An innovative compact system for advanced treatment of combined sewer overflows (CSOs) discharged into large lakes: Pilot-scale validation.

Combined sewer overflows discharging into natural water bodies could potentially contaminate them in terms of conventional wastewater parameters and coliform bacteria. When green water infrastructures are not technically feasible or practically sustainable for stormwater management, innovative compact and effective end-of-pipe systems can be of interest. This study presents long-term and real-environment validated data of a compact and rapid treatment system specifically applicable to CSOs that consists of a dynamic rotating belt filter, adsorption on granular activated carbon and UV disinfection steps. The results of treatment for Lake Garda in Italy, showed great potential for TSS, COD and E. coli removal efficiencies with more than 90%, 69% and 99% respectively. Due to the short contact time of GAC adsorption, nutrients removals were not very high. TN and TP removal of around 41% and 19% were observed respectively that suggests further specific nutrients removal processes are required for achieving higher efficiencies. The treatment system, due to its compactness and rapidness could be a great asset for water utilities in different EU catchments that are dealing with the frequent CSO events. In addition, the possibility of using different combinations of treatment steps allows the choice of different treatment scenarios depending on the treatment goals for any specific catchment.

A case of medulloblastoma in adult patient affected by anaplastic oligoastrocytoma.

Medulloblastomas and high-grade gliomas (HGG) are two distinct brain tumor, with different peculiarities in terms of age of onset, localizations and prognosis. The coexistence of the two neoplasms in the same adult patient is an extremely rare event. We present the case of a woman treated with radio-chemotherapy for an HGG, who developed a cerebellar medulloblastoma 7 years later. Considering the poor prognosis of these tumors, the lack of knowledge about the mechanisms of onset as well as effective therapies, it is necessary to determine the exact role of irradiation and the presence of any potential molecular genetic abnormalities in the developing of the two tumors.

Safety and efficacy of primary central nervous system lymphoma treatment in elderly population.

Elderly patients represent an important subgroup in primary central nervous system lymphoma (PCNSL) that accounts for approximately half the cases. Furthermore age represents one of the heaviest prognostic factors and in some cases it has more effect on survival than therapies. We performed a retrospective analysis to assess the toxicity and the efficacy of high-dose methotrexate (HDMTX) chemotherapy in a PCNSL population older than 70 years. Seventeen consecutive immunocompetent patients older than 70 years, with histologically confirmed PCNSL, without systemic involvement, treated with HDMTX at our institution between May 2005 and April 2013, were retrospectively evaluated. Main outcome measures were acute toxicity and tumour response. No evidence of haematological toxicity was recorded in 47 % of patients and no deaths related to toxicity grade were reported. Patients achieved a partial response after 3 cycles of chemotherapy in 53 % of cases. The median overall survival (m-OS) from diagnosis was 20.9 months (range 5.2-34 months), with OS-12 of 58.8 % and an OS-24 of 45.4 %. Since there is no standard of care in the treatment of PCNSL in elderly population, it should be taken into account that elderly patients not always can be considered "fragile" and the general tendency to less treat to avoid severe toxicity should not be the rule.

Clinical management of grade III oligodendroglioma.

Oligodendrogliomas represent the third most common type of glioma, comprising 4%-15% of all gliomas and can be classified by degree of malignancy into grade II and grade III, according to WHO classification. Only 30% of oligodendroglial tumors have anaplastic characteristics. Anaplastic oligodendroglioma (AO) is often localized as a single lesion in the white matter and in the cortex, rarely in brainstem or spinal cord. The management of AO is deeply changed in the recent years. Maximal safe surgical resection followed by radiotherapy (RT) was considered as the standard of care since paramount findings regarding molecular aspects, in particular co-deletion of the short arm of chromosome 1 and the long arm of chromosome 19, revealed that these subsets of AO, benefit in terms of overall survival (OS) and progression-free survival (PFS), from the addition of chemotherapy to RT. Allelic losses of chromosomes 1p and 19q occur in 50%-70% of both low-grade and anaplastic tumors, representing a strong prognostic factor and a powerful predictor of prolonged survival. Several other molecular markers have potential clinical significance as IDH1 mutations, confirming the strong prognostic role for OS. Malignant brain tumors negatively impacts on patients' quality of life. Seizures, visual impairment, headache, and cognitive disorders can be present. Moreover, chemotherapy and RT have important side effects. For these reasons, "health-related quality of life" is becoming a topic of growing interest, investigating on physical, mental, emotional, and social well-being. Understanding the impact of medical treatment on health-related quality of life will probably have a growing effect both on health care strategies and on patients.

Cognitive strategies and quality of life of patients with high-grade glioma.

The purpose of this study was to analyze the psychological well-being, quality of life, and cognitive strategies activated by patients with high-grade glioma. We hypothesized that the self-perceived quality of life is modulated by physical and psychological factors and that in order to understand this modulation more psychometric approaches are necessary. Data were collected from a sample of 73 consecutive patients with a histological diagnosis of primary malignant brain cancer (grade IV glioblastoma and grade III anaplastic astrocytoma) hospitalized in a specialized Italian center. The Functional Assessment of Cancer Therapy (FACT) scale and the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) scale were used to assess quality of life. The mean FACT-Brain (Br) score was 122.37. Similarly, the median SEIQoL-DW score was 72.9 out of a maximum value of 100. No gender effect was found in relation to overall quality of life. Patients with high depression and/or anxiety scores reported lower quality of life (QoL) scores in all the instruments considered. We did not find any gender effect concerning depression and anxiety levels. However, we found that men and women, though having similar physical and functional well-being, reported different QoL determinants, since men seem to rely more on physical adjustment, while women activate more introspective strategies. Positive actions, family issues, negative thoughts, health, and positive thoughts were found to be the most reported themes. In conclusion, the present study strongly suggests that a positive psychological adjustment is possible also in the event of a severe diagnosis and during aggressive treatments, but QoL determinants might be considered too in order to help health professionals to understand patients' experience and to meet their needs.

Update on treatment strategies for anaplastic glioma: a review of literature.

Anaplastic gliomas (AG) include 6-10% of all newly diagnoses of primary brain tumors. They have an unfavourable prognosis and, to date, there is not an established treatment universally recognized. Four recent randomized clinical trials were identified for a total of 1,170 patients (anaplastic-astrocytomas, anaplasticoligoastrocytoma, anaplastic-oligodendroglioma), in order to define the better sequence and timing of chemo-radiotherapy, Three studies compared radiotherapy (RT) treatment vs. radio-chemotherapy with procarbazine-lomustine-vincristine (PCV) or temozolomide (TMZ) or dibromodulcitol and bichloroethylnitrosurea (DBD/BCNU) and only one compared RT vs chemotherapy (CT) with PCV or TMZ. Results show no significant differences in terms of PFS/OS between RT/CT alone or combined treatment although a trend toward an improvement of OS was observed after RT + CT treatment (m-OS in RT + adjuvant PCV was 42.3 vs. 30.6 months in RT alone p=0.0003). Grade 3-4 mielotoxicity has been observed in almost all cases of patients treated with PCV + RT. None of four studies reviewed conducted a head to head comparison between PCV vs. TMZ. Only a study randomized patients to PCV/TMZ without however providing data in terms of PSF and OS between the two treatments. It found no significant differences in PFS from initial RT and adjuvant CT (PCV-TMZ) at progression compared to initial CT followed by RT at progression. The optimal treatment of AG should reasonably consider not only the histology as well as the molecular markers of the tumor, but also clinical conditions, age of patients, life expectancy, Karnofsky-performance-status and tumor resection to achieve in future the personalization of care.

Safety of bevacizumab in patients with malignant gliomas: a systematic review.

Angiogenesis has recently become a major target for the development of new antineoplastic drugs. The most serious adverse events linked to angiogenesis inhibitors are venous or arterial thromboembolism and haemorrhage. Thus, there is need to define with more certainty the impact of these new drugs in terms of adverse effects in neurological patients. The aim of the study is to assess the risk of venous thromboembolism (VTE) and bleeding in patients with malignant gliomas treated with bevacizumab with or without concomitant anticoagulant therapy. A review of published literature was performed in Medline, from which 476 records were identified. A total of 27 full-text articles, including retrospective analyses, retrospective reviews, and open label trials, were assessed for eligibility. The investigated drugs included bevacizumab alone, bevacizumab plus chemotherapy with/without concomitant radiation therapy; only two articles dealt with bevacizumab in association with anticoagulant treatment. A total of 2,208 patients with malignant gliomas, were identified and included in the analysis. From data it appears that patients receiving bevacizumab had a major risk of developing VTE that increased when bevacizumab is associated with radio-chemotherapy (4.27 vs 7.46 %). Regarding bleeding, data showed that patients treated with anticoagulant had a significantly increased risk of severe central nervous system (CNS) bleeding compared to patients not receiving anticoagulant therapy (0.6 vs 8.2 %). The use of bevacizumab combined with chemo-radiotherapy seems to be associated with a higher risk for VTE compared to patients receiving antiangiogenic therapy alone. The associated use of anticoagulants and bevacizumab far increases the risk of developing CNS and non-CNS bleeding higher than grade 3, compared to patients receiving bevacizumab alone.

Liposomal cytarabine in neoplastic meningitis from primary brain tumors: a single institutional experience.

Neoplastic meningitis (NM) is diagnosed in 1-2 % of patients with primary brain tumors. Standard treatment of NM includes single-agent or combination chemotherapy, with compounds such as methotrexate, thiotepa, and cytarabine (Ara-C) or its injectable, sustained-release formulation Depocyte(®). In this Report, we reported the data of efficacy and tolerability of an intrathecal Depocyte(®) regimen for patients presenting with NM from primary brain tumors. We described 12 patients with NM confirmed at magnetic resonance imaging (MRI) and with a positive cerebrospinal fluid (CSF) cytology. Patients were treated with repeated courses of intrathecal Depocyte(®) (once every 2 weeks for 1 month of induction therapy and as consolidation therapy on a monthly base in responding patients). Twelve patients (10 males and 2 females) were treated by our Institution. The diagnosis of primitive brain tumor was medulloblastoma in six patients, germinoma in two patients, pylocitic astrocytomas with spongioblastic aspects, teratocarcinoma, meningeal melanoma, and ependimoma in the other four patients. The total number of Depocyte(®) cycles ranged from one to nine. In 7/12 patients, there was clinical and/or radiological response after Depocyte(®), and the toxicity was moderate and transient, mainly due to the lumbar puncture procedure. In the two patients with germinoma, we observed a normalization of MRI Imaging and negativization of CSF with disappearance of the tumor cells. OS was 180 days (range 20-300, CI 95 %).

Brain tuberculoma (Mycobacterium africanum): high index of suspicion helps in avoiding biopsy/surgery.

Partial seizures can be due to a growing cerebral lesion, which may be tumoral or inflammatory/infectious in nature. The differential diagnosis is obviously important; increasing immigration to Europe from Africa is leading to an increase of infectious disease involving also the central nervous system. The authors report imaging the a case of a brain tuberculoma due to Mycobacterium africanum mimicking brain tumor, in which diagnosis was possible by inoculum in guinea-pig of material obtained by mediastinal biopsy of enlarged lymph nodes. Specific treatment led to marked reduction in the size of the brain lesion.

Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a single institutional experience.

In 1991, a prospective phase II trial was initiated to evaluate the efficacy of treatment for adults with medulloblastoma (MB). After surgery, patients were staged with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology. All patients received three cycles of upfront cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio-spinal radiation therapy. The current article reports on the long-term results from that trial. After a median follow-up of 14.9 years, among a total of 28 adults with MB, the overall progression-free survival and overall survival (OS) rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole group of patients was 11.3 years. The observed toxicity was mainly hematological, with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our small series of patients, the role of combination administration of CDDP + VP16 started before the initiation of radiotherapy in reducing recurrences, particularly distant recurrences, remains unclear. To know whether adding chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.

Neuro-oncological diagnosis in patients without histological confirmation.

The impossibility to conduct a histological diagnosis could be due to different reasons: (1) patient's refusal to undergo surgery/biopsy. (2) Technical difficulties: despite the advance in surgical procedures, the removal of lesions that are located either in critical or in deep areas represents a considerable risk for patients. (3) Quality/quantity of the sample. In rare cases even when the surgical sample is achieved it could be impossible to reach a histological confirmation, for example due to the small amount of tissue obtained. The lack of histology leads to suboptimal therapy, incorrect prognosis, and misinterpretation of clinical trials and furthermore undermines the possibility to perform most radiation and chemotherapy protocols. In this setting the morphological data obtained with conventional MR imaging may be integrated with the metabolic, structural and perfusional information provided by new MR and metabolic techniques (spectroscopy, SPECT, PET in particular).

Malignant gliomas: early diagnosis and clinical aspects.

Brain tumor symptoms vary greatly from person to person because of two factors: location and size of tumors. The size of a tumor, however, does not necessarily affect the severity of symptoms. Manifestations depend on the cause of the symptoms: an increase in ICP, direct compression of gray or white matter, shifting of intracranial contents, or secondary cerebral ischemia. Symptoms may be non-specific and include headache, altered mental status, ataxia, nausea, vomiting, weakness, and gait disturbance. Left-sided weakness may be seen in a patient with a tumor pressing on the contra-lateral motor strip or speech difficulties may occur if a tumor is in the dominant hemisphere. Up to a third of people report having seizures prior to being diagnosed with a brain tumor. Rarely, brain tumor can present with psychiatric symptoms but without other neurological signs or symptoms. Evaluation for brain tumor is indicated in any patient with chronic, persistent headache associated with protracted nausea, vomiting, seizures, changes in headache pattern, neurologic symptoms, and change in personality.

Metabolic, electrolytes disorders and tromboembolic risk in malignant glioma patients.

In malignant gliomas, the management of symptoms and minimization of side effects assume major importance. Corticosteroids provide transient relief from neurological symptoms. However, treatment with steroids is also commonly associated with considerable side-effects including: hyperglycemia, osteoporosis, myopathy, lymphopenia and others. Sometimes, antiepileptic drugs may contribute to clinical decline of neuro-oncological patients in stable disease not only by neuropsychological impairment but also by metabolic interations. Several studies have demonstrated a high frequency of hyponatremia among patients treated with carbamazepine and particularly with oxacarbamazepine. Venous thromboembolism is a common complication in patients with cancer and it is particularly high in malignant gliomas, occurring in approximately 20-30% of such patients. Prophylactic treatment in patients with glioblastoma is a key topic. The role of prophylaxis has not yet been established with certainty. Overall the data show a clear reduction of venous thromboembolic events in patients treated with intermittent pneumatic compression (IPC). The addition of enoxaparin dose of 6.000 UI, starting in the perioperative period, induces an increase of major bleeding events. In the absence of availability of IPC, the use of enoxaparin 4.000 UI in addition to graduated compression stockings, reduces thromboembolic events without major bleeding events.

Rechallenge with temozolomide in recurrent glioma.

Despite a confirmed survival benefit associated with adjuvant radio- and chemotherapy, the majority of patients with malignant glioma relapse after initial therapy. Recurrent malignant glioma treatment has not been standardised and usually the response rate to standard chemotherapy protocols for recurrent malignant glioma is less than 30%. The growing body of evidence demonstrating the clinical importance of O6-methylguanine methyltransferase (MGMT) has generated a considerable interest in the exploration of strategies to overcome MGMT-mediated resistance to alkylating agents; for example protracted administration of Temozolomide (TMZ) may result in more extensive and sustained depletion of MGMT; for this reason a variety of dosing schedules that increase the duration of exposure and the cumulative dose of TMZ are being investigated for the treatment of patient with recurrent malignant glioma after standard treatment. The most widely studied regimens in this setting include (1) 21 of 28-day schedule at a dose of 75-100 mg/m(2)/day; (2) 7 of 14-day schedule at a dose of 150 mg/m(2)/day, also referred to as the ''one week on/one week off'' schedule; (3) Continuous daily schedule at a dose of 50 mg/m(2)/day. An alternative dosing schedule of TMZ may be a reasonable option in patients having high-grade gliomas with recurrence after standard therapy.

Lecture: fotemustine in brain tumors.

Fotemustine (FTMS) is a third-generation nitrosourea, in preclinical studies, FTMS compared favorably with carmustine (BCNU) and lomustine (CCNU) against several human tumor cell lines. In conventional schedule, FTMS is administered at a dose of 100 mg/sqm/week for three consecutive weeks as induction (I) treatment, followed by 100 mg/sqm every three weeks, after a 5-week rest, as maintenance (M). Several Italian groups reported the results using FTMS in malignant glioma patients recurring after temozolomide standard treatment. In these papers, the 6-progression free survival are ranging from 20 to 52%. With the schedule (I + M) myelosuppression is observed in more than 30% of patients, and thrombocytopenia and leukopenia are more frequent and significant in Temozolomide pretreated patients. On the bases of the hematological toxicities several authors experimented new schedules of FTMS administrated at low doses. Recently, some authors reported the interesting results of a multicenter study on recurrent glioblastoma multiforme patients combining FTMS with new antiangiogentic agent bevacizumab.

Consent and awareness: mental conditions at diagnosis.

Informed consent is often talked about in an abstract manner, as if consent and information necessarily have to go together, and almost as if consent is "naturally" the quintessence of a good professional relationship in modern medicine. The United States is considered as the place of origin of informed consent. In Italy the concept of informed consent can be found for the first time in the 1990s. Informed consent is based on the principles of autonomy and benefit, on awareness and information. Already at the moment of the diagnosis, in addition to motor deficits, focal cognitive deficits are often present. It is important for the doctor to consider and evaluate the actual ability to comprehend and process the clinical situation on the part of the patient. At the Neuro-Oncology Division of the Carlo Besta Neurological Institute of Milan, we sought to analyse how and to what extent the brain tumour alters and conditions cognitive functionality, and hence the ability to process, comprehend and retain information during a diagnostic communication, and whether and how this moment is influenced by the presence of any global or specific cognitive deficits. Preliminary and performed on a numerically limited sample, 30 patients out of 42, in a specific neuropsychological survey, display cognitive attention and memory deficits despite achieving an adequate score on a global cognitive assessment. The physician's attention to the cognitive faculties of a patient to whom a pathological condition and a therapeutic approach are being presented is fundamental.

Infections in neuro-oncology.

Infections represent a serious and frequent complication in neuro-oncology patients. Decreased immune defences, along with poor nutritional status are the main predisposition factors. The combined therapeutic strategies of chemotherapy and radiotherapy may favour bone marrow depression and further increase the risk of developing opportunistic infections in brain tumour patients. The spectrum of infections in neuro-oncology patients is large and includes opportunistic infections by bacteria, viruses, fungi and parasites. Importantly, a high index of suspicion for opportunistic infections in general should be maintained, especially in glioma patients receiving dose-dense schedules of temozolomide. After neurosurgical procedures, infections most commonly present as meningitis, subdural empyema, or cerebral abscess. Infections represent a frequent and possibly serious complication in general immunocompromised oncology population. It should be underlined that infections are not limited to immunocompromised patients, being also present at the early disease stages, especially due to therapeutic strategies (chemo and radiotherapy, surgical procedures). Therefore this issue deserves more attention in neuroncology setting.

Privacy-solidarity conflict: the communication with the support group.

Actually guidelines require that patient must be informed about his condition so that he can choose the persons he wants to share these information with. Nonetheless, the caregiver usually gets an intermediary role in doctor-patient communication thus becoming the doctor's main conversation partner and claiming to be given more information than the patient himself. A more complex situation is about brain tumours patients sometimes affected by cognitive deficiencies, compromising their comprehension skills or their capability of keeping the information they are being given. A preliminary study allowed to submit separately to brain tumour patients and their family members a semi-structured interview. Although doctors communicate diagnosis and therapeutic plans, patients and their family members often do not seem to remember the information they are given. An important percentage of patients and their carers cannot tell correctly what they was said by the doctors. Only a minor percentage of patients do not want to know all details of their disease. Instead, most of the family members, would rather their beloved were given just partial information on their conditions or even not given information at all. Communication with patients and their carers requires careful re-negotiation in a multiple time-points, rather than a one-off communication episode.

The impact of decision models on self-perceived quality of life: a study on brain cancer patients.

Quality of life (QoL) is an increasingly important outcome measure in medicine. Health, in fact, is not only based on functional status but also on psychological and social well being. Since QoL is related to the patient's perception of their position in life in relation to their goals, expectations, standards and concerns, the way in which the medical context is experienced may be critical. We then hypothesised that self-perceived QoL may be linked to unmet needs in information management and decision involvement. To analyse this hypothesis, we conducted a quantitative study on 84 consecutive patients with a diagnosis of primary high-grade glioma. The functional assessment of cancer therapy-Brain (FACT-Br) scales, the hospital anxiety and depression (HAD) scale and the need evaluation questionnaire (NEQ) questionnaire were used, in order to measure quality-of-life dimension, mood and unmet needs. Patients were classified as having no need (cluster 1), a moderate need (cluster 2) or a high need (cluster 3) to be more involved in the clinical process.Our data confirmed previous studies in other clinical areas, showing that shared decision might contribute to a better adaptation process to the illness [1]. In fact, patients in cluster 1 showed a significant better self-perceived QoL, despite the lack of clinical differences between clusters. The study showed that patients satisfied with respect to decisional involvement seem to be able to better cope with their disease. Finally, the study suggests the need for a more attuned decision-making process in approaching clinical decisions. Physicians need to better understand patient preferences related to information and decision sharing.

Methotrexate based chemotherapy and deferred radiotherapy for primary central nervous system lymphoma (PCNSL): single institution experience.

In the following study, we present our experience in the treatment of PCNSL patients using a multi-step schedule combining chemotherapy and deferred radiotherapy. Patients were treated with two modified M-BACOD cycles and then differently according to radiological response For PR, SD and PD patients, chemotherapy was interrupted and radiotherapy initiated immediately (45 Gy Whole-brain RT). With CR patients, chemotherapy was continued with a combination of HMTX, VCZ, PCB and HD Ara-C up to a total of nine cycles. In 36 patients suitable for evaluation (2 patients had undergone tumour resection): 69.4% (25 of 36) had a complete response (CR), 19.4% (7 of 36) had a partial response(PR), 8.3% (3 of 36) had stable disease(SD), and 2.7% (one of 36) had progressive disease (PD). The PR, SD and PD patients were immediately treated by radiotherapy. In this cohort of patients, we observed 6 CR, 4 PR and 2 PD, respectively, following radiotherapy. At first relapse, a total of 16 CR patients were treated by radiotherapy for a total dose of 45 Gy. The OS was 42.1 months for the entire group of patients. In CR patients treated at the moment of recurrence by salvage radiotherapy, the TTP (time lasting from histological diagnosis until recurrence of disease before RT) was 28.3 months, with a 43.4% of disease free patients observed at 2 years. The median disease-free time observed after complete response to radiotherapy was 10.5 months. In 16 patients (34%), further progression of disease was observed following radiotherapy. Two patients developed extra-CNS disease in the breast and testis. When taking into account the patients with radiotherapy delayed at recurrence, the OS was 48 months and the survival rates were 70% and 60% at 2 years and 5 years, respectively.