Novel Ultrastructural Insights into the Clear-Cell Carcinoma of the Pancreas: A Case Report.

Pancreatic cancer, most frequently as ductal adenocarcinoma (PDAC), is the third leading cause of cancer death. Clear-cell primary adenocarcinoma of the pancreas (CCCP) is a rare, aggressive, still poorly characterized subtype of PDAC. We report here a case of a 65-year-old male presenting with pancreatic neoplasia. A histochemical examination of the tumor showed large cells with clear and abundant intracytoplasmic vacuoles. The clear-cell foamy appearance was not related to the hyperproduction of mucins. Ultrastructural characterization with transmission electron microscopy revealed the massive presence of mitochondria in the clear-cell cytoplasm. The mitochondria showed disordered cristae and various degrees of loss of structural integrity. Immunohistochemistry staining for NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) proved specifically negative for the clear-cell tumor. Our ultrastructural and molecular data indicate that the clear-cell nature in CCCP is linked to the accumulation of disrupted mitochondria. We propose that this may impact on the origin and progression of this PDAC subtype.

Proteomic Characterization of Two Extracellular Vesicle Subtypes Isolated from Human Glioblastoma Stem Cell Secretome by Sequential Centrifugal Ultrafiltration.

Extracellular vesicles (EVs) released from tumor cells are actively investigated, since molecules therein contained and likely transferred to neighboring cells, supplying them with oncogenic information/functions, may represent cancer biomarkers and/or druggable targets. Here, we characterized by a proteomic point of view two EV subtypes isolated by sequential centrifugal ultrafiltration technique from culture medium of glioblastoma (GBM)-derived stem-like cells (GSCs) obtained from surgical specimens of human GBM, the most aggressive and lethal primary brain tumor. Electron microscopy and western blot analysis distinguished them into microvesicles (MVs) and exosomes (Exos). Two-dimensional electrophoresis followed by MALDI TOF analysis allowed us to identify, besides a common pool, sets of proteins specific for each EV subtypes with peculiar differences in their molecular/biological functions. Such a diversity was confirmed by identification of some top proteins selected in MVs and Exos. They were mainly chaperone or metabolic enzymes in MVs, whereas, in Exos, molecules are involved in cell-matrix adhesion, cell migration/aggressiveness, and chemotherapy resistance. These proteins, identified by EVs from primary GSCs and not GBM cell lines, could be regarded as new possible prognostic markers/druggable targets of the human tumor, although data need to be confirmed in EVs isolated from a greater GSC number.

Safety measures and clinical outcome of Nuclear Cardiology Department during Covid-19 lockdown pandemic: Northern Italy experience.

BACKGROUND: The Covid-19 pandemic led to a complete renewal of clinical activities of Italian hospitals. During the lockdown, all hospitals in Italy had to suspend non-urgent clinical activities. The prolonged suspension of elective activities could have caused a series of problems. METHODS: A new ad hoc protocol was designed. Single-day fast-imaging protocol with regadenoson-stress 99mTc-tetrofosmin imaging was preferred. Patients were contacted by phone 4 days before the test and answered to a questionnaire which will be repeated on the day of the exam. Body temperature <37.5 degrees C and no Covid-19 symptoms were necessary to enter the unit. Patients wore surgical mask and gloves. Social distancing was maintained throughout the examination. Healthcare professionals wore a personal protective equipment. RESULTS: A total of 46 patients were studied from April 7 to May 15, 2020, before the publication of the recommendations from ASNC and SNMMI. None of the patients experienced complications. Follow-up of patients discharged was carried by phone. No Covid-19 infection symptoms were reported. On May 18, 2020 all the healthcare providers of nuclear cardiology department underwent serological testing IgG and IgM and none were positive. CONCLUSION: Strict ad hoc hygiene protocol for Covid-19 pandemic avoids diagnostic-therapeutic delay and lengthening of waiting lists. Our experience confirms that pursuing WHO recommendations and recent indication of ASNC and SNMMI is safe for both health providers and patients. Moreover, the incidence of significant inducible ischemia rises when correct stratification of patients is performed.

Embolic Stroke of Undetermined Source and Carotid Intraplaque Hemorrhage on MRI : A Systemic Review and Meta-Analysis.

BACKGROUND: Embolic stroke of undetermined source (ESUS) has traditionally discounted the significance of internal carotid artery stenosis of <50%; however, recent studies have examined the role of carotid artery intraplaque hemorrhage (IPH) as an etiology in nonstenotic carotid arteries. We performed a systemic review of the literature to determine the prevalence of carotid artery IPH on magnetic resonance imaging (MRI) of the vessel wall in patients with ESUS. METHODS: We used PubMed, Epub ahead of print, Ovid MEDLINE in-process and other non-indexed citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane central register of controlled trials, Ovid Cochrane database of systematic reviews and Scopus. Our study consisted of all case series with >10 patients with IPH and ESUS published through October 2018. Additionally, we included 123 patients from an institutional database from 2015-2019. Random effects meta-analysis was used for pooling across studies. Meta-analysis results were expressed as odds ratio (OR) with respective 95% confidence intervals (CI). RESULTS: A total of 7 studies with 354 patients were included. The mean age was 67.5 years old. The overall prevalence estimate for prevalence of IPH ipsilateral to the ischemic lesion was 25.8% (95% CI 13.1-38.5). The odds of having IPH on the ipsilateral side versus the contralateral side was 6.92 (95% CI 3.04-15.79). CONCLUSION: Patients with ESUS have IPH in the carotid artery ipsilateral to the ischemic stroke in 25.8% of cases. Carotid artery vessel wall MRI should be considered as part of the standard work-up in patients with ESUS.

Sclerotherapy for Venous Malformations of Head and Neck: Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis of studies performing sclerotherapy for treatment of venous malformations (VMs) of the face, head and neck. It is our hope that data from this study could be used to better inform providers and patients regarding the benefits and risks of percutaneous sclerotherapy for treatment of face, head and neck VMs. We searched PubMed, MEDLINE, and EMBASE from 2000-2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy of neck, face and head VMs. Two independent reviewers selected studies and abstracted data. The primary outcomes were complete and partial resolution of the VM. Data were analyzed using random-effects meta-analysis. Thirty-seven studies reporting on 2,067 patients were included. The overall rate of complete cure following percutaneous sclerotherapy with any agent was 64.7% (95% confidence interval [CI], 57.4-72.0%). Sodium tetradecyl sulfate had the lowest complete cure rate at 55.5% (95% CI, 36.1-74.9%) while pingyangmycin had the highest cure rate at 82.9% (95% CI, 71.1-94.7%). Overall patient satisfaction rates were 91.0% (95% CI, 86.1-95.9%). Overall quality of life improvement was 78.9% (95% CI, 67.0-90.8%). Overall permanent morbidity/mortality was 0.8% (95% CI, 0.3-1.3%) with no cases of mortality. Our systematic review and meta-analysis of 37 studies and over 2,000 patients found that percutaneous sclerotherapy is a very safe and effective treatment modality for treatment of VMs of the head, neck and face.

Sclerotherapy for low-flow vascular malformations of the orbital and periocular regions: Systematic review and meta-analysis.

Percutaneous sclerotherapy is an alternative strategy for the treatment of vascular malformations of the orbital and periorbital regions. The safety and efficacy of sclerotherapy in this setting have not been fully established. We present the results of a systematic review and meta-analysis examining the safety and efficacy of percutaneous sclerotherapy for the treatment of vascular malformations of the orbit. We searched PubMed, MEDLINE, and EMBASE from 2000 to 2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy for orbital and periorbital vascular malformations. Two independent reviewers selected studies and abstracted data. The primary outcome of this study is the efficacy of sclerotherapy which includes complete response, partial response, or no response to sclerotherapy. Data were analyzed using random-effects meta-analysis. Thirteen studies reporting on 154 patients were included. The rate of complete cure after percutaneous sclerotherapy was 54.9% (95% confidence interval [CI] = 34.2%-75.7%). The rate of emergent decompressive surgery was 3.4% (95% CI = 0.5%-6.2%), and the rate of vision loss was 2.7% (95% CI = 0.1%-5.3%). I2 values were above 50% for most outcomes indicating substantial heterogeneity. Our systematic review and meta-analysis of 13 studies and over 150 patients found that percutaneous sclerotherapy is a safe and effective treatment modality for the treatment of low-flow vascular malformations of the orbit.

Sclerotherapy for lymphatic malformations of head and neck: Systematic review and meta-analysis.

BACKGROUND: Percutaneous sclerotherapy is a commonly used modality for treatment of lymphatic malformations (LMs) of the head, face, and neck. The safety and efficacy of sclerotherapy with various agents for diverse pathologic types of LMs have not been fully established. We present the results of a systematic review and meta-analysis examining the safety and efficacy of percutaneous sclerotherapy for treatment of LMs of the head, face, and neck. METHODS: We searched PubMed, MEDLINE, and Embase from 2000 to 2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy of head, face, and neck LMs. Two independent reviewers selected studies and abstracted data. The primary outcomes were complete and partial resolution of the LM. Data were analyzed using random-effects meta-analysis. RESULTS: There were 25 studies reporting on 726 patients included. The overall rate of complete cure of any pathologic type of LM after percutaneous sclerotherapy with any agent was 50.5% (95% confidence interval, 36.6%-64.3%). Macrocystic lesions had a cure rate of 53.1% compared with cure rates of 35.1% for microcystic lesions and 31.1% for mixed lesions. Regarding agents, doxycycline had the highest cure rate (62.4%) compared with all other agents. Overall permanent morbidity or mortality was 1.2% (95% confidence interval, 0.4%-2.0%) with no deaths. I2 values were >50% for most outcomes, indicating substantial heterogeneity. CONCLUSIONS: Our systematic review and meta-analysis of 25 studies and >700 patients found that percutaneous sclerotherapy is a safe and effective modality for treatment of LMs of the head, neck, and face.

Communicating hydrocephalus after radiosurgery for vestibular schwannomas: does technique matter? A systematic review and meta-analysis.

BACKGROUND: Communicating hydrocephalus (cHCP) after radiosurgery (RS) for vestibular schwannomas (VS) has been reported. Many hypothetical mechanisms for this pathology have been proposed without consensus. The aim of this study is to determine if the platform used to treat the disease, Gamma Knife (GK) versus linear accelerator (LINAC)-based RS, makes a difference in outcome. METHODS: We conducted a meta-analysis of databases PubMed and Cochrane to identify all articles for the period January 2000-August 2018 with the following inclusion criteria: (1) VS treated with single fraction SRS (2) > 10 patients (3) original reports only (4) hydrocephalus reported as complication (5) human study. RESULTS: A total of 7039 and 988 VS patients reported in 35 and 10 papers were treated with GK or LINAC RS, respectively. Demographic baseline characteristics not reported in aggregate did not differ between the two groups. The incidence of cHCP was 3% [95% CI 2-4] and 2% [95% CI 1-3] for GK and LINAC RS patients, respectively. Surgical CSF diversion was performed in 88% and 68% of patients evaluated for cHPC in the GK and LINAC group, respectively. Follow-up range was 30-150 and 29-92 months for GK and LINAC, respectively. CONCLUSIONS: The incidence of cHCP following RS for VS is very low in both GK and LINAC treated patients, albeit not identical. The higher reported surgical intervention rate for VS patients treated with GK RS might be multi-factorial, including longer follow-up in the GK group.

The History of Decompressive Craniectomy in Traumatic Brain Injury.

Decompressive craniectomy consists of removal of piece of bone of the skull in order to reduce intracranial pressure. It is an age-old procedure, taking ancient roots from the Egyptians and Romans, passing through the experience of Berengario da Carpi, until Theodore Kocher, who was the first to systematically describe this procedure in traumatic brain injury (TBI). In the last century, many neurosurgeons have reported their experience, using different techniques of decompressive craniectomy following head trauma, with conflicting results. It is thanks to the successes and failures reported by these authors that we are now able to better understand the pathophysiology of brain swelling in head trauma and the role of decompressive craniectomy in mitigating intracranial hypertension and its impact on clinical outcome. Following a historical description, we will describe the steps that led to the conception of the recent randomized clinical trials, which have taught us that decompressive craniectomy is still a last-tier measure, and decisions to recommend it should been made not only according to clinical indications but also after consideration of patients' preferences and quality of life expectations.