Absent or impaired rectoanal inhibitory reflex as a diagnostic factor for high-grade (grade III–V) rectal prolapse: a retrospective study

Abstract Background Clinically diagnosing high-grade (III–V) rectal prolapse might be difficult, and the prolapse can often be overlooked. Even though defecography is the significant diagnostic tool for rectal prolapse, it is noticed that rectoanal inhibitory reflex (RAIR) can be associated with rectal prolapse. This study investigated whether RAIR can be used as a diagnostic factor for rectal prolapse. Methods In this retrospective study, we evaluated 107 patients who underwent both anorectal manometry and defecography between July 2012 and December 2019. Rectal prolapse was classified in accordance with the Oxford Rectal Prolapse Grading System. Patients in the high-grade (III–V) rectal prolapse (high-grade group, n = 30), and patients with no rectal prolapse or low-grade (I, II) rectal prolapse (low-grade group, n = 77) were analyzed. Clinical variables, including symptoms such as fecal incontinence, feeling of prolapse, and history were collected. Symptoms were assessed using yes/no surveys answered by the patients. The manometric results were also evaluated. Results Frequencies of fecal incontinence (p = 0.002) and feeling of prolapse (p < 0.001) were significantly higher in the high-grade group. The maximum resting (77.5 vs. 96 mmHg, p = 0.011) and squeezing (128.7 vs. 165 mmHg, p = 0.010) anal pressures were significantly lower in the high-grade group. The frequency of absent or impaired RAIR was significantly higher in the high-grade group (19 cases, 63% vs. 20 cases, 26%, p < 0.001). In a multivariate analysis, the feeling of prolapse (odds ratio [OR], 23.88; 95% confidence interval [CI], 4.43–128.78; p < 0.001) and absent or impaired RAIR (OR, 5.36; 95% CI, 1.91–15.04, p = 0.001) were independent factors of high-grade (III–V) rectal prolapse. In addition, the percentage of the absent or impaired RAIR significantly increased with grading increase of rectal prolapse (p < 0.001). The sensitivity of absent or impaired RAIR as a predictor of high-grade prolapse was 63.3% and specificity 74.0%. Conclusions Absent or impaired RAIR was a meaningful diagnostic factor of high-grade (III–V) rectal prolapse. Furthermore, the absent or impaired reflex had a positive linear trend according to the increase of rectal prolapse grading.

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Stereology in Grading and Prognosis of Canine Cutaneous Mast Cell Tumors

Veterinary Pathology ◽

10.1177/0300985820985138 ◽

2021 ◽

pp. 030098582098513

Author(s):

Mafalda Casanova ◽

Sandra Branco ◽

Inês Berenguer Veiga ◽

André Barros ◽

Pedro Faísca

Keyword(s):

Mast Cell ◽

Clinical Outcome ◽

Prognostic Value ◽

Histological Grade ◽

Intraobserver Variability ◽

Low Grade ◽

High Grade ◽

Mast Cell Tumors ◽

Cutaneous Mast Cell ◽

Grade Iii

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume ([Formula: see text]), a stereological estimation that provides information about nuclear size and its variability. [Formula: see text] of 55 ccMCTs was estimated using the “point-sampled intercept” method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in [Formula: see text] were found between grade II ([Formula: see text]= 115 ± 29 µm3) and grade III ccMCTs ([Formula: see text]= 197 ± 63 µm3), as well as between low-grade ([Formula: see text]= 113 ± 28 µm3) and high-grade ccMCTs ([Formula: see text]= 184 ± 63 µm3). An optimal cutoff value of [Formula: see text] ≥ 150 µm3 and [Formula: see text] ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, [Formula: see text] was not able to predict the clinical outcome in 42% of the cases; however, cases with [Formula: see text]<125 µm3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, [Formula: see text] is highly reproducible and is associated with histological grade as well as with benign behavior.

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Early Evidence of Anti-Lymphoma Activity of the Cyclin Dependent Kinase Inhibitor Dinaciclib (SCH 727965) In Heavily Pre-Treated Low Grade Lymphoma and Diffuse Large Cell Lymphoma Patients

Blood ◽

10.1182/blood.v116.21.3966.3966 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3966-3966 ◽

Cited By ~ 4

Author(s):

Robert A Baiocchi ◽

Joseph M. Flynn ◽

Jeffrey A. Jones ◽

Kristie A. Blum ◽

Craig C. Hofmeister ◽

...

Keyword(s):

Cell Lymphoma ◽

Median Number ◽

Low Grade ◽

High Grade ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Employment Equity ◽

Grade Group ◽

Tumor Mass ◽

Equity Ownership

Abstract Abstract 3966 Background: Dinaciclib (SCH 727965) is a potent and selective inhibitor of the cyclin dependent kinases CDKs 1, 2, 5, and 9, with in vitro activity against lymphoma. Methods: A phase 1 trial of dinaciclib administered by 2-hour i.v. infusion on days 1, 8 and 15 of a 28-day cycle was undertaken in solid tumor patients with 12 mg/m2 established as the recommended phase 2 dose (RPTD). The RPTD was explored in expansion cohorts of up to 10 patients each with low grade lymphomas (primarily follicular lymphoma (FL)), and intermediate/high grade lymphomas (diffuse large B-cell lymphoma (DLBCL)). Sixteen patients have been treated with dinaciclib, including 7 with FL, 1 with mantle cell lymphoma (MCL) and 1 with marginal zone lymphoma (MZL) in the low grade group and 7 with DLBCL in the intermediate/high grade group. Patient median age was 66 (range 43–82) and the median number of prior therapies was 2.5 (range 1–8). All patients received prior rituximab and 4 patients had previously received flavopiridol. All patients were treated with dinaciclib at the 12 mg/m2 dose. Dose de-escalation to 10 mg/m2 was required in 2 patients during treatment. The median number of cycles administered was 3 (range 1–9) with 3 patients continuing treatment for 3 cycles, 4 for 6 cycles, and 1 for 9 cycles. Of the 16 lymphoma patients treated, 2 remain on treatment. Response: Responses were assessed using the revised Cheson criteria for lymphoma (J Clin Oncol 25: 579-86, 2007). One partial response in a patient with DLBCL was observed with an 85% decrease in tumor mass. This patient, previously treated with R-CHOP from May-August 2008 and R-ICE from December 2008-March 2009, was able to continue on to autologous stem cell transplantation for potential curative salvage. Activity not meeting criteria for partial response was seen in 2 patients with FL (decreased tumor mass of 27% and 39%, respectively) and one patient with MCL (8% decrease in tumor mass). Toxicity: Treatment-related adverse events occurring in ≥ 25% of pts included anemia, cytokine release syndrome, nausea, vomiting, diarrhea, fatigue, leucopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common CTCAE v3.0 treatment-related grade 3 and 4 toxicities, occurring in 3 or more patients, were leukopenia, lymphopenia, and neutropenia. Cytokine release syndrome was observed in 4 patients, was manageable with dexamethasone and did not prevent continued treatment on protocol. Conclusion: Dinaciclib demonstrates clinical responses in heavily pre-treated lymphoma patients supporting further study in lymphoma and other hematologic malignancies. Updated information with longer follow-up will be presented. Disclosures: Off Label Use: SCH 727965 is an investigational drug. Small:Merck & Co.: Employment, Equity Ownership. Statkevich:Merck & Co.: Employment, Equity Ownership. Bannerji:Merck & Co: Employment, Equity Ownership.

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Correlation of PD-L1 with VEGF and KI-67 index in patients with primary glioma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.7_suppl.94 ◽

2017 ◽

Vol 35 (7_suppl) ◽

pp. 94-94

Author(s):

Song Xue ◽

Man Hu ◽

Jinming Yu ◽

Bingjie Fan ◽

Ji Ma

Keyword(s):

Immune Escape ◽

Treatment Strategies ◽

High Grade Glioma ◽

Continuous Variable ◽

Low Grade ◽

High Grade ◽

Grade Group ◽

Ki 67 ◽

Primary Glioma ◽

The Mean

94 Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p <0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.

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Immuno-Phenotyping of High-Grade Glioma Infiltrating Immune Cells Reveals Grade Specific Differences in Cells of Myeloid Origin

10.1101/2020.09.26.314542 ◽

2020 ◽

Author(s):

Raksha A. Ganesh ◽

Jayashree V. Raghavan ◽

Pranali Sonpatki ◽

Divya Naik ◽

Priyanka Arunachalam ◽

...

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Myeloid Cells ◽

Suppressor Cells ◽

High Grade Glioma ◽

Low Grade ◽

High Grade ◽

High Grade Gliomas ◽

Cell Phenotypes ◽

Grade Iii

AbstractGliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade III and IV) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, grade IV) or grade III gliomas. Our data show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade III glioma tissue. In addition, we observe that neutrophils are highly heterogeneous among individuals with glioma, and a greater proportion of granulocytic myeloid-derived suppressor cells are present in grade III gliomas when compared to GBM. Finally, we show that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor, and suggest that these may be used as possible markers for prognosis.

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Integration and Comparison of Transcriptomic and Proteomic Data for Meningioma

Cancers ◽

10.3390/cancers12113270 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3270

Author(s):

Jemma Dunn ◽

Vasileios P. Lenis ◽

David A. Hilton ◽

Rolf Warta ◽

Christel Herold-Mende ◽

...

Keyword(s):

Cellular Adhesion ◽

Integrated Analysis ◽

Low Grade ◽

Intracranial Tumour ◽

High Grade ◽

Fatty Acid Binding ◽

Proteomic Data ◽

Molecular Landscape ◽

Approved Drugs ◽

Grade Iii

Meningioma are the most frequent primary intracranial tumour. Management of aggressive meningioma is complex, and development of effective biomarkers or pharmacological interventions is hampered by an incomplete knowledge of molecular landscape. Here, we present an integrated analysis of two complementary omics studies to investigate alterations in the “transcriptome–proteome” profile of high-grade (III) compared to low-grade (I) meningiomas. We identified 3598 common transcripts/proteins and revealed concordant up- and downregulation in grade III vs. grade I meningiomas. Concordantly upregulated genes included FABP7, a fatty acid binding protein and the monoamine oxidase MAOB, the latter of which we validated at the protein level and established an association with Food and Drug Administration (FDA)-approved drugs. Notably, we derived a plasma signature of 21 discordantly expressed genes showing positive changes in protein but negative in transcript levels of high-grade meningiomas, including the validated genes CST3, LAMP2, PACS1 and HTRA1, suggesting the acquisition of these proteins by tumour from plasma. Aggressive meningiomas were enriched in processes such as oxidative phosphorylation and RNA metabolism, whilst concordantly downregulated genes were related to reduced cellular adhesion. Overall, our study provides the first transcriptome–proteome characterisation of meningioma, identifying several novel and previously described transcripts/proteins with potential grade III biomarker and therapeutic significance.

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A preliminary study of micro-RNAs as minimally invasive biomarkers for the diagnosis of prostate cancer patients

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01875-0 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Simona Giglio ◽

Cosimo De Nunzio ◽

Roberto Cirombella ◽

Antonella Stoppacciaro ◽

Omar Faruq ◽

...

Keyword(s):

Prostate Cancer ◽

Minimally Invasive ◽

Cancer Patients ◽

Strong Predictor ◽

Diagnostic Model ◽

Low Grade ◽

High Grade ◽

Grade Group ◽

Prostate Biopsies ◽

Micro Rnas

Abstract Background A prostate cancer diagnosis is based on biopsy sampling that is an invasive, expensive procedure, and doesn’t accurately represent multifocal disease. Methods To establish a model using plasma miRs to distinguish Prostate cancer patients from non-cancer controls, we enrolled 600 patients histologically diagnosed as having or not prostate cancer at biopsy. Two hundred ninety patients were eligible for the analysis. Samples were randomly divided into discovery and validation cohorts. Results NGS-miR-expression profiling revealed a miRs signature able to distinguish prostate cancer from non-cancer plasma samples. Of 51 miRs selected in the discovery cohort, we successfully validated 5 miRs (4732-3p, 98-5p, let-7a-5p, 26b-5p, and 21-5p) deregulated in prostate cancer samples compared to controls (p ≤ 0.05). Multivariate and ROC analyses show miR-26b-5p as a strong predictor of PCa, with an AUC of 0.89 (CI = 0.83–0.95;p < 0.001). Combining miRs 26b-5p and 98-5p, we developed a model that has the best predictive power in discriminating prostate cancer from non-cancer (AUC = 0.94; CI: 0,835-0,954). To distinguish between low and high-grade prostate cancer, we found that miR-4732-3p levels were significantly higher; instead, miR-26b-5p and miR-98-5p levels were lower in low-grade compared to the high-grade group (p ≤ 0.05). Combining miR-26b-5p and miR-4732-3p we have the highest diagnostic accuracy for high-grade prostate cancer patients, (AUC = 0.80; CI 0,69-0,873). Conclusions Noninvasive diagnostic tests may reduce the number of unnecessary prostate biopsies. The 2-miRs-diagnostic model (miR-26b-5p and miR-98-5p) and the 2-miRs-grade model (miR-26b-5p and miR-4732-3p) are promising minimally invasive tools in prostate cancer clinical management.

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The role of radiotherapy and chemotherapy in adult optic nerve gliomas: a SEER-based analysis

10.21203/rs.3.rs-214021/v2 ◽

2021 ◽

Author(s):

Xiaoning Lin ◽

Rong Huang ◽

Jinyun Su ◽

Heng Li ◽

Zhong Liu ◽

...

Keyword(s):

Optic Nerve ◽

Cox Regression ◽

Tumor Grade ◽

Adult Patients ◽

Age At Diagnosis ◽

Low Grade ◽

High Grade ◽

Grade Group ◽

Kaplan Meier ◽

The Central Nervous System

Abstract Background: Optic nerve gliomas (ONGs) are uncommon tumors of the central nervous system in adults. The aim of this study was to define their characteristics, prognostic factors, and the impacts of adjuvant radiotherapy (RT) and chemotherapy on outcomes.Methods: Adult patients (age ≥18 years) with ONGs from the Surveillance, Epidemiology, and End Results (SEER) database were included. Univariate and multivariate Cox regression models were utilized to analyze the factors associated with survival. Kaplan-Meier method was used to evaluate the impacts of adjuvant therapies on overall survival (OS).Results: A total of 179 adult patients diagnosed with ONGs were identified between 1991 and 2016, with a median follow-up period of 64.0 months. The median age at diagnosis was 41.0 years. After excluding 18 patients with unknown information, the remaining patients included 142 (88.2%) low-grade tumors and 19 (11.8%) high-grade tumors. Multivariate analysis showed age at diagnosis, tumor grade, adjuvant chemotherapy were significant factors for OS. The 5-year OS rates for patients with low- and high-grade ONGs were 85.5% and 10.5%, respectively. The employment of adjuvant RT or chemotherapy would significantly shorten OS time in the low-grade group and could not prolong OS time in the high-grade group.Conclusions: This is the largest retrospective study of adult ONGs up to date. The overall prognosis of high-grade ONGs in adult patients is still poor despite multi-modality treatments. Adjuvant RT or chemotherapy might not be considered in adult patients with low-grade ONGs unless the malignant transformation or aggressive progression has been confirmed.

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Oncology is changing: the challenge of effectively assessing response within clinical trials in low-grade gliomas

Oncology Reviews ◽

10.4081/oncol.2011.19 ◽

2011 ◽

pp. 75-76

Author(s):

Ilaria Imarisio ◽

Chiara Fumagalli

Keyword(s):

Central Nervous System ◽

Clinical Trials ◽

Nervous System ◽

Who Classification ◽

Low Grade ◽

High Grade ◽

Low Grade Gliomas ◽

Microvascular Proliferation ◽

Grade Iii

The current WHO classification of primary central nervous system (CNS) tumors recognizes four separate tumor grades (I–IV), which can be grouped into low-grade (I and II) or high-grade (III and IV), depending on the absence or presence of high-grade histopathological features, such as microvascular proliferation and necrosis...

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Preoperative Ultrasonographic Evaluation for Malignancy of Soft-Tissue Sarcoma: A Retrospective Study

The Open Orthopaedics Journal ◽

10.2174/1874325001812010075 ◽

2018 ◽

Vol 12 (1) ◽

pp. 75-83 ◽

Cited By ~ 4

Author(s):

Takeshi Morii ◽

Tomonori Kishino ◽

Naoko Shimamori ◽

Mitsue Motohashi ◽

Hiroaki Ohnishi ◽

...

Keyword(s):

Retrospective Study ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Odds Ratio ◽

Scoring System ◽

Operating Characteristic ◽

Low Grade ◽

High Grade ◽

Tumor Margin ◽

Malignant Soft Tissue

Background: Ultrasonography is useful for distinguishing between benign and malignant soft-tissue tumors. However, no study has focused on its usefulness in the differential diagnosis between low-grade and high-grade soft-tissue sarcomas. We conducted a retrospective study to determine the usefulness of the parameters of ultrasonograph and to develop a practical scoring system for distinguishing between high-grade and low-grade sarcomas. Methods: Twenty-two cases of low-grade and 43 cases of high-grade malignant soft-tissue sarcoma were enrolled. Ultrasonography parameters including the longest diameter, depth of the tumor, echogenicity, tumor margin, and vascularity defined according to Giovagnorio’s criteria were analyzed as factors to distinguish between the two types of sarcoma. Significant factors were entered into a multivariate model to define the scores for distinction according to the odds ratio. The usefulness of the score was analyzed via receiver operating characteristic analyses. Results: In univariate analysis, tumor margin, echogenicity, and vascularity were significantly different between low- and high-grade sarcomas. In the multivariate regression model, the odds ratio for high-grade vs. low-grade sarcoma was 8.8 for tumor margin, 69 for echogenicity, and 8.3 for vascularity. Scores for the risk factors were defined as follows: 1, ill-defined margin; 2, hypoechoic echogenicity; and 1, type IV in Giovagnorio’s criteria. The sum of each score was confirmed by receiver operating characteristic analysis. The area under the curve was 0.95, with a cut-off score of 3, indicating that the scoring system was useful. Conclusion: The ultrasonography parameters of tumor margin, echogenicity, and vascularity are useful for distinguishing between low- and high-grade sarcomas.

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The role of radiotherapy and chemotherapy in adult optic nerve gliomas: a SEER-based analysis

10.21203/rs.3.rs-214021/v1 ◽

2021 ◽

Author(s):

Rong Huang ◽

Yanlin Huang ◽

Jinyun Su ◽

Heng Li ◽

Zhong Liu ◽

...

Keyword(s):

Cox Regression ◽

Tumor Grade ◽

Adult Patients ◽

Age At Diagnosis ◽

Low Grade ◽

High Grade ◽

Grade Group ◽

Kaplan Meier ◽

The Central Nervous System

Abstract PurposeOptic nerve gliomas (ONGs) are uncommon tumors of the central nervous system in adults. The aim of this study was to define their characteristics, prognostic factors, and the impacts of adjuvant radiotherapy (RT) and chemotherapy on outcomes.MethodsAdult patients (age ≥ 18 years) with ONGs from the Surveillance, Epidemiology, and End Results (SEER) database were included. Univariate and multivariate Cox regression models were utilized to analyze the factors associated with survival. Kaplan-Meier method was used to evaluate the impacts of adjuvant therapies on overall survival (OS).ResultsA total of 179 adult patients diagnosed with ONGs were identified between 1991 and 2016, with a median follow-up period of 64.0 months. The median age at diagnosis was 41.0 years. After excluding 18 patients with unknown information, the remaining patients included 142 (88.2%) low-grade tumors and 19 (11.8%) high-grade tumors. Multivariate analysis showed age at diagnosis, tumor grade, adjuvant chemotherapy were significant factors for OS. The 5-year OS rates for patients with low- and high-grade ONGs were 85.5% and 10.5%, respectively. The employment of adjuvant RT or chemotherapy would significantly shorten OS time in the low-grade group and could not prolong OS time in the high-grade group.ConclusionsThis is the largest retrospective study of adult ONGs up to date. The overall prognosis of high-grade ONGs in adult patients is still poor despite multi-modality treatments. Adjuvant RT or chemotherapy might not be considered in adult patients with low-grade ONGs unless the malignant transformation or aggressive progression has been confirmed.

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