Manfred Weidenbecher

Olfactory neuroblastoma: The University Of Erlangen–Nuremberg experience 1975-2000

OBJECTIVE: Olfactory neuroblastoma constitutes a rare and, in clinical terms, biologically variable tumor of the nasal cavity, paranasal sinuses, and the base of the skull and presents a challenge to a modern multidisciplinary therapy. Generally acknowledged prognostic factors and a standard therapy fail to exist. METHODS: Between 1975 and 2000 we diagnosed and treated 26 patients with an olfactory neuroblastoma. According to Kadishs classification, 1 patient (4%) showed stage A, 16 patients (53%) stage B, and 11 cases (43%) stage C. Hyams grading was established in 81% of all cases. Fifty-two percent were thus classified as low-grade and 48% as highgrade tumors. Surgical therapy was performed on 23 patients (88.5%), surgery being the exclusive form of therapy (monotherapy) in 5 of these patients. Combined therapy was carried out in 18 cases (surgery, radiotherapy, chemotherapy). RESULTS: Currently, 16 of 26 treated patients (61.5%) are alive. The disease-specific 10- and 15-year survival determined according to Kaplan-Meier is 76.2%. Fifteen-year survival amounts to 86.7% for smaller tumors (Kadish A/B) and 63.6% for advanced tumors (Kadish C). Seven (26.9%) of the overall group of treated patients developed a recurrence. Salvage therapy was successful in 60% (3 of 5 patients). Fifteen-year survival following salvage therapy amounts to 60%. Patients with highgrade tumors exhibit a significantly reduced 10-year survival (40%) compared to patients with low-grade tumors (100%). CONCLUSIONS: The therapy of olfactory neuroblastoma calls for an interdisciplinary multimodal therapeutic strategy, particularly in the case of advanced tumors. Tumor staging and histopathologic grading according to Hyams are important factors for survival and prognosis. Aggressive salvage therapy can lead to a distinct improvement of long-term survival. (Otolaryngol Head Neck Surg 2004; 130:567-74.)

Squamous cell carcinoma of the oropharynx: Ki-67 and p53 can identify patients at high risk for local recurrence after surgery and postoperative radiotherapy

PURPOSE To assess the prognostic value of biologic (p53, Ki-67) and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). METHODS AND MATERIALS Between 1985 and 1995, a total of 102 patients with 104 tumor sites were entered onto the study. Fifty-five primary tumors (53%) involved the tonsils, 26 (25%) the soft palate, and 23 (22%) the base of the tongue. Median age was 53 years (range 36-80 years). The clinical T- and N-categories (UICC 1997) were: T1 (30), T2 (47), T3 (22), T4 (5), N0 (33), N1 (28), N2 (42), and N3 (1). Histologically-clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given, to a total of 60 Gy in 6 weeks, and single daily fractions of 2 Gy. The expression of the nuclear p53- and Ki-67-labeling index (LI) was investigated by immunostaining using the monoclonal antibodies DO-7 and MIB 1. The nuclear p53-intensity (p53-I) was graded into 4 categories (0/+/++/) by densitometry. Median follow-up was 43 months (range 14-132 months). RESULTS Cancer-specific survival, disease-free survival, and locoregional tumor control rates were 74%, 69%, and 75%, respectively, at 5 years. Significant prognostic factors for disease-free survival were: T-category (T1/2: 77% vs. T3/4: 53%, p = 0.02), tumor site (tonsils: 79% vs. soft palate: 70% vs. base of tongue: 45%, p = 0.05), duration of RT (< or = 46 days: 80% vs. > 46 days: 60%, p = 0.04), Ki-67 LI (< or = 20%: 84% vs. > 20%: 49%, p = 0.006) and p53-I (0/+: 56% vs. ++/ : 79%, p = 0.008). A significant prognostic impact on locoregional control was noted for the duration of RT (< or = 46 days: 86% vs. > 46 days: 68%, p = 0.01), tumor site (tonsils: 88% vs. soft palate: 67% vs. base of tongue: 51%, p = 0.02), Ki-67 LI (< or = 20% LI: 87% vs. > 20% LI: 56%, p = 0.018), and the p53-I (0/+: 58% vs. ++/ : 88%, p = 0.0006). On multivariate analysis, the p53 nuclear intensity (p = 0.002) and the Ki-67 index (p = 0.01) remained the only significant factors for locoregional control. CONCLUSION Ki-67 labeling index above 20% and a weak p53 nuclear intensity (0/+) are both able to identify patients with squamous cell carcinoma of the oropharynx being at high risk for local recurrence after surgery and postoperative RT. Consequently, in this subgroup an intensification of treatment may be contemplated in prospective trials.

Cranial Nerve and Hearing Function after Combined-Approach Surgery for Glomus Jugulare Tumors

In this retrospective study, oncologic and functional results of 46 patients treated for glomus jugulare tumor are reported. The standard surgical approach was the combined transmastoid-transcervical approach, modified according to the individual tumor growth, and eventually combined with a transtemporal or a suboccipital approach. Complete tumor removal resulted in a cure rate of 90%. New-onset cranial nerve palsies developed in less than 22% of patients. In 54% of cases it was possible to retain middle ear function. From a total of 12 patients with incomplete tumor removal and postoperative irradiation, progressive tumor growth was noted in 4 patients, and was controlled by salvage irradiation or surgery. Radical tumor removal by ablative surgery can be modified by efforts to reduce mutilating resections. In their place, individually tailored and combined multidirectional surgical approaches may allow total tumor removal with lower morbidity.

Chronic mechanical trauma in the aetiology of oro-pharyngeal carcinoma

Tumours of the oral cavity and the oropharynx account for 12% of the malignancies in our patient material. The group of patients included a high percentage of smokers (83%), heavy drinkers and persons neglectful of oral hygiene. The majority of the patients mainly male were labourers or (small) farmers. In contrast to other reports in the literature, chronic mechanical trauma due to sharp remaining teeth, less than ideal fillings, badly fitting dentures or unsuitable denture-bearing tissue, and loose anchoring attachments were frequently present. Commensurate with the clinical findings, permanent damage to the covering squamous epithelium was demonstrated histologically. In addition to all forms of inflammation, parakeratosis and hyperkeratosis, dysplasia, including carcinoma in situ, and manifest carcinomas also presented. Surface-inert dentures and regular oral hygiene must therefore be considered an important requirement for the prevention of oral-cavity carcinoma.

Nasopharynxkarzinom: Nur Bestrahlung oder simultane Radiochemotherapie?

Hintergrund: Von 1979 bis 1997 wurden an den Kliniken der Universität Erlangen insgesamt 92 Patienten wegen eines primären Nasopharynxkarzinoms behandelt. Bis 1988 war die Therapie der Wahl die alleinige Bestrahlung, danach wurde die Radiotherapie durch eine simultane cisplatinhaltige Chemotherapie ergänzt. Ziel dieser Untersuchung war es zu klären, ob durch die Kombinationsbehandlung ein Überlebensvorteil für die Patienten entsteht. Außerdem sollten Prognosefaktoren für das tumorspezifische Gesamtüberleben, die lokoregionäre Tumorkontrolle und das metastasenfreie Überleben evaluiert werden. Patienten und Methodik: 53 Patienten (58%) erhielten eine alleinige Strahlentherapie und 39 Patienten (42%) eine simultane Radiochemotherapie mit zwei Kursen 5-Fluorouracil und Cisplatin. Die Gesamtdosis am zervikalen Lymphabflußgebiet war im Median 60 Gy (Spanne 50 bis 62 Gy), am Primärtumor 74 Gy (Spanne 56 bis 88 Gy). Die mediane Nachbeobachtungszeit der noch lebenden Patienten betrug 8 Jahre. Ergebnisse: Nach der simultanen Radiochemotherapie betrug die Fünf-Jahres-Überlebensrate 67%, nach der alleinigen Bestrahlung 48% (p=0,06). Frauen hatten eine deutlich bessere Prognose als die männlichen Patienten (Fünf-Jahres-Überlebensrate 77% vs. 44%, p=0,01). Lag ein Hirnnervenausfall vor, so waren nach fünf Jahren alle Patienten am Tumor verstorben, während beim Fehlen einer neurologischen Symptomatik die Überlebensrate 61% war (p=0,01). Das fernmetastasenfreie Überleben nach fünf Jahren wurde vom Lymphknotenstatus (N0: 82% vs. N1 bis N3: 68%; p=0,04), dem Geschlecht (Frauen 88% vs. Männer 64%; p=0,01), der Therapiemodalität (Strahlentherapie: 63% vs. Radiochemotherapie: 86%; p=0,02) und vom Hirnnervenausfall (42% mit vs. 76% ohne; p=0,04) beeinflußt. Schlußfolgerung: Die simultane Radiochemotherapie bringt gegenüber der alleinigen Strahlentherapie eine Reduktion der Fernmetastasen und eine Verbesserung des Gesamtüberlebens. Da die chronische Toxizität beider Behandlungsstrategien gleich ist und die etwas verstärkten Akutnebeneffekte der Radiochemotherapie mit einer Standardsupportivtherapie zu beherrschen sind, kann die primäre Radiochemotherapie als Behandlung der Wahl des Nasopharynxkarzinoms empfohlen werden.Background: Between 1979 and 1997, a total of 92 patients with primary nasopharyngeal carcinoma were treated at the Hospitals of the University of Erlangen. Until 1988, radiotherapy alone was the treatment of choice and simultaneous radiochemotherapy was consistently applied thereafter. This retrospective analysis was performed to evaluate the influence of concurrent radiochemotherapy on survival and to identify possible prognostic factors on cause-specific survival-, locoregional tumor control- and distant-metastases-free survival rates. Patients and Methods: Fifty-three patients (58%) received treatment by radiotherapy alone and 39 (42%) underwent primary radiochemotherapy with 2 courses of 5-FU and cisplatin. Median total dose to the bilateral neck region was 60 Gy (range, 50 to 62 Gy), and 74 Gy (range, 56 to 88 Gy) to the primary tumor. Median follow-up of the surviving patients was 8 years. Results: Following radiochemotherapy and radiotherapy alone, the 5-year-survival rates were 67% and 48%, respectively (p=0.06). Female patients had a survival advantage as compared to male patients (5-year-survival rate 77% vs. 44%, p=0.01). Patients with and without cranial nerve palsy at presentation had survival rates of 0% and 61%, respectively, at 5 years (p=0.01). Distant-metastases-free survival was influenced by the following factors: lymph-node involvement (N0: 82% vs. N1 to N3: 68%, p=0.04), gender (female: 88% vs. male: 64%, p=0.01), type of treatment (radiochemotherapy: 86% vs radiotherapy: 63%, p=0.02) and cranial nerve involvement (76% without and 42% with involvement, p=0.04). Conclusion: In primary nasopharyngeal carcinoma simultaneous radiochemotherapy can significantly reduce distant metastases and improve survival as compared to radiotherapy alone. Since late toxicity rates were similiar in both treatment groups and the slightly increased acute side effects following radiochemotherapy were effectively compensated by standard supportive care, patients with advanced nasopharyngeal carcinoma may benefit from simultaneous radiochemotherapy.

Funktionserhaltende Chirurgie von Glomus-jugulare-Tumoren Ein realisierbares Ziel?

ZusammenfassungEine radikale Entfernung ausgedehnter Glomus-jugulare-Tumoren hinterläßt häufig schwere Einschränkungen durch Lähmungen der kaudalen Hirnnerven und die Obliteration des Mittelohrs. Die Operationsstrategie der Erlanger HNO-Klinik setzte sich zum Ziel, die postoperative Morbidität zu senken, und gleichzeitig die Sicherheit der Tumorkontrolle zu erreichen. Die vorliegende Untersuchung stellt die onkologischen und funktionellen Resultate retrospektiv an 24 Patienten mit Glomus-jugulare-Tumoren der Größen C und D dar. Der mittlere Nachbeobachtungszeitraum betrug 3,7 Jahre. Als Standardmethode der Operation diente der transmastoidale-transzervikale Zugangsweg, der je nach Wachstum des Tumors modifiziert und gegebenenfalls mit einer transtemporalen Freilegung des Felsenbeins oder mit Hilfe eines retrosigmoidalen Zugangs kombiniert wurde. Präoperativ wurde eine superselektive Embolisation, soweit möglich, ausgeführt. Eine Ergänzung mit postoperativer Strahlentherapie erfolgte in 7 Fällen. Eine Heilungsrate von 100% wurde nach vollständiger Entfernung des Tumors mit Hilfe eines multidirektionalen Vorgehens erzielt. Bei 38% dieser Patienten traten postoperativ neue Hirnnervenlähmungen auf. In 54% der Fälle konnten ein normal konturierter äußerer Gehörgang und das Mittelohr entweder erhalten oder rekonstruiert werden. Residualtumore mußten in 2 Fällen nach inkompletter Resektion und postoperativer Radiotherapie beobachtet werden. Die individuelle Anpassung des chirurgischen Vorgehens erlaubt eine funktionsschonende Therapie ausgedehnter Glomus-jugulare-Tumore. Die entsprechend der Tumorausbreitung gewählten Zugangswege und operativen Schritte gestatten vollständige Tumorresektion mit minimierter Morbidität.SummaryIn this retrospective study, oncologic and functional results of 24 patients treated for glomus jugulare tumor stages C and D are reported. The surgical approach used was a combined transmastoid-transcervical approach, which was modified according to individual tumor growth. As needed, this was combined with a transtemporal or retrosigmoid approach. Complete tumor removal resulted in a cure rate of 100%. Surgically induced cranial nerve palsies developed in 38% of the patients. In 54% of cases it was possible to retain middle ear function. Seven patients had incomplete tumor removal requiring postoperative irradiation, with tumor progression occurring in 2 patients. Radical tumor removal was modified by efforts to reduce mutilating resections. These results show that individually tailored and combined multidirectional surgical approaches can allow total tumor removal to be performed with lower morbidity.

Meatoplastik mit allogenem, konserviertem Knorpel. Histomorphologische Modellstudie im Tierexperiment

SummaryThe reconstruction of the posterior wall of the external acoustic meatus destroyed by surgery or a cholesteatoma is necessary for the complete restoration of function. For this purpose, allogen cartilage preserved in thiomersalate has been transplanted on the anterior wall of the air-containing mastoid bone in 160 clinical cases. The histomorphological reaction of the recipient to unilaterally uncovered transplant material has previously been unknown. In 10 guinea pigs, 15 fenestrated bullae (hypotympanum equivalents) were closed with cartilage transplants fixed in place with tissue adhesive. After a period varying between 7 1/2 and 11 months, the walls of the bullae with the transplant were then examined histomorphologically. Despite the variations in the period in situ, the avital cartilage transplant, which remained largely constant in volume and shape, was always to be found. It was tolerated without reaction and was “enveloped” — also on the primarily uncovered surface — by a capsule of bone and connective tissue. In no case was rejection observed. Marked foreign-body reaction was, however, found in the vicinity of the tissue adhesive, which was absorbed only slowly.The clinically well-known tissue-compatible and complicationfree behaviour of the allogenic cartilage transplant preserved in thiomersalate, is thus explained by the histomorphological findings. In contrast, the fact that marked foreign-body reaction was demonstrable even after almost one year, suggests that tissue adhesive should not be used.

Recurrent basal cell carcinoma of the facial region — a clinico-pathological challenge

SummaryThe observation that the majority of patients with basal cell carcinomas of the face presenting for surgical treatment did previously have radiotherapy or have undergone inadequate excision due to cosmetic considerations of the surgeon, induced us to review our own case material. According to this reassessment, a concept of radical removal was developed which took particular account to the direction of growth of basal cell carcinoma into the depth. Of considerable importance seems to be the unequivocal marking of the excised material prior to its histological work up and the additional removal of sub-focal specimens for separate histological examination.

Beschwerden und funktionelle Ausfälle nach radikaler Neck-dissection Spätergebnisse

SummaryIn 200 patients with uni- or bilateral neck dissection the long range cosmetic results, subjective complaints, and the neurologic status were studied at postoperative time intervals between 3 months and 10 years. The main disorders were related to both the absence of resected, tumorinvolved structures and to hyperesthesia of the lateral neck skin.The function of the muscle portions of the shoulder was less disturbed than being expected, and recovered with some time.Cases with bilateral neck dissections showed postoperative edema of the head, being resorbed, with a little persisting submental edema.Postoperative irradiation gave rise to an increasing number of neuralgiform symptoms.

Malignant tumors of the anterior cranial skull base

Malignant tumors of the anterior cranial skull base are still a challenge for radical surgical treatment. Several different techniques and approaches have been developed over the years and the results, with mortality rates over 50%, are still not encouraging.Here we present our results of an interdisciplinary, onestage, neurohino transfronto-transbasal surgical approach in twelve patients with such tumors.The long-term survival rate in our patients is now 83% with a mean postoperative follow-up of 19.3 months. Two patients died due to early recurrencies and metastasis after 10 and 13 months after initial treatment and postoperative irradiation.Another five patients with a follow-up of 34.2 months have had tumor recurrencies diagnosed at 19.5 months postoperatively. These patients have survived their recurrent tumor for 14.7 months.Five patients, 41% of the whole group, have been living without evidence of tumor recurrence for between 2 and 35 months.