Survival superiority of females with melanoma. A multivariate analysis of 6383 patients exploring the significance of gender in prognostic outcome.

OBJECTIVE: To evaluate the effects of gender on prognostic outcome of patients with melanoma. DESIGN: Retrospective cohort study, including 20 years of follow-up. SETTING: Duke University Melanoma Clinic, Durham, NC, a referral center for patients with melanoma. PATIENTS: Patients with melanoma (N = 6383), consisting of 45% females and 55% males, obtained from a referred sample. Eligibility requirements were nonocular melanomas and white race. MAIN OUTCOME MEASURES: Time to metastases and survival. RESULTS: Females with melanoma demonstrated a superior prognostic outcome over males, with a 34% survival advantage and a 28% disease-free advantage. When each of the variables of age, site, Clark's level, histologic type, and tumor thickness was explored for possible influences on prognostic outcome, female survival advantage persisted, although modified by independent variables. The greatest influence came from the variables of site, Clark's level, and Breslow's thickness. Age, specifically in premenopausal vs postmenopausal age groups, was not significant in altering females' prognostic advantage. A multivariate analysis combining the effects of all the variables resulted in females still maintaining a 22% survival advantage and a 17% disease-free advantage. CONCLUSIONS: Females with melanoma have a significant prognostic advantage over their male counterparts that cannot be fully explained by influences from the variables of age, site, Clark's level, histology, and Breslow's thickness. This superior prognostic outcome does not appear to be associated with menstrual status. Evidence does suggest that the protective factor for females occurs at the level of metastases.

Modulation of specific active immunization against murine melanoma using recombinant cytokines.

Specific active immunization with tumour cells and IL-1beta or IL-2 was examined in a murine model. Mice were treated with irradiated B16 melanoma, IL-1beta or IL-2 only, or with B16 plus cytokines prior to i.v. challenge with viable B16. Lung metastases were recorded after 28 days. Treatment with cytokine alone was not protective. Treatment with B16 alone afforded moderate protection. Treatment with B16 in combination with either cytokine resulted in a significant level of B16 specific protection which was dependent on the dose of cytokine used. Multiple immunizations with B16 provided limited protection which was significantly improved with IL-2. Immunization with B16 in combination with both cytokines at doses that alone failed to enhance immunity resulted in significant protection, suggesting that the two cytokines act at least additively. These studies demonstrate the significant benefit of specific active immunization with tumour cells in combination with low doses of IL-1beta or IL2.

Implementation of a clinical pathway in management of the postoperative vestibular schwannoma patient.

OBJECTIVE: The purpose of the study was to evaluate the effectiveness of a new clinical pathway in management of patients with postoperative vestibular schwannoma. The impact on duration of hospitalization and quality of care was evaluated. STUDY DESIGN: The study was a retrospective review of 59 consecutive patients undergoing surgical intervention for vestibular schwannoma between January 1995 and July 1999. METHODS: A new clinical pathway for management of postoperative vestibular schwannoma patients was implemented at The California Ear Institute at Stanford (Palo Alto, CA) in January 1995. All patients undergoing surgical intervention subsequent to initiation of the pathway were included in the study. Data including surgical approach, patient age, sex, and tumor size were included. Duration of hospitalization and postoperative complications were recorded. During the same time period, data for patients undergoing radiation therapy for vestibular schwannomas were evaluated for length of hospital stay and in-hospital complications. Data were compared with norms recorded in the literature for duration of hospitalization and complications following surgical intervention. RESULTS: Fifty-nine patients underwent 35 middle fossa approaches and 24 translabyrinthine approaches to their tumors. The average patient age was 53 years; there were 34 female and 25 male patients. The average length of hospital stay was 3.83 days (SD = 1.4 days) with a range from 2 to 10 days. Postoperative complications were observed in 19% of patients, including eight (13%) cerebrospinal fluid (CSF) leaks, two requiring lumbar drains (3.4%); one hematoma (1.6%), one postoperative fever (1.6%), and one dural tear with associated hyponatremia (1.6%). These results compared favorably with previously recorded average hospital stays of 5.95 to 9.5 days 1,5-7 and CSF leak complication rates of 7% to 15%.9,10 CONCLUSIONS: Implementation of a clinical pathway for management of the patient with postoperative vestibular schwannoma improves efficiency of patient care, allowing decreased duration of hospitalization. This goal is achieved without increasing complication rates and, in our experience, actually improving the quality of clinical care. The cost-effectiveness of clinical pathways may become increasingly important in a managed care-driven environment.

Hearing improvement after middle fossa resection of vestibular schwannoma.

OBJECTIVE: The preoperative, intraoperative, and postoperative variables of patients experiencing hearing improvement after middle fossa resection of vestibular schwannomas were evaluated as potential prognostic indicators. STUDY DESIGN: Retrospective case review with new objective postoperative data collected on patients with documented hearing improvement. SETTING: California Ear Institute at Stanford and Stanford University Hospital, a tertiary referral center. PATIENTS: The patient group consisted of 30 consecutive patients undergoing middle fossa approach to vestibular schwannoma between October 24, 1994, and November 11, 1998. INTERVENTION: Hearing preservation surgery via the middle cranial fossa approach was performed on all patients. MAIN OUTCOME MEASURES: Pure-tone averages (PTAs) and speech discrimination scores (SDS) were used to document hearing preoperatively and postoperatively. Preoperative electrophysiologic studies of auditory brainstem response, electronystagmography, electrical neuronography, transient evoked otoacoustic emissions, and distortion product otoacoustic emissions were evaluated. Intraoperative continuous nerve action potential and auditory brainstem response tracings were reviewed. Postoperative auditory brainstem response and transient evoked otoacoustic emissions were obtained when possible on patients whose hearing improved. Statistical analysis was completed using Student's t test and chi-square test. RESULTS: Seventeen (57%) of 30 patients with tumors ranging from 2 to 31 mm maintained hearing postoperatively. Among patients with hearing preservation, 7 (41% or 23% of the overall group) exhibited hearing improvement (PTA 2 improved by > or =5 dB and/or SDS improved by > or =12%). Three of these 7 patients moved from nonfunctional (AAOHNS class C/D) to functional (AAOHNS class A/B) categories. All patients who enjoyed postoperative hearing improvement had preoperative absence or abnormality of ABRs. No patient with normal preoperative ABR experienced hearing improvement. Hearing improvement patients also had lower preoperative caloric function on electronystagmography compared with the entire group (p < 0.02) and were more likely to have superior vestibular nerve tumors. No differences were noted for electrical neurography and otoacoustic emissions. CONCLUSIONS: Middle fossa resection of vestibular schwannoma offers patients the possibility of hearing improvement after treatment. The chance of hearing improvement is significantly higher than with other forms of treatment such as radiation therapy or translabyrinthine surgery. Although preoperative ABR abnormality may be an indicator of poor prognosis for hearing preservation, those patients who enjoy hearing improvement come from the group of patients with abnormal preoperative ABRs. Other factors identified as associated with hearing improvement include poor SDS with more normal PTA 2, and significantly decreased electronystagmographic caloric function (as an indicator of superior vestibular nerve tumors). Hearing improvement to the functional range after surgical resection is possible in some patients previously thought to be poor candidates for hearing preservation attempts. Hearing improvement may continue for many months after surgery.

Effects of estrogen and tamoxifen on growth of human vestibular schwannomas in the nude mouse.

Vestibular schwannomas have been noted to have increased frequency and aggressivity in female patients, suggesting a possible role of estrogen. This study evaluated the effects of estrogen and tamoxifen on the growth of human vestibular schwannoma tissue implanted in subcutaneous pockets of nude mice. Animals were implanted with 1 of 3 human vestibular schwannomas and observed for 28 days. Mice were then separated into 3 treatment groups: controls, estrogen (receiving 1.7 mg of 17B-estradiol), and estrogen + tamoxifen (receiving 1.7 mg of 17B-estradiol + 10 mg of tamoxifen), and treated for 28 days. Mice treated with estrogen showed increased growth that was statistically significant (P < 0.05) when compared with that of both the controls and the animals treated with estrogen + tamoxifen. Controls and animals treated with estrogen + tamoxifen showed a general trend of decreased volume during the treatment period. These early results support the hypothesis that estrogen modulates the growth of vestibular schwannomas in the nude mouse model and that these effects can be blocked by tamoxifen administration.

Cochlear implantation: minimal hair removal technique.

This prospective study was undertaken to evaluate the safety and patient acceptance of minimal hair removal during cochlear implantation. Forty-six consecutive patients (17 adults, 29 children; age range 13 months to 84 years) received cochlear implantation with a minimal hair removal technique. A questionnaire was used to evaluate acceptance and value of this technique among the first 15 patients and parents. Postoperative examinations were completed 1 and 4 weeks after implantation. Patients were monitored for complications, which included 3 cases of transient seroma, 2 cases of transient dysequilibrium, 2 individual electrode failures, and 1 facial nerve stimulation. Importantly, no wound infections were documented. Use of a small shave technique did not increase surgical risk. This technique has proved to be cosmetically and psychologically more desirable for the patients and their families than complete hair removal in the operative field.

Cochlear hook anatomy: evaluation of the spatial relationship of the basal cochlear duct to middle ear landmarks.

The cochlear hook is an important anatomical area for the otologist performing cochlear implants and other otological procedures, who requires knowledge of the basal cochlea. A total of 15 human temporal bones were dissected and the spatial relationship of the hook segment of the cochlear duct to the stapes, round window, cochleariform process and ductus reuniens were evaluated. Inter-individual variability was noted for widths of scala tympani (average width 1.36 +/- 0.25 mm) and scala vestibuli (average width 1.18 +/- 0.18 mm) in the region of typical cochlear implant placement, with the scala vestibuli occasionally being wider than the scala tympani. The cochlear duct was in closest proximity to the stapes at the midportion of the footplate, with an average distance of 1.23 mm at this narrowest width. A fibrous anchor, not previously described in otology literature, was identified securing the most basal end of the cochlear duct. Knowing the spatial relationship of the cochlear duct to the middle and inner ear structures could prevent damage to the basilar membrane in procedures around or involving the basal cochlear, such as cochlear implantation, stapedotomy, or implantable hearing devices.

Human vestibular schwannoma growth in the nude mouse: evaluation of a modified subcutaneous implantation model.

HYPOTHESIS: Based on the hypothesis that vestibular schwannomas can be successfully implanted and grown in the nude mouse model, an in vivo experiment was designed for subcutaneous implantation of solid vestibular schwannoma tissue. BACKGROUND: Vestibular schwannomas are benign tumors arising from Schwann cells of cranial nerve VIII. Little in vivo research has been carried out with these tumors, due in part to the difficulty to grow cells in culture or maintain tumor in an animal model. Recently, vestibular schwannomas have been implanted in nude mice with moderate success. The current study evaluates a modification of prior techniques in an effort to establish a dependable research model. METHODS: Thirty-six nude mice were implanted with variable-sized vestibular schwannoma tissue from three human subjects. Volumes implanted ranged from 14-170 mm3. Mice were observed for 28 days and individual volumes recalculated. Eleven of the mice were observed for a total of 56 days with volumes re-evaluated, and tumors subsequently were removed for assessment of viability and vascularity. RESULTS: At 28 days, 36 tumors (100%) showed take with 34 tumors (94%) showing macroscopic growth. The 11 tumors observed for 56 days showed a trend of stable or decreased size at 56 days compared with that of the 28-day measurement. Overall growth from time of implantation to measurements at 56 days was noted in 8 (73%) of 11 tumors when measured at the skin and in 10 (91%) of 11 tumors when direct tumor volume was measured. One hundred percent of tumors evaluated microscopically at 56 days was viable. All tumors at the time of removal had significant vascularity with a mean of 70.68% (SD = 23.42) of surface covered with vessels. There were no significant differences in take and growth for the larger tumor specimens compared with those of smaller sizes. CONCLUSION: Human vestibular schwannomas successfully can be implanted and maintained in the subcutaneous pocket of the nude mouse. This in vivo tumor model provides a reliable, accessible base for further research with vestibular schwannomas.

Surgical management of regional lymph nodes in patients with melanoma. Experience with 4682 patients.

OBJECTIVE: The purpose of this study was to evaluate a large number of patients with cutaneous melanoma who had or who were at risk for lymph node metastases to contribute to the understanding of the behavior of and appropriate management of draining nodes. A major goal of the study was to reassess the clinical impact of elective lymph node dissections (ELND) in a large patient population. SUMMARY BACKGROUND DATA: Large retrospective studies suggest that ELND may improve the prognosis of patients with intermediate thickness melanomas; however, that improvement has not been observed in two randomized prospective controlled trials. METHODS: The charts of 4682 patients treated at a single institution for localized or regional disease were reviewed individually. The median follow-up was 4.7 years, with 814 patients followed more than 10 years. The data were tabulated and evaluated with the aid of a computer data base system. RESULTS: Among patients with nodal metastases, 10% of nodal metastases were to contralateral nodes, and 6% were to nodal basins that would not be predicted by classic models of lymphatic drainage; in 13% of patients, nodal metastases occurred to greater than one nodal basin (3% of the entire study group). For all thickness ranges, the incidence of nodal metastases was comparable to the incidence of distant metastases; intermediate-thickness lesions had no relative predilection for nodal metastases. At the initial evaluation, regional nodal basins were clinically negative in 3550 patients, of whom 911 (25.7%) underwent ELND. Stratified into five thickness groups (< 0.76 mm, 0.76 to 1.5 mm, 1.5 to 2.5 mm, 2.5 to 4 mm, and > 4 mm), pathologically positive nodes were identified in 0%, 5%, 16%, 24%, and 36%, respectively (16% overall). Among the 911 patients who underwent ELND, 214 (23%) had nodal metastases, 143 at the time of ELND and 71 at a later date. Of these 71 patients, 31 (44%) had nodal metastases in a previously dissected nodal basin, and 40 (56%) had them in basins not previously dissected. The survival of patients with clinically negative nodes treated with and without ELND were compared. The two groups were well matched for major prognostic factors. Stratified by Breslow thickness and primary site, no significant improvement in survival was observed with ELND. CONCLUSIONS: Because of the significant incidence of metastases to contralateral and atypical nodal basins, lymphoscintigraphy may be justified for the preoperative evaluation of patients for ELND. However, the therapeutic value of ELND is questionable as a result of (1) the finding that the risk of nodal metastases is not relatively more common than is that of distant metastases among patients with intermediate-thickness melanomas, (2) the fact that only 16% of ELND were positive, (3) the finding that ELND may not prevent recurrent nodal disease in the dissected basin, and (4) the absence of any apparent impact on survival among patients who underwent ELND.