Search

For initial reconstruction, Dr. Burget suggests that he would have advanced the cheek flap medially toward the nasal septum and, subsequently, reconstructed the missing right half of the nose with a forehead flap and cartilage grafts. Dr. Panje suggested early prosthetic rehabilitation, while Dr. Krause's concepts were similar to Dr. Burget's, with forehead flap nasal reconstruction, after cheek reconstruction to the nasofacial and nasolabial lines with a medially advanced cheek flap. Dr. Panje recommended an immediate maxillary denture prosthesis, as did Dr. Krause (who supplemented this with foam rubber). Dr. Burget placed the prosthesis 3 weeks after tumor ablation. For skin grafts, Drs. Panje and Burget suggested split thickness grafts to all new surfaces to decrease wound contracture, while Dr. Krause used dermis grafts for the same purpose. Other reconstructive methods mentioned were the (1) cervical tubed flap, (2) free scapular flap, (3) Washio flap, (4) tissue expansion, and (5) nasolabial flap. Suggestions for isolated defects included: Lower eyelid--increase internal support by building up the prosthesis; release lower lid from deltopectoral flap and V-Y advancement; support graft or irradiated cartilage (1-2 mm sheet) under orbicularis oculi. Nasal ala--bring present ala down and insert cartilage graft; turn internal skin down and fill the resulting defect with a composite graft. Upper lip--multiple Z-plasty. Retrodisplacement of cheek due to maxillectomy--release buccal scar; skin graft the raw internal surface and build up prosthesis.

We added high-dose oral leucovorin to the combination of cisplatin and fluorouracil (5-FU) to assess the efficacy of this regimen in the treatment of patients with head and neck cancer. Cisplatin, 100 mg/m2, was followed by a 5-FU continuous infusion at 600 mg/m2/d for five days. Leucovorin, 50 mg/m2, was administered at the start of cisplatin and every six hours throughout the duration of the 5-FU infusion. The dose of 5-FU was escalated to 800 mg/m2 and 1,000 mg/m2 according to observed toxicity. In a second phase of the study, the dose of leucovorin was escalated to 50 mg/m2 every four hours. A total of 25 patients were registered: 23 had recurrent disease after extensive prior treatment; and two had newly diagnosed metastatic disease. The maximally tolerated dose of 5-FU was 800 mg/m2/d with leucovorin administered every six hours. Toxicities at that level included mild to moderate myelosuppression and dose-limiting mucositis in the previously irradiated field. Identical toxicities were observed when administering 800 mg/m2/d of 5-FU with leucovorin every four hours. Eighteen patients were evaluated for response: one had a pathologic complete response; nine had a partial response (including four who received prior cisplatin and 5-FU as induction chemotherapy); and eight patients failed to respond. The mean peak and trough plasma leucovorin concentrations were 2.61 (+/- 1.07) mumol/L and 2.46 (+/- 0.95) mumol/L with administration of the drug every six hours, and 2.75 (+/- 2.15) mumol/L and 2.52 (+/- 1.48) mumol/L with administration every four hours. We conclude that the combination of cisplatin, 5-FU, and leucovorin has activity in the treatment of recurrent head and neck cancer. The maximally tolerated dose of 5-FU in this study was 800 mg/m2/d, with mucositis in previously irradiated sites being dose-limiting. Plasma leucovorin concentrations exceeding 1 mumol/L are achieved following oral administration of this drug.

The in vivo administration of a prostaglandin-synthetase inhibitor inhibited or reduced tumor growth in cancer patients and experimental animals. Indomethacin, a prostaglandin-synthetase inhibitor and nonsteroidal anti-inflammatory agent commonly used in the management of arthritic patients, acted as an immune adjuvant by decreasing the production of prostaglandins. Seven cases demonstrated that indomethacin taken in the usually recommended dosages causes regression and stabilization of head and neck cancer. The following factors were also considered in this study: prostaglandin production, a survey of other reports of solid neoplasm response to prostaglandin-synthetase inhibitor administration, drug toxicity, irradiation therapy and metastases, the need for tumor biopsy, and the role that reduction in inflammation plays in tumor shrinkage.

Between 1960 and 1983, 63 of 3,489 patients treated for squamous cell carcinoma of the head and neck at the University of Iowa Hospitals and Clinics, Iowa City, were under the age of 40 years. Malignancies in these patients occurred in the oral cavity (41%), pharynx (28%), larynx (25%), and other sites (6%). One third of the patients were females and half the patients were smokers. Approximately 50% of the patients presented with a cervical mass. Management consisted of surgery, radiation, or a combination of the two. Actuarial five-year survival for the entire group was 67%. The best prognosis was for patients with cancer of the larynx, while the poorest was for those with cancer of the pharynx.

Both cisplatin and leucovorin may increase the activity of 5-fluorouracil (5-FU) by increasing the intracellular concentration of reduced folates. Therefore, a Phase I study was conducted in patients with recurrent or metastatic head and neck cancer in which high doses of oral leucovorin were added to the combination of cisplatin and 5-FU. Patients received intravenous cisplatin 100 mg/m2 on day 1, followed by a continuous intravenous infusion of 5-FU at 600 mg/m2/day for 5 days. Leucovorin 50 mg/m2 orally was administered from the start of the cisplatin infusion and then every 6 hours throughout the 5-FU infusion. The dose of 5-FU was increased to 800 mg/m2/day and 1 g/m2/day according to observed toxicity. In a second phase of the study, the dose of leucovorin was increased to 50 mg/m2 orally every 4 hours. Twenty-five patients were registered: 23 had recurrent head and neck cancer after extensive treatment; two had newly diagnosed metastatic disease. The maximum tolerated dose of 5-FU was 800 mg/m2/day with leucovorin administered every 6 hours. Toxicities at that level included mild-to-moderate myelosuppression. Mucositis in the previously irradiated field prevented the further increase of the 5-FU dose to 1 g/m2/day. Identical toxicities were observed when administering 5-FU at 800 mg/m2/day with 50 mg/m2 of leucovorin every 4 hours. Eighteen patients were evaluated for response: one had a pathologic complete response; nine had a partial response (including four who had previously received cisplatin and 5-FU as induction chemotherapy). Eight patients did not respond. The median survival for all 25 patients was 6.5 months. It was concluded that the combination of cisplatin, 5-FU, and leucovorin is active in the treatment of recurrent head and neck cancer. The maximum tolerated dose of 5-FU in previously treated patients is 800 mg/m2/day, with mucositis being the dose-limiting toxicity. Further investigation of this regimen as neoadjuvant chemotherapy in previously untreated patients with locally advanced head and neck cancer is in progress.

Osteoradionecrosis can involve the mandible following radical irradiation for treatment of oral cavity cancer. The radionecrosis of the mandible is often associated with severe intractable pain, local or extensive deformity, including pathologic fracture, orocutaneous fistula formation, and frequent loss of function. Treatment has ranged from analgesia and antibiotics to hyperbaric oxygen treatments to local or extensive sequestrectomies with partial or total mandibulectomy and restoration of tissue losses with unirradiated tissue. To our knowledge, this is the first report of the successful use of a free greater omental flap for immediate treatment of mandibular osteoradionecrosis and concomitant reconstruction. We found the omentum to be an excellent vascular bed that rapidly resolved the osteoradionecrosis and pain, promoted healing, and restored mandibular function with minimal discomfort to the patient.

In this report 21 cases of primary malignant melanoma arising from the mucosa of the upper aerodigestive tract are reviewed. The patients ranged in age from 30 to 86; mean age was 67 years. There were 10 men and 11 women. All but one patient were white. Sites of involvement were: nose and paranasal sinuses, oral cavity and labial mucosa, parotid duct, and larynx. Surgery was the primary method of treatment. The 2-year survival rate was 44% (7/16) and the 5-year survival rate was 13% (2/15). Regional metastases were seen in 19% (4/21) while distant metastases was seen in 55% (11/21). The local recurrence rate was 69% (11/16). Distant metastases were usually associated with uncontrolled disease at the primary site. This fact as well as the low incidence of regional metastases lead us to conclude that better local control rather than regional lymphatic control is necessary if decreased distant metastases and increased survival are to be achieved.

This study is, to our knowledge, the first attempt to evaluate cellular immune mechanisms in regional lymph nodes of patients with head and neck cancer. Twenty lymph nodes from eight patients with stage III-IV squamous cell carcinoma were evaluated using an in vitro culture system. The T-cell mitogenic (concanavalin A) response of patients' peripheral blood mononuclear cells was modulated by the addition of cells from regional lymph nodes removed at neck dissection. Modulatory activity showing augmentation was significantly correlated with the size of the primary tumor and histopathologic grade of the tumor. Modulatory activity did not correlate with the histologic pattern of lymph node reactivity. Although these relationships suggest that regional immunity may be important in tumor-host interactions, further study is necessary to establish their biologic and prognostic importance.

The purpose of this study was to develop and describe in detail a reproducible porcine model for musculocutaneous flap study. The model was required to demonstrate the following: 1. consistent, easily identifiable anatomical landmarks for muscles and muscular vascular pedicles; 2. flap survival, consistent with the musculocutaneous perforator arrangement of blood supply; 3. ease of islanded- or free-flap formation; 4. arrangement of flaps on each animal, allowing paired studies of control and experimental flaps; and 5. a maximum number of flaps per animal, without undue morbidity or mortality. Pilot dissections were made of the pectoralis, trapezius, latissimus dorsi, gracilis, biceps femoris, and tensor fasciae latae muscles and their major vascular pedicles. After establishing the anatomical landmarks, we formed musculocutaneous flaps at each site to verify the above five requirements. A total of 72 muscle/vessel pedicle dissections were performed, incorporating formation of 61 island musculocutaneous flaps. The skin component overlying an islanded muscle block survived in 60 instances, confirming the reliability of the flap model. We concluded that five pairs of musculocutaneous flaps could be fashioned on one pig, using the bilateral control/experimental paradigm if desired. The pectoralis, latissimus dorsi, trapezius, gracilis, and biceps femoris muscles were used. The ventral muscle group (pectoralis, gracilis) was raised in one operating session, and the lateral muscles (trapezius, latissimus dorsi, biceps femoris) were raised in one further session per side. Three new porcine flaps are described--the pectoralis, biceps femoris, and trapezius. Morbidity was confined to mild splinting of the limbs for one day. This is also the first example of the use of ten musculocutaneous island flaps on one pig, and represents an opportunity for performing physiological, pathological, or pharmacological experiments on the musculocutaneous flap.

A simple surgical technique prevents or corrects tracheostoma stenosis. Forty-eight (96%) of patients undergoing laryngectomy in whom this technique was used have maintained adequate stomal size for cleaning, ventilation, and tracheoesophageal fistula speech restoration.

There is general concern among otolaryngologists that irradiation of a stainless steel prosthesis used in mandibular reconstruction may cause irradiation overdosage to adjacent tissues. A tissue-equivalent plastic/steel model, simulating the characteristics of a stainless steel, reconstructed mandible, was irradiated and measurements were made with a parallel plate ionization chamber. The results of our measurements show that irradiation of an implanted steel plate results in an overdosage (120%) "in front" and an underdosage (80%) "behind" the steel plate. The regions of overdosage and underdosage are 2 to 3 mm thick. The overall dose modification is greatly reduced when two opposing fields are used. We conclude that irradiation of a stainless steel, reconstructed mandible with a 6-mV photon beam through opposing fields does not significantly alter the amount of radiation delivered to surrounding tissues.

We attempted to provide free flaps with nutrient circulation by retrograde venous circulation through microsurgically created arteriovenous (AV) fistulas. We used the rabbit auricle as the animal model because of its accessible central and marginal veins. We created four experimental groups to (1) determine flap survival without blood supply, (2) establish efficacy of microvascular anastomosis, (3) test an end-to-end AV fistula, and (4) test an end-to-side fistula that was converted after one week to an end-to-end version. The nutrient blood supply in two groups existed only as retrograde venous perfusion. We found that retrograde venous perfusion alone was sufficient for flap survival, which equaled or exceeded that achieved with conventional microvascular flap reimplantation. This experiment suggests cutaneous free flaps can be created any place on the body wherein an AV fistula can be developed.

Patients who undergo oral or oropharyngeal surgery usually require a tracheostomy for postoperative airway maintenance. However, the development in recent years of soft endotracheal tubes now provides the alternative of short-term endotracheal intubation, with minimal sequelae. Our favorable experience with the use of short-term intubation in children with epiglottitis prompted us to apply the technique to adults. Over a 2-year period at the University of Chicago Medical Center, we successfully used postoperative endotracheal intubation for 19 adult and pediatric patients who underwent major intraoral procedures, thus avoiding the possible complications, discomfort, and anxiety associated with tracheostomy. The patients were given intravenous steroids and antibiotics concomitantly, so that tissue edema and inflammation were minimized. No complications related to intubation and no postextubation airway compromise were noted in any of the patients.

The musculocutaneous flap has limits on survival of its skin segment. Random skin extensions beyond muscle margins have, by clinical experience, been shown to survive. It has not been proved, however, what quantity of random skin will survive or whether its viable dimensions can be augmented by surgical delay. Twenty-five porcine musculocutaneous island flaps were created with a random skin extension running beyond the likely limit of survival. Twenty-five paired contralateral flaps subjected to a surgical delay one week earlier were raised simultaneously. The surviving dimensions of random skin on both control and experimental flaps were measured 14 days after delay. The control flaps sustained random skin segments one to 48 times their area of muscle while the delay doubled this, engendering more predictable survival. A new, successful experimental technique of increasing skin survival in musculocutaneous flaps is documented.

A review of 150 cases of mid-face skin cancers treated by the fresh tissue technique of microscopic controlled excision has revealed local epithelial cancer spread to be markedly influenced by embryological fusion planes. Knowledge of facial embryology which is reviewed in this article should allow the surgeon to better predict and treat mid-facial skin cancer.

Augmentation of the phytohemagglutinin (PHA)-induced lymphoproliferation of peripheral blood mononuclear cells by indomethacin, a drug which blocks prostaglandin (PG) synthesis, was assessed in 37 patients with squamous cell carcinoma of the head and neck. Indomethacin enhanced the uptake of 3H-thymidine in stimulated cultures both from patients and normal individuals. However, because lymphoid cells from cancer patients were less reactive than those from normal controls, the proportionate increase in PHA-stimulated 3H-thymidine incorporation caused by indomethacin was greater in this population than in the normal population. The degree of enhancement induced by indomethacin did not correlate with the percent of esterase-positive mononuclear cells in the preparations. The amounts of PGE synthesized at 48 h by patients' or normal cells were similar. Cell populations that exhibited elevated levels of augmentation in the presence of indomethacin were approximately 3 times as sensitive to inhibition by 3 nM PGE2. The degree of augmentation detected in the presence of Ro-20-5720, which also prevents PG synthesis, was related to that produced by indomethacin. These results suggested that: the enhancing effect of indomethacin on lymphoproliferation in vitro was related to its inhibition of PG synthesis; and the sensitivity of lymphoid cells to inhibition by PGE2 was slightly, but significantly, increased in individuals with elevated augmentation values.

The murine subrenal capsule assay was used to determine chemotherapeutic sensitivities of metastatic, primary, or recurrent head and neck cancers. Tumor fragments (1 cu mm) were implanted under the renal capsule of 2- to 4-month-old normal female C57 BL/6 X DBA/2 F1 hybrid mice. Xenografts included 20 squamous cell carcinomas (SCCs), one mucoepidermoid carcinoma, one adenoid cystic carcinoma, and two melanomas. Groups of tumor-bearing mice were treated with chemotherapy daily for five days. Sensitivities of the tumor were assessed on day 6 by comparison of final implant size with initial implant size. Significant oncolytic activity was detected against 16 of 24 tumors (14 of 20 SCCs and both melanomas). Correlations between the in vivo assay and clinical studies are needed to determine its predictive value.

Human costal cartilage is an excellent implant material for orbital and periorbital reconstruction because of its light weight, strength, homogeneous consistency and the ease with which it can be carved. Its use has been limited by the necessity of a separate surgical procedure to obtain the material. Preserved irradiated homologous cartilage has been shown to have almost all the autogenous cartilage and is concenient to use. Preserved irradiated homologous cartilage transplants do not elicit rejection reactions, resist infection and rarely undergo absorption.

To assess the effectiveness of delayed skin grafting for the reconstruction of facial defects following Mohs excision of cutaneous malignant neoplasms, an analysis was done on 40 patients. All grafts in this series survived. Satisfactory results were obtained in 95% of the patients. Complications were minor and uncommon. Results of this study demonstrate indications for the use of delayed skin grafting to include recurrent or aggressive primary lesions and defects that are large, deep, and favorably located. Advantages of delayed skin grafting are as follows: improved recipient bed vascularity providing high survival of a thicker graft; provision of additional tissue bulk; reduced length of time for healing; less contracture than with granulation healing; and elimination of additional scarring adjacent to the defect. In properly selected patients, this technique offers an additional method of reconstruction of facial defects.

A carbon dioxide laser was used on 71 patients for the removal of oral cavity or oropharyngeal cancers, premalignant lesions, benign tumors, or elongated soft palates. Evaluation of patient morbidity, speech, and swallowing, as well as survival data, suggests that the use of this modality for treatment of these conditions is highly successful, with excellent preservation of oral and pharyngeal function and minimal patient morbidity. Deep excisions of tumors that could lead to restricted motion of the tongue and/or jaw tended to have an adverse effect on both speech and swallowing. Immediate reconstruction should be considered, especially for defects created by excision of large tumors in the anterior oral cavity or in the lateral oropharyngeal wall cancers. Multimodality cancer therapy should be considered for large oral cavity and oropharyngeal cancers that have been treated by carbon dioxide laser excision.

We tested the combination of hydroxyurea (HU), 5-fluorouracil (5-FU), and concomitant radiotherapy (XRT) in a group of patients with advanced or recurrent head and neck cancer. Both drugs are effective single agents, have shown synergistic activity in vitro, and can act as radiation sensitizers. A 5-day course of radiotherapy, with simultaneous HU and continuous infusion 5-FU, was followed by a 9-day rest period; cycles were repeated until completion of XRT. Sixteen patients have completed their therapy. Eleven patients had recurrent disease after previous therapy with surgery (11 patients), radiotherapy (9 patients), and combination chemotherapy (4 patients). Five patients had not received previous local therapy. These patients had persistent disease after induction chemotherapy and/or were inoperable because of poor general medical condition. Of 15 patients evaluable for response, 9 had complete response, including 5 patients who had earlier local therapy; 5 had partial response; and 1 failed to respond. Toxicities included mild myelosuppression and mucositis. No unusual complication related to previous radiotherapy was observed. This regimen has shown impressive activity in a cohort of patients who are not usually responsive to other types of currently available therapy. We are continuing our investigation to further define efficacy, toxicity, and maximally tolerated doses of this regimen.

The use of the trapezius osteomusculocutaneous island flap for mandibular reconstruction was first described in the American literature by Panje and Cutting in 1980. Since that initial description, we have utilized this composite flap to reconstruct the lower jaw in 24 patients. Approximately 85% of the cases were done for anterior arch defects and/or osteoradionecrosis. With an overall success rate of 87%, this surgical technique offers an especially useful method for immediate reconstruction of the lower jaw.

Anterior mandibulectomy can precipitate the development of sleep apnea. All head and neck tumor patients having had extensive composite anterior oral cavity resections should be evaluated for sleep apnea before decannulation of their tracheostomy tube. Subsequent flap and/or rigid reconstruction of the lower jaw appears to prevent the development of sleep apnea. Fascial sling suspension of the lower lip does not appear to prevent sleep apnea.

Thirty-eight previously untreated patients with locally advanced head and neck cancer received three cycles of induction chemotherapy with methotrexate (120 mg/m2) followed by cisplatin (100 mg/m2) and a 5-day continuous infusion of 5-fluorouracil (1,000 mg/m2 per day). The response rate in 34 evaluable patients was 94%, with a complete response rate of 26%. Thirty-one patients underwent local therapy following induction chemotherapy, and 25 (81%) were rendered free of disease: 14 of 15 treated with surgery and radiotherapy and 11 of 16 treated with radiotherapy alone. At a median follow-up of 11 months, 8 patients have relapsed while the remaining 17 patients continue free of disease. The dose-limiting toxicity of chemotherapy was mucositis resulting in reduction of the 5-fluorouracil dose in 28 patients. This regimen is highly effective in inducing responses in patients with locally advanced head and neck cancer; 81% of the patients who complete local therapy are rendered free of disease with this multimodal approach. Due to short follow-up, the relapse rate, overall survival, and disease-free survival cannot yet be determined.

Large defects in the upper two thirds of the face, skull, and skull base pose challenging reconstructive problems. There are a number of applicable reconstructive techniques, all with various advantages and disadvantages, available to otolaryngologists-head and neck surgeons. One method, originally described in the late 1800s, was evaluated by us. Applications of the technique included reconstruction of large defects of the forehead, dura, and anterior skull base, closure of orbital defects, and soft-tissue augmentation of the face. Advantages of this reconstructive technique are the flap's proximity to the defects and its simplicity of execution.

In this report, 11 cases of angiosarcoma of the head and neck are reviewed. The patients ranged in age from newborn to 78 years; mean age was 64 years. There were eight men and three women. Sites of involvement included the scalp and forehead, cheek, nose and ethmoid sinuses, neck, and mandible. Surgery was the primary method of treatment. The 2-year survival rate was 50% (5/10) and the 5-year survival rate was 22% (2/9). Regional metastases were seen in 18% (2/11). We found that the tumors were poorly circumscribed and spread horizontally within the dermis for considerable distances, especially in the scalp. Total surgical excision using frozen section control before reconstruction may offer the best chance for control of disease.

The present study demonstrates that a free island flap with microvascular anastomosis may be used for the closure of a large defect in the oral cavity of the pig. In control cases, when a similar flap was transferred without microvascular anastomosis, a total and rapid slough occurred. Technical details are important in this kind of surgery. The island flap should be sized appropriately, cautiously defatted, and sutured into the defect before doing the microvascular anastomosis. Tension, torsion, or kinking of the vessels to be anastomosed must be meticulously avoided. In suturing these small vessels, microvascular techniques must be strictly adhered to. No anticoagulation is needed. The free island flap does not need to be perfused. Close observation of the flap's capillary refill, tissue turgor, and color is essential in the early postoperative period. More recently, Doppler technique has enabled us to monitor blood flow in the flap more accurately. If initial signs of venous congestion or arterial insufficiency are noted, examination of the anastomotic site can and should be done. Revision, if indicated, may result in rescue of the flap (as it was described in pig No. 8). The results of this experimental study allowed us recently to use this method successfully in two patients. Both had oral cavity carcinomas. In the first, the flap measured 5x7x2 cm and in the second 9x10x1.5 cm. They are now nine weeks and five weeks respectively, without any signs of failure. The details will be given when we have a series of patients adequate for a definitive report.

Butyl-2-cyanoacrylate (Histoacryl Blue) tissue adhesive successfully sealed three cases of CSF leaks encountered during orbital surgery. The application of tissue adhesive was followed by prompt cessation of leak. We have found this tissue adhesive to be a valuable technical adjunct in the intraoperative management of this difficult problem and have not seen any general or local toxic reaction to the material.

The established follicle envelope of Necturus maculosus consists of a layer of follicle cells (granulosa) surrounding the developing oocyte, a layer of theca comprised of connective tissue cells, fibers, and matrix, and a layer of serosal cells. The changes in shape and fine structure of these layers during differentiation accompanying oogenesis are described. The cells and capillaries of the follicle envelope are engaged in an extensive pinocytotic activity, the details of which are described. We used cytochemical techniques to analyze the activity of the follicle envelope with respect to lipid accumulation and alkaline phosphatase activity. Radioautographic results indicate that cells of the follicle envelope are capable of incorporating tritium-labeled uridine and amino acids at certain times during oocyte growth. A comparative analysis was made of the soluble proteins in follicle envelopes isolated from immature oocytes and of those in follicle envelopes isolated from nearly mature oocytes and in postovulatory follicles. After the oocyte is ovulated, the cells of the follicle envelope are converted into a postovulatory follicle. The cells of the postovulatory follicle undergo further differentiation resulting in their becoming actively engaged in the formation of a secretion, the details of which are described at the electron microscope level. Analysis of the postovulatory follicle by thin-layer chromatography and cytochemistry demonstrated the presence of a wide variety of lipid substances and the possible presence of steroid. That the postovulatory follicle may be engaged in steroid biosynthesis is also suggested by studies involving the demonstration of 3 beta-hydroxysteroid dehydrogenase activity with cytochemical techniques applied to frozen sections and to soluble proteins separated by gel electrophoresis.