Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients.

BACKGROUND: Nowadays, 65-80% of pheochromocytoma and paraganglioma (PPGL) cases are explained by germline or somatic mutations in one of 22 genes. Several genetic testing algorithms have been proposed, but they usually exclude sporadic-PPGLs (S-PPGLs) and none include somatic testing. We aimed to genetically characterise S-PPGL cases and propose an evidence-based algorithm for genetic testing, prioritising DNA source. METHODS: The study included 329 probands fitting three criteria: single PPGL, no syndromic and no PPGL family history. Germline DNA was tested for point mutations in RET and for both point mutation and gross deletions in VHL, the SDH genes, TMEM127, MAX and FH. 99 tumours from patients negative for germline screening were available and tested for RET, VHL, HRAS, EPAS1, MAX and SDHB. RESULTS: Germline mutations were found in 46 (14.0%) patients, being more prevalent in paragangliomas (PGLs) (28.7%) than in pheochromocytomas (PCCs) (4.5%) (p=6.62×10(-10)). Somatic mutations were found in 43% of those tested, being more prevalent in PCCs (48.5%) than in PGLs (32.3%) (p=0.13). A quarter of S-PPGLs had a somatic mutation, regardless of age at presentation. Head and neck PGLs (HN-PGLs) and thoracic-PGLs (T-PGLs) more commonly had germline mutations (p=2.0×10(-4) and p=0.027, respectively). Five of the 29 metastatic cases harboured a somatic mutation, one in HRAS. CONCLUSIONS: We recommend prioritising testing for germline mutations in patients with HN-PGLs and T-PGLs, and for somatic mutations in those with PCC. Biochemical secretion and SDHB-immunohistochemistry should guide genetic screening in abdominal-PGLs. Paediatric and metastatic cases should not be excluded from somatic screening.

Management of vagal paragangliomas: review of 17 patients.

Vagal paragangliomas are very rare benign vascular tumors of neuroendocrine nature, and are much less frequent than carotid and jugulo-tympanic tumors. The goal of this retrospective study is to review the clinical and genetic findings, surgical treatment, and complications of vagal paragangliomas, as well as to discuss the management options. During the period 1990-2013, 17 patients with vagal paragangliomas were referred to our institution. There were ten patients with isolated tumors, and seven with multicentric paragangliomas. There were nine women and eight men. Mean age of patients was 51.4 years. Five cases had a positive family history of paraganglioma (29.4 %). Germline mutations of SDH genes were found in six of our patients (35.3 %). Many options were considered in the management of vagal paragangliomas. Surgical treatment was performed in 11 young patients (64.7 %) using different approaches: in 4 patients the tumor was resected through a transcervical approach; in 3 through a transcervical-transmandibular approach; in 1 it was resected using a transcervical-transmastoid approach, and in 3 a type A infratemporal fossa approach was performed. In all operated cases, the removal of the tumor led to sacrificing of the vagus nerve. Postoperative hypoglossal nerve deficit was reported in 4 cases (36.3 %). In six elderly patients (35.3 %), we decided to "wait-and-scan" in order to avoid creating greater morbidity than that of the tumor itself. Many factors should be considered in the treatment of vagal paragangliomas: the age and general condition of the patient, the biological behavior of the tumor, tumor size, genetic results, bilaterality, multicentricity, lower cranial nerve function, and of course the potential morbidity of the surgical treatment itself. Rehabilitation and, possibly surgery, are necessary to treat postoperative lower cranial nerve deficits.

[Systematic review and meta-analysis of diagnostic accuracy of 18F-FDG PET in suspected recurrent head and neck cancer]. / Revisión sistemática y metaanálisis de la eficacia diagnóstica de la PET 18F-FDG en recurrencia tumoral de cánceres de cabeza y cuello.

OBJECTIVES: A meta-analysis of the literature was performed in this article in order to evaluate the diagnostic accuracy of 18F-FDG PET in suspected recurrent head and neck cancer. MATERIAL AND METHODS: A systematic review of the literature was performed using 1987 to 2007 MEDLINE and CANCERLIT databases, applying selection criteria to the studies found. Sensitivity, specificity, positive and negative likelihood ratios, and odds ratio were calculated. The diagnostic accuracy was evaluated with ROC (receive-operating-characteristics) curves. RESULTS: Nineteen articles were included in the meta-analysis. Sensitivity of 18F-FDG PET was 94 %, specificity 80 %, and the summary ROC curve showed a good trade-off between sensitivity and specificity. CONCLUSIONS: 18F-FDG PET was useful in patients with suspected recurrence of head and neck cancer, showing a high sensitivity and intermediate-high specificity.

Peritonsillar and deep neck infections: a review of 330 cases.

INTRODUCTION: Deep neck infections are defined as suppurative infectious processes of deep visceral spaces of the neck. OBJECTIVE: The aim of this study is to review different factors that may influence peritonsillar and deep neck infections and may play a role as bad prognosis predictors. METHODS: We present a retrospective study of 330 patients with deep neck infections and peritonsillar infections who were admitted between January 2005 and December 2015 in a tertiary referral hospital. Statistical analysis of comorbidities, diagnostic and therapeutic aspects was performed with Excel and SPSS. RESULTS: There has been an increase in incidence of peritonsilar and deep neck infections. Systemic comorbidities such as diabetes or hepatopathy are bad prognosis factors. The most common pathogen was S. viridans (32.1% of positive cultures). 100% of the patients received antibiotics and corticosteroids, 74.24% needed surgical treatment. The most common complications were mediastinitis (1.2%) and airway obstruction (0.9%). CONCLUSION: Systemic comorbidities are bad prognosis predictors. Nowadays mortality has decreased thanks to multidisciplinary attention and improvements in diagnosis and treatment.

[Necrosis of the tongue secondary to bilateral carotid thrombosis after radiotherapy]. / Necrosis lingual secundaria a la trombosis carotídea bilateral tras radioterapia.

Necrosis of the tongue is an atypic process, because it has a high irrigation that depends of the right and left lingual arteries. But, there isn't a good anastomosis between both arteries except in the tip and the tongue base. We focus on an exceptional case report about a patient that presented a great necrotic lesion in the middle of the tongue due to a bilateral external carotid thrombosis, because of a radiation therapy some years before.

[Surgical complications in salvage surgery of patients with head and neck carcinomas treated with concomitant chemoradiotherapy (CCR)]. / Complicaciones quirúrgicas en la cirugía de rescate de pacientes con carcinomas de cabeza y cuello tratados con quimioterapia y radioterapia concomitantes.

INTRODUCTION: One way of treating head and neck carcinomas is using concomitant chemoradiotherapy (CCR). In this study we will try to evaluate the incidence of complications in rescue surgery after CCR. MATERIAL AND METHOD: We have studied data from 103 patients diagnosed as having stage III or IV squamous head and neck carcinoma between 1997 and 2005. They were treated following two different CCR protocols. RESULTS: Of the 103 patients, 26 (25 %) required rescue surgery. Eight patients in this group (30.76 % of those operated on) presented complications. The average stay in our department was 52.8 days (7-197 days). CONCLUSIONS: Patients treated with CCR who have needed rescue surgery apparently have a higher rate of complications and a longer stay than those treated with surgery alone.

Practical management of periprosthetic leakage in patients rehabilitated with a Provox® 2 voice prosthesis after total laryngectomy. / Manejo práctico de fugas periprótesis en pacientes rehabilitados con prótesis fonatorias tipo Provox®2 tras laringectomía total.

INTRODUCTION AND OBJECTIVES: Periprosthetic leakage of liquids is a common complication in patients rehabilitated with voice prostheses. Our objective was to describe and review the results of procedures for treating periprosthetic leakage. MATERIALS AND METHODS: This was a retrospective analysis of 41 patients rehabilitated with Provox® 2 voice prostheses between 1997 and 2015. We describe 3 techniques: periprosthetic silicon collar placement, injection of hyaluronic acid into the tracheoesophageal wall and the combination of the 2 techniques. We present a method to reduce the diameter of the tracheoesophageal fistula by removing the voice prosthesis and placing a nasogastric tube through the fistula. RESULTS: In the 3 groups treated with silicone collar (n=5, 13 procedures), hyaluronic acid injection (n=5, 9 procedures) and the combination of both techniques (n=3, 5 procedures), we observed an increase in prosthesis lifespan of an average of 56 days (range 7-118 days), 32 days (range 3-55 days) and 63 days (range 28-136 days), respectively. The tracheoesophageal fistula diameter reduction was performed in 100% (n=6) of patients. CONCLUSIONS: The use of silicone collars, injection of hyaluronic acid into the tracheoesophageal wall and the combination of both techniques for the treatment of periprosthesis leakage increase the lifespan of the prosthesis. Temporary prosthesis removal and placement of nasogastric tube has also been shown effective in our experience. These techniques are simple, inexpensive and reproducible, thereby reducing healthcare costs.

Surgical treatment of vestibular schwannoma. Review of 420 cases. / Tratamiento quirúrgico del schwannoma vestibular. Revisión de 420 casos.

INTRODUCTION AND OBJECTIVES: Vestibular schwannoma is the most frequent cerebellopontine angle tumor. The aim of our study is to reflect our experience in the surgical treatment of this tumor MATERIAL AND METHODS: Retrospective study of 420 vestibular schwannomas operated in our hospital between 1994-2014. We include tumor size, preoperative hearing, surgical approaches, definitive facial and hearing functional results, and complications due to surgery. RESULTS: A total of 417 patients with 420 tumors were analyzed, 209 female (50.1%) and 208 male (49.9%). Mean age at diagnosis was 49.8±13.2 years. The majority of the tumors were resected through a translabyrinthine approach (80.2%). Total tumor removal was achieved in 411 tumors (98.3%), and anatomic preservation of facial nerve in 404 (96.2%). Definitive facial nerve outcome was House-Brackmann grade I and II in 69.9%, and was significantly better in tumors under 20mm. Surgical complications included cerebrospinal fluid leakage in 3 patients (0.7%) and retroauricular subcutaneous collection in 16 (3.8%), 5 cases of meningitis (1.2%), 4 patients with intracraneal bleeding (0.9%), and death in 3 patients (0.7%). CONCLUSIONS: Surgery is the treatment of choice for vestibular schwannoma in the majority of patients. In our experience, the complication rate is very low and tumor size is the main factor influencing postoperative facial nerve function.

Head and neck paragangliomas: Experience in 126 patients with 162 tumours.

INTRODUCTION: Head and neck paragangliomas are rare tumours of a neuroendocrine nature. The aim of this study was to show our experience in the management of these kind of tumours. METHODS: This was a retrospective study of head and neck paragangliomas diagnosed between 1978 and 2014. A total of 126 patients with 162 tumours were analysed. The paragangliomas included 88 jugulotympanic tumours, 53 carotid tumours and 21 vagal paragangliomas. RESULTS: Mean age at diagnosis was 53.1 years; 87 patients were female (69.1%) and 39, male (30.9%). Multifocality was present in 24 patients (19.1%). Germline mutations were found in 20 patients analysed; SDHD and SDHB were the most frequent. Surgery was performed on 72 isolated paragangliomas: these were 9 carotid, 21 tympanic, 37 jugular and 5 vagal paragangliomas. There were 25 isolated tumours that were observed periodically: 7 carotid, 3 tympanic, 9 jugular and 6 vagal paragangliomas; 5 jugular tumours were irradiated. Multifocal paragangliomas were individually treated, with a total of 26 surgical procedures and 36 tumours resected, 9 irradiated and 12 tumours periodically observed. Postoperative cranial nerve deficits in isolated carotid paragangliomas were lower (15%) compared with jugular tumours (45.5%, P=.04). Nerve deficit was found more frequently in tumours with intradural extension (100%) than in extradural tumours (37.5%, P=.007). CONCLUSIONS: Management of head and neck paragangliomas include surgery, radiotherapy and wait and scan policies. A combination of all of them is usually needed in patients with multifocal paragangliomas.

Conservative management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is a benign, slow-growing tumour originating in the 8th cranial nerve. The treatment includes microsurgery, stereotactic radiotherapy and conservative management of tumours with periodic radiological tests. METHODS: This was a retrospective study of patients with VS following conservative management in a tertiary hospital between 1993 and 2013. A total of 73 patients were enrolled in our protocol. The mean age at diagnosis was 59.7 years. The average size was 11.9mm (4-27mm); 58.9% of the tumours were intracanalicular and 41.1%, extracanalicular. The mean follow-up period was 35.75 months. RESULTS: In 87.7% of patients there was no evidence of tumour growth. A total of 9 tumours (12.3%) increased in size. The average growth rate was 0.62mm/year. The percentage of extracanalicular tumours that grew (20%) was higher than that of intracanalicular tumours (7%). Seven patients (9.5%) experienced significant changes in their symptoms and 6 of these (8.2%) experienced a loss of useful hearing. Six patients (8.2%) left follow-up and underwent surgery. CONCLUSIONS: Periodic monitoring of vestibular schwannomas with magnetic resonance imaging represents an option for management, because most small tumours experience little or no growth over time.