Change in FGF-2 circulating levels after arterial embolization in patients with bone metastases.

Arterial embolization, aimed at the mechanical occlusion of tumor-feeding vessels, represents a satisfactory palliative therapy for bone metastases. In this study, we evaluated if the circulating levels of three factors related to the metastatic process change in response to embolization. Seven patients who underwent embolization of a single skeletal metastasis from carcinomas were analyzed prospectively. Circulating levels of Vascular Endothelial Growth Factor A (VEGF-A), Fibroblast Growth Factor 2 (FGF-2), and Tartrate-Resistant Acid Phosphatase-5b Isoform (TRACP5b) were evaluated before and after embolization at 1, 3, and 6 months. According to morphological and clinical evaluations, all the embolizations were successful. VEGF-A and TRACP5b did not show significant changes after the treatment. On the contrary, FGF-2 signifi- cantly decreased 1 month after the treatment. FGF-2 appears as a promising candidate for monitoring the efficacy of emboli- zation in patients with osteolytic metastases.

Cisplatin can be safely administered to ovarian cancer patients with hypersensitivity to carboplatin.

OBJECTIVE: Hypersensitivity reactions (HSR) are frequently reported in patients rechallenged with carboplatin for recurrent ovarian cancer (ROC) and represent a critical issue, since discontinuation of the platinum-based therapy could affect prognosis. Several strategies to allow platinum rechallenge have been described, with controversial outcomes. The aim of this study is to illustrate a 10-year experience with cisplatin in patients with a previous HSR to carboplatin or at risk for allergy. METHODS: A retrospective review of all patients with platinum sensitive ROC retreated with carboplatin was performed between January 2007 and May 2016 at the Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples. RESULTS: Among 183 patients, 49 (26.8%) presented HSR to carboplatin, mainly during second line therapy. Mean number of cycles before HSR was 8 (range 3-17). G2, G3 and G4 reaction were detected in 83%, 15% and 2% of patients, respectively. In a multivariate analysis including age, hystotype, BRCA status, previous known HSR, and combination drug administered, only the type of carboplatin-based doublet used as 2nd line therapy was found to significantly affect HSR development, with a protective effect of PLD (pegylated liposomal doxorubicin) (p = 0.014, OR = 0.027). Thirty seven patients (77%) with a previous HSR to carboplatin were rechallenged with cisplatin. Treatment was generally well tolerated. 5 patients (13.1%) experienced mild HSR to cisplatin, successfully managed in all cases. 14 patients were treated with cisplatin even without a carboplatin-related HSR due to other allergies. Among these, only one developed HSR (7.1%). CONCLUSIONS: Cisplatin rechallenge is a feasible approach in patients experiencing HSR to carboplatin to maintain the beneficial effect of platinum while reducing hypersensitivity-related risks.

Intravesical chemo-immunotherapy in non muscle invasive bladder cancer.

Non-Muscle-Invasive-Bladder-Cancer represents 75-85% of the new bladder cancer cases per year. Trans-uretral vesical resection is the milestone for diagnosis and therapy. After primary treatment, recurrence is frequent depending on the presence of several established risk factors: multiplicity, T dimension, prior recurrence. In some patients disease progress to an advanced stage. Adjuvant chemo-immunotherapy has been widely used depending on the risk category assigned on the basis of the risk factors for recurrence. In low risk categories a one shot treatment with chemotherapy is considered the standard treatment without any maintenance therapy. In intermediate risk patients, adjuvant induction therapy and maintenance chemotherapy or immunotherapy for at least one year is recommended. In high risk patients adjuvant induction and maintenance immunotherapy until 3 years is considered the best strategy. In this review data on the different drugs used in this setting will be discussed.

An Italian multicenter retrospective real-life analysis of patients with brain metastases from renal cell carcinoma: the BMRCC study.

BACKGROUND: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC). PATIENTS AND METHODS: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS). RESULTS: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59). CONCLUSIONS: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients.

Improved Survival and Quality of Life Through an Integrative, Multidisciplinary Oncological Approach: Pathophysiological Analysis of Four Clinical Cancer Cases and Review of the Literature.

Objectives: According to the National Cancer Institute, the integrative medicine (IM) approach to medical care combines standard medicine with complementary and alternative medicine practices that have proved safe and effective. Methods: We describe the clinical cases of four patients with malignant pleural mesothelioma (MPM), diffuse malignant peritoneal mesothelioma (DMPM), intrahepatic cholangiocarcinoma, and breast cancer (BC) who received supportive treatment (ST) according to an IM approach after the failure of standard cancer treatments or the appearance of serious adverse events caused by antiblastic chemotherapy. The critical role of complementary drugs in reducing the side effects of cancer treatments and normalizing the white cell count is especially apparent in the case of the patient with metastatic BC, who experienced prolonged neutropenia. Results: The IM approach was well-tolerated and had no adverse side effects. It improved the quality of life (QoL) of all patients and in two cases extended overall survival. Conclusion: The extended clinical and instrumental response to IM of the patients with malignant mesothelioma and the improved health-related QoL and good tolerance of the ST demonstrated in all cases support the value of this approach in patients whose cancer therapies have failed but who show a good performance status. Our data require confirmation in a well-designed prospective clinical trial.

Management of systemic prostate cancer: current algorithm from castration sensitive to castration resistant setting.

In recent years, the advanced knowledge of clinical, biological and molecular features of prostate cancer have led to the introduction of new drugs and have allowed the relocation of old drugs in different settings. In this way, the new concepts of systemic disease arise: high risk or high volume vs. low risk and low volume disease castration sensitive prostate cancer (CSPC), diversifying the use of previously approved drugs (CRPC) and opening new scenarios for sequence therapy. The aim of this review is to integrate new developments into the medical management of systemic prostate cancer.

Follow-up with CA125 after primary therapy of advanced ovarian cancer: in favor of continuing to prescribe CA125 during follow-up.

Serum cancer antigen 125 (CA125) is widely used in ovarian cancer to monitor the effectiveness of therapy both in first line and recurrence. It is also widely used during follow-up, where it is able to identify a percentage of patients with asymptomatic recurrence. Although a recent Medical Research Council (UK)/European Organisation for Research and Treatment of Cancer trial has demonstrated that early chemotherapy in asymptomatic patients based only on CA125 increase does not prolong survival, we still believe that CA125 monitoring should be prescribed to patients during follow-up. In fact, it can help to identify patients who should undergo radiology in order to select those that can benefit from surgery or from early treatment before the onset of symptoms, which are usually related to an excessive disease burden. The delay of disease symptoms, such as those associated with the appearance of ascites or bowel occlusion, is in our view an important goal of our treatment of recurrence. Moreover, research should be done in patients with asymptomatic CA125 increase in order to identify more effective therapies that will improve survival. Finally, the reliability of CA125 as a surrogate of response under treatment with biological agents should be validated in prospective trials.

The Easy Thing (ET) observational study: evaluation of adherence to Mediterranean diet and role of a program of nutritional intervention performed by North Naples 2 Local Health Unit.

OBJECTIVE: The present observational study has the aim to describe the nutritional habits and adherence to Mediterranean diet within a dietary intervention performed by North Naples 2 Local Health Unit in some areas of Campania region. PATIENTS AND METHODS: A semi-quantitative food frequency questionnaire which takes in consideration several kinds of food and the related daily or weekly portions has been administered to people evaluated in the study. An increased score reflects an increased adherence to Mediterranean diet. Patients have been grouped by age, body mass index, education, socio-economic level, income, and score reported to the administered survey. Nutritional intervention has also been evaluated as concerns weight reduction during time. RESULTS: Surveys were administered to 200 patients aged from 12 to 79 years from 21 November 2018 to 27 November 2019. Obese patients were 61.5% in this population. 67.7% of obese people participating to this study had primary/lower secondary school education. 61.5% of study population have been categorized as having a low or low-medium socio-economic level and 68% of them were obese. An intermediate adherence to Mediterranean Diet has been the most represented (76.5%), a significant difference has been found among the groups normal weight, overweight and obese for the variables age, education and income. Obese patients in the present study had metabolic diseases more frequently than normal-weight patients. CONCLUSIONS: A high rate of obese people requesting nutritional counseling showed intermediate/bad adherence to Mediterranean Diet, reflecting the diffuse change from Mediterranean Diet to Western habits in nutrition. The nutritional intervention was found to be effective, especially for overweight patients. These data underline the need for further larger epidemiological analysis and public health interventions.

Endocannabinoid system expression in ovarian epithelial tumors according to the dualistic model of ovarian carcinogenesis.

OBJECTIVE: Our study aimed to confirm the expression of the endocannabinoid system in the human epithelial ovarian tumors, assessing the immunohistochemical expression of Cannabinoid Receptor Type 1 and Fatty Acid Amide Hydrolase in benign, borderline and malignant tumors. MATERIALS AND METHODS: Cannabinoid Receptor Type 1 and Fatty Acid Amide Hydrolase immunohistochemical expression was determined in 118 epithelial ovarian tumors sequentially treated during the last decade in our department: 36 benign, 34 borderline and 48 malignant neoplasms. Cannabinoid Receptor type 1 and Fatty Acid Amide Hydrolase expression resulted predominantly weak-moderate in the benign and borderline forms. RESULTS: concerning malignant tumors, Cannabinoid Receptor Type 1 expression resulted predominantly moderate-strong in Type I tumors and negative-weak in Type II tumors. Fatty Acid Amide Hydrolase expression resulted, instead, independent by the tumor types. Furthermore, there was no significant difference in the Cannabinoid Receptor Type 1 and Fatty Acid Amide Hydrolase expression relatively to the tumoral stages. CONCLUSIONS: The present study confirmed a variable expression of the endocannabinoid system in human ovarian tumors. Cannabinoid Receptor Type 1 expression was significantly different in malignant epithelial ovarian tumors according to dualistic model of ovarian carcinogenesis. Thus, in the most aggressive types II ovarian tumors, Cannabinoid Receptor Type 1 expression resulted predominantly negative or weak.

A growth model driven by curvature reproduces geometric features of arboreal termite nests.

We present a simple three-dimensional model to describe the autonomous expansion of a substrate whose growth is driven by the local mean curvature of its surface. The model aims to reproduce the nest construction process in arboreal Nasutitermes termites, whose cooperation may similarly be mediated by the shape of the structure they are walking on, for example focusing the building activity of termites where local mean curvature is high. We adopt a phase-field model where the nest is described by one continuous scalar field and its growth is governed by a single nonlinear equation with one adjustable parameter d. When d is large enough the equation is linearly unstable and fairly reproduces a growth process in which the initial walls expand, branch and merge, while progressively invading all the available space, which is consistent with the intricate structures of real nests. Interestingly, the linear problem associated with our growth equation is analogous to the buckling of a thin elastic plate under symmetric in-plane compression, which is also known to produce rich patterns through nonlinear and secondary instabilities. We validated our model by collecting nests of two species of arboreal Nasutitermes from the field and imaging their structure with a micro-computed tomography scanner. We found a strong resemblance between real and simulated nests, characterized by the emergence of a characteristic length scale and by the abundance of saddle-shaped surfaces with zero-mean curvature, which validates the choice of the driving mechanism of our growth model.

COVID-19 and radiotherapy: potential new strategies for patients management with hypofractionation and telemedicine.

COVID-19 disease is one of the biggest public health challenges in Italy and global healthcare facilities, including radiotherapy departments, faced an unprecedented emergency. Cancer patients are at higher risk of COVID-19 infection because of their immunosuppressive state caused by both tumor itself and anticancer therapy adopted. In this setting, the radiation therapy clinical decision-making process has been partly reconsidered; thus, to reduce treatment duration and minimize infection risk during a pandemic, hypofractionated regimens have been revised. Moreover, telemedicine shows its helpfulness in the radiotherapy field, and patients get the supportive care they need minimizing their access to hospitals. This review aims to point out the importance of hypofractionated RT and telemedicine in cancer patient management in the COVID-19 era.

Advanced/metastatic bladder cancer: current status and future directions.

In 2015 bladder cancer was the fourth most frequent malignancy and the eighth cause of death for cancer. At diagnosis, about 30% of bladder cancer (BC) patients present a muscle-invasive bladder cancer (MIBC) and 5% a metastatic bladder carcinoma (MBC). For fit MBC patients, combination chemotherapy (CC) is the standard of care for first-line treatment. CC includes both the treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) either the classical or the dose-dense MVAC regimen, and the doublet therapy with cisplatin and gemcitabine (CG). Median progression free survival (PFS) was 7 months and median overall survival (OS) was 15 months. The present review provides an update on the management of MBC, with focus on target therapies, immune checkpoint inhibition, looking for prognostic and predictive factors.

Penile cancer: prognostic and predictive factors in clinical decision-making.

Penile cancer (PC) is a typical tumor of non-industrialized countries. The incidence is 20-30 times higher in Africa and South America, considering the elevated prevalence of sexually transmitted diseases. Histologically, PC includes squamous cell carcinoma (SCPC), the most frequent, and nonsquamous carcinoma (NSCPC). Early diagnosis is the goal, whereas later diagnosis relates to poor functional outcomes and worse prognosis. The 5-year survival rate is 85% for patients with histologically regional negative lymph nodes, compared to 29%-40% for those with histologically regional positive lymph nodes. To date no new drugs are approved, and there are few new data about molecular mechanisms underlying tumorigenesis. The SCPC remains a rare tumor and the current therapeutic algorithm is based principally on retrospective analysis and less on prospective trials. In this review article, biomarkers of prognosis and efficacy of current treatments are summarized with a focus on those that have the potential to affect treatment decision-making in SCPC.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

Influence of lymph node dissection in patients undergoing radical nephrectomy for non-metastatic renal cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Whether lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for non-metastatic renal carcinoma has still been controversial recently. We conducted a meta-analysis assessing oncologic outcomes of radical nephrectomy with lymph node dissection (LND) and without lymph node dissection (non-LND) in non-metastatic renal cell carcinoma (NMRCC). PATIENTS AND METHODS: A systematic review was performed until April 2018 using a comprehensive search in PubMed, EMBASE, and Cochrane Library databases to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing radical nephrectomy with LND and radical nephrectomy with non-LND for cT1-T4NxM0 tumors. Furthermore, a subgroup analysis for locally advanced renal cell carcinoma (cT3-T4NxM0) was conducted. RESULTS: Thirteen studies on patients with LND and non- LND were identified and included in the analysis. LND group did not have a significantly better survival than non-LND group for cT1-T4NxM0 tumors (HR 0.93, 95% CI 0.78-1.11, p=0.45), However, in the subgroup of locally advanced renal cell carcinoma (cT3-T4NxM0), it showed a significantly better OS rate in patients who had undergone LND compared to those without LND (HR 0.73, 95% CI 0.60-0.90; p=0.003). CONCLUSIONS: LND offers better cancer control and better long-term survival in locally advanced renal cell carcinomas (cT3-T4NxM0). This conclusion should be confirmed by a prospective randomized clinical trial.

Prognostic and predictive factors in testicular cancer.

OBJECTIVE: Testicular cancer is a relatively rare neoplasia, with an incidence of about 1,5% among male malignancies, usually in the third and fourth decade of life. Although several histological variants are known, with some histotypes affecting older patients (e.g., spermatocytic seminoma), there is a clear predominance (90-95%) of germ cell tumors among young adults patients1. Testicular Germ Cell Tumor (TGCT), undoubtedly the seminoma histological variant more than non-seminoma one, is definitely a highly curable disease, with a distinctive sensitivity to cisplatin-based therapy (and for seminomas to radiotherapy) and an outstanding cure rate of nearly 80% even for patients with advanced disease. So far, clinical and pathohistological features supported our efforts to choose the best treatment option for patients suffering from this malignancy, but we don't clearly enough know molecular and pathological features underlying different clinical behaviors, mostly in early-stage disease: by improving this knowledge, we should better "shape" therapeutic or surveillance programs for each patient, also in order to avoid unnecessary, if not harmful, treatments.

Pulmonary masses in a patient with blue-gray cutaneous hyperpigmentation.

Authors describe a case of pulmonary masses and estensive skin pigmentation: "blue-gray syndrome" occurred in a patient in amiodarone therapy who presented with progressive dyspnea, cough, and fever. The diagnosis was suspected by detection of a high attenuation of the pulmonary masses on the nonenhanced chest computed tomography (CT) and lots of foamy macrophages in the bronchoalveolar lavage fluid. Relief of respiratory symptoms and radiological improvement was achieved when amiodarone treatment was stopped.

Health-related quality of life and psychosocial implications in testicular cancer survivors. A literature review.

OBJECTIVE: In this review, we focused our attention on Quality of Life (QoL) of testicular cancer survivors (TCSs), in general and in the most relevant areas. Several key findings have been highlighted in our review. MATERIALS AND METHODS: PubMed, MEDLINE and PsycINFO databases were consulted to find published studies, from 1980 to May 2017, that met our inclusion criteria. RESULTS: The majority of studies investigated older adult TCSs, while few studies on adolescent and young adult patients were available. Many studies indicate that health-related QoL (HRQoL) is similar among the TCSs and the general population. Even if QoL deteriorates so clear at the time of diagnosis and throughout treatment, afterward returns to normal levels, as defined by the matched controls. However, there are numerous chronic conditions consequent to diagnosis and treatment of testicular cancer that plague survivors and affect QoL, like Raynaud-like phenomena, peripheral neuropathy, fatigue, anxiety, sexual, fertility and body image problems. Even if these problems can have no effects on the measures of global QoL, they have an impact on the quality of life. Differences between TCSs with and without a partner bring to different outcomes in the adjustments to cancer. CONCLUSIONS: It is necessary to identify TCSs with higher risks of poorer QoL outcomes, to focus interventions on the areas with the greatest impairments. Further researches should consider the effects of testicular cancer on the impaired areas, collecting more data to better identify survivor's needs and consequent interventions, with a special focus on adolescent and young adult TCSs. Other works are requested on therapies, preventive and ameliorative, to reduce chronic side effects of testicular cancer treatment.

The clinical response on bone metastasis from breast and lung cancer during treatment with zoledronic acid is inversely correlated to skeletal related events (SRE).

Current management of bone metastases involves a multimodal approach. Aminobisphosphonates (BPs) are a valid weapon in the treatment of skeletal localization of tumour disease. Patients with bone metastases from breast and lung cancer were enrolled in order to evaluate the impact of the addition of bisphosphonates therapy to standard treatments in terms of (i) pain control, (ii) quality of life (QoL) and (iii) toxicity and to evaluate (iv) any relations between clinical activity and the occurrence of SREs. A total of 60 patients were included in the study. Median age was 76 years (range 40-83). The majority of patients were treated with chemotherapy or hormonal therapy. All patients received zoledronic acid (ZOL) (4 mg) every 3-4 weeks for at least 3 cycles. No significant improvement in Performance Status of patients after 12 cycles of ZOL (p = 0.1672) was recorded. A statistically significant early and long-lasting amelioration of both pain, narcotic scores and QoL was found. Twenty-one patients (48%) experienced at least one SRE during the study. The most common SRE was radiation to bone (30% of patients). An inverse correlation between bone tumour response and SREs was also found (p = 0.019). ZOL addition induces a clinical benefit and improves QoL of patients with bone metastases. Moreover, the occurrence of bone clinical response is related to a reduced risk of SREs.

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.