Muscle Invasion Research Articles

THU516 An Unusual Neck Mass

Abstract Disclosure: P. Rios: None. N. Kalara: None. T. Shyam: None. J. Velez: None. C. Gomez: None. S. Gra Menendez: None. Background: Parathyroid carcinoma is a rare tumor which presents with a neck mass and hypercalcemia. Non-functional parathyroid tumors account for 10% of all parathyroid carcinomas and are associated with decrease or impaired secretion of PTH, having normal calcium, being difficult to diagnose. We present a case of a patient who presented with a neck mass and normocalcemia, who was diagnosed of non-functional parathyroid tumor, were immunohistochemistry played a useful role in differentiating an unsuspected parathyroid lesion from a thyroid neoplasm. Clinical Case: 49-year-old woman presented with a 6-month history of a firm mass on the left side of her neck that was initially stable but then started to grow and was painful. On examination, she was noted to have a 5 cm firm thyroid mass with bilateral level 2 lymphadenopathy. Patient had a calcium of 9.9 mg/dL (8.6-10.3 mg/dL), normal kidney function and was euthyroid. An ultrasound of the thyroid revealed a left mass near the thyroid lobe, measuring 3.1 x 4 x 2.5 cm. Fine-needle aspiration of the mass revealed a poorly differentiated carcinoma possible originating from the thyroid. The patient underwent total thyroidectomy with central compartment dissection, bilateral neck dissection and radical resection of the tumor. Frozen section revealed malignancy highly concerning for anaplastic thyroid. Immunohistochemistry (IHC) showed that the differentiated component was positive for PTH, chromogranin, PAX8 and GATA-3, while negative for TTF-1, thyroglobulin, BRAF and p53. The higher-grade component was positive for GATA-3, p53, TTF1 (weak focal), PAX-8 (weak focal) and negative for thyroglobulin, chromogranin, PTH and BRAF which was suggestive of parathyroid tissue. The final pathology report was a differentiated parathyroid carcinoma transitioning to a high-grade carcinoma with anaplastic features, 5.6 cm in the largest dimension with invasion to thyroid tissue, skeletal muscle and angiolymphatic invasion. The tumor was a pT3N0Mn/a. Next-Generation Sequencing (NGS) of the tumor showed a high tumor mutational burden as well as high microsatellite instability being beneficial Pembrolizumab for treatment if required. IHC showed PD-L1, were Nivolumab and Pembrolizumab could work in the future if needed. Also, TP53 was detected on the NGS. She completed 32 Gy/16 fractions of adjuvant radiotherapy and continues to be on active surveillance 8 months after diagnosis without evidence of recurrence of the cancer. Conclusion: Non-functional parathyroid carcinoma is a very rare tumor that should be on the differential diagnosis in a patient with normocalcemia and neck mass. Immunohistochemistry would help in the diagnosis between thyroid or parathyroid lesion as described in this case. Presentation: Thursday, June 15, 2023

Sequential endoluminal gemcitabine and docetaxel for the treatment of clinically non-invasive high-grade upper tract urothelial carcinoma

PurposeThere is an unmet need for effective renal sparing treatments for upper tract urothelial carcinoma (UTUC). Gemcitabine/Docetaxel (Gem/Doce) has shown favorable efficacy in nonmuscle invasive bladder cancer. We report the outcomes of patients treated with endoluminal Gem/Doce for noninvasive high-grade UTUC. MethodsA retrospective review of patients treated with Gem/Doce for clinically noninvasive high-grade UTUC with no radiographic or endoscopically visible disease, either at diagnosis or following ablation, was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. Induction instillations were performed weekly for 6 weeks, followed by 6 monthly instillations if disease-free. Recurrence was defined as biopsy-proven disease or high-grade (HG) cytology. Progression was defined by development of muscle invasion, metastases, or death due to cancer. Survival was assessed with the Kaplan-Meier method. ResultsThe final cohort included 31 patients with 41 upper tract units, 51% of which would have been dialysis dependent with nephroureterectomy. Median (IQR) age was 74 years (68–81). Median follow-up was 29 months (IQR 20–58). Prior to treatment, 37 (90%) units presented with a localizing HG cytology (presumed occult CIS), and 4 (9.8%) with HG biopsy-proven disease. Sixteen (52%) patients reported any side effects; 5 were Grade 3 and 1 was Grade 5. Recurrence-free survival was 76%, 54%, and 40% at 1, 2, and 3 years, respectively. Five patients died from urothelial carcinoma. The 3-year progression-free and overall survival were 75% and 75%, respectively. ConclusionsGem/Doce demonstrates promising safety and efficacy as a renal-sparing treatment option for high-grade UTUC in appropriately selected patients.

Novel Use of Circulating Tumor DNA to Identify Muscle-invasive and Non–organ-confined Upper Tract Urothelial Carcinoma

BackgroundOptimal patient selection for neoadjuvant chemotherapy prior to surgical extirpation is limited by the inaccuracy of contemporary clinical staging methods in high-risk upper tract urothelial carcinoma (UTUC). ObjectiveTo investigate whether the detection of plasma circulating tumor DNA (ctDNA) can predict muscle-invasive (MI) and non–organ-confined (NOC) UTUC. Design, setting, and participantsPlasma cell-free DNA was prospectively collected from chemotherapy-naïve, high-risk UTUC patients undergoing surgical extirpation and sequenced using a 152-gene panel and low-pass whole-genome sequencing. Outcome measurements and statistical analysisTo test for concordance, whole-exome sequencing was performed on matching tumor samples. The performance of ctDNA for predicting MI/NOC UTUC was summarized using the area under a receiver-operating curve, and a variant count threshold for predicting MI/NOC disease was determined by maximizing Youden’s J statistic. Kaplan-Meier methods estimated survival, and Mantel-Cox log-rank testing assessed the association between preoperative ctDNA positivity and clinical outcomes. Results and limitationsOf 30 patients enrolled prospectively, 14 were found to have MI/NOC UTUC. At least one ctDNA variant was detected from 21/30 (70%) patients, with 52% concordance with matching tumor samples. Detection of at least two panel-based molecular alterations yielded 71% sensitivity at 94% specificity to predict MI/NOC UTUC. Imposing this threshold in combination with a plasma copy number burden score of >6.5 increased sensitivity to 79% at 94% specificity. Furthermore, the presence of ctDNA was strongly prognostic for progression-free survival (PFS; 1-yr PFS 69% vs 100%, p < 0.001) and cancer-specific survival (CSS; 1-yr CSS 56% vs 100%, p = 0.016). ConclusionsThe detection of plasma ctDNA prior to extirpative surgery was highly predictive of MI/NOC UTUC and strongly prognostic of PFS and CSS. Preoperative ctDNA demonstrates promise as a biomarker for selecting patients to undergo neoadjuvant chemotherapy prior to nephroureterectomy. Patient summaryHere, we show that DNA from upper tract urothelial tumors can be detected in the blood prior to surgical removal of the kidney or ureter. This circulating tumor DNA can be used to predict that upper tract urothelial carcinoma is invasive into the muscular lining of the urinary tract and may help identify those patients who could benefit from chemotherapy prior to surgery.

Outcomes Specific to Spinal Metastases with Paraspinal Disease Extension Following Spine Stereotactic Body Radiotherapy

Spinal metastases with paraspinal disease (PD) extension are known to have worse outcomes following stereotactic body radiotherapy (SBRT). Characteristics of the PD itself have not been investigated to determine the impact on outcomes such as local control, which is the purpose of this study. We retrospectively reviewed those patients who had SBRT for spinal metastases with PD disease, identified from a prospectively maintained database. Spinal metastases previously irradiated or surgical resected were excluded. The extent of PD was classified as involving the rib, neuroforamina, and muscle invasion. The gross tumor volume of PD (GTV_PD) and the clinical target volume of PD (CTV_PD) were segregated from the bony compartments based on the treatment plan contours. The outcomes of interest included the cumulative risk of local failure (LF), re-irradiation rates (ReRT), and overall survival (OS). LF and ReRT were estimated for each treated sites using the competing risk model (death as the competing risk), while OS was evaluated per patient using the Kaplan Meier method. A total of 86 patients with 96 spinal metastases sites with PD were included. Of the 96 treated sites, 65% (62/96), 29% (28/96) and 6% (6/96) of PD spanned 1, 2, and 3 vertebral levels respectively. The median follow-up was 12.4months (range: 0.6-100months). The 6- and 12-month OS for the cohort was 81% and 51%, respectively. 33/86 (38%) patients had radioresistant cancer (gastrointestinal, renal cell carcinoma, thyroid, sarcoma, or melanoma). Involvement of rib, neuroforamina and muscle invasion were observed in 39% (37/96), 65% (62/96) and 21% (20/96) of the treated sites, respectively. Epidural disease was present in 57% (55/96) of treated sites. The median GTV_PD volume was 7cc (range: 0.3-114cc), and the median CTV_PD volume was 24cc (range: 0.4-248cc). The prescribed doses were 24 Gy/2 fractions (fx) (80%), 28 Gy/2 fx (10%) and 30 Gy/4 fx (10%). There were 84 treated sites with at least one post-treatment MRI available for LF assessment. The crude LF risk was 32% (27/84), and the 6- and 12-month cumulative LF rates were 12% and 28%, respectively. There was a trend towards an increased risk of LF when PD involved the rib (35% vs 24% at 1 year respectively, P = 0.07) and muscle (67% vs 20% at 1 year respectively; P = 0.06), but no difference in LF for neuroforamina involvement (26% vs 34% at 1 year respectively, P = 0.5). There were no differences in LF based on cancer radioresistance (P = 0.6), GTV_PD volume (P = 0.3) or CTV_PD volume (P = 0.4). Of the 96 treated sites, 14% (14/96) were re-irradiated (9 with repeat SBRT and 5 with conventional EBRT) at a median of 15 months (range: 4.7-59 months) post initial SBRT. The cumulative incidence of ReRT at 6- and 12-months were 1.2% and 7.3%, respectively. PD involving adjacent rib and muscle may be associated with worse LF following SBRT. Further expansion of the cohort and dosimetric analyses are ongoing.

Biophysical phenotype mixtures reveal advantages for tumor muscle invasion in vivo

Bladder, colon, gastric, prostate, and uterine cancers originate in organs surrounded by laminin-coated smooth muscle. In human prostate cancer, tumors that are organ confined, without extracapsular extension through muscle, have an overall cancer survival rate of up to 97% compared with 32% for metastatic disease. Our previous work modeling extracapsular extension reported the blocking of tumor invasion by mutation of a laminin-binding integrin called α6β1. Expression of the α6AA mutant resulted in a biophysical switch from cell-ECM (extracellular matrix) to cell-cell adhesion with drug sensitivity properties and an inability to invade muscle. Here we used different admixtures of α6AA and α6WT cells to test the cell heterogeneity requirements for muscle invasion. Time-lapse video microscopy revealed that tumor mixtures self-assembled into invasive networks in vitro, whereas α6AA cells assembled only as cohesive clusters. Invasion of α6AA cells into and through live muscle occurred using a 1:1 mixture of α6AA and α6WT cells. Electric cell-substrate impedance sensing measurements revealed that compared with α6AA cells, invasion-competent α6WT cells were 2.5-fold faster at closing a cell-ECM or cell-cell wound, respectively. Cell-ECM rebuilding kinetics show that an increased response occurred in mixtures since the response was eightfold greater compared with populations containing only one cell type. A synthetic cell adhesion cyclic peptide called MTI-101 completely blocked electric cell-substrate impedance sensing cell-ECM wound recovery that persisted in vitro up to 20 h after the wound. Treatment of tumor-bearing animals with 10 mg/kg MTI-101 weekly resulted in a fourfold decrease of muscle invasion by tumor and a decrease of the depth of invasion into muscle comparable to the α6AA cells. Taken together, these data suggest that mixed biophysical phenotypes of tumor cells within a population can provide functional advantages for tumor invasion into and through muscle that can be potentially inhibited by a synthetic cell adhesion molecule.

Prognostic impact of muscle invasion in buccal mucosa squamous cell carcinoma.

The objective of the study was to assess the prognostic value of muscle invasion (MI), a key histopathological feature of tumor aggressiveness, and construct a superior prognostic prediction model combining the current TNM staging system. MI was analyzed in the whole-slide images from a total of 301 patients with primary buccal mucosa squamous cell carcinoma (BMSCC). Survival times of patients with/without MI were evaluated by Kaplan-Meier analysis. MI was further combined with the TNM staging system to explore its predictive value for prognosis. Moreover, 204 cases of head and neck carcinoma from the TCGA database were included. MI positive rate reached to 76% (229/301) in patients with BMSCC. MI was associated with poor overall survival (p = 0.012) and disease-free survival (p = 0.022). The novel system (TNM staging combined with MI) revealed strong predictive performance, with the largest area under the curve (OS: p < 0.001, DFS: p < 0.004). MI and the established classification system were also had good predictive ability in the TCGA cohort. MI is an independent predictor of poor prognosis of BMSCC. The inclusion of MI in prediction system can augment the risk stratification of patients with oral squamous cell carcinoma and may assist in the clinical decision-making process.

Can Only the Shape Feature in Radiomics Help Machine Learning Show That Bladder Cancer Has Invaded Muscles?

The presence of muscle invasion is an important factor in establishing a treatment strategy for bladder cancer (BCa).The aim of this study is to reveal the diagnostic performance of radiomic shape features in predicting muscle-invasive BCa. In this study, 60 patients with histologically proven BCa who underwent a preoperative MRI were retrospectively recruited. The whole tumor volume was segmented on apparent diffusion coefficient (ADC) maps and T2W images. Afterward, the shape features of the volume of interest were extracted using PyRadiomics. Machine learning classification was performed using statistically different shape features in MATLAB® (The MathWorks, Inc., Natick, Massachusetts, United States). The findings revealed that 27 bladder cancer patients had muscle invasion, while 33 had superficial bladder cancer (53 men and seven women; mean age: 62±14). Surface area, volume, and relevant features were significantly greater in the invasive group than in the non-invasive group based on the ADC maps (P<0.05). Superficial bladder cancer had a more spherical form compared to invasive bladder cancer (P=0.05) with both imaging modalities. Flatness and elongation did not differ significantly between groups with either modality (P>0.05). Logistic regression had the highest accuracy of 83.3% (sensitivity 82.8%, specificity 84%) in assessing invasion based on the shape features of ADC maps, while K-nearest neighbors had the highest accuracy of 78.2% (sensitivity 79.1%, specificity 69.4%) in assessing invasion based on T2W images. Shape features can be helpful in predicting muscle invasion in bladder cancer using machine learning methods.

Biparametric versus Multiparametric Magnetic Resonance Imaging for Assessing Muscle Invasion in Bladder Urothelial Carcinoma with Variant Histology Using the Vesical Imaging-Reporting and Data System

BackgroundThe diagnostic performance of contrast medium–free biparametric magnetic resonance imaging (bpMRI; combining T2-weighted imaging [T2WI] and diffusion-weighted imaging [DWI]) for evaluating variant-histology urothelial carcinoma (VUC) remains unknown. ObjectiveTo compare the diagnostic performance of bpMRI and multiparametric MRI (mpMRI; combining T2WI, DWI, and dynamic contrast-enhanced MRI]) for assessing muscle invasion of VUC. Design, setting, and participantsThis multi-institution retrospective analysis included 118 patients with pathologically verified VUC who underwent bladder mpMRI before transurethral bladder tumor resection between 2010 and 2019. Outcome measurements and statistical analysisThree board-certified radiologists separately evaluated two sets of images, set 1 (bpMRI) and set 2 (mpMRI), in accordance with the Vesical Imaging Reporting and Data System (VI-RADS). The histopathology results were utilized as a reference standard. Receiver operating characteristic curve analysis, Z test, and Wald test were used to assess diagnostic abilities. Results and limitationsSixty-six (55.9%) and 52 (44.1%) of the 118 patients with VUC included in the analysis (mean age, 71 ± 10 yr; 88 men) had muscle-invasive bladder cancer (MIBC) and non-MIBC, respectively. For the diagnosis of MIBC, the areas under the curve for bpMRI were significantly smaller than those for mpMRI (0.870–0.884 vs 0.902–0.923, p < 0.05). The sensitivity of bpMRI was significantly lower than that of mpMRI for all readers with a VI-RADS cutoff score of 4 (65.2–66.7% vs 77.3–80.3%, p < 0.05). The specificity of bpMRI and mpMRI did not differ significantly for all readers (88.5–90.4 vs 88.5–92.3, p > 0.05). A limitation of the study is the limited sample size because of the rarity of VUC. ConclusionsIn patients with VUC, on applying VI-RADS, the diagnostic results of bpMRI were inferior to those of mpMRI for evaluating muscle invasion. Therefore, mpMRI-based methods are recommended for evaluating muscle invasiveness of VUC. Patient summaryContrast medium–free biparametric magnetic resonance imaging (bpMRI)-based Vesical Imaging Reporting and Data System (VI-RADS) can accurately diagnose pure urothelial carcinomas, similar to conventional multiparametric magnetic resonance imaging–based VI-RADS. However, bpMRI-based VI-RADS may misdiagnose muscle invasiveness of urothelial carcinoma with variant histology, particularly when its cutoff score is 4.

Vesical Imaging-Reporting and Data System (VI-RADS): Inter-Observer Agreement and Impact of Reader's Experience

Background The Vesical Imaging Reporting and Data System (VI-RADS) is based on multiparametric MRI (mpMRI), to provide accurate information to differentiate between muscleinvasive bladder cancer (MIBC) and non-muscle –invasive bladder cancer (NMIBC). Aim of the Work To evaluate inter-observer agreement according to observer experience and diagnostic performance of the new scoring system based on magnetic resonance imaging called Vesical Imaging-Reporting and Data System (VI-RADS) to differentiate between invasive and non-invasive bladder cancer. Patients and Methods This study included 38 patients who were diagnosed with Transitional Cell Carcinoma (TCC) who underwent multiparametric Magnetic Resonance Imaging (mpMRI) at the department of Radiodiagnosis in Ain-Shams University from April 2021 till October 2021. Three radiologists with different levels of experience reviewed and scored all MRI examinations according to VI-RADS, compared them with the histopathological findings and inter-observer agreement was assessed. Results This study included 38 patients; the patients’ age ranged from 47 to 83 years old with mean age 62.26 (+8.18 SD). The total number of lesions in all cases were 43; 12 of them (27.9 %) were non-muscle-invasive urothelial carcinoma and 31 (72.1%) were muscle invasive. Using a VI-RADS score of 4 or greater as the cutoff value, the sensitivity, specificity, accuracy, PPV, and NPV for reader 1 were 96.8%, 83.3 %, 93%, 93.8%, and 90.9%, and for reader 2 were 93.5 %, 91.7%, 93%, 96.7% and 84.6%, and finally for reader 3 were 96.8%, 83.3%, 93 %, 93.8% and 90.9%. The agreement was excellent between each reader with the pathology and the readers with each other (Kappa over 0.75). Conclusion The Vesical Imaging-Reporting and Data System (VI-RADS) is an effective comprehensive scoring system, with satisfactory sensitivity, specificity, and diagnostic value for detecting detrusor muscle invasion. We can recommend VI-RADS scoring for use in the prediction of detrusor muscle invasion in patients with bladder cancer, but further multicenter validation studies containing multiple magnetic field strength devices also must be conducted.

A Nomogram of MRI Features to Assess Muscle Invasion in VI-RADS 2 Tumors With Stalk.

Vesical Imaging-Reporting and Data System (VI-RADS) is widely used to assess the muscle-invasive status of bladder cancer. However, the current classification efficacy of VI-RASD 2 tumors of stalk is unsatisfactory. To develop a nomogram to assess muscle-invasive bladder cancer (MIBC) in VI-RADS 2 tumors with stalk. Retrospective. A total of 186 patients (age: 67.8 ± 12.7 years) with 15.1% females, divided randomly into a training cohort (N = 130) and validation cohort (N = 56). 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). Twenty-one MRI features of tumors and stalks were developed from training cohort. The mean apparent diffusion coefficient (ADC) values of the tumor, stalk, and psoas muscles were calculated from the three circular regions of interest. The normalized T . The normalized ST . Three readers assessed the morphology of tumors and stalks. The final features of nomogram were selected by univariable logistic and the least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis. In VI-RADS 2 tumors with stalk, tumor size over 3 cm, increased stalk width, stalk morphology, decreased normalized T value, and increased normalized ST value were selected as the risk factors for MIBC. The AUC, accuracy, sensitivity, and specificity of the nomogram to assess MIBC were 0.969 (95% CI: 0.941-0.997), 92.3%, 94.1%, and 92.0% in training cohort and 0.940 (95% CI: 0.859-1.000), 89.3%, 75.0%, and 91.7% in validation cohort. This study constructed a nomogram for preoperative assessment of MIBC and modifying the current VI-RADS. 3 TECHNICAL EFFICACY: Stage 2.

Surveillance for Nonmuscle Invasive Bladder Cancer: Identifying the Point of Diminishing Returns

To characterize first and second recurrence patterns using 26years of cohort-level follow-up and microsimulation modeling. Patients diagnosed with nonmuscle-invasive bladder cancer in Stockholm County between 1995 and 1996 were included. Clinical, pathological, and longitudinal follow-up data were gathered. Logistic regressions, Kaplan Meier curves, and Cox proportional hazards models were run to generate assumptions for a microsimulation model, simulating first and second recurrence and progression for 10,000 patients. Three hundred eighty-six patients were included: 67.4% were male; >50% were TaLG; and 37.5% were American Urological Association high-risk. Median time to recurrence was 300days. Three patients had missing data. Cohort follow-up has been carried out for 26years. For simulated first-recurrences, low-risk patients recurred at 56.6% over 15years of follow-up, with 2.2% muscle-invasive (MI) progression; intermediate-risk patients recurred at 62.8%, with 4.3% MI progression; high-risk patients recurred at 48.7% over 15years, with MI progression at 14.3%. For second recurrences, 70.7%, 75.7%, and 84.7% of low, medium, and high-risk patients recurred. No patients were seen to have first recurrences after 9years, with low, but notable, rates beyond 5years. These data suggest that low-, intermediate-, and high-risk patients without recurrence at 5years may be potentially transitioned to less invasive monitoring.

The Value of Epidermal Growth Factor Receptor Expression in Predicting Aggressive Behaviors of Bladder Neoplasms

Background: It has been shown that some cancers express the epidermal growth factor receptor (EGFR). Several variables influence bladder cancer prognosis, including stage, grade, and gene expression. Objectives: We used immunohistochemistry to measure the prevalence and prognostic significance of EGFR expression in bladder tumors in our population. Methods: Thirty bladder tumors were the subjects of this cross-sectional study. To evaluate the biological behavior of the tumors, histopathological analysis was performed. We carried out EGFR immunohistochemical staining to evaluate gene expression. Results: EGFR was expressed in 25 (83.3%) patients. Expression of this biomarker was independent of tumor characteristics such as lymphatic invasion, muscle invasion, and tumor grade and stage (P value &gt; 0.05). Conclusions: Remembering each patient's tumor characteristics determine that prognosis is crucial. The prognostic value of EGFR expression in predicting aggressive behavior in bladder tumors is marginal, but it is necessary to evaluate therapeutic response.

Preoperative CT-based radiomics for diagnosing muscle invasion of bladder cancer

BackgroundThe primary objective of the research was to develop a method using radiomics-based computed tomography (CT) to predict muscle invasion in bladder cancer (BCa) before surgery.MethodsA total of 269 patients with bladder cancer were divided into two groups; training group (n = 188 cases) and validation group (n = 81 cases). Radiomics characteristics were determined by analyzing the CT images of each patient. The least absolute shrinkage and selection operator (LASSO) technique was used for developing a radiomics signature. Furthermore, logistic regression (LR), the support vector machine (SVM), decision tree (DT), and Artificial Neural Network (ANN) models were applied to differentiate between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Their performance was determined using the area under the receiver operating characteristic curve (AUC-ROC). In addition, accuracy, specificity, and sensitivity evaluations were also conducted.ResultsThe radiomics signature was found to be successful in its prediction. A total of 1036 radiomics features were found in the 269 patients, and out of those, 16 were selected as the best predictors of radiomics features. The results revealed that the ANN classifier had the best performance, with a validation set accuracy of 0.950.ConclusionsThe current work used machine learning and radiomics techniques to successfully construct a prediction model for muscle invasion in bladder cancer. The ANN model produced significant outcomes that may be used in clinical diagnosis or therapy.

Role of high resolution T2&amp; diffusion-weighted images in detection of muscle invasion of the urinary bladder carcinoma

Role of high resolution T2&amp; diffusion-weighted images in detection of muscle invasion of the urinary bladder carcinoma

CD105 and CD34 as Markers of Angiogenesis of Urothelial Carcinoma: A Cross Sectional Study

Background Urothelial carcinoma (UC) of the bladder is a major cause of morbidity and mortality throughout the world. The present study was carried out to see the expression of CD105 and CD34 as marker of angiogenesis in UC and study their relationship with grades and muscle invasion. Methods 50 cases of histopathologically diagnosed UC were included. CD105 and CD34 IHC staining was performed. Microvessel density (MVD) evaluation by CD105 and CD34 was compared. The number of microvessels were counted in high power in three hot spots. The highest value obtained amongst three fields were reported as MVD. Statistical analysis was done by (SPSS 28.00 version for windows) using independent t-test. Results There were 45 high grade cases UC 5 low grade cases of UC. Invasive papillary UC was seen in 25 cases (50%) followed by invasive UC seen in 13 cases (26%). Both Lamina propria (LP) invasion and muscularis propria invasion were noted in 16 cases of high-grade urothelial carcinoma. Only LP invasion was seen in 3 cases of low grade and 25 cases of high-grade UC respectively. Evaluation of MVD CD105 and MVD CD34 did not show any significant association of MVD with grade with a p value of 0.214 &amp; 0.429 respectively. Aso there was no significant association of MVD CD105 (p=0.580) &amp; CD34 (p=0.747) with muscularis propria invasion. Overall mean CD105 and CD34 were similar with no statistical difference between the two markers. Conclusion Both CD105 and CD34 can be used as marker to assess angiogenesis. However, there is no significant association of MVD with grade or muscle invasion in UC.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Expression of androgen receptor in bladder cancer: A tertiary care center study

IntroductionThe significance of androgen receptor (AR) expression in bladder cancer is the focus of current research. This study aimed to assess the significance of AR expression in bladder urothelial carcinoma. MethodsA total of 206 cases of urothelial carcinoma of the urinary bladder were reviewed and immunohistochemical staining for AR was performed. The histological score was calculated as the product of the staining intensity and percentage of cells with positive nuclear staining. The staining results were correlated with demographic parameters, tumor grade, and detrusor muscle invasion status. ResultsSeventy-eight percent (n = 161) of cases tested positive for AR expression. AR was significantly overexpressed in non-muscle-invasive tumors (p = 0.042). Moreover, A higher AR expression was associated with increased disease-free survival (p = 0.019). However, AR expression was not significantly associated with cancer-specific survival, patient sex, or tumor grade (0.359, 0.747, and 0.867, respectively). AR expression is inversely related to muscle invasion and recurrence in bladder cancer. ConclusionThe results of this study support those of several reports worldwide. Further molecular studies are required to elucidate the role of androgens in bladder cancer pathogenesis and therapy.

Can magnetic resonance imaging differentiate muscle invasion (T2) and lamina propria invasion (T1) urothelial carcinoma of the bladder? A systematic review and meta-analysis of Vesical Imaging-Reporting and Data System accuracy.

Vesical Imaging-Reporting and Data System (VI-RADS) was developed as a structured reporting tool to anticipate the possibility of muscle invasion. This study is aimed to investigate the diagnostic accuracy of VI-RADS for discriminating T2 from T1 bladder cancer. Scopus, Web of Science, PubMed, and Embase were searched on October 4, 2021, for studies with the following characteristics: (1) bladder cancer patient population, (2) VI-RADS as an index test, (3) retransurethral resection of bladder tumor/cystectomy as a reference, and (4) adequate VI-RADS score data for T1 and T2 lesions. The analyses were performed using the binary regression model of MIDAS in Stata. Six studies with 624 magnetic resonance imaging reports were included. The receiver operating characteristics curve for differentiation of T2 from T1 bladder cancer showed an area under the curve of 0.93 (95% confidence interval [CI], 0.91-0.95) for a VI-RADS ≥3 and 0.75 (95% CI, 0.71-0.79) for a VI-RADS ≥4. A VI-RADS ≥3 showed high sensitivity of 93% (95% CI, 85%-97%), specificity of 61% (95% CI, 30%-86%), positive likelihood ratio of 2.4 (95% CI, 1.1-5.3), and negative likelihood ratio of 0.11 (95% CI, 0.05-0.24). A total of 10.4% of T2 lesions were scored as VI-RADS 2, while 10% of T1 lesions were scored as VI-RADS 4 or 5. The VI-RADS ≥3 has high accuracy and sensitivity for detecting muscle invasion in borderline populations of T1 or T2 bladder cancer. Thus, the VI-RADS could be a good non-invasive screening test for the detection of T2 urothelial lesions.

Comparison of the diagnostic performance of biparametric and multiparametric MRI in detecting muscle invasion of bladder cancer located at the ureteral orifice.

To assess the diagnostic performance of biparametric magnetic resonance imaging (bp-MRI) in predicting detrusor muscle invasion for bladder cancer (BC) located at the ureteral orifice by comparing it with the Vesical Imaging Reporting and Data System (VI-RADS) system based on multiparametric MRI (mp-MRI). Patients with histopathologically proven BC located at the ureteral orifice from December 2019 to November 2022 were analyzed retrospectively. Two sets, bp-MRI (set 1) and mp-MRI (set 2), were formed from the images. Both sets were evaluated independent of histopathology by three radiologists with different levels of experience in abdominal radiology. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of VI-RADS in the prediction of muscle invasion. The intraclass correlation coefficient (ICC) was used to evaluate inter-reader agreement. Of 68 patients with BCs located at the ureteral orifice, 50 (48 males, median age: 72 years) met the study criteria. Out of the 50 patients, 36 had non-muscle invasive BC (pTa-T1) and 14 had muscle invasive BC (MIBC) (pT2-T4). In the comparison of VI-RADS categories with histopathologic data for MIBC detection, the area under the curve of the ROC analysis for the bp- and mp-MRI protocol was 1.000-0.986 for reader 1, 0.893-0.901 for reader 2, and 0.808-0.865 for reader 3. There was no statistically significant difference in predicting detrusor muscle invasion with the bp- and mp-MRI-based on VI-RADS categories for all readers (p=0.126, 0.203, and 0.322, respectively). The ICCs between all the readers showed excellent agreement and were similar for both protocols. The bp-MRI consisting of DWI and T2-WI can be used as an alternative to the mp-MRI in predicting detrusor muscle invasion for BCs located at the ureteral orifice; however, less experienced readers should exercise caution.

Experience in using the VI-RADS system in assessing the depth of invasion of bladder tumors

Introduction. Survival rates and treatment algorithms for patients with bladder cancer (BC) depend on the depth of tumor invasion, in particular on the presence of the bladder muscle layer invasion and extraorganic spread. To assess the depth of bladder invasion, the VI-RADS system was developed in 2018, which is based on multiparametric MRI (mpMRI). According to published studies on the VI-RADS effectiveness, there is a high diagnostic accuracy for identifying formations with probable invasion into the muscle layer. The data on BC extraorganic spread are limited and the issue of assessing the sensitivity and specificity of this system requires further study.Aim of the study. To evaluate the diagnostic performance of mpMRI using the VI-RADS system in detecting muscle invasion and BC extraorganic growth.Materials and methods. A prospective study was conducted in the clinics of the National Medical Research Radiological Centre and included 75 patients aged 19 to 85 years, of which 39 (52%) had been newly diagnosed with BC, 36 (48%) had a relapse or continuous tumor growth. All patients underwent pelvic organs mpMRI on a tomograph with a magnetic field induction of 1.5T, followed by transurethral resection (TUR), TUR-biopsy of the bladder or cystectomy no later than 6 weeks after scanning.. The description of the bladder tumor included its measurements, localization and VI-RADS scale assessment. The data obtained by mpMRI were compared with the results of the morphological study using statistical analysis.Results. According to the results of the study, the overall VI-RADS scale sensitivity for categories above 3 (the presence of muscle invasion is equivocal) was 95.15% [90.11%; 99.95%], above 4 (muscle invasion is likely) – 92.59% [82.11%; 97.94%], specificity was determined at the level of 47.62% [25.71%; 70.22%] and 80.95% [58.09%; 94.55%] respectively. When assessing extraorganic spread in 30 patients, the sensitivity was 83.33% [62.62%; 95.26%], specificity – 83.33% [35.88%; 99.58%]. The accuracy and positive predictive value also had high levels from 80 to 95%, in contrast to the negative predictive value (55.56%).Conclusion. The scale for BC invasion depth assessing VI-RADS is characterized by high rates of sensitivity, specificity and accuracy, in particular when used in determining extraorganic spread.