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A retrospective analysis was performed to investigate potential prognostic factors for complete remission to neoadjuvant chemotherapy and overall survival in patients with previously untreated stage III and stage IV head and neck cancer. Eighty consecutive patients were treated in one of two studies investigating three or four courses of neoadjuvant chemotherapy. Before local therapy and surgery and/or radiotherapy, 29% attained a complete remission. No strong significant and independent predictor of complete remission was identified. Only nodal stage (N) was found moderately associated with complete remission (p = 0.06). Node-negative patients had higher remission rates. Less important predictors were tumor stage (T) and site of disease; nasopharyngeal patients had superior remission rates (56%). With a median followup of 45 months and estimated 3-year survival rate of 38% (median 23.7 months), individual factors predictive of survival included pretherapy weight loss, performance status, alcohol use, pretherapy serum albumin level, site of disease, and N stage. In multivariate testing weight loss was identified as the strongest independent predictor of survival (p less than 0.0001) and surpassed other health status measures, such as performance status and serum albumin level. In addition, N stage (p = 0.019) and alcohol use (p = 0.017) were found to be predictive. A cross-classification by N stage and weight loss revealed risk groups with distinctly different prognoses, which may be useful for design and analysis in future trials.

A 62-year-old woman who was being treated for squamous cell carcinoma of the head and neck developed a chemotherapy-related hemolytic-uremic syndrome during the second cycle of neoadjuvant chemotherapy consisting of cisplatin, bleomycin, and methotrexate. Though the syndrome was suspected early, attempts at reversing the hematologic and renal abnormalities were unsuccessful. At postmortem examination, the characteristic microvascular lesions of the hemolytic-uremic syndrome were found in the kidneys.

Two regimens of neoadjuvant chemotherapy for previously untreated patients with locally advanced head and neck cancer were compared with the goal of identifying a regimen with a greater than 50% complete response (CR) rate. Patients with a performance status of 0 to 2 and normal end-organ function were randomized to receive either four cycles of neoadjuvant methotrexate, cisplatin, and continuous infusion 5-fluorouracil (5-FU) (MPF) (arm A), or four cycles of bleomycin, cisplatin, and methotrexate (PBM) alternating with cisplatin and 5-FU (PF) (arm B). Patients with a performance status of greater than 2 or a carbon monoxide diffusion capacity of less than 50% of the predicted value were assigned to the arm A regimen but were analyzed separately (arm C). Local therapy consisted of surgery (for patients with resectable disease) or radiation therapy followed by two cycles of adjuvant chemotherapy with the regimen that was administered initially. Of the 42 patients who were evaluated, 16 were randomized to arm A, 13 to arm B, and 13 to arm C. The clinical CR rate was 19% on arm A (95% confidence interval, 0% to 38%), 39% on arm B (95% confidence interval, 12% to 66%) (P = 0.41), and 54% on arm C (95% confidence interval, 27% to 81%). At a median follow-up time of 35 months, the 2-year actuarial survival rate was 61% on arm A, 69% on arm B (the P value was not significant), and 38% on arm C. The 2-year survival rate for all 42 patients who were treated was 57% and the median survival time was 31 months. Toxicities of neoadjuvant chemotherapy on all arms consisted of mild to moderate myelosuppression and renal toxicity. The incidence of moderate to severe mucositis was significantly higher on arm A than arm B (P = 0.02). Two cycles of adjuvant chemotherapy were administered to only 11 of 42 patients due to patient refusal or cumulative toxicity. In conclusion, both neoadjuvant chemotherapy regimens resulted in similar response and survival rates, but mucositis was more severe with arm A. However, since neither regimen was likely to cause a CR rate of greater than 50%, this study was closed to further patient accrual.

Blindness following facial trauma may occur with what appears to be a minor insult to the periorbital area. This report deals with our experience in treating five patients who had sudden blindness following frontal head trauma. Unselected optic nerve decompression was in general unrewarding in reversing blindness. However, the early administration of pharmacologic doses of corticosteroids does appear effective in reversing blindness in this select patient population and may indicate which patient is a good candidate for decompression. Examination of holographic experiments performed on dried skulls, in addition to clinical findings, appears to suggest that the cause of blindness associated with frontal head trauma may be related to stretching of the optic nerve and not necessarily to compression.

This study was designed to evaluate the safety, reliability, and patient acceptance of outpatient continuous intravenous infusion (CVI) chemotherapy. Twenty-two patients with locally advanced head and neck cancer received induction chemotherapy with methotrexate, cisplatin and a 5-day CVI of 5-fluorouracil (5-FU). Patients were randomized to receive the 5-FU portion of cycle 1 either by a standard inpatient CVI chemotherapy delivery device (standard pump) or by the Infusor (Baxter Healthcare Corporation, Deerfield, IL), a portable chemotherapy delivery system that provides a constant flow of drug over a period of 24 hours. For cycle 2, patients crossed over to the alternative drug delivery method. Patients receiving chemotherapy via the Infusor could choose to be either inpatients or outpatients. Daily plasma concentrations of 5-FU were determined during the first two cycles of chemotherapy. There was no significant difference in the mean steady state plasma 5-FU levels achieved with either drug delivery method (329.7 +/- 95.8 ng/ml for infusor cycles vs. 352.8 +/- 114.9 ng/ml for standard pump cycles). Clinical toxicities consisted primarily of mucositis for both methods of drug delivery. Eight patients declined to receive CVI chemotherapy as outpatients citing as reasons fear of malfunction of the device, inconvenience of the frequent clinic visits necessitated by daily monitoring of plasma 5-FU concentrations, and restrictions in daily home activities. Eleven patients underwent CVI chemotherapy via Infusor as outpatients. All reported outpatient CVI chemotherapy as convenient and effective and, when eligible, chose it again in subsequent cycles. A comparison of estimated costs revealed reductions in daily costs of +366.00 (+2,200.00 per cycle) for outpatient chemotherapy. Outpatient CVI chemotherapy is a reliable drug delivery method that was accepted by a majority of patients in this study. These factors may help to establish outpatient CVI chemotherapy as a viable alternative to hospitalization.

The effects of the addition of indomethacin to PHA or Con A stimulated lymphocytes from patients with untreated squamous cell carcinoma of the head and neck or from patients with the disease who have just finished irradiation therapy from the disease was quantitated and compared to those of the control group. Lymphocytes from eight of 26 patients with untreated carcinoma were significantly augmented by the addition of indomethacin. The remaining eighteen patients were equal to the controls. For all 17 patients who had just finished extensive field irradiation therapy, significant enhancement of PHA and Con A reactivity by indomethacin was found, which did not appear to be solely a function of low baseline mitogen reactivity. In additional studies, stimulated lymphocytes of irradiated patients were tested for their sensitivity to the inhibitory effect of PGE2. The mitogen treated lymphocytes from all patients that had just finished irradiation therapy were found to be significantly more sensitive to the inhibition by PGE2 as compared to the normal lymphocyte response. This effect was also found not to be related merely to a low PHA or Con A reactivity of the lymphocytes. In both patient groups there was a striking correlation between the percent augmentation of indomethacin and the percent inhibition of PGE2 in that when the percent augmentation values were low so were percent inhibition values and when the degree of augmentation by indomethacin was elevated so was the inhibition by PGE2. This data suggests that increase sensitivity of stimulated lymphocytes to PGE2 may be responsible, at least in part, for the depressed mitogen response and the significant augmentation of this immune response by indomethacin in about 1/3 of the untreated patients with advanced head and neck carcinoma and in those patients who have just finished irradiation therapy. The results of this study support the hypothesis that perhaps patients receiving irradiation therapy may benefit by the oral administration of indomethacin, an approach that needs further consideration.

The fluorescein test is widely used in clinical and experimental studies for prediction of the viability of skin flaps. A thorough search of the literature revealed that the accuracy of this test had never been studied. Therefore, this study was designed to evaluate the accuracy of the fluorescein test in predicting the viability of skin flaps. A total of 212 unipedicle porcine skin flaps were used in this study. Statistical analysis demonstrated that the surviving area of the flap was significant greater than the staining area of the flap. We suggest that caution be exercised when the fluorescein dye test is used to assess skin flap viability and that the test be used for an approximate indication and not for an accurate prediction of the surviving flap area.

The purpose of this article is to familiarize th surgeon with the latissimus dorsi flap and some particularly useful applications of it. This flap has proved extremely versatile, with many uses, among them immediate coverage for extensive head and neck wounds. It has been equally successful in repairing defects in both normal and irradiated tissue. The range of the arc of utilization has been exceptional, easily reaching the skull vertex from the chest wall. However, to be able to extend this flap so far requires careful dissection of the neurovascular pedicle and intimate anatomic knowledge of the posterior axilla region. This flap's muscle bulk is quite acceptable and the donor site may almost always be closed primarily. There appears to be less functional disability from sacrifice of this muscle than with pectoralis or trapezius myocutaneous flaps. Accordingly, it is ideal when much tissue is needed for single-stage coverage. Additional uses are available when flaps from other sites have failed.

As a result of prolonged hospitalizations and the frequent administration of sclerosing antibiotics and/or chemotherapeutic agents, vascular access frequently becomes difficult in patients with advanced head and neck carcinoma. Eighty-six totally implantable venous access devices were placed in 83 patients with advanced head and neck cancer to facilitate the administration of continuous intravenous infusion chemotherapy. Complications relating to surgical placement or usage of the device occurred in 29 of 86 ports (34%), leading to the removal of eight devices (9%). The implantation of two devices required revision. There were no serious sequelae from any of the complications. The port facilitated the administration of home chemotherapy in 11 patients. Because of our favorable experience, we now routinely recommend placement of these devices to all patients with advanced head and neck cancer at our institution.

Giant cervical lymph node metastasis originating from head and neck epidermoid carcinoma has traditionally indicated a poor prognosis. However, some patients with stage IV disease may live many years. In order to identify factors which might contribute to long-term survival, a retrospective analysis of 94 patients with head and neck squamous cell carcinoma and metastatic cervical lymph nodes greater than 4 cm was performed. At the time of study, 15 patients were alive; 62 of the remaining 79 patients had died due to related causes. Of the 15 survivors, mean survival time was 10.3 years, and the determinate five-year or greater survival rate was 20%. In contrast, mean survival of the 62 determinate nonsurvivors was 1.4 years. Recommended treatment for stage IV head and neck cancer patients with giant cervical lymph nodes consists of preoperative radiation therapy followed by wide-field en bloc resection.

A random pattern flap, such as the nape-of-the-neck flap, is a delayed cutaneous flap that relies on collateral circulation based on the skin pedicle. The myocutaneous trapezius flap, however, is a cervical flap that does not need to be delayed since it receives its blood supply from a musculocutaneous artery. The author has radiographic and clinical evidence that demonstrates that the upper one-half of the trapezius muscle is primarily, and abundantly, supplied by the transverse cervical artery. If this artery is kept intact during resection and reconstruction, a flap as large as 12 x 42 cm may be maintained. This flap has been used in various types of reconstruction on 23 patients, and it has been successful in terms of viability, versatility, safety, and cosmesis.

Complicated wounds of the head and neck involve a severe deficiency of tissue in a contaminated or irradiated area that is predisposed to infection and necrosis. Reconstruction of these wound areas frequently requires multiple operations and prolonged hospitalization. We have successfully reconstructed complicated head and neck wounds in thirteen patients by means of a single-stage microvascular tissue transfer of the greater omentum with or without an attached segment of the stomach wall. There were 11 complete successes, two partial failures, and no complete failures. We describe four cases to illustrate the basic fundamentals of this reconstructive technique.

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.

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.

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.

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.