Smoking’s Negative Effect on Pathological Grade and Stage in Patients with Primary, Single, < 3cm Bladder Cancer

Introduction: We investigated the potential effect of smoking on pathological staging in clinically low-risk patients. Material-Methods: Data of 59 patients who were diagnosed with a bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated, retrospectively. A total of 33 patients who currently smoke or smoked were classified as ever smokers group and 26 patients who did not ever smoke were classified as never smokers group. Pathological diagnoses of the patients in both groups were compared. Results: A total of 9 patients (27.3%) in ever smokers group and 18 patients (69.2%) in never smokers group had Ta disease (p<0.05). Morover, 19 patients (57.6%) in ever smokers group and 5 patients (19.2%) in never smokers group had T1 disease (p<0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in ever smoking and never smoking groups, respectively (p<0.05). The number of patients with high grade (HG) tumor were 25 (75.8%) and 7 (26.9%) in ever smoking and never smoking groups, respectively (p<0.05). Ta HG was detected in 9 (27.3%) patients in ever smoking group. In contrast, no patients in never smoking group had Ta HG disease (p<0.05). The number of patients with T1 HG was 17 (51.5%) in ever smoking group and 2 (7.69%) in never smoking group (p<0.05). Conclusion:Smoking seems to associate with pathologically worse stage and grade in patients with primary, single, < 3cm bladder cancer.

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Effect of Smoking on Pathological Grade and Stage in Clinically Low-Risk Patients

10.20944/preprints201805.0320.v1 ◽

2018 ◽

Author(s):

Ercan Öğreden ◽

Ural Oğuz ◽

Erhan Demirelli ◽

Orhan Yalçın

Keyword(s):

Bladder Tumor ◽

Low Risk ◽

Low Grade ◽

Group I ◽

Number Of Patients ◽

Risk Patients ◽

The Mean ◽

Group Ii ◽

First Time ◽

Single Lesion

AbstractWe investigated the effect of cigarette smoking on pathological staging in clinically low-risk patients. Data of 59 patients who were diagnosed with bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated retrospectively. 33 patients who smoked were classified as Group I, and 26 patients who did not smoke were classified as Group II. Pathological diagnoses of the patients in both groups were compared. The mean age of the patients were 64.8 (20–86) years. In Group II, 5 (19.2%) were female and 21 (80.8%) were male (p < 0.05). Nine patients (27.3%) in Group I and 18 patients (69.2%) in Group II had Ta disease (p < 0.05). Nineteen patients (57.6%) in Group I and 5 patients (19.2%) in Group II had T1 disease (p < 0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in Group I and in Group II, respectively (p < 0.05). The number of patients with high grade(HG) tumor were 25 (75.8%) and 7 (26.9%) in Group I and in Group II, respectively (p < 0.05). TaHG was detected in 9 (27.3%) patients in Group I. In contrast, no patients in Group II had TaHG disease (p < 0.05). The number of patients with T1HG was 17(51.5%) patients in Group I and 2 (7.69%) patients in Group II (p < 0.05). Smoking is associated with pathologically HG and stage in patients with first time bladder tumor which is single and smaller than 3 cm.

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466 Surveillance Flexible Cystoscopy in Bladder Cancer Follow-up

British Journal of Surgery ◽

10.1093/bjs/znab259.055 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

D Goodman ◽

R Taggart ◽

J Salmond ◽

E H Day

Keyword(s):

Bladder Cancer ◽

Low Risk ◽

Cancer Surveillance ◽

Low Grade ◽

Intermediate Risk ◽

Less Is More ◽

Upper Tract ◽

Risk Patients ◽

Disease Free

Abstract Aim This study addresses surveillance cystoscopy in patients diagnosed with bladder and upper tract cancer. Managed Clinical Network (MCN) guidelines have clear recommendations for the timetable of follow-up cystoscopy, and we conducted this audit to study regional compliance. Method Using a multisite pathology database of bladder cancer cases from 2016, we collected and analysed data on 100 non-muscle invasive bladder cancers. We took the first 10 cases from each month to ensure cross-regional representation. Each case was stratified according to MCN guidelines. Electronic medical records were examined to assess upper tract follow up. We allowed for +/- 1 month each side of the target timeframe. Results We had 64 male and 36 female subjects. In our risk categories, we had 31 low risk, 37 intermediate risk and 32 high risk bladder cancers. 67 were new cases, 33 were recurrent tumours. 10 (43.4%) of low-risk and 19 (79.2%) of intermediate-risk patients underwent surveillance cystoscopy earlier than the recommended 12-month timeframe. 18 (78.3%) of low-risk patients continued to have further surveillance cystoscopies after a 12-month disease-free period. Conclusions 43.4% of low-risk bladder cancer patients are receiving surveillance cystoscopy earlier than recommended. 78.3% of these patients are then undergoing unnecessary procedures following a 12-month disease-free period against regional guidelines and recommendations. This places an increased burden on clinic/theatre time and contributes to patient anxiety surrounding cancer follow-up. Evidence-based medicine guidelines have shown that less is more when it comes to low-grade bladder cancer surveillance. We now need to assess why we are deviating from our own guidelines.

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Improving the inclusion rate in clinical trials of bladder cancer despite COVID-19 pandemic by using ASCO quality training program.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18674 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18674-e18674

Author(s):

Natalia Vidal ◽

Juan Gomez ◽

Isabel Galante ◽

Jose Luis Senovilla ◽

Jose-Luis Gonzalez-Larriba ◽

...

Keyword(s):

Bladder Cancer ◽

Clinical Trials ◽

Training Program ◽

Cancer Patients ◽

Stage Iv ◽

Invasive Disease ◽

Enrollment Rate ◽

Number Of Patients ◽

Inclusion Rate ◽

First Time

e18674 Background: In 2019, we used the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP) as an instrument to improve the inclusion rate in clinical trials (CTs) for bladder cancer patients from 24% in 2018 to 43,75% in 2019. CTs play an important role in developing new treatments, expanding or refining treatments that are already available, and/or identifying behavioral changes that can prolong or improve the lives of subjects. Therefore, we believe it is important for patients and for society to maintain the inclusion rate in clinical trials despite COVID-19 pandemic. Methods: We collected the number of bladder cancer patients evaluated for the first time in the Oncology department, the number of patients who were offered a clinical trial, the screen failures and the number of patients enrolled in CTs. Results: In 2019, we were able to increase the enrollment rate in CTs for bladder cancer patients to from 24% to 43,75% thanks to the ASCO-QTP. With this program we created a list of measures and identified the ones that would have a greater impact. The one that seems to have had the highest impact is the diffusion of CTs in the Investigation Unit and the Genitourinary (GU) board. In 2020, thanks to this measure and despite the COVID-19 pandemic, we were able to maintain a 40,81% enrollment rate. When analyzing the patients evaluated for the first time in the Oncology department, 48 in 2019 and 49 in 2020, there were some interesting differences. In 2020, 42,86% had stage IV disease with respect to 39,6% in 2019, and only 22,44% had non-muscle invasive disease (NMIBC) versus 33,33% in 2019. However, thanks to the diffusion of CTs in the Investigation Unit and in the GU-board, which translates in an early derivation of patients to Medical Oncology and an increase in the number of available CTs, we were able to offer a CT to 73,5% of patients in 2020 against 60,4% in 2019. Although there was an increase of screen failures in 2020 (32,65% vs. 16,66%), 50% of them were due to the absence of a biomarker in a biomarker driven CT, with respect to 25% in 2019. Conclusions: Using ASCO-QTP as an instrument, we identified the importance of the diffusion of CTs and the close collaboration between departments. Maintaining these measures, we were able to uphold the inclusion rate in CTs for bladder cancer patients in 40,81% despite the later diagnosis of patients due to COVID-19 pandemic.

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A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer

Clinical Epigenetics ◽

10.1186/s13148-021-01073-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Weimei Ruan ◽

Xu Chen ◽

Ming Huang ◽

Hong Wang ◽

Jiaxin Chen ◽

...

Keyword(s):

Dna Methylation ◽

Bladder Cancer ◽

Risk Stratification ◽

Early Stage ◽

Operative Risk ◽

Low Grade ◽

Single Center ◽

Detection Model ◽

Methylation Assay ◽

Muscle Invasive

Abstract Background Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. Methods A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. Results The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7–77.8% vs. 0.0–22.2%, 0.0–22.2%), Ta tumor (83.3% vs. 22.2–41.2%, 44.4–52.9%) and non-muscle invasive BC (NMIBC) (80.0–89.7% vs. 51.5–52.0%, 59.4–72.0%) in both cohorts. The assay also had higher accuracies (88.9–95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6–70.8%) and FISH (72.2–77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. Conclusions The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

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Diagnostic Value of Telomerase Activity in Patients With Bladder Cancer: A Meta-Analysis of Diagnostic Test

Frontiers in Oncology ◽

10.3389/fonc.2020.570127 ◽

2020 ◽

Vol 10 ◽

Author(s):

Lei Peng ◽

Jinze Li ◽

Chunyang Meng ◽

Jinming Li ◽

Dandan Tang ◽

...

Keyword(s):

Bladder Cancer ◽

Subgroup Analysis ◽

Meta Analysis ◽

Negative Likelihood Ratio ◽

High Specificity ◽

Diagnostic Value ◽

Telomerase Activity ◽

Low Grade ◽

Potential Biomarker ◽

Significant Difference

BackgroundThis study aimed to evaluate the diagnostic value of telomerase activity (TA) for bladder cancer (BC) by meta-analysis.MethodsWe conducted a systematic search of studies published on PubMed, Embase, and Web of Science up to June 1, 2019. We used Stata 15 and Review Manager 5.3 for calculations and statistical analysis.ResultsTo evaluate the diagnostic value of TA for BC, we performed a meta-analysis on 22 studies, with a total of 2,867 individuals, including sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR), and 95% confidence intervals (CIs). The pooled parameters were calculated from all studies, and we found a sensitivity of 0.79 (95% CI: 0.72–0.84), a specificity of 0.91 (95% CI: 0.87–0.94), a PLR of 8.91 (95% CI: 5.91–13.43), an NLR of 0.24 (95% CI: 0.15–0.37), a DOR of 37.90 (95% CI: 23.32–61.59), and an AUC of 0.92 (95% CI: 0.90–0.94). We also conducted a subgroup analysis based on the different stages and grades of BC. Results from the subgroup analysis showed that there was no significant difference in TA in either high and low stages of BC, but that low-grade tumors had a lower TA than high-grade tumours.ConclusionsTA can be used as a potential biomarker for the diagnosis of bladder cancer with its high specificity. Rigorous and high-quality prospective studies are required to verify our conclusion.

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Specific Seminal Plasma Fractions Are Responsible for the Modulation of Sperm–PMN Binding in the Donkey

Animals ◽

10.3390/ani11051388 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1388

Author(s):

Jordi Miró ◽

Jaime Catalán ◽

Henar Marín ◽

Iván Yánez-Ortiz ◽

Marc Yeste

Keyword(s):

Molecular Weight ◽

Sperm Motility ◽

Seminal Plasma ◽

Potential Effect ◽

Polymorphonuclear Neutrophils ◽

Low Fertility ◽

Plasma Fractions ◽

Complex Fluid ◽

First Time

While artificial insemination (AI) with frozen-thawed sperm results in low fertility rates in donkeys, the addition of seminal plasma, removed during cryopreservation, partially counteracts that reduction. Related to this, an apparent inflammatory reaction in jennies is induced following AI with frozen-thawed sperm, as a high amount of polymorphonuclear neutrophils (PMN) are observed within the donkey uterus six hours after AI. While PMN appear to select the sperm that ultimately reach the oviduct, two mechanisms, phagocytosis and NETosis, have been purported to be involved in that clearance. Remarkably, sperm interacts with PMN, but the presence of seminal plasma reduces that binding. As seminal plasma is a complex fluid made up of different molecules, including proteins, this study aimed to evaluate how different seminal plasma fractions, separated by molecular weight (<3, 3–10, 10–30, 30–50, 50–100, and >100 kDa), affect sperm–PMN binding. Sperm motility, viability, and sperm–PMN binding were evaluated after 0 h, 1 h, 2 h, 3 h, and 4 h of co-incubation at 38 °C. Two seminal plasma fractions, including 30–50 kDa or 50–100 kDa proteins, showed the highest sperm motility and viability. As viability of sperm not bound to PMN after 3 h of incubation was the highest in the presence of 30–50 and 50–100 kDa proteins, we suggest that both fractions are involved in the control of the jenny’s post-breeding inflammatory response. In conclusion, this study has shown for the first time that specific fractions rather than the entire seminal plasma modulate sperm–PMN binding within the donkey uterus. As several proteins suggested to be involved in the control of post-AI endometritis have a molecular weight between 30 and 100 kDa, further studies aimed at determining the identity of these molecules and evaluating their potential effect in vivo are much warranted.

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A prospective observational study on oral administration of Ellagic Acid and Annona Muricata in patients affected by non-muscle invasive bladder cancer not undergoing maintenance after 6-week intravesical prophylaxis

Urologia Journal ◽

10.1177/03915603211022285 ◽

2021 ◽

pp. 039156032110222

Author(s):

Vincenzo Serretta ◽

Ettore De Berardinis ◽

Alchiede Simonato ◽

Alessio Guarneri ◽

Nino Dispensa ◽

...

Keyword(s):

Bladder Cancer ◽

Oral Administration ◽

Ellagic Acid ◽

Invasive Bladder Cancer ◽

Prophylactic Effect ◽

Annona Muricata ◽

Muscle Invasive Bladder Cancer ◽

Number Of Patients ◽

Muscle Invasive

Introduction: BCG and MMC shortage and Covid-19 pandemic, more recently, limit accessibility to maintenance regimen in intravesical prophylaxis against recurrence of non-muscle invasive bladder cancer (NMIBC). Ellagic acid (EA) and Annona muricata (AM) exert antitumor activity against different human tumours. An observational prospective study on the prophylactic effect of oral administration of EA+AM in patients avoiding maintenance regimen is presented. Materials and methods: Patients affected by NMIBC and not undergoing maintenance after a 6-week course of intravesical prophylaxis with MMC or BCG were entered. Tis and very high-risk tumours were excluded. After informed consent, the patients were subdivided in relation to the oral assumption or not of EA (100 mg) plus AM (100 mg), daily for 6 months. All patients were submitted to 3-month cytology and cystoscopy. Results: 162 (90%) of 180 entered patients are evaluable, 90 and 72 receiving or not EA+AM. No difference emerged in patients’ characteristics between the two groups. BCG was given in 86 (54%) and chemotherapy in 74 (46%) patients. The recurrence free rate at 3, 6 and 12 months in patients assuming or not EA was 96.5% versus 84.6% ( p = 0.003), 85.4% versus 64.8% ( p = 0.005) and 74.2% versus 60.6% ( p = 0.246), respectively. The recurrence free survival at 12 months in patients assuming or not EA was 63.0% versus 34.5% ( p < 0.0001). Discussion and conclusions: Our study suffers several limits: not randomized trial although prospective, limited number of patients and short follow-up, nevertheless it shows the prophylactic effect of oral EA+AM in absence of maintenance after intravesical chemotherapy or immunotherapy induction.

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Alternating Cystoscopy with Bladder EpiCheck ® in the Surveillance of Low-Grade Intermediate-Risk NMIBC: A Cost Comparison Model

Bladder Cancer ◽

10.3233/blc-211528 ◽

2021 ◽

pp. 1-9

Author(s):

Yair Lotan ◽

Georgios Gakis ◽

Matteo Manfredi ◽

Juan Morote ◽

Hugh Mostafid ◽

...

Keyword(s):

Bladder Cancer ◽

High Specificity ◽

Cancer Surveillance ◽

European Countries ◽

Cost Comparison ◽

Sensitivity Analyses ◽

Low Grade ◽

Intermediate Risk ◽

Tree Model ◽

Urine Marker

BACKGROUND: Bladder cancer surveillance is invasive, intensive and costly. Patients with low grade intermediate risk non-muscle invasive bladder cancer (NMIBC) are at high risk of recurrence. OBJECTIVE: The objective of this model is to compare the cost of a strategy to alternate surveillance with cystoscopy and a urine marker, Bladder EpiCheck, to standard surveillance. METHODS: A decision tree model was built using TreeAge Pro Healthcare to compare standard surveillance (Standard) with a modified surveillance incorporating Bladder EpiCheck. The model was based on 2 years of surveillance. Outcomes were obtained from literature. Costs were obtained from US and 9 European countries. Sensitivity analyses were performed. RESULTS: The efficacy of the model was equivalent in terms of recurrence for each arm with median recurrence rate of 22%. When setting marker price at 200 local currency, the marker arm was less expensive in the USA, Netherlands, Switzerland, Belgium, Italy, Austria and UK by 154€ to 329€ per patient, for a 2-year period. Cost was higher in France, Spain, and Germany by 33–103€. Cost parity was achieved with marker price between 148€ and $421. Marker cost and specificity have the greatest impact on the overall model cost. CONCLUSIONS: A strategy alternating the urine marker Bladder EpiCheck with cystoscopy in the surveillance of patients with low grade intermediate risk bladder cancer is cost equivalent in the US and European countries when the marker is priced 148€ –$421, as a result of the marker’s high specificity (86%). Prospective studies will be necessary to validate these findings.

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The Remarkable Antioxidant and Anti-Inflammatory Potential of the Extracts of the Brown Alga Cystoseira amentacea var. stricta

Marine Drugs ◽

10.3390/md19010002 ◽

2020 ◽

Vol 19 (1) ◽

pp. 2

Author(s):

Gina De La Fuente ◽

Marco Fontana ◽

Valentina Asnaghi ◽

Mariachiara Chiantore ◽

Serena Mirata ◽

...

Keyword(s):

Oxidative Stress ◽

No Production ◽

Low Grade ◽

Raw 264.7 ◽

Ros Scavenging ◽

Ligurian Sea ◽

Raw 264.7 Macrophages ◽

Pharmaceutical Industries ◽

Anti Inflammatory ◽

First Time

Inflammation and oxidative stress are part of the complex biological responses of body tissues to harmful stimuli. In recent years, due to the increased understanding that oxidative stress is implicated in several diseases, pharmaceutical industries have invested in the research and development of new antioxidant compounds, especially from marine environment sources. Marine seaweeds have shown the presence of many bioactive secondary metabolites, with great potentialities from both the nutraceutical and the biomedical point of view. In this study, 50%-ethanolic and DMSO extracts from the species C. amentacea var. stricta were obtained for the first time from seaweeds collected in the Ligurian Sea (north-western Mediterranean). The bioactive properties of these extracts were then investigated, in terms of quantification of specific antioxidant activities by relevant ROS scavenging spectrophotometric tests, and of anti-inflammatory properties in LPS-stimulated macrophages by evaluation of inhibition of inflammatory cytokines and mediators. The data obtained in this study demonstrate a strong anti-inflammatory effect of both C. amentacea extracts (DMSO and ethanolic). The extracts showed a very low grade of toxicity on RAW 264.7 macrophages and L929 fibroblasts and a plethora of antioxidant and anti-inflammatory effects that were for the first time thoroughly investigated. The two extracts were able to scavenge OH and NO radicals (OH EC50 between 392 and 454 μg/mL; NO EC50 between 546 and 1293 μg/mL), to partially rescue H2O2-induced RAW 264.7 macrophages cell death, to abate intracellular ROS production in H2O2-stimulated macrophages and fibroblasts and to strongly inhibit LPS-induced inflammatory mediators, such as NO production and IL-1α, IL-6, cyclooxygenase-2 and inducible NO synthase gene expression in RAW 264.7 macrophages. These results pave the way, for the future use of C. amentacea metabolites, as an example, as antioxidant food additives in antiaging formulations as well as in cosmetic lenitive lotions for inflamed and/or damaged skin.

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Imaging of Bladder Cancer: Standard Applications and Future Trends

Medicina ◽

10.3390/medicina57030220 ◽

2021 ◽

Vol 57 (3) ◽

pp. 220

Author(s):

Rasha Taha Abouelkheir ◽

Abdalla Abdelhamid ◽

Mohamed Abou El-Ghar ◽

Tarek El-Diasty

Keyword(s):

Bladder Cancer ◽

Malignant Tumors ◽

Cancer Staging ◽

Low Grade ◽

Diagnostic Modality ◽

Positron Emission ◽

Standard Application ◽

Muscle Invasive ◽

Muscle Invasion ◽

Low Sensitivity

The evolution in imaging has had an increasing role in the diagnosis, staging and follow up of bladder cancer. Conventional cystoscopy is crucial in the diagnosis of bladder cancer. However, a cystoscopic procedure cannot always depict carcinoma in situ (CIS) or differentiate benign from malignant tumors prior to biopsy. This review will discuss the standard application, novel imaging modalities and their additive role in patients with bladder cancer. Staging can be performed with CT, but distinguishing between T1 and T2 BCa (bladder cancer) cannot be assessed. MRI can distinguish muscle-invasive from non-muscle-invasive tumors with accurate local staging. Vesical Imaging-Reporting and Data System (VI-RADS) score is a new diagnostic modality used for the prediction of tumor aggressiveness and therapeutic response. Bone scintigraphy is recommended in patients with muscle-invasive BCa with suspected bony metastases. CT shows low sensitivity for nodal staging; however, PET (Positron Emission Tomography)/CT is superior and highly recommended for restaging and determining therapeutic effect. PET/MRI is a new imaging technique in bladder cancer imaging and its role is promising. Texture analysis has shown significant steps in discriminating low-grade from high-grade bladder cancer. Radiomics could be a reliable method for quantitative assessment of the muscle invasion of bladder cancer.

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