESED leave a residual pouch of 1.5 cm when unmodified. The modified anvil staplers gave a smaller residual pouch by 4 to 5 mm. An additional septal reduction can be accomplished by suturing the area distal to the staple line and incising the party wall beyond the stapler cut. The absolute amount of residual pouch with an additional myotomy is 3 mm. The combined staple-suture technique has proven relatively safe thus far. To provide a maximally efficient myotomy in a patient with a short pouch, the surgeon needs to be aware of the stapler differences. Modifications of the staplers may decrease the depth of the residual pouch, but may carry an added liability. A minimum residual pouch can be achieved with a combination of stapler and suture techniques, but is more technically demanding than the original ESED description.

Three-dimensional models for head and neck tumor treatment planning

The authors have evaluated two types of practical maxillofacial model systems useful to the head and neck surgeon: 1. plastic mandibular model generated by three‐dimensional computerized tomography (CT) reconstruction, and 2. dental impression model of the maxilla. The first model is expensive and technology intensive; the second is simple but limited. Both three‐dimensional models offer several advantages: 1. they provide segmental mandibular relationships that are not known because of oncologic restrictions or previous surgery; 2. they allow preoperative reconstructive planning including prosthesis fabrication and visualization of tumor extent not obvious by two dimensional imaging; and 3. they provide a permanent record for future needs or reconstructions. The disadvantages include cost, time, and possible inaccuracies secondary to image artifacts. We find both models to be of significant practical value in selected head and neck tumor patients.

Identification of sialyl Lewis‐x in squamous cell carcinoma of the head and neck

Sialyl Lewis‐x (sLx) is a cellular adhesion molecule (CAM) that has been implicated in the inflammatory reaction and cancer metastasis. The sLx is the carbohydrate ligand of endothelial‐selectin (E‐selectin), an inducible vascular endothelial CAM. The role of sLx has been investigated in several cancers, and its presence has been correlated with advanced disease stage, decreased disease‐free survival, and greater metastatic potential. A recent study has found that cultured head and neck (HN) squamous cell carcinoma (SCC) cell lines express sLx and that binding of these cells to cytokine activated endothelium correlates with the endothelial expression of E‐selectin. The purpose of this study was to identify sLx in the tumors of patients with HNSCC and to see if the presence of sLx correlated with disease status.

Selective, histamine-mediated immunosuppression in laryngeal cancer.

Immunosuppression observed even in the earliest laryngeal cancers can be, in part, reversed with H2 histamine antagonists. In an effort to explain this, we tested whether histamine could evoke changes in endogenous antitumor lympholdne production using tonsil lymphocytes as test cells. We have observed that lymphocytes, treated in vitro with histamine, display a significant suppression of lymphokine production and mixed lymphocyte proliferation response following galactose oxidase treatment. Interferon gamma production was reduced to less than 2% of control value in the presence of histamine. In contrast, the lymphokine-activated killer cell activity induced by purified, natural interleukin-2 was not affected by similar concentrations of histamine. Histamine appears to exert its inhibitory effect by stimulating the production of a substance released by suppressor T cells. The suppressive effects observed could be reversed by concomitant or sequential treatment with cimetidine or ranitidine and not by H1 histamine antagonists, indicating that it occurs through an H2 histamine receptor. These experiments suggest that histamine may have a profound suppressive effect on the lymphocyte population studied.