Acrometastases to the Hand: A Systematic Review.

Background and Objectives: The term acrometastases (AM) refers to secondary lesions sited distally to the elbow and knee, representing 0.1% of all bony metastases. By frequency, pulmonary cancer and gastrointestinal and genitourinary tract neoplasms are the most responsible for the reported AM. Improvements in oncologic patient care favor an increase in the incidence of such rare cases. We performed a systematic review of acrometastases to the hand to provide further insight into the management of these fragile patients. We also present a peculiar case of simultaneous acrometastasis to the ring finger and pathological vertebral fracture. Material and Methods: A literature search according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted using the PubMed, Google Scholar, and Scopus databases in December 2020 on metastasis to the hand and wrist, from 1986 to 2020. MeSH terms included acrometastasis, carpal metastasis, hand metastasis, finger metastasis, phalangeal metastasis, and wrist metastasis. Results: In total, 215 studies reporting the follow-up of 247 patients were analyzed, with a median age of 62 years (range 10-91 years). Overall, 162 out of 247 patients were males (65.6%) and 85 were females (34.4%). The median reported follow-up was 5 months (range 0.5-39). The median time from primary tumor diagnosis to acrometastasis was 24 months (range 0.7-156). Acrometastases were located at the finger/phalanx (68.4%), carpal (14.2%), metacarpal (14.2%), or other sites (3.2%). The primary tumors were pulmonary in 91 patients (36.8%). The average interval from primary tumor diagnosis to acrometastasis varied according to the primary tumor type from 2 months (in patients with mesenchymal tumors) to 64.0 months (in patients with breast cancer). Conclusions: Acrometastases usually develop in the late stage of oncologic disease and are associated with short life expectancy. Their occurrence can no longer be considered rare; physicians should thus be updated on their surgical management and their impact on prognosis and survival.

Characterization of matrix metalloproteinase-2 and -9, ADAM-10 and N-cadherin expression in human glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in humans, whose invasiveness and proliferation are associated with poor prognosis. Matrix metalloproteinases (MMPs) and the related family of "a disintegrin and metalloproteinase" (ADAM) both contribute to increase cell invasion, and its substrate N-cadherin is involved in proliferation and metastatic capacities of tumor cells. However, these molecular determinants of aggressiveness have not been adequately characterized in GBM. In an attempt to better define these pathogenetic signatures, in the present study we evaluated the comparative expression of two main MMPs (MMP-2 and -9), as well as of ADAM-10 and N-cadherin in surgical samples from patients diagnosed with WHO grade IV GBM (n = 25) and in cortical tissue specimens obtained from untreatable epileptic patients (controls, n = 8) through a series of histopathological, immunohistochemical and biochemical tests. Our studies revealed that both MMP-2 and -9 immunoreactivities (IRs) were upregulated in 13 of 25 (52 %) and 19 of 25 (76 %) GBMs, respectively, and the extent of the increase was highly significant with respect to controls (p < 0.001). ADAM-10 IR was also found to be increased (p < 0.001) in 16 of 25 GBM specimens (64 %). Conversely, N-cadherin IR was remarkably decreased (p < 0.001) in almost the totality of tumor samples (22 of 25, 88 %). A similar trend was also obtained at the mRNA and protein level by qPCR and western blot analyses, respectively. Collectively, the current study provides a comprehensive molecular portrayal of some of the major pathological hallmarks of GBM aggressiveness, which could be exploitable as potential targets for a new therapeutic approach.

Delirium and IL-6 added to clinical scores improves their performance: a prospective analysis of CALL, PREDI-CO, MRS score applied to a population of patients admitted to internal medicine ward.

This study aimed to evaluate the effectiveness of various scoring systems in predicting in-hospital mortality for COVID-19 patients admitted to the internal medicine ward. We conducted a prospective collection of clinical data from patients admitted to the Internal Medicine Unit at Santa Maria Nuova Hospital in Florence, Italy, with confirmed pneumonia caused by SARS-CoV-2. We calculated three scoring systems: the CALL score, the PREDI-CO score, and the COVID-19 in-hospital Mortality Risk Score (COVID-19 MRS). The primary endpoint was in-hospital mortality. : A total of 681 patients were enrolled in the study, with a mean age of 68.8 ± 16.1 years, and 54.8% of them were male. Non-survivors had significantly higher scores in all prognostic systems compared to survivors (MRS: 13 [12- 15] vs. 10 [8-12]; CALL: 12 [10-12] vs. 9 [7-11]; PREDI-CO: 4 [3-6] vs. 2 [1-4]; all p<0.001). The receiver operating characteristic (ROC) analysis yielded the following area under the curve (AUC) values: MRS 0.85, CALL 0.78, PREDI-CO 0.77. The addition of Delirium and IL6 to the scoring systems improved their discriminative ability, resulting in AUC values of 0.92 for MRS, 0.87 for CALL, and 0.84 for PREDI-CO. The mortality rate increased significantly across increasing quartiles (p<0.001). In conclusion the COVID-19 in-hospital Mortality Risk Score (MRS) demonstrated reasonable prognostic stratification for patients admitted to the internal medicine ward with SARS-CoV-2-induced pneumonia. The inclusion of Delirium and IL6 as additional prognostic indicators in the scoring systems enhanced their predictive performance, specifically in determining in-hospital mortality among COVID-19 patients.

Hypofractionated Gamma Knife Radiosurgery: Institutional Experience on Benign and Malignant Intracranial Tumors.

BACKGROUND/AIM: We investigated the treatment outcomes and complications associated with hypofractionated GKRS for the treatment of benign and malignant intracranial tumors. PATIENTS AND METHODS: Patients with intracranial tumors not candidate or refusing surgery were evaluated to assess eligibility to undergo hypofractionated Gamma Knife radiosurgery (GKRS). Targeted volumes were calculated using the GammaPlan® workstation, and GKRS protocols were delivered with 3 or 5 daily fractions and a maximal total dose of 25 Gy. The thermoplastic mask was used to immobilize the patient's head without pin-based fixation frames. RESULTS: A total of 41 patients, affected with 6 different histologies, were treated and followed-up for a median of 12 months (range=4-24 months). Meningiomas were the most common tumors (33, 80.5%), followed by brain metastases (4, 9.7%). At last follow-up, 33 patients (80.5%) had stable disease, 8 tumor regression (19.5%), and 0 tumor progression. No acute radiation toxicity was observed. Death was reported in 3 patients (7.3%) due to malignant tumor progression. CONCLUSION: Our hypofractionated GKRS protocol proved to be effective and safe in the treatment of patients with benign and malignant intracranial tumors. Local tumor control was achieved in all patients, with 8 patients showing tumor regression and no cases of acute radiation toxicity.

Extra-Neural Metastases From Primary Intracranial Ependymomas: A Systematic Review.

Background: Primary intracranial ependymomas (IE) are rare brain tumors rarely metastasizing outside the central nervous system. We systematically reviewed the literature on extra-neural metastases from primary IEs. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of extra-neural metastases from primary IEs. Clinical features, management strategies, and survival were analyzed. Results: We collected 48 patients from 43 studies. Median age was 13 years (range, 2-65). Primary IEs were frequently located in the parietal (22.9%) and frontal (16.7%) lobes, and mostly treated with resection (95.8%) and/or radiotherapy (62.5%). Most IEs were of grade-III (79.1%), and few of grade-I (6.3%) or grade-II (14.6%). 45 patients experienced intracranial recurrences, mostly treated with resection (86.7%), radiotherapy (60%), and/or chemotherapy (24.4%). Median time-interval from primary IEs was 28 months (range, 0-140). Most extra-neural metastases were diagnosed at imaging (37.5%) or autopsy (35.4%). Extra-neural metastases were multifocal in 38 patients (79.1%), mostly involving cervical or hilar lymph-nodes (66.7%), lung/pleura (47.9%), and/or scalp (29.1%). Surgical resection (31.3%), chemotherapy (31.3%) and locoregional radiotherapy (18.8%) were the most common treatments for extra-neural metastases, but 28 (58.3%) patients were not treated. At last follow-up, 37 patients died with median overall-survivals from primary IEs of 36 months (range, 1-239), and from extra-neural metastases of 3 months (range, 0.1-36). Overall-survival was significantly longer in patients with grade-I and II IEs (P=0.040). Conclusion: Extra-neural metastases from primary IEs are rare, but mostly occur at later disease stages. Multidisciplinary management strategies should be intended mostly for palliation.

Detection of "Incidentalomas" on Brain and Body 68Ga-DOTATOC-PET Scans: A Retrospective Study and Case Illustration.

BACKGROUND/AIM: One of the main limitations of standard imaging modalities is microscopic tumor extension, which is often difficult to detect on magnetic resonance imaging (MRI) and computer tomography (CT) in the early stages of the tumor. (68)Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide positron-emission tomography/computed tomography (68Ga-DOTATOC PET/CT) has shown efficacy in detecting lesions previously undiagnosed by neuroimaging modalities, such as MRI or CT, and has enabled the detection of multiple benign tumors (like multiple meningiomas in a patient presenting with a single lesion on MRI) or additional secondary metastatic locations. PATIENTS AND METHODS: We retrospectively reviewed data from the Cannizzaro Hospital on brain and body 68Ga-DOTATOC PET/CT "incidentalomas", defined as tumors missed on CT or MRI scans, but detected on 68Ga-DOTATOC PET/CT scans. "Incidentalomas" were classified into "brain" and "body" groups based on their location. The standardized uptake values (SUVs) were compared between the two groups. RESULTS: A total of 61 patients with "incidentalomas" documented on the 68Ga-DOTATOC PET/CT were identified: 18 patients with 25 brain lesions and 43 patients with 85 body lesions. The mean SUV at baseline was 9.01±7.66 in the brain group and 14.8±14.63 in the body group. CONCLUSION: We present the first series on brain and body "incidentalomas" detected on 68Ga-DOTATOC PET/CT. Whole-body 68Ga-DOTATOC PET/CT may be considered in selected patients with brain tumors with high expression of somatostatin receptors to assist radiosurgical or surgical planning and, simultaneously, provide accurate follow-up with early detection of potential metastases.

Navigated Transcranial Magnetic Stimulation Motor Mapping Usefulness in the Surgical Management of Patients Affected by Brain Tumors in Eloquent Areas: A Systematic Review and Meta-Analysis.

Background: The surgical strategy for brain glioma has changed, shifting from tumor debulking to a more careful tumor dissection with the aim of a gross-total resection, extended beyond the contrast-enhancement MRI, including the hyperintensity on FLAIR MR images and defined as supratotal resection. It is possible to pursue this goal thanks to the refinement of several technological tools for pre and intraoperative planning including intraoperative neurophysiological monitoring (IONM), cortico-subcortical mapping, functional MRI (fMRI), navigated transcranial magnetic stimulation (nTMS), intraoperative CT or MRI (iCT, iMR), and intraoperative contrast-enhanced ultrasound. This systematic review provides an overview of the state of the art techniques in the application of nTMS and nTMS-based DTI-FT during brain tumor surgery. Materials and Methods: A systematic literature review was performed according to the PRISMA statement. The authors searched the PubMed and Scopus databases until July 2020 for published articles with the following Mesh terms: (Brain surgery OR surgery OR craniotomy) AND (brain mapping OR functional planning) AND (TMS OR transcranial magnetic stimulation OR rTMS OR repetitive transcranial stimulation). We only included studies regarding motor mapping in craniotomy for brain tumors, which reported data about CTS sparing. Results: A total of 335 published studies were identified through the PubMed and Scopus databases. After a detailed examination of these studies, 325 were excluded from our review because of a lack of data object in this search. TMS reported an accuracy range of 0.4-14.8 mm between the APB hotspot (n1/4 8) in nTMS and DES from the DES spot; nTMS influenced the surgical indications in 34.3-68.5%. Conclusion: We found that nTMS can be defined as a safe and non-invasive technique and in association with DES, fMRI, and IONM, improves brain mapping and the extent of resection favoring a better postoperative outcome.

68Ga-DOTATOC PET/CT Follow Up after Single or Hypofractionated Gamma Knife ICON Radiosurgery for Meningioma Patients.

68Ga-DOTATOC represents a useful tool in tumor contouring for radiosurgery planning. We present a case series of patients affected by meningiomas on who we performed 68Ga-DOTATOC positron emission tomography (PET)/CT pre-operatively, a subgroup of which also underwent a post-operative 68Ga-DOTATOC PET/CT to evaluate the standardized uptake value (SUV) modification after Gamma Knife ICON treatment in single or hypofractionated fractions. Twenty patients were enrolled/included in this study: ten females and ten males. The median age was 52 years (range 33-80). The median tumor diameter was 3.68 cm (range 0.12-22.26 cm), and the median pre-radiotherapy maximum SUV value was 11 (range 2.3-92). The average of the relative percentage changes between SUVs at baseline and follow up was -6%, ranging from -41% to 56%. The SUV was reduced in seven out of 12 patients (58%), stable in two out of 12 (17%), and increased in three out of 12 (25%), suggesting a biological response of the tumor to the Gamma Knife treatment in most of the cases. 68Ga-DOTATOC-PET represents a valuable tool in assessing the meningioma diagnosis for primary radiosurgery; it is also promising for follow-up assessment.

Primary Extracranial Meningiomas of the Head and Neck.

Meningiomas represent the most common benign histological tumor of the central nervous system. Usually, meningiomas are intracranial, showing a typical dural tail sign on brain MRI with Gadolinium, but occasionally they can infiltrate the skull or be sited extracranially. We present a systematic review of the literature on extracranial meningiomas of the head and neck, along with an emblematic case of primary extracranial meningioma (PEM), which provides further insights into PEM management. A literature search according to the PRISMA statement was conducted from 1979 to June 2021 using PubMed, Web of Science, Google Scholar, and Scopus databases, searching for relevant Mesh terms (primary extracranial meningioma) AND (head OR neck). Data for all patients were recorded when available, including age, sex, localization, histological grading, treatment, possible recurrence, and outcome. A total of 83 published studies were identified through PubMed, Google Scholar, and Scopus databases, together with additional references list searches from 1979 to date. A total of 49 papers were excluded, and 34 manuscripts were considered for this systematic review, including 213 patients. We also reported a case of a 45-year-old male with an extracranial neck psammomatous meningioma with sizes of 4 cm × 3 cm × 2 cm. Furthermore, whole-body 68Ga-DOTATOC PET/CT was performed, excluding tumor spread to other areas. Surgical resection of the tumor was accomplished, as well as skin flap reconstruction, obtaining radical removal and satisfying wound healing. PEMs could suggest an infiltrative and aggressive behavior, which has never found a histopathological correlation with a malignancy (low Ki-67, <5%). Whole-body 68Ga-DOTATOC PET/CT should be considered in the patient's global assessment. Surgical removal is a resolutive treatment, and the examination of frozen sections can confirm the benignity of the lesion, reducing the extension of the removal of healthy tissue surrounding the tumor.

Brain Mapping as Helpful Tool in Brain Glioma Surgical Treatment-Toward the "Perfect Surgery"?

Gliomas are the most common primary malignant brain tumours in adults, representing nearly 80%, with poor prognosis in their high-grade forms. Several variables positively affect the prognosis of patients with high-grade glioma: young age, tumour location, radiological features, recurrence, and the opportunity to perform post-operative adjuvant therapy. Low-grade gliomas are slow-growing brain neoplasms of adolescence and young-adulthood, preferentially involving functional areas, particularly the eloquent ones. It has been demonstrated that early surgery and higher extent rate ensure overall longer survival time regardless of tumour grading, but nowadays, functional preservation that is as complete as possible is imperative. To achieve the best surgical results, along with the best functional results, intraoperative mapping and monitoring of brain functions, as well as different anaesthesiology protocols for awake surgery are nowadays being widely adopted. We report on our experience at our institution with 28 patients affected by malignant brain tumours who underwent brain mapping-aided surgical resection of neoplasm: 20 patients underwent awake surgical resection and 8 patients underwent asleep surgical resection. An analysis of the results and a review of the literature has been performed.

Preliminary Experience with a Novel System of Facet Fixation to Treat Patients with Lumbar Degenerative Disease. A New Perspective in Minimally Invasive Spine Surgery?

PURPOSE: We report our experience with a novel surgical device for the treatment of lumbar degenerative microinstability. Facet Wedge (DePuy Synthes, Raynham, Massachusetts, United States) is a novel technique of intra-articular lumbar facet fixation that provides a minimally invasive alternative to standard posterior fixation. MATERIALS AND METHODS: From November 2014 to July 2015, 38 patients underwent single-level Facet Wedge implantation. The main surgical indications included herniated disk (18 patients), spinal canal and foraminal stenosis (14 patients), and Meyerding grade I degenerative spondylolisthesis (6 patients). All the patients showed radiologic signs of microinstability: hyperintensity in both facet joints (facet fluid signal) in T2-weighted magnetic resonance imaging and a black disk as a sign of degenerative disease. No slippage was evident at dynamic radiograph. After a period of conservative treatment (minimum of 6 months), surgery was performed. All patients' follow-up lasted over at least 12 months. RESULTS: The low back visual analog scale score decreased significantly after surgery (from an average of 8.2 to 3.1 at final follow-up). Postoperatively, the Oswestry Disability Index showed a significant reduction (14.7 on average). No slippage or signs of adjacent segment degeneration was detected in neuroimaging follow-up. CONCLUSION: Facet Wedge allows facet fixation in lumbar degenerative microinstability. To the best of our knowledge, this is the first clinical series reported in the literature on this novel device.

Survey on current practice within the European Low-Grade Glioma Network: where do we stand and what is the next step?

Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.