Objective
To assess diagnostic validity and reliability of VI-RADS in predicting muscle invasion by bladder cancer (BCa) and evaluate reviewer acceptance of VI-RADS for clinical routine.
Methods
A ...prospective multicenter study enrolled 331 patients with suspected/untreated BCa who underwent preoperative multiparametric MRI examination (mp-MRI) of the urinary bladder. Four experienced radiologists independently evaluated all mp-MRI using VI-RADS. The diagnostic validity of VI-RADS for predicting muscle invasion by BCa was calculated using histopathology of the first transurethral resection bladder tumor (TURBT) and second TURBT as the reference standards. The kappa statistics (
κ
) were applied to assess the interreader agreement (IRA). Reviewer acceptance was evaluated with questionnaires.
Results
The risk of muscle invasion in VI-RADS 2, 3, 4, and 5 after the first and second TURBT was 21.8%, 45.8%, 69.6%, and 96.4% and 24.4%, 58.3%, 87%, and 99.2%, respectively. The overall diagnostic validity of VI-RADS was high. The optimal cut-off value for predicting muscle invasion after first TURBT was > VI-RADS 3 (sensitivity = 84.1% and specificity = 92.3%), and after second TURBT was > VI-RADS 2 (sensitivity = 89.9% and specificity = 90.1%). VI-RADS categorization showed a very good IRA (
κ
= 0.93). Reviewers fully agreed with the statement, “The application of structured reporting of bladder tumor should be encouraged” (score = 20).
Conclusions
VI-RADS showed high diagnostic validity and reliability for predicting muscle invasion by BCa, especially VI-RADS 4 and 5. However, VI-RADS 2 and 3 require further modifications to enhance their diagnostic validity. VI-RADS is highly encouraged to be used in daily practice.
Key Points
• VI-RADS showed high diagnostic validity and reliability in predicting BCa muscle invasion, especially VI-RADS 4 and 5.
• In VI-RADS 2 and 3, we observed a notable percentage of BCa with muscle invasion and this would require further modifications to enhance the diagnostic validity for these scores.
• Overall VI-RADS is well-accepted by radiologists who recommend it for daily practice.
To compare the efficacy of the levonorgestrel intrauterine system (LNG-IUS) versus megestrol acetate (MA) in inducing complete regression among women with atypical endometrial hyperplasia (AEH) who ...declined hysterectomy.
In this single-center, open-label randomized controlled trial, we included 148 women with AEH who declined hysterectomy. We randomized participants to receive either daily oral MA 160 mg (n=74) or apply LNG-IUS (n=74) and scheduled their follow-up by endometrial sampling at 3, 6, 9, 12, 18, and 24 months. The success rate and duration until complete regression were the primary outcomes.
The mean duration until complete regression was 5.52 months (95% confidence interval CI=4.85-6.18) for the LNG-IUS group versus 6.87 months (95% CI=6.09-7.64) for the megestrol group (log-rank test p-value=0.011). The cumulative regression rate after 12 months was 91.9% with the LNG-IUS versus 77% with MA (p=0.026). Weight gain in the MA group vs LNG-IUS group after one year (4.7±4 kg vs. 2.7±2.6 kg, 95% CI=0.89-3.12; p=0.001) and after two years of therapy (7.8±5.1 kg vs. 4.1±2.9 kg, 95% CI=2.29-5.06; p<0.001).
Compared to MA, the LNG-IUS was more efficacious in treating AEH in women who declined hysterectomy, especially those with moderate/severe obesity, with fewer adverse effects and less weight gain. Extending therapy to 12 months for persistent cases would improve regression rates with reasonable safety. Alternate hysteroscopic and office sampling seemed convenient for follow-up.
ClinicalTrials.gov Identifier: NCT04385667.
Objective
The American College of Radiology (ACR) recently published the ovarian-adnexal reporting and data system (O-RADS) to provide guidelines to physicians who interpret ultrasound (US) ...examinations of adnexal masses (AM). This study aimed to compare the O-RADS with two other well-established US classification systems for diagnosis of AM.
Methods
This retrospective multicenter study between May 2016 and December 2019 assessed consecutive women with AM detected by the US. Five experienced consultant radiologists independently categorized each AM according to O-RADS, gynecologic imaging reporting and data system (GI-RADS), and international ovarian tumor analysis (IOTA) simple rules. Pathology and adequate follow-up were used as reference standards for calculating the validity of three US classification systems for diagnosis of AM. Kappa statistics were used to assess the inter-reviewer agreement (IRA).
Results
A total of 609 women (mean age, 48 ± 13.7 years; range, 18–72 years) with 647 AM were included. Of the 647 AM, 178 were malignant and 469 were benign. Malignancy rates were comparable to recommended rates by previous literature in O-RADS and IOTA, but higher in GI-RADS. O-RADS had significantly higher sensitivity for malignancy than GI-RAD and IOTA (
p
= 0.003 and 0.0007, respectively), but non-significant slightly lower specificity (
p
> 0.05). O-RADS, GI-RADS, and IOTA showed similar overall IRA (
κ
= 0.77, 0.69, and 0.63, respectively) with a tendency toward higher IRA with O-RADS than with GI-RADS and IOTA.
Conclusions
O-RADS compares favorably with GI-RADS and IOTA. O-RADS had higher sensitivity than GI-RADS and IOTA simple rules with relatively similar specificity and reliability.
Key Points
• The malignancy rates were comparable to recommended rates by previous literature in O-RADS and IOTA, but higher in GI-RADS.
• The O-RADS had significantly higher sensitivity for malignancy than GI-RADS and IOTA (96.8% vs 92.7% and 92.1%; p = 0.003 and 0.0007, respectively), but non-significant slightly lower specificity (92.8% vs 93.6% and 93.2%, respectively; p > 0.05).
• The O-RADS, GI-RADS, and IOTA showed similar overall inter-reviewer agreement (IRA) (κ = 0.77, 0.69, and 0.63, respectively), with a tendency toward higher IRA with O-RADS than with GI-RADS and IOTA.
World Health Organization classified Listeria monocytogenes as a major notable foodborne pathogen associated with high mortality and hospitalization. The study reports the prevalence, antibiogram, ...virulence determination and genetic characterization of L. monocytogenes from different food products. A total of 250 food samples, fifty samples each from raw milk, ice cream, minced meat, fish fillet and sausage were collected from the Menoufiya governorate in Egypt. L. monocytogenes was detected in 17 (6.8%) of the tested food samples including minced meat (14%), fish fillet (8%), sausage (6%) and raw milk (6%). The antimicrobial susceptibility assay of 17 L. monocytogenes isolates against seventeen antibiotics belonging to eight antibiotics classes revealed a high susceptibility to norfloxacin (82.3%), amoxicillin-clavulanic acid (76.4%), cefotaxime (70.5%), erythromycin (64.6%), amoxicillin (64.6%), gentamicin (58.7%) and vancomycin (58.7%). While, high resistance was observed against oxytetracycline (76.4%), trimethoprim-sulfamethoxazole (76.4%), chloramphenicol (70.5%), doxycycline (64.6%), levofloxacin (41.2%) and azithromycin (41.2%). Of note, all L. monocytogenes isolates were multidrug-resistant. The multiplex PCR successfully amplified L. monocytogenes in all tested isolates. Screening of the five virulence-related genes revealed the hlyA and iap as the most prevalent genes followed by actA gene, however, the inlA and prfA genes were not detected in any of the studied isolates. The partial 16S rRNA gene sequencing of three L. monocytogenes isolates showed a high nucleotide similarity (99.1–99.8%) between the study isolates and various global clones, and phylogenetic analysis clustered these L. monocytogenes strains with other Listeria species including L. welshimeri, L. seeligeri and L. innocua. This study demonstrates the impact of L. monocytogenes as a major contaminant of various food products and suggests more attention to the awareness and hygienic measures in the food industry.
Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require ...accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry.
The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values.
SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC (
0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression (
=0.038 and
=0.019, respectively).
The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.
HOXB8 is a protein that was found to promote cancer proliferation and invasion. ILK is a protein kinase which has a role in carcinogenesis. FAT4 is a tumor homologue that has a role in EMT and ...autophagy regulation.
To identify expression of Human HOXB8, Integrin-linked kinase (ILK1) and FAT homolog 4 (FAT4) in colorectal cancer (CRC) correlating their expression with pathological, prognostic and clinical parameters of CRC.
We assessed the expression of HOXB8, ILK and FAT4 in fifty CRC patients and ten samples from nearby non-neoplastic colonic mucosa using immunohistochemistry.
The expression of HOXB8 and ILK in CRC was positively associated with high tumor grade, advanced tumor stage, lymph node involvement (
< 0.001), occurrence of distant metastases (
= 0.003 and 0.024 respectively), higher incidence of tumor recurrence (
= 0.03,
< 0.001 respectively), worse survival rates (
= 0.038 and 0.003 respectively). The expression of FAT4 in CRC was correlated with lower grade, early stage of the tumor, absence of lymph node involvement (
< 0.001) and lack of distant metastases (
= 0.011). High FAT4 expression was associated with absence of tumor recurrence (
< 0.001) and favorable survival rates (
< 0.001 and 0.003).
High immunohistochemical expression of HOXB8 and ILK in addition to low immunohistochemical expression of FAT4 was associated with unfavorable prognostic and pathological parameters of CRC.
Triple-negative breast cancer (TNBC) is a markedly aggressive molecular subtype of breast cancer; there is an urgent need to clarify the molecular mechanisms underlying the progression and metastases ...of BLBC, in order to find a novel targeted therapy. Microfibrillar-associated protein 5 (MFAP5) plays an essential role in the regulation of cell behaviour and survival. Integral membrane protein 2A (ITM2A) is a type II transmembrane protein, which is a member of a family of autophagy related proteins.The aim of this study was to assess the expression of MFAP5 and ITM2A proteins in tissues of BLBC using immunohistochemistry, in order to correlate the expression with clinicopathological and prognostic parameters of such aggressive cancer.
The present study included sections from archived paraffin blocks retrieved from 120 patients with TNBC. We collected cases from three years, i.e. from 2016 to 2019. We assessed expression of MFAP5 and ITM2A using immunohistochemistry.
High expression of MFAP5 and low expression of ITM2A was associated with advanced stage (
= 0.007), higher grade of tumour (
= 0.005 and
= 0.004, respectively), the presence of lymph nodes metastases (
< 0.001 and
= 0.002, respectively), lower three-year RFS rate (
< 0.001 and
= 0.016, respectively), and lower three-year OS rate (
< 0.001).
MFAP5 and ITM2A are novel prognostic biomarkers for breast cancer and might be considered as promising therapeutic targets for patients with breast cancer, particularly TNBC molecular subtype, in the future.
Cytokeratin 19 (CK19) is highly expressed in epithelial tumours such as breast cancer (BC). Octamer-binding transcription factor 4 (OCT4), a transcription factor of the POU (Pit-Oct-UNC) family, ...plays a criti-cal role in the self-renewal and maintenance of pluripotency of embryonic stem cells; therefore, it has been used as a promising CSC marker.
CK19 was assessed in peripheral blood using flow-cytometric analysis while OCT4 was evaluated in breast tissue samples by immunohistochemistry from 70 patients (non-metastatic BC, meta-static BC, and non-malignant breast tumours).
CK19 and OCT4 were significantly associated with BC patients compared to control (
< 0.001). CK19 was detected in 38 patients with BC (62.2%); meanwhile, OCT4 was positive in 37 BC patients (60.6%). CK19 was positively associated with grade (
= 0.002), HER2 (
= 0.009), metastasis (
= 0.026), molecular subtypes and LN (
< 0.001), and stage (
= 0.001) while OCT4 expression was positively associated with BMI (
< 0.023), aggressive molecular subtype (
< 0.019), ER expression (
= 0.025), presence of LN metastases (
< 0.017), and distant metastasis (
< 0.018). A non-significant relation was found between the expression of CK19 and OCT (
= 0.291). The positive expression of CK19 and OCT4 was significantly and inversely associated with both 3-year OS and 3-year PFS.
CK19 and OCT4 are associated with BC, so they can be considered as prognostic and predictive markers for poor OS and PFS in non-metastatic as well as metastatic BC patients.
Background
there is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. ...SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues.
Aim: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients.
PATIENTS AND METHODS: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60).
RESULTS: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001).
In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival.
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