Tissue microarray analysis reveals that cofilin expression is a poor prognostic factor in juvenile nasopharyngeal angiofibroma.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) has a high recurrence rate after surgery. Cofilin overexpression is associated with increased tumor cell metastasis, and progression of various human cancers. However, studies on cofilin expression in JNA are rare. The purpose of this study was to investigate the expression and localization of cofilin in a tissue microarray (TMA) of JNA specimens. In addition, we also analyzed its correlation with clinicopathological features and recurrence. METHODS: Immunohistochemistry was performed to detect cofilin expression in a TMA of samples from 70 JNA patients and 10 control subjects. The association between clinicopathological variables and cofilin immunostaining was analyzed using Pearson's chi-square test. Kaplan-Meier survival analysis was used to calculate the disease-free survival rate, and investigate the effect of cofilin expression on time to recurrence (TTR) in JNA patients. The Cox regression model was used for multivariate survival analysis. RESULTS: Cofilin was detected in irregular smooth muscle cells, pericytes, less differentiated stromal cells, and plump cells, but not in inactive fibroblasts and mature vascular endothelial cells of JNA specimens. The presence of cofilin in JNA was correlated with tumor stage (p = 0.012) and volume of intraoperative hemorrhage (p < 0.001). JNA patients with high cofilin expression had a higher recurrence rate than those with low cofilin expression (p = 0.012). Cofilin expression and patient's age were significant predictors of TTR, and cofilin was a better predictor for disease recurrence (area under the receiver operating curve [AUROC; 0.711; p = 0.005) than other clinicopathological features. CONCLUSION: Cofilin is an independent prognostic marker for JNA patients who have undergone surgical treatment and may represent a novel therapeutic target for extensive JNA.

Management of persistent juvenile angiofibroma after endoscopic resection: Analysis of a single institution series of 74 patients.

BACKGROUND: Management of persistent juvenile angiofibroma (pJA) after transnasal endoscopic resection is controversial. To better understand its behavior, optimize treatment, and minimize morbidity, we report our experience in pJA focusing on follow-up strategies and disease progression. METHODS: A retrospective review of clinical records of all JA cases treated with endoscopic surgery at the Unit of Otorhinolaryngology of the University of Brescia between January 1994 and October 2015 was performed. RESULTS: Seventy-four cases were included. Mean follow-up was 113 months (6-266 months). Evolution of pJA was analyzed in 6 cases. Residual lesion size significantly decreased in 3 cases and 2 lesions did not show size variations; significant growth was detected in 1 case of intentional pJA, with diameter increasing by 2.2 mm/yr. CONCLUSIONS: pJAs may have the tendency to regress spontaneously or remain stable. In selected cases, avoiding treatment of nongrowing pJA in critical areas is a prudent option.

Juvenile nasopharyngeal angiofibroma: vascular determinates for operative complications and tumor recurrence.

OBJECTIVES/HYPOTHESIS: Operative complications and tumor recurrence in juvenile nasopharyngeal angiofibroma (JNA) are measurable and meaningful outcomes. This study aimed to assess the association of these two outcomes to various clinical indices and in particular, vascular determinates. STUDY DESIGN: Retrospective cohort study. METHODS: An 18-year retrospective chart review of an academic tertiary center was undertaken. Data from clinical notes, imaging studies, and arteriograms were analyzed. RESULTS: Thirty-seven male (mean age, 14.4 years) patients were included in the study. Tumor stages included: IA (three), IB (three), IIA (14), IIB (three), IIC (five), IIIA (five), and IIIB (four). Four complications (cerebrospinal fluid leak, cerebral vascular accident, and two transient ocular defects) occurred. Eight recurrences occurred within 24 months following surgery. Complications were associated with estimated intraoperative blood loss (EBL) (P = .045). Tumor recurrence was associated with feeding vessels from the contralateral internal carotid artery (ICA) (P = .017). EBL was significantly associated with surgical technique used. EBL, tumor stage, and tumor vascular supply were significantly associated with each other. CONCLUSIONS: Vascular factors were associated with JNA complication and tumor recurrence. EBL might affect complications, and contralateral ICA as a feeding vessel might affect recurrence. EBL was influenced by procedure choice and was interrelated to size and vascular supply of the tumor. This study bolsters the need to decrease intraoperative blood loss by preoperative embolization and use of endoscopic removal techniques. Furthermore, when branches of the ICA are found to be feeding vessels, greater surgical attention for a dry surgical field is encouraged.

Transnasal endoscopic management of recurrent juvenile nasopharyngeal angiofibroma.

OBJECTIVES: The purpose of this study was to present our experience with definitive endoscopic surgical management of the recurrent juvenile nasopharyngeal angiofibroma. STUDY DESIGN: Retrospective study. SETTING: Tertiary care centre. MATERIALS AND METHODS: This study includes 13 male adolescence patients with recurrent nasopharyngeal angiofibroma who received treatment at our centre between 2005 and 2010. The patient age ranged from 12 to 21 years (mean age, 15.7 years). Endoscopic two surgeons' technique had been used. Follow up MRI every four months. RESULTS: Complete removal of the recurrent tumor was achieved in 10 cases. Three patients had incomplete removal with further recurrences. These recurrences were two in lateral wall of the sphenoid sinus (2 patients), and soft palate (one patient). CONCLUSION: Recurrent JNAs are residual disease resulting from incomplete removal of the primary tumor. Transnasal endoscopic sinus surgery is an effective method for treating recurrent JNA. Follow up is essential and integral point in management of JNAs.

[Surgical treatment of maxillary tumors].

OBJECTIVES: Tumors originating in the maxillary sinus are relativeLy rare. The aim of this article is to review the indications, diagnosis and treatment of patients with maxillary tumors operated at Tel Aviv Sourasky Medical Center during the period 1999 - 2008. METHODS: A total of 174 patients underwent surgery due to neoplasms originating in the maxillary sinus: 118 patients (68%) had malignant and 54 (32%) had benign tumors. RESULTS: The most common malignancy was squamous cell carcinoma (40%), and the most common benign tumor was juvenile nasopharyngeal angiofibroma (36%). A total of 146 patients (84%) underwent partial maxillectomy and 28 (16%) total maxillectomy. In 9 cases, resection was extended to include the eye socket or base of skull, due to tumor invasion. Thirty-five patients had post-operative complications, with local wound infection being the most common complication (n = 12). Among patients with malignant tumors, 75 are alive without disease (67%), 12 (10%) are alive with disease and 31 (23%) died of disease or other causes. CONCLUSIONS: The surgical approach to malignancies of the maxilla is safe and effective. A multidisciplinary team approach is essential to deliver appropriate therapeutic means for these patients.

Juvenile nasopharyngeal angiofibroma: The expanded endonasal approach.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a benign but locally aggressively vascular tumor that may involve the skull base and extend intracranially. Endoscopic excision has become the new standard for smaller tumors but remains a challenge for large tumors, leading some to advocate radiation therapy. We reviewed our experience managing JNA, specifically with respect to utility of the expanded endonasal approach (EEA) for lesions with skull base and intracranial extension. METHODS: All cases of JNA at the University of Pittsburgh Medical Center from 1995 to 2006 were reviewed with respect to tumor size and location, vascular supply and results of embolization, skull base involvement and intracranial extension, surgical approach, blood loss, intraoperative and postoperative complications, and recurrence. RESULTS: Thirty-one cases of JNA were identified. The majority of tumors were completely excised using the EEA, regardless of size or extension into adjacent compartments. Surgical excision of some tumors with intracranial blood supply was staged. Recurrence rates were not associated with extent of tumor or surgical technique. Long-term morbidity was minimal. CONCLUSION: Most JNA, regardless of tumor extent, may be completely excised using EEA alone or in combination with minor sublabial incisions avoiding the morbidity associated with larger open approaches or postoperative radiation therapy.

Juvenile nasopharyngeal angiofibroma: clinical factors associated with recurrence, and proposal of a staging system.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a vascular tumor of the nasopharynx. Our aim is to analyze prognostic factors, report results obtained with radiation therapy and propose a staging system. MATERIALS AND METHODS: Retrospective study of patients with JNA. Clinical, radiological and therapeutic data were assessed for recurrence- and disease free survival-associated prognostic factors. Bivariate and multivariate analyses were performed. RESULTS: Fifty-four males were analyzed. Invasion to anterior infratemporal fossae (ITF) +/or to pterygomaxillary fossae, to posterior infratemporal fossae, or intracranial extension were associated with recurrences in 2 of 15, in 8 of 18, and in 8 of 12 cases, respectively. Tumors < or > or =6 cm were associated with zero and with 18 recurrences, respectively (P = 0.006). A staging system is constructed considering extension patterns and size. Multivariate analyses conferred significance (P = 0.002) to a model including this staging system and surgical margins. CONCLUSION: Our system stratifies recurrence risk and disease-free survival efficiently. Since radiotherapy at young age has potential to induce malignancies, it should be used with caution. It could be considered as primary treatment in stage IV cases with major invasion to cavernous sinus or orbital apex. Therapy design may be improved.

Transbasal approach to skull base tumors: evaluation and proposal of classification.

A clinical study of the TBA was performed in 22 patients harboring tumors of the skull base. The follow-up ranged from 3 to 89 months (average, 30.5 months). The main complications were intracerebral hematoma, ptosis, and infection. One patient died (4.5%) because of an extradural hematoma. Eight patients died during the follow-up because of tumor complications. Among the survivals, the median of the Karnofsky index was 96.4. Based on this study, we propose a classification for the TBA, according to its extension.

Preoperative embolization of hypervascular skull base tumors.

The purpose of the present study is to review the results and complications of preoperative embolization of hypervascular skull base tumors at a neurosurgical center with a team of neurosurgeons cross-experienced in the application of both microsurgery and endovascular techniques. One hundred and twenty-eight endovascular approaches were performed in 66 patients treated for skull base meningiomas (n = 41), paragangliomas of the temporal bone (n = 18), and juvenile nasopharyngeal angiofibromas (n = 7). One death and 2 permanent disabilities were attributable to endovascular therapy. These complications occurred early in our experience (1982-1989) and were related to thromboembolic events rather than complications of transcatheter embolization itself. Our current standard is to perform transfemoral superselective embolizations with either finely corpuscular embolizing substances (PVA particles) or cyanoacrylates (NBCA) under local anesthesia. Using this protocol no embolization-related complications have occurred over the last 9 years. We thus conclude that preoperative embolization of hypervascular skull base tumors can be accomplished safely with the endovascular techniques now available.

Staging and treatment of nasopharyngeal angiofibroma.

To analyze the prognostic value of clinical-radiologic staging, morbidity, mortality and results of treatment used in the Instituto Nacional de Cancerologia, Mexico, a retrospective study of angiofibroma was performed. Charts were reviewed from patients who attended the institute from 1977 to 1993. History and physical examination, rhinoscopy and fiber-optic nasopharyngolaryngoscopy were done in every patient. Radiologic evaluation was done with computed tomography, after which Chandler's staging system was used. Disease-free interval curves were estimated for patients who had presented with stage III or IV tumors. Thirty-one patients were treated with surgery and/or radiotherapy. Most of the patients had stage III (70.9%) or stage JV (25.8%) disease. Surgical procedures included lateral rhinotomies (15 cases), transpalatal dissections (11 cases), transantral degloving (3 cases), median rhinotomies (2 cases), infratemporal transzygomatic dissections (2 cases), frontotemporal craniotomy (1 case) and suprahyoid pharyngotomy (1 case). Radiotherapy (as 3000-5500 cGy) was administered to 16 patients: 7 patients with stage III persistent or recurrent tumor and 8 patients as initial treatment for stage IV disease. The disease-free interval of patients with stage III and IV disease was 80.3% and 19%, respectively, after 36 months of follow-up. Findings demonstrated that surgery was the treatment chosen in patients with stage II and III disease, with low morbidity and mortality, and good results in disease control. In contrast, radiotherapy was usually the treatment in stage IV disease, but had low effectiveness, indicating the need to carefully investigate the value of craniofacial approaches in these tumors.

Juvenile nasopharyngeal angiofibroma: an update of therapeutic management.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor of the nasopharynx composed of fibrous connective tissue and an abundance of endothelium-lined vascular spaces. The name of the disease is derived from the fact that it occurs during adolescence, almost exclusively in boys. METHODS: This study examines the natural characteristics of JNA, the imaging techniques used to diagnose and stage the neoplasm, and the treatment approaches used to manage the disease. RESULTS: Forty-three cases of JNA diagnosed and treated at the University of Texas M. D. Anderson Cancer Center over a 38-year period were reviewed for the study. The cases were divided into two groups, those occurring between 1955 and 1974 and those occurring between 1975 and 1991, to accurately represent the developments in diagnostic and treatment methodology during those time periods. CONCLUSION: The results of our study show that: (1) the imaging techniques used after 1965 (angiography, computed tomography, and magnetic resonance imaging) greatly improve the staging of JNA; (2) morbidity, recurrence, and intraoperative complications decrease when preoperative embolization and skull-based surgical approaches are used; and (3) surgical resection is the most common primary treatment, with chemotherapy and radiotherapy recommended as possible other options.