NCOG-02. PROGNOSTIC VALIDATION OF THE EANO ESMO CLASSIFICATION OF LEPTOMENINGEAL METASTASIS

Abstract BACKGROUND The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear and nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these EANO ESMO LM subtypes for choice of treatment and outcome. PATIENTS AND METHODS We retrospectively assembled data from 254 patients with newly diagnosed LM from different solid tumors, including as main primary tumors breast cancer (n=98, 45%), lung cancer (n=65, 25.5%) and melanoma (n=51, 13.5%). Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test. RESULTS Median age at LM diagnosis was 56.5 years (range 20-82 years). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n=33, 13%), C (n=54, 21%) and D (n=50, 19.5%) were less common. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Patients with confirmed LM had inferior outcome than patients with probable or possible LM (p=0.0063). Type I patients had inferior outcome than type II patients (p=0.0019). Nodular disease was a negative prognostic factor in type II LM, but not in type I LM (p=0.0138). CONCLUSION The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

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41. PROGNOSTIC VALIDATION OF THE EANO ESMO CLASSIFICATION OF LEPTOMENINGEAL METASTASIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.029 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii7-ii8

Author(s):

Emilie Le Rhun ◽

Patrick Devos ◽

Johannes Weller ◽

Katharina Seystahl ◽

Francesca Mo ◽

...

Keyword(s):

Tumor Cells ◽

Leptomeningeal Metastasis ◽

Rank Test ◽

Type I ◽

Type Ii ◽

Primary Tumors ◽

Log Rank Test ◽

Kaplan Meier ◽

Negative Prognostic Factor

Abstract BACKGROUND The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear and nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these EANO ESMO LM subtypes. PATIENTS AND METHODS We retrospectively assembled data from 254 patients with newly diagnosed LM from different solid tumors, including as main primary tumors breast cancer (n=98, 45%), lung cancer (n=65, 25.5%) and melanoma (n=51, 13.5%). Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test. RESULTS Median age at LM diagnosis was 56.5 years (range 20–82 years). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n=33, 13%), C (n=54, 21%) and D (n=50, 19.5%) were less common. Tumor cells were observed in the CSF in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Patients with confirmed LM had inferior outcome than patients with probable or possible LM (p=0.0063). Type I patients had inferior outcome than type II patients (p=0.0019). Nodular disease was a negative prognostic factor in type II LM, but not in type I LM (p=0.0138). CONCLUSION The presence of tumor cells in the CSF appears to have a greater prognostic role than the neuroimaging presentation. EANO ESMO LM subtypes are highly prognostic and should be considered in the design of clinical trials.

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Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors

Neuro-Oncology ◽

10.1093/neuonc/noaa298 ◽

2020 ◽

Author(s):

Emilie Le Rhun ◽

Patrick Devos ◽

Johannes Weller ◽

Katharina Seystahl ◽

Francesca Mo ◽

...

Keyword(s):

Solid Tumors ◽

Leptomeningeal Metastasis ◽

Rank Test ◽

Type I ◽

Type Ii ◽

Csf Cytology ◽

Kaplan Meier ◽

Clinical Magnetic Resonance Imaging ◽

Magnetic Resonance Imaging Mri

Abstract Background The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes. Patients and methods We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test. Results Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (p=0.006). Type I patients had inferior outcome than type II patients (p=0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (p=0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (p=0.020) or systemic pharmacotherapy (p=0.0004) was associated with improved outcome in type I LM, but not in type II LM. Conclusion The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

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Morphological types of spermatheca in Coreidae: bearing on intra-familial classification and tribal-groupings (Hemiptera: Heteroptera)

Zootaxa ◽

10.11646/zootaxa.4834.4.1 ◽

2020 ◽

Vol 4834 (4) ◽

pp. 451-501

Author(s):

DOMINIQUE PLUOT-SIGWALT ◽

PIERRE MOULET

Keyword(s):

Western Hemisphere ◽

Type I ◽

Type Ii ◽

Type Iii ◽

Spermathecal Duct ◽

Eastern Hemisphere ◽

Intermediate Part ◽

Muscular Pump ◽

Familial Classification

The morphology of the spermatheca is described in 109 species of 86 genera representing all four currently recognised subfamilies of Coreidae, covering the undivided Hydarinae, both tribes of Pseudophloeinae, all three tribes of Meropachyinae and 27 of the 32 tribes of Coreinae. Three types of spermatheca are recognised. Type I is bipartite, consisting only of a simple tube differentiated into distal seminal receptacle and proximal spermathecal duct and lacks the intermediate part present in most Pentatomomorpha, in which it serves as muscular pump. Type II is also bipartite but more elaborate in form with the receptacle generally distinctly wider than the duct. Type III is tripartite, with receptacle, duct and an often complex intermediate part. Four subtypes are recognised within type III. Type I is found only in Hydarinae and type II only in Pseudophloeinae. Type III is found in both Coreinae and Meropachyinae. Subtype IIIA (“Coreus-group”) unites many tribes from the Eastern Hemisphere and only one (Spartocerini) from the Western Hemisphere. Subtypes IIIB (“Nematopus-group”) and IIID (“Anisoscelis-group”) are confined to taxa from the Western Hemisphere and subtype IIIC (“Chariesterus-group”) is found in tribes from both hemispheres. The polarity of several characters of the intermediate part and some of the spermathecal duct is evaluated, suggesting autapomorphies or apomorphies potentially relevant to the classification of Coreidae at the sufamilial and tribal levels. Characters of the intermediate part strongly indicate that the separation of Meropachyinae and Coreinae as currently constituted cannot be substantiated. The tribes Anisoscelini, Colpurini, Daladerini and Hyselonotini are heterogeneous, each exhibiting two subtypes of spermatheca, and probably polyphyletic. Two tribes, Cloresmini and Colpurini, requiring further investigation remain unplaced. This study demonstrates the great importance of characters of the spermatheca, in particular its intermediate part, for research into the phylogeny and taxonomy of Pentatomomorpha.

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Split spinal cord malformations in children

Journal of Neurosurgery ◽

10.3171/jns.1998.88.1.0057 ◽

1998 ◽

Vol 88 (1) ◽

pp. 57-65 ◽

Cited By ~ 72

Author(s):

Yusuf Ersşahin ◽

Saffet Mutluer ◽

Sevgül Kocaman ◽

Eren Demirtasş

Keyword(s):

Spinal Cord ◽

Neurological Deficits ◽

Single Type ◽

Type I ◽

Type Ii ◽

Content Type ◽

Spinal Lesion ◽

The Mean ◽

Fine Print

Object. The authors reviewed and analyzed information on 74 patients with split spinal cord malformations (SSCMs) treated between January 1, 1980 and December 31, 1996 at their institution with the aim of defining and classifying the malformations according to the method of Pang, et al. Methods. Computerized tomography myelography was superior to other radiological tools in defining the type of SSCM. There were 46 girls (62%) and 28 boys (38%) ranging in age from less than 1 day to 12 years (mean 33.08 months). The mean age (43.2 months) of the patients who exhibited neurological deficits and orthopedic deformities was significantly older than those (8.2 months) without deficits (p = 0.003). Fifty-two patients had a single Type I and 18 patients a single Type II SSCM; four patients had composite SSCMs. Sixty-two patients had at least one associated spinal lesion that could lead to spinal cord tethering. After surgery, the majority of the patients remained stable and clinical improvement was observed in 18 patients. Conclusions. The classification of SSCMs proposed by Pang, et al., will eliminate the current chaos in terminology. In all SSCMs, either a rigid or a fibrous septum was found to transfix the spinal cord. There was at least one unrelated lesion that caused tethering of the spinal cord in 85% of the patients. The risk of neurological deficits resulting from SSCMs increases with the age of the patient; therefore, all patients should be surgically treated when diagnosed, especially before the development of orthopedic and neurological manifestations.

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High Expression of Cathepsin D in Non-Hodgkin’s Lymphomas Negatively Impacts on Clinical Outcome

Disease Markers ◽

10.1155/2010/465040 ◽

2010 ◽

Vol 28 (3) ◽

pp. 167-183 ◽

Cited By ~ 4

Author(s):

Giuseppina Nicotra ◽

Federica Manfroi ◽

Carlo Follo ◽

Roberta Castino ◽

Nicola Fusco ◽

...

Keyword(s):

Clinical Outcome ◽

Tumor Cells ◽

Survival Probability ◽

Cathepsin D ◽

Rank Test ◽

Lysosomal Protease ◽

T Cell Lymphomas ◽

Kaplan Meier ◽

Punctate Pattern ◽

Hodgkin's Lymphomas

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin’s Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as ‘low expressing’ (< 20% of tumor cells) or ‘highly expressing’ (≥ 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases;p= 0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases;p= 0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (~20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells (~70% at 5 year). This correlation was statistically significant (log-rank test,p= 0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs.

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Type I Versus Type II Endometrial Cancer: Differential Impact of Comorbidity

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001184 ◽

2018 ◽

Vol 28 (3) ◽

pp. 586-593 ◽

Cited By ~ 8

Author(s):

Mette Calundann Noer ◽

Sofie Leisby Antonsen ◽

Bent Ottesen ◽

Ib Jarle Christensen ◽

Claus Høgdall

Keyword(s):

Cox Regression ◽

Type I ◽

Prognostic Impact ◽

Type Ii ◽

Regression Analyses ◽

Differential Impact ◽

Kaplan Meier ◽

Prediction Of Survival ◽

Comorbidity Index ◽

The Impact

ObjectiveTwo distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC.Materials and MethodsThis nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC.ResultsThe distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population.ConclusionsComorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.

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Histological Investigation of the Palatine Bone in Prenatal Trisomy 21

The Cleft Palate-Craniofacial Journal ◽

10.1597/1545-1569_2001_038_0492_hiotpb_2.0.co_2 ◽

2001 ◽

Vol 38 (5) ◽

pp. 492-497 ◽

Cited By ~ 3

Author(s):

Halfdan Lauridsen ◽

Birgit Fischer Hansen ◽

Ingermarie Reintoft ◽

Jean W. Keeling ◽

Inger Kjær

Keyword(s):

Trisomy 21 ◽

Type I ◽

Histological Investigation ◽

Type Ii ◽

Human Fetuses ◽

Type Iv ◽

Different Types ◽

Horizontal Part ◽

Palatine Bone

Objective: The purpose of the present study was to investigate the horizontal part of the palatine bone in palates from human fetuses with trisomy 21 to improve the phenotypic classification of the genotypic anomaly. Methods: Material from 23 human trisomy 21 fetuses was included in the study. The crown rump lengths of the fetuses ranged from 80 mm to 190 mm, corresponding to about 12 to 21 weeks of gestational age. The material was examined histologically. Results and Conclusions: Histological examination demonstrated four different palatal phenotypes on the basis of the development of the horizontal part of the palatine bone: type I, palatine bone complete; type II, the mesial region of the horizontal part of the palatine bone is lacking; type III, complete absence of the horizontal part of the palatine bone; and type IV, auxiliary bones in the region of the transpalatine suture. This finding shows that different types of malformations may occur in the horizontal part of the palatine bone in human trisomy 21 fetuses.

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Proposed Conceptual Taxonomy for Proper Identification and Classification of Tornado Events

Weather and Forecasting ◽

10.1175/2008waf2222163.1 ◽

2009 ◽

Vol 24 (2) ◽

pp. 609-617 ◽

Cited By ~ 13

Author(s):

Ernest Agee ◽

Erin Jones

Keyword(s):

Global Warming ◽

First Century ◽

Cold Pool ◽

Type I ◽

Field Observations ◽

Type Ii ◽

Data Archiving ◽

Convective Systems ◽

Supercell Storms

Abstract A practical approach is recommended for identifying and archiving tornado events, based on the use of definitions that label all vortices as either type I, II, or III tornadoes. This methodology will provide a more meaningful tornado climatology in Storm Data, which separates and classifies all vortices associated in any manner with cumuliform clouds. Tornadoes produced within the mesocyclone of discrete supercell storms, with strong local updrafts (SLUs), will be classified as type I tornadoes. Frequently, these type I tornadoes result from the interaction of the SLU with strong rear-flank downdrafts (RFDs), or with shear vortices in the PBL. Tornadoes produced in association with quasi-linear convective systems (QLCS) will be classified as type II tornadoes (including cold pool, rear-inflow jets, bookend, and mesovortex events along the line). All other vortex types (including landspouts, waterspouts, gustnadoes, cold air vortices, and tornadoes not associated with mesocyclones or QLCS) will be labeled as type III tornadoes. A general discussion is provided that further clarifies the differences and categorization of these three classifications (which encompass 15 tornado species), along with a recommendation that NOAA adopt this taxonomy in operational and data archiving practices. Radar analysis and field observations, combined with storm-scale meteorological expertise, should allow for the official “typing” of tornado reports by NOAA personnel. Establishment of such a climatological database in Storm Data may be of value in assessing the effects (if any) of twenty-first-century global warming on U.S. tornado trends.

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Syntheses of Post-Iboga Alkaloids

Synthesis ◽

10.1055/s-0037-1612061 ◽

2019 ◽

Vol 51 (14) ◽

pp. 2737-2758 ◽

Cited By ~ 9

Author(s):

Hyeonggeun Lim ◽

Sikwang Seong ◽

Sunkyu Han

Keyword(s):

Secondary Metabolites ◽

Type I ◽

Type Ii ◽

Type Iii ◽

Type Iv ◽

Synthetic Studies ◽

Type V

Post-iboga alkaloids are secondary metabolites that are biosynthetically derived from iboga-type alkaloids via rearrangements of the indole and/or isoquinuclidine moieties. Herein, we categorize post-iboga alkaloids into five types based on the biosynthetic mode of transformation of the iboga scaffold. We then describe reported syntheses of post-iboga alkaloids, including our laboratory’s recent contributions, based on our own categorization.1 Introduction1.1 Iboga and Post-Iboga Alkaloids1.2 Classification of Post-Iboga Alkaloids1.2.1 Introduction to Type I Post-Iboga Alkaloids1.2.2 Introduction to Type II Post-Iboga Alkaloids1.2.3 Introduction to Type III Post-Iboga Alkaloids1.2.4 Introduction to Type IV Post-Iboga Alkaloids1.2.5 Introduction to Type V Post-Iboga Alkaloids2 Syntheses of Post-Iboga Alkaloids2.1 Syntheses of Type I Post-Iboga Alkaloids2.1.1 Syntheses of Monomeric Type I Post-Iboga Alkaloids2.1.2 Syntheses of Dimeric Type I Post-Iboga Alkaloids2.2 Syntheses of Type II Post-Iboga Alkaloids2.3 Synthetic Studies Toward Type III Post-Iboga Alkaloids2.4 Syntheses of Type IV Post-Iboga Alkaloids2.5 Synthesis of Type V Post-Iboga Alkaloids3 Conclusion and Outlook

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Sonographic Analysis of the Upper Labial Orbicularis Oris and Its Clinical Implications

Aesthetic Surgery Journal ◽

10.1093/asj/sjz341 ◽

2019 ◽

Vol 40 (7) ◽

pp. 778-783

Author(s):

Hyun Jin Park ◽

Kyu-Lim Lee ◽

Young-Chun Gil ◽

Ji-Hyun Lee ◽

Kyung-Seok Hu ◽

...

Keyword(s):

Botulinum Toxin ◽

Type I ◽

Type Ii ◽

Upper Lip ◽

Reference Information ◽

Reliable Source ◽

Orbicularis Oris Muscle ◽

Morphological Differences ◽

Sonographic Imaging

Abstract Background Purse string lips, which include the vertical wrinkles over the lips, are frequently observed in aged individuals. Botulinum toxin and fillers are routinely injected into these areas to remove the wrinkles; however, the anatomy of the orbicularis oris muscle (OOr) near the vermilion border area has not been well defined. Objectives The aim of this study was therefore to identify any morphological differences of the upper OOr via sonographic imaging. Methods The upper lip muscles as observed utilizing an ultrasound device were divided into 2 muscles (pars peripheralis and pars marginalis) that were subsequently divided into a further 2 types (Type I and Type II) associated with the development of the pars marginalis. Type II was further divided into Type IIa and Type IIb depending on whether the muscle fibers were well developed and connected. Results On the midline of the lip, Type I, in which the pars marginalis was rarely observed and only appeared in traces, was observed in 20.0% of the volunteers. Type IIa, in which the pars marginalis was well-developed and appeared continuous, was observed in 42.9% of the volunteers. Type IIb, in which the pars marginalis was observed but appeared discontinuous, was observed in 37.1% of the volunteers. Conclusions The shapes of the upper pars marginalis of the OOr varied markedly between volunteers. Type classification of the OOr based on its shape and the lip appearance serves as a reliable source of reference information to be utilized when injecting botulinum toxin into the upper lip.

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