Brain and Placental Pathology in Fetal COL4A1 Related Disease

2021 ◽  
pp. 109352662098408
Author(s):  
Patrick Shannon ◽  
Courtney Hum ◽  
Tony Parks ◽  
GM Schauer ◽  
David Chitayat ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ventricular Zone ◽  
Fetal Brain ◽  
Small Vessel ◽  
Low Grade ◽  
High Grade ◽  
Placental Pathology ◽  
Cell Degeneration ◽  
Genetic Sequencing ◽  
Related Disease

Introduction Although fetal brain injury due to COL4A1 gene mutation is well documented, fetal central nervous system (CNS) and placental histopathology lack description. We report CNS and placental pathology in fetal cases with symptomatic COL4A1 mutation. Methods We retrieved four autopsy cases of COL4A1 related disease, confirmed by genetic sequencing after fetal brain injury was detected. Results One case was a midgestation fetus with residua of ventricular zone hemorrhage and normal placental villi. Three cases were 30-32 week gestation fetuses: two demonstrated CNS small vessel thrombosis, with CNS injury. Both demonstrated high grade placental fetal vascular malperfusion (FVM). One additionally showed villous dysmorphism, the other demonstrated mild villous immaturity. The fetus whose placenta demonstrated high grade FVM was growth restricted. A fourth fetus demonstrated schizencephaly with a CNS arteriopathy with smooth muscle cell degeneration and cerebral infarcts; the placenta demonstrated severe villous dysmorphism and low grade FVM. Discussion These cases confirm that small vessel disease is important in producing intracranial pathology in COL4A1mutation. We report an arteriopathy distinct from microvascular thrombosis and demonstrate that placental pathology is common in fetal COL4A1 related disease. This tentatively suggests that placental pathology may contribute to CNS abnormalities by affecting circulatory sufficiency.

Formulating a Meaningful and Comprehensive Placental Phenotypic Classification

2021 ◽  
pp. 109352662110084
Author(s):  
Alexa A Freedman ◽  
Lauren S Keenan-Devlin ◽  
Ann Borders ◽  
Gregory E Miller ◽  
Linda M Ernst
Keyword(s):  
Preterm Birth ◽  
Birth Outcomes ◽  
Gestational Age ◽  
Web Application ◽  
Acute Inflammation ◽  
Low Grade ◽  
Adverse Birth Outcomes ◽  
High Grade ◽  
Placental Pathology ◽  
Pathology Reports

Introduction While many placental lesions have been identified and defined, the significance of multiple overlapping lesions has not been addressed. The purpose of our analysis was to evaluate overlapping patterns of placental pathology and determine meaningful phenotypes associated with adverse birth outcomes. Methods Placental pathology reports were obtained from a single hospital between 2009 and 2018. Placental lesions were grouped into four major categories: acute inflammation (AI), chronic inflammation (CI), maternal vascular malperfusion (MVM), and fetal vascular malperfusion (FVM). Within each category, lesions were classified as not present, low grade or high grade. Combinations of pathologies were evaluated in relation to preterm birth (<37 weeks) and small for gestational age (SGA) infant (birthweight <10th percentile). Results During the study period, 19,027 placentas were reviewed by pathologists. Results from interaction models indicate that MVM and MVM in combination with CI and/or FVM are associated with the greatest odds of SGA infant and PTB. When incorporating grade, we identified 21 phenotype groups, each with characteristic associations with the SGA infant and patterns of PTB. Discussion We have developed a comprehensive and meaningful placental phenotype that incorporates severity and multiplicity of placental lesions. We have also developed a web application to facilitate phenotype determination ( https://placentaexpression.shinyapps.io/phenotype ).

Klinische Wertigkeit der Positronen-Emissions-Tomographie (PET) bei onkologischen Fragestellungen: Ergebnisse einer interdisziplinären Konsensuskonferenz

1996 ◽  
Vol 35 (02) ◽  
pp. 42-52 ◽  
Author(s):  
R. Bares ◽  
U. Bull ◽  
A. Guhlmann ◽  
E. Moser ◽  
M. F. Wannenmacher ◽  
...  
Keyword(s):  
Low Grade ◽  
High Grade ◽  
Klinische Anwendung ◽  
Wissenschaftliche Studien

Zusammenfassung Ziel: Es ist das Ziel der vorliegenden Arbeit, an Hand bisher publizierter Studienergebnisse eine Beurteilung des klinischen Stellenwertes von PET in der Onkologie zu erarbeiten. Methoden: Im Rahmen einer interdisziplinären Konferenz mit namhaften Experten wurde eine Wertung des gegenwärtigen Stands von PET in der Onkologie an Hand der in der Literatur dokumentierten Studienergebnisse erarbeitet. Angestrebt wurde eine differenzierte Bewertung von PET für die klinische Anwendung in fünf Klassen (1a, 1b, 2a, 2b, 3) von »angemessen« (1a), »akzeptabel« (1b), »hilfreich« (2a), »noch keine Bewertung möglich« (2b), »ohne Nutzen« (3). Ergebnisse: Für den klinischen Einsatz in der Onkologie ist 2-F18-Fluorodeoxyglukose (FDG) das Radiopharmakon der Wahl. PET ist klinisch in der Patientenversorgung zur Rezidivdiagnostik von high-grade Gliomen (FDG), low-grade Gliomen (C-11 Methionin oder F-18 Tyrosin), für die Dignitätsdiagnostik des peripheren Lungenrundherdes bei Risikopatienten sowie für die Diagnostik des Pankreaskarzioms indiziert (Indikation 1a). PET kann in der Patientenversorgung bei folgenden Indikationen (1b) eingesetzt werden: »low-grade« Gliome, Suche nach unbekanntem Primärtumor bei Kopf-Hals-Tumoren, Rezidivdiagnostik des nicht kleinzelligen Bronchialkarzinoms sowie des Rektumkarzinoms, Lymphknotenstaging beim nicht kleinzelligen Bronchial-Karzinom, Pan-kreas-Karzinom, muskelinvasiven Blasen-Karzinom und Hoden-Karzinom. Staging bei M. Hodgkin (Stad. I/II versus III), frühe Therapiekontrolle bei Resttumor und Rezidivdiagnostik bei M. Hodgkin und hochmalignen Non-Hodgkin-Lymphomen, Lymphknoten-Staging und Fern-metastasensuche beim malignen Melanom (Breslow >1,5 mm), Lymphknoten- und Fernmetastasen-Nachweis beim Schilddrüsen-Karzinommit erhöhtem hTg und nicht radiojodspeichernden Metastasen. Zahlreiche weitere Indikationen zeichnen sich bereits jetzt ab, sind jedoch noch weniger gut durch wissenschaftliche Studien belegt. Für die meisten Indikationen außerhalb wissenschaftlicher Studien ist eine individuelle Kosten-Nutzen-Betrachtung durch den verantwortlichen Arzt geboten. Schlußfolgerungen: Die metabolische Bildgebung von PET besitzt für eine Vielzahl onkologischer Fragestellungen prinzipielle Vorteile gegenüber der anatomisch-morphologisch orientierten Schnittbilddiagnostik. Für die klinische Indikationsstellung ist allerdings eine differenzierte Betrachtung der spezifischen Leistungsfähigkeit von PET geboten.

CD133/CD166/Ki-67 Triple Immunouorescence Assessment for Putative Cancer Stem Cells in Colon Carcinoma*

2014 ◽  
Vol 23 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Claudiu Margaritescu ◽  
Daniel Pirici ◽  
Irina Cherciu ◽  
Alexandru Barbalan ◽  
Tatiana Cârtâna ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Colon Carcinoma ◽  
Sodium Dodecyl ◽  
High Grade Dysplasia ◽  
Early Event ◽  
Low Grade ◽  
High Grade

Background & Aims: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers.Methods. A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization.Results. Both CD133 and CD166 were expressed to different extents in all cancer specimens, with apredominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166.Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/ CD166 was obvious at the level of cells membranes, with higher coeficients in high grade dysplasia, followed by well and moderate differentiated tumours.Conclusions. CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with thehighest coeficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic andtherapeutically stratification of patients with colon cancer.Abbreviations: AJCC - American Joint Committee on Cancer; CCD - charge-coupled device camera sensor; CD133 - prominin-1 (PROM1); CD166 - Activated Leukocyte Cell Adhesion Molecule (ALCAM); CRC - colorectal cancer; CSC - cancer stem cells; DAB - 3,3'-diaminobenzidine chromogen; DAPI - 4',6-diamidino- 2-phenylindole; HE - Hematoxylin and eosin staining; HGD - high grade dysplasia; HRP - horseradish peroxidase; LGD - low grade dysplasia; SDS - sodium dodecyl sulfate*Part of this work has been accepted as a poster presentation at the Digestive Disease Week (DDW) meeting, Chicago, IL, USA May 3-6, 2014

MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Molecular Subtypes ◽  
Survival Rates ◽  
Consensus Algorithm ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

Low Utility in Colposcopy-directed Biopsies for Non-high Grade Cytological Abnormalities on PAP Smear

2020 ◽  
Vol 16 (1) ◽  
pp. 18-22
Author(s):  
Eronmwon E. Gbinigie ◽  
Joshua Fogel ◽  
Maggie Tetrokalashvili
Keyword(s):  
Pap Smear ◽  
Multinomial Logistic Regression ◽  
Cervical Dysplasia ◽  
Outcome Variable ◽  
Low Grade ◽  
High Grade ◽  
Squamous Intraepithelial Lesion ◽  
Intraepithelial Lesion ◽  
Cytologic Abnormalities ◽  
Cytology Screening

Background: Clinicians commonly perform colposcopy directed biopsies on patients with low grade squamous intraepithelial lesion (LSIL) on PAP cytology even when not consistent with clinical guidelines. Objective: We study the association of PAP cytology screening results with cervical intra-epithelia neoplasia (CIN) 2-3 high-grade dysplasia, as confirmed by colposcopy-directed biopsy. Methods: A retrospective study of 263 women with an abnormality on the PAP smear. Multinomial logistic regression was performed with predictors of PAP cytology screening results with the outcome variable of colposcopy-directed biopsy. Results: High grade squamous intraepithelial lesion (HSIL) had significantly increased relative risk for CIN 2-3 (RR: 9.85, 95% CI: 1.84, 52.79, p=0.008). LSIL was not significantly associated with CIN 2-3. In the comparisons of negative with CIN-1, both HSIL and LSIL were not significantly associated with a negative biopsy. Conclusion: HSIL is associated with cervical dysplasia of CIN 2-3 while LSIL is not associated with cervical dysplasia of CIN 2-3. We do not recommend routine biopsies in patients with LSIL cytologic abnormalities unless additional compelling factors exist.

scholarly journals The management and outcome of paediatric splenic injuries in the Netherlands

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Maike Grootenhaar ◽  
Dominique Lamers ◽  
Karin Kamphuis-van Ulzen ◽  
Ivo de Blaauw ◽  
Edward C. Tan
Keyword(s):  
The Netherlands ◽  
Hospital Stay ◽  
Operative Management ◽  
Trauma Centre ◽  
Management Approach ◽  
Haemodynamic Instability ◽  
Low Grade ◽  
High Grade ◽  
Level 1 ◽  
Non Operative Management

Abstract Background Non-operative management (NOM) is generally accepted as a treatment method of traumatic paediatric splenic rupture. However, considerable variations in management exist. This study analyses local trends in aetiology and management of paediatric splenic injuries and evaluates the implementation of the guidelines proposed by the American Paediatric Surgical Association (APSA) in a level 1 trauma centre. Methods The charts of paediatric patients with blunt splenic injury (BSI) who were admitted or transferred to a level 1 trauma centre between 2003 and 2020 were retrospectively assessed. Information pertaining to demographics, mechanism of injury, injury description, associated injuries, intervention and outcomes were analysed and compared to international literature. Results There were 130 patients with BSI identified (63.1% male), with a mean age of 11.3 ± 4.0 and a mean Injury Severity Score (ISS) of 21.6 ± 13.7. Bicycle accidents were the most common trauma mechanism (23.1%). Sixty-four percent were multi-trauma patients, 25% received blood transfusions, and 31% were haemodynamically unstable. Mean injury grade was 3.0, with 30% of patients having a high-grade injury. In total, 75% of patients underwent NOM with a 100% efficacy rate. Total splenectomy rate was 6.2%. Four patients died due to brain damage. Patients with a high-grade BSI (grades IV–V) had a significantly higher ISS and longer bedrest and more often presented with an active blush on computed tomography (CT) scans than patients with a low-grade BSI (grades I–III). Non-operative management was mainly the choice of treatment in both groups (76.6% and 79.5%, respectively). Haemodynamic instability was a predictor for operative management (OM) (p = 0.001). Predictors for a longer length of stay (LOS) included concomitant injuries, haemodynamic instability and OM (all p < 0.02). Interobserver agreement in the grading of BSI is moderate, with a Cohens Kappa coefficient of 0.493. Conclusion Non-operative management has proven to be a realistic management approach in both low- and high-grade splenic injuries. Consideration for operative management should be based on haemodynamic instability. Compared to the anticipated length of bedrest and hospital stay outlined in the APSA guidelines, the Netherlands can reduce the length of bedrest and hospital stay through their non-operative management. Level of evidence Therapeutic study, level III

scholarly journals Desquamation in Kawasaki Disease

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 317
Author(s):  
Ling-Sai Chang ◽  
Ken-Pen Weng ◽  
Jia-Huei Yan ◽  
Wan-Shan Lo ◽  
Mindy Ming-Huey Guo ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Kawasaki Disease ◽  
Laboratory Data ◽  
Ivig Treatment ◽  
Low Grade ◽  
High Grade ◽  
Laboratory Findings ◽  
Coronary Artery Abnormalities ◽  
Cell Counts ◽  
Hands And Feet

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.

Sign in / Sign up

Export Citation Format

Share Document