Esthesioneuroblastoma: reflections of a 21-year experience.

OBJECTIVES: To evaluate the results of standardized treatment of esthesioneuroblastoma at a single institution during a 21-year period and calculate pertinent parameters, i.e., metastatic disease (local, regional, distant), disease-free survival, and complications of treatment. STUDY DESIGN: A retrospective review was conducted of all patients treated at a single institution from September 1976 through May 1998. METHODS: Only those patients who received their complete evaluation and treatment at our institution were included in this analysis. Thirty-five patients met this criterion. In addition, results of epidemiological, pathological, and molecular analyses were evaluated to seek accurate indicators for clinical outcomes. RESULTS: Six percent of patients presented with cervical metastatic disease, but ultimately 25.7% developed at least one episode of cervical metastases; 14.3% of patients developed a local recurrence an average of 6 years after diagnosis; and 37% of the patients ultimately developed at least one episode of metastatic disease. The disease-free survival for this cohort of 35 patients was 80.4% at 8 years. CNS complications occurred in 25.7% of the patients, 22.9% had orbital complications, 20% had systemic posttreatment problems, 18.2% had chemotoxic sequelae, 8.6% had infectious complications, and 14.3% had cosmetic sequelae. No epidemiological, pathological, or molecular factors appeared to be more accurate clinical indicators than the Kadish staging system. CONCLUSIONS: This series of esthesioneuroblastoma patients (N=35) reflects an 8-year disease-free survival of 80.4%, representing a significant number of patients treated and followed at one institution for an extended period of time. No valuable pathological or molecular indicators to predict aggressive clinical behavior were found. The average time interval before recurrent disease developed was more than 6 years, far greater than that expected for other sinonasal malignancies. Therefore, extended follow-up is necessary for this patient group.

The role of preoperative adjuvant treatment in the management of esthesioneuroblastoma: the University of Virginia experience.

OBJECTIVE: Multidisciplinary management of esthesioneuroblastoma has effected markedly increased survival during the past 20 years. The potential for radical craniofacial surgery for complete en bloc resection, the availability of advanced neuroimaging modalities, and the incorporation of neoadjuvant therapy into treatment strategies for tumor remission have all contributed to this accomplishment. However, a standard protocol for the management of these lesions has not been accepted; preoperative radiation and chemotherapy have been advocated, but neither radiographic nor clinical response has been quantified. METHODS: Thirty-four consecutive patients with biopsy-proven esthesioneuroblastoma treated at one institution from 1976 to 1994 were reviewed to determine the effects of preoperative radiation therapy, with or without chemotherapy, on tumor size and long-term survival. RESULTS: In a multivariate regression analysis, advanced age was predictive of decreased disease-free survival (P=0.008), whereas advanced Kadish stage was associated with a borderline higher rate of disease-related mortality (P=0.056). Two-thirds of the patients showed a significant reduction in tumor burden with adjuvant therapy. Patients with response to neoadjuvant therapy demonstrated a significantly lower rate of disease-related mortality (P=0.050). In this series, the overall 5- and 10-year survival rates were 81.0 and 54.5%, respectively. CONCLUSION: Preoperative neoadjuvant therapy provides a valuable complement to radical craniofacial resection, leading to reduction in tumor burden. Patients experiencing reduction in tumor volume by neoadjuvant therapy demonstrate an improved prognosis.

Preservation of the eye in the treatment of sinonasal malignant neoplasms with orbital involvement. A confirmation of the original treatise.

OBJECTIVE: To continue the retrospective analysis reported in 1988 that supported preservation of the eye in the treatment of sinonasal cancers when bony erosion of the orbit was noted on pretreatment radiographic analysis. DESIGN: Using the eye-sparing protocol previously reported, which included preoperative radiotherapy (with or without chemotherapy, depending on tumor size, involvement, or other characteristic) for malignant neoplasms of the superior nasal vault that had eroded the bony orbit, retrospective analysis of the results of therapy for the additional 33 patients treated between 1986 and 1993 was performed. These data were added to those from the original series to provide a total of 74 patients. Forty-one patients (55%) showed bony erosion at initial evaluation and 14 (19%) had periorbital involvement. During surgery, the periorbita was evaluated by frozen section control. If tumor was found, that region of periorbita was resected and, if necessary, replaced with fascia or split-thickness graft. RESULTS: Five patients from the original series had orbital sacrifice. Of the remaining 36 patients, 4 (11%) had recurrent disease involving the orbit, but not at the primary site. Twenty (55%) of the 36 patients had no orbital complications, and only 1 (3%) had a permanent motility disturbance and 4 (13%) developed cataracts after radiotherapy. CONCLUSION: With the use of preoperative radiotherapy in resection of involved periorbita with frozen section control in tumors of the sinonasal vault that involve the bony orbit, the eye can be spared in most instances without compromising oncologic safety.

Nasal reconstruction using an osteoconductive collagen gel matrix.

BACKGROUND: Congenital malformations, granulomatous diseases, and trauma can all cause destruction of the nasal structural framework, resulting in functional nasal obstruction and altered facial cosmesis. Current methods of nasal reconstruction include cartilaginous and bony grafts, Silastic implants, and homograft only materials. However, these techniques have significant functional and cosmetic drawbacks and are not risk free. Native, isotonic, neutral-pH, space-filling type I collagen gels have been shown to mediate total repair of critical-size collagen grafts provide a framework for rapid intramembranous ossification and osteoconduction of bone from the perimeter of a defect, resulting in total bony coverage. OBJECTIVE: To evaluate a novel approach to nasal reconstruction using a major defect of the bony nasal dorsum with a type I collagen gel matrix. DESIGN: Sixteen retired male breeder Sprague-Dawley rats were divided into control and experimental groups. The nasal bones were exposed through a dorsal incision and completely removed with a bone-cutting drill to the level of the mucosal membranes of the nasal vestibule. Defects in the experimental animals were then implanted with 200 micrograms of type I collagen gel, with control animals receiving no inlay. After 6 weeks, the animals were examined with three-dimensional computed tomography before necropsy, at which time the defects were photographed, measured by planimetry, and sectioned for histologic analysis. RESULTS: Experimental defects were observed to manifest 100% surface area healing with a thin layer of bone using a type I collagen gel osteoconductive implant for nasal reconstruction. Conversely, control animals showed only a 5.7% (+/- 3.7% SD) healing by area. Histologic sections of the collagen gel implant revealed restoration of the anatomy with a thin plate of immature bone spanning the defect in continuity with the cartilage of the nasal septum and with apparent preservation of maxillonasalis suture lines. CONCLUSIONS: Native, isotonic, neutral-pH, space-filling collagen gels positively influenced the repair of large nasal defects, which showed minimal bone closure in untreated animals. Their use in this role merits further investigation.

Evolution of hydrogel polymers as contact lenses, surface coatings, dressings, and drug delivery systems.

Hydrogel polymers are hydrophilic resins that display excellent biocompatibility, which has allowed their application in diverse fields of surgery and medicine. The original hydrogel polymer, a copolymer of 2-hydroxyethyl methacrylate and ethylene dimethacrylate, was developed by Wichterle and Lim in 1954. The development of the first soft hydrogel contact lenses by Wichterle in 1961 represented the first successful clinical application of hydrogel polymers and remains one of the most important uses of hydrogels today. The biocompatibility of hydrogel polymers may be adapted to diverse tissue types by small variations in the makeup of the polymer, including varying the type and amount of monomers and differing the amounts and characteristics of the cross-linking agents used to create the polymer chains. Hydrogels have been successfully developed for use as coatings, soft contact lenses, wound dressings, and drug delivery systems.

Definitive radiotherapy for T1 and T2 squamous cell carcinoma of the tonsil.

BACKGROUND: To assess whether survival or local control of early squamous cell carcinoma of the tonsil has been compromised by a moderate-dose approach. METHODS: Between 1970 and 1989, 185 patients with SCCa of the tonsil were seen at our institution. Fifty-three patients with T1 (30) and T2 (23) lesions treated with definitive radiotherapy were reviewed. Median follow-up was 60 months. The effects of total dose and site of the primary on survival and local regional control were analyzed. RESULTS: Three-year determinate survival was 77%. Mean total dose was 63.1 Gy. Site of the primary significantly affected survival (86% for fossa, 54% for pillars, p < 0.025). Local control at 2 years was 81% and was independent of dose > or = 63 Gy or site of the primary. Grade 4 complications defined by the RTOG/EORTC Acute Morbidity criteria occurred in three patients. CONCLUSIONS: Tumor doses on the order of 63 Gy or less result in excellent local control and survival rates for T1 and T2 carcinomas of the tonsil. Local control rates are better for fossa lesions than for pillar lesions.

Comparison of topical fibrin glue, fibrinogen, and thrombin in preventing seroma formation in a rat model.

Fibrin glue has been shown to decrease seroma formation in animal models. To further delineate this mechanism, the efficacy of fibrin glue was compared to topical fibrinogen and thrombin in preventing postoperative seromas. A model consistently producing seromas was developed by bilateral neck dissection, lymphadenectomy, and submandibular sialoadenectomy in the Sprague-Dawley rat. Groups of 20 rats underwent this procedure and were blindly treated with either fibrin glue, fibrinogen, thrombin, or saline control. Necropsy on postoperative day 5 revealed a statistically significant (chi-squared) decrease in seroma incidence using fibrin glue (0%) and fibrinogen (15%), while thrombin (95%) and saline (100%) were ineffective in preventing seromas. The use of fibrin glue and fibrinogen in this role merits further investigation.

Craniofacial resection at the University of Virginia (1976-1992): survival analysis.

BACKGROUND: The purpose of this study is to evaluate the survival of patients treated at the University of Virginia Health Sciences Center with an anterior craniofacial resection in conjunction with radiotherapy and/or chemotherapy for malignancies of the superior sinonasal cavity. In addition, the impact of aggressive salvage therapy for patients with recurrent disease is considered. METHODS: Between June 1976 and December 1992, a total of 45 patients underwent a craniofacial resection by the Departments of Otolaryngology-Head and Neck Surgery and Neurological Surgery at the University of Virginia. One patient was excluded from the analysis because his neoplasm was benign. Another patient died 2 days postoperatively from multiple strokes. The remaining 43 patients were divided into two subgroups: (1) patients with esthesioneuroblastoma (24 patients) and patients with non-esthesioneuroblastoma malignancies (19). Their survival curves were estimated for the percent survival free of disease by month of follow-up using the product limit of Kaplan and Meier. In addition, the salvage treatment for recurrences was examined for both groups. RESULTS: The 5-year disease-free survival rate for the entire group was 77%, with a 2.3% postoperative mortality. The 5-year disease-free survival for the esthesioneuroblastoma patients was 90%, and that for the non-esthesioneuroblastoma group was 59.1% (p = 0.028). Four of 8 esthesioneuroblastoma patients who recurred and were treated with aggressive salvage therapy were without evidence of disease 5 years after completion of therapy, and 3 of the 10 non-esthesioneuroblastoma patients salvaged were without evidence of disease 57.3 months after therapy (39% surgical salvage). CONCLUSIONS: There is a statistically significant difference between the 5-year disease-free survival for the esthesioneuroblastoma patients and the non-esthesioneuroblastoma patients (90% vs 59.1%; p = 0.028), and aggressive salvage therapy appears to be a more successful option in the esthesioneuroblastoma group of patients.

Esthesioneuroblastoma. Long-term outcome and patterns of failure--the University of Virginia experience.

BACKGROUND: Esthesioneuroblastoma is a rare tumor arising from olfactory epithelium. This retrospective review analyzed the patterns of failure and long term outcome of patients with esthesioneuroblastoma evaluated at a single institution. METHODS: Forty patients with esthesioneuroblastoma were evaluated at the University of Virginia, with a median follow-up of 130 months. In most cases, treatment consisted of combined-modality therapy, including radiotherapy and surgery for Stages A and B disease and the addition of chemotherapy for Stage C disease. Fifteen patients received chemotherapy that included cyclophosphamide plus vincristine. Thirty-eight patients received radiotherapy, with a median dose of 50 Gy. Initial surgery for 23 patients included craniofacial resection, whereas the remainder had less extensive surgery (3 had no initial surgery). Five patients were salvaged with high dose chemotherapy and autologous bone marrow transplantation (CTX/BMT). RESULTS: Actuarial survivals at 5, 10, and 15 years are 78%, 71%, and 65% respectively. Fifty-five percent of patients failed therapy, and 68% of the failures were locoregional. Thirty-nine percent of recurrences occurred later than 5 years from diagnosis. Three of the five patients were successfully salvaged with CTX/BMT compared with four of seventeen patients who underwent conventional salvage therapy. CONCLUSIONS: Esthesioneuroblastoma is associated with long term survival and late recurrences. Multimodality therapy should be used initially. Durable remissions of failures can be achieved with CTX/BMT:

Preliminary report: endoscopic versus external surgery in the management of inverting papilloma.

Since January 1977, twenty-four patients with inverting papilloma of the nose and paranasal sinuses have been treated at the University of Virginia. Two patients had bilateral disease, for a total of 26 surgically treated sides. Patients were aged from 10 to 83 years, and 71% were male. Most tumors originated on the lateral nasal wall, with 62% involving the adjacent sinuses. Nineteen sides were treated by external approach and 7 were treated intranasally. There was a total of 5 recurrences in 4 patients and no associated squamous cell carcinomas. Seven patients were treated with endoscopic excision (4 primary tumors and 3 recurrences). There have been no recurrences since endoscopic treatment. These preliminary data give further evidence that endoscopic excision is a viable surgical option for many inverting papillomas.

Sinonasal undifferentiated carcinoma: a ray of hope.

In 1987, we published a case series of a newly-described, highly malignant neoplasm, termed sinonasal undifferentiated carcinoma, in which treatment results were poor. In this updated study, we report the followup for the original three surviving patients and for six additional cases whose tumors were diagnosed between January 1987 and October 1991. These data suggest that the prognosis for patients with localized disease may be better than originally described.

The serratus anterior free tissue transfer for craniofacial reconstruction.

The serratus anterior muscle was used as a free tissue transfer to reconstruct complex craniofacial defects in 5 patients. Serratus anterior muscle alone and serratus anterior muscle with rib were the transfers made. All flaps survived and scapular winging did not occur. The serratus anterior muscle has several advantages for the reconstruction of medium-sized craniofacial defects. Because of its position, a two-team approach is possible. It has a consistent pedicle anatomy and low donor site morbidity. It has a large caliber vessel and a long pedicle. When compared with the commonly employed rectus abdominis flap for moderate-sized defects, the serratus muscle offers greater versatility in design and has the option of incorporating bone and innervated muscle without increasing significant donor site morbidity.

Neurological deterioration after lumbar cerebrospinal fluid drainage.

Large-bore lumbar spinal fluid drainage is used frequently as part of the preoperative and intraoperative management of patients undergoing cranial base tumor resection. Such drainage allows displacement of the brain with minimal force, thereby potentially decreasing retraction damage to it. We document 2 patients in whom serious complications resulted from lumbar drainage systems. These patients deteriorated into a coma state following cerebrospinal fluid (CSF) drainage. Reinfusion of synthetic CSF solutions caused a brisk return to normal neurological status. These plus other potential complications associated with lumbar drainage, such as persistent CSF leaks into the back and soft-tissue nerve root injury, warranted abandoning the lumbar cistern drainage route of CSF drainage in favor of drainage directly from the intracranial compartment. Depending on the particular operation performed, drainage of CSF near the cribriform plate, the suprachiasmatic cistern, or from the sylvian fissure may be effective sites for CSF drainage. Unlike lumbar drainage, intracranial CSF drainage does not have the added risk of promoting cerebral herniation.

Anterior skull base reconstruction with the pericranial flap after craniofacial resection.

No one reconstructive method is always satisfactory, especially when considering repair of a region such as the anterior skull base. Increased morbidity and mortality is directly related to failure of the reconstruction to adequately isolate the cranial cavity from the respiratory tract. Those surgeons performing craniofacial resections for lesions of the paranasal sinuses and anterior skull base must be familiar with a variety of reconstructive techniques which they can utilize depending upon the surgical defect that must be closed. For those small to moderate size defects of the anterior fossa we recommend using the inferiorly based pericranial flap to effect a repair. For larger defects extending laterally from the midline to involve a portion of the orbital roof, a laterally based flap of temporalis and pericranium can be used to provide successful anterior skull base reconstruction. Larger defects of the cranio-orbito-facial region will require additional methods of repair utilizing distant vascularized flaps.