Moving From CT to MRI Paradigm in Acute Ischemic Stroke: Feasibility, Effects on Stroke Diagnosis and Long-Term Outcomes.

BACKGROUND: The relative value of computed tomography (CT) and magnetic resonance imaging (MRI) in acute ischemic stroke (AIS) is debated. In May 2018, our center transitioned from using CT to MRI as first-line imaging for AIS. This retrospective study aims to assess the effects of this paradigm change on diagnosis and disability outcomes. METHODS: We compared all consecutive patients with confirmed diagnosis of AIS admitted to our center during the MRI-period (May 2018-August 2022) and an identical number of patients from the preceding CT-period (December 2012-April 2018). Univariable and multivariable analyses were performed to evaluate outcomes, including the number and delay of imaging exams, the rate of missed strokes, stroke mimics treated with thrombolysis, undetermined stroke mechanisms, length of hospitalization, and 3-month disability. RESULTS: The median age of the 2972 included patients was 76 years (interquartile range, 65-84), and 46% were female. In the MRI-period, 80% underwent MRI as first acute imaging. The proportion of patients requiring a second acute imaging modality for diagnostic ± revascularization reasons increased from 2.1% to 5% (Punadj <0.05), but it decreased in the subacute phase from 79.0% to 60.1% (Padj <0.05). In thrombolysis candidates, there was a 2-minute increase in door-to-imaging delay (Padj <0.05). The rates of initially missed AIS diagnosis was similar (3.8% versus 4.4%, Padj=0.32) and thrombolysis in stroke mimics decreased by half (8.6% versus 4.3%; Padj <0.05). Rates of unidentified stroke mechanism at hospital discharge were similar (22.8% versus 28.1%; Padj=0.99). The length of hospitalization decreased from 9 (interquartile range, 6-14) to 7 (interquartile range, 4-12) days (Padj=0.62). Disability at 3 months was similar (common adjusted odds ratio for favorable Rankin shift, 0.98 [95% CI, 0.71-1.36]; Padj=0.91), as well as mortality and symptomatic intracranial hemorrhage. CONCLUSIONS: A paradigm shift from CT to MRI as first-line imaging for AIS seems feasible in a comprehensive stroke center, with a minimally increased delay to imaging in thrombolysis candidates. MRI was associated with reduced thrombolysis rates of stroke mimics and subacute neuroimaging needs.

Absorbable gelatin compressed sponge (Gelfoam) embolization of distal external carotid artery branches in intra-arterial chemotherapy for retinoblastoma.

BACKGROUND: In intra-arterial chemotherapy for retinoblastoma, a backflow from unreachable external carotid artery branches in the ophthalmic artery can be challenging. OBJECTIVE: To describe a new endovascular technique using Gelfoam pledgets to temporarily occlude distal branches of the external carotid artery to reverse the competitive backflow into the ophthalmic artery in order to perform intra-arterial chemotherapy via the ostium of the ophthalmic artery in selected cases. METHODS: We queried our prospectively collected database of 327 consecutive patients treated for retinoblastoma by intra-arterial chemotherapy and identified those employing Gelfoam pledgets. We describe this new technique with emphasis on feasibility and safety. RESULTS: We treated 11 eyes with 14 infusions of intra-arterial chemotherapy using Gelfoam pledgets to occlude the distal branches of the external carotid artery. We report no perioperative complications due to this occlusion technique. At the ophthalmologic follow-up 1 month after the injection of Gelfoam pledgets, all cases showed tumor regression or stable disease. Two injections into the same eye as the rescue intra-arterial chemotherapy infusion resulted in a transient exudative retinal detachment, and one injection in a heavily pretreated case was followed by iris neovascularization and retinal ischemia. None of the pledget injections led to irreversible vision-threatening intraocular complications. CONCLUSIONS: Intra-arterial chemotherapy in retinoblastoma using Gelfoam to transiently occlude the distal branches of the external carotid artery and reverse the backflow into the ophthalmic artery seems feasible and safe. Larges series will help to confirm the effectiveness of this new technique.

Perfusion Imaging Mismatch Profiles in the Early Thrombectomy Window: A Single-Center Analysis.

BACKGROUND: Little is known on the role of mismatch profile in patients undergoing early endovascular treatment (EVT). We aimed to describe pretreatment perfusion parameters and mismatch profiles in anterior circulation large vessel occlusion acute ischemic stroke undergoing EVT in the early time window and assess their association with time from stroke onset and outcomes. METHODS: Retrospective single-center study, including early (<6 hours) EVT-treated large vessel occlusion acute ischemic stroke with baseline perfusion data, assessing perfusion parameters (ischemic core volume, mismatch volume and mismatch ratio) and mismatch profiles (favorable versus unfavorable, based on criteria adopted in EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial], SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment], DEFUSE 3 [Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3], and DAWN [Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo] trials). We evaluated their association with time from stroke onset (rs [for parameters] or χ2 for trend [for profiles]) and association with modified Rankin Scale score >2, symptomatic intracranial hemorrhage, and mortality (multivariate regression analyses [each parameter/profile entered into a separate logistic regression model, adjusted for baseline variables associated with each outcome in the univariate analysis at the P<0.1 level]). RESULTS: Among 357 patients, unfavorable mismatch profiles ranged from 21% to 60%, depending on the criterion, and were not correlated with time from stroke onset (P=0.490). All individual perfusion parameters and unfavorable mismatch profiles were associated with poor functional outcome: ischemic core volume adjusted odds ratio (aOR), 1.49 ([95% CI, 1.13-1.97] P=0.005); penumbral volume aOR, 0.30 ([95% CI, 0.10-0.84] P=0.022); mismatch ratio aOR, 0.67 ([95% CI, 0.50-0.90] P=0.007); EXTEND-IA aOR, 2.61 ([95% CI, 1.23-5.51] P=0.012); SWIFT PRIME aOR, 2.50 ([95% CI, 1.30-4.57] P=0.006); DEFUSE 3 aOR, 2.28 ([95% CI, 1.14-4.57] P=0.020); and DAWN aOR, 4.19 ([95% CI, 2.13-8.26] P<0.001). EXTEND-IA and DEFUSE 3 unfavorable profiles were also independently associated with symptomatic intracranial hemorrhage (aOR, 3.82 [95% CI, 1.42-10.3]; P=0.008 and aOR, 2.83 [95% CI, 1.09-7.36]; P=0.033) and death (aOR, 3.26 [95% CI, 1.33-8.02]; P=0.010 and aOR, 2.52 [95% CI, 1.10-5.82]; P=0.030). CONCLUSIONS: Pretreatment perfusion parameters and mismatch profiles in early EVT-treated patients were not correlated with time from stroke onset but were independently associated with functional outcome. Mismatch assessment in the early time window may improve EVT patient selection, independently of onset-to-treatment time.

Brain image quality according to beam collimation width and image reconstruction algorithm: A phantom study.

PURPOSE: To compare quantitatively and qualitatively brain image quality acquired in helical and axial modes on two wide collimation CT systems according to the dose level and algorithm used. METHODS: Acquisitions were performed on an image quality and an anthropomorphic phantoms at three dose levels (CTDIvol: 45/35/25 mGy) on two wide collimation CT systems (GE Healthcare and Canon Medical Systems) in axial and helical modes. Raw data were reconstructed using iterative reconstruction (IR) and deep-learning image reconstruction (DLR) algorithms. The noise power spectrum (NPS) was computed on both phantoms and the task-based transfer function (TTF) on the image quality phantom. The subjective quality of images from an anthropomorphic brain phantom was evaluated by two radiologists including overall image quality. RESULTS: For the GE system, noise magnitude and noise texture (average NPS spatial frequency) were lower with DLR than with IR. For the Canon system, noise magnitude values were lower with DLR than with IR for similar noise texture but the opposite was true for spatial resolution. For both CT systems, noise magnitude was lower with the axial mode than with the helical mode for similar noise texture and spatial resolution. Radiologists rated the overall quality of all brain images as "satisfactory for clinical use", whatever the dose level, algorithm or acquisition mode. CONCLUSIONS: Using 16-cm axial acquisition reduces image noise without changing the spatial resolution and image texture compared to helical acquisitions. Axial acquisition can be used in clinical routine for brain CT examinations with an explored length of less than 16 cm.

Evolution of the Cross-Sectional Area of the Osseous Lumbar Spinal Canal across Decades: A CT Study with Reference Ranges in a Swiss Population.

Spinal canal dimensions may vary according to ethnicity as reported values differ among studies in European and Chinese populations. Here, we studied the change in the cross-sectional area (CSA) of the osseous lumbar spinal canal measured in subjects from three ethnic groups born 70 years apart and established reference values for our local population. This retrospective study included a total of 1050 subjects born between 1930 and 1999 stratified by birth decade. All subjects underwent lumbar spine computed tomography (CT) as a standardized imaging procedure following trauma. Three independent observers measured the CSA of the osseous lumbar spinal canal at the L2 and L4 pedicle levels. Lumbar spine CSA was smaller at both L2 and L4 in subjects born in later generations (p < 0.001; p = 0.001). This difference reached significance for patients born three to five decades apart. This was also true within two of the three ethnic subgroups. Patient height was very weakly correlated with the CSA at both L2 and L4 (r = 0.109, p = 0.005; r = 0.116, p = 0.002). The interobserver reliability of the measurements was good. This study confirms the decrease of osseous lumbar spinal canal dimensions across decades in our local population.

Perfusion Imaging and Clinical Outcome in Acute Minor Stroke With Large Vessel Occlusion.

BACKGROUND: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy. METHODS: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume). RESULTS: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P=0.03. However, mismatch volume modified the effect of bridging on clinical outcome (Pinteraction=0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only (Pinteraction=0.002). CONCLUSIONS: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Revascularization of carotid artery occlusion using stenting versus non stenting in endovascular management of tandem occlusion stroke.

INTRODUCTION: The use of extracranial internal carotid artery (ICA) stents after mechanical thrombectomy (MT) may be a source of morbidity and mortality. Studies comparing patients who received stenting to patients who do not receive stenting have a higher number of patients with failed intracranial reperfusion in the non-stenting cohort. In this study, we analyzed the impact of extracranial ICA stenting in tandem occlusion stroke in patients with successfully intracranial reperfusion. METHODS: This monocentric, retrospective cohort observational study reviewed all consecutive MT patients from January 2013 to January 2018. All patients with occlusions in the anterior circulation due to ICA atherosclerotic plaque embolus, TOAST 1, and were successfully reperfusion of at least 50% of the initially occluded target territory were included. Patients with a concomitant extracranial, or tandem, ICA occlusion which required MT and permanent stenting (stenting cohort) were compared to patients with extracranial atheromatous ICA plaques, which did not require permanent carotid stenting but were treated only by MT (non-stenting cohort). The three endpoints of this analysis were mortality rate at 90 days, good functional outcome defined as modified rankin scale (mRS) scores 0-2 at 90 days and symptomatic ICH (sICH). Outcomes were reported as odds ratios (ORs), indicating the odds that the intervention would lead to increased mortality rate, an improvement of at least one point on the mRS in a shift analysis and decreased rate of sICH. RESULTS: One hundred and two patients were included of which 42 were treated by MT and ICA stenting (stenting cohort) and 60 were treated by MT without stenting (non-stenting cohort). No significant differences observed as it relates to demographic data, stroke characteristics, symptom onset to groin puncture or groin puncture to final reperfusion time intervals. Univariate logistic regression showed a higher probability of mortality at 90 days in the stenting cohort than that in the non-stenting cohort (OR 2.78, 95% CI 1.21-7.25, P=0.03). Stenting was not associated with a significant difference in functional independence at 90 days or rate of sICH compared to the non-stenting cohort. CONCLUSION: Stroke patients with successful intracranial reperfusion after MT had a higher probability of mortality within 90 days when concomitant stenting of the extracranial ICA was performed compared those patients who did not receive stenting.

Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO+ cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.

ASPECTS-based selection for late endovascular treatment: a retrospective two-site cohort study.

INTRODUCTION: The DAWN trial demonstrated the effectiveness of late endovascular treatment in acute ischemic stroke patients selected on the basis of a clinical-core mismatch. We explored in a real-world sample of endovascular treatment patients if a clinical-ASPECTS (Alberta Stroke Program Early CT Score) mismatch was associated with an outcome benefit after late endovascular treatment. METHODS: We retrospectively analyzed all consecutive acute ischemic stroke patients admitted 6-24 h after last proof of good health in two stroke centers, with initial National Institutes of Health Stroke Scale (NIHSS) ≥10 and an internal carotid artery or M1 occlusion. We defined clinical-ASPECTS mismatch as NIHSS ≥ 10 and ASPECTS ≥ 7, or NIHSS ≥ 20 and ASPECTS ≥ 5. We assessed the interaction between the presence of the clinical-ASPECTS mismatch and late endovascular treatment using ordinal shift analysis of the three-month modified Rankin Scale and adjusting for multiple confounders. RESULTS: The included 337 patients had a median age of 73 years (IQR = 61-82), admission NIHSS of 18 (15-22), and baseline ASPECTS of 7 (5-9). Out of 196 (58.2%) patients showing clinical-ASPECTS mismatch, 146 (74.5%) underwent late endovascular treatment. Among 141 (41.8%) mismatch negative patients, late endovascular treatment was performed in 72 (51.1%) patients. In the adjusted analysis, late endovascular treatment was significantly associated with a better outcome in the presence of clinical-ASPECTS mismatch (adjusted odd ratio, aOR = 2.83; 95% confidence interval, CI: 1.48-5.58) but not in its absence (aOR = 1.32; 95%CI: 0.61-2.84). The p-value for the interaction term between clinical-ASPECTS mismatch and late endovascular treatment was 0.073. CONCLUSIONS: In our retrospective two-site analysis, late endovascular treatment seemed effective in the presence of a clinical-ASPECTS mismatch, but not in its absence. If confirmed in randomized trials, this finding could support the use of an ASPECTS-based selection for late endovascular treatment decisions, obviating the need for advanced imaging.

Differentiation between benign and malignant vertebral compression fractures using qualitative and quantitative analysis of a single fast spin echo T2-weighted Dixon sequence.

OBJECTIVES: To determine and compare the qualitative and quantitative diagnostic performance of a single sagittal fast spin echo (FSE) T2-weighted Dixon sequence in differentiating benign and malignant vertebral compression fractures (VCF), using multiple readers and different quantitative methods. METHODS: From July 2014 to June 2020, 95 consecutive patients with spine MRI performed prior to cementoplasty for acute VCFs were retrospectively included. VCFs were categorized as benign (n = 63, mean age = 76 ± 12 years) or malignant (n = 32, mean age = 63 ± 12 years) with a best valuable comparator as a reference. Qualitative analysis was independently performed by four radiologists by categorizing each VCF as either benign or malignant using only the image sets provided by FSE T2-weighted Dixon sequences. Quantitative analysis was performed using two different regions of interest (ROI1-2) and three methods (signal drop, fat fraction (FF) from ROIs, FF maps). Diagnostic performance was compared using ROC curves analyses. Interobserver agreement was assessed using kappa statistics and intraclass correlation coefficients (ICC). RESULTS: The qualitative diagnostic performance ranged from area under the curve (AUC) = 0.97 (95% CI: 0.91-1.00) to AUC = 0.99 (95% CI: 0.95-1.0). The quantitative diagnostic performance ranged from AUC = 0.82 (95% CI: 0.73-0.89) to AUC = 0.97 (95% CI: 0.91-0.99). Pairwise comparisons showed no statistical difference in diagnostic performance (all p > 0.0013, Bonferroni-corrected p < 0.0011). All five cases with disagreement among the readers were correctly diagnosed at quantitative analysis using ROI2. Interobserver agreement was excellent for both qualitative and quantitative analyses. CONCLUSIONS: A single FSE T2-weighted Dixon sequence can be used to differentiate benign and malignant VCF with high diagnostic performance using both qualitative and quantitative analyses, which can provide complementary information. KEY POINTS: • Qualitative analysis of a single FSE T2-weighted Dixon sequence yields high diagnostic performance and excellent observer agreement for differentiating benign and malignant compression fractures. • The same FSE T2-weighted Dixon sequence allows quantitative assessment with high diagnostic performance. • Quantitative data can readily be extracted from the FSE T2-weighted Dixon sequence and may provide complementary information to the qualitative analysis, which may be useful in doubtful cases.

Pathfinders in oncology from the time the causal relation between tobacco use and lung cancer was established to publication of the first Cancer Staging Manual by the American Joint Committee on Cancer.

During the period from 1962 to 1977, several antigens, notably carcinoembryonic antigen and prostate-specific antigen, were discovered and entered clinical use. Ultrasonography, positron emission tomography scanning, and magnetic resonance imaging were introduced, and adjuvant radiation and chemotherapy after limited surgery became routine procedures. Radioimmunoassay and immunohistochemistry techniques were standardized. The announcement in England and the United States that tobacco is a potent lung carcinogen was long delayed, important news. The US Cancer Act of 1971 made it possible to experiment with newly discovered drugs, transfer promising therapeutic agents from the laboratory to the clinic, and finance randomized clinical trials. Oncologists achieved a series of successes with combination chemotherapy in childhood cancers, adult lymphomas, and testis tumors. Clinical trials demonstrated that breast-conserving therapy is as effective as mastectomy. The discovery of retroviruses, reverse transcriptase, and vascular endothelial growth factor was coupled with learning about oncogenes. The 2-hit theory and the reciprocal translocation of chromosomes helped to solve some of the riddles of oncogenesis. The staging classification of cancers by the American Joint Committee on Cancer unified clinical and pathologic handling and prognostication of malignant tumors. The progress made in oncology between 1962 and 1977 came about through the dedicated work of many individuals. However, there were 9 pathfinders (3 medical oncologists, 2 surgeons, 1 medical nuclear physicist, 1 pediatrician geneticist, 1 hematologist geneticist, and 1 virologist) who, despite their diverse backgrounds, personalities, and interest, made extraordinary contributions to oncology.

Association of Time of Day When Endovascular Therapy for Stroke Starts and Functional Outcome.

OBJECTIVE: To investigate the association between EVT start time in acute ischemic stroke (AIS) and mid-term functional outcome. METHODS: This retrospective cohort study included all AIS cases treated with EVT from two stroke center registries from January 2012 to December 2018. The primary outcome was the score on the modified Rankin Scale (mRS) and the utility-weighted mRS (uw-mRS) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention at a given EVT start time would lead to lower scores on the mRS (shift analysis). RESULTS: One thousand five hundred fifty-eight cases were equally allotted into twelve EVT-start-time periods. The primary outcome favored EVT start times in the morning at 08:00-10:20 and 10:20-11:34 (common odds ratio (OR), 0.53; 95% confidence interval (CI), 0.38 to 0.75; P<0.001; OR, 0.62; 95% CI, 0.44 to 0.87; P=0.006, respectively), while it disfavored EVT start times at the end of the working day at 15:55-17:15 and 18:55-20:55 (OR, 1.47; 95% CI, 1.03 to 2.09; P=0.034; OR, 1.49; 95% CI, 1.03 to 2.15; P=0.033). Symptom onset-to-EVT start time was significantly higher and use of IV t-PA significantly lower between 10:20-11:34 (P<0.004 and P=0.012, respectively). CONSLUSION: EVT for AIS in the morning leads to better mid-term functional outcome, while EVT at the end of the work day leads to poorer mid-term functional outcome. Neither difference in baseline factors, standard workflow and technical efficacy metrics could be identified as potential mediators of this effect.

Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke: Frequency and Clinical Impact.

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) in acute ischemic stroke is effective in the late time window in selected patients. However, the frequency and clinical impact of procedural complications in the early versus late time window has received little attention. METHODS: We retrospectively studied all acute ischemic strokes from 2015 to 2019 receiving EVT in the Acute Stroke Registry and Analysis of Lausanne. We compared the procedural EVT complications in the early (<6 hours) versus late (6-24 hours) window and correlated them with short-term clinical outcome. RESULTS: Among 695 acute ischemic strokes receiving EVT (of which 202 were in the late window), 113 (16.3%) had at least one procedural complication. The frequency of each single, and for overall procedural complications was similar for early versus late EVT (16.2% versus 16.3%, Padj=0.90). Procedural complications lead to a significantly less favorable short-term outcome, reflected by the absence of National Institutes of Health Stroke Scale improvement in late EVT (delta-National Institutes of Health Stroke Scale-24 hours, -2.5 versus 2, Padj=0.01). CONCLUSIONS: In this retrospective analysis of consecutive EVT, the frequency of procedural complications was similar for early and late EVT patients but very short-term outcome seemed less favorable in late EVT patients with complications.

Pathfinders in oncology from the first clinical use of single-agent chemotherapy to the introduction of mammography.

During the period from 1942 to 1962, treatment attempts with single-agent chemotherapy such as nitrogen mustard and urethan gained limited application. However, the groundbreaking success with aminopterin in the treatment of patients with pediatric acute leukemia and methotrexate in the treatment of gestational choriocarcinoma established single-agent chemotherapy as a pioneering contribution to oncology. The landmark discovery that early-stage Hodgkin disease is curable with radiation made radiotherapy into an essential specialty of oncology. Although radical surgical treatment dominated the field of surgery, the excision of localized cancers with or without adjuvant radiation emerged as new modality in therapy. Cytopathology and surgical pathology became new fields in medicine and pathologists became an integral part of the preoperative, intraoperative, and postoperative care of patients with cancer. The discovery of multiple new drugs demonstrated promising results and widened the field of oncology from the laboratory to the clinic. In the etiology of cancer, precancerous conditions were named and carcinoma of the lung was definitively linked to cigarette smoking. All things considered, the progress made between 1942 and 1962 came about through the dedicated work of many individuals. However, there were 7 distinguished pathfinders (2 pathologists, 1 pediatric pathologist-oncologist, 1 radiation therapist, 1 physician-actuary, 1 gynecologist-oncologist, and 1 chemist) who, despite their different backgrounds, interests, and sex, made groundbreaking contributions to oncology.

Meningeal Relapse of Nodular Lymphocyte Predominant Hodgkin Lymphoma Transformed to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Case Report.

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis.

Stereotactic Gamma Knife Radiosurgery for Extracranial Arteriovenous Malformations.

INTRODUCTION: Head and neck extracranial arteriovenous malformations (AVMs) are rare pathological conditions which pose diagnostic and reconstruction challenges. Stereotactic radiosurgery (SRS) is nowadays an established treatment method for brain AVMs, with high obliteration and low complication rates. Here we describe the first report of head extracranial AVMs successfully treated by Gamma Knife (GK) as a retrospective historical cohort. METHODS: Over a 9-year period, 2 cases of extracranial AVMs were treated by GK Perfexion (Elekta Instruments AB, Stockholm, Sweden) at a single institution. A stereotactic frame and multimodal imaging, including digital subtraction angiography (DSA), were used. The prescribed dose was 24 Gy at the 50% isodose line. RESULTS: The first case was of a patient with pulsating tinnitus and left superficial parotido-condylian AVM. Embolization achieved partial obliteration. Tinnitus disappeared during the following 6 months after GK. The second case was a patient with repetitive gingival hemorrhages and right superior maxillary AVM, fed by the right internal maxillary and facial arteries. Embolization achieved partial obliteration with recurrence of symptoms. GK was further performed. DSA confirmed complete obliteration in both patients. CONCLUSIONS: Single-fraction GK radiosurgery appears to be safe and effective for extracranial AVMs. We recommend prescribing doses that are comparable to the ones used for brain AVMs (i.e., 24 Gy). A stereotactic frame is an important tool to ensure higher accuracy in the context of these particular locations. However, in selected cases, a mask could be applied either for single fraction purposes (if in a non-mobile location) or for hypofractionation, in case of larger volumes. These findings should be validated in larger cohorts, inclusively in terms of dose prescription.

Association of initial imaging modality and futile recanalization after thrombectomy.

OBJECTIVE: To test the hypothesis that selection by initial imaging modality (MRI vs CT) is associated with rate of futile recanalizations (FRs) after mechanical thrombectomy (MT), we assessed this association in a multicenter, retrospective observational registry (BEYOND-SWIFT [Registry for Evaluating Outcome of Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy], NCT03496064). METHODS: In 2,011 patients (49.7% female, median age 73 years [61-81]) included between 2009 and 2017, we performed univariate and multivariate analyses regarding the occurrence of FR. FRs were defined as 90-day modified Rankin Scale (mRS) score 4-6 despite successful recanalization in patients selected by MRI (n = 690) and CT (n = 1,321) with a sensitivity analysis considering only patients with mRS 5-6 as futile. RESULTS: MRI as compared to CT resulted in similar rates of subsequent MT (adjusted odds ratio [aOR] 1.048, 95% confidence interval [CI] 0.677-1.624). Rates of FR were as follows: 571/1,489 (38%) FR mRS 4-6 including 393/1,489 (26%) FR mRS 5-6. CT-based selection was associated with increased rates of FRs compared to MRI (44% [41%-47%] vs 29% [25%-32%], p < 0.001; aOR 1.77 [95% CI 1.25-2.51]). These findings were robust in sensitivity analysis. MRI-selected patients had a delay of approximately 30 minutes in workflow metrics in real-world university comprehensive stroke centers. However, functional outcome and mortality were more favorable in patients selected by MRI compared to patients selected with CT. CONCLUSIONS: CT selection for MT was associated with an increased risk of FRs as compared to MRI selection. Efforts are needed to shorten workflow delays in MRI patients. Further research is needed to clarify the role of the initial imaging modality on FR occurrence and to develop a reliable FR prediction algorithm.

Acute Stroke Management During the COVID-19 Pandemic: Does Confinement Impact Eligibility for Endovascular Therapy?

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), (P<0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time (P<0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

Pathfinders in oncology from the beginning of modern surgery of intracranial tumors to the introduction of the Pap smear.

During the period from 1922 to 1942, several carcinogens were identified in coal tar, industrial oils, and petroleum, and radium was added to x-ray as a potential carcinogen. It was proven that some viruses are capable of causing cancer, and the dependency of prostatic and mammary hyperplasia and carcinoma on naturally occurring hormones was established. Colon cancer was linked to hereditary and nonhereditary polyposis. A permanent place for diagnostic radiology was defined and radiation therapy advanced to preoperative and postoperative modalities using x-ray and radium. The trend toward the use of radical surgery for primary and metastatic cancers continued. Although several new radical surgical procedures were developed and advanced as far as the technical skills of surgeons and the anatomic setting permitted, several innovative, less radical procedures were introduced. In chemotherapy, the basic principle of the treatment of advanced cancers with hormones was inaugurated. Pathologists synthesized what was known in tumor pathology, named new microscopic entities, recognized carcinoma in situ, developed histologic grading and pathologic staging of cancers, and introduced aspiration cytology and exfoliative cytology as new fields in oncology. It is interesting that despite profound global economic, social, and political upheaval and wars and preparation for wars, writers and producers of musicals and movies presented more memorable works than ever before. In the fields of science and technology, particularly nuclear physics and chemistry, profound discoveries were made that became a permanent part of human life. The progress made in oncology between 1922 and 1942 came about through the dedicated work of many individuals. However, there were 7 pathfinders (3 surgeons, 2 pathologists, 1 physician-chemist, and 1 physician-cytologist) who, despite their widely diverse backgrounds, personalities, and interest, made outstanding contributions to oncology to the magnitude that they deserve a permanent place in the history of medicine and oncology.