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The repair of septal perforations represents a challenging problem, with numerous techniques existing to address the defect. The use of sinonasal endoscopy represents a novel approach to solving this problem. By using the endoscope, excellent visualization and exposure can be achieved without excessive dissection. In addition, the use of the camera and monitor allows for excellent teaching capabilities.

Objective: Abnormalities in genes regulating cell proliferation and death may affect disease outcome in squamous cell carcinoma (SCC) of the head and neck., Methods: Proliferative activity (Histone H3 in-situ-hybridization (HISH) labeling index (LI)) and the genes and/or gene products of Cyclin D-1, c-erbB-2, Bcl-2, p21, and p53, were investigated in 35 patients with SCC of the oral cavity and oropharynx, previously studied for p27 expression., Results: Overexpression or very low expression of Cyclin D-1 was associated with unfavorable disease outcome and shorter time-to-recurrence. High c-erbB-2 expression was significantly associated with shorter overall survival and was synergistic with low p27 expression. Bcl-2, HISH LI, p21 expression, and p53 mutation and protein analysis were not significantly predictive, but there were trends suggesting shorter disease-free/overall survival for patients with undetectable Bcl-2, high HISH, and mutant p53., Conclusions: Several cell proliferation and death regulators appeared to predict disease outcome. Limited evidence of cooperativeness among regulators was also seen.

Successful skin grafting of intraoral defects can be challenging. The tie-over bolster method is the most popular technique in use today. We describe an alternate method of securing intraoral skin grafts--the "parachute" bolster technique--and we present a case report.

The purpose of this article is to introduce the concept of endoscopic and electroporation therapy for the treatment of sinonasal carcinomas. Electroporation therapy is a technique that combines intralesional injection of bleomycin combined with application of high-voltage square wave electrical impulse into the tumor. A transient increase in cell membrane permeability allows intracellular entry of bleomycin, with subsequent cytotoxicity. Two cases of sinonasal cancer were treated with this technique. One patient had complete response and is free of disease at 20 months. The other had partial response with control of the disease up to a year. Endoscopic electroporation therapy is potentially a minimally invasive method for the treatment of sinonasal malignancies in an experimental setting where other treatment options do not exist. Phase II/III national clinical trials have been initiated to study the efficacy of electroporation therapy.

The purpose of this paper is to introduce the concept of electroporation therapy and present our results from using this new technique combined with intralesional bleomycin in head and neck cancer patients. Electroporation therapy is a technique wherein high-voltage electric impulses delivered into a neoplasm transiently increase cell membrane permeability to large molecules, including cytotoxic agents. In this phase I/II study, extremely low-dose bleomycin sulfate was electroporated into head and neck malignant neoplasms in 10 patients. Tumor responses included 2 nonresponders, 3 partial responders, and 5 complete responders, with a mean follow-up of 40 weeks. We conclude that this technique offers promising possibilities in the local treatment of head and neck cancer.

Expression of interrelated gene products regulating cell proliferation and apoptosis may be disordered in squamous cell carcinoma (SCC) of the larynx compared with normal squamous mucosa. Certain of these abnormalities, alone or in combination, may be of prognostic significance in low-stage carcinomas of the larynx. A retrospective study of archival material was made. Expression of the Bcl-2 family of apoptosis-related genes (bcl-2, bcl-X, mcl-1, and bax) and the proliferation- and apoptosis-related genes p53 and cyclin D-1 were determined in 40 low-T-stage laryngeal carcinomas and in uvular epithelium from patients without SCC. Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1 showed more intense and widespread staining than Bcl-2 itself in both normal squamous mucosa and SCC. The well-ordered expression patterns of Bcl-2-related proteins found in normal epithelium were lost in SCC, and patterns of expression varied widely among individual tumors. Also, mean expression levels for Bax and cyclin D-1 were significantly lower than in normal epithelium (P = .036 and P = .009, respectively), whereas expression of p53 was higher in tumors (P = .034). Expression of Bcl-X and Mcl-1 was greater in poorly differentiated than in well-differentiated tumors (P = .014 and P = .031, respectively). No associations were seen between marker expression patterns and clinical outcome in this group of patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed antiapoptotic proteins of the Bcl-2 family in both normal squamous mucosa and SCC of the larynx. Multiple genes regulating proliferation and apoptosis are expressed abnormally in laryngeal SCC compared with normal epithelium. In particular, loss or measurable decrease in expression of the proapoptotic protein Bax in tumors may contribute to the deranged growth control of SCC. Further study is needed to evaluate the prognostic significance of particular patterns of disordered expression of proteins regulating proliferation and apoptosis in SCC of different head and neck sites.

Lack of universal success with both transantral ligation of the internal maxillary artery and percutaneous embolization of the distal branches of the internal maxillary distribution has led to consideration of alternative techniques to control intractable posterior epistaxis. One such technique takes advantage of advances in endoscopic technology and instrumentation, as well as a nearly constant anatomic configuration. The internal maxillary artery divides into terminal branches within the pterygomaxillary fossa, sending branches through the bony maxilla to exit the posterolateral nasal wall in the posterior aspect of the middle meatus. Endoscopic identification and ligation of these terminal branches of the internal maxillary artery (the sphenopalatine and nasopalatine arteries) as they exit the maxilla has been performed on 10 patients with a 100% success rate and no morbidity or mortality associated with the procedure. These results compare favorably to the average reported success rates of 89% for transantral ligation and 94% for percutaneous embolization, and average complication rates of 28% and 27%, respectively. This endonasal procedure has been performed for spontaneous epistaxis as well as postsurgical nasal bleeding with equal success. The ascending scale of treatment previously outlined in the literature may be amended, as a potentially definitive procedure is available, and we believe that this technique is easier to perform, has less associated morbidity, and has equal efficacy in comparison to transantral ligation or percutaneous embolization in the treatment of intractable posterior epistaxis.

This retrospective study evaluated the use of percutaneous craniofacial implants for the prosthetic rehabilitation of patients with a history of orbital exenteration and irradiation for oncologic tumors of the head and neck. A total of 24 implants were placed in six patients. All implants were determined to be osseointegrated at the time of uncovering. Three implants were subsequently resubmerged beneath the soft tissue because of positional interferences with prosthesis fabrication. The remaining 21 implants were ultimately used to retain six orbital prostheses. Two implants failed to maintain osseointegration during the follow-up period and were subsequently removed without complications. This represents an overall integration success rate of 90.5% over a mean follow-up period of 32.8 months (range = 11 to 68 months). The significance of these findings and their relationship to comparable reports in the literature are discussed.

Tracheoesophageal puncture (TEP) is a highly successful procedure for voice restoration. Occasionally, however, patients fail to achieve satisfactory voice or develop salivary leakage through the fistula into the trachea. Closure of the TEP is then necessary. In most cases, spontaneous closure occurs once the prosthesis has been removed. When the fistula does not close spontaneously, surgical closure is indicated to prevent aspiration and pulmonary complications. We describe a three-layer technique that employs interposition of dermal graft. The technique was used on 14 patients over a 7-year period. Most patients received irradiation to the neck. Complete closure was achieved in 13 of 14 cases; 1 patient developed partial breakdown of the closure. Our technique is relatively easy to perform and has a high success rate (92%). Irradiation did not adversely affect the closure rate.

Rapid proliferation of squamous cell carcinomas of the head and neck (SCCHN) during therapy may contribute to treatment failure. We have investigated the presence of p53 abnormalities in patients with SCCHN as a correlate of proliferation rate and other pathologic and clinical variables. p53 Mutation, as determined by polymerase chain reaction and single-strand conformation polymorphism analysis of microdissected frozen sections of tumor biopsies, was significantly associated with a high labeling index, as determined by in vivo infusion of IUdR and BrdU (P = 0.017). p53 Protein expression was detected by immunohistochemistry with two different antibodies, followed by quantitative image analysis. Many cases exhibited strong p53 protein expression in the absence of mutations within the conserved region of the gene, and expression was not related to proliferation. The presence of p53 mutations was related to tumor differentiation in this group of patients.

The repair of contour defects of craniofacial bone can be accomplished by several methods, including autogenous bone grafts, demineralized bone, and alloplastic materials. The objective of this study was to assess a biodegradable, xenogeneic, osteoinductive implant for craniofacial onlay bone augmentation. Twelve New Zealand White rabbits each had craniofacial onlays consisting of three experimental materials: 1) autograft; 2) allogeneic, demineralized block implant; and 3) partially purified osteoinductive protein (osteogenin) with allogeneic collagen and 50:50 poly (DL-lactide-co-glycolide). Implants with host bone were recovered after 20 weeks and assessed by histomorphometric methods. There was no evidence of adverse local reaction to the three treatments. No significant difference in bone replacement or bone density resulting from each of the implant types was demonstrated. In conclusion, the osteoinductive implants were well tolerated, and over the 20-week period they appeared to maintain their contour as onlays.

Extensive bilateral midfacial defects including the upper jaw, palate, and sinuses present a formidable reconstructive challenge. Prosthetic restorations require a solid anchor point to be successful, since orofacial motion would otherwise cause instability of the prosthesis. We report on a series of eight patients who underwent transmalar placement of a Steinmann pin at the time of definitive tumor resection. The Steinmann pin was used immediately to securely anchor a prosthesis to the skull base. The maximum follow-up time is 9 years. The Steinmann pin has remained firmly anchored without significant loosening in six of these eight patients, and no major complications have resulted from its use. In conclusion, the transmalar Steinmann pin is an effective and immediate single-stage method of permanently retaining a midface prosthesis.

Craniofacial implants have been used successfully for the retention of facial prostheses. However, complications occur that can lead to the loss of implant integration. One such complication is infection possibly resulting from crevicular microflora activity. As part of an ongoing study, samples from crevicular sites surrounding 17 craniofacial implants were collected and submitted for microbiological assay. The results demonstrated the presence of opportunistic pathogens in many sites regardless of subjects' hygiene efforts. The significance of the findings is reviewed.

Stainless steel has adequate strength, flexibility, ductility, and bio-compatibility for most maxillofacial implant applications. In addition, it is relatively cheap and easy to manufacture. Stainless steel may be effectively used in the maxillofacial region in the form of wires, pins, and plates. This article presents a technique for using a transmalar Steinmann pin to secure a midface prosthesis in cases of bilateral midfacial, bilateral maxillectomy, and total rhinectomy defects. The stainless steel pin may serve as a stable long-term anchoring if used for retention rather than load bearing. This method offers the potential for single-stage reconstruction and allows for prosthesis removal to inspect the surgical defect for early evidence of recurrence.

The simultaneous use of chemotherapy and radiotherapy (concomitant therapy) has exceptional promise in the treatment of head and neck cancer. In this limited review, seven head and neck cancer patients who underwent prior concomitant therapy and subsequent surgery developed wound-healing complications that were delayed (22-day average) in onset. Paranasal sinus and base of skull operations had less significant wound morbidity than those cases requiring simultaneous transgression of the neck and upper aerodigestive tract. The use of arterialized flaps did not in itself prevent wound breakdown. The formation of controlled fistulae, delay of reconstruction, and avoidance of simultaneous neck and upper aerodigestive tract entry are important considerations in avoiding wound-healing complications after concomitant therapy. In this select group of patients, surgery should be approached with extreme caution and conservatism.

The purpose of this article is to describe transplantation of jejunal grafts without microvascular anastomoses for reconstruction of the pharynx and/or upper esophagus following oncologic resections. Even though use of free flaps including jejunum, a method that requires revascularization, continues to offer superior results in pharyngoesophageal reconstruction, the technique described in this article provides a readily available alternative. This timesaving technique is particularly useful if the surgeon encounters intraoperative complications related to either the microvascular anastomoses or to an unstable patient. The principal advantages of jejunal graft reconstruction include the absence of a need for microvascular anastomoses, a decreased operating time, a one-stage operation, and the replacement of pharyngoesophageal mucosa with like tissue. The disadvantages include the need for laparotomy, the requirement for a well-vascularized tissue bed, delayed wound healing, the need for stenting, and delayed initiation of oral intake.

To determine the efficacy of multimodality treatment for stage III and IV, advanced paranasal carcinoma, we have retrospectively reviewed local control rate and disease-free survival in patients treated at the University of Chicago (Ill). Twelve consecutive patients with stage III or IV, newly diagnosed paranasal sinus carcinoma treated between 1984 and 1991 were included in this study. Multimodality therapy was composed of a sequence of fluorouracil-cisplatin-based neoadjuvant chemotherapy (in 12 of 12 patients) followed by standard surgical resection (11 of 12 patients) and radiotherapy (12 of 12 patients, 45 to 73 Gy) with or without concomitant chemotherapy. Eleven patients (92%) are currently alive and free of disease, with a median follow-up of 55 months (range, 13 to 105 months). One patient died of persistent disease. Failure was attributed to incomplete surgical resection. There was only one major irreversible treatment complication (cisplatin ototoxic reaction). Our preliminary data suggest improved local control and survival with multimodality therapy that includes systemic neoadjuvant chemotherapy and standard tumor resection in patients with advanced paranasal sinus carcinoma. These results are superior to the reported 40% survival with bimodal therapy and are better than those achieved in our institution for other head and neck primaries with the same treatment regimens.

Malignant scalp neoplasms initially spread by radial extension with deep invasion occurring relatively late in the course of disease. Basal cell carcinomas have the highest incidence followed by squamous cell carcinomas and melanomas. Surgical excision provides the best chance of cure in the majority of cases. Tumor histology influences decisions about margins of resection and regional lymph node dissection. Primary closure usually can be obtained for scalp defects measuring up to 3 cm in diameter. Larger defects can be reconstructed with skin grafts, local flaps, musculocutaneous flaps, free flaps, or transposition flaps following tissue expansion.

Purpose: To increase the activity of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) through further biochemical modulation and study the pharmacologic interaction of 5-FU and interferon alfa-2b (IFN)., Patients and Methods: Escalating doses of IFN (0.5 to 4.0 x 10(6) U/m2/d x 6) were added to cisplatin 100 mg/m2, continuous infusion 5-FU 800 or 640 mg/m2/d x 5, and leucovorin 100 mg orally every 4 hours. Forty-eight previously untreated patients with locoregionally advanced head and neck cancer received up to three cycles of PFL-IFN., Results: Twenty-one patients were treated during a phase I cohort study. Dose-limiting mucositis was seen with 800 mg/m2/d of 5-FU and 0.5 x 10(6) U/m2/d of IFN. After decreasing the 5-FU dose to 640 mg/m2/d, the maximally tolerated dose (MTD) of IFN was 2.0 x 10(6) U/m2/d. Mucositis and myelosuppression were dose-limiting. Of 34 patients treated at this MTD, 56% (95% confidence interval, 39% to 73%) had a complete remission. There was no correlation between 5-FU clearance and IFN dose. Pharmacodynamic analyses at the MTD showed that older age, female sex, and higher 5-FU area under the time versus concentration curve (AUC) were associated with lower nadir counts and/or increased mucositis. Seven patients with diabetes mellitus had significantly increased myelosuppression, serum creatinine, hypocalcemia, higher 5-FU concentrations, and lower 5-FU clearance compared with nondiabetics., Conclusion: The recommended doses for PFL-IFN are 640 mg/m2/d for 5-FU and 2.0 x 10(6) U/m2/d for IFN. Sex, age, 5-FU AUC, and diabetes mellitus may have an impact on the pharmacodynamics of this regimen.

Concomitant chemoradiotherapy has resulted in small increases in disease-free or overall survival for patients with advanced head and neck cancer when single-agent chemotherapy is used. To increase the efficacy of this approach, combination chemotherapy also has been explored. In this setting, acute toxicities are frequently increased, necessitating interruption or protraction of radiotherapy. Despite this fact, pilot trials using 5-fluorouracil-based chemotherapy have indicated high response and encouraging survival rates. Some of these trials will be reviewed, with a focus on studies with 5-fluorouracil, hydroxyurea, and cisplatin conducted at the University of Chicago.

Background: The majority of patients with head and neck cancer die of locoregional recurrence of disease following surgery and/or radiotherapy., Purpose: Our purpose was to administer induction chemotherapy, perform surgery, and administer concomitant chemoradiotherapy in rapid sequence and to evaluate their impact on locoregional and distant tumor control., Methods: Sixty-four patients with previously untreated, locoregionally advanced head and neck cancer received two cycles of cisplatin, bleomycin, and methotrexate (PBM) (33 patients) or cisplatin, fluorouracil (5-FU), and leucovorin (PFL) (31 patients). PFL was given to patients who were unable to receive bleomycin. Local therapy consisted of surgery and/or concomitant chemoradiotherapy with 5-FU, hydroxyurea, leucovorin, and radiotherapy (FHX-L), all administered every other week., Results: Complete and overall induction response rates were 21% and 79%, respectively, for PBM and 29% and 81%, respectively, for PFL. At completion of local therapy, 81% of the patients were disease-free. With a median follow-up of 35 months, the median survival and time to progression are 22 and 17 months, respectively, for PBM and have not been reached for PFL. Locoregional recurrence of disease is 30% for PBM and 26% for PFL. Distant disease progression is 24% for PBM and only 3% for PFL., Conclusions: The sequencing of induction chemotherapy and concomitant chemoradiotherapy is feasible and results in a high local control rate and in an encouraging survival rate with PFL. The high distant failure (i.e., outside the head and neck area) rate of PBM suggests insufficient systemic activity for that regimen., Implications: Concomitant FHX-L chemoradiotherapy may improve regional control rates of advanced head and neck cancer. Effective systemic therapy may be needed to control systemic micrometastases. PFL, but not PBM, appears to be suitable to accomplish that goal.

Based on encouraging results with 5-fluorouracil (5-FU), hydroxyurea, and concomitant radiotherapy in patients with advanced or recurrent head and neck cancer, an attempt was made to modulate the regimen by the addition of cisplatin as a third active agent. A cohort of 26 patients with head and neck cancer of all histologies were entered into a broad phase I study investigating simultaneous radiation therapy, 5-FU (with or without leucovorin), HU, and infusional cisplatin administered on an alternate-week schedule. Eleven patients (group 1) had failed prior curative local therapy and 15 patients (group 2) were considered to have a poor prognosis with standard therapy. The median follow-up was 30 months. The response rate for all evaluable patients was 82% (14/17), and the complete response rate was 65% (11/17). Patients in group 1 demonstrated a high failure rate (9/11), while few group 2 patients failed after treatment (2/15). The median time to progression was 4.4 months in group 1 and has not been reached in group 2. Patients in group 1 failed locally (7/11), while no local failures were observed in group 2. Acute and cumulative hematologic toxicity was encountered at all dose levels and schedules tested and prevented escalation of the cisplatin dose beyond the desired level of 100 mg/m2 per months. Mucositis was a second significant toxicity in patients with head and neck cancer and was more pronounced during cycles containing leucovorin. A detailed analysis of survival, time to progression, and site of failure is presented.

Hydroxyurea is an active single agent in squamous cell cancer of the head and neck. It has been used clinically, most frequently as a radiation-enhancing agent with concomitant radiotherapy. Pilot trials testing hydroxyurea in this setting reported encouraging results. Two randomized trials have been conducted with inconclusive results, possibly relating to study cohort size and short period of follow-up. More recently, hydroxyurea has been investigated with 5-fluorouracil and concomitant radiotherapy. A sound theoretic rationale can be made for this approach and data derived from a phase I/II study are presented. These support the further investigation of this regimen.

We used positron emission tomography (PET) to evaluate cerebral metabolic changes in five patients who underwent resection of the internal carotid artery (ICA) for malignant tumors of the head and neck. These patients received a thorough clinical neurologic examination as well as neuroradiologic evaluation, including computed tomography (CT), magnetic resonance imaging (MRI), and PET of the head, before and after balloon occlusion of the ICA. All five were free of cerebral or peripheral vascular disease. In addition, each patient was evaluated with an electroencephalogram (EEG) before and during the balloon occlusion for signs of ischemic changes. No abnormalities were noted on clinical neurologic examination, CT, MRI, or EEG, either before or after occlusion, and excision of the ICA. The PET examination showed a mean preoperative metabolic rate of 7.52 mg of glucose/min/100 gm of brain tissue and a mean postoperative rate of 6.32 mg/min/100 gm of brain tissue; these values were within the normal range of 5.00 to 9.00 mg of glucose/min/100 gm of tissue observed at this center. Only one subject showed asymmetry of glucose metabolism; this subject had received radiation treatment to one side of the brain after the initial PET evaluation. The results of this study support our clinical experience with occlusion and resection of the ICA in patients with head and neck tumors that in the past have been considered inoperable.

Thirty-nine patients with head and neck cancer were entered into Phase I-II study of simultaneous radiation therapy with continuous infusion fluorouracil at 800 mg/m2/day and escalating doses of hydroxyurea. Twenty of these patients had recurrent disease after previous surgery and/or radiation therapy (group 1). Nineteen patients had not received prior local therapy but had advanced-stage disease (group 2). Cycles were repeated every other week until the completion of radiation therapy. The median follow-up was 32 months. Patients with recurrent disease were generally treated with palliative doses of radiation (median dose 5,000 cGy) while previously untreated patients received radiation with curative intent (median dose 7,040 cGy). The response rate for 15 evaluable patients with recurrent disease was 93% with 40% of patients achieving a complete response. For 17 evaluable patients without recurrent disease the response rate was 100%, with a complete response rate of 71%. This regimen exhibited a high activity and significant palliative benefit in group 1 patients. However the local control rate was 25% (5/20) because the majority of patients in this group eventually developed a local recurrence. The local control rate for group 2 patients was 84% (16/19). The higher local failure rate in group 1 patients appeared to be attributable to the palliative doses of radiation delivered and the fewer cycles of treatment received. We conclude that this regimen has palliative benefit in patients who have failed prior local therapy and has the potential for cure in patients with poor prognosis advanced stage disease as well.

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.

New methods in head and neck cancer treatment have enabled the oncologic surgeon to pursue the goals of conservation of head and neck physiologic function, reduce the morbidity and mortality associated with advanced head and neck cancers, and increase the cure rates for cancers once considered inoperable. Advances in multimodality therapy may lead in the next decade to less surgical mutilation and higher cure rates.

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.

The temporoparietal-galeal system of flaps provides the head and neck surgeon with a reliable source of pliable, well vascularized local tissue capable of reconstructing auricular, oropharyngeal/base of tongue/lateral floor of mouth, dural, mandibular, and facial defects. This report provides a description of the types of flaps available, methods of dissection, and examples of reconstructive uses with this versatile tissue.

A retrospective study was performed with use of tumor registry data to evaluate tumor population characteristics, the patterns of care, and patient survival in 4,506 patients with head and neck cancers seen at The University of Iowa Hospitals and Clinics between 1960 and 1985. The total number of patients with head and neck cancers seen per year and the distribution by anatomic site remained relatively stable over the 26-year period. However, there was a general trend toward more advanced stages in later years. The selection of a treatment modality for this patient population correlated well with the site and stage of the disease and with the treatment philosophy of the managing physicians. Patient survival rates correlated well with the site and stage of the disease. There was a gradual improvement in 5-year survival rates over the 26-year period, from approximately 39% in 1960 to approximately 47% in 1984. This was principally due to an improvement in the 5-year survival rate for patients with "regional stage" disease, from approximately 22% in 1960 to approximately 41% in 1985.

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.

In this study, collagen sheeting is used for correction of various contour deformities of the face. This material, which was used in 16 patients, is easily implanted, does not lead to infection, and has an average resorption rate of 21% at 6 months. It provides excellent cosmetic results.

The radiobiological parameters of 33 tumor cell lines were studied in biopsy samples obtained from patients prior to radiotherapy. Epithelial tumor cells derived from head and neck cancer patients were more radioresistant than tumor cell lines derived from patients with sarcoma regardless of method of analysis. The presence of radioresistant tumor cell lines was associated with local failure in some patients. However, the presence of radiosensitive tumor cells did not necessarily predict local control. Our data suggest radiocurability is complex and inherent radiobiological parameters of tumor cells may be only one factor in radiotherapy outcome.

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.