This study evaluated interobserver and intraobserver reliability of a novel grading system for oral squamous cell carcinoma (OSCC) based on tumour budding and cell nest size. Three pathologists independently scored 108 OSCC cases using this system. Interobserver agreement between experienced pathologists was excellent (Cohen's kappa 0.97). A pathologist in training initially showed lower agreement but agreement improved significantly after training. Intraobserver agreement for one pathologist was also high (kappa 0.95), demonstrating reproducibility of the grading system. This study supports the suitability of this novel grading system for routine use in assessing OSCC.
Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in Vitr...Peter Pachmann
ABSTRACT
Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empiri- cally developed recommendations derived from statistical relapse rates occurring years after the treatment in the adju- vant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient’s body for chemosensitiv- ity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percent- ages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.
11.expression of emerging novel tumor markers in oral squamous cell carcinoma...Alexander Decker
This document summarizes a systematic review of 12 emerging novel tumor markers that have been studied for their expression in oral squamous cell carcinoma (OSCC) between 2006-2011. The review finds that none of the 12 tumor markers (TROP2, Periostin, SENP5, mGluR5, Septin1, Stathmin, IMP3, Tapasin, Stromal Versican, STAT1, Cyr61) demonstrated all the qualities of an ideal tumor marker, such as good sensitivity and specificity for diagnosis or prognosis. Some markers like TROP2, Stathmin, IMP3, Tapasin, and Cyr61 showed potential as prognostic markers or therapeutic targets, but more research is still
Objective: The association between telomerase reverse transcriptase (TERT) promoter mutation and outcome of melanoma is unclear and controversial. We aim to conduct a meta-analysis and investigate whether the TERT promoter mutation is a prognostic factor of melanoma.
Study Design: Appropriate studies were searched in 3 databases: PubMed, Web of Science, and Embase. Pooled hazard ratios (HRs) were counted through random effects model.
Results: Heterogeneity was moderate in overall survival (OS) (I2=43.7%, p=0.059) and low in disease-free survival (DFS) (I2=0.0%, p=0.587). Sensitivity analysis indicated that the removal of any of the study did not affect the final results. Evidence for publication bias was not found (Begg’s test, p=0.281; Egger’s test, p=0.078). The pooled OS HRs from combined effects analysis was determined (HR 1.07; 95% CI 0.83–1.39, p=0.585), together with the pooled HRs of DFS (HR 1.65; 95% CI 1.02–2.66, p=0.042). TERT promoter mutation predicted a good outcome in meta-static melanoma patients (HR 0.66; 95% CI 0.46–0.96, p=0.042). The pooled HRs of combined mutation in TERT promoter and BRAF (HR 6.27; 95% CI 2.7–14.58, p=0.000) predicted a bad outcome in melanoma patients.
Conclusion: TERT promoter mutation significantly predicted poor DFS outcome but, on the contrary, predicted a good outcome in metastatic melanoma patients. The combined TERT promoter and BRAF mutation was a significant independent factor of OS in melanoma patients.
Keywords: melanoma; meta-analysis; mutation; prognosis; promoter regions, genetic; skin neoplasms; telomerase; TERT promoter mutation; TERT protein, human
This document provides an overview of colitis-associated cancer (CAC). CAC occurs more frequently in patients with longstanding ulcerative colitis or Crohn's disease due to chronic inflammation damaging colon tissue over many years. CAC differs from typical colorectal cancer in its pathogenesis and histological characteristics. The document discusses risk factors for CAC and the genetic and molecular changes involved in inflammatory colonic carcinogenesis. It also covers prevention, diagnosis and treatment approaches for CAC.
Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous c...Enrique Moreno Gonzalez
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo.
Correlation between vascular endothelial growth factor-A expression and tumor...UniversitasGadjahMada
Vascular endothelial growth factor-A (VEGF-A) has been observed as the predominant angiogenic factor in colorectal cancer (CRC) and the assessment of microvessel density (MVD) has been used to quantify tumor neoangiogenesis. This study aimed to determine clinicopathological and prognostic significance of both angiogenic markers in the local CRC patients. We analyzed tissue samples obtained from 81 cases with CRC. VEGF-A expression and MVD counts were immunohistochemically detected using anti VEGF-A and CD31. The assessments of both markers were classified as low and high. Correlation between VEGF-A expression and MVD value and clinicopathological characteristics were examined using Chi-square test. The overall survival (OS) was plotted using the Kaplan-Meier method. The results indicated a high VEGF-A expression was found more frequently in the rectal location (P=0.042) and T4 tumors (P=0.041) compared to their counterparts. Older patients tended to show a higher MVD value compared to younger cases (P=0.062). In addition, survival analysis showed that males had a worse OS compared to females (P=0.029), and VEGF-A expression and MVD count did not correlate with patients’ survival. In conclusion, there were significant differences of VEGF-A expression according to tumor location and T invasion. Sex, but not angiogenic markers, had an influence on the survival of CRC patients.
This document describes the development and evaluation of a high-resolution melting (HRM) test to screen for common numerical chromosomal abnormalities in products of conception from recurrent pregnancy loss patients. The authors developed 5 HRM assays targeting different chromosomes and evaluated the test on 765 samples with known karyotypes, finding it had high sensitivity and specificity for detecting abnormalities. They then compared the cost-effectiveness of 4 different strategies for evaluating recurrent pregnancy loss that used different genetic tests, finding the HRM test alone or as an initial screen followed by other tests improved cost-effectiveness. Thus, the HRM test shows potential as an initial screening tool or alternative to improve the evaluation of recurrent pregnancy loss.
This study examined the diagnostic validity of three swab techniques for identifying chronic wound infection by comparing quantitative cultures from swab specimens to quantitative cultures from tissue specimens. The three swab techniques tested were wound exudate, the Z-technique, and Levine's technique. Of the 83 chronic wounds studied, 30 (36%) were found to be infected based on the tissue culture results. Levine's technique was found to have the highest accuracy at 0.80 when compared to the tissue cultures. A critical threshold of 37,000 organisms per swab using Levine's technique provided a sensitivity of 90% and specificity of 57% for detecting infected wounds. The mean concordance between swab specimens using Levine's technique and tissue specimens was 78%.
Chemosensitivity Testing of Circulating Epithelial Tumor Cells (CETC) in Vitr...Peter Pachmann
ABSTRACT
Background: Chemotherapy is a mainstay of tumor therapy, however, it is predominantly applied according to empiri- cally developed recommendations derived from statistical relapse rates occurring years after the treatment in the adju- vant situation and from progression-free interval data in the metastatic situation, without any possibility of individually determining the efficacy in the adjuvant situation and with loss of time and quality of life in the metastatic situation if the drugs chosen are not effective. Here, we present a method to determine the efficiency of chemotherapeutic drugs using tumor cells circulating in blood as the part of the tumor actually available in the patient’s body for chemosensitiv- ity testing. Methodology/Principal Findings: After only red blood cell lysis, omitting any enrichment (analogous to other blood cell enumeration methods, including rare CD34 cells), the white cells comprising the circulating epithelial tumor cells (CETC) are exposed to the drugs in question in different concentrations and for different periods of time. Staining with a fluorescence-labeled anti-epithelial antibody detects both vital and dying tumor cells, distinguishing vital from dying cells through membrane permeability and nuclear staining with propidium iodide. Increasing percent- ages of dying tumor cells are observed dependent on time and concentration. The sensitivity can vary during therapy and was correlated with decrease or increase in CETC and clinical outcome. Conclusions/Significance: Thus, we are able to show that chemosensitivity testing of circulating tumor cells provides real-time information about the sensitivity of the tumor present in the patient, even at different times during therapy, and correlates with treatment success.
11.expression of emerging novel tumor markers in oral squamous cell carcinoma...Alexander Decker
This document summarizes a systematic review of 12 emerging novel tumor markers that have been studied for their expression in oral squamous cell carcinoma (OSCC) between 2006-2011. The review finds that none of the 12 tumor markers (TROP2, Periostin, SENP5, mGluR5, Septin1, Stathmin, IMP3, Tapasin, Stromal Versican, STAT1, Cyr61) demonstrated all the qualities of an ideal tumor marker, such as good sensitivity and specificity for diagnosis or prognosis. Some markers like TROP2, Stathmin, IMP3, Tapasin, and Cyr61 showed potential as prognostic markers or therapeutic targets, but more research is still
Objective: The association between telomerase reverse transcriptase (TERT) promoter mutation and outcome of melanoma is unclear and controversial. We aim to conduct a meta-analysis and investigate whether the TERT promoter mutation is a prognostic factor of melanoma.
Study Design: Appropriate studies were searched in 3 databases: PubMed, Web of Science, and Embase. Pooled hazard ratios (HRs) were counted through random effects model.
Results: Heterogeneity was moderate in overall survival (OS) (I2=43.7%, p=0.059) and low in disease-free survival (DFS) (I2=0.0%, p=0.587). Sensitivity analysis indicated that the removal of any of the study did not affect the final results. Evidence for publication bias was not found (Begg’s test, p=0.281; Egger’s test, p=0.078). The pooled OS HRs from combined effects analysis was determined (HR 1.07; 95% CI 0.83–1.39, p=0.585), together with the pooled HRs of DFS (HR 1.65; 95% CI 1.02–2.66, p=0.042). TERT promoter mutation predicted a good outcome in meta-static melanoma patients (HR 0.66; 95% CI 0.46–0.96, p=0.042). The pooled HRs of combined mutation in TERT promoter and BRAF (HR 6.27; 95% CI 2.7–14.58, p=0.000) predicted a bad outcome in melanoma patients.
Conclusion: TERT promoter mutation significantly predicted poor DFS outcome but, on the contrary, predicted a good outcome in metastatic melanoma patients. The combined TERT promoter and BRAF mutation was a significant independent factor of OS in melanoma patients.
Keywords: melanoma; meta-analysis; mutation; prognosis; promoter regions, genetic; skin neoplasms; telomerase; TERT promoter mutation; TERT protein, human
This document provides an overview of colitis-associated cancer (CAC). CAC occurs more frequently in patients with longstanding ulcerative colitis or Crohn's disease due to chronic inflammation damaging colon tissue over many years. CAC differs from typical colorectal cancer in its pathogenesis and histological characteristics. The document discusses risk factors for CAC and the genetic and molecular changes involved in inflammatory colonic carcinogenesis. It also covers prevention, diagnosis and treatment approaches for CAC.
Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous c...Enrique Moreno Gonzalez
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo.
Correlation between vascular endothelial growth factor-A expression and tumor...UniversitasGadjahMada
Vascular endothelial growth factor-A (VEGF-A) has been observed as the predominant angiogenic factor in colorectal cancer (CRC) and the assessment of microvessel density (MVD) has been used to quantify tumor neoangiogenesis. This study aimed to determine clinicopathological and prognostic significance of both angiogenic markers in the local CRC patients. We analyzed tissue samples obtained from 81 cases with CRC. VEGF-A expression and MVD counts were immunohistochemically detected using anti VEGF-A and CD31. The assessments of both markers were classified as low and high. Correlation between VEGF-A expression and MVD value and clinicopathological characteristics were examined using Chi-square test. The overall survival (OS) was plotted using the Kaplan-Meier method. The results indicated a high VEGF-A expression was found more frequently in the rectal location (P=0.042) and T4 tumors (P=0.041) compared to their counterparts. Older patients tended to show a higher MVD value compared to younger cases (P=0.062). In addition, survival analysis showed that males had a worse OS compared to females (P=0.029), and VEGF-A expression and MVD count did not correlate with patients’ survival. In conclusion, there were significant differences of VEGF-A expression according to tumor location and T invasion. Sex, but not angiogenic markers, had an influence on the survival of CRC patients.
This document describes the development and evaluation of a high-resolution melting (HRM) test to screen for common numerical chromosomal abnormalities in products of conception from recurrent pregnancy loss patients. The authors developed 5 HRM assays targeting different chromosomes and evaluated the test on 765 samples with known karyotypes, finding it had high sensitivity and specificity for detecting abnormalities. They then compared the cost-effectiveness of 4 different strategies for evaluating recurrent pregnancy loss that used different genetic tests, finding the HRM test alone or as an initial screen followed by other tests improved cost-effectiveness. Thus, the HRM test shows potential as an initial screening tool or alternative to improve the evaluation of recurrent pregnancy loss.
This study examined the diagnostic validity of three swab techniques for identifying chronic wound infection by comparing quantitative cultures from swab specimens to quantitative cultures from tissue specimens. The three swab techniques tested were wound exudate, the Z-technique, and Levine's technique. Of the 83 chronic wounds studied, 30 (36%) were found to be infected based on the tissue culture results. Levine's technique was found to have the highest accuracy at 0.80 when compared to the tissue cultures. A critical threshold of 37,000 organisms per swab using Levine's technique provided a sensitivity of 90% and specificity of 57% for detecting infected wounds. The mean concordance between swab specimens using Levine's technique and tissue specimens was 78%.
Ong et al._Translational utility of next-generation sequencing_2013_GenomicsFrank Ong, MD, CPI
Next-generation sequencing (NGS) has made DNA sequencing rapid, cost-effective and highly accurate. NGS has translational utility in several areas: 1) It can detect genetic variations associated with disease risk and treatment response; 2) It enables non-invasive prenatal testing for fetal abnormalities; 3) Cancer genome sequencing can improve diagnosis, prognosis and treatment by deciphering a cancer's genetic makeup. NGS also has utility in rare genetic disease diagnosis and in precision medicine by matching patients to targeted therapies.
Abstract—Lymphadenopathy is one of the commonest presentation in inflammatory and neoplastic cases. Pathological diagnosis of enlarged lymph nodes is crucial in further management of patients. Fine Needle Aspiration cytology (FNAC) is quick and cost effective OPD procedure for establishing etiology of enlarged lymph nodes. This study was aimed to observed the pattern of lymphadenopathy as per FNAC and its diagnostic accuracy assuming histopathology as gold standard. This study was conducted on two hundred and thirty one consecutive enlarged lymph nodes attended for FNAC in a secondary care level Government Hospital, Gandhi Nagar, Jammu in a study period of two and a half years. Lymph nodes of these cases were aspirated and subjected to cytomorphological evaluation with Papanicolaou (PAP) and Giemsa stain. After that histopathological examination was done of excised biopsies. Then pattern of lymphadenopathy as per FNAC was observed and its diagnostic accuracy was found out assuming histopathology as gold standard. Maximum number of patients was in the age group of 21-30 years age group with male to female ratio 1.2:1. Out of 231 lymphadenopathy cases 4 remain inconclusisve whereas 200 (88.11%)cases were benign and 27 (11.89%) were malignant including 14 (6.1%) cases of metastatic tumors. Among benign cases, majority had non specific reactive lymphadenitis (42.29%) followed by tubercular lymphadenitis. And among malignant tumors, metastatic tumors (6.1%). were most common. Diagnostic accuracy of FNAC was observed as fairly good i.e. ranging from 100% to 83.3% in various type of lymphadenopathies. So it can be depicted that FNAC is very useful first line investigation in patients presenting with enlarged lymph nodes especially in secondary level health care hospitals/centers where advanced diagnostic modalities are not available. The suspicious cases can always be referred for further evaluation.
Mate Choice Optimizes Offspring MHC Genetics and Drives Sexual Reproductionscience journals
Sexual reproduction can be maintained only in an ever-changing world of diseases generating a never-ending coevolutionary arms race between infectious diseases and their hosts.
The histomorphological study of prostate lesionsiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Diagnosis of endometriosis in the 21 st centuryArunSharma10
Diagnosis of endometriosis is a challenge
Unmet needs in diagnosis of endometriosis
Non-invasive diagnosis of endometriosis
Urinary biomarkers
Peripheral biomarkers
Genetic predisposition in endometriosis
Genetic tests in endometriosis
Tissue biomarkers
miRNAs in the diagnosis of endometriosis
Endometriosis diagnosis
The Level of Expression of Ki-67 in Invasive Cervical Cancers and Cervical I...Crimsonpublishers-IGRWH
The Level of Expression of Ki-67 in Invasive Cervical Cancers and Cervical Intraepithelial Neoplasia in Ghanaian Women by Ama Afrah in Womens Health Journal
A quicker tzanck smear with methylene blue stain in diagnosis ofEva Yustiana
This study compared the diagnostic accuracy of methylene blue stain versus Giemsa stain for Tzanck smears in the diagnosis of herpesvirus skin infections. Tzanck smears were performed on 156 patient skin samples using both stains. Methylene blue staining took 10-15 seconds while Giemsa staining took 25 minutes. Both stains showed similar sensitivity (81% for methylene blue, 78% for Giemsa) and specificity (100% for both). PCR analysis of 72 samples confirmed methylene blue was non-inferior to Giemsa. The study demonstrated that methylene blue stain provides a quick and reliable alternative to Giemsa for point-of-care diagnosis of herpesvirus skin infections
This document summarizes and compares different methods for comprehensive chromosome screening (CCS) of human oocytes and embryos. It discusses the capabilities and limitations of various CCS methodologies, including:
1) Array comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) microarrays, quantitative real-time PCR (qPCR), and other technologies can screen all 24 human chromosomes, unlike previous fluorescence in situ hybridization (FISH) methods.
2) CCS methods vary in terms of accuracy, minimum detectable imbalance, ability to predict monogenic diseases and origins of aneuploidy, and time required to obtain results. SNP microarrays and qPCR allow for results in time for fresh
1. The study found that lncRNA PCAT29 was downregulated in renal carcinoma tissues, while the expression of FLOT1 was upregulated.
2. Overexpression of PCAT29 inhibited cell proliferation, invasion, and migration of renal carcinoma cells by downregulating FLOT1.
3. In a mouse model of renal carcinoma, overexpression of PCAT29 inhibited tumor growth, suggesting PCAT29 suppresses renal carcinoma progression by downregulating FLOT1.
COMPARISON BETWEEN SUTURING AND STAPLE APPROXIMATION OF SKIN IN ABDOMINAL INC...KETAN VAGHOLKAR
Background: Skin approximation is a very important step in a surgical operation. The quality of skin
approximation affects the quality of the scar. Traditional skin suturing is associated with quite a few wound complications.
Staple approximation is an innovative alternative with good results. Aim: The aim of the study is to compare
traditional suturing of skin edges versus staple approximation and to evaluate the impact of these techniques on wound
complications such as pain, surgical site infections, scarring and patient satisfaction. Materials and methods: 150 patients
are included in the study and divided into two groups. Group A (skin suturing) and group B (staple approximation).
The effect of the technique on wound healing is evaluated. Results: Patients belonging to group B (staple approximation)
had less pain, shorter skin closure duration, no wound complications, fine scarring and greater patient satisfaction.
Conclusion: Staple approximation of skin edges during the closure of laparotomy incisions is recommended.
MINING OF IMPORTANT INFORMATIVE GENES AND CLASSIFIER CONSTRUCTION FOR CANCER ...ijsc
Microarray is a useful technique for measuring expression data of thousands or more of genes
simultaneously. One of challenges in classification of cancer using high-dimensional gene expression data
is to select a minimal number of relevant genes which can maximize classification accuracy. Because of the
distinct characteristics inherent to specific cancerous gene expression profiles, developing flexible and
robust gene identification methods is extremely fundamental. Many gene selection methods as well as their
corresponding classifiers have been proposed. In the proposed method, a single gene with high classdiscrimination
capability is selected and classification rules are generated for cancer based on gene
expression profiles. The method first computes importance factor of each gene of experimental cancer
dataset by counting number of linguistic terms (defined in terms of different discreet quantity) with high
class discrimination capability according to their depended degree of classes. Then initial important genes
are selected according to high importance factor of each gene and form initial reduct. Then traditional kmeans
clustering algorithm is applied on each selected gene of initial reduct and compute missclassification
errors of individual genes. The final reduct is formed by selecting most important genes with
respect to less miss-classification errors. Then a classifier is constructed based on decision rules induced
by selected important genes (single) from training dataset to classify cancerous and non-cancerous samples
of experimental test dataset. The proposed method test on four publicly available cancerous gene
expression test dataset. In most of cases, accurate classifications outcomes are obtained by just using
important (single) genes that are highly correlated with the pathogenesis cancer are identified. Also to
prove the robustness of proposed method compares the outcomes (correctly classified instances) with some
existing well known classifiers.
Clinical investigational studies for validation of a next-generation sequenci...Frank Ong, MD, CPI
Clinical investigational studies were conducted to demonstrate the accuracy and reproducibility of the Illumina MiSeqDx CF System, a next-generation sequencing (NGS) in vitro diagnostic device for cystic fibrosis testing. Two assays were evaluated in both an Accuracy Study and a Reproducibility Study, with comparison to reference methods. The studies found that both assays achieved high positive agreement, negative agreement, and overall agreement compared to reference methods. Sample pass rates were also high. This is the first systematic evaluation of a NGS platform for broad clinical use as an in vitro diagnostic for cystic fibrosis testing.
Whole genome scanning, resolving clinical diagnosis and management amaist com...koda004
This document discusses the challenges of using whole genome scanning microarrays in clinical settings. It notes that while these technologies can revolutionize genetic diagnosis, the large amount of complex data they generate can complicate clinical utility and patient benefit. It highlights issues physicians and healthcare professionals will face as testing resolution increases towards full genome sequencing. Addressing these issues now and evolving healthcare systems in response will be important to avoid potential harms and realize benefits.
Accuracy and reliability_of_tzanck_test_compared_t (1)Eva Yustiana
This document compares the accuracy of the Tzanck test to histopathology for diagnosing basal cell carcinoma (BCC). The Tzanck test is a simple cytological examination that is faster and cheaper than histopathology, the gold standard. The study examined 26 patients clinically diagnosed with BCC using both tests. Histopathology confirmed BCC in 23 cases. The Tzanck test correctly identified BCC in 12 cases and ruled out the 3 non-BCC cases, but missed diagnosing BCC in 11 cases. The Tzanck test had a sensitivity of 52.2% and specificity of 100% compared to histopathology. While the Tzanck test can rapidly identify some BCC, it has
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
This study compared the expression of E-cadherin, β-catenin, and MUC1 in multicentric/multifocal breast cancers versus unifocal breast cancers of identical tumor size and grade. The study found significantly downregulated expression of E-cadherin in multicentric/multifocal cancers compared to unifocal cancers. In contrast, no significant differences were seen in β-catenin expression between the two groups. Within the unifocal group, E-cadherin and β-catenin expression were positively correlated, but this was not seen in the multicentric/multifocal group. The results suggest multicentric/multifocal and unifocal breast cancers differ in E-
Circulating cell-free DNA (cfDNA) found in blood can be used as a "blood biopsy" for cancer management. Compared to traditional tissue biopsies, blood biopsies are non-invasive, allow for longitudinal monitoring throughout treatment, and provide a representation of overall tumor heterogeneity. Advanced technologies like next-generation sequencing can analyze cfDNA to identify genetic mutations and guide targeted therapy. While promising, further large clinical studies are still needed to validate the clinical utility of using cfDNA for treatment decisions and monitoring treatment response over time.
Advances and Problems in Preclinical Models for Childhood Cancerijtsrd
Microblogging today has gotten an acclaimed specific instrument among Neuroblastoma is a sympathetic nervous system disease in children and is the most prevalent solid tumor in childhood, accounting for 15 of all pediatric oncology deaths. Nearly 80 of patients with this clinically active condition do not react to current treatments in the long run. The precise portrayal of tumor biology and diversity is the key obstacle in the discovery and evaluation of novel agents for pediatric drug growth. In addition to this restriction, the low prevalence of neuroblastoma renders it difficult to enroll qualifying patients for early phase clinical trials, emphasizing the importance of thorough preclinical studies to ensure that the right drugs are chosen. To address these issues, researchers need new preclinical models, technologies, and principles. Tissue engineering provides appealing methods for developing three dimensional 3D cell models utilizing different biomaterials and manufacturing techniques that replicate the geometry, dynamics, heterogeneity, metabolic gradients, and cell connectivity of the native tumor microenvironment. We address existing laboratory models and evaluate their ability to reflect the systemic organization and physiological conditions of the human body, as well as current and emerging strategies to recapitulate the tumor niche utilizing tissue engineered platforms in this study. Finally, well talk about how innovative 3Din vitroculture systems might be used to answer unanswered questions in neuroblastoma biology. V. Sah "Advances and Problems in Preclinical Models for Childhood Cancer" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-4 , June 2021, URL: https://www.ijtsrd.compapers/ijtsrd42379.pdf Paper URL: https://www.ijtsrd.combiological-science/neurobiology/42379/advances-and-problems-in-preclinical-models-for-childhood-cancer/v-sah
This meta-analysis examined the relationship between programmed death-ligand 1 (PD-L1) expression and prognosis in patients with osteosarcoma. Nine studies with 538 patients were included. The results showed that high PD-L1 expression was significantly associated with poorer overall survival. Subgroup analysis found this relationship held regardless of patient ethnicity or sample size. High PD-L1 expression was also significantly associated with metastasis. However, no significant relationship was found between PD-L1 expression and disease-free survival. This meta-analysis suggests PD-L1 may be a potential prognostic marker for osteosarcoma patients.
This document discusses early cancer detection technologies and methods. It begins with a debate on the pros and cons of early detection screening, then discusses the history of cervical cancer screening and its success. It also covers the high costs of cancer care. The bulk of the document focuses on liquid biopsy technologies for detecting cancer DNA in blood and their potential for early detection and monitoring. Specific technologies like Grail and Cologuard stool DNA testing are discussed. Challenges to adoption like guidelines, costs, regulation and education are also covered.
This document summarizes a study that developed a CT-based radiomics score to noninvasively evaluate the tumor immune microenvironment (TIME) in 2272 gastric cancer patients. The radiomics score achieved good performance in predicting the neutrophil-to-lymphocyte ratio (NLR) status in the TIME. Notably, the radiomics score was comparable to the immunohistochemistry-derived NLR status in predicting patient survival outcomes. Furthermore, the study found that objective response rates to anti-PD-1 immunotherapy were significantly higher in patients with a low radiomics score compared to those with a high radiomics score. The radiomics imaging biomarker provides a noninvasive method for evaluating the TIME and its correlation with prognosis and response to
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...daranisaha
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Ong et al._Translational utility of next-generation sequencing_2013_GenomicsFrank Ong, MD, CPI
Next-generation sequencing (NGS) has made DNA sequencing rapid, cost-effective and highly accurate. NGS has translational utility in several areas: 1) It can detect genetic variations associated with disease risk and treatment response; 2) It enables non-invasive prenatal testing for fetal abnormalities; 3) Cancer genome sequencing can improve diagnosis, prognosis and treatment by deciphering a cancer's genetic makeup. NGS also has utility in rare genetic disease diagnosis and in precision medicine by matching patients to targeted therapies.
Abstract—Lymphadenopathy is one of the commonest presentation in inflammatory and neoplastic cases. Pathological diagnosis of enlarged lymph nodes is crucial in further management of patients. Fine Needle Aspiration cytology (FNAC) is quick and cost effective OPD procedure for establishing etiology of enlarged lymph nodes. This study was aimed to observed the pattern of lymphadenopathy as per FNAC and its diagnostic accuracy assuming histopathology as gold standard. This study was conducted on two hundred and thirty one consecutive enlarged lymph nodes attended for FNAC in a secondary care level Government Hospital, Gandhi Nagar, Jammu in a study period of two and a half years. Lymph nodes of these cases were aspirated and subjected to cytomorphological evaluation with Papanicolaou (PAP) and Giemsa stain. After that histopathological examination was done of excised biopsies. Then pattern of lymphadenopathy as per FNAC was observed and its diagnostic accuracy was found out assuming histopathology as gold standard. Maximum number of patients was in the age group of 21-30 years age group with male to female ratio 1.2:1. Out of 231 lymphadenopathy cases 4 remain inconclusisve whereas 200 (88.11%)cases were benign and 27 (11.89%) were malignant including 14 (6.1%) cases of metastatic tumors. Among benign cases, majority had non specific reactive lymphadenitis (42.29%) followed by tubercular lymphadenitis. And among malignant tumors, metastatic tumors (6.1%). were most common. Diagnostic accuracy of FNAC was observed as fairly good i.e. ranging from 100% to 83.3% in various type of lymphadenopathies. So it can be depicted that FNAC is very useful first line investigation in patients presenting with enlarged lymph nodes especially in secondary level health care hospitals/centers where advanced diagnostic modalities are not available. The suspicious cases can always be referred for further evaluation.
Mate Choice Optimizes Offspring MHC Genetics and Drives Sexual Reproductionscience journals
Sexual reproduction can be maintained only in an ever-changing world of diseases generating a never-ending coevolutionary arms race between infectious diseases and their hosts.
The histomorphological study of prostate lesionsiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Diagnosis of endometriosis in the 21 st centuryArunSharma10
Diagnosis of endometriosis is a challenge
Unmet needs in diagnosis of endometriosis
Non-invasive diagnosis of endometriosis
Urinary biomarkers
Peripheral biomarkers
Genetic predisposition in endometriosis
Genetic tests in endometriosis
Tissue biomarkers
miRNAs in the diagnosis of endometriosis
Endometriosis diagnosis
The Level of Expression of Ki-67 in Invasive Cervical Cancers and Cervical I...Crimsonpublishers-IGRWH
The Level of Expression of Ki-67 in Invasive Cervical Cancers and Cervical Intraepithelial Neoplasia in Ghanaian Women by Ama Afrah in Womens Health Journal
A quicker tzanck smear with methylene blue stain in diagnosis ofEva Yustiana
This study compared the diagnostic accuracy of methylene blue stain versus Giemsa stain for Tzanck smears in the diagnosis of herpesvirus skin infections. Tzanck smears were performed on 156 patient skin samples using both stains. Methylene blue staining took 10-15 seconds while Giemsa staining took 25 minutes. Both stains showed similar sensitivity (81% for methylene blue, 78% for Giemsa) and specificity (100% for both). PCR analysis of 72 samples confirmed methylene blue was non-inferior to Giemsa. The study demonstrated that methylene blue stain provides a quick and reliable alternative to Giemsa for point-of-care diagnosis of herpesvirus skin infections
This document summarizes and compares different methods for comprehensive chromosome screening (CCS) of human oocytes and embryos. It discusses the capabilities and limitations of various CCS methodologies, including:
1) Array comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) microarrays, quantitative real-time PCR (qPCR), and other technologies can screen all 24 human chromosomes, unlike previous fluorescence in situ hybridization (FISH) methods.
2) CCS methods vary in terms of accuracy, minimum detectable imbalance, ability to predict monogenic diseases and origins of aneuploidy, and time required to obtain results. SNP microarrays and qPCR allow for results in time for fresh
1. The study found that lncRNA PCAT29 was downregulated in renal carcinoma tissues, while the expression of FLOT1 was upregulated.
2. Overexpression of PCAT29 inhibited cell proliferation, invasion, and migration of renal carcinoma cells by downregulating FLOT1.
3. In a mouse model of renal carcinoma, overexpression of PCAT29 inhibited tumor growth, suggesting PCAT29 suppresses renal carcinoma progression by downregulating FLOT1.
COMPARISON BETWEEN SUTURING AND STAPLE APPROXIMATION OF SKIN IN ABDOMINAL INC...KETAN VAGHOLKAR
Background: Skin approximation is a very important step in a surgical operation. The quality of skin
approximation affects the quality of the scar. Traditional skin suturing is associated with quite a few wound complications.
Staple approximation is an innovative alternative with good results. Aim: The aim of the study is to compare
traditional suturing of skin edges versus staple approximation and to evaluate the impact of these techniques on wound
complications such as pain, surgical site infections, scarring and patient satisfaction. Materials and methods: 150 patients
are included in the study and divided into two groups. Group A (skin suturing) and group B (staple approximation).
The effect of the technique on wound healing is evaluated. Results: Patients belonging to group B (staple approximation)
had less pain, shorter skin closure duration, no wound complications, fine scarring and greater patient satisfaction.
Conclusion: Staple approximation of skin edges during the closure of laparotomy incisions is recommended.
MINING OF IMPORTANT INFORMATIVE GENES AND CLASSIFIER CONSTRUCTION FOR CANCER ...ijsc
Microarray is a useful technique for measuring expression data of thousands or more of genes
simultaneously. One of challenges in classification of cancer using high-dimensional gene expression data
is to select a minimal number of relevant genes which can maximize classification accuracy. Because of the
distinct characteristics inherent to specific cancerous gene expression profiles, developing flexible and
robust gene identification methods is extremely fundamental. Many gene selection methods as well as their
corresponding classifiers have been proposed. In the proposed method, a single gene with high classdiscrimination
capability is selected and classification rules are generated for cancer based on gene
expression profiles. The method first computes importance factor of each gene of experimental cancer
dataset by counting number of linguistic terms (defined in terms of different discreet quantity) with high
class discrimination capability according to their depended degree of classes. Then initial important genes
are selected according to high importance factor of each gene and form initial reduct. Then traditional kmeans
clustering algorithm is applied on each selected gene of initial reduct and compute missclassification
errors of individual genes. The final reduct is formed by selecting most important genes with
respect to less miss-classification errors. Then a classifier is constructed based on decision rules induced
by selected important genes (single) from training dataset to classify cancerous and non-cancerous samples
of experimental test dataset. The proposed method test on four publicly available cancerous gene
expression test dataset. In most of cases, accurate classifications outcomes are obtained by just using
important (single) genes that are highly correlated with the pathogenesis cancer are identified. Also to
prove the robustness of proposed method compares the outcomes (correctly classified instances) with some
existing well known classifiers.
Clinical investigational studies for validation of a next-generation sequenci...Frank Ong, MD, CPI
Clinical investigational studies were conducted to demonstrate the accuracy and reproducibility of the Illumina MiSeqDx CF System, a next-generation sequencing (NGS) in vitro diagnostic device for cystic fibrosis testing. Two assays were evaluated in both an Accuracy Study and a Reproducibility Study, with comparison to reference methods. The studies found that both assays achieved high positive agreement, negative agreement, and overall agreement compared to reference methods. Sample pass rates were also high. This is the first systematic evaluation of a NGS platform for broad clinical use as an in vitro diagnostic for cystic fibrosis testing.
Whole genome scanning, resolving clinical diagnosis and management amaist com...koda004
This document discusses the challenges of using whole genome scanning microarrays in clinical settings. It notes that while these technologies can revolutionize genetic diagnosis, the large amount of complex data they generate can complicate clinical utility and patient benefit. It highlights issues physicians and healthcare professionals will face as testing resolution increases towards full genome sequencing. Addressing these issues now and evolving healthcare systems in response will be important to avoid potential harms and realize benefits.
Accuracy and reliability_of_tzanck_test_compared_t (1)Eva Yustiana
This document compares the accuracy of the Tzanck test to histopathology for diagnosing basal cell carcinoma (BCC). The Tzanck test is a simple cytological examination that is faster and cheaper than histopathology, the gold standard. The study examined 26 patients clinically diagnosed with BCC using both tests. Histopathology confirmed BCC in 23 cases. The Tzanck test correctly identified BCC in 12 cases and ruled out the 3 non-BCC cases, but missed diagnosing BCC in 11 cases. The Tzanck test had a sensitivity of 52.2% and specificity of 100% compared to histopathology. While the Tzanck test can rapidly identify some BCC, it has
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
This study compared the expression of E-cadherin, β-catenin, and MUC1 in multicentric/multifocal breast cancers versus unifocal breast cancers of identical tumor size and grade. The study found significantly downregulated expression of E-cadherin in multicentric/multifocal cancers compared to unifocal cancers. In contrast, no significant differences were seen in β-catenin expression between the two groups. Within the unifocal group, E-cadherin and β-catenin expression were positively correlated, but this was not seen in the multicentric/multifocal group. The results suggest multicentric/multifocal and unifocal breast cancers differ in E-
Circulating cell-free DNA (cfDNA) found in blood can be used as a "blood biopsy" for cancer management. Compared to traditional tissue biopsies, blood biopsies are non-invasive, allow for longitudinal monitoring throughout treatment, and provide a representation of overall tumor heterogeneity. Advanced technologies like next-generation sequencing can analyze cfDNA to identify genetic mutations and guide targeted therapy. While promising, further large clinical studies are still needed to validate the clinical utility of using cfDNA for treatment decisions and monitoring treatment response over time.
Advances and Problems in Preclinical Models for Childhood Cancerijtsrd
Microblogging today has gotten an acclaimed specific instrument among Neuroblastoma is a sympathetic nervous system disease in children and is the most prevalent solid tumor in childhood, accounting for 15 of all pediatric oncology deaths. Nearly 80 of patients with this clinically active condition do not react to current treatments in the long run. The precise portrayal of tumor biology and diversity is the key obstacle in the discovery and evaluation of novel agents for pediatric drug growth. In addition to this restriction, the low prevalence of neuroblastoma renders it difficult to enroll qualifying patients for early phase clinical trials, emphasizing the importance of thorough preclinical studies to ensure that the right drugs are chosen. To address these issues, researchers need new preclinical models, technologies, and principles. Tissue engineering provides appealing methods for developing three dimensional 3D cell models utilizing different biomaterials and manufacturing techniques that replicate the geometry, dynamics, heterogeneity, metabolic gradients, and cell connectivity of the native tumor microenvironment. We address existing laboratory models and evaluate their ability to reflect the systemic organization and physiological conditions of the human body, as well as current and emerging strategies to recapitulate the tumor niche utilizing tissue engineered platforms in this study. Finally, well talk about how innovative 3Din vitroculture systems might be used to answer unanswered questions in neuroblastoma biology. V. Sah "Advances and Problems in Preclinical Models for Childhood Cancer" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-4 , June 2021, URL: https://www.ijtsrd.compapers/ijtsrd42379.pdf Paper URL: https://www.ijtsrd.combiological-science/neurobiology/42379/advances-and-problems-in-preclinical-models-for-childhood-cancer/v-sah
This meta-analysis examined the relationship between programmed death-ligand 1 (PD-L1) expression and prognosis in patients with osteosarcoma. Nine studies with 538 patients were included. The results showed that high PD-L1 expression was significantly associated with poorer overall survival. Subgroup analysis found this relationship held regardless of patient ethnicity or sample size. High PD-L1 expression was also significantly associated with metastasis. However, no significant relationship was found between PD-L1 expression and disease-free survival. This meta-analysis suggests PD-L1 may be a potential prognostic marker for osteosarcoma patients.
This document discusses early cancer detection technologies and methods. It begins with a debate on the pros and cons of early detection screening, then discusses the history of cervical cancer screening and its success. It also covers the high costs of cancer care. The bulk of the document focuses on liquid biopsy technologies for detecting cancer DNA in blood and their potential for early detection and monitoring. Specific technologies like Grail and Cologuard stool DNA testing are discussed. Challenges to adoption like guidelines, costs, regulation and education are also covered.
This document summarizes a study that developed a CT-based radiomics score to noninvasively evaluate the tumor immune microenvironment (TIME) in 2272 gastric cancer patients. The radiomics score achieved good performance in predicting the neutrophil-to-lymphocyte ratio (NLR) status in the TIME. Notably, the radiomics score was comparable to the immunohistochemistry-derived NLR status in predicting patient survival outcomes. Furthermore, the study found that objective response rates to anti-PD-1 immunotherapy were significantly higher in patients with a low radiomics score compared to those with a high radiomics score. The radiomics imaging biomarker provides a noninvasive method for evaluating the TIME and its correlation with prognosis and response to
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...daranisaha
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...eshaasini
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...semualkaira
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...semualkaira
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...semualkaira
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
This study prospectively evaluated 54 patients with ovarian sex cord-stromal tumors (OSCST) to develop diagnostic standards and risk-adapted treatment strategies. Most patients presented with stage IA tumors confined to the ovary and were followed regularly, while some with stage IC or higher received cisplatin-based chemotherapy. After a median follow-up of 59 months, event-free survival was 86% and overall survival was 89%. Prognosis correlated with stage, and chemotherapy seemed effective for advanced-stage tumors. The study provides a standardized approach to classify and treat OSCST.
Kshivets O. Cancer, Computer Sciences and Alive SupersystemsOleg Kshivets
1. The document presents research on 12,162 cancer patients analyzing blood, biochemical and immune system parameters to establish relationships between these factors and cancer progression.
2. Statistical analysis revealed complex networks between patient homeostasis and tumor characteristics that determine tumor behavior and patient prognosis. Higher ratios of healthy to cancer cells correlated to better prognosis.
3. The cancer-patient system is found to pass through three phase transitions from normal to invasive cancer that qualitatively change tumor aggressiveness and patient survival chances.
The document provides guidelines for the treatment of breast cancer. It discusses the rising incidence of breast cancer in the US but declining mortality, suggesting benefits from early detection and treatment. It then covers breast cancer risk factors, staging, pathology assessment, treatment approaches, and treatment options for specific breast cancer stages and types. The guidelines are intended to help clinicians provide high-quality, evidence-based care for their breast cancer patients.
This document reviews rare types of breast cancer. It summarizes information on 16 epithelial subtypes classified by the World Health Organization, including histopathology descriptions and clinical parameters. While rare cancers cannot be studied through large randomized trials, this review aims to provide clinicians an understanding to help determine optimal treatment approaches. It discusses cancers such as tubular carcinoma and mucinous carcinoma, which typically have a good prognosis and are often estrogen receptor positive with low lymph node involvement.
A convenient clinical nomogram for small intestine adenocarcinomanguyên anh doanh
The document describes a study that developed a nomogram to predict cancer-specific survival for patients with small-intestine adenocarcinoma. Researchers analyzed data on 4,971 patients from the SEER database and identified 8 factors associated with survival: age, sex, marital status, insurance status, grade, stage, surgery status, and chemotherapy. These factors were used to create a nomogram that assigns a score to each variable to predict 3- and 5-year survival probabilities. Validation tests found the nomogram predicted survival more accurately than the AJCC staging system and closely matched actual survival rates.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...JohnJulie1
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...NainaAnon
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Development and Validation of a Nomogram for Predicting Response to Neoadjuva...semualkaira
Retrospective analysis of clinical data on female patients with breast cancer was performed. Model 1 was developed by entering variables from the univariate analysis (P < 0.1) into a multivariate logistic regression analysis. Model 2 was developed via the stepwise forward-backward variable selection technique in partial least squares regression. For model 3, the least absolute shrinkage and selection operator (LASSO) method was used to choose suitable variables, followed by the multivariate logistic regression analysis.
Development and Validation of a Nomogram for Predicting Response to Neoadjuva...semualkaira
Retrospective analysis of clinical data on female
patients with breast cancer was performed. Model 1 was developed by entering variables from the univariate analysis (P < 0.1)
into a multivariate logistic regression analysis. Model 2 was developed via the stepwise forward-backward variable selection technique in partial least squares regression. For model 3, the least
absolute shrinkage and selection operator (LASSO) method was
used to choose suitable variables, followed by the multivariate
logistic regression analysis. Harrell’s C-index, calibration curves,
and decision curve analyses (DCA) were used to compare the
performance of the models. In the validation cohort, these results
were validated
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...semualkaira
Human Thymidine kinase 1 (hTK1), a key enzyme involved in the DNA synthesis during S-phase of the cell cycle and upregulation of cell proliferation, thus it is reliable tumor proliferating biomarker for assessment of tumor proliferation rate in serum and in tissue in oncology. This meta-analysis is investigation whether the serum TK1 concentration(STK1p)based on hTK1-IgY-polyclonal-antibody can provide a benefit for risk assessment from gastric neoplasm progression to gastric carcinoma (GC) as well as for evaluation of treatment effect in GC.
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...eshaasini
This meta-analysis examined 27 studies to determine if serum thymidine kinase 1 concentration (STK1p) can provide benefit for risk assessment of gastric neoplasm progression to gastric carcinoma (GC) and for evaluating GC treatment effects. The studies included 1,909 GC patients, 1,229 gastric neoplasm patients, and 2,260 tumor-free individuals. The results showed that STK1p levels increased significantly from tumor-free to superficial gastritis to chronic gastritis to atrophic gastritis to gastric ulcer to GC. STK1p levels in 251 GC patients declined significantly by 66% one month after surgery compared to pre-surgery levels. This suggests that STK1p has
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...semualkaira
Human Thymidine kinase 1 (hTK1), a key enzyme involved in the DNA synthesis during S-phase of the cell cycle and upregulation of cell proliferation, thus it is reliable tumor proliferating biomarker for assessment of tumor proliferation rate in serum and in tissue in oncology. This meta-analysis is investigation whether the serum TK1 concentration(STK1p)based on hTK1-IgY-polyclonal-antibody can provide a benefit for risk assessment from gastric neoplasm progression to gastric carcinoma (GC) as well as for evaluation of treatment effect in GC.
Benefit of Serum-Thymidine Kinase 1 Concentration for Risk Assessment from Ga...semualkaira
Human Thymidine kinase 1 (hTK1), a key enzyme involved in the DNA synthesis during S-phase of the cell cycle and upregulation of cell proliferation, thus it is reliable tumor proliferating biomarker for assessment of tumor proliferation rate in serum and in tissue in oncology. This meta-analysis is investigation whether the serum TK1 concentration(STK1p)based on hTK1-IgY-polyclonal-antibody can provide a benefit for risk assessment from gastric neoplasm progression to gastric carcinoma (GC) as well as for evaluation of treatment effect in GC.
Role of the pathologist in assessing response to treatment of ovarian and end...Alejandro Palacio
The document discusses the role of pathologists in assessing treatment response for ovarian and endometrial cancers. It describes two areas where pathological assessment is used: 1) The chemotherapy response score (CRS) system evaluates response of high-grade serous ovarian carcinoma to neoadjuvant chemotherapy, with a CRS of 3 indicating complete or near-complete response and improved survival. 2) Conservative progestogen therapy for low-grade endometrial carcinoma and atypical hyperplasia is assessed by serial biopsies to evaluate histological response parameters. The CRS has been validated and incorporated into guidelines, while pathological classification of progestogen response is still under development.
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
low birth weight presentation. Low birth weight (LBW) infant is defined as the one whose birth weight is less than 2500g irrespective of their gestational age. Premature birth and low birth weight(LBW) is still a serious problem in newborn. Causing high morbidity and mortality rate worldwide. The nursing care provide to low birth weight babies is crucial in promoting their overall health and development. Through careful assessment, diagnosis,, planning, and evaluation plays a vital role in ensuring these vulnerable infants receive the specialize care they need. In India every third of the infant weight less than 2500g.
Birth period, socioeconomical status, nutritional and intrauterine environment are the factors influencing low birth weight
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
Are you looking for a long-lasting solution to your missing tooth?
Dental implants are the most common type of method for replacing the missing tooth. Unlike dentures or bridges, implants are surgically placed in the jawbone. In layman’s terms, a dental implant is similar to the natural root of the tooth. It offers a stable foundation for the artificial tooth giving it the look, feel, and function similar to the natural tooth.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
2. 2 Boxberg M, et al. J Clin Pathol 2018;0:1–10. doi:10.1136/jclinpath-2018-205454
Original article
Table 1 Grading algorithm for oral squamous cell carcinomas as
proposed by Boxberg et al15
SCC grading algorithm
Implemented criteria Point(s)
Tumour budding activity/10 HPF
No budding 1
15 budding foci 2
≥15 budding foci 3
Smallest cell nest size
15 cells 1
5–15 cells 2
2–4 cells 3
Single cell invasion 4
Tumour grading Total score
Well differentiated (G1) 2–3
Moderately differentiated (G2) 4–6
Poorly differentiated (G3) 7
HPF, high power field; SCC, squamous cell carcinoma.
But the validity and usefulness of a given grading system for
diagnostic practice depends on its prognostic impact and on
its reproducibility, including interobserver and intraobserver
agreement.25 26
Interobserver disagreement may have thera-
peutic consequences for patients as summarised by Fleming:27
‘…if a [histopathologic pattern] cannot be reliably and repro-
ducibly identified … by a broad group of pathologists, the fact
that it is clinically important is almost meaningless and, at worst,
misleading…’.
Measurement of interobserver agreement for categorical
outcomes in general is performed by calculating Cohen’s Kappa
(κ). According to Altman,28
values of κ0.20 represent poor
agreement, 0.21–0.40 fair, 0.41–0.60 moderate, 0.61–0.80 good
and values ≥0.81 and higher very good agreement. Reported
interobserver reliability for the various grading systems including
the WHO grading system varies from 0.25 for the pattern of
invasion grading up to 0.84 for the HR model.11 29–32 33–37
Thus, the aim of the present study was to assess the interob-
server and intraobserver reliability of our proposed grading
system in prototypical OSCC cases. To this end, 108 OSCC were
evaluated according to our scoring system by two experienced
head and neck pathologists and one resident in pathology before
and after training and interobserver reliability was calculated by
Cohen’s Kappa. Furthermore, one of the experienced patholo-
gists repeated scoring to determine intraobserver reliability.
Material and methods
Tissue
Total 108 cases of a previously characterised cohort of n=157
OSCC15
were evaluated. To focus our evaluation on prototypical
oral squamous cell carcinomas, cases which exceeded the oral
cavity as well as those with p16 expression on immunohisto-
chemistry15
were excluded from our study as were cases in which
tumour area covered below 20% of the HE stained slide. All
carcinomas were surgically resected in the department of Oral
and Maxillofacial Surgery of the Klinikum Rechts der Isar,
University Hospital of the Technical University Munich between
2007 and 2012 according to a standard protocol derived from
the German guidelines for treatment of OSCC.38
For each case,
the slide with the highest tumour burden out of all slides gener-
ated for routine diagnostics was chosen for evaluation by the
reviewers.
Reviewers
Three reviewers, blinded to each other’s scoring results as well
as clinical information, participated in the study. KJ (reviewer 1)
from the Charité University Hospital in Berlin and MB (reviewer
2) from the Institute of Pathology of the TU Munich are board
certified pathologists with expert knowledge in head and neck
pathology. CB (reviewer 3) from the Institute of Pathology of the
TU Munich is a pathologist in training in her second year with
general knowledge in surgical pathology but without special
training in head and neck pathology.
Six months after the first scoring round, CB was trained by MB
on a subgroup of 50 independent cases. Following the training,
she undertook a second scoring round. To analyse intraobserver
variability, the slide set was evaluated a second time by MB. Time
between scorings was 6 months for both reviews. Cases were
scrambled every time between the different evaluation rounds.
Histopathological evaluation
Histopathological evaluation of tumour budding activity in 10
high power fields (HPF) and cell nest size was carried out as previ-
ously described15
(Field diameter 0.55 mm). Tumour budding
was defined as branching of small tumour nests harbouring 5
tumour cells into the surrounding parenchyma/stroma with low
budding activity defined as 1–14 and high budding activity ≥15
budding nests per 10 HPF. Clustered tumour cells surrounded
by tumour stroma were defined as cell nests. OSCC nest size
was classified according to the size of the smallest invasive cell
nest. This means that in principle already one small nest in a
general background of large nests leads to a higher nest size
score. Tumour cell clusters composed of 15 tumour cells were
classified as large nests, 5–15 tumour cells as intermediate nests,
small nests consisted of 2–4 tumour cells. Single cell invasion was
defined as isolated discohesive tumour cells showing no nested
architecture. The final grading score was calculated by adding
up the score for budding activity in 10 HPF and cell nest size as
previously described. OSCC with a grading score 2 or 3 were
classified as well differentiated (G1), OSCC with a grading score
between 4 and 6 were considered to be intermediately differen-
tiated OSCC (G2) and poor differentiation (G3) was assigned to
OSCC with a grading score of 7 (table 1).
Statistics
All calculations were done using SPSS V
.24 (IBM, Armonk, New
York, USA). Absolute and relative frequencies are presented for
categorical variables. Cohen’s kappa was used to assess interob-
server and intraobserver reliability. All statistical significance
tests were performed considering a two-sided 5% significance
level.
Results
Histopathological evaluation
Table 2 summarises the results of the histopathological evalua-
tion of all reviewers. The subsequent section includes the values
obtained by reviewer 1: tumour budding activity was observed
in 75/108 (69.4%) cases. Among these, low budding activity
was observed in 50/108 (46.3%) and high budding activity in
25/108 (23.1%) cases. Cell nest size was distributed as follows:
large cell nests 16/108 (14.8%), intermediate cell nests 17/108
(15.7%), small cell nests 29/108 (26.9%), single cell invasion
46/108 (42.6%).
Calculation of the previously described grading score resulted
in score 2 in 16/108 (14.8%), score 3 in 17/108 (15.7%), score
5 in 28/108 (24.9%), score 6 in 23/108 (21.3%) and score 7
on
17
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2018
by
guest.
Protected
by
copyright.
http://jcp.bmj.com/
J
Clin
Pathol:
first
published
as
10.1136/jclinpath-2018-205454
on
8
December
2018.
Downloaded
from
3. 3
Boxberg M, et al. J Clin Pathol 2018;0:1–10. doi:10.1136/jclinpath-2018-205454
Original article
Table 2 Results of histopathological evaluation of oral squamous cell carcinomas of reviewers R1, R2 (first and second evaluation) and R3 (before
and after training)
Reviewer
R1;
KJ
R2;
MB
R2;
MB (second round)
R3;
BC
R3;
BC (after training)
n % n % n % n % n %
Cell nest size Large 16 14.8 15 13.9 15 13.9 9 8.3 14 13.0
Intermediate 17 15.7 17 15.7 15 13.9 15 13.8 15 13.9
Small 29 26.9 29 26.9 28 25.9 41 38.0 32 29.6
Single cells 46 42.6 47 43.5 50 46.3 43 39.8 47 43.5
Budding activity Absent 33 30.6 32 29.6 30 27.8 24 22.2 29 26.9
Low 50 46.3 50 46.3 51 47.2 47 39.8 46 42.5
High 25 23.1 26 24.1 27 25.0 37 34.3 33 30.6
Grading score 2 16 14.8 15 13.9 16 14.8 9 8.3 14 13.0
3 17 15.7 17 15.7 14 13.0 15 13.9 15 13.8
5 28 24.9 27 25.0 27 25.0 39 36.1 29 26.9
6 23 21.3 24 22.2 25 23.1 10 9.3 19 17.6
7 24 22.2 25 23.1 26 24.1 35 32.4 31 28.7
Grading G1 33 30.6 32 29.6 30 27.8 24 22.2 29 26.9
G2 51 47.2 51 47.2 52 48.1 49 45.5 47 43.5
G3 24 22.2 25 23.1 26 24.1 35 32.4 32 29.6
Figure 1 Representative HE stained oral squamous cell carcinomas
(OSCC). (A), (C) showing OSCC with tumour budding activity as
indicated by presence of cell nests containing 5 tumour cells (small
cell nestsand single cell infiltration *). (B), (D) showing OSCC with
intermediate and large cell nest sizes without evidence of tumour
budding activity.
in 24/108 (22.2%) cases. According to the grading scheme, G1
(well differentiation; score 2 and 3) was assigned to 33/108
(30.6%), G2 (intermediate differentiation; score 4–6) to 51/108
(47.2%) and G3 (poor differentiation; score 7) to 24/108
(22.2%; figure 1) of OSCC.
Interobserver variability—correlation of morphological
patterns
Scores obtained for cell nest size and budding activity by
reviewers 1 and 2 were concordant in 101/108 (93.5%) and
106/108 (98.1%) cases, respectively. Calculation of Cohen’s
Kappa for the pattern cell nest size revealed κ=0.91 (p0.001).
The corresponding value for the pattern budding activity was
κ=0.97 (p0.001). As expected, the level of consensus between
reviewers 1/2 (head and neck pathologists) and reviewer 3
(resident in training) was considerably lower. Concerning cell
nest size, concordance of scores between reviewer 1/2 and 3
was found in 74/108 (68.5%) and 73/108 (67.6%), respectively.
The resulting Kappa value was κ=0.55 and κ=0.53. Concor-
dance rates concerning budding activity were similarly with
κ=0.55 for reviewers 1 and 3 and κ=0.54 for reviewers 2 and
3 (p0.001; figures 2 and 3). Table 3 shows cross tables of
interobserver concordance for both patterns between reviewer
1 versus 2 and 1 versus 3, and online supplementary table 1
includes cross tables of interobserver concordance between
reviewers 2 and 3.
Interobserver variability—correlation of grading
Reviewers 1 and 2 reached identical histopathological grades
(G1-G3) in 106/108 cases (98.1%). Consequently, Cohen’s
Kappa was 0.97, indicating an extremely high interobserver
agreement. With 77/108 (71.3%) cases rated similar, discor-
dance was higher between reviewers 1 and 3 as well as 2 and 3
resulting in κ=0.55 for both calculations (table 3, online supple-
mentary table 1, figure 4). Online supplementary table 2 gives
additional information for underlying grading scores.
Interobserver variability after training
After training of rater 3, the concordance between the experi-
enced rater 1/2 and rater 3 increased considerably concerning
both, the patterns cell nest size (concordant cases reviewer 1 vs 3:
83/108 (76.9%); reviewer 2 vs 3 86/108 (79.6%)) and budding
activity (concordant cases reviewer 1 vs 3: 97/108 (89.8%);
reviewer 2 vs 3 99/108 (91.7%)) as well as with respect to the
final grading (concordant cases reviewer 1 vs 3: 97/108 (89.8%);
reviewer 2 vs 3 99/108 (91.7%)). Cohen’s Kappa for rater 1
and rater 3 was calculated as κ=0.67 for cell nest size, κ=0.87
for budding activity and κ=0.84 for grading (p0.001). The
respective values for rater 2 vs rater 3 were as follows: cell nest
size κ=0.71; budding activity κ=0.87; grading 0.87 (p0.001;
figures 2–4). Corresponding cross tables are shown in table 3
and online supplementary table 1.
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Figure 2 Kappa values for evaluation of the patterns budding activity and cell nest size as well as final grading comparing scoring of reviewers 1, 2
and 3.Although reviewers 1 and 2 were not trained, kappa values for their comparison are given in both graphs for better comparability. Upper row:
kappa values before training of reviewer 3; lower row: kappa values after training for reviewer 3. Kappa κ≥0.81 (dashed line) indicating very good
interobserver agreement according to Altman.28
Intraobserver variability
To assess intraobserver variability, reviewer 2 scored the slide set
twice after a time gap of more than 6 months. Concordance for
the patterns cell nest size and budding activity was high, resulting
in a Cohen’s Kappa of κ=0.74 (89/108; 82.4% concordant
cases) for nest size and κ=0.97 (105/108; 97.2% concordant
cases) for budding activity, respectively. The resulting grading
was concordant in 105/108 (97.2%) OSCC with a kappa value
κ=0.95 (p0.001; table 4).
Discussion
The histopathological diagnosis of a tumour includes the eval-
uation of its differentiation, which is reflected by the tumour
grade. It represents the basis for clinical patient stratification
to achieve optimal therapy decision-making. The purpose of a
grading system is therefore to give exact prognostic and predic-
tive information about the patient’s disease course and potential
response to treatment schemes.25 39
Consequently, the clinical
value of a histopathological grading system depends on (1) the
correlation between the aggressiveness of the individual tumour
and the corresponding histopathological tumour differentiation
evaluation scheme and (2) on the reproducibility of the applied
grading system in terms of interobserver and intraobserver
agreement of pathologists.25 26
Our recently proposed histopathological grading scheme
for OSCC15
consists of the morphological patterns ‘cell nest
size’—scored from 1 (large cell nests15 cells) to up to 4 (single
cell invasion)—and ‘tumour budding activity’—scored from 1
(no budding activity) to up to 3 (15 budding nests/10HPF).
Both criteria, cell nest size and budding activity, have previously
been described as surrogate parameters for tumour aggressive-
ness in head and neck SCC40–44
and in a variety of other solid
cancers.15 18 19 21 22
Both morphological patterns are related
to loss of cancer cell adhesion and might thus also represent
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Figure 3 Number of cases with agreement/disagreement concerning scoring of the pattern cell nest size (score 1–4) comparing ratings of reviewers
1, 2 and 3 before and after training. (A) Y-axis: reviewer 1; x-axis: reviewer 2; (B) y-axis: reviewer 1; x-axis: reviewer 3 before training; (C) y-axis:
reviewer 1; x-axis: reviewer 3 after training.
morphologic features of epithelial-mesenchymal transition, a
biological phenomenon which enables tumour cells to acquire a
more motile, infiltrative phenotype.45–48
The above-mentioned studies, including ours, suggest that
these two histopathological features reflect a given OSCC’s
biological potential better than ‘established’ grading factors such
as nuclear pleomorphism, degree of keratinization, mitotic count
and host response, which are parts of various other proposed
OSCC grading systems including the grading scheme currently
endorsed by the WHO.4 8–12 30 33 49
Our histopathological grade is defined by the sum of nest size
and budding activity scores, resulting in well differentiated (G1;
2–3 points), moderately differentiated (G2; 4–6 points) and
poorly differentiated (G3; 7 points) OSCC. In principle, one
small cell nest is enough for a tumour to be placed in a higher
nest size category even if all other nests in a given tumour are
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Table 3 Cross tables of interobserver concordance between reviewers 1 and 2 as well as 1 and 3 before and after training for histomorphological
patterns cell nest size and budding activity and final grading
Cell nest size Reviewer 1
Large cell nests Intermediate cell nests Small cell nests Single cell infiltration Kappa
n % n % n % n %
Reviewer 2 Large cell nests 15 13.9 0 0.0 0 0.0 0 0.0 0.91
Intermediate cell nests 1 0.9 16 14.8 0 0.0 0 0.0
Small cell nests 0 0.0 2 1.9 26 24.1 1 0.9
Single cell infiltration 0 0.0 0 0.0 7 6.5 40 37.0
Reviewer 3 Large cell nests 9 8.3 0 0.0 0 0.0 0 0.0 0.55
Before training Intermediate cell nests 4 3.7 9 8.3 2 1.9 0 0.0
Small cell nests 2 1.9 8 7.4 23 21.3 8 7.4
Single cell infiltration 1 0.9 1 0.9 8 7.4 33 30.6
Reviewer 3 Large cell nests 11 10.2 3 2.8 0 0.0 0 0.0 0.67
After training Intermediate cell nests 4 3.7 11 10.2 0 0.0 0 0.0
Small cell nests 0 0.0 3 2.8 22 20.4 7 6.5
Single cell infiltration 1 0.9 0 0.0 7 6.5 39 36.1
Budding activity Reviewer 1
No budding activity Low budding activity High budding activity Kappa
n % n % n %
Reviewer 2 No budding activity 32 29.6 0 0.0 0 0.0 0.97
Low budding activity 1 0.9 49 45.4 0 0.0
High budding activity 0 0.0 1 0.9 25 23.1
Reviewer 3 No budding activity 21 19.4 3 2.8 0 0.0 0.55
Before training Low budding activity 11 10.2 33 30.6 3 2.8
High budding activity 1 0.9 14 13.0 22 20.4
Reviewer 3 No budding activity 29 26.9 0 0.0 0 0.0 0.87
After training Low budding activity 3 2.8 43 39.8 0 0.0
High budding activity 1 0.9 7 6.5 25 23.1
Grading Reviewer 1
G1 G2 G3 Kappa
n % n % n %
Reviewer 2 G1 32 29.6 0 0.0 0 0.0 0.97
G2 1 0.9 50 46.3 0 0.0
G3 0 0.0 1 0.9 24 22.2
Reviewer 3 G1 21 19.4 3 2.8 0 0.0 0.55
Before training G2 11 10.2 35 32.4 3 2.8
G3 1 0.9 13 12.0 21 19.4
Reviewer 3 G1 29 26.9 0 0.0 0 0.0 0.84
After training G2 3 2.8 44 40.7 0 0.0
G3 1 0.9 7 6.5 24 22.2
considerably larger. This strictly categorical approach has been
chosen to avoid subjectivity for this parameter as good as possible.
However, we acknowledge that there is still an element of subjec-
tivity, since it has to be decided by the pathologist whether rare
small ‘nests’ represent cross cut artefacts or ‘real’ tumour buds,
particularly in the context of a tumour morphology with almost
exclusively large tumour cell nests. Likely, most pathologists
would put very few small nests (unless they are unmistakeably
‘real’) in such a scenario in the ‘artefact’ category.
In a previous study,15
we showed a high prognostic impact of
this recently introduced histopathological grading system inde-
pendent of patient age, gender and tumour stage. Furthermore,
the proposed grading system showed a strong correlation with
pN-stage—the worse the grading, the higher the probability
of lymph node metastasis. In this context, it is interesting that
recently published studies suggest , that tumour budding in
particular might serve as a predictor of occult metastasis in in
patients with OSCC and cN0 necks, supporting a potential deci-
sion towards a neck dissection in these patients.50 51
As described above, a reliable histopathological grading
system is expected to be valid and be reproducible (above-men-
tioned criterion 2). Measurement of interobserver and intraob-
server agreement in general is performed by calculating Cohen’s
kappa. Altman considers a value of κ0.20 to represent poor
agreement, 0.21–0.40 as fair, 0.41–0.60 as moderate, 0.61–
0.80 as good and values of 0.81 or higher as very good agree-
ment.28
It has been proposed that a marker, on which treatment
schemes are based, should reach a kappa value of at least 0.41
for interobserver agreement,27 28
whereas others still assume a
value of 0.50 to be poor agreement.52
With a Cohen’s Kappa
of κ=0.97 between experienced pathologists, our proposed
grading system shows an almost perfect interobserver reliability.
One of the scoring expert pathologists (KJ) in the current study
was not involved in previous studies15 17 18
—suggesting that the
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Figure 4 Number of cases with agreement/disagreement concerning final histopathological grading (G1–G3) of reviewers 1, 2 and 3 before and
after training. (A) Y-axis: reviewer 1; x-axis: reviewer 2; (B) y-axis: reviewer 1; x-axis: reviewer 3 before training; (C) y-axis: reviewer 1; x-axis: reviewer
3 after training.
implicated categories are clearly defined, rendering the grading
system simple, easy to assess and highly reliable. Intraobserver
reliability of the grading was also comparably high with κ=0.95.
Agreement on final grading was initially moderate with the
participating pathologist without expertise in head and neck
pathology. However, the consensus could be markedly improved
by training, emphasising the importance of training sessions for
pathologists with less diagnostic experience not yet accustomed
to the system. Detailed analysis of the contributing histopatho-
logical patterns tumour budding activity and cell nest size before
and after training revealed that the less experienced scorer
initially significantly overestimated the presence of budding
activity and small cell nest sizes/single cell infiltration—a point,
which should be considered in teaching sessions.
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Table 4 Cross tables of intraobserver concordance of reviewer 2 for first and second evaluation of oral squamous cell carcinomas including
histomorphological patterns cell nest size and budding activity, grading score and final grading.
Cell nest size
Reviewer 2 first evaluation
Large cell nests Intermediate cell nests Small cell nests Single cell infiltration Kappa
n % n % n % n %
Reviewer 2
Large cell
nests 10 9.3 5 4.6 0 0.0 0 0.0 0.74
second
evaluation
Intermediate
cell nests 5 4.6 10 9.3 0 0.0 0 0.0
Small cell
nests 0 0.0 2 1.9 24 22.2 2 1.9
Single cell
infiltration 0 0.0 0 0.0 5 4.6 45 41.7
Budding Activity
Reviewer 2 first evaluation
no budding activity low budding activity high budding activity Kappa
n % n % n %
Reviewer 2
no budding
activity 30 27.8 0 0.0 0 0.0 0.97
second evaluation
low budding
activity 2 1.9 49 45.4 0 0.0
high budding
activity 0 0.0 1 0.9 26 24.1
Grading Score
Reviewer 2 first
evaluation
2 3 5 6 7 Kappa
n % n % n % n % n %
Reviewer 2 2 10 9.3 6 5.6 0 0.0 0 0.0 0 0.0 0.74
second
evaluation 3 5 4.6 9 8.3 0 0.0 0 0.0 0 0.0
5 0 0.0 2 1.9 22 20.4 3 2.8 0 0.0
6 0 0.0 0 0.0 5 4.6 20 18.5 0 0.0
7 0 0.0 0 0.0 0 0 1 0.9 25 23.1
Grading
Reviewer 2 first evaluation
G1 G2 G3 Kappa
n % n % n %
Reviewer 2 G1 30 27.8 0 0.0 0 0.0 0.97
second evaluation G2 2 1.9 50 46.3 0 0.0
G3 0 0.0 1 0.9 25 23.1
The kappa values achieved in the present study are higher than
expected when compared with other grading systems. Interob-
server reliability analysed for the MG model (including the
patterns keratinisation, mitotic count, pattern of invasion and
lymphocytic host response)11 29–32
resulted in Cohen’s kappa
values between 0.30 and 0.47. Regarding the single histopatho-
logical features, Sawair et al found moderate Kappa values for
keratinisation (0.48) and even worse ones for pattern of inva-
sion.33
Analysis of Kappa values for the pattern of invasion as
defined by the Royal College of Pathologists34
resulted in kappa
values between 0.43 and 0.58 in a study by Beggan et al,35
whereas Heerema et al found values between 0.25 and 0.5853
and Chang et al a value of 0.72.36
Interobserver agreement of the
HR model was good with κ=0.84.37
Data on interobserver and
intraobserver reliability of the Broder’s/WHO grading system is
available for penile SCC by Naumann et al54
and Gunia et al.55
In this entity, essentially the same grading criteria as in OSCC are
used. The authors both observed between fair and good interob-
server agreement (κ=0.378 to κ=0.692) and moderate to very
good intraobserver agreement (κ=0.575 to κ=0.942), which is
a surprisingly good result. However, Broder’s/WHO grading, as
mentioned above, is doubtlessly suboptimal in supplying inde-
pendent prognostic information.
Since we believe that an initial analysis of interobserver vari-
ation should focus on prototypical cases, we selected cases
from our previous study15
according to certain criteria. Thus,
we included only cases in which one fifth of the respective slide
was covered by carcinoma. In addition, we omitted those cases
which extended beyond the oral cavity or were p16 positive
on immunohistochemistry, to be fully sure, that we are dealing
with a ‘pure’ not human papilloma virus (HPV) related cohort
of prototypical oral SCC. Clearly, specifically in the scenario of
HPV associated non-keratinising tumours usually consisting of
larger tumour cell nests, follow on studies are clearly warranted.
In more general terms, additional retrospective multicentre
studies and/or prospective trials as well as concordance analysis
between biopsies and resection specimen and/or a correlation
of biopsy grading with presurgical clinical data for improve-
ment of therapeutic patient stratification (eg, whether or not
to perform a prophylactic neck dissection on a patient with
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a clinically N-zero neck) are required to argue in favour of
a clinical implementation of this grading system into routine
diagnostics.
One limitation of our study is that the number of reviewers
comprised only three pathologists. Therefore, it is crucial to
conduct further studies to confirm our data. Nevertheless, the
current study strongly implies that the grading algorithm is
easy to apply and reliable with a high level of interobserver
and intraobserver agreement for both the histopathological
patterns cell nest size and budding activity as well as the final
grading.
We are convinced that the results presented here strengthen
the diagnostic certainty and clinical spread of our recently
introduced grading scheme for OSCC which has the potential
to build one cornerstone of a highly desirable future universal
novel grading algorithm for SCC of the upper aerodigestive
tract.
Take home messages
►
► Oral squamous cell carcinomas grading based on our recently
proposed novel scheme yields an excellent inter-reader and
intrareader agreement, supporting the suitability of this
grading system for routine pathological practice.
►
► High inter-reader and intrareader agreement suggests that
the implicated categories are clearly defined, rendering the
grading system simple, easy to assess and highly reliable.
►
► Grading performance of more inexperienced readers can
be markedly improved by a short training, emphasising the
importance of training sessions for pathology residents with
less diagnostic experience not yet accustomed to the system.
Handling editor Dr Cheok Soon Lee.
Contributors MB and WW designed this study and wrote this paper with
assistance from CB and KJ. MB, CB and KJ performed tissue analyses with assistance
from MJ, P-HK and KS. K-DW and AK helped gain clinical data, BH contributed to
statistical analysis.
Funding This study has been supported by the German Cancer Consortium (to
WW) and the Else-Kröner Fresenius-Stiftung (to MB).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Ethics Committee TU Munich, Faculty of Medicine.
Provenance and peer review Not commissioned; externally peer reviewed.
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