PET/CT prior to salvage surgery in recurrent head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to assess the use of 18F-FDG PET/CT scans for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma (HNSCC) and investigate the treatment and survival of patients with recurrence. METHODS: In this retrospective study, consecutive head and neck cancer patients referred for FDG PET/CT scan between 2012 and 2014 were included. Patient records were reviewed and only patients with recurrence of HNSCC were enrolled for further analysis. Information on distant metastases, surgery and survival was collected. A Kaplan-Meier analysis was used to report survival. RESULTS: Overall 275 PET/CT scans were performed due to suspected recurrence, and in 166 scans (144 patients), recurrence of HNSCC was confirmed, making them eligible for further analysis. Distant metastases were revealed in 29.8% of the scans (n = 51) and the proportion of revealed metastases remained constant at approximately 30% each year. Although the number of performed scans increased twofold each year, there was no statistically significant change in the proportion of scans with distant metastasis (p = 0.55). The distant metastases were most often seen in the lungs (n = 44) and bone (n = 15). A few patients had widespread dissemination to other areas. Salvage surgery was performed following 81 of the 166 PET/CT scans. Seven of the patients who underwent salvage surgery had M-site oligo-metastases. Patients who underwent salvage surgery had a median survival of 22 months whereas patients not treated with salvage surgery had a median survival of 6 months. After 5 years, 21% of the patients selected for salvage surgery were alive. CONCLUSIONS: Distant metastases occur frequently in patients with recurrent HNSCC disease and the proportion of revealed distant metastases remained the same (30%). Imaging with FDG PET/CT can be recommended in patients with recurrent HNSCC prior to putative salvage surgery.

Impact of Time to Treatment Initiation in Patients with Human Papillomavirus-positive and -negative Oropharyngeal Squamous Cell Carcinoma.

AIMS: The distinct difference in disease phenotype of human papillomavirus-positive (HPV+) and -negative (HPV-) oropharyngeal squamous cell cancer (OPSCC) patients might also be apparent when assessing the effect of time to treatment initiation (TTI). We assessed the overall survival and progression-free survival (PFS) effect from increasing TTI for HPV+ and HPV- OPSCC patients. MATERIALS AND METHODS: We examined patients who received curative-intended therapy for OPSCC in eastern Denmark between 2000 and 2014. TTI was the number of days from diagnosis to the initiation of curative treatment. Overall survival and PFS were measured from the start of treatment and estimated with the Kaplan-Meier estimator. Hazard ratios and 95% confidence intervals were estimated with Cox proportional hazard regression. RESULTS: At a median follow-up of 3.6 years (interquartile range 1.86-6.07 years), 1177 patients were included (59% HPV+). In the adjusted analysis for the HPV+ and HPV- patient population, TTI influenced overall survival and PFS, most evident in the HPV- group, where TTI >60 days statistically significantly influenced overall survival but not PFS (overall survival: hazard ratio 1.60; 95% confidence interval 1.04-2.45; PFS: hazard ratio 1.46; 95% confidence interval 0.96-2.22). For patients with a TTI >60 days in the HPV+ group, TTI affected overall survival and PFS similarly, with slightly lower hazard ratio estimates of 1.44 (95% confidence interval 0.83-2.51) and 1.15 (95% confidence interval 0.70-1.88), respectively. CONCLUSION: For patients treated for a HPV+ or HPV- OPSCC, TTI affects outcome, with the strongest effect for overall survival among HPV- patients. Reducing TTI is an important tool to improve the prognosis.

Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure: a 10-year retrospective longitudinal study in eastern Denmark.

OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 142 patients in eastern Denmark undergoing salvage total laryngectomy for squamous cell carcinoma of the larynx or hypopharynx. MAIN OUTCOME MEASURES: 5-year overall survival, 5-year disease-specific survival, 5-year disease-free survival and prognostic factors for these outcomes. RESULTS: 5-year overall survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease-specific survival and disease-free survival. Residual tumour/recurrence was negatively associated with overall survival, close or involved resection margins with disease-specific survival, and second primary cancer was associated with longer disease-specific survival and disease-free survival. Nine per cent of all patients had residual tumour and 33.8% developed a recurrence. CONCLUSION: Our overall survival, disease-specific survival and disease-free survival findings are in accordance with previous studies. With the purpose of identifying recurrent tumour, we suggest extra attention being given to patients with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed.

Risk factors for postoperative complications after total laryngectomy following radiotherapy or chemoradiation: a 10-year retrospective longitudinal study in Eastern Denmark.

OBJECTIVES: To determine the rates of and risk factors for postoperative complications following total laryngectomy in patients treated with radiotherapy or chemoradiation. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 143 patients undergoing total laryngectomy for squamous cell carcinoma of the larynx or hypopharynx. MAIN OUTCOME MEASURES: Overall postoperative complications and fistula formation. RESULTS: Overall postoperative complications, fistula formation, wound infection, bleeding and wound necrosis within one year after total laryngectomy occurred in 56.6%, 42.3%, 31.0%, 11.3% and 9.2% of patients, respectively. Stenosis of the pharynx/oesophagus and stoma shrinkage within five years after surgery were each seen in 18.2% of cases. In 66.7% of cases, conservative treatment of the fistulas was chosen. Rehospitalisations within five years occurred for 44.8% with a median rate of 1.5 (range 1-11). Smoking status (P = 0.005 and 0.013) and chronic obstructive pulmonary disease (COPD) (P = 0.013 and 0.011) were significant risk factors for both overall postoperative complications and fistula formation in uni- and multivariate analysis. Tumour localisation in the hypopharynx was associated with overall postoperative complications (P = 0.036). Residual tumour or cancer recurrence was associated with late-onset fistulas (P < 0.001). CONCLUSION: The frequencies of postoperative complications after total laryngectomy were comparable with similar international studies, although fistula formation rate is increasing in Denmark. We suggest optimising treatment of COPD and to further encourage to smoking cessation. We propose that development of fistulas >2 months after surgery prompts immediate biopsies. Additionally, we suggest standardised registration of surgical techniques to identify variables affecting the frequency of postoperative complications.

[Vestibular schwannoma. A new interpretation of tumor growth]. / Vestibularisschwannomer. En ny fortolkning af vaekstresultater.

INTRODUCTION: The goal of the present paper was to investigate the growth of vestibular schwannoma (VS). MATERIAL AND METHOD: A series of 123 patients with 127 tumours were allocated to the wait and scan group in the period 1973 to 1999. The material was updated three times medio 1993, medio 1996 and medio 1999. Via the Danish national register, data on whether the included patients were alive or dead were collected medio 1999. Three sets of growth results were obtained. RESULTS: The results medio 1993 revealed: tumour growth in 94 tumours (74%), no growth in 23 tumors (18%) and negative growth in 10 tumors (8%). Medio 1996 the results changed to: tumour growth in 104 tumors (82%), no growth in 15 tumours (12%) and negative growth in eight tumours (6%). The growth figures changed again in medio 1999 to: tumour growth in 108 tumours (85%), no growth in 11 tumours (9%) and negative growth in eight tumours (6%). However, the results may also be interpreted in another way: 52 patients (42%) are alive, tumour growth did not demand any intervention, 23 patients (19%) died due to non-tumour related causes and 35 patients (28%) were previously treated and alive by the termination of the third observation period. CONCLUSION: It is concluded that tumour growth is time dependent, surgery at diagnosis is the ultimate solution, however the current study provides a number of arguments in favour of the wait and scan policy.

Vestibular schwannoma growth: the continuing controversy.

OBJECTIVE: To investigate the growth of vestibular schwannoma (VS) in a series of 123 patients with 127 tumors allocated to the "wait and scan" group in the period 1973-1999. STUDY DESIGN: Retrospective review of prospectively registered data on all patients with VSIE from the entire country who were allocated to the wait and scan group. METHOD: Clinical charts, audiometric data, and neuroradiological images were reviewed and tabulated for age, hearing level expressed as speech reception threshold (SRT) and speech discrimination score (SDS), maximum extra-canalicular tumor extension, and possible changes in tumor diameter. The material was updated three times (in June 1993, June 1996, and June 1999). Via the Danish national register, data on whether the included patients were alive or dead were collected in 1999. RESULTS: The tumor growth, growth rate, and growth patterns were calculated in three periods 1973 to 1993 (mean observation period, 3.4 y), 1973 to 1996 (mean observation period, 3.8 y), and from 1973 to 1999 (mean observation period, 4.2 y). By termination of the first period, 94 tumors (74%) exhibited measurable growth, 23 tumors (18%) no measurable growth, and 10 tumors (8%) revealed negative growth. By the end of the extended observation period, tumor growth was observed in 104 tumors (82%), no tumor growth in 15 tumors (12%), and negative growth in 8 tumors (6%). Subsequent to the third observation period, growth was observed in 108 tumors (85%), no growth in 11 tumors (9%) and negative growth in 8 tumors (6%). However, the results may also be interpreted in another way: 52 patients (42%) were alive at the time of writing, tumor growth did not demand any intervention, 23 patients (19%) died as a result of non-tumor-related causes, and 35 patients (28%) were previously treated and alive by the termination of the third observation period. CONCLUSION: Depending on the observation period, three sets of growth results were obtained. The long observation period, updating and re-updating the results, gave us the opportunity for a de novo interpretation of the results and the long-term consequences of the wait and scan policy. Combined with other factors, the achieved results should be considered when timing of surgery is to be decided.

Vestibular schwannoma growth--long-term results.

The growth of vestibular schwannoma (VS) was investigated in a series of 123 patients with 127 tumours during 3 periods: 1973 to 1993 (mean observation period 3.4 years), 1973 to 1996 (mean observation period 3.8 years) and 1973 to 1999 (mean observation period 4.2 years). Three sets of growth results were obtained. At the end of the first period, 94 tumours (74%) exhibited measurable growth, 23 tumours (18%) no measurable growth and 10 tumours (8%) negative growth. Tumour growth was observed in 104 tumours (82%), no tumour growth in 15 tumours (12%) and negative growth in 8 tumours (6%) at the end of the extended observation period. Growth was observed in 108 tumours (85%), no growth in 11 tumours (9%) and negative growth in 8 tumours (6%) subsequent to the third observation period. However, the results can be interpreted in another way: 52 patients (42%) are alive, tumour growth required no intervention; 23 patients (19%) died due to non-tumour-related causes; and 35 patients (28%) were previously treated and alive by the end of the third observation period. Together with other factors, the results reported here should be considered when timing of surgery is to be decided.

Cystic vestibular schwannoma--clinical and experimental studies.

The cystic variant of vestibular schwannoma (VS) presents a therapeutic dilemma. Several studies have previously demonstrated that the surgical outcome in this tumour entity is less favourable than that of solid tumours of comparable size. The "wait and scan" policy has not been recommended for these tumours, as the cystic elements expand, causing displacement of the brainstem and compression of the 4th ventricle, resulting in hydrocephalus. The large tumour size at diagnosis and the cystic contents do not support the role of radiosurgery as a therapeutic option. We have previously published the surgical outcome of 23 cystic VS. The present study includes 44 patients (44 cystic tumours) in a series of 773 tumours (5.7%) who underwent surgery in the period 1976 to 1996. This paper presents the neuroradiological and histological features of the tumours, as well as the results of tumour specimen implantation and surgery in athymic nude mice. Therapeutic options are also discussed.

Intracanalicular vestibular schwannoma--therapeutic options.

The growth of purely intrameatal vestibular schwannoma (VS) was investigated in a series of 40 patients with 40 unilateral VS in the period 1973 to 1996 (mean 3.6 years). Twenty-seven tumours (67.5%) revealed growth and 13 tumours (32%) had no measurable growth. Four growth patterns were observed: (i) 15 tumours (37.5%) exhibited constant growth; (ii) 13 tumours (32.5%) had no measurable growth; (iii) 8 tumours (20%) revealed growth subsequent to a no-growth period; and (iv) 4 tumours (10%) manifested different growth patterns during the observation period. The mean diameter growth per year was 3.2 mm. The findings of the present study, especially those achieved in groups B (the non-growing tumours) and C (tumour growth subsequent to a silent period), question the reliability of the results achieved by radiosurgery, as no tumour growth may occur with no intervention.

Cystic hygroma of the head and neck--a long-term follow-up of 44 cases.

Cystic hygroma of the neck is a relatively rare congenital malformation usually diagnosed during the first years of infancy. Complete surgical extirpation may be impossible without sacrificing important neurovascular structures. This paper reports the long-term outcome of surgical treatment during a 35-year period. A follow-up examination of 44 patients (24 males and 20 females) treated in our departments during the last 35 years was performed. Median age at first operation was 1.5 years (0-28 years) The observation period ranged between 1 and 36 years, median 16.2 years. Indications for operation were space occupying lesion, haemorrhage, dysphagia, difficulties in pronunciation or breathing and infection or nerve lesions. Fifty percent of the patients revealed residual or recurrent hygroma at the time of follow-up. Forty-four percent suffered from impaired speech, food intake, breathing or swallowing. Thirty-six percent were cosmetically bothered, and only 11% reported reduced quality of life. A significant correlation was noted between the extension of the lesion and (i) the number of operations performed and (ii) the rate of recurrent or residual hygroma. The rate of residual or recurrent hygroma was statistically higher for the suprahyoid lesions compared with the infrahyoid lesions. The localization and extent of the lesion is related to the surgical outcome. Surgical intervention should be centralized and should be considered carefully. Neurovascular structures should not be damaged in an attempt to effect complete removal. The above-mentioned results lead to a search for a new therapeutic modality, and the authors have recently taken up the Japanese way of treating hygromas by intralesional injection of OK-432. The first two patients treated by this technique had total regression of the lesion, and the method seems to be promising as an alternative to surgery.

Oral cancer--results of treatment in the Copenhagen University Hospital.

During the period 1992-96, 304 patients with malignant tumours of the oral cavity were referred to the Department of Head & Neck Oncology, Copenhagen University Hospital. The female:male ratio was 1:2. Age ranged between 20 and 96 years, median 61 years. Ninety-five percent of the tumours were squamous cell carcinomas. Twenty-two percent were in stage I, 21% were in stage II, 21% were in stage III and 36% were in stage IV. Sixty percent of the patients underwent primary surgical resection, combined with reconstructive procedures if necessary. In 39% of all cases, surgery was followed by radiotherapy, while 21% of the patients, mainly stage I and II patients, were only treated surgically. Radiotherapy alone was received by 36% of the patients, mainly stage III and IV. Four percent of the patients received no treatment due to advanced disease or general poor condition. The overall recurrence rate was 42%, ranging from 23% in stage I to 61% in stage IV. Thirty-eight percent of these patients were treated for recurrence, almost exclusively by surgery. The survival rate 1 year after treatment of recurrence was 90%, 60% and 50% for patients in stage I, II and III respectively, while only 1 of 16 patients in stage IV was alive after 1 year. Three-year crude survival for the whole material was 42%, ranging from 58% in stage I to 18% in stage IV. This is an improvement of 12% compared with a similar group of patients treated in our departments in the period 1978-82, when the primary treatment of choice was external irradiation. The survival rate was, as expected, closely related to T- and N-stage at time of diagnosis. In conclusion, we recommend primary surgery followed by irradiation therapy for patients in stages II, III and IV. Surgical treatment of recurrence in patients who were formerly treated by irradiation therapy should be reserved for patients in good general condition and in a low TNM stage, stage IV patients will only benefit from salvage surgery in a few exceptional cases.

Surgical outcome in malignant parotid tumours.

Of 494 parotid gland tumours treated in Copenhagen county (population 600,000 inhabitants) in the period 1986-95, 50 patients (34 males, 16 females) had tumours that were proven to be malignant, making an incidence of 0.62/100,000/year. The patients age ranged from 14 to 87 years, mean 64 years. According to the UICC classification system, 6 tumours (12%) were classified as stage I, 23 (46%) as stage II, 14 (28%) as stage III, and 7 (14%) as stage IV. The material included 41 primary parotid gland tumours, histologically the tumours were verified as mucoepidermoid carcinoma (n = 13), adenocarcinoma (n = 9), squamous cell carcinoma (n = 6), carcinoma ex pleomorph adenoma (n = 3), acinic cell carcinoma (n = 3), adenoid cystic carcinoma (n = 3) and other histological diagnoses (n = 4). Primary malignant lymphoma of the parotid gland was diagnosed in six tumours and the last three tumours were metastatic carcinoma. Four therapeutic modalities were applied: surgery only, surgery + radiation, surgery + chemotherapy, and surgery + chemotherapy + radiation. Surgical radicality was achieved in 76% and radicality was unrelated to tumour histology. Normal or nearly normal facial nerve function (HB1&2) was noted at last follow-up in 60%. Five-year crude survival for all patients was 68%. Survival was not dependent on N-classification. Patients in stage I had a better survival than did patients in stages II, III and IV. No significant difference was observed in 5-year crude survival or in the post-operative facial nerve function between the radically operated patients (n = 38) and patients with residual tumour (p = 0.27, Log-rank test), (p = 0.48, chi 2 test).

[Treatment of malignant parotid tumors. Results from the county of Copenhagen]. / Behandling af maligne parotistumorer. Resultater fra københavns amt.

Out of 494 parotid gland tumours treated in Copenhagen county (population 600,000 inhabitants) in the period 1986 to 1995, 50 patients (tumours) were proven to be malignant, making an incidence of 0.62/100,000 per year. Age ranged between 14 and 87, mean 64 years. According to the UICC classification system, six tumours (12%) were classified as stage I, 23 (46%) as stage II, 14 (28%) as stage III and 7 (14%) in stage IV. Four therapeutic modalities were applied: surgery only, surgery + radiation, surgery + chemotherapy and surgery + chemotherapy + radiation. Surgical radicality was achieved in 76% and radicality was unrelated to tumour histology. Normal or nearly normal facial nerve function (HB1&2) was noted at last follow up in 60%. Five year crude survival for all patients were 68%. Survival was not depends on N-classification. Patients in stage I had a better survival compared to patients in stage II, III and IV. No statistically significant difference in five year crude survival between the radically operated patients (n = 38) and patients with residual tumour (p = 0.27, log rank-test), (p = 0.48 chi2-test was found.

[Intraoral cancer in the county of Copenhagen]. / Intraoral cancer i Københavns Amt.

A retrospective study of patients treated for intra-oral squamous cell carcinoma in Copenhagen county is reported. The material included 156 patients, 66 females and 90 males. Age at diagnosis varied between 35 and 95 years with a mean of 65 years. Mean age of females/males was 70/62 years. Twelve therapeutic modalities were performed; surgery, radiotherapy, chemotherapy and different combinations of these. Five year disease specific survival related to tumours' T-classification was 84% for T1, 35% for T2, 20% for T3 and 27% for T4. A statistically significant relation between the tumours' T-classification and the disease specific survival was noted (p < 0.00001). Five year disease specific survival related to N-classification was 62% for N0, 30% for N1, 25% for N2 and 0% for N3. Crude five year survival was 37% overall, 61% for patients in stage I, 32% for patients in stage II, 16% for patients in stage III and 17% for patients in stage IV. The results are similar to those achieved in other centres. Since no significant improvement has been noted in patient survival during the last five to six decades and since the therapeutic morbidity has not always been acceptable to the patients, other therapeutic principles, such as the so called minimal invasive therapy should be considered in future treatment of intra-oral cancer.

Management of intrameatal vestibular schwannoma.

The growth of purely intrameatal vestibular schwannoma (VS) was investigated, in the period 1973-96 in a series of 40 patients with 40 unilateral VS. In the present study, the material was analysed and updated. By the end of the observation period (mean 3.6 years), 27 tumours (67.5%) revealed growth and 13 tumours (32%) had no measurable growth. Four growth patterns were observed: (A) 15 tumours (37.5%) exhibited constant growth; (B) 13 tumours (32.5%) had no measurable growth; (C) 8 tumours (20%) revealed growth subsequent to a no-growth period; and (D) 4 tumours (10%) showed different growth patterns during the observation period. The annual diameter growth rate ranged between 00 mm/year and 6.5 mm/year and the mean diameter growth per year was 3.2 mm. The findings of the present study, especially those for group B (the non-growing tumours) and C (tumour growth subsequent to a silent period) bring into question the reliability of the results achieved by radiosurgery, as without any intervention it may be that no tumour growth occurs.

Acoustic neuroma/vestibular schwannoma growth: past, present and future.

The growth of vestibular schwannoma (VS) was investigated in a series of 123 patients with 127 tumors in the period 1973 1993. The material was reanalysed and updated 3 years later in 1996. By termination of the first observation period (mean 3.4 years), 94 tumors (74%) exhibited measurable growth, 23 tumors (18%) no measurable growth and 10 tumors (8%) negative growth. By the end of the extended observation period (mean 3.8 years), tumor growth was observed in 104 tumors (82%), no tumor growth in 15 tumors (12%) and negative growth in eight tumors (6%). Several growth patterns were noticed: however, these were not static as the growth patterns of the tumors changed during the extended observation period. Accordingly, the expected growth figures by the end of this century (mean observation period approximately 4 years) will probably be: growth in 111 tumors (87%), no growth in 10 tumors (8%) and negative growth in six tumors (5%). The results indicate that neither the present study nor the previously published studies on tumor growth reflect the natural history of VS, but they only provide information on tumor growth, growth rates and growth patterns during a given observation period.

Squamous cell carcinoma of the oral cavity: the results of the surgical and non-surgical therapeutic modalities in a consecutive series of 156 patients treated in Copenhagen county.

A retrospective study on patients, treated for intraoral squamous cell carcinoma in Copenhagen county, is reported. The material included 156 patients, 66 females and 90 males. Age at diagnosis varied between 35 and 95 years with a mean of 65 years. Mean age of females/males was 70/62 years. Twelve therapeutic modalities were performed; surgery, radiotherapy, chemotherapy and different combinations of these. Three and five years crude survival were 43% and 37%. Three and five years crude survival rates were 70% and 61% for patients in stage I, 39% and 32% for patients in stage II, 29% and 16% for patients in stage III and 19% and 17% for patients in stage IV. The results are similar to those achieved in other centers. Since no significant improvement has been noted in patient survival during the last 5-6 decades and since the therapeutic morbidity has not always been acceptable to the patients, other therapeutic principles such as the so-called minimal invasive therapy should be considered in future treatment of intraoral cancer.

Growth of vestibular schwannomas: in situ model employing the monoclonal antibody Ki-67 and DNA flow cytometry.

Vestibular schwannoma (VS) growth potentials were studied in an in situ model, in which the cycling cellular fraction was determined immunohistochemically by applying the mouse monoclonal Ki-67 antibody, and the tumor ploidy was estimated by DNA flow cytometry in a consecutive series of 124 VSs. The tumors were classified according to the average number of positively stained nuclei in 10 high-power fields into three groups: 28 highly (> 10), 33 moderately (> 5-10) and 63 low proliferating (< or = 5). The intratumoral proliferative variation was studied in 10 tumors. Only slight variation in the number of the positively stained nuclei were observed. Six of seven tumors removed because of macroscopically documented growth by computed tomography (CAT) scan were moderately or highly proliferative. Proliferation of VS was correlated to prospectively registered clinical data. A statistically significant relation was found between VS proliferation and the prediagnostic duration of symptoms (p = 0.0001). The proliferative status was unrelated to age, sex, and tumor size. Flow-cytometric determination of DNA index of the 124 tumors revealed 12 tetraploid (DNA index = 2), 110 diploid (DNA) index = 1) and two nondiploid tumors. A statistically significant relation was noted between tumor ploidy and proliferation status expressed by Ki-67 (p = 0.024). The tetraploid tumors showed significantly lower proliferation compared with the diploid tumors. Tumor ploidy was statistically unrelated to age, sex, tumor size, and duration of symptoms. The results of this study provide a link between the immunohistochemical, flow cytometric findings, and clinical data, which could probably be relevant in identifying patients at risk for rapid tumor growth and tumor recurrences, because a rapid test for cell proliferation is now available.

Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.

[Acoustic neurinomas/vestibular schwannomas. Diagnostic evidence vs. surgery]. / Acusticusneurinomer/vestibularisschwannomer. Observation versus kirurgi.

+-f having vestibular schwannoma (VS) was conducted in a series of 123 patients (127 tumours), over a 20 year-period from 1973 to 1993. Mean follow up period was 3.4 years, mean annual growth rate was 3.2 mm/year. Tumour growth was observed in 90 patients (94 tumours, 74%), no growth was seen in 23 patients (23 tumours, 18%) and negative tumour growth in 10 patients (10 tumours, 8%). Surgery due to tumour growth was performed in 35 patients (35 tumours, 28%). Seven patients (seven tumours, 6%) were treated with gamma radiation and/or shunt insertion. Seven patients (6%) died of brainstem herniation induced by tumour compression. Nine patients (7%) died of non tumour related causes. Twenty-eight patients were classified as candidates for hearing preservation surgery and 21 patients (75%) lost their candidature during the observation period due to tumour growth and/or deterioration of hearing. The results may limit indications for allocation of patients with VS to the "wait and see" group.