Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas

'Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations (AU)

Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.

[Incidence of cancer in Navarre]. / Incidencia de cáncer en Navarra (1998-2000).

Between 1998 and 2000 an annual average of 3,303 cases of invasive cancer were registered in Navarre, 58% of them in men. If we except non melanoma skin tumours, the annual number of cases was 2,495, with gross incidence rates of 559 and 372 per 100,000 in men and women, and rates adjusted to the world population of 312 and 203 per 100,000 respectively. Amongst men, the four most frequently diagnosed tumoural localisations were the prostate, lung, colorectal and bladder, accounting for 57% of all cases. The most notable due to their frequency amongst women were tumours of the breast, colorectal, uterus body and ovary, accounting for 54% of all cases. With respect to the five year period from 1993 to 1997, the global incidence of cancer in the three year period from 1998 to 2000 has increased 4.2% in men and 7.4% in women. The incidence of lung cancer and non-Hodgkin lymphomas in both sexes and of breast cancer in women and prostate cancer in men are notable. There continues to be a fall in the incidence rates of stomach cancer in both sexes, following the tendency begun in the 1970s.

Espondilodiscitis. Análisis de una serie de 25 casos / Spondylodiscitis. Analysis of 25 cases

BACKGROUND: Spondylodiscitis is a rare but prolonged inflammation of two adjacent vertebral bodies and the disk in between. AIM: To report the clinical features of a series of patients with spondylodiscitis. MATERIAL AND METHODS: A retrospective analysis of medical records of patients with spondylitis, identified between 1989 and 2002. RESULTS: A total of 25 cases were identified, 15 female, aged 49.8 years as a mean. Their mean evolution before admission was 4.3 months. Main complaints were back or radicular pain. Mild anemia was present in most patients. Mean erythrocyte sedimentation rate and C reactive protein values were 66 mm/h and 60 mg/L, respectively. Forty four percent of patients had neurological complications. Vertebral computed tomography and scintigraphic studies were done in 72 per cent of patients, but magnetic resonance imaging was done only in 4 (16 per cent). In 18 patients, a tissue sample for pathological and microbiological analysis, was obtained by imaging guiding or surgically. Tuberculosis, diagnosed on pathology, was the leading cause of spondylitis in nine cases (36 per cent), followed by Staphylococcus aureus infection in five (20 per cent). Other agents found were E coli and group D Streptococcus (one each). Age, symptoms, evolution time and different laboratory parameters did not differ between patients with tuberculosis and patients with other causes. A microbiological cause was not established in 36 per cent of cases. Most patients evolved satisfactorily and recovered from neurological complications (88 per cent). One patient with tuberculosis did not improve after prolonged treatment and 2 patients infected with S aureus died (8 per cent). CONCLUSIONS: Spondylodiscitis is associated to a diversity of microbial agents and in most cases has a favorable prognosis.

Identification of internal acoustic canal in the middle cranial fossa approach: a safe technique.

BACKGROUND: The middle cranial fossa approach (MCFA) is a very valuable functional approach in the armamentarium of the neuro-otologic surgeon. Identification of the internal acoustic canal (IAC) in MCFA is one of the most tedious steps. Many techniques have been described to locate the IAC safely when using the MCFA. OBJECTIVE: We sought to describe a safe technique for identification of the IAC and to demonstrate its feasibility in temporal bone dissections, as well as to discuss our clinical experience with this technique. METHODS: The surgical anatomy of the 20 temporal bones were evaluated and measured, especially by defining the medial and lateral ends of the IAC and relations to the nearby located structures. Measurements were obtained at 3 levels: the width of the IAC at the level of the fundus, the width of the IAC at the level of the porus, and the safe distance around the IAC at the meatal level. The medial and lateral IAC end widths were compared with each other and with the safe area at the meatal level. RESULTS: The smallest, the largest, and the mean values were recorded. The mean width of the IAC at the level of the porus was found to be more than 3-fold that of the width of the IAC at the level of the Bill's bar, and the ratio between the width of the medial safe area around the IAC and the lateral end of the IAC was found to be more than 7-fold as wide. CONCLUSION: This technique offers direct quick exposure of the IAC, without handling the facial nerve and the inner ear structures. Forty-five cases of operations with the same technique showed excellent ease and safety of identifying the IAC medially in the MCFA.

[Molecular diagnosis of fragile X syndrome with polymerase chain reaction: application of a diagnostic protocol in 50 families from northern Spain]. / Diagnóstico molecular por reacción en cadena de la polimerasa del síndrome X frágil: aplicación de un protocolo diagnóstico en 50 familias del norte de España.

OBJECTIVES: The aim of this study was to develop a rapid, non-radioactive and effective method for the molecular diagnosis of fragile X syndrome (FXS) by the polymerase chain reaction (PCR) of the CGG repeat and to establish a protocol to be used in: a)ruling out FXS in patients with non-specific mental retardation; b)determining the exact genotype of affected individuals; c)studying all at-risk individuals from families with FXS and identifying asymptomatic carriers, and d)offering accurate genetic and reproductive counselling to families with FXS. MATERIALS AND METHODS: Samples from 438 individuals from 50 families with FXS were studied using three different PCR tests: the first to detect ethidium bromide through ultraviolet light, the second to detect digoxigenin and CSPD after blotting and hybridisation with the (CGG)5 oligoprobe, and the third to amplify and detect the DXS548 microsatellite. RESULTS: Of the 438 individuals studied, 121 had full mutations (60 males and 61 females), 86 had pre-mutations (7 males and 79 females), 16 showed mosaic patterns and 215 had no mutations. PCR techniques amplified up to 120-150 repeats, and direct study with probes was required when no bands or only one band was detected in females. PCR was more accurate than genomic DNA Southern blot analysis in pre-mutated carriers. In one family, recombination between the FRAXA locus and the DXS548 microsatellite was found. CONCLUSIONS: These non-radioactive PCR protocols permit rapid and accurate diagnosis of FXS. They and are especially useful in prenatal diagnosis and in the identification of carriers.

Retrolabyrinthine vestibular nerve section: a current appraisal.

We report our experience (1987-1993) with Meniere's disease patients treated with a retrolabyrinthine vestibular neurectomy. The current literature was reviewed and our results have been compared with those of previous reports. The overall success rate for vertigo relief was 96.7%, with no serious or permanent complications resulting from the procedure. The technical elements of the operation, as they apply to our approach and those of others, have been analyzed, with special attention given to the anatomical features of the region and their influence on success or failure. We conclude that the retrolabyrinthine approach for vestibular nerve section remains a safe and highly successful technique which merits continued use.

[Glomus jugulare tumor: perioperative management]. / Tumor glómico yugular: manejo perioperatorio.

Surgical treatment of glomus jugulare tumors yields high rates of perioperative morbidity and mortality for several reasons, among them neuroendocrine secretory activity, a high degree of vascularization, intracranial extension, duration of surgery and cranial nerve lesion. Secretory activity (e.g. catecholamines and serotonin) should be investigated before surgery and treated appropriately. Carotid arteriography (and ball occlusion) are useful to assess vascularization of the tumor and determine the need to clamp the carotid artery during the procedure. Potential complications such as hemodynamic alterations (bleeding or endocrine response), pulmonary embolism (air or thrombotic), hypothermia, facial nerve lesion, should be monitored for during surgery. After surgery cranial nerve involvement, which can lead to dysphagia and bronchoaspiration, must be looked for; the risk of cerebro-spinal fluid fistula is also high. We report the case of a woman who underwent surgery for a non secreting glomus jugulare tumor with extradural intracranial invasion. The main complications during surgery were bleeding with hemodynamic repercussions, pulmonary embolism, lesions in the VII, VIII and X cranial nerves, and opening of the dura mater (which required insertion of an intradural drain to prevent formation of a fistula). After surgery oral intake was delayed until intestinal function was established and glottic sphincter competence was verified by fiberoptic laryngoscopy. The only complication presenting at this time was cephalea, which disappeared upon removal of the drain on day 4. The patient was released on day 10.

[Vestibular neurectomy by retrolabyrinthine approach in cases of untreatable Meniere's disease]. / La neurectomia vestibolare per via retrolabirintica nei casi di Malattia di Ménière intrattabili. Gruppo Otologico Piacenza.

We report on a series of 35 Ménière's disease patients, all of whom had undergone retrolabyrinthine vestibular neurectomy between 1987-1993. The overall success rate of vertigo relief was 96.7% with no serious or permanent complications resulting from the procedure. The current literature is reviewed and our results are compared with those of previous reports. The technical elements of the operation, regarding our approach and those of the others are analyzed with special attention given to the anatomical features of the region and their influence on success or failure. We conclude that the retrolabyrinthine approach for nerve section remains a safe and highly successful technique which continues to be widely used.

Normal hearing in acoustic neuroma patients: a critical evaluation.

A series of 128 acoustic neuromas (ANs) managed in our center in the last 6 years were evaluated. Sixteen cases (12.5%) were found to have normal pure tone audiograms. A comparatively younger age was an important characteristic of these patients. Tinnitus, dysequilibrium, and subjective hearing loss or distortion were their most common complaints. Pure tone audiometry showed a mean pure tone average of 14.5 dB. Speech discrimination score and performance intensity phonetically balanced index were very insensitive and showed very high false-negative results. Auditory brainstem responses proved to be a reliable test, being positive in 93.8% of cases. The mean tumor size did not show any significant difference when compared with acoustic neuroma cases with abnormal hearing. The combination of otologic and neurotologic symptoms in a young patient should prompt the clinician to investigation further even if hearing is within normal limits. A high index of suspicion is a prerequisite for the early diagnosis of such subtle lesions.

[Meningoencephalic herniation into the middle ear]. / Ernie meningoencefaliche nell'orecchio medio.

Herniation of meningeal and/or encephalic tissue into the middle ear is a pathology which, even if rarely found by the otologist, can be life-threatening for the patient because of eventual infective intracranial complications. Four different etiological types are possible, infective, post-surgical, traumatic and spontaneous. From a pathogenic point of view, all types are characterized by a bony and dural defect localized in the tegmen through which meningeal and encephalic tissue can herniate. Symptomatology is often non-specific so that some cases are diagnosed during surgery. When there is strong suspicion of herniation neuroradiological assessment procedures must be carried out in order to make a correct pre-operative diagnosis, High Resolution Computed Tomography (HRCT) of the temporal bone in particular, can show the exact limits and location of the bone defect, while Magnetic Resonance Imaging (MRI) allows the nature of the tissue in the middle ear to be determined. Surgery is the only appropriate therapy. Different approaches have been described amongst which the transmastoid with or without temporal minicraniotomy and the middle cranial fossa (MCF) are the most frequently reported literature. From June 1982 to March 1994, 27 consecutive cases underwent surgery at the Gruppo Otologico, Piacenza. As a result of the occurrence of postoperative meningitis in one case, a new surgical technique through the MCF was standardized. The main step of this procedure consist in leaving the herniated tissue in situ so as to make a barrier between the middle ear and subdural space. The technique is indicated either in the case of large, multiple or very anteriorly located bony defects or when there is an infection in the middle ear.

[The modified transcochlear approach to the petroclival area and the prepontine cistern: indications, techniques and results]. / La vía transcoclear modificada para el abordaje del área petroclival y de la cisterna prepontina: indicaciones, técnica y resultados.

This paper presents the modification made for a transcochlear approach which would permit reaching the pertoclivis area and proeponten cistern. The disadvantage, inconvenience of the approach used on 5 patient is discussed here.

Meningoencephalic herniation into the middle ear: a report of 27 cases.

Meningoencephalic herniation into the middle ear is a rare and potentially life-threatening condition that may require prompt surgical intervention. Preoperative diagnosis is based on a high index of suspicion. Sometimes, however, meningoencephalic herniation is discovered during surgery. High-resolution computed tomography and magnetic resonance imaging should be performed to confirm the diagnosis and to evaluate the extension of the herniated tissue. This article discusses the diagnostic approach, management strategy, and surgical technique used in 27 patients with meningoencephalic herniation. In an attempt to avoid infective complications, the authors used the middle cranial approach in patients with large herniations.

Lower skull base: anatomic study with surgical implications.

With advances in the lateral approaches to the skull base and the increasing success of the management of jugular foramen lesions, a thorough knowledge of the anatomy of this region is needed. The purpose of the present work is to study the detailed microsurgical anatomy of the lower skull base and the jugular foramen area as seen through the lateral approaches. Forty preserved skull base specimens and 5 fresh cadavers were dissected. The shape of the jugular bulb and its relationship to nearby structures were recorded. The different venous connections of the bulb were noted. The hypoglossal canal was identified and its contents were observed. The lower cranial nerves were studied at the level of the upper neck, at their exit from the inferior skull base, and in the jugular foramen. The results of the present study showed the complex and variable anatomy of this area. The classic compartments of the jugular foramen were not always present. Cranial nerves IX through XI followed different patterns while passing through the jugular foramen, being separated from the jugular bulb by bone, thick fibrous tissue, or thin connective tissue.

Surgical management of epitympanic cholesteatoma with intact ossicular chain: the modified Bondy technique.

The results of 37 cases surgically treated with the modified Bondy technique during a 6-year period at the Gruppo Otologico-Piacenza, Italy, are reported. This technique, indicated in epitympanic cholesteatoma with good hearing and intact ossicular chain and pars tensa, provides a one-stage mastoid cavity exteriorization with radical removal of cholesteatoma while preserving the preoperative hearing levels. The technique, indications, results, and comparison with other current techniques are discussed in this article.

Revision stapes surgery: a critical evaluation.

Fifty-six revision stapes surgeries performed during the last 9 years were evaluated retrospectively for their preoperative symptoms, intraoperative findings, and postoperative results according to the causes of failure, at the Gruppo Otologico, Piacenza, Italy. The most frequent causes of failure were found to be prosthetic misalignments, a reaction to the surgical trauma in the form of excess fibrous tissue reaction or new bony regrowth at the oval window, and ossicular chain problems. The location of the pathology was found to be an important factor in the outcome. Sixty percent of cases resulted in 0- to 20-dB air-bone gap. The causes of these failures, management, and their prevention during primary surgeries are also discussed.

Surgical anatomy of the petrous apex as it relates to the enlarged middle cranial fossa approaches.

This work was designed to study the surgical anatomy of the petrous apex as it relates to the enlarged middle cranial fossa approaches, on 25 temporal bones. In this study we suggest dividing the petrous apex into two topographic areas: an anterior triangular and a posterior quadrangular area with respect to the posterior border of the Gasserian ganglion. Anatomic descriptions endorsed by relevant measurements of these areas are provided in this study.

Giant cell tumor of the lateral skull base: a case report.

Giant cell tumors of the temporal bone are very rare lesions. They should be differentiated from other giant cell lesions of bone, mainly reparative granulomas. A case with a very huge giant cell tumor of the temporal bone extending to the infratemporal fossa, temporomandibular joint, and greater wing of the sphenoid has been presented. Because of their tendency for recurrence, total removal is the treatment of choice for these tumors and was accomplished through the infratemporal fossa approach type B. A follow-up of 2 years and 9 months revealed no evidence of tumor recurrence.

The enlarged translabyrinthine approach for removal of large vestibular schwannomas.

This study was carried out to validate the enlarged translabyrinthine approach for the surgical management of large vestibular schwannomas. A retrospective review of the charts of 53 patients with large tumours removed via the enlarged translabyrinthine approach at the Gruppo Otologico, Piacenza, Italy, during the last five years was carried out. The ability to control large tumours and the achievement of total removal with low morbidity and very few complications, demonstrate that tumour size does not influence the use of the enlarged translabyrinthine approach for managing large tumours.

[Treatment of petrous bone cholesteatoma]. / Tratamiento del colesteatoma intrapetroso (CIP).

Cholesteatoma involving the petrous compartment of the temporal bone is rare and is a difficult surgical challenge for the neuro-otological surgeon. A series of 60 cases of petrous bone cholesteatoma is presented. The diagnosis, surgical treatment, results, and complications are discussed. Our present surgical attitude is based on closed obliterative procedures that allow a wide field exposure with radical removal excision, control and protection of vital structures, and management of problems related to the facial nerve. The treatment of dura mater involved by matrix is still unsolved. Regular follow-up with CT and MRI is mandatory.