Radiomics-based machine learning approach for the prediction of grade and stage in upper urinary tract urothelial carcinoma: a step towards virtual biopsy.

OBJECTIVES: Upper tract urothelial carcinoma (UTUC) is a rare, aggressive lesion, with early detection a key to its management. This study aimed to utilise computed tomographic urogram data to develop machine learning models for predicting tumour grading and staging in upper urothelial tract carcinoma patients and to compare these predictions with histopathological diagnosis used as reference standards. METHODS: Protocol-based computed tomographic urogram data from 106 patients were obtained and visualised in 3D. Digital segmentation of the tumours was conducted by extracting textural radiomics features. They were further classified using 11 predictive models. The predicted grades and stages were compared to the histopathology of radical nephroureterectomy specimens. RESULTS: Classifier models worked well in mining the radiomics data and delivered satisfactory predictive machine learning models. The multilayer panel showed 84% sensitivity and 93% specificity while predicting UTUC grades. The Logistic Regression model showed a sensitivity of 83% and a specificity of 76% while staging. Similarly, other classifier algorithms [e.g. Support Vector classifier (SVC)] provided a highly accurate prediction while grading UTUC compared to clinical features alone or ureteroscopic biopsy histopathology. CONCLUSION: Data mining tools could handle medical imaging datasets from small (<2 cm) tumours for UTUC. The radiomics-based machine learning algorithms provide a potential tool to model tumour grading and staging with implications for clinical practice and the upgradation of current paradigms in cancer diagnostics. CLINICAL RELEVANCE: Machine learning based on radiomics features can predict upper tract urothelial cancer grading and staging with significant improvement over ureteroscopic histopathology. The study showcased the prowess of such emerging tools in the set objectives with implications towards virtual biopsy.

Radiogenomics Map-Based Molecular and Imaging Phenotypical Characterization in Localised Prostate Cancer Using Pre-Biopsy Biparametric MR Imaging.

To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson's correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer.

Radiomics Machine Learning Analysis of Clear Cell Renal Cell Carcinoma for Tumour Grade Prediction Based on Intra-Tumoural Sub-Region Heterogeneity.

BACKGROUND: Renal cancers are among the top ten causes of cancer-specific mortality, of which the ccRCC subtype is responsible for most cases. The grading of ccRCC is important in determining tumour aggressiveness and clinical management. OBJECTIVES: The objectives of this research were to predict the WHO/ISUP grade of ccRCC pre-operatively and characterise the heterogeneity of tumour sub-regions using radiomics and ML models, including comparison with pre-operative biopsy-determined grading in a sub-group. METHODS: Data were obtained from multiple institutions across two countries, including 391 patients with pathologically proven ccRCC. For analysis, the data were separated into four cohorts. Cohorts 1 and 2 included data from the respective institutions from the two countries, cohort 3 was the combined data from both cohort 1 and 2, and cohort 4 was a subset of cohort 1, for which both the biopsy and subsequent histology from resection (partial or total nephrectomy) were available. 3D image segmentation was carried out to derive a voxel of interest (VOI) mask. Radiomics features were then extracted from the contrast-enhanced images, and the data were normalised. The Pearson correlation coefficient and the XGBoost model were used to reduce the dimensionality of the features. Thereafter, 11 ML algorithms were implemented for the purpose of predicting the ccRCC grade and characterising the heterogeneity of sub-regions in the tumours. RESULTS: For cohort 1, the 50% tumour core and 25% tumour periphery exhibited the best performance, with an average AUC of 77.9% and 78.6%, respectively. The 50% tumour core presented the highest performance in cohorts 2 and 3, with average AUC values of 87.6% and 76.9%, respectively. With the 25% periphery, cohort 4 showed AUC values of 95.0% and 80.0% for grade prediction when using internal and external validation, respectively, while biopsy histology had an AUC of 31.0% for the classification with the final grade of resection histology as a reference standard. The CatBoost classifier was the best for each of the four cohorts with an average AUC of 80.0%, 86.5%, 77.0% and 90.3% for cohorts 1, 2, 3 and 4 respectively. CONCLUSIONS: Radiomics signatures combined with ML have the potential to predict the WHO/ISUP grade of ccRCC with superior performance, when compared to pre-operative biopsy. Moreover, tumour sub-regions contain useful information that should be analysed independently when determining the tumour grade. Therefore, it is possible to distinguish the grade of ccRCC pre-operatively to improve patient care and management.

The Performance of Different Parametric Ultrasounds in Prostate Cancer Diagnosis: Correlation with Radical Prostatectomy Specimens.

BACKGROUND: Prostate cancer is a prevalent cancer among men. Multiparametric ultrasound [mpUS] is a diagnostic instrument that uses various types of ultrasounds to diagnose it. This systematic review aims to evaluate the performance of different parametric ultrasounds in diagnosing prostate cancer by associating with radical prostatectomy specimens. METHODOLOGY: A review was performed on various ultrasound parameters using five databases. Systematic review tools were utilized to eliminate duplicates and identify relevant results. Reviewers used the Quality Assessment of Diagnostic Accuracy Results [QUADAS-2] to evaluate the bias and applicability of the study outcomes. RESULT: Between 2012 and 2023, eleven studies were conducted to evaluate the performance of the different ultrasound parametric procedures in detecting prostate cancer using grayscale TRUS, SWE, CEUS, and mpUS. The high sensitivity of these procedures was found at 55%, 88.6%, 81%, and 74%, respectively. The specificity of these procedures was found to be 93.4%, 97%, 88%, and 59%, respectively. This high sensitivity and specificity may be associated with the large lesion size. The studies revealed that the sensitivity of these procedures in diagnosing clinically significant prostate cancer was 55%, 73%, 70%, and 74%, respectively, while the specificity was 61%, 78.2%, 62%, and 59%, respectively. CONCLUSIONS: The mpUS procedure provides high sensitivity and specificity in PCa detection, especially for clinically significant prostate cancer.

Comparative Analysis of Enbloc or Piecemeal Removal After Enbloc Resection of Gastrointestinal Stromal Tumors.

OBJECTIVE: To investigate the safety and prognosis of enbloc or piecemeal removal after enbloc resection of a gastric GIST by comparing the clinical data of endoscopic en block resection and piecemeal removal (EP) and en block resection and complete removal (EC) of gastric GISTs. METHODS: A total of 111 (43 endoscopic piecemeal, and 68 complete removal) patients with gastric GIST's ≥ 2 cm in diameter who underwent endoscopic therapy from January 2016 to June 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. In all cases, it was ensured that the tumor was intact during the resection, however, it was divided into EP group and EC group based on whether the tumor was completely removed or was cut into pieces which were then removed. The patients' recurrence-free survival rate and recurrence-free survival (RFS) were recorded. RESULTS: There was no statistically significant difference in RFS rates between the two groups (P = 0.197). The EP group had relatively high patient age, tumor diameter, risk classification, and operation time. However, there was no statistically significant difference in the number of nuclear fission images, postoperative hospitalization time, postoperative fasting time, complication rate and complication grading between the two groups (P > 0.05). CONCLUSION: Endoscopic piecemeal removal after en block resection of gastric GIST is safe and effective and achieves similar clinical outcomes as complete removal after en block resection.

Cost-effectiveness of quality improvement intervention to reduce time between CT-detection and ureteroscopic laser fragmentation in acute symptomatic ureteric stones management.

OBJECTIVE: To prospectively assess clinical and cost effectiveness of emergency ureteroscopic laser fragmentation of urinary stones causing symptoms or obstruction. PATIENTS AND METHODS: 100 consecutive patients with an average (median) age 55.6 (57.5) years and average (median) stone size of 8.2 mm (± 7 mm) between October 2018 and December 2021 who underwent emergency ureteroscopy and laser fragmentation formed the study cohort as part of a clinical service quality improvement. Primary outcome was single procedure stone-free rate and cost-effectiveness. The secondary outcomes were complications, re-admission and re-intervention. A decision analysis model was constructed to compare the cost-effectiveness of emergency ureteroscopy with laser fragmentation (EUL) and emergency temporary stenting followed by delayed ureteroscopy with laser fragmentation (DUL) using our results and success rates for modelling. RESULTS: Single procedure stone-free rates (SFR) for EUL and DUL were 85%. The re-intervention rate, re-admission and complication rates of the study cohort (EUL) were 9%, 18%, and 4%, respectively, compared to 15%, 20%, and 5%, respectively for the control cohort (DUL). The decision analysis modelling demonstrated that the EUL treatment option was more cost-efficient, averting £2868 (€3260) per patient for the UK health sector. Total cost of delayed intervention was £7783 (€8847) for DUL in contrast to £4915 (€5580) for EUL. CONCLUSIONS: Implementation of quality improvement project based on a reduction in CT detection-to-laser fragmentation time interval in acute ureteric obstruction or symptoms caused by stones had similar clinical effectiveness compared to delayed ureteroscopic management, but more cost-effective.

Predictive accuracy of boosted regression model in estimating risk of venous thromboembolism following minimally invasive radical surgery in pharmacological prophylaxis-naïve men with prostate cancer.

BACKGROUND: Venous thromboembolism (VTE) is a potentially life-threatening but preventable complication after urological surgery. Physicians are faced with the challenges of weighing the risks and benefits of thromboprophylaxis given scanty evidence for or against and practice variation worldwide. OBJECTIVE: The primary objective of the study was to explore the possibility of a risk-stratified approach for thromboembolism prophylaxis following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: A prospective database was accessed to cross-link venous thromboembolism events in 522 men who underwent minimally invasive prostatectomy between February 2010 and October 2021. A deterministic data linkage method was used to record events through electronic systems. Community Health Index (CHI) numbers were used to identify patients via electronic health records. Patient demographics and clinical characteristics such as age, comorbidities, Gleason staging, and readmission details accrued. OUTCOMES: VTE within 90 days and development of a risk-stratified scoring system. All statistical analysis was performed using R-Statistical Software and the risk of VTE within 90 days of surgery was estimated via gradient-boosting decision trees (BRT) model. RESULTS AND LIMITATIONS: 1.1% (6/522) of patients developed deep vein thrombosis or pulmonary embolism within 3 months post-minimally invasive prostatectomy. Statistical analysis demonstrated a significant difference in the body mass index (p = 0.016), duration of hospital stay (p < 0.001), and number of readmissions (p = 0.036) between patients who developed VTE versus patients who did not develop VTE. BRT analysis found 8 variables that demonstrated relative importance in predicting VTE. The receiver operating curves (ROC) were constructed to assess the discrimination power of a new model. The model showed an AUC of 0.97 (95% confidence intervals [CI]: 0.945,0.999). For predicting VTE, a single-center study is a limitation. CONCLUSIONS: The incidence of VTE post-minimally invasive prostatectomy in men who did not receive prophylaxis with low molecular weight heparin is low (1.1%). The proposed risk-scoring system may aid in the identification of higher-risk patients for thromboprophylaxis. In this report, we looked at the outcomes of venous thromboembolism following minimally invasive radical prostatectomy for prostate cancer in consecutive men. We developed a new scoring system using advanced statistical analysis. We conclude that the VTE risk is very low and our model, if applied, can risk stratify men for the development of VTE following radical surgery for prostate cancer.

Distribution of neurovascular structures within the prostate gland and their relationship to complications after radical prostatectomy.

BACKGROUND: Radical prostatectomy remains the main choice of treatment for prostate cancer. However, despite improvements in surgical techniques and neurovascular sparing procedures, rates of erectile dysfunction, and urinary incontinence remain variable. This is due, at least in part, to an incomplete understanding of neurovascular structures associated with the prostate. The objective of this study was to provide a comprehensive, detailed histological overview of the distribution of nerves and blood vessels within the prostate, facilitating subsequent correlation of prostatic neurovascular structures with patients' clinical outcomes after radical prostatectomy. METHODS: Neurovascular structures within the prostate were investigated in a total of 309 slides obtained from 15 patients who underwent non-nerve-sparing radical prostatectomy. Immunohistochemical staining was performed to identify and distinguish between parasympathetic and sympathetic nerves, whereas hematoxylin and eosin staining was used to identify blood vessels. The total number, density, and relative position of nerves and blood vessels were established using quantitative morphometry and illustrated using visualization approaches. Patient-specific outcome data were then used to establish whether the internal distribution of nerves and blood vessels within the prostate correlated with the nature and extent of complications after surgery. One-way analysis of variance tests and unpaired t tests were applied to establish statistically significant differences across the measured variables. RESULTS: Nerves and blood vessels were present across all prostatic levels and regions. However, their number and density varied considerably between regions. Assessment of the precise positioning of neurovascular structures revealed that the majority of nerve fibers were located within the dorsal and peripheral aspects of the gland. In contrast, blood vessels were predominantly located within ventral and dorsal midline regions. The number of intraprostatic nerves was found to be significantly lower in patients who recovered their continence within 12 months of surgery, compared to those whose recovery took 12 months or longer. CONCLUSION: We report an unexpected disconnect between the localization and positioning of nerve fibers and blood vessels within the prostate. Moreover, individual variability in the density of intraprostatic neurovascular structures appears to correlate with the successful recovery of urinary continence after radical prostatectomy, suggesting that differences in intrinsic neurovascular arrangements of the prostate influence postoperative outcomes.

HMG co-reductase expression and response to intravesical Bacillus Calmette-Guérin in patients with high grade non-muscle invasive urinary bladder cancer receiving statins.

BACKGROUND: Cardiovascular disease affects over 7 million people in the UK and statins are often prescribed to mitigate cardiovascular risks. The effect of statins on a number of cancers is debated and their effect on Bacillus Calmette-Guérin (BCG) responsiveness in non-muscle invasive urinary bladder cancer (NMIBC) is not fully understood. AIMS: This study aims to explore the difference in HMG Co-A reductase (HMGCR) expression in NMIBC on immunochemistry in BCG responders and non-responders while on statins. METHOD: Three hundred and thirty-two cases of intravesical BCG treatment for high-risk NMIBC between November 2003 and December 2017 were identified. Patients taking statins for at least 12 months before the diagnosis of NIMBC and with a follow-up of at least 5 years were included. They were divided into BCG responders and non-responders. Tumour tissue from these patients was immunohistochemically stained and quantitative image analysis carried out to assess and compare HMGCR expression in the groups. RESULTS & CONCLUSION: This study showed a differential expression of HMGCR in responders vs. non-responders to BCG for high-risk NMIBC on statins. This data should form the basis of a further research and multi-centre study in a larger cohort, using HMGCR as a biomarker of response in patients on statins.

Detection Rate of PSMA PET Using Different Ligands in Men with Biochemical Recurrent Prostate Cancer Following Radical Treatment: A Systematic Review and Meta-analysis of Prospective Studies.

BACKGROUND: Despite the acknowledged diagnostic detection rate of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in prostate cancer, little is known about the quality of evidence, particularly focusing on prospective studies. Most systematic reviews are based on retrospective reports. RATIONALE AND OBJECTIVES: To conduct systematic review and meta-analysis of prospective studies reporting the diagnostic detection rate of PSMA PET (computed tomography (CT) and MR) for the detection of biochemically recurrent metastatic prostate cancer. MATERIALS AND METHODS: We systematically searched PubMed, MEDLINE, Embase, and Scopus, from database until March 1, 2023 for randomized controlled trials and prospective studies using PSMA PET imaging in prostate cancer. The primary endpoint was to assess diagnostic detection rate of PSMA PET imaging in the detection of recurrent prostate cancer in men with biochemical relapse following radical treatment. We calculated the pooled overall diagnostic detection rate with 95% CI using a random-effects model and assessed the heterogeneity between the studies including risk of biases estimation. RESULTS: A total of 6800 patients from 32 articles were included in this study. The overall detection rate of PSMA PET for prostate cancer was 0.67 (95% CI, 0.63, 0.71). For histologically confirmed lymph nodes, the PPV from 13 prospective studies containing 1496 patients was 0.96 (95% CI, 0.93, 0.99). We performed a subgroup analysis of PSMA PET detection rates according to categorically grouped Prostate Specific Antigen (PSA) values of 0-0.5, 0.5-1.0, 1.0-2.0, and >2.0 ng/ml and obtained detection rates of 0.44, 0.63, 0.82, and 0.94, respectively. The detection rate of 18F PSMA was better in men with a PSA between 1 ng/ml and 2 ng/ml in comparison to 68Ga PSMA (0.91 with 95% CI 0.81-0.99 vs. 0.79 with 95% CI 0.73, 0.85). CONCLUSION: PSMA PET imaging provides a good detection rate for the metastatic recurrence of prostate cancer in men with biochemical relapse following radical treatment. The detection rate improves significantly above a serum PSA value of 1 ng/ml. The diagnostic detection rate of 18F-PSMA is best at PSA values between 1 and 2 ng/ml, in comparison to 68Ga PSMA. This conclusion is heavily biased, further research needs to focus on better methodology to minimize the risk of biases.

Validation of the updated Bosniak classification (2019) in pathologically confirmed CT-categorised cysts.

INTRODUCTION: The updated Bosniak classification in 2019 (v2019) addresses vague imaging terms and revises the criteria with the intent to categorise a higher proportion of cysts in lower-risk groups and reduce benign cyst resections. The aim of the present study was to compare the diagnostic accuracy and inter-observer agreement rate of the original (v2005) and updated classifications (v2019). METHOD: Resected/biopsied cysts were categorised according to Bosniak classifications (v2005 and v2019) and the diagnostic accuracy was assessed with reference to histopathological analysis. The inter-observer agreement of v2005 and v2019 was determined. RESULTS: The malignancy rate of the cohort was 83.6% (51/61). Using v2019, a higher proportion of malignant cysts were categorised as Bosniak ≥ III (88.2% vs 84.3%) and a significantly higher percentage were categorised as Bosniak IV (68.9% vs 47.1%; p = 0.049) in comparison to v2005. v2019 would have resulted in less benign cyst resections (13.5% vs 15.7%). Calcified versus non-calcified cysts had lower rates of malignancy (57.1% vs 91.5%; RR,0.62; p = 0.002). The inter-observer agreement of v2005 was higher than that of v2019 (kappa, 0.70 vs kappa, 0.43). DISCUSSION: The updated classification improves the categorisation of malignant cysts and reduces benign cyst resection. The low inter-observer agreement remains a challenge to the updated classification system.

Anesthesia and surgery induce changes in endogenous brain protective protein (RNF146) and delirium-like behavior in aged rats.

BACKGROUND: Postoperative delirium (POD) is a common complication after anesthesia and surgery, especially in the elderly. RNF146 has neuroprotective effects in cerebral ischemia, hypoxia, and chronic neurological diseases. However, whether RNF146 expression is related to the occurrence and development of POD remains unclear. Therefore, in this study, we aimed to determine whether RNF146 is involved in the occurrence of POD. METHODS: (Sprague-Dawley) male rats (18 months old) were splenectomized under sevoflurane anesthesia. The cognitive function of rats at 1, 3, and 7 d after anesthesia and surgery was evaluated. Changes in the expression of neuroinflammatory cytokines, IL-6 and IL-10, and RNF146 were measured in the hippocampus in both control group (con) and anesthesia (AS) group. We examined cognitive outcomes and expression of inflammatory factors and RNF146 in con and AS mice using cluster analysis. RESULTS: The cognitive ability and mobility of rats after anesthesia and surgery at day 1, 3, and 7 decreased, especially at day 3. Similarly, the expression of neuroinflammatory factors and RNF146 increased after anesthesia and surgery at day 1, 3, and 7, and the increase was highest at day 3. The clustering and correlation analysis of RNF146 expression in the hippocampi of elderly rats revealed a correlation between POD and neuroinflammation resulting from anesthesia and surgery. CONCLUSION: Anesthesia and surgery can lead to POD and neuroinflammation. The expression of RNF146 correlates with delirium and neuroinflammation caused by anesthesia and surgery.

Exosome and lipid metabolism-related genes in pancreatic adenocarcinoma: a prognosis analysis.

OBJECTIVE: The purpose of the study was to investigate the role of exosome and lipid metabolism-related genes (EALMRGs) mRNA levels in the diagnosis and prognosis of Pancreatic Adenocarcinoma (PAAD). METHODS: The mRNA expression pattern of PAAD and pan-cancers with prognostic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. EALMRGs were acquired from GeneCards and MSigDB database after merging and deduplication. Prognostic EALMRGs were screened through univariate COX regression analysis, and a prognostic model was constructed based on these genes by least absolute shrinkage and selection operator (LASSO) regression. The prognostic value of EALMRGs was then validated in pan-cancer data. The time characteristics ROC curve analysis was performed to evaluate the effectiveness of the prognostic genes. RESULTS: We identified 5 hub genes (ABCB1, CAP1, EGFR, PPARG, SNCA) according to high and low-risk groups of prognoses. The risk formula was verified in three other cohort of pancreatic cancer patients and was explored in pan-cancer data. Additionally, T cell and dendritic cell infiltration was significantly increased in low-risk group. The expression of the 5 hub genes was also identified in single-cell sequencing data of pancreatic cancer with pivotal pathways. Additionally, functional enrichment analysis based on pancreatic cancer data in pancreatic cancer showed that protein serine/threonine kinase activity, focal adhesion, actin binding, cell-substrate junction, organic acid transport, and regulation of transporter activity were significant related to the expression of genes in EALMRGs. CONCLUSIONS: Our risk formula shows potential prognostic value in multiple cancers and manifest pivotal alterations in immune infiltration and biological pathway in pancreatic cancer.

Immune regulation in gastric adenocarcinoma is linked with therapeutic efficacy and improved recovery.

Adenocarcinomas are one of the most common histological types of gastric cancer. It has been ranked fifth among common cancers and is the third among death causing cancers worldwide. The high mortality rate among patients with gastric cancer is because of its silent evolution, genetic heterogeneity, high resistance to chemotherapy as well as unavailability of highly effective therapeutic strategy. Until now a number of several treatment strategies have been developed and are being practiced such as surgery, chemotherapy, radio therapy, and immunotherapy, however, further developments are required to improve the treatment responses and reduce the side effects. Therefore, novel personal therapeutic strategies based on immunological responses should be developed by targeting different check points and key immune players. Targeting macrophages and related molecular elements can be useful to achieve these goals. In this minireview, we discuss the available treatment options, molecular underpinnings and immunological regulations associated with gastric adenocarcinoma. We further describe the possible check points and immunological targets that can be used to develop novel therapeutic options.

Comparative Assessment of Different Ultrasound Technologies in the Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.

The present study aimed to assess the diagnostic test accuracy of different ultrasound scanning technologies in the detection of prostate cancer. A systematic search was conducted using the Cochrane Guidelines for Screening and Diagnostic Tests. We performed a systematic search in the international databases PubMed, Medline, Ovid, Embase and Cochrane Library. Searches were designed to find all studies that evaluated Micro-US, mpUS, SWE and CEUS as the main detection modalities for prostate cancer. This study was registered with Research Registry of systematic review and meta-analysis. The QUADAS-2 tool was utilized to perform quality assessment and bias analysis. The literature search generated 1376 studies. Of these, 320 studies were screened for eligibility, with 1056 studies being excluded. Overall, 26 studies with a total of 6370 patients met the inclusion criteria. The pooled sensitivity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.66 (95% CI 0.54-0.73) 0.73 (95% CI 0.58-0.88), 0.82 (95% CI 0.75-0.90), 0.85 (95% CI 0.76-0.94) and 0.87 (95% CI 0.71-1.03), respectively. Moreover, the pooled specificity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.56 (95% CI 0.21-0.90), 0.78 (95% CI 0.67-0.88), 0.76 (95% CI 0.65-0.88), 0.43 (95% CI 0.28-0.59) and 0.68 (95% CI 0.54-0.81), respectively. In terms of sensitivity, substantial heterogeneity between studies was detected (I2 = 72%, p = 0.000 < 0.05). In relation to specificity, extreme heterogeneity was detected (I2 = 93%, p = 0.000 < 0.05). Some studies proved that advanced ultrasound modalities such as mpUS, Micro-US, shear-wave elastography, contrast enhanced and micro-ultrasound are promising methods for the detection of prostate cancer.

Circadian rhythm as a key player in cancer progression as well as a therapeutic target in HER2-positive advanced gastric cancer treatment.

Gastric cancer is one of the most common cancer types with less than one year prognosis in metastatic disease, which poses a huge disease burden. One of the key players in poor prognosis is human epidermal growth factor receptor 2 (HER2), which also contributes to the pathogenesis of HER2-positive advanced gastric cancer. Trastuzumab is used as first-line chemotherapy that targets the expression of HER2, however, trastuzumab resistance is an inevitable major problem. To overcome this problem, readjustment of the circadian system may play a crucial role, as dysregulation in the expression of circadian clock genes has been observed in tumors. Therefore, pharmacological modulation of clock components can be considered for better efficacy of trastuzumab. In this review, we discuss the association of circadian clock with cancer progression, development, and treatment. Metformin-based chronotherapy can disrupt BMAL1-CLOCK-PER1-HK2 axis, thereby affecting glycolysis oscillation to overcome trastuzumab resistance in HER2-positive advanced gastric cancer.

Multicenter Randomized Trial Assessing MRI and Image-guided Biopsy for Suspected Prostate Cancer: The MULTIPROS Study.

Background The optimal diagnostic pathway for prostate cancer (PCa) is evolving, requiring further evaluation in a randomized controlled trial. Purpose To assess the diagnostic accuracy of prebiopsy multiparametric MRI in the identification of clinically significant PCa (csPCa) using radical prostatectomy (RP) specimens as the reference standard, and to test the diagnostic accuracy of combined US and MRI fusion-targeted biopsy with systematic biopsies. Materials and Methods In a prospective randomized controlled trial including university hospitals, men with suspected PCa were recruited between January 2015 and August 2020 to assess the diagnostic accuracy of multiparametric MRI before biopsy in detection of csPCa at biopsy and RP histopathologic structure (primary outcome). Men with lesions suspicious for cancer (Prostate Imaging and Reporting Data System [PI-RADS] ≥3) at multiparametric MRI were first randomized to either systematic random prostate biopsies alone (control group) or US and MRI fusion-targeted biopsies with systematic random prostate biopsies (intervention group) at a one-to-one ratio to compare the diagnostic accuracy of systematic random versus combined fusion with systematic random biopsies (secondary outcome). A subset of recruited participants (n = 89) underwent RP and histologic sectioning. Results There were 582 participants who were eligible to undergo multiparametric MRI (mean age, 65 years ± 6 [SD]). In total, 413 had a PI-RADS score of at least 3 and were randomized into either the intervention group (207 of 413; 50.1%) or control group (206 of 413; 49.9%). The csPCa detection rate in the intervention group was higher, with an adjusted odds ratio of 1.79 (95% CI: 1.14, 2.79; P = .01). A subgroup of 89 men underwent RP (21.5%; 89 of 413). Multiparametric MRI helped correctly identify 131 of 182 csPCa foci in 89 men (sensitivity, 72%; 95% CI: 65, 78). The specificity, positive predictive value, and negative predictive value were 71% (91 of 128), 78% (131 of 168), and 64% (91 of 142), respectively. Conclusion Prebiopsy multiparametric MRI was accurate in the depiction of clinically significant PCa. Combining US and MRI fusion-targeted biopsies with systematic biopsies helped detect more clinically significant lesions than did systematic biopsies alone. Clinical trial registration no. NCT02745496 © RSNA, 2023 Supplemental material is available for this article.

Preoperative imaging accuracy in size determination of prostate cancer in men undergoing radical prostatectomy for clinically localised disease.

OBJECTIVES: To compare the accuracy of pre-surgical prostate size measurements using mpMRI and USWE with imaging-based 3D-printed patient-specific whole-mount moulds facilitated histopathology, and to assess whether size assessment varies between clinically significant and non-significant cancerous lesions including their locations in different zones of the prostate. METHODS: The study population included 202 men with clinically localised prostate cancer opting for radical surgery derived from two prospective studies. Protocol-based imaging data was used for measurement of size of prostate cancer in clinically localised disease using MRI (N = 106; USWE (N = 96). Forty-eight men overlapped between two studies and formed the validation cohort. The primary outcome of this study was to assess the accuracy of pre-surgical prostate cancerous size measurements using mpMRI and USWE with imaging-based 3D-printed patient-specific whole-mount moulds facilitated histopathology as a reference standard. Independent-samples T-tests were used for the continuous variables and a nonparametric Mann-Whitney U test for independent samples was applied to examine the distribution and median differences between mpMRI and USWE groups. RESULTS: A significant number of men had underestimation of prostate cancer using both mpMRI (82.1%; 87/106) and USWE (64.6%; 62/96). On average, tumour size was underestimated by a median size of 7 mm in mpMRI, and 1 mm in USWE. There were 327 cancerous lesions (153 with mpMRI and 174 for USWE). mpMRI and USWE underestimated the majority of cancerous lesions (108/153; 70.6%) and (88/174; 50.6%), respectively. Validation cohort data confirmed these findings MRI had a nearly 20% higher underestimation rate than USWE (χ2 (1, N = 327) = 13.580, p = 0.001); especially in the mid and apical level of the gland. Clinically non-significant cancers were underestimated in significantly higher numbers in comparison to clinically significant cancers. CONCLUSIONS: Size measurement of prostate cancers on preoperative imaging utilising maximum linear extent technique, underestimated the extent of cancer. Further research is needed to confirm our observations using different sequences, methods and approaches for cancer size measurement.

Venous Thromboembolism (VTE) in Post-Prostatectomy Patients: Systematic Review and Meta-Analysis.

Radical prostatectomy (RP) is one of the recommended treatments to achieve oncological outcomes in localized prostate cancer. However, a radical prostatectomy is a major abdominopelvic surgery. Venous thromboembolism (VTE) is a well-known complication associated with surgical procedures, including RP. There is a lack of consensus regarding VTE prophylaxis in urological procedures. The aim of this systematic review and meta-analysis was to investigate different aspects of VTE in post-radical prostatectomy patients. A comprehensive literature search was performed, and relevant data were extracted. The primary aim was to perform a systematic review and meta-analysis (wherever possible) of VTE occurrence in post-RP patients in relation to surgical approach, pelvic lymph node dissection, and type of prophylaxis (mechanical or combined prophylaxis). The secondary aim was to investigate the incidence and other risk factors of VTE in post-RP patients. A total of 16 studies were included for quantitative analysis. Statistical methods for analysis included the DerSimonian-Laird random effects. We were able to conclude that the overall incidence of VTE in post-radical prostatectomy is 1% (95% CI) and minimally invasive procedures (MIS), including laparoscopic, as well as robotic procedures for radical prostatectomy and RP without pelvic lymph node dissection (PLND), are associated with less risk of developing VTE. Additional pharmacological prophylaxis to mechanical methods may not be necessary in all cases and should be considered in high-risk patients only.

Radiogenomics Reveals Correlation between Quantitative Texture Radiomic Features of Biparametric MRI and Hypoxia-Related Gene Expression in Men with Localised Prostate Cancer.

OBJECTIVES: To perform multiscale correlation analysis between quantitative texture feature phenotypes of pre-biopsy biparametric MRI (bpMRI) and targeted sequence-based RNA expression for hypoxia-related genes. MATERIALS AND METHODS: Images from pre-biopsy 3T bpMRI scans in clinically localised PCa patients of various risk categories (n = 15) were used to extract textural features. The genomic landscape of hypoxia-related gene expression was obtained using post-radical prostatectomy tissue for targeted RNA expression profiling using the TempO-sequence method. The nonparametric Games Howell test was used to correlate the differential expression of the important hypoxia-related genes with 28 radiomic texture features. Then, cBioportal was accessed, and a gene-specific query was executed to extract the Oncoprint genomic output graph of the selected hypoxia-related genes from The Cancer Genome Atlas (TCGA). Based on each selected gene profile, correlation analysis using Pearson's coefficients and survival analysis using Kaplan-Meier estimators were performed. RESULTS: The quantitative bpMR imaging textural features, including the histogram and grey level co-occurrence matrix (GLCM), correlated with three hypoxia-related genes (ANGPTL4, VEGFA, and P4HA1) based on RNA sequencing using the TempO-Seq method. Further radiogenomic analysis, including data accessed from the cBioportal genomic database, confirmed that overexpressed hypoxia-related genes significantly correlated with a poor survival outcomes, with a median survival ratio of 81.11:133.00 months in those with and without alterations in genes, respectively. CONCLUSION: This study found that there is a correlation between the radiomic texture features extracted from bpMRI in localised prostate cancer and the hypoxia-related genes that are differentially expressed. The analysis of expression data based on cBioportal revealed that these hypoxia-related genes, which were the focus of the study, are linked to an unfavourable survival outcomes in prostate cancer patients.