Granular cell tumor of the trachea as a rare cause of dyspnea in a young woman.

Tracheal granular cell tumors are rare neurogenic neoplasms characterized by an indolent behavior. We report the case of a young woman affected by this tumor with non-specific clinical presentation. We performed a literature search in order to identify all the cases of tracheal granular cell tumor and to summarize the current state of knowledge about this rare disease.

Patient-derived solitary fibrous tumour xenografts predict high sensitivity to doxorubicin/dacarbazine combination confirmed in the clinic and highlight the potential effectiveness of trabectedin or eribulin against this tumour.

BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. RESULTS: Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. CONCLUSION: Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients.

Radiotherapy in the management of gist: state of the art and new potential scenarios.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. The main treatment for localized gastrointestinal stromal tumors is surgical resection. Unresectable or advanced GIST are poorly responsive to conventional cytotoxic chemotherapy but the introduction of tyrosine kinase inhibitors (TKIs) marked a revolutionary step in the treatment of these patients, radically improving prognosis and clinical benefit. Historically GIST has been considered radiation-resistant, and the role of radiotherapy in the management of patients with GIST is currently restricted to symptomatic palliation in current treatment guidelines. CASE PRESENTATION: Here we report two patients affected by metastatic GIST, treated with radiotherapy and radiosurgery in combination with TKIs, achieving an unexpected objective response in the first case and a significant clinical benefit associated with a local tumor control of several months in the second case. CONCLUSIONS: These and other successful experiences that are progressively accumulating, open up new scenarios of use of radiation therapy in various settings of treatment. GIST is not universally radioresistant and radiotherapy, especially if combined with molecularly targeted therapy, can improve the outcomes for patients diagnosed with GIST.

Successful selective arterial embolizations for bone metastases in renal cell carcinoma integrated with systemic therapies: A case report.

Herein is described the case of a 64-year-old patient affected by metastatic clear-cell carcinoma, with exclusive bone disease, subjected after the initial cytoreductive nephrectomy to 3 successive lines of medical treatment (sunitinib, everolimus, and sorafenib) and multiple locoregional treatments (spinal surgery, radiation therapy, and selective arterial embolization), resulting in a surprisingly long survival of over 75 months. In the era of target therapy, integration strategies, including additional locoregional treatment to medical therapy, are essential to optimize the clinical benefit, to maximize treatment duration overcoming focal progressive disease, and to improve the quality of life. In this context, we would highlight that selective transcatheter embolization of bone metastases from renal cell carcinoma should be considered as an effective and safe option in the palliative setting for patients with bone metastasis, especially for pain relief.

Post stroke sleep apnea hypopnea syndrome: a series of 12 consecutive stable stroke cases.

OBJECTIVES: Sleep Disordered Breathing (SDB) is a negative prognostic factor for stroke patients. In order to reveal: (1) the frequency of Sleep Apnea-Hypopnea Syndrome (SAHS) in the stable phase of the illness; (2) the type of SAHS, either obstructive (OSAHS) or central (CSAHS); (3) the possible association between SAHS and daily sleepiness, cardiac arrhythmias, stroke / TIA recurrence and location of the brain lesion, an observational study is on-going at Sapienza University of Rome. We report here the results of cases included in the feasibility study. PATIENTS AND METHODS: clinical evaluations, brain images and polisomnographic study were performed at discharge and after 4 and 9 months of stroke. RESULTS: Eleven out of the 12 patients included (91.6%) had an Apnea/Hypopnea Index-AHI >= 5. In 5 cases, the majority of total respiratory events were purely central in origin. In 3 of these 5 cases, a concomitant obstruction of the upper airways was revealed; the 2 remaining had risk factors for OSAHS (smoke, hypertension, BMI > 25). A significant association was found between central apnea/hypopnea events and cardiac arrhythmias (p value 0.017). CONCLUSIONS: These findings confirm the high prevalence of SDB, either obstructive or/and central, even in the stable phase of the illness, which in those patients who had accumulated risk factors for OSAHS result in Complex-sleep apnea/hypopnea syndrome (CompSAHS). As patients with CompSAHS are left with very disrupted breathing on continuous positive airway pressure, in order to select cases with stable stroke who benefit from continuos-positive airway pressure (C-PAP) treatment, further and more detailed clinical studies are needed to better distinguish CompSAHS from mixed SAHS.

Renin-angiotensin-aldosterone system in patients with sleep apnoea: prevalence of primary aldosteronism.

Obstructive sleep apnoea (OSA) is a sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, representing an independent risk factor for cardiovascular disease, such as myocardial infarction, stroke, congestive heart failure and resistant hypertension. Several neurohormonal mechanisms have been suggested to account for blood pressure increases, such as sympathetic nervous system hyperactivity, oxidative stress, renin-angiotensin-aldosterone system (RAAS) activation, endothelin system activation, and endothelial dysfunction. The aim of this study was to evaluate the behaviour of RAAS and the presence of primary aldosteronism (PA) in these patients and possible correlations between RAAS and the severity of OSA. From October 2007 to November 2008 we studied 325 consecutive newly diagnosed hypertensive patients; 71 patients (21.8%) presented with clinical signs of sleep disorders, evaluated also through a specific questionnaire (Epworth Sleepiness Scale). In hypertensive patients with sleep disorders, 53 patients were affected by OSA; in this group 18 patients were affected by PA (five with aldosterone-producing adenoma (APA) and 13 with bilateral hyperplasia (IHA)); obesity was also demonstrated (BMI > 30 kg/m(2)). Overall, in patients with OSA PRA levels correlated positively with apnoea/hypopnoea index (AHI; r = 0.35; p<0.01), and in all groups the waist circumference and the neck circumference were correlated positively with AHI (r = 0.3 p<0.02 and r = 0.3 p<0.03, respectively). We revealed a high prevalence of PA in patients with OSA, and we can conclude that patients with hypertension and OSA, especially those who are newly diagnosed, must be evaluated for PA.

Surgical debulking of gastrointestinal stromal tumors: is it a reasonable option after second-line treatment with sunitinib?

INTRODUCTION: After imatinib treatment, the surgical management of patients affected by gastrointestinal stromal tumor (GIST) has been widely reported and often considered by many oncologists in clinical practice. Surgical results are correlated with disease responsiveness to tyrosine kinase inhibitors and with complete extirpation of all tumor sites. By now, no report specifically addressing surgical management after second-line treatment with sunitinib is still available. Most patients have an unresectable disease and do not have any other therapeutical options except for clinical trials. MATERIALS AND METHODS: We report two clinical cases of patients with metastatic GISTs, who underwent surgery after sunitinib, and discuss the surgical management option in this clinical setting. RESULTS: Both our patients had a long, durable stable disease on sunitinib, but one developed a chronic mild bleeding that does not call for emergency surgical interventions and the other one developed chronic heart toxicity. They were proposed to undergo surgery despite the unresectable diseases and received an incomplete resection because of residual metastatic lesions. They restarted sunitinib after surgery. CONCLUSIONS: The poor prognosis after sunitinib treatment and the absence of alternative validated options open the debate on the assessment of surgical management of metastatic GISTs in this setting. The role of surgery should be investigated in clinical trials; however, the enrollment may be difficult. In clinical practice and after a multidisciplinary case patient discussion, surgery could represent a reasonable choice for advanced GISTs especially if the risk of surgery-related death is not too high.

Targeted therapies in solid tumours: results and promises.

In these last few years novel approaches to the treatment of solid tumours have been proposed. Therapeutic agents addressed to specific functions of the neoplastic cells seems to be very promising tools, with a low grade of toxicities. These agents are the basis of the so called targeted therapies. Small molecules inhibiting the proliferative cascade of the cancer cells and monoclonal specific antibodies against growth factor or vascular endothelial growth factor have been claimed as the promise in cancer therapy. Unfortunately, the very good results obtained in preclinical experiments have not been completely confirmed in the clinical practice. A selection of patients who could have beneficial effects from the novel agents is mandatory to avoid inappropriate therapies and also unjustified expenses.

Cortisol circadian rhythm and 24-hour Holter arterial pressure in OSAS patients.

Obstructive sleep apnea syndrome (OSAS) is a syndrome in which the principal symptom is apnea during sleep. Hypoxia in OSAS is a stress condition, which when prolonged in time, could alter hypothalamo-hypophysial-suprarenal control and the cortisol cicadian rhythm. We studied 28 patients with OSAS (30-60 years old), 20 female and 8 male. We calculated the OSAS class according to the Simmons classification. Twenty of the 28 patients maintained unmodified cortisol circadian rhythms, while 8 had cortisol levels more elevated in late and nocturnal hours. Holter monitoring showed arterial hypertension in 8 of the 28 patients (the same patients with cortisol circadian rhythm alteration). Our data seem to indicate that when the OSAS patients lack cortisol circadian rhythm they are having arterial hypertension.

Solitary crystal-storing histiocytosis of the tongue in a patient with rheumatoid arthritis and polyclonal hypergammaglobulinemia.

A 73-year-old woman with a long history of rheumatoid arthritis and polyclonal hypergammaglobulinemia developed a solitary mass in the tongue, which on morphologic and immunohistochemical analyses was consistent with crystal-storing histiocytosis, a rare condition commonly described in association with clonal lymphoplasmacytic disorders. The lesion consisted of a localized collection of histiocytes filled with numerous eosinophilic crystals immunoreactive for both kappa and lambda light chain and gamma heavy chain antibodies. Mature lymphocytes and plasma cells were present both throughout and around the lesion. Since a clonal lymphoplasmacytic neoplasm was ruled out by clinical and immunohistochemical studies, we consider that, in this case, crystal-storing histiocytosis was consequent to polyclonal hypergammaglobulinemia and suggest that this rare histiocytosis is not specific to lymphoplasmacytic neoplasms, but may represent a reaction to high values of normal (or abnormal) immunoglobulins.

Auditory evoked potentials for the assessment of noise induced hearing loss.

As it has been demonstrated in many animal experiments, noise can damage the cochlea and the central auditory pathways. It is very difficult in clinical studies to separate the relative contribution of both these sites. Auditory evoked potentials ABR, MLR and SVR study retrocochlear nervous conduction and collectively the results of these techniques proved an objective evaluation of the cochlear function. The Authors have studied a group of 130 sport shooters with high frequency hearing loss and found that in 38 ears a clear retrocochlear component could be recognised. Correlation with intensity, frequency and length of exposure to the traumatic noise demonstrates that explosive noise is an agent for NIHL. However athletes exposed to similar noises did not suffer from similar hearing loss, probably because of the well known individual noise susceptibility.

Wolfram's syndrome: a clinical, diagnostic, and interpretative contribution.

Four cases (belonging to two different families) of Wolfram's syndrome (WS), a rare congenital disease characterized in its complete form by insulin-dependent diabetes mellitus, optic atrophy, diabetes insipidus, deafness, and dilation of the urinary tracts are presented, and a review of the literature is included. Three of four patients are characterized by HLA-DR2 haplotype, which is rare in IDDM. The neurodegenerative nature of some symptoms and the possible pathogenesis of diabetes mellitus connected with it are discussed.

Vestibular ototoxicity in children: a retrospective study of 52 cases.

We have carried out a study on 52 patients treated during childhood with potentially ototoxic drugs. The evaluation of vestibular function was carried out long after treatment. In most of the cases there was a parallelism between hearing and vestibular deficit. Manifest impairment of the vestibular function was demonstrated in 4 subjects, without remarkable hearing loss, who had previously been treated with streptomycin during childhood. Furthermore, in the case of 19 subjects, a considerable deambulation delay was noticed (in one case it revealed itself after the fourth year of life) which was attributable to a real injury to the vestibular structures. Finally, almost all examined subjects showed a dysfunction of equilibrium and a noticeable tendency to kinetopathy.