A new therapy concept in esthesioneuroblastoma

BACKGROUND: We introduce a new concept in treatment of esthesioneuroblastomas, developed in the University Medical School of Graz, Austria. PATIENTS AND METHODS: Six patients suffering from esthesioneuroblastoma have been treated in the years 1993-1999; five of them with a curative aspect, one with a palliative one. Three tumours were classified according to Kadish as stage B, three as stage C. The selection criteria included tumours without deep infiltration into the orbit nor into the pterygopalatine fossa and without any involvement of the posterior wall of the frontal sinus. The treatment consists of endoscopic nasal and paranasal sinus surgery and consecutive stereotactic radiosurgery by means of the Gamma-Knife unit. RESULTS: Over an average follow-up period of 38 months all patients remained free of disease. Because of the minimally invasive character of our concept the complications and side effects are minimised and the patients are less traumatised in comparison to conventional treatment such as craniofacial resection or irradiation. CONCLUSION: Due to the excellent outcome of our six patients we recommend this new treatment concept, in selected cases, as an alternative to the usual therapeutic modalities for esthesioneuroblastoma.     

Long-term carcinologic results of advanced esthesioneuroblastoma: a systematic review

Surgical resection followed by radiotherapy can be considered like the optimal treatment modality for limited esthesioneuroblastoma. However, therapeutic management of locally advanced tumors remains a challenge. The aim of our study was to access and compare the oncologic results of the different treatment modalities in advanced esthesioneuroblastoma. We performed a systematic review using the Medline, and Cochrane database in accordance with PRISMA criteria and included all the cases of advanced esthesioneuroblastoma published between 2000 and 2013. We also retrospectively included 15 patients with an advanced esthesioneuroblastoma managed at our tertiary care medical center. Long-term survival rates defined as the time from diagnosis or randomization to the date of death or last follow-up were evaluated for each treatment with Kaplan–Meier survival curve analyses. 283 patients have been included. The mean follow-up was 78 months. Five-year highest survival rates were obtained in patients treated by surgery associated with radiotherapy. Ten-year highest survival rates were obtained in patients treated by the association of surgery, radiotherapy and chemotherapy (p = 0.0008). Within the surgical group, 5-year highest survival rates were obtained in patients treated by endoscopic resection (p = 0.003). Surgical resection combined with radiotherapy offers the gold standard of care. Adjuvant chemotherapy seems to improve the long-term survival in patients with locally advanced esthesioneuroblastoma. Endoscopic resection in advanced tumors should be discussed on a case-by-case basis.     

Metastatic esthesioneuroblastoma. Challenge in interdisciplinary combined modality therapy

Esthesioneuroblastoma is a rare tumor, which in many cases is diagnosed at an advanced stage with an high recurrence rate and incidence of metastases. Regionary metastases predict a poor prognosis. There is no standard therapy approach for these tumors. The most widly accepted primary therapy is radical craniofacial enbloc resection followed by radiation therapy. Today chemotherapy is getting more important and is administered with curative intention. Multidisciplinary management results in significantly longer survival in advanced tumor stages and recurrence. A clinical staging system as well as histopathological grading according of Hyams could be from importance for selection and timing of the different therapeutic modalities. We present a case of a 34-year-old female patient who was diagnosed with an advanced olfactory neuroblastoma of the upper nasal cavity with bilateral cervical lymph node metastasis (modified Kadish-stage D). Craniofacial resection and bilateral neck dissection was performed, followed by postoperative radiotherapy. Reviewing the recent literature the different therapeutic approaches are compared and discussed.     

成人嗅神经母细胞瘤20例综合治疗结果分析

目的 回顾性分析与比较20例经综合治疗的嗅神经母细胞瘤患者的生存差异,探讨最佳治疗策略.方法 1998年1月至2005年1月中山大学肿瘤防治中心采用综合疗法治疗了≥14岁的嗅神经母细胞瘤患者20例,6例为Kadish B期,14例为Kadish C期.12例采用诱导化疗联合放疗,8例为手术联合放疗.以Kaplan-Meier法统计患者的生存率和无瘤生存率,采用Log-rank法比较两种治疗方法 的生存率差异,Fisher精确概率法检验其组间均衡性.结果 自治疗开始之日随访至2008年3月31日,20例综合治疗患者3年生存率50.0%.诱导化疗联合放疗组12例的3年生存率和3年无瘤生存率分别为25.0%和16.7%;手术联合放疗组8例的3年生存率和3年无瘤生存率分别为87.5%和75.0%.手术联合放疗组的生存率和无瘤生存率均优于诱导化疗联合放疗组(X2值分别为6.81和7.33,P值分别为0.0091和0.0068).结论 对于中晚期成人嗅神经母细胞瘤,手术联合放疗的疗效可能优于诱导化疗联合放疗,积极手术联合放疗及化疗的综合治疗策略有望进一步改善其生存率.     

嗅神经母细胞瘤误诊原因分析

目的：探讨嗅神经母细胞瘤的误诊原因。方法：回顾分析1993年1月至2004年12月收治的24例嗅神经母细胞瘤的临床资料，主要包括临床诊断、影像学术前诊断、术前术后病理学诊断。结果：24例中男14例、女10例，4．70岁，平均37．92岁，病程10d-19个月，平均6个月。Kadish分期：A期4例，B期7例，C期13例。临床误诊13例（54．16％），分别为鼻息肉5例（20．83％），鼻窦炎3例（12．50％）、淋巴瘤2例（8．33％）、视神经萎缩1例（4．17％）、血管球瘤1例（4．17％）。术前影像与实际不符16例（66．67％）。病理误诊6例（25．00％），分别为胚胎性横纹肌肉瘤2例（8．33％）、原始神经外胚叶肿瘤2例（8．33％）、浆细胞肉瘤1例（4．17％）。病理诊断不明确为小细胞恶性肿瘤1例（4．17％）。结论：对有鼻塞或鼻出血并伴有鼻腔顶部可疑新生物者要警惕本病；CT及MRI显示中心位于鼻腔顶部和筛窦，密度较均匀的大片状组织肿块，侵犯邻近结构（眼眶、颅内），筛板及眼眶内侧壁被侵蚀性破坏，应首先考虑嗅神经母细胞瘤；对临床可疑而初次病理诊断为非本病的病例，应反复取活检并结合形态学特点及免疫组化结果尽早确诊。     

Endoscopic treatment of esthesioneuroblastoma

Esthesioneuroblastoma is an uncommon malignant tumor of the nasal vault. Treatment consists of craniofacial resection. As endoscopic techniques have advanced, this approach has been recommended to avoid morbidity and to reduce costs.AimTo evaluate outcomes in patients with esthesioneuroblastoma treated by an endoscopic technique.MethodsA prospective study of patients diagnosed with esthesioneuroblatoma and treated by an endoscopic technique. The literature over the past 20 years was reviewed for an update on the pathology.ResultsWe present 4 patients, 3 males and 1 female, staged according to Kadish and Dulguerov. All were treated surgically with endoscopic techniques, followed by radiotherapy. One patient was also submitted to neck dissection and chemotherapy because of regional metastasis. There were no significant postoperative complications. The mean hospital stay was 3 days; one patient stayed in the ICU for 24 hours after surgery. Follow-up is recent; so far there are no recurrences.ConclusionEsthesioneuroblastoma is a potentially curable malignancy. Endoscopic techniques help reduce hospital costs and decrease the morbidity. Adequate margins of healthy tissue are obtained with endoscopic resection, as with craniofacial resection. The literature suggests that outcomes after endoscopic resection are similar to those of the conventional external approach.     

Interstitial high-dose-rate-brachytherapy in advanced esthesioneuroblastoma

Esthesioneuroblastoma is a rare neuroectodermal tumor of the nasal vault with an aggressive biological behavior that is characterized by local recurrence, atypical distant metastasis, and poor long-term prognosis. The treatment regimen consists of surgical resection, radiation therapy, and chemotherapy in various, mainly stage-dependent, combinations. We report two cases of primary metastatic and locally recurrent disease, which were treated with computed tomography-guided interstitial high-dose-rate brachytherapy in palliative and curative intent, respectively. Computed tomography-guided interstitial high-dose-rate brachytherapy should be considered as a feasible treatment option for advanced esthesioneuroblastoma.     

Endoscopic removal of esthesioneuroblastoma

Esthesioneuroblastoma is a rare tumor of neural crest origin that arises in the nasal cavity. There is still no consensus on the optimal treatment for this neoplasm, and the literature contains very few accounts of endoscopic excision in these cases. We described a case report of 12-year-old girl with esthesioneuroblastoma that was confined to the nasal cavity and paranasal sinuses, with no orbital or intracranial extension. The tumor was removed via intranasal endoscopic approach and radiotherapy was administered postoperatively. The patient is currently being followed, and there has been no recurrence in 24 months after surgery.     

Endoscopic resection of esthesioneuroblastoma

Esthesioneuroblastoma (olfactory neuroblastoma) is a rare malignant neoplasm originating from neuroepithelial cells. Treatment for this tumor has traditionally required a craniofacial resection through an external approach. The safety and efficacy of transnasal endoscopic resection is uknown. A series of five patients with Kadish stage A or B lesions of the anterior skull base were resected and immediately reconstructed endoscopically over a nine-year period. There were 2 males and 3 females with a mean age of 64 years. Three patients were treated primarily and two were treated secondarily for recurrences after failing a traditional external craniofacial resection and postoperative radiotherapy. All primary lesions received adjuvant radiotherapy. The mean follow-up time was 31 months. All patients were discharged within 4 days or less. Operative complications included temporary postoperative infraorbital anesthesia (1 patient), unplanned cerebrospinal fluid leak (1 patient), and can orbital hematoma (1 patient). None of these complications resulted in any permanent sequelae. Two patients had prolonged nasal crusting for up to one year due to a variety of factors; large cavities, radiation therapy, and exposed lyophilized dural graft. However, all skull base defects healed without any short- or long-term sequelae. There have been no local recurrences. Two patients (1 primary and 1 secondary) developed regional metastasis to the orbit or cervical lymph nodes managed with primary transorbital excision or modified neck dissection, respectively. All but one patient remain free of disease by clinical, endoscopic, and radiographic (CT or MRI) surveillance. The remaining patient recurred distally as an undifferentiated carcinoma in his temporal bone and lungs 12 months after the initial resection. In experienced hands select cases of esthesioneuroblastoma can be safely excised and reconstructed endoscopically with comparable degrees of tissue removal as with external approaches. Short-term oncologic results in this mall series of patients appear to be comparable to traditional methods. Longer follow-up on a larger series of patients is warranted.     

Isolated esthesioneuroblastoma of sphenoid sinus

Esthesioneuroblastoma is a rare neuroendocrine tumor that arises from the olfactory epithelium and accounts for approximately 3% of all intranasal tumors. The tumor involvement in the nasal cavity with extension to paranasal sinuses, orbit, and anterior cranial fossa, is reported in the literature. In this report, we present an interesting case of isolated sphenoid sinus esthesioneuroblastoma, which is the first case to be reported in the literature, and discuss the pathology, clinical manifestations, and various treatment options for this tumor.     

嗅神经母细胞瘤的诊断与治疗

目的探讨嗅神经母细胞瘤的临床特点及诊断治疗方法。方法回顾性分析我科1998~2005年手术切除的8例嗅神经母细胞瘤临床资料,结合文献对其临床表现、诊断和治疗进行探讨。结果本组单纯手术1例,手术 放疗6例,手术 放疗及化疗1例。5例行鼻旁-改良翼点入路,2例行扩大额下硬脑膜外入路,1例行额下入路,均于显微镜下行肿瘤切除。1例于2个月内肿瘤复发,病人拒绝再次手术,于1个月后死亡;2例于1年后肿瘤复发,行放疗控制;1例于3年后肿瘤复发,再次手术并联合放、化疗控制;至今仍有3例存活。结论嗅神经母细胞瘤早期诊断困难。经鼻旁-改良翼点入路联合切除是较理想的手术方式。术后联合放疗或化疗十分重要。     

Diagnosis and management of esthesioneuroblastoma

Esthesioneuroblastoma is an uncommon malignant neoplasm of the nasal vault that in the past was considered benign or low-grade malignant. Surgical approaches in the main were transnasal, with a high recurrence rate and ultimate patient death. With the modern imaging of CT and MRI, should the patient be willing and fit enough, esthesioneuroblastoma currently should be approached using a craniofacial resection. Large tumors should be considered for preoperative chemotherapy and postoperative radiotherapy. Local tumor recurrence is not uncommon and is generally related to the attention to local anatomic dissection. Neck metastases, when they present, should be excised using a modified neck dissection. Distant metastases may present at any time during the course of the disease, generally within 36 months, and may respond to local radiotherapy or systemic chemotherapy. Five-year survival currently appears to be optimized by surgery followed by postoperative radiotherapy and is approximately 65%.     

A case report of esthesioneuroblastoma

Esthesioneuroblastoma (Olfactory Neuroblastoma) arises from the olfactory placode in the olfactory area of the nasal cavity. The age incidence ranges from 3 years to 79 years. It usually presents with nasal symptoms like obstructed nasal breathing and epistaxis. The diagnosis may be delayed for several months due to its slow growing nature. It may be misdiagnosed with other small round cell tumors. One such case is reported here due to its rare incidence, difficulty in early diagnosis and very aggressive behaviour compared to the reported series inspite of recommended treatment by different modalities.     

鼻腔鼻窦嗅神经母细胞瘤的手术径路探讨

目的　总结鼻腔鼻窦嗅神经母细胞瘤 (esthesioneuroblastoma,ENB)的临床经验。方法　对Fulda医院耳鼻咽喉 头颈及面部整形外科 1 988年 7月～ 2 0 0 1年 1 2月经治的 1 7例ENB的临床资料、手术治疗的径路、方法及预后进行回顾性分析。结果　据Morita等的临床分期标准 ,1 7例中A期1例 ,B期 6例 ,C期 9例 ,D期 1例。术后 8～ 1 63个月 (平均 44个月 )的随访观察结果表明 :2年既无复发、亦无转移的总生存率 90 90 % (1 0 / 1 1 ) ,其中A期为 1 / 1、B期为 6/ 6、C期为 3/ 3、D期为 0 / 1。所有经鼻内径路手术的 6例患者至今均存活 ,临床和影像学检查都无复发和转移迹象 ,存活最长者已达1 30个月 ;2例经额下径路手术的C期患者在随访的 8、2 7个月内均未发现复发和转移 ;经面正中掀翻径路手术的B、C期患者各 1例已分别存活 1 63个月和 82个月 ,均无复发和转移。 6例在此观察期间死于ENB :其中C期 5例、D期 1例 ;Ⅱ级 1例、Ⅲ级 1例、Ⅳ级 3例 (另 1例未行分级诊断 )。 1例 (C期/Ⅱ级 )于ENB术后 7年死于星形细胞瘤 ,此间一直无ENB复发。结论　联合应用手术和放射治疗ENB的效果最佳。前颅底恶性肿瘤的手术治疗径路选择应按照以下原则 :若病变组织没有浸润至颅内或眶内 ,采用鼻内径路 ;若肿瘤主要向侧向生长已     

Patterns of failure and outcome in esthesioneuroblastoma

OBJECTIVES: To evaluate the results of standardized treatment of esthesioneuroblastoma (ENB) during a 17-year period and to identify pertinent factors for clinical outcome. DESIGN: Review of clinical and radiographic data and retrospectively staging ENB according to 3 staging systems: Kadish, Biller, and Dulguerov and Calcaterra. SETTING: Hospital do Cancer I-Instituto Nacional de Cancer, Rio de Janeiro, Brazil. PATIENTS: Thirty-six patients with histologically confirmed ENB treated between January 1, 1983, and December 31, 2000; 35 fulfilled study inclusion criteria. INTERVENTIONS: Treatment included gross tumor resection through a transfacial approach with postoperative radiotherapy (RT) in 11 patients, craniofacial resection (CFR) and postoperative RT in 7, exclusive RT in 14, CFR alone in 1, and a combination of chemotherapy and RT in 2. Histopathological slides were reviewed and graded using the Hyams staging system. Analysis of prognostic factors was performed. MAIN OUTCOME MEASURES: Evaluation of survival rates using the Kaplan-Meier method. Analysis of prognostic factors carried out with the Fisher exact test and the log-rank test. RESULTS: Analysis of survival showed that the Kadish classification best predicted disease-free survival (P =.046). The presence of regional and distant metastases adversely affected prognosis (P<.001 and P =.01, respectively). Craniofacial resection plus postoperative RT provided a better 5-year disease-free survival rate (86%) compared with the other therapeutic options used (P =.05). The 5-year disease-specific survival rate was 64% and 43% for the low- and high-grade tumors, respectively (P =.20). Disease-free survival for this cohort of 35 patient was 46% and 24% at 5 and 10 years, respectively. Overall survival was 55% and 46% at 5 and 10 years of follow-up, respectively. CONCLUSIONS: The development of cervical nodal metastases and distant metastases had a significant adverse impact on prognosis. The value of the Kadish staging system was confirmed in our study, significantly correlating with prognosis. Tumor grade according to the Hyams staging system also seems to be an important factor in determining prognosis for tumor recurrence and survival. Aggressive multimodality therapeutic strategies, particularly CFR and adjuvant RT, yielded the best treatment outcome.     

鼻腔鼻窦嗅神经母细胞瘤的手术径路探讨

目的 总结鼻腔鼻窦嗅神经母细胞瘤(esthesioneuroblastoma，ENB)的临床经验。方法 对Fulda医院耳鼻咽喉-头颈及面部整形外科1988年7月-2001年12月经治的17例ENB的临床资料、手术治疗的径路、方法及预后进行回顾性分析。结果 据Morita等的临床分期标准，17例中A期1例，B期6例，C期9例，D期1例。术后8～163个月(平均44个月)的随访观察结果表明：2年既无复发、亦无转移的总生存率90.90％(10／11)，其中A期为1／1、B期为6／6、C期为3／3、D期为0／1。所有经鼻内径路手术的6例患者至今均存活，临床和影像学检查都无复发和转移迹象，存活最长者已达130个月；2例经额下径路手术的C期患者在随访的8、27个月内均未发现复发和转移；经面正中掀翻径路手术的B、C期患者各1例已分别存活163个月和82个月，均无复发和转移。6例在此观察期间死于ENB：其中C期5例、D期1例；Ⅱ级1例、Ⅲ级1例、Ⅳ级3例(另1例未行分级诊断)。1例(C期／Ⅱ级)于ENB术后7年死于星形细胞瘤，此间一直无ENB复发。结论 联合应用手术和放射治疗ENB的效果最佳。前颅底恶性肿瘤的手术治疗径路选择应按照以下原则：若病变组织没有浸润至颅内或眶内，采用鼻内径路；若肿瘤主要向侧向生长已达翼腭窝，采用面正中掀翻径路；肿瘤已浸润至脑组织内，采用额下径路；只对肿瘤已广泛浸润至眶内、须同期行眶内容物剜除的病例采用鼻侧切开径路。