Multiple vertebral metastases from brain glioblastoma: An insidious complication

Abstract Glioblastoma (GBM) is the most malignant and the most frequent of primary astrocytomas, typically involving the Central Nervous System (CNS) alone. Extra-CNS localizations (ECM) are exceptional, and vertebral dissemination is extremely uncommon. We present the case of a patient with vertebral dissemination from an intracranial GBM without intra-dural space invasion. The patient underwent a gross total tumor removal followed by radiation therapy (RT) with concomitant temozolomide chemotherapy (STUPP protocol). Following the appearance of back pain, patient underwent whole body computed tomography (CT) and spinal magnetic resonance imaging (MRI) scan. Spinal-MRI highlighted multiple vertebral lesions not infiltrating dura mater being confined to vertebral bodies. CT scan demonstrated the absence of other repetitive lesions in both thorax and abdomen. Histological examination from a percutaneous CT-guided vertebral biopsy confirmed the suspicious of secondary localization from intracranial GBM. To the best of our knowledge this is the second reported case of vertebral metastases from GBM in absence of other ECM. This case raises the need for clinical suspicious of vertebral dissemination in case of GBM patient presenting with radicular, myelopathic symptoms or less specifically, back pain

Surgical Brain Metastases: Management and Outcome Related to Prognostic Indexes: A Critical Review of a Ten-Year Series

Brain metastasis are the most common neoplastic lesions of the nervous system. Many cancer patients are diagnosed on the basis of a first clinical presentation of cancer on the basis of a single or multiple brain lesions. Brain metastases are manifestations of primary disease progression and often determine a poor prognosis. Not all patients with a brain metastases undergo surgery: many are submitted to alternative or palliative treatments. Management of patients with brain metastases is still controversial, and many studies have been developed to determine which is the best therapy. Furthermore, management of patients operated for a brain metastasis is often difficult. Chemotherapy, stereotactic radiosurgery, panencephalic radiation therapy, and surgery, in combination or alone, are the means most commonly used. We report our experience in the management of a ten-year series of surgical brain metastasis and discuss our results in the preoperative and postoperative management of this complex condition

Brain tumours in the time of COVID-19: An online survey on patients’ disease experience in one Italian region

BackgroundSince the outbreak, in 2019, of COVID-19, the world has experienced marked changes in daily habits, partly reflecting the exceptional social restrictions and health measures adopted to contain the disease. All these measures significantly affected not only peoples’s daily lives and psychological well-being but also the possibility for the healthcare system to function properly. In this setting, brain tumour patients were at risk due to their higher physical and mental fragility and their need for regular care. The aim of the present study was to assess, using a self-reported online questionnaire, the patients’s perceptions regarding their disease experience.Materials and methodsWe developed an online anonymous self-report survey to assess patients’s disease experience during the pandemic. We investigated the impact of the COVID-19 pandemic on patients’s cancer care schedules, their psychological distress and emotions felt during the pandemic, their levels of worry about COVID-19, and their oncological conditions.Results107 patients answered our survey, most of them suffering from a glioma. Less than one-third of the sample had their appointments cancelled, delayed or converted into online visits due to the pandemic. Of the patients who answered the survey, 95% declared they were satisfied with their Institute’s oncological management. The feelings reported most often were peacefulness or anxiety/worry; the majority of the sample reported high levels of loneliness, which tended to increase with age, whilst the psychological distress was correlated with age and with having a recurrence of the disease. Half of the sample declared severe worry about their oncological condition, in particular subjects with a recurrence or who were receiving adjuvant therapies. Patients with recurrence tended to worry more about the possibility of contracting COVID-19, and its effects.ConclusionOur findings illustrate how fragile and in need of care patients with a brain tumour may be, especially those with more severe clinical conditions. These data may help boost healthcare professionals’s knowledge about brain tumour patients’s needs and fears, so as to be able to offer them a better hospital experience and improve their clinical management, while possibly also reducing the psychological burden on patients and their families

Epigenetic Rewiring of Metastatic Cancer to the Brain: Focus on Lung and Colon Cancers

Distant metastasis occurs when cancer cells adapt to a tissue microenvironment that is different from the primary organ. This process requires genetic and epigenetic changes in cancer cells and the concomitant modification of the tumor stroma to facilitate invasion by metastatic cells. In this study, we analyzed differences in the epigenome of brain metastasis from the colon (n = 4) and lung (n = 14) cancer and we compared these signatures with those found in primary tumors. Results show that CRC tumors showed a high degree of genome-wide methylation compared to lung cancers. Further, brain metastasis from lung cancer deeply activates neural signatures able to modify the brain microenvironment favoring tumor cells adaptation. At the protein level, brain metastases from lung cancer show expression of the neural/glial marker Nestin. On the other hand, colon brain metastases show activation of metabolic signaling. These signatures are specific for metastatic tumors since primary cancers did not show such epigenetic derangements. In conclusion, our data shed light on the epi/molecular mechanisms that colon and lung cancers adopt to thrive in the brain environment

Use of the stable isotope 65Cu test for the screening of Wilson's disease in a family with two affected members

An improved method for the study of copper metabolism in Wilson's disease, using a stable, rather than radioactive, copper isotope (65Cu) has recently been described. We report on the use of this method for the study of a family with two members affected by Wilson's disease. SUBJECTS: The family comprised parents and four siblings: one 20-year-old male and three females, aged 22, 17 and 5 years, respectively. The boy and the 17-year-old girl both presented with liver cirrhosis. Diagnosis of Wilson's disease was suggested by elevated liver copper content and/or low caeruloplasmin levels and Kayser-Fleischer ring. METHODS: All family members were given an oral dose of 3 mg of 65Cu. Blood samples were taken at 0, 1, 2, 6, 24, 48, and 72 hours. In 4 subjects, additional blood samples were drawn at 7, 14 and 21 days after dosage. The ratio 65Cu:63Cu in serum was determined in all samples by means of Inductively Coupled Plasma Mass Spectrometry. RESULTS: The diagnosis of Wilson's disease was confirmed in the two symptomatic members by the unequivocal decrease observed in the 65Cu percent enrichment, which approached zero by 72 hours. In contrast, Wilson's disease could be definitely excluded in both siblings, one of whom only 5 years old, on the evidence of net secondary peaks, showing normal incorporation of 65Cu into caeruloplasmin. These findings were later confirmed by genetic analysis. Parents, who carried defective genes with different mutations, also showed different abnormalities of copper metabolism. CONCLUSIONS: The oral test with the stable copper isotope 65Cu is a safe, non invasive option able to exclude Wilson's disease in patients with a difficult diagnosis or in a presymptomatic stage. However, positive tests must still be confirmed by copper dosage in liver biopsies, as heterozygotes can present with severe alterations of copper metabolism, without developing symptoms of the disease. The use of this test in conjunction with genetic analysis on a larger number of heterozygous subjects may add to the understanding of the Wilson's disease defect

Relationship between testosterone and HIV-related comorbidities: secondary hypogonadism is associated with a poor health status in HIV-infected men

ABSTRACT INTRODUCTION: Testosterone (T) deficiency is very common in men with Human Immunodeficiency Virus (HIV), and it is more often associated with inappropriately low/normal luteinizing hormone (LH). However, the underlying causes remain poorly understood. Moreover, the role of HIV and/or HIV infection treatments, as well as the role of the general health status on the gonadal axis have been rarely investigated. AIM: The aim of this study is to evaluate the association between gonadal function and health status in men with HIV infection. METHODS: We performed a cross-sectional, observational study on 1359 consecutive HIV male outpatients. Morning serum Total T (TT), LH, estradiol, HIV parameters were measured. Frailty Index and number of comorbidities were extracted from the Clinical Database in which all patients data are recorded. TT<300 ng/dL was used as the threshold for biochemical T deficiency. RESULTS: T deficiency was found in 212 subjects (15.6%), and most of them (n=183; 13.4%) had secondary hypogonadism. TT resulted inversely related to Frailty Index in all patients (r=0.302, r2=0.091), this correlation being strengthened in HIV- infected men with secondary hypogonadism (r=0.403, r2=0.162). The percentage of HIVinfected men with TT 5 comorbidities, respectively). CONCLUSION: Poor health status in HIV-infected men might be involved in the pathogenesis of hypogonadism. This mechanism could reflect an adaptive response to illness in unhealthy patients similarly to what happens in other clinical conditions such as anorexia nervosa. Thus, low TT could be considered a biomarker of frailty and might confer an advantage for both the sick patients (in terms of sparing energy) and the species (preventing fatherhood). Furthermore, frailty related hypogonadism could be part of the process of premature aging already demonstrated in HIVinfected patients

Feasibility and utility of re-treatment with 177Lu-DOTATATE in GEP-NENs relapsed after treatment with 90Y-DOTATOC

Purpose: Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 â\u80\u93 3 years. In the present study, we investigated the use of low dosage re-treatment with 177Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with 90Y-DOTATOC (Y-PRRT). Methods: Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 â\u80\u93 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated. Results: Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6 %, median PFS was 22 months (95 % CI 16 months â\u80\u93 not reached) compared to 28 months (95 % CI 20 â\u80\u93 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity. Conclusion: Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment