Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS.

BACKGROUND: We aimed to better discriminate (occult) metastasised from non-metastasised seminoma based on transcriptional changes of small RNAs in the primary tumour. METHODS: Total RNAs including small RNAs were isolated from five testicular tumours of each, lymphogenic, occult and non-metastasised patients. Next-generation sequencing (SOLID, Life Technologies) was used to examine transcriptional changes. Small RNAs showing ⩾50 reads and a significant ⩾2-fold difference using non-metastasised tumours as the reference group were examined in univariate logistic regression analysis and combinations of two small RNAs were further examined using support vector machines. RESULTS: On average, 1.3 × 10(7), 1.4 × 10(7) and 1.7 × 10(7) small RNA reads were detectable in non-metastasised, occult and lymphogenic metastasised seminoma, respectively, of which 30-32% remained after trimming. Between 59 and 68% represented annotated reads and between 8.6 and 11% were annotated small RNA tags. Of them, 137 small RNAs showed>50 reads and a two-fold difference to the reference. In univariate analysis, 32-38 small RNAs significantly discriminated lymphogenic/occult from non-metastasised seminoma, and among these different comparisons, it were the same small RNAs in 51-88%. Many combinations of two of these small RNAs allowed a complete discrimination of metastasised from non-metastasised seminoma irrespective of the metastasis subtype. CONCLUSIONS: Metastasised and non-metastasised seminoma can be completely discriminated with a combination of two small RNAs.

Prediction of metastatic status in non-seminomatous testicular cancer.

PURPOSE: To examine the significance of 90 biomarkers for predicting metastatic status in non-seminomatous germ cell tumors (NSGCT). By predicting metastatic status, it may be possible to eliminate unnecessary therapeutic or diagnostic efforts. MATERIALS AND METHODS: We investigated 552 males who were diagnosed with non-metastatic (n = 273) and metastatic (n = 279) NSGCT between 2000 and 2011. The sample included cancers of different histologies: embryonal cell carcinoma (n = 131), teratoma (n = 55), and mixed histology (n = 366). We collected and analyzed more than 90 parameters via logistic regression: demographic characteristics, medical history, histopathological parameters, and levels of tumor markers and hormones. RESULTS: Testis histology (p = 0.004), clinical symptoms (p = 0.0005), tumor length (p = 0.005), infiltration of the rete testis (p = 0.008), invasion of lymphatic (pL1) and blood vessels (pV1) (p < 0.0001), and levels of enzymes such as LDH, ßHCG, AFP, and FSH (p values as small as <0.0001) were associated with metastatic status. With one model, we identified 14 out of 76 (18.4 %) metastatic NSGCT cases with 93-100 % certainty (positive predictive value) at 99 % specificity by the peripheral blood levels of LDH (day of operation) in combination with FSH measurements (1 day after operation). A second model included pV, tumor length, and FSH (1 day after operation). It identified 25 out of 90 (27.8 %) non-metastatic NSGCT with approximately 90 % certainty (negative predictive value) at 94-98 % sensitivity. CONCLUSIONS: No single parameter was able to discriminate metastatic from non-metastatic NSGCT, but combinations of parameters in two predictive models accurately identified the metastatic status in 23 % of the cases in our sample.

Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group.

BACKGROUND: The treatment of testicular intraepithelial neoplasia (TIN), the progenitor of testicular germ cell tumours (GCTs), is based on little data. PATIENTS AND METHODS: Two hundred and twenty-eight GCT patients with contralateral TIN were retrospectively enrolled. Ten had surveillance, 122 radiotherapy to testis with 18-20 Gy, 30 cisplatin-based chemotherapy (two cycles), 51 chemotherapy (three cycles), and 15 carboplatin. The study end point was a malignant event (ME), defined as detection of TIN upon control biopsy or occurrence of a second GCT. The Secondary end point was hypogonadism during follow-up. RESULTS: Numbers, proportions of ME, and median event-free survival (EFS) times were: radiotherapy N = 3, 2.5%, 11.08 years; chemotherapy (two cycles) N = 15, 50%, 3.0 years; chemotherapy (three cycles) N = 12, 23.5%, 9.83 years; carboplatin N = 10, 66%, 0.9 years; surveillance N = 5, 50%, 7.08 years. EFS is significantly different among the groups. Hypogonadism rates were in radiotherapy patients 30.8%, chemotherapy (two cycles) 13%, chemotherapy (three cycles) 17.8%, carboplatin 40%, surveillance 40%. CONCLUSIONS: Local radiotherapy is highly efficacious in curing TIN. Chemotherapy is significantly less effective and the cure rates are dose-dependent. Though hypogonadism occurs in one-third of patients, radiotherapy with 20 Gy remains the standard management of TIN.

The search for biomarkers of metastatic seminoma.

PURPOSE: We screened 90 potential parameters as biomarkers of metastatic seminoma to facilitate detection and eliminate unnecessary therapeutic or diagnostic efforts. MATERIALS AND METHODS: A total of 527 men with pure seminoma (diagnosed 2000 to 2011) were followed during therapy. More than 90 demographic/anamnestic (eg age, height, weight) histopathological parameters (testicular/tumor size, testicular intraepithelial neoplasia) and levels of tumor markers (eg α-fetoprotein, ß-human chorionic gonadotropin, lactate dehydrogenase) in peripheral blood and testicular vein were collected for analysis via logistic regression. Previously described risk factors (tumors larger than 4 cm, infiltration of rete testis) were assessed separately. RESULTS: Established parameters such as tumor length (p = 0.0003), involvement of lymphatic (p <0.0001) or vascular channels (p = 0.0009), extent of primary tumor (p <0.0001) and infiltration of the tunica albuginea (p = 0.02) as well as new biomarkers such as absence of testicular intraepithelial neoplasia in tumor bearing testis (p = 0.03), testicular volume (p = 0.04) and tumor volume (p = 0.02) showed a significant association with metastatic disease. This association was also true of lactate dehydrogenase, human chorionic gonadotropin and α-fetoprotein (p <0.0001 at maximum). However, the discriminatory capacity of these biomarkers (concordance or ROC area) did not exceed 65% when examined alone or in combination, and higher values (up to 80%) were detected for enzyme levels. A subset of metastatic seminoma (2% to 27%) was detectable with high accuracy (positive predictive value 92% to 100%) based on enzyme measurements (p <0.0006). CONCLUSIONS: New biomarkers of metastatic seminoma were identified and previously described risk factors were validated. Further prospective studies of these novel parameters are warranted to verify our findings and to explore a potential use for detecting occult metastases.

Probabilistic Fiber-Tracking Reveals Degeneration of the Contralateral Auditory Pathway in Patients with Vestibular Schwannoma.

BACKGROUND AND PURPOSE: Vestibular schwannomas cause progressive hearing loss by direct damage to the vestibulocochlear nerve. The cerebral mechanisms of degeneration or plasticity are not well-understood. Therefore, the goal of our study was to show the feasibility of probabilistic fiber-tracking of the auditory pathway in patients with vestibular schwannomas and to compare the ipsi- and contralateral volume and integrity, to test differences between the hemispheres. MATERIALS AND METHODS: Fifteen patients with vestibular schwannomas were investigated before surgery. Diffusion-weighted imaging (25 directions) was performed on a 3T MR imaging system. Probabilistic tractography was performed for 3 partial sections of the auditory pathway. Volume and fractional anisotropy were determined and compared ipsilaterally and contralaterally. The laterality ratio was correlated with the level of hearing loss. RESULTS: Anatomically reasonable tracts were depicted in all patients for the acoustic radiation. Volume was significantly decreased on the hemisphere contralateral to the tumor side for the acoustic radiation and diencephalic section, while fractional anisotropy did not differ significantly. Tracking did not yield meaningful tracts in 3 patients for the thalamocortical section and in 5 patients for the diencephalic section. No statistically significant correlations between the laterality quotient and classification of hearing loss were found. CONCLUSIONS: For the first time, this study showed that different sections of the auditory pathway between the inferior colliculus and the auditory cortex can be visualized by using probabilistic tractography. A significant volume decrease of the auditory pathway on the contralateral hemisphere was observed and may be explained by transsynaptic degeneration of the crossing auditory pathway.

Contralateral biopsies in patients with testicular germ cell tumours: patterns of care in Germany and recent data regarding prevalence and treatment of testicular intra-epithelial neoplasia.

The precursor of testicular germ cell tumours (GCTs), called testicular intra-epithelial neoplasia (TIN/CIS), is safely diagnosed immunohistologically. Testicular biopsy provides a valuable tool for early detection of GCTs in risk groups. Although this knowledge is undisputed, testicular biopsies are utilized poorly. The patterns of care regarding the use of biopsies remain unknown. Uncertainty exists about the prevalence and specific treatment of TIN/CIS. We asked clinical urologists in Germany whether or not they employed contralateral biopsies in GCT patients. We evaluated the prevalence of contralateral TIN/CIS in a retrospective analysis of 780 consecutive GCT patients. All had contralateral double biopsies. Discordance of TIN/CIS findings among biopsy pairs as well as age, histology of the primary tumour and clinical stage was noted. Evaluation of data comprised descriptive statistical methods. To evaluate treatment options for TIN/CIS, we performed a literature search. 52.1% of German urologists always perform the biopsy, 17% do it mostly, 27.3% in select cases, 3.5% never. Curiously, there was a geographic north-south gradient regarding biopsy use. Contralateral TIN/CIS was found in 5%. The median ages of patients with TIN/CIS and those without were 31.8 and 34.9 years respectively (p = 0.02). The discordance rate among biopsy pairs was of 33%. Two-site biopsies provide a 17% gain in diagnostic sensitivity. Local radiotherapy with 20 Gy is the safest treatment of TIN/CIS failing in 2%. Chemotherapy has significantly lower efficacy. Contralateral testicular biopsies in GCT patients are well accepted among German urologists. The prevalence of contralateral TIN/CIS found in this series is in accordance with previous reports. Double biopsies should be the diagnostic standard because of their diagnostic superiority. Local radiotherapy with 20 Gy is the safest way of eradicating TIN/CIS. Failures occur in only 2%, usually many years after irradiation. Cisplatin-based chemotherapy is dose dependent and less effective.

Energy conservation in fermentative glutarate degradation by the bacterial strain WoG13.

Dicarboxylic acids with 2-5 carbon atoms can be degraded fermentatively by pure cultures of various strictly anaerobic bacteria. The small amount of free energy released in these decarboxylations (about 20-25 kJ mol-1) is conserved as sole source of growth energy either through sodium-pumping decarboxylases or through electrogenic substrate/product transport devices. In the glutarate-fermenting bacterial strain WoG13 a glutaconyl-CoA-decarboxylating enzyme activity was detected. This enzyme was inhibited by avidin and was stimulated by sodium ions. The enzyme activity was partially associated with the cytoplasmic membrane, indicating that energy conservation is accomplished through a sodium-ion-pumping glutaconyl-CoA decarboxylase enzyme.

Management of 1000 vestibular schwannomas (acoustic neuromas): hearing function in 1000 tumor resections.

OBJECTIVE: The realistic chances of hearing preservation and the comparability of international results on hearing preservation in complete microsurgical vestibular schwannoma resections were the focus of this study in a large patient population treated by uniform principles. METHODS: One thousand vestibular schwannomas were operated on at Nordstadt Neurosurgical Department, from 1978 to 1993, by the senior surgeon (MS). There were 1000 tumors in 962 patients, i.e., 880 patients with unilateral tumors and 82 patients operated on for bilateral tumors in neurofibromatosis-2 (120 cases). Preservation of the cochlear nerve was attempted whenever possible. The audiometric data were analyzed by the Nordstadt classification system and graded in steps of 30 dB by audiometry and in steps of 10 to 30% by speech discrimination; for comparability, the data were also evaluated by the criteria of Gardner, Shelton, and House, and they were assessed in relation to the Hannover tumor extension grading system. RESULTS: Anatomic cochlear nerve preservation was achieved in 682 of 1000 cases (68%), as well as in some preoperatively deaf patients, a very few of whom regained some hearing. Of a total of 732 cases with some preoperative hearing, anatomic cochlear nerve preservation was achieved in 580 cases (79%) and functional cochlear nerve preservation in 289 (39.5%); analysis over time revealed an actual preservation rate of 47% in the most recent 200 cases. Specific factors, such as gender, tumor extension, preoperative hearing quality, and symptom duration, were investigated for their predictive value for hearing preservation. Male gender, small to medium tumor size (mainly extending within the cerebellopontine cistern; Classes T2 and T3), good to moderate hearing (up to 40-dB loss), and short duration of hypoacusis (< 1.5 yr) or of vestibular disturbances (< 0.7 yr) were advantageous factors, with chances of hearing preservation between 47 and 88%. CONCLUSION: Functional cochlear nerve preservation in complete microsurgical resection should belong to the contemporary standard of treatment goals.

Management of vestibular schwannomas (acoustic neuromas): the value of neurophysiology for intraoperative monitoring of auditory function in 200 cases.

OBJECTIVE: The present study investigated the significance of the presence or absence of auditory brain stem response (ABR) Waves I, III, and V as functional representatives of the cochlea, the nucleus cochlearis, and the colliculus inferior, respectively, and attempted to identify the microsurgical maneuvers that were especially likely to cause isolated or combined component losses and subsequent hearing losses. METHODS: Based on the previously described ABR classification system, 201 patients with preserved Waves I, III, and V or Waves I and V were investigated for the peak latencies and amplitudes of the waves at 15 defined microsurgical stages. Analysis was performed with respect to the presence or absence of ABR components during specific microsurgical actions and the related danger of deafness. RESULTS: Temporary or permanent losses of Waves V, I, and III occurred with 21, 27, and 29% of surgical actions, respectively, leading to deafness in 65 to 78% of the patients. Wave III disappearance was identified as the earliest and most sensitive sign. Wave V loss was usually preceded by disappearances of Waves I and III. During the most dangerous actions (drilling, pulling downward, medially, or laterally, and direct nerve manipulation), special attention ws paid to deterioration of Wave-III and then Wave I; if impairment was seen, intermittent breaks or changes in the type or site of microsurgical action were used to enable wave recovery. Acute, simultaneous, and permanent loss of all waves occurred in 27.5% of postoperatively deaf patients, whereas stepwise wave deterioration and losses occurred in 72.5%. CONCLUSION: Useful (in-time) recognition of significant waveform changes is possible and enables a change of microsurgical maneuvers to favor ABR recovery.

Management of 1000 vestibular schwannomas (acoustic neuromas): the facial nerve--preservation and restitution of function.

OBJECTIVE: Although the rate of reported facial nerve preservation after surgery for vestibular schwannomas continuously increases, facial nerve paresis or paralysis is a frequent postsurgical sequelae of major concern. The major goal of this study was to define criteria for the right indication, timing, and type of therapy for patients with palsies despite anatomic nerve continuity and those with loss of anatomic continuity. METHODS: One thousand vestibular schwannomas were surgically treated at the Department of Neurosurgery at Nordstadt Hospital from 1978 to 1993. Of 979 cases of complete removal and 21 cases of deliberately partial removal, the facial nerve was anatomically preserved in 929 cases (93%). The rate of preservation is increasing, as is evidenced in the most recent cases, and preservation is supported by special electrophysiological monitoring. The facial nerve was anatomically severed in 60 cases (6%). It was anatomically lost in previous operations that were performed elsewhere in 11 cases (1%). In case of nerve discontinuity (42 cases), immediate nerve reconstruction by one of three available intracranial procedures (within the cerebellopontine angle, intracranial-intratemporal, intracranial-extracranial) was performed in the same surgical setting. In case of loss of the proximal facial nerve stump at the brain stem, early reanimation by combination with the hypoglossal nerve was achieved in most patients within weeks after tumor surgery. In a few patients with anatomic nerve continuity but absence of reinnervation for 10 to 12 months, a hypoglossal-facial combination was applied. All the patients with partial or with complete palsies were treated in a special follow-up program of regular controls and of modulation of physiotherapeutic treatment every 3 to 6 months. RESULTS: In intracranial nerve reconstruction at the cerebellopontine angle, 61 to 70% of patients regained complete eye closure and an overall result equivalent to House-Brackmann Grade 3. Hypoglossal-facial reanimation led to Grade 3 in 79%. The duration between the onset of paralysis and the reconstructive procedure is decisive for the quality of the outcome. These data are discussed in view of other treatment options and certain parameters influencing outcome. CONCLUSIONS: This management contains three major principles as follows: 1) preservation of facial nerve continuity in function by the aid of intraoperative monitoring, 2) early nerve reconstruction in case of lost continuity, and 3) scheduled follow-up program for all patients with incomplete or complete palsies.

Management of 1000 vestibular schwannomas (acoustic neuromas): clinical presentation.

OBJECTIVE: Despite good knowledge of the key symptoms of vestibular schwannomas and their significance for surgical results, the evolution of symptoms and signs and their relation to tumor extension still need thorough investigation. METHODS: From 1978 to 1993, operations were performed by the same surgeon (M.S.) on 1000 vestibular schwannomas at the Neurosurgical Department of Nordstadt Hospital. The vestibular schwannomas were diagnosed in 962 patients, including 522 female patients (54%) and 440 male patients (46%); the mean age was significantly higher in female patients (47.6 yr) than in men (45.2 yr). We focused our analysis on the incidence of subjective disturbances versus objective morbidity, on the sequence of symptom onset, and on symptom duration and symptomatology versus tumor size and extension. RESULTS: The most frequent clinical symptoms were disturbances of the acoustic (95%), vestibular (61%), trigeminal (9%), and facial (6%) nerves. Symptom duration was 3.7 years for hearing loss, 1.9 years for facial paresis, and 1.3 years for trigeminal disturbances. Symptom incidence and duration did not strictly correlate with tumor size. Key symptoms of various tumor extension classes precipitated the diagnosis, such as trigeminal disturbances in large tumors with brain stem compression or tinnitus in small neuromas. In cases of trigeminal or facial nerve symptoms, the overall duration of symptomatology was much shorter. According to the subjective perception of the patients, between only one- and two-thirds of nerve disturbances were noticed. Patients with preoperative deafness had become deaf either chronically (23%) or suddenly (3%); even in cases of moderate hearing deficit that lasts a long time, deafness can occur suddenly. The rate of tinnitus was higher in hearing than in deaf patients; however, deafness does not mean relief from tinnitus, because this symptom persists in 46% of preoperatively deaf patients. Vestibular disturbances most often occur as some unsteadiness while walking or as vertigo, and the symptoms frequently are fluctuating, not constant. CONCLUSION: Differences in tumor biology can be underestimated and are not visible on radiological scans. For example, intrameatal tumors, despite their small size, present with a duration of symptoms that is representative of the larger tumors and are most frequently associated with vestibular symptoms and with tinnitus. Large tumors with brain stem compression present with relatively shorter symptom durations and at a younger age; both factors are suggestive of especially fast tumor growth. The clinical findings presented in this study promote new consideration of the dynamics of tumor growth and of the affected neural tissues.

Management of 1000 vestibular schwannomas (acoustic neuromas): surgical management and results with an emphasis on complications and how to avoid them.

OBJECTIVE: To identify the actual benefits and persisting problems in treating vestibular schwannomas by the suboccipital approach, the results and complications in a consecutive series of 1000 tumors surgically treated by the senior author were analyzed and compared with experiences involving other treatment modalities. METHODS: Pre- and postoperative clinical statuses were determined and radiological and surgical findings were collected and evaluated in a large database for 962 patients undergoing 1000 vestibular schwannoma operations at Nordstadt's neurosurgical department from 1978 to 1993. RESULTS: By the suboccipital transmeatal approach, 979 tumors were completely removed; in 21 cases, deliberate partial removal was performed either in severely ill patients for decompression of the brain stem or in an attempt to preserve hearing in the last hearing ear. Anatomic preservation of the facial nerve was achieved in 93% of the patients and of the cochlear nerve in 68%. Major neurological complications included 1 case of tetraparesis, 10 cases of hemiparesis, and caudal cranial nerve palsies in 5.5% of the cases. Surgical complications included hematomas in 2.2% of the cases, cerebrospinal fluid fistulas in 9.2%, hydrocephalus in 2.3%, bacterial meningitis in 1.2%, and wound revisions in 1.1%. There were 11 deaths occurring at 2 to 69 days postoperatively (1.1%). The techniques that were developed for avoidance of complications are reported. The analysis identifies preexisting severe general and/or neurological morbidity, cystic tumor formation, and major caudal cranial nerve deficits as relevant risk factors. CONCLUSION: The current treatment options of complete tumor resection with ongoing reduction of morbidity are well fulfilled by the suboccipital approach. By careful patient selection, the mortality rate should be further reduced to below 1%.

Management of vestibular schwannomas (acoustic neuromas): the value of neurophysiology for evaluation and prediction of auditory function in 420 cases.

OBJECTIVE: From 1978 to 1993, 1000 vestibular schwannomas were operated on at the Department of Neurosurgery at Nordstadt Hospital. The goal was to improve the chances of hearing preservation by recording auditory brain stem responses (ABRs). ABRs can be used for preoperative classification of cochlear nerve impairment and for prediction of the chances of hearing preservation. PATIENTS AND METHODS: In addition to the previously described audiometric testing, the patients underwent perioperative and intraoperative bilateral ABR recording at 100-dB condensation and rarefaction click stimulation. The classification system of five types of ABRs, as presented before, is based on the presence and on the latencies of Waves I, III, and V, with a special emphasis on Wave III's representing the activity of the first brain stem nuclei within the auditory pathway. According to an analysis of 420 preoperative ABRs, in case of a preoperative Type 1 or 2, the rate of hearing preservation is 80%. DISCUSSION: In the case of good clinical and audiometric hearing, a severely deteriorated ABR is mostly an indicator of severe nerve compression and adhesion by the tumor. In view of subsequently reported experiences with intraoperative ABR monitoring, the value of the presented system emphasizing the importance of Wave III is stressed and discussed with other views in the literature. The criteria presented here are not designed for recognition of retrocochlear disease but aim for evaluation of the state of the auditory nerve and its perspective. CONCLUSION: By the presented classification of ABR Type B1 through B5, preoperative prediction of the likelihood of hearing preservation is improved.

Intracanalicular acoustic neurinomas.

The cases of 16 patients with acoustic neurinomas confined to the intracanalicular area are presented. These represent 2.7% of the 600 patients with acoustic neurinomas consecutively operated upon at the Neurosurgical Clinic at Nordstadt Hospital during the last 8 years. The comparatively earlier onset of vestibular symptoms and signs was characteristic of this group and precipitated diagnosis. The diagnostic reliability of magnetic resonance imaging was at least equivalent to that of air computed tomographic cisternography. Complete tumor removal was accomplished via the suboccipital approach in all patients, with 100% preservation of facial nerve and facial function; the cochlear nerve was preserved anatomically in 100% of the patients and functionally in 57%. No recurrence has occurred during follow-up periods of up to 8 years in all 16 patients. A broad spectrum of the current literature is considered, and purely intracanalicular acoustic neurinomas are discussed with regard to clinical characteristics, diagnostic steps-including neuroradiological and neurophysiological approaches-and surgical treatment and results.

Acoustic neurinoma in the elderly: factors predictive of postoperative outcome.

The authors present the results of acoustic neurinoma surgery in 61 elderly patients (age, > or = 65 years). All the patients were operated upon via the lateral suboccipital approach. Complete tumor removal was achieved in all but two patients. There was no operative mortality. Fifty-seven patients (93%) were independent of nursing assistance at the time of discharge from the hospital. Preservation of the facial nerve was achieved in 95% of the patients, and hearing was preserved in 41%. A risk analysis identified three factors exerting a significant influence on the outcome in these cases: the American Society of Anesthesiology score, the preoperative Karnofsky score, and the size of the tumor. The patients' age was not correlated with the postoperative outcome. These results suggest that, in the majority of elderly patients with acoustic tumors, complete tumor removal can be achieved safely and with minimal postoperative morbidity. Preoperative clinical, neurological, and radiological factors can be helpful in the selection of patients for surgical treatment and may predict postoperative outcome.

Management of vestibular schwannomas (acoustic neuromas): radiological features in 202 cases--their value for diagnosis and their predictive importance.

OBJECTIVE: Tumor-induced bony and soft tissue findings might reflect, in part, the biological characteristics of vestibular schwannomas and could predict clinical findings. In addition, the role of the individual anatomic conditions of the posterior fossa is of interest to the surgeon. METHODS: Of 1000 vestibular schwannomas treated surgically at the neurosurgical department at Nordstadt Hospital, 202 cases, which were consecutively investigated at the same computed tomography (CT) unit and using the same technique (high-resolution CT at bone windows before and after surgery, contrast-enhanced high-resolution CT before surgery, and native high-resolution CT after surgery), were evaluated for special radiological features. Evaluation included, in 103 cases, anatomic parameters of the petrous bone and posterior fossa cavity and, in 202 cases, tumor-induced changes of bony structures, tumor relations with bony structures and with neural structures, and postoperative findings of bony structures and of neural tissues. These radiological parameters and the related clinical pre- and postoperative findings were transferred to a database for statistical evaluation of their positive or negative correlations, i.e., for their reliability in diagnosis and their importance in predicting postsurgical outcome. RESULTS: As important parameters, the following could be identified. The length of the posterior auditory canal wall and the interear difference of the maximum porus width both correlate with the degree of preoperative hearing deterioration (P < 0.05). The extent of the widening of the internal auditory canal is of predictive importance for the chances of postoperative hearing preservation or hearing loss (P < 0.01). The extent of tumor growth anterior and caudal to the internal auditory canal in large tumors is of significant importance for prediction of postoperative hearing function (P < 0.05). The tumor extension in all directions and the extent of cystic tumor components correlate with the pre- and postoperative function of the facial and cochlear nerves. The positions of the labyrinthine structures and their geographical relations to the fundus and the sigmoid sinus and, thereby, to the suboccipital route, enable reliable calculations of the danger of labyrinthine destruction and help improve the planning of the surgical strategy. DISCUSSION AND CONCLUSIONS: In addition to the importance for surgical planning, preoperative bone window CT and contrast-enhanced images offer the opportunity to identify traits of tumor biology, such as bony destruction of the internal auditory canal, tumor shape and cyst formation, and aspects with predictive importance for postoperative outcome. The average size for hearing preservation in tumors was 14.5 x 16.5 x 11.8 mm (coronal x sagittal x axial). The recent finding (8) of a higher presentation age in female patients has an apparently anatomic basis, which is a relatively larger internal auditory meatus.

Management of vestibular schwannomas (acoustic neuromas): auditory and facial nerve function after resection of 120 vestibular schwannomas in patients with neurofibromatosis 2.

OBJECTIVE: Vestibular schwannomas (VSs) affect young patients with Neurofibromatosis 2 (NF-2) and cause very serious problems for hearing, facial expression, and brain stem function. Our objective was to determine a therapy concept for the right timing and indication of neurosurgical therapy. METHODS: In 1000 consecutive VS resections, 120 tumors in 82 patients with NF-2 were surgically treated by the same surgeon (MS) at the Department of Neurosurgery at Nordstadt Hospital from 1978 to 1993. The mean age of the patients was 27.5 years. Sixty tumors were surgically treated in 41 male patients, and 60 tumors were surgically treated in 41 female patients. Bilateral tumor resection was performed in 38 patients (76 operations, after previous partial surgery in 15 cases elsewhere), and unilateral operations were performed in 44 patients, 5 of whom had undergone ipsi- or contralateral surgery that was performed elsewhere. The operative and clinical findings are evaluated and compared with the data of patients without NF-2. RESULTS: In 105 cases, complete tumor resections were achieved. In 15 cases, deliberate subtotal resections were performed. These were for brain stem decompression in 4 cases and for hearing preservation in the last hearing ear in 11 cases, with successful preservation in 8 of the 11. Pre- and postoperative hearing rates were higher in male than in female patients (70% in male versus 65% in female patients before surgery and 40.5 versus 31%, respectively, after surgery). Hearing was preserved in 29 of 81 ears (36%). The rate of preservation was 24% in cases of large tumors and 57% in cases of small tumors (<30 mm). Twenty-one of 82 patients (26%) were bilaterally deaf before surgery. Twenty-five patients had uni- or bilateral hearing after surgery (i.e., 41 % of those with preoperative hearing or 30.5% of the whole group). Anatomic facial nerve preservation was achieved in 85%. The facial nerve was reconstructed intracranially at the cerebellopontine angle by sural grafting in 17 cases and by hypoglossal-facial reanimation in 5. Two deaths occurred 1 and 3 months postsurgically as a result of malignant tumor growth with brain stem dysfunction and respiratory problems. In summary, for patients with NF-2, the presentation ages are lower, tumor progression is faster, the chances of anatomic and functional nerve preservation are lower, the chances of good outcomes are best when surgery is performed early and when there is good preoperative hearing function, and the danger of sudden hearing loss is higher. The chances and danger often differ from side to side among individual patients. CONCLUSION: The indication and the timing of tumor resections are in some respects different from normal VS handling and are dependent on the tumor extension and related necessity of brain stem decompression and on the auditory function. As an optimal goal, completeness of resection with functional cochlear nerve preservation is formulated, and as an acceptable compromise, subtotal microsurgical resection with functional cochlear nerve preservation in the last hearing ear is suggested.

Microendoscopy of the internal auditory canal in vestibular schwannoma surgery.

Intraoperative microendoscopy was performed for eight patients to access the fundus of the internal auditory canal after retrosigmoid transmeatal surgery of vestibular schwannomas. The transmeatal procedure is usually limited laterally by the labyrinth block. The restricted opening of the internal auditory canal bears a potential risk of incomplete tumor resection. For eight patients with vestibular schwannomas, intraoperative microendoscopy was performed after tumor resection to expose the "blind" area of the internal auditory canal fundus. An excellent view of the fundus contents was obtained, including Cranial Nerves VII and VIII and the crista transversa. Tumor remnants were not observed in this series. Microendoscopy was shown to be an ideal adjunct to hearing-preserving transmeatal surgery of vestibular schwannomas, enabling the removal of intracanalicular tumors with direct control of the lateral intracanalicular nerve portions.

Impact of computed tomographic and magnetic resonance imaging findings on surgical outcome in petroclival meningiomas.

OBJECTIVE: The preoperative radiological findings of computed tomographic and magnetic resonance imaging scans of 70 patients with petroclival meningioma were evaluated and statistically compared with the degree of surgical resection and patients' outcomes to depict the most important radiological findings that may influence surgical radicality and outcome. METHODS: The following parameters were evaluated: 1) tumor diameters; 2) tumor extension toward the middle fossa, the internal auditory canal, the brainstem, and the foramen magnum; 3) bone changes; 4) peritumoral edema; 5) signs of tumor infiltrative pattern; and 6) surgical radicality. Postoperative results were analyzed immediately after the surgery and in a long-term follow-up study. RESULTS: Larger tumors affected a younger population and presented a significantly shorter time until symptom onset. In the majority of cases (67%), the tumor extended to the parasellar region. Tumor extension toward the jugular foramen was found in 24% of the patients and reached the level of the foramen magnum in 18%. Irregular tumor margins were found in 67% of the tumors, and 50% of them presented peritumoral edema in addition. Interestingly, edema also was found in 20% of tumors with well-delineated margins. CONCLUSION: Tumor size, brainstem compression, and tumor extension laterally to the internal auditory canal did not influence either the degree of surgical resection or the long-term outcome (P > 0.05). Supratentorial tumor extension to the middle fossa and downward involving the caudal cranial nerves displayed a significant importance in regard to the surgical radicality and the patient's outcome, respectively (P < 0.05). Radiological evidence of infiltrative tumor pattern and peritumoral edema at the brainstem surface were important parameters regarding surgical radicality (P < 0.05). However, only peritumoral edema influenced the long-term results significantly.

Surgical management of meningiomas originating in Meckel's cave.

OBJECTIVE: To define the difference of meningiomas that originate in the area of Meckel's cave (MC) (primary MC meningiomas) in regard to the different surgical approaches and postoperative results. METHODS: A retrospective analysis of all meningiomas involving the cranial base displayed 21 cases of meningiomas originating in MC (primary MC meningiomas). These cases were classified according to the tumor extension in four different types: Type I, tumors mainly confined to MC; Type II, MC meningiomas with extension into the middle fossa; Type III, MC meningiomas with extension into the posterior fossa; and Type IV, MC meningiomas with extension into both middle and posterior fossae. RESULTS: Trigeminal neuralgia resolved in all cases in this series, despite tumor type. Trigeminal hypesthesia showed postoperative improvement only in Type III MC meningiomas. In Types I and III, total removal without further morbidity was frequently achieved. Cavernous sinus infiltration, especially in Types II and IV, limited (in some cases) the extent of tumor extirpation. CONCLUSION: Types I, II, and III MC meningiomas have a good prognosis. In most cases, very good outcomes are achieved. Radical tumor removal can usually be achieved without further morbidity and with postoperative improvement of the preexisting symptoms, especially in Types I and III MC meningiomas. On the contrary, Type IV MC meningiomas are usually only subtotally resected. Surgery in such cases may carry a high risk of additional morbidity, especially with regard to the IIIrd, IVth, and VIth cranial nerves. The postoperative outcome regarding facial pain in cases of all tumor types is usually very good. Trigeminal hypesthesia may persist after tumor removal in the majority of cases.