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Objective: To evaluate short-term (2008-2017) cancer incidence trends in Italy for individuals aged 20-49 years by sex and cancer type., Methods: Observational study from population-based data collected by 20 Italian Cancer Registries, covering 33% of the Italian population. The age-standardized incidence rates (ASRs), overall and stratified by area, sex, cancer site or type, and major age groups (i.e., 20-39, 40-49), were computed., Results: In 2008-2017, cancer incidence rates were almost two times higher in Italian women aged 20-49 than in age-corresponding men (202.2 vs 112.4 per 100,000) on account of elevated rates of breast and thyroid cancers. Contrasting trends emerged according to cancer sites/types. ASRs for female breast cancer increased steadily from 2008 (82.4) to 2014 (86.2) and remained unchanged thereafter (i.e., 86.5 in 2017). During the study period, there was an increase for testicular cancer, skin melanoma in both sexes, and thyroid cancer until 2013 (followed by a slight decrease from 2014 to 2017). Conversely, ASRs consistently declined for colorectal cancer and were substantially stable or slightly decreasing for cervix uteri (from 8.1 to 7.7), ovary (from 7.5 to 6.9) and non-Hodgkin lymphoma (from 8.3 to 7.6 in men and from 5.9 to 5.5 in women)., Conclusions: Study findings do not support a unique temporal pattern for the incidence of early-onset cancer in Italy until 2017, as reported in other countries. Increases in incidence documented in both sexes for some tumor sites was counterbalanced by a decrease in other sites. The importance of supporting prevention strategies from the youngest of ages must be emphasized, and the role of anticipated screening should be carefully addressed., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Peri-electrode edema after deep brain stimulation (DBS) surgery for Parkinson Disease (PD) has been reported in up to 100% of cases. The clinical significance of this finding is unclear, with most papers suggesting a benign course. The risk factors are also poorly defined. We aimed at defining the incidence rate, the clinical significance and the predictive factors of peri-electrode edema in patients undergoing DBS for PD., Methods: We reviewed data of 119 patients treated with frameless stereotactic DBS for PD between 2012 and 2022 at our Institution. A mixed-technique targeting was adopted. Awake surgery was used in 64.7% cases; in most cases, microelectrode recording (MER) was adopted. The target was the subthalamic nucleus (STN) in 91.2% cases., Results: Ninety patients were included. Postoperative edema related to lead placement was noticed in 40% patients after a median time of 2 days since surgery; in 88.9% of these cases, it was limited to subcortical white matter. Symptomatic edema was registered only in one case (1.1%), confirming previous reports on the benign clinical course. The only independent predictive factor for edema onset was asleep surgery (p = 0.0451). Notably, the use of directional electrodes was not associated with an increased risk of edema at multivariable analysis. Clinical parameters including age, and timing of CT scanning, did not affect edema onset., Conclusions: We confirmed the very low rate of symptomatic edema in DBS for PD. When feasible, awake DBS using MER is the ideal technique to reduce the risk of radiologic postoperative edema., (© 2024. The Author(s).)

The use of microelectrode recording (MER) during deep brain stimulation (DBS) for Parkinson Disease is controversial. Furthermore, in asleep DBS anesthesia can impair the ability to record single-cell electric activity.The purpose of this study was to describe our surgical and anesthesiologic protocol for MER assessment during asleep subthalamic nucleus (STN) DBS and to put our findings in the context of a systematic review of the literature. Sixty-three STN electrodes were implanted in 32 patients under general anesthesia. A frameless technique using O-Arm scanning was adopted in all cases. Total intravenous anesthesia, monitored with bispectral index, was administered using a target controlled infusion of both propofol and remifentanil. A systematic review of the literature with metanalysis on MER in asleep vs awake STN DBS for Parkinson Disease was performed. In our series, MER could be reliably recorded in all cases, impacting profoundly on electrode positioning: the final position was located within 2 mm from the planned target only in 42.9% cases. Depth modification > 2 mm was necessary in 21 cases (33.3%), while in 15 cases (23.8%) a different track was used. At 1-year follow-up we observed a significant reduction in LEDD, UPDRS Part III score off-medications, and UPDRS Part III score on medications, as compared to baseline. The systematic review of the literature yielded 23 papers; adding the cases here reported, overall 1258 asleep DBS cases using MER are described. This technique was safe and effective: metanalysis showed similar, if not better, outcome of asleep vs awake patients operated using MER. MER are a useful and reliable tool during asleep STN DBS, leading to a fine tuning of electrode position in the majority of cases. Collaboration between neurosurgeon, neurophysiologist and neuroanesthesiologist is crucial, since slight modifications of sedation level can impact profoundly on MER reliability., (© 2024. The Author(s).)

Objective: To refine a reliable and reproducible intraoperative visual evoked potentials (iVEPs) monitoring protocol during endoscopic transsphenoidal surgery. To assess the reliability of baseline iVEPs in predicting preoperative visual status and perioperative iVEP variation in predicting postoperative visual outcome., Methods: Sixty-four patients harboring tumors of the pituitary region were included. All patients underwent endoscopic endonasal approach (EEA) with iVEPs monitoring, using a totally intravenous anesthetic protocol. Ophthalmological evaluation included visual acuity and visual field studies., Results: Preoperatively, visual acuity was reduced in 86% and visual field in 76.5% of cases. Baseline iVEPs amplitude was significantly correlated with preoperative visual acuity and visual field (p = 0.001 and p = 0.0004, respectively), confirming the reliability of the neurophysiological/anesthetic protocol implemented. Importantly, perioperatively the variation in iVEPs amplitude was significantly correlated with the changes in visual acuity (p < 0.0001) and visual field (p = 0.0013). ROC analysis confirmed that iVEPs are an accurate predictor of perioperiative visual acuity improvement, with a 100% positive predictive value in patients with preoperative vision loss., Conclusions: iVEPs during EEA is highly reliable in describing preoperative visual function and can accurately predict postoperative vision improvement., Significance: iVEPs represent a promising resource for carrying out a more effective and safe endoscopic transsphenoidal surgery., (© 2023. The Author(s).)

Introduction: The increasing survival of patients with breast cancer has prompted the assessment of mortality due to all causes of death in these patients. We estimated the absolute risks of death from different causes, useful for health-care planning and clinical prediction, as well as cause-specific hazards, useful for hypothesis generation on etiology and risk factors., Materials and Methods: Using data from population-based cancer registries we performed a retrospective study on a cohort of women diagnosed with primary breast cancer. We carried out a competing-cause analysis computing cumulative incidence functions (CIFs) and cause-specific hazards (CSHs) in the whole cohort, separately by age, stage and registry area., Results: The study cohort comprised 12,742 women followed up for six years. Breast cancer showed the highest CIF, 13.71%, and cardiovascular disease was the second leading cause of death with a CIF of 3.60%. The contribution of breast cancer deaths to the CIF for all causes varied widely by age class: 89.25% in women diagnosed at age <50 years, 72.94% in women diagnosed at age 50-69 and 48.25% in women diagnosed at age ≥70. Greater CIF variations were observed according to stage: the contribution of causes other than breast cancer to CIF for all causes was 73.4% in women with stage I disease, 42.9% in stage II-III and only 13.2% in stage IV. CSH computation revealed temporal variations: in women diagnosed at age ≥70 the CSH for breast cancer was equaled by that for cardiovascular disease and "other diseases" in the sixth year following diagnosis, and an early peak for breast cancer was identified in the first year following diagnosis. Among women aged 50-69 we identified an early peak for breast cancer followed by a further peak near the second year of follow-up. Comparison by geographic area highlighted conspicuous variations: the highest CIF for cardiovascular disease was more than 70% higher than the lowest, while for breast cancer the highest CIF doubled the lowest., Conclusion: The integrated interpretation of absolute risks and hazards suggests the need for multidisciplinary surveillance and prevention using community-based, holistic and well-coordinated survivorship care models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Contiero, Boffi, Borgini, Fabiano, Tittarelli, Mian, Vittadello, Epifani, Ardizzone, Cirilli, Boschetti, Marguati, Cascone, Tumino, Fanetti, Giumelli, Candela, Scuderi, Castelli, Bongiorno, Barigelletti, Perotti, Veronese, Turazza, Crivaro, Tagliabue and the MAPACA Working Group.)

Purpose: The aim of this study was to compare the functional characteristics of two computer-based systems for quality control of cancer registry data through analysis of their output differences., Methods: The study used cancer incidence data from 22 of the 49 registries of the Italian Network of Cancer Registries registered between 1986 and 2017. Two different data checking systems developed by the WHO International Agency for Research on Cancer (IARC) and the Joint Research Center (JRC) with the European Network of Cancer Registries (ENCR) and routinely used by registrars were used to check the quality of the data. The outputs generated by the two systems on the same dataset of each registry were analyzed and compared., Results: The study included a total of 1,305,689 cancer cases. The overall quality of the dataset was high, with 86% (81.7-94.1) microscopically verified cases and only 1.3% (0.03-3.06) cases with a diagnosis by death certificate only. The two check systems identified a low percentage of errors (JRC-ENCR 0.17% and IARC 0.003%) and about the same proportion of warnings (JRC-ENCR 2.79% and IARC 2.42%) in the dataset. Forty-two cases (2% of errors) and 7067 cases (11.5% of warnings) were identified by both systems in equivalent categories. 11.7% of warnings related to TNM staging were identified by the JRC-ENCR system only. The IARC system identified mainly incorrect combination of tumor grade and morphology (72.5% of warnings)., Conclusion: Both systems apply checks on a common set of variables, but some variables are checked by only one of the systems (for example, checks on patient follow-up and tumor stage at diagnosis are included by the JRC-ENCR system only). Most errors and warnings were categorized differently by the two systems, but usually described the same issues, with warnings related to "morphology" (JRC-ENCR) and "histology" (IARC) being the most frequent. It is important to find the right balance between the need to maintain high standards of data quality and the workability of such systems in the daily routine of the cancer registry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tagliabue, Perotti, Fabiano, Tittarelli, Barigelletti, Contiero, Mazzucco, Fusco, Bidoli, Vicentini, Pesce, Stracci and The Collaborative Working Group.)

The prognosis of colorectal cancer is affected by factors such as site of origin, tumor morphology, and metastasis at diagnosis, but also age and sex seem to play a role. This study aimed to investigate within the Italian population how sex and age interact in influencing certain aspects of the disease and how they affect patient survival, particularly in the metastatic cohort. Data from four cancer registries were collected, and patients were classified by sex and age (<50, 50-69, and >69 years). Two separate analyses were conducted: one for patients having right or left colon cancer with adenocarcinoma or mucinous morphology, and one for patients having metastases at diagnosis. Women showed significant differences in right colon cases from the youngest to oldest age group (36% vs. 45% vs. 60%). Men <50 years had a significantly higher mucinous carcinoma percentage than their female counterparts (22% vs. 11%), while in the oldest age group women had the highest percentage (15% vs. 11%). The metastatic pattern differed between men and women and by age. The three-year relative survival in the <50 age group was better for women than men, but this survival advantage was reversed in the oldest group. In conclusion, sex and age are factors that influence the biological and clinical characteristics of colorectal cancer, affecting the metastatic pattern as well as patient survival.

Cancer patients are identified as fragile patients who are often immunodepressed and subject to secondary diseases. The Ada cohort comprises cancer survivors aged 15-39 years at diagnosis included in 34 Italian cancer registries. This study aimed to analyze the possible excess of non-cancer medicines use on the basis of the medicine database of the Ada cohort. Records of medicines present in the pharmaceutical flows collected by eight Lombardy cancer registries and used by patients with any type of cancer were extracted for the year 2012. Medicine consumption data were processed to assign a defined daily dose value and to evaluate the consumption of medicines belonging to different groups of the ATC (Anatomical Therapeutic Chemical) classification. The values were compared with values in the Lombardy population. Medicine consumption related to 8150 patients was analyzed, for a total of 632,675 records. ATC groups A and C for females and group N for both sexes showed significant increases. Group J for males and group M for females showed intermediate increases, and group H for both sexes showed smaller increases. This method allowed the identification of excess medicine use to reduce cancer therapy side effects and primary disease sequelae in this group of patients.

The main objective of this study was to analyse the space-time epidemiological differences by sex during the 2009-2020 period in the total mortality recorded among residents in each of the 25 districts of the Genoa municipality, net of the age effect. The analysis was based on official statistical data relating to total mortality and on the resident population. An estimate of the expected deaths was made to calculate the sex-specific age-standardised mortality ratio (SMR). The temporal trends and age-standardized death rates (SDRs) with respect to those of the European population specific to sex and calendar year were identified for each district. Over the entire observation period, the SMR for males ranged from 124.4 (Cornigliano) to 82.0 (Albaro); for females, the values ranged between 133.4 (Cornigliano) and 85.6 (Nervi-Quinto-S. Ilario). Between 2019 and 2020, Genoa recorded an increase in SDR of 24.5%, more pronounced in males (+26.7%) than in females (+22.4%). This epidemiological methodology is replicable and allows to quickly identify spatial, temporal, sex, and age differences in the general mortality within a municipality.

Aims: In this work, the survival and mortality data of 54 consecutive patients admitted to the Intensive Care Unit (ICU) and suffering from severe respiratory insufficiency imputable to viral SARS - CoV - 2 infection were analyzed and shared, after a critical review of the evidence in order to optimize the most dedicated clinical and treatment strategy, for a future 'targeted' management in the care of the possible return flu outbreak., Methods: At our Emergency Department of the Crema Hospital, from the beginning of the pandemic until the end of June 2020, 54 consecutive patients admitted to ICU suffering from severe acute respiratory infection (SARI) and severe respiratory distress (ARDS) attributable to viral SARS - CoV - 2 infection were recruited. The recruitment criterion was based on refractory hypoxia, general condition and clinical impairment, comorbidities and CT images. The incoming parameters of the blood chemistry and radiology investigations and the timing of the gold - tracheal intubation were compared. Medical therapy was based on the application of shared protocols., Results: The onset of symptoms was varyng, i.e. within the range of 1-14 days. The average time from the admission to the emergency room to the admission to intensive care was approximately 120 h. The average number of days of hospitalization in the ICU was 28 days. With a majority of male patients, the most significant age group was between 60 and 69 years. There were 21 deaths and, compared to the survivors, the deceased ones were older at an average age of about 67 years (vs an average age of the survivors of about 59 years). From the available data entering the ICU, the surviving patients presented average better values of oximetry and blood gas analysis, with a lower average dosage of D-Dimer than the deceased. Ones with a presence of bilateral pneumonia in all patients, the worsening of the ARDS occurred in 31 patients. 9 out of 25 patients early intubated died, while 12 out of 23 patients died when intubation was performed after 24 h of non-invasive ventilation. The presence of multiple comorbidities was shown in 17 of 28 patients and revealed an additional adverse prognostic factor. Also, more than one complication in the same patient were detected; after respiratory worsening, renal failure was more frequently found in 16 patients. Some particular complications such as lesions induced by ventilation with barotrauma mechanism (VILI), ischemic heart disease and the appearance of central and peripheral neurological events were detected too., Considerations: SARS - CoV - 2 disease is caused by a new coronavirus that has its main route of transmission through respiratory droplets and close contact, resulting in a sudden onset of the clinical syndrome with acute respiratory infection (SARI) and severe respiratory distress (ARDS). But it can also appear with other symptoms such as gastrointestinal or neurological events, as to be considered as a disease with multisystem phenotype. This pathology evolves towards a serious form of systemic disease from an acute lung damage to venous and arterial thromboembolic complications and multi-organ failure, mostly associated with high mortality. All patients received empirical or targeted antibiotic therapy for prevention and control of infections of potential pathogens, together with low molecular weight heparin therapy. The majority of patients was subjected to the off - label protocol with antivirals and hydroxychloroquine therapy, we used cortisone support therapy under surveillance and in 3 cases the protocol with anti - IL6 monoclonal antibody (Tolicizumab). In a simplified classification of the tomographic examination of the chest, mostly 3D and 2C lesions were found in the deceased patients with a prevalence of severe and moderate forms, whilst in the survivors the distribution appears with a prevalence of medium and moderate forms. Among the intubated patients, 21 patients, all suffering from worsening ARDS, died whilst there was no mortality in patients subjected to non-invasive ventilation it so. The heterogeneity of the respiratory syndromes and the presence of multiple comorbidities represent an unfortunate prognostic factor. Among the complications, besides the respiratory worsening, renal failure, liver failure and the state of sepsis were most frequently found; less frequent complications were lesions induced by ventilation with a barotrauma mechanism, ischemic heart disease, the appearance of central neurological events of sensory alterations, meningo - encephalitis and cerebral hemorrhage, and peripheral neurological events with polyneuro - myopathies. Mechanical ventilation can adversely affect the prognosis due to lung damage induced, protective ventilation remains the necessary treatment during severe hypoxia in patients with SARS - CoV - 2. The essential prerequisite remains the search for optimal 'customized' values since conditions can vary from patient to patient and, in the same patient, during different times of ventilation., Conclusions: In these extraordinary circumstances, our reality was among the most affected and was able to hold the impact thanks to the immediate great response set in place by the operators, although it costed us an effort especially the one to try to guarantee a high quality level of assistance and care compared to the huge wave of patients in seriously bad conditions. Further research on this heterogeneous pathology and data sharing could help identify a more dedicated clinical decision-making and treatment pathway that, together with a resource planning, would allow us to better face any new disease outbreak., Competing Interests: Declaration of Competing Interest This study does not have any financial support from manufacturer or other sources. None of the Authors has any conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neurofibromatosis Type 1 (NF1) is a neurocutaneous tumour syndrome characterised by mutations in the NF1 gene and resultant neurofibromin protein. The condition is associated with several stigmata of variable penetrance, including various tumours. Massive and fatal haemorrhage arising from plexiform neurofibromas has been described in NF1 patients, though it is a rare clinical entity. The aetiology of massive haemorrhage in NF1 patients appears to be related to vasculopathy, including aneurysms and pseudoaneurysms, often arising within plexiform neurofibromas. There is currently no evidence-based consensus for managing this rare clinical emergency, likely as a result of its low incidence. We describe a case of massive haemorrhage in an NF1 patient managed via embolisation and discuss the literature., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: Pain management after surgery is crucial to decrease perioperative morbidity and mortality. Acute pain services (APS) are multidisciplinary teams that represent a modern strategy to address pain inside hospitals. The APS defines and applies pain treatment protocols specific for each surgery. To evaluate the performance of the APS at our institute, we performed a large retrospective cohort study focusing on complications of epidural analgesia and IV opiates., Methods: Data from the 10 years of activity of the APS were collected. Pain was assessed using the VAS at rest (VASr) and during movement (VASm) at each daily visit; the presence of side effects and complications was also assessed., Results: A total of 17,913 adult patients were followed by APS during the study period. Epidural analgesia was used in 7,776 cases (43%), while 9,239 (52%) patients used IV patient-controlled analgesia (PCA). A combination of the 2 was used in 87 patients (0.5%). A total of 456 perineural catheters (2.6%) were placed, while 442 patients(2.5%) used other analgesic techniques. We recorded 163 dural punctures during catheter placement, with no epidural hematoma, epidural abscess, or meningitis, and no permanent modification in sensitive or motor functions., Conclusions: In our large case series, APS was confirmed safe and effective in treating postoperative pain, using both epidural analgesia and IV PCA with morphine., (© 2019 World Institute of Pain.)

Discovery of new actionable targets and functional networks in melanoma is an urgent need as only a fraction of metastatic patients achieves durable clinical benefit by targeted therapy or immunotherapy approaches. Here we show that NFATc2 expression is associated with an EMT-like transcriptional program and with an invasive melanoma phenotype, as shown by analysis of melanoma cell lines at the mRNA and protein levels, interrogation of the TCGA melanoma dataset and characterization of melanoma lesions by immunohistochemistry. Gene silencing or pharmacological inhibition of NFATc2 downregulated EMT-related genes and AXL, and suppressed c-Myc, FOXM1, and EZH2. Targeting of c-Myc suppressed FOXM1 and EZH2, while targeting of FOXM1 suppressed EZH2. Inhibition of c-Myc, or FOXM1, or EZH2 downregulated EMT-related gene expression, upregulated MITF and suppressed migratory and invasive activity of neoplastic cells. Stable silencing of NFATc2 impaired melanoma cell proliferation in vitro and tumor growth in vivo in SCID mice. In NFATc2 + EZH2 + melanoma cell lines pharmacological co-targeting of NFATc2 and EZH2 exerted strong anti-proliferative and pro-apoptotic activity, irrespective of BRAF or NRAS mutations and of BRAF inhibitor resistance. These results provide preclinical evidence for a role of NFATc2 in shaping the EMT-like melanoma phenotype and reveal a targetable vulnerability associated with NFATc2 and EZH2 expression in melanoma cells belonging to different mutational subsets.

Background: Ventriculoatrial (VA) shunt is a routine technique for the treatment of hydrocephalus. The correct position at the superior vena cava-right atrium junction is generally assessed by radiography. We present the first experience of an alternative, nonradiographic technique to assess the distal end of the VA shunts through an electrocardiographic (EKG) method. The technique has developed from the large experience of central venous catheters (CVC) worldwide; the EKG-guided method is a common and validated alternative to standard radiologic control of the location of the tip of any CVC., Methods: Five consecutive patients underwent VA shunt with venous catheter positioned with the EKG-guided technique. The position of the catheter tip was verified by standard chest radiography., Results: Four men and 1 woman (mean age, 45.4 years) underwent VA shunt for hydrocephalus with the EKG-guided technique. The side of internal jugular vein puncture was the right side in 4 cases and the left side in 1 case. As confirmed by radiography, all VA shunt tips were located within the correct range. There was no radiologic evidence of procedure-related complication or catheters that had to be replaced., Conclusions: The EKG-guided technique for VA shunts is as accurate as fluoroscopy, but simpler, more readily available, less expensive, safer, and more cost effective. It reduces the need of radiography and radiologic exposition for both patients and operators. The EKG method may be a valid and cost-effective alternative to standard radiologic control in VA shunts, as for any central venous access device, and could become the preferential method for confirming tip position during VA shunt surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Anesthetic management of patients undergoing endovascular procedures for treating intracranial aneurysms or cerebrovascular malformations must consider a number of specific challenges, in addition to those associated with anesthesia for other specialties. In addition to maintenance of physiological stability, manipulation of systemic and cerebral hemodynamic parameters may be required to treat any sudden unexpected catastrophic neurological events. A multidisciplinary group including neuro- and pediatric anesthesiologists, interventional neuroradiologists, neurosurgeons, and a clinical methodologist contributed to this document. This consensus working group from 21 Italian institutions identified open questions regarding the best practices for management of anesthesia during endovascular neuroradiological procedures for intracranial aneurysms and cerebrovascular malformations, and addressed these by formulating practical consensus statements. At the first meeting in November 2015, nine key areas were identified regarding choice of anesthetic, patient monitoring, hemodynamic targets, postoperative care, and the management of neuromuscular blockade, anticoagulant and/or antiplatelet therapy, and special considerations for pediatric patients. Nine subgroups were established and a medical librarian performed literature searches in the Cochrane and MEDLINE/PubMed databases for each group. Groups drafted literature summaries and provisional responses in the form of candidate consensus statements based on evidence, when possible, and clinical experience, when this was lacking. Final wording was agreed at a meeting in April 2016 and where possible evidence was graded using United States Preventive Services Task Force criteria. Consensus (defined as >90% agreement) was based on evidence, clinical experience, clinician preference, feasibility in the Italian healthcare system, and cost/benefit considerations.

The uptake of F-fluorocholine (FCH), a radiopharmaceutical used to study patients with prostate cancer, follow both the phosphorylcholine and acetylcholine synthesis. FCH uptake is not specific of neoplastic cells because phospholipids are a structural constituent of the membrane of all cells. Thus, PET/CT with FCH show several areas of physiologic uptake. The skeleton concentrates only mild amounts of FCH, thus a diffuse faint uptake of the radiopharmaceutical is present at a PET/CT study. Herein we present the case of a patient in which PET/CT evidenced a sharply defined vertebral "cold" area of reduced FCH uptake corresponding to a vertebral hemangioma.