Parapharyngeal space tumors: a twenty-year single-center retrospective analysis on the effectiveness of transcervical and transoral approaches on local control and disease-specific survival.

INTRODUCTION: To retrospectively analyzed our twenty-years single-center experience in the treatment of PPS tumors, focusing on the selection of surgical approach and the survival outcome. METHODS: Tumors involving the PPS between January 2000 and February 2022 were retrospectively included. The surgical approach was dictated by the localization of the tumor, its dimensions, the relation to anatomic structures and its etiology. RESULTS: 34 patients were included in the study. The median age was 50.5 yr, with a gender female prevalence. Most tumors were benign and non recurrent. 20 tumors were treated through lateral approach (transcervical or transcervical-transparotid), 11 through medial approach (transoral), and only 3 tumors were approached by multiple corridors. The 5 years disease free survival (DFS) was 78.8 % (CI 78-79.3 %). CONCLUSIONS: In our experience, the transcervical and transoral approaches can be considered the ideal surgical approach to manage tumors of PPS, especially in cases of benign neoplasms.

The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo.

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na+/K+-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21Waf1/Cip1 and p27Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133+ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non-Homologous End-Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS.

Relationship between Salivary Amylase and Xerostomia in Intensity-Modulated Radiation Therapy for Head and Neck Cancer: A Prospective Pilot Study.

PURPOSE: A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices. RESULTS: Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = -0.70) and late (ρ = -0.80) xerostomia. CONCLUSION: Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.

A surgical challenge: resection of giant follicular thyroid carcinoma in a 92-year-old woman. Case report and considerations on thyroid surgery in geriatric population.

The aim of this paper is to present the clinical features and the diagnostic and surgical management of a 92-year-old patient with giant goiter. She was admitted to our Emergency Department for evaluation of a cervical mass increased in volume over the past five years. She complained of mild dyspnea pressure symptoms in the neck. Neck and mediastinal noncontrast computed tomography showed a huge goiter with a clear prominent right thyroid lobe, with external compression of the trachea. Consequently, she underwent a right thyroid lobectomy. Patient followed up closely; she is asymptomatic with no evidence of recurrence on RAI scan at the end of six months follow-up. In conclusion, the treatment choice for elderly patients with FTC should be based on medical assessments; in these patients, especially those with larger goiter and compressive symptoms, surgery is the first choice. KEY WORDS: Elderly, Emergency Surgery, Follow up, Thyroid carcinoma, Thyroid lobectomy.

Modulating the dose-rate differently affects the responsiveness of human epithelial prostate- and mesenchymal rhabdomyosarcoma-cancer cell line to radiation.

Purpose: Radiation therapy (RT), by using ionizing radiation (IR), destroys cancer cells inducing DNA damage. Despite several studies are continuously performed to identify the best curative dose of IR, the role of dose-rate, IR delivered per unit of time, on tumor control is still largely unknown.Materials and methods: Rhabdomyosarcoma (RMS) and prostate cancer (PCa) cell lines were irradiated with 2 or 10 Gy delivered at dose-rates of 1.5, 2.5, 5.5 and 10.1 Gy/min. Cell-survival rate and cell cycle distribution were evaluated by clonogenic assays and flow cytometry, respectively. The production of reactive oxygen species (ROS) was detected by cytometry. Quantitative polymerase chain reaction assessed the expression of anti-oxidant-related factors including NRF2, SODs, CAT and GPx4 and miRNAs (miR-22, -126, -210, -375, -146a, -34a). Annexin V and caspase-8, -9 and -3 activity were assessed to characterize cell death. Senescence was determined by assessing ß-galactosidase (SA-ß-gal) activity. Immunoblotting was performed to assess the expression/activation of: i) phosphorylated H2AX (γ-H2AX), markers of DNA double strand breaks (DSBs); ii) p19Kip1/Cip1, p21Waf1/Cip1 and p27Kip1/Cip1, senescence-related-markers; iii) p62, LC3-I and LC3-II, regulators of autophagy; iv) ATM, RAD51, DNA-PKcs, Ku70 and Ku80, mediators of DSBs repair.Results: Low dose-rate (LDR) more efficiently induced apoptosis and senescence in RMS while high dose-rate (HDR) necrosis in PCa. This paralleled with a lower ability of LDR-RMS and HDR-PCa irradiated cells to activate DSBs repair. Modulating the dose rate did not differently affect the anti-oxidant ability of cancer cells.Conclusion: The present results indicate that a stronger cytotoxic effect was induced by modulating the dose-rate in a cancer cell-dependent manner, this suggesting that choose the dose-rate based on the individual patient's tumor characteristics could be strategic for effective RT exposures.

Nanotechnology in Oral Cavity Carcinoma: Recent Trends and Treatment Opportunities.

Oral cavity carcinoma (OCC) remains an ongoing public health problem. Emerging nanotechnology provides alternative treatment approaches. This review covers the up-to-date literature in the human OCC treatment field. We explored the growing body of evidence to reveal novel and highly promising diagnostic and therapeutic applications of nanotechnology in this field. Various types of nanoparticles have been tested for applications in OCC. Imaging modalities in addition to nanocarriers are discussed. The encouraging contribution of lymphotropic nanoparticles contrast in the diagnosis of metastatic cervical lymph nodes needs to be confirmed. The development of the sentinel lymph node procedure and photodynamic therapy may lead to breakthrough therapies in order improve clinical outcomes and quality of life. In this perspective, cancer nanotechnology has the potential to revolutionize the treatment of OCC patients.

Pro-differentiating and radiosensitizing effects of inhibiting HDACs by PXD-101 (Belinostat) in in vitro and in vivo models of human rhabdomyosarcoma cell lines.

This study describes the in vitro and in vivo activity of PXD-101 (Belinostat), a novel hydroxamic acid-type pan-HDACs inhibitor characterized by a larger safety and efficacy, on myogenic-derived PAX3/FOXO1 fusion protein positive (RH30) or negative (RD) expressing rhabdomyosarcoma (RMS) cell lines. PXD-101 at low doses efficiently inhibited HDACs activity and counteracted the transformed phenotype of RMS by inducing growth arrest and apoptosis, affecting cancer stem cells population and inducing differentiation in RD. Notably, PXD-101 induced oxidative stress promoting DNA damages and affected the ability of RMS to assemble mitotic spindle. PXD-101 radiosensitized by inducing G2 cell cycle growth arrest, enhancing the radiation's ability to induce ROS accumulation and compromising both the ability of RMS to detoxify from ROS and to repair DNA damage. PXD-101 transcriptionally and post-transcriptionally affected c-Myc expression, key master regulator of rhabdomyosarcomagenesis and RMS radioresistance. All in vitro data were corroborated by in vivo experiments showing the cytostatic effects of PXD-101 when used alone and at low dose and its ability to promote the RT-induced killing of RMS. Taken together, our data confirm that altered HDACs activity plays a key role in RMS genesis and suggest PXD-101 as a valid therapeutic strategy particularly in combination with RT.

Leiomyoma of the External Auditory Canal.

Angioleiomyomas (ALMAs) are benign tumors that arise from smooth muscle cells that form the tunica media of vascular structures. To our knowledge, only five cases of ALMA of the external auditory canal (EAC) have been reported. We report the case of a 52-year-old man with left otalgia, otorrhea, auricular fullness, and hearing loss. On otomicroscopic examination, a reddish and smooth mass completely occluding the EAC was seen. Computed tomography scan showed a soft tissue mass with a complete opacification of the left EAC. A possible diagnosis of ALMA should be considered when finding a tumor inside the external ear canal. An accurate pathological examination should be performed to differentiate benign vascular ALMA from malignant leiomyosarcomas. Complete surgical excision is the treatment of choice in benign tumors.

Prognostic Significance of the Neutrophil/Lymphocyte Ratio in Patients with Non-Human Papilloma Virus-Related Oropharyngeal Cancer: A Retrospective Cohort Study.

PURPOSE: To investigate the effects of the pretreatment neutrophil-to-lymphocyte ratio (N/L) on non-human papilloma virus (HPV)-related oropharyngeal cancer. MATERIALS AND METHODS: N/L was calculated by dividing the neutrophil count by the lymphocyte count. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of N/L and other clinical factors on survival outcomes. High/low N/L groups were defined as > 4.7 and ≤4.7, respectively. RESULTS: Data of 57 consecutive patients with non-HPV-related oropharyngeal cancer were analyzed. The 3-year disease-free survival was 79 versus 36.9% in favor of the low N/L group (p = 0.04). The 5-year overall survival was 71.6 versus 53.3% in the low N/L and high N/L group, respectively (p = 0.07). CONCLUSION: N/L could play an important role in non-HPV-related oropharyngeal cancer progression and indicate prognosis.

Management of salivary gland malignant tumor: the Policlinico Umberto I, "Sapienza" University of Rome Head and Neck Unit clinical recommendations.

Salivary gland malignant tumor (SGMT) is a malignant disease requiring multidisciplinary approach. The rare incidence and the consequent lack of robust evidence-based medicine has called for a comprehensive update to draw recommendations for clinical practice. This paper is a summary of the XXX Head and Neck Unit guidelines regarding the management of SGMT. Recommendations include the indications for exclusive and adjuvant therapy, as well as metastatic management, for both major and minor SGMT.

Radiation therapy and serum salivary amylase in head and neck cancer.

Radiation therapy (RT) is a valid treatment option for head and neck cancer (HNC). The risk of RT-induced toxicities is significant, especially due to extended treatment fields. The raise in amylase activity is strictly dependent on the volume of salivary glands included in the irradiated target volume and it is firmly related to the dose. The aim of this review is to report the effects on salivary amylase activity after radiation exposure of salivary glands, in patients with HNC.

Recovery from Repeated Sudden Hearing Loss in a Patient with Takayasu's Arteritis Treated with Hyperbaric Oxygen Therapy: The First Report in the Literature.

Hearing loss has been rarely reported in Takayasu's arteritis, may present as Sudden Sensorineural Hearing Loss, and usually responds well to corticosteroid therapy. Hyperbaric Oxygen Therapy is commonly used as a supplementary treatment to corticosteroids for Sudden Sensorineural Hearing Loss. We present the case of a 36-year-old woman with Takayasu's arteritis who had two episodes of sudden hearing loss involving one ear at a time with an 11-month delay between each episode. During the first episode, the patient was treated with high-dose intramuscular corticosteroids with a temporary improvement of auditory threshold that deteriorated 14 days after cessation of therapy. In the second episode, Hyperbaric Oxygen Therapy was associated with corticosteroids, with improvements in both ears, including the one that was unresponsive in the long term to previous pharmacologic therapy. In this case, Hyperbaric Oxygen Therapy could have acted synergically with corticosteroids playing a role in hearing restoration.

Trophic and neurotrophic factors in human pituitary adenomas (Review).

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors ß (TGF­ß), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.

Prospective evaluation of Quasistatic Ultrasound Elastography (USE) compared with Baseline US for parotid gland lesions: preliminary results of elasticity contrast index (ECI) evaluation.

AIMS: To assess the diagnostic value of elasticity contrast index (ECI) elastography, in comparison with conventional ultrasound for the differentiation of benign and malignant parotid lesions. MATERIAL AND METHODS: Sixty-three consecutive patients with parotid gland tumors, treated surgically at a single tertiary center were enrolled. Ultrasound evaluation consisted of B-mode, color-Doppler and quasistatic ultrasound elastography (USE), conducted with the ECI technique. For each lesion the echogenicity, margins, vascularization, and capsulation were considered to determine benign or malignant lesions. Histology was considered the gold standard. RESULTS: Using conventional parameters, the observer suggested malignant lesions in 20 cases and benign lesions in 43 cases (accuracy: 61.8%). ECI>3.5 alone was the most accurate parameter (accuracy: 90.5%), with sensitivity of 93.7% and specificity of 89.4%. However, when combined with the other US criteria, no statistically significant diagnostic accuracy improvement was achieved. CONCLUSIONS: Our results show that USE with ECI index measurement can help to discriminate preoperatively benign from malignant lesions, with the exception of pleomorphic adenoma which is stiff. We suggest that USE can be used as an additional tool to conventional US evaluation of salivary gland lesions.

Vestibular Schwannoma and Ipsilateral Endolymphatic Hydrops: An Unusual Association.

Vestibular schwannoma and endolymphatic hydrops are two conditions that may present with similar audio-vestibular symptoms. The association of the two in the same patient represents an unusual finding that may lead clinicians to errors and delays in diagnosis and clinical management of affected subjects. We discuss the case of a patient with an intrameatal vestibular schwannoma reporting symptoms suggestive for ipsilateral endolymphatic hydrops. The patient presented with fluctuating hearing loss, tinnitus, and acute rotatory vertigo episodes, and underwent a full audiological evaluation and imaging of the brain with contrast-enhanced Magnetic Resonance Imaging. Clinical audio-vestibular and radiological examination confirmed the presence of coexisting vestibular schwannoma and endolymphatic hydrops. Hydrops was treated pharmacologically; vestibular schwannoma was monitored over time with a wait and scan protocol through conventional MRI. The association of vestibular schwannoma and endolymphatic hydrops is rare, but represents a possible finding in clinical practice. It is therefore recommended investigating the presence of inner ear disorders in patients with vestibular schwannoma and, similarly, to exclude the presence of this condition in patients with symptoms typical of inner ear disorders.

Combined modality therapy for thoracic and head and neck cancers: a review of updated literature based on a consensus meeting.

PURPOSE: Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial. METHODS: The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress. RESULTS: The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial. CONCLUSIONS: Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.

Chyle Leak Following Neck Dissection: Could Radiotherapy Be Considered a Management Option?

Chyle leak after neck dissection is a relatively rare complication in head and neck cancer scenario.This review summarizes the basic knowledge of chyle leak underlying the potential benefit induced by low-dose radiation therapy and may serve as basis for future studies, necessary to optimize chyle leak management in head and neck cancer patients.

Microscopic polyangiitis: Advances in diagnostic and therapeutic approaches.

Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. The disease predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). Microscopic polyangiitis was considered to be a disease entity by Savage et al. in 1985. Microscopic polyangiitis has a reported low incidence and a slight male predominance. The aetiology of MPA remains unknown. There is, however, increased evidence that MPA is an autoimmune disease in which ANCAs, particularly those reacting with MPO, are pathogenic. MPA belongs to the systemic vasculitides, indicating that multiple organs can be affected. The major organs involved in MPA are the kidneys and the lungs. As expected for an illness that affects multiple organ systems, patients with MPA can present with a myriad of different symptoms. Ear, nose and throat (ENT) manifestations are not considered to be clinical symptoms of MPA, but in the majority of populations described, ENT involvement was found in surprisingly high percentages. MPA is part of the ANCA-associated vasculitides, which are characterized by necrotizing vasculitis of small vessels. Diagnosis is mainly established by clinical manifestations, computed tomography (TC), ANCA antibody detection and renal and pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has substantially improved the prognosis. The standardized therapeutic regimen is based on cyclophosphamide and corticosteroids. Using this regimen, remission can be achieved in most of the patients. Rituximab may represent an important alternative to cyclophosphamide for patients who may not respond adequately to antimetabolite therapies.

Kawasaki disease: an evolving paradigm.

Kawasaki disease (KD) is a self-limited childhood systemic vasculitis that exhibits a specific predilection for the coronary arteries. KD predominantly affects young children between the ages of 6months and 4years. Incidence rates in Asians are up to 20 times higher than Caucasians. The aetiology of KD is not known. One reasonable open hypothesis is that KD is caused by an infectious agent that produces an autoimmune disease only in genetically predisposed individuals. The typical presentation of KD is a young child who has exhibited a high swinging fever for five or more days that persists despite antibiotic and/or antipyretic treatment. The lips are dry and cracked. There is a characteristic strawberry tongue, and a diffuse erythema of oropharyngeal mucosal surfaces. Lymphadenopathy is usually unilateral and confined to the anterior cervical triangle. Coronary aneurysms generally appear during the convalescence phase (beginning during the second week). The absence of any laboratory tests for KD means that the diagnosis is made by the presence of a constellation of clinical features. The aim of echocardiography is to assess the presence of coronary artery dilatation or aneurysm formation. Effective therapies exist for most patients with acute KD, but the exact mechanisms of action are not clear. Treatment with aspirin and intravenous immunoglobulins (IVIG) are first-line therapies. However, options are plentiful for the children who fail this treatment, but these treatments are not as beneficial. Some centres attempt to salvage resistant patients using intravenous pulsed doses of methylprednisolone. Other centres use infliximab or combinations of these approaches.