Thoracic outlet syndrome: a rare case with bilateral cervical ribs and bilateral anterior scalene hypertrophy.

Thoracic outlet syndrome (TOS) is a rare neurovascular disorder generally caused by the presence of a cervical rib or hypertrophic scalene anterior muscle that can compress the brachial plexus and/or subclavian vessels. In the vascular form, the symptoms are caused by the compression of the artery and/or the subclavian vein. In the first case, the compression is caused by the cervical rib and leads to hypo-perfusion with cooling and cyanosis of the upper limb, while in the second case, the compression is caused by the anterior scalene muscle and leads to congestion, cyanosis, swelling and pain in the higher limb. In this paper, we describe a case with the simultaneous presence of a bilateral cervical rib and bilateral hypertrophy of the anterior scalene muscle. TOS diagnosis is based on neurological, clinical and instrumental tests, such as chest radiography and color Doppler ultrasonography. The treatment of these patients can be surgical or conservative.

Gender Differences and Outcomes in Melanoma Patients.

INTRODUCTION: Melanoma is one of the most common cancers in younger people. The incidence of cutaneous melanoma is increasing in patients of both sexes, with female patients generally living longer than their male counterparts. The aim of this retrospective study was to evaluate and confirm the sex-based difference in survival of melanoma patients and the relationship of this difference with pathological features. METHODS: A total of 1023 patients who had been treated at the Department of Medical Oncology, Università Politecnica Marche (Ancona, Italy) and the INRCA-IRCCS Department of Dermatology (Ancona, Italy) between 1987 and 2014 were enrolled in the study. RESULTS: In terms of stage of disease at onset, there was a significant difference in disease-free survival (DFS) and overall survival (OS) in favor of female patients in disease stage I (P = 0.001 and P = 0.01, respectively) and II (P = 0.02 and P = 0.009, respectively). Female patients also showed a significant improvement in 12-year DFS and 12-year OS adjusted for pathological features (Breslow thickness, ulceration, "absent" tumor-infiltrating lymphocyte (TIL) melanomas, "non-brisk" TIL pattern). Globally, female patients had an advantage over with male patients in both DFS and OS (P < 0.001). CONCLUSIONS: Our results show that women have a survival benefit over with men after adjustment for many variables that can reduce mortality risk in female melanoma patients. In a future investigation we wish to examine possible biological sex differences in tumor-host interactions.

[Giant parathyroid adenoma: a rare cause of severe hypercalcemia].

We report the case of a 37-year-old woman that developed severe hypercalcemia due to a parathyroid gland mass. After the initial medical treatment, only a minimal reduction of calcemia was observed and her clinical condition worsened; thus, she required continuous renal replacement therapy (CRRT) that resulted in the normalization of calcium serum level. She then underwent a left thyroid lobectomy with exeresis of the associated parathyroid glands; the histological diagnosis revealed a giant parathyroid adenoma (GPA). CRRT, initially recommended only in case of severe refractory hypercalcemia poorly responsive to pharmacological approaches, is now being evaluated in the first line treatment of life-threatening cases, with or without associated acute kidney injury (AKI).

Systemic Treatment for Metastatic Hormone Sensitive Prostate Cancer: A Comprehensive Meta-Analysis Evaluating Efficacy and Safety in Specific Sub-Groups of Patients.

BACKGROUND AND OBJECTIVES: Several systemic treatments are available for metastatic hormone sensitive prostate cancer (mHSPC) including docetaxel (D), abiraterone and prednisone (A + P) and new anti-androgens (NA). In our study we performed a systematic review and meta-analysis assessing efficacy outcomes (survival and radiological-free survival), safety and survival on specific subgroups of patients. METHODS: Outcomes of interest were: (i) Risk of death, biochemical and radiological progression among all patients. (ii) Risk of death according to different pathological/clinical features. (iii) Evaluation of the relative risk (RR) and risk difference of serious toxicity defined as adverse events (AEs) with grade ≥ 3 specific AEs. Hazard ratios (HRs) and RR were measures adopted for endpoints 1-3. RESULTS: Overall, eight randomized trials were included in meta-analysis for a total of 9987 patients. Administration of D, A + P and NA resulted in improved overall survival (OS) and radiological progression-free survival (rPFS). Survival benefit was not confirmed in patients receiving NA and previously exposed to docetaxel (HR 0.948, 95% CI 0.671-1.338). Patients with visceral metastases and high lactate dehydrogenase (LDH) did not benefit from NA treatment, while it seems that patients with low Gleason score do not benefit from A + P. NA showed the more favorable safety profile. CONCLUSION: NA may not provide survival benefit when adopted subsequently or in concomitant to D. Specific subgroups of patients may benefit more from A + P, D or NA. Safety profiles significantly differ among agents evaluated.

The role of angiogenetic single-nucleotide polymorphisms in thymic malignancies and thymic benign lesions.

BACKGROUND: We previously showed that selected single-nucleotide-polymorphisms (SNPs) of genes involved in angiogenesis influence the aggressiveness of thymic epithelial tumors (TETs). This study analyzes their role in TETs and in thymic benign lesions, in order to investigate potential correlation with risk and outcome. METHODS: Genomic DNA was extracted from paraffin-embedded tissue of 92 patients, undergoing surgery at our Institution. We investigated by Real-Time PCR the SNPs of the following genes: platelet-derived growth factor receptor-α (PDGFRα), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor-2 and 3 (VEGF-2, VEGFR-3), excision repair cross-complementation group-1 (ERCC1). RESULTS: Fifty-seven TETs and 35 thymic benign lesions were included into the study. Frequency of SNPs was as follows: rs2057482 C, rs11158358 C and rs11549465 C polymorphisms of HIF1-a: thymomas < general population (P=0.008, P=0.007, and P=0.044 respectively). HIF1-a alleles: general population > study groups, rs1951795C SNP (P=0.026 for benign lesions and P=0.0007 for thymomas), rs10873142T SNP (P=0.008 and P=0.001 respectively), rs12434438 A SNP (P=0.034 and P=0.0007) and rs2301113A SNP (P=0.027 and P=0.010). rs699947C polymorphism of VEGF-A: benign lesions > general population (P=0.012). CONCLUSIONS: This is the first study investigating the angiogenetic polymorphisms in thymic benign lesions and TETs. SNPs analysis may represent a further asset in identification of patients who could benefit from anti-angiogenetic therapy.

Endoscopic stapedotomy: safety and audiological results in 150 patients.

OBJECTIVE: The most widely accepted treatment for otosclerosis is currently microscopic stapes surgery under either local or general anesthesia. The aim of the study is to describe the surgical steps in endoscopic stapes surgery and to evaluate the audiologic and surgical outcomes. MATERIALS AND METHODS: All patients who underwent exclusive endoscopic stapes surgery or revision surgery for previous stapedotomy between November 2014 and September 2018 were enrolled in this study. Demographic data, surgical information, preoperative and postoperative pure tone averages and air bone gaps, intraoperative and postoperative complications and follow-up data were summarized and gathered in a database for further consideration and analysis. RESULTS: In the period examined, 181 stapes surgical procedures were performed and out of these 150 met the inclusion criteria. There were no cases of major intraoperative complications. Sensorineural hearing loss was observed in one case. In one patient a gusher effect occurred during surgery. The postoperative air-bone gap improved significantly compared to the preoperative gap (8 vs 29 dB HL, respectively), and the mean air-bone gap closure was 20 dB HL. In 78.7% of cases, the observed postoperative air-bone gap was less than 10 dB HL and in 14% it was between 11 dB HL and 20 dB HL. An ABG closure lower than 20 dB HL was achieved in a total of 92.7% of patients. CONCLUSIONS: Endoscopic stapes surgery is a safe procedure with a low risk of peri- or postoperative complications and is a possible alternative to the traditional microscopic surgical procedure in the treatment of otosclerosis.

Targeted therapy for solid tumors and risk of hypertension: a meta-analysis of 68077 patients from 93 phase III studies.

Objective: Hypertension is a common adverse event with targeted agents in cancer patients and can lead to serious and sometimes lethal cardiovascular complications. The authors performed a meta-analysis of clinical trials aiming to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade Hypertension Events (HE) in patients with solid tumors receiving targeted therapy.Methods: A review of citations from PubMed was performed and studies were selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was limited to randomized phase III trials published in English focused on the efficacy and safety of targeted agents in cancer patients, reporting data on HE. Incidence, RR and relative 95% CIs were analyzed using random or fixed-effects models. Overall incidences were calculated and further compared with the chi-squared test for proportions.Results: Ninety-three phase III trials were included, with a total of 68,077 patients. Prostate cancer was the most represented (18.9%), followed by breast cancer (17.3%) and colorectal cancer (16.4%). The incidence of all- and high-grade HE was 23.47% and 8.57%, respectively, with the highest incidence of serious HE reported by adjuvant Sunitib/Sorafenib (29.03%). The highest RR of high-grade HE was observed with Bevacizumab in patients with advanced cervical cancer. By drug category, the highest RR of high-grade HE was reported by VEGFR/EGFR TKIs.Conclusion: According to these data, monitoring this class of toxicities is of primary importance to avoid hypertension worsening and, thus, the risk of major cardiovascular events.

Cervical margin relocation: case series and new classification system.

PURPOSE: The present clinical study aimed to investigate the safety and feasibility of cervical marginal relocation (CMR) procedures in cases of deep caries involving supracrestal tissue attachment (STA). MATERIALS AND METHODS: Fifteen patients were selected from those attending the Studio Ghezzi Dental Clinic, Settimo Milanese, Milan, Italy. After following an oral hygiene program with specific counseling sessions, the selected patients were included in a periodic supportive periodontal therapy program. Depending on the treatment they received, the patients were divided into three groups according to a new classification system: a) Class 1: Nonsurgical CMR; b) Class 2a: Surgical CMR (gingival approach); c) Class 2b: Surgical CMR (osseous approach). The primary and secondary outcomes were pocket depth (PD) on probing and residual bleeding on probing (BOP) after 1 year. RESULTS: No differences were found among the three CMR approaches for PD (overall mean value after 1 year: 2.5 ± 0.64 mm; overall mean value after 5.7 years: 2.3 ± 0.49 mm) or residual BOP (40% of the cases after 1 year). CONCLUSION: Based on the study results, the authors can conclude that CMR procedures do not negatively affect the periodontal health status of patients when the connective compartment of the STA is not violated.

Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors.

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

Risk of fatigue in cancer patients treated with anti programmed cell death-1/anti programmed cell death ligand-1 agents: a systematic review and meta-analysis.

AIM: We aimed to assess the incidence and relative risk (RR) of fatigue in cancer patients treated with anti programmed cell death-1 (PD-1) and anti programmed cell death ligand-1 (PD-L1) agents. PATIENTS & METHODS: Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Incidence, RR and 95% CIs were calculated using random or fixed-effects models. RESULTS: Thirty-eight studies were included in this analysis, with a total of 11,719 patients. The incidences were 23.4 and 2.1% for all- and high-grade fatigue, respectively. The highest incidence of high-grade fatigue was reported by the combination of nivolumab and ipilimumab. Overall RR of high-grade fatigue with anti-PD-1/PD-L1 compared with chemotherapy or targeted therapy was 0.48. CONCLUSION: Treatment with anti-PD-1/PD-L1 agents correlates with lower incidence and RR of fatigue compared with standard therapies.

Autophagic Gene Polymorphisms in Liquid Biopsies and Outcome of Patients with Metastatic Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Autophagy has been shown to be involved in cancer development and response to cancer therapy. In this study, genotypes of autophagic genes were analyzed to assess their correlation with the risk of clear cell renal cell carcinoma (ccRCC) and the outcome of patients treated with pazopanib for metastatic ccRCC. MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs)were selected in the following genes: ATG4A (rs7880351), ATG4B (rs6709768), ATG4C (rs2886770, rs6670694, rs6683832), ATG5 (rs9373839, rs3804333, rs490010), ATG16L1 (rs6752107), ATG16L2 (rs10751215) and IRGM (rs10059011). The Kaplan-Meier method and log-rank test were used to evaluate differences between groups. RESULTS: Forty patients with metastatic ccRCC treated with pazopanib were included in the analysis. ATG16L2rs10751215 was significantly less frequent in patients with ccRCC compared to the general population, suggesting its potential protective role, while ATG4Ars7880351, ATG4C rs6670694 and rs6683832 and ATG5 rs490010 were correlated with the progression-free survival (PFS) of patients treated with pazopanib. CONCLUSION: Our results suggest, for the first time, that autophagic gene SNPs are associated with ccRCC risk and patient outcome.

Emerging Biomarkers in Bladder Cancer Identified by Network Analysis of Transcriptomic Data.

Bladder cancer is a very common malignancy. Although new treatment strategies have been developed, the identification of new therapeutic targets and reliable diagnostic/prognostic biomarkers for bladder cancer remains a priority. Generally, they are found among differentially expressed genes between patients and healthy subjects or among patients with different tumor stages. However, the classical approach includes processing these data taking into consideration only the expression of each single gene regardless of the expression of other genes. These complex gene interaction networks can be revealed by a recently developed systems biology approach called Weighted Gene Co-expression Network Analysis (WGCNA). It takes into account the expression of all genes assessed in an experiment in order to reveal the clusters of co-expressed genes (modules) that, very probably, are also co-regulated. If some genes are co-expressed in controls but not in pathological samples, it can be hypothesized that a regulatory mechanism was altered and that it could be the cause or the effect of the disease. Therefore, genes within these modules could play a role in cancer and thus be considered as potential therapeutic targets or diagnostic/prognostic biomarkers. Here, we have reviewed all the studies where WGCNA has been applied to gene expression data from bladder cancer patients. We have shown the importance of this new approach in identifying candidate biomarkers and therapeutic targets. They include both genes and miRNAs and some of them have already been identified in the literature to have a role in bladder cancer initiation, progression, metastasis, and patient survival.

Immunotherapy in renal cell carcinoma: latest evidence and clinical implications.

Advances in understanding the mechanisms of tumour-induced immunosuppression have led to the development of immune-checkpoint inhibitors in cancer patients, including those with renal cell carcinoma (RCC). The optimal combination between immunotherapy and targeted agents (as well as the possible favourable sequential therapy of these two classes of drugs) remains an open question at this moment. Several trials are currently underway to assess the combination of anti-programmed-death 1 (PD-1) or anti-PD-ligand(L)1 agents with other immunotherapies or with anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). In this editorial, we described the results of the most recent clinical trials on the use of immunotherapies in RCC and the emerging data on the research for reliable biomarkers of tumour response in this setting. In addition, we have focused on the role of the gut microbiome and tumour microenvironment in the development of future therapeutic strategies for RCC patients.

Thyroid adenolipoma: a case report.

Generally, small quantities of adipose tissue is present in the thyroid gland. The adenolipoma of the thyroid gland is considered a rare finding. It consists in a benign, encapsulated neoplasm composed of mature adipose tissue and glandular elements. We report a case of a 71 year-old female patient presenting with swelling of the anterior neck and history of airway obstruction. Ultrasound (US) examination showed a bulky multinodular goiter which caused dislocation and compression of the trachea. The scans performed at the level of the isthmic region showed the presence of a hyperechoic oval formation with a homogeneous echostructure and regular contours; these characteristics suggested the lipomatous nature of the nodule. The patient was subsequently subjected to a Computer Tomography (CT) of the neck for a pre-operative balance of the goitre and to exclude extra-thyroid pathologies. The CT scan confirmed the sonographic findings, and the probable adipose nature of the isthmic formation. After the patient has been subjected to total thyroidectomy and histological examination confirmed the diagnosis of adenolipoma.

Wilkie's syndrome.

Superior mesenteric artery syndrome, also known as Wilkie's syndrome, is a rare vascular disease caused by the anomalous course of the superior mesenteric artery arising from the abdominal aorta with a smaller angle than the norm (<22°). The reduced angle compresses the structures situated between the aorta and the superior mesenteric artery, such as the duodenum and left renal vein; this can determine painful crises, intestinal subocclusions, and left varicocele. This syndrome can be congenital or acquired. The acquired type is more common and is generally caused by reduced perivascular fat surrounding the abdominal aorta and the superior mesenteric artery; this form is common among anorexic patients that have had a rapid weight loss. We present the case of a female patient who suffered from repeated postprandial vomiting and who lost 12 kg in 4 months. B-mode ultrasound imaging revealed evidence of a reduced angle between the aorta and the superior mesenteric artery, as found in Wilkie's syndrome. After diagnosis, the patient followed a high-calorie diet, and 2 months later an ultrasound scan proved the restoration of the aorto-mesenteric angle as a consequence of increased perivascular fat with regression of symptoms.

Copeman nodule: a case report.

The Copeman nodule is a disease of the subcutaneous soft tissue consisting in subcutaneous adipose tissue herniation through the superficial muscular fascia. A 30-year-old female patient presented with chronic left pain just above the iliac crest. Ultrasound examination showed subcutaneous adipose tissue herniation through the superficial muscular fascia with a hernia gap of 15.9 mm in diameter. Then the patient underwent surgery under local anesthesia with suturing of the hernia gap and immediate regression of chronic pain. Ultrasound can accurately highlight or exclude the presence of Copeman nodule and, in our view, should be used as first examination in patients with superficial chronic pain to the right or left side.

Assessing the relationship between toxicity and economic cost of oncological target agents: A systematic review of clinical trials.

Target agents are peculiar oncological drugs which differ from the traditional therapies in their ability of recognizing specific molecules expressed by tumor cells and microenvironment. Thus, their toxicity is generally lower than that associated to chemotherapy, and they represent nowadays a new standard of care in a number of tumors. This paper deals with the relationship between economic costs and toxicity of target agents. At this aim, a cluster analysis-based exploration of the main features of a large collection of them is carried out, with a specific focus on the variables leading to the identification of their toxicity and related costs. The analysis of the toxicity is based on the Severe Adverse Events (SAE) and Discontinuation (D) rates of each target agent considering data published on PubMed from 1965 to 2016 in the phase II and III studies that have led to the approval of these drugs for cancer patients by US Food and Drug Administration. The construction of the dataset represents a key step of the research, and is grounded on the critical analysis of a wide set of clinical studies. In order to capture different evaluation strategies of the toxicity, clustering is performed according to three different criteria (including Voronoi tessellation). Our procedure allows us to identify 5 different groups of target agents pooled by similar SAE and D rates and, at the same time, 3 groups based on target agents' costs for 1 month and for the median whole duration of therapy. Results highlight several specific regularities for toxicity and costs. This study present several limitations, being realized starting from clinical trials and not from individual patients' data. However, a macroscopic perspective suggests that costs are rather heterogeneous, and they do not clearly follow the clustering based on SAE and D rates.

Incidence and risk of cardiotoxicity in cancer patients treated with targeted therapies.

BACKGROUND: Cardiotoxicityis a serious side effect of molecularly targeted agents. The purpose of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade cardiotoxicity in patients with solid tumors receiving targeted agents through a revised meta-analysis of available clinical trials. METHODS: The scientific literature regarding cardiotoxicity was extensively analyzed using MEDLINE, PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. RESULTS: Our search yielded a total of 4998 clinical studies; of them, 31 trials were finally considered for this meta-analysis. A total of 28,538 patients were included; 7995 of these patients had breast cancer (28%), 6151 (22%) prostate cancer and 14,392 (50%) were treated for other malignancies. The highest RR of high-grade events was observed with Vandetanib (RR=7.71, 95% CI 1.04-56.99), followed by Ramucirumab (RR=5.0) and Aflibercept (RR=4.1). Grouping by drug category, the highest incidence of high-grade cardiotoxicity was shown by anti-VEGFR-TKIs (RR 5.62, 95% CI 1.49-21.24) and anti-VEGF mAbs/VEGF-trap (RR 1.82, 95% CI 1.24-2.69). Grouping by tumor type, the highest incidence of cardiotoxicity was observed in thyroid cancer (8%), followed by gastric cancer (4%). CONCLUSIONS: Treatment with targeted agents in cancer patients is correlated with a significant increase in the risk of cardiotoxicity. Frequent clinical monitoring should be emphasized when using these and newer biological agents.

Update on histopathological evaluation of lymphadenectomy specimens from prostate cancer patients.

BACKGROUND: Metastases to lymph nodes (LNs) represent an unfavorable prognostic factor in patients with prostate cancer (PCa). Histological examination represents the gold standard in the evaluation of the lymphadenectomy (LND) specimens for the presence of secondary deposits. METHODS AND RESULTS: The metastatic detection rate can vary according to the approach adopted in the microscopic analysis of the LNs, which includes frozen-section examination, total inclusion of the tissue with and without whole-mount sections, serial sectioning, and the application of immunohistochemistry. The assessment of the sentinel LN, the search for micrometastases, and the evaluation of atypical LN metastatic sites further contribute to the detection of the metastatic spread. CONCLUSION: In this review, an update on the histopathological evaluation of LND specimens in patients with PCa is given, and focus is made on their clinical and prognostic significance.