Comparing fluorodeoxyglucose positron emission tomography with computed tomography in staging for nodal and distant metastasis in urothelial/bladder cancer.

Objectives: We aim to assess the clinical value of 18F-fluorodeoxyglucose positron (18F-FDG-PET) scan in detecting nodal and distant metastasis compared with computed tomography (CT) scan in patients with urothelial carcinoma or bladder cancer, aiming to improve staging accuracy and thereby better prognosticate and determine therapy. Methods: A retrospective review of 75 patients with invasive bladder cancer (≥T1) who were staged with both CT and 18F-FDG-PET within an 8-week interval was performed for the period between 2015 and 2020. Seventy-two per cent (54/75) had formal pelvic lymph node (LN) dissection or biopsy of lesions suspicious for metastases. FDG-PET definitions for positive sites were assessed depending on SUV Max (nodes with SUVmax >4 at any size, SUV > 2 for lymph nodes >8 mm, or any SUV if the lymph node was >10 mm on axial images). For CT scanning, enlarged LN by RECIST 1.1 criteria (>10 mm) as well as qualitative findings suggesting metastasis were considered positive. The analysis was based on the comparison of CT and 18F-FDG-PET findings to histopathology results from LN dissection or biopsies. Results: Sensitivity, specificity, positive predictive values (PPV) and negative predictive value (NPV) of CT versus FDG-PET for detecting metastasis, in patients who underwent pelvic LN dissection or biopsy of lesions suspicious of metastases, were 46.6% (95% CI: 21%-70%) versus 60% (95% CI: 32%-84%), 100% (95% CI: 91%-100%) versus 83.78% (95% CI: 69%-94%), 100% (95% CI: 63%-100%) versus 60% (95% CI: 32%-84%), and 82.2% (95% CI: 68%-92%) versus 83.78% (95% CI: 69%-94%), respectively. 7/75 (9.3%) patients avoided cystectomy due to 18F-FDG-PET features of metastases that were not detected by CT. Conclusion: FDG-PET may be more sensitive than CT for metastases in the staging of bladder cancer, which resulted in significant avoidance of aggressive local management in cases with occult metastasis.

Antibiotic use reduces the efficacy of immune checkpoint inhibitors in patients with urothelial carcinoma: A systematic review and meta-analysis.

CONTEXT: Antibiotics have been suggested to diminish the efficacy of immune checkpoint inhibitors (ICIs) by alterations of the gut microbiota. OBJECTIVE: To perform a meta-analysis summarizing the effect of antibiotics on the overall survival (OS) and progression-free survival (PFS) of urothelial cancer (UC) patients receiving ICI. EVIDENCE ACQUISITION: PubMed, EMBASE (Ovid), and the Cochrane Library were searched to identify studies published up to July 14, 2023. Studies reporting the associations between antibiotics use and OS and PFS in UC patients treated with ICI were included in this systematic review and meta-analysis. The random-effect model was used to pool the Hazard Ratios (HRs) for OS and PFS with 95% confidence interval (95%CI). The ROBINS-I was used to assess the risk of bias in the included studies, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to inform the quality of evidence. EVIDENCE SYNTHESIS: Thirteen nonrandomized studies involving a total of 5,095 ICI-treated UC patients were included in this review, of which 1434 (28%) received antibiotics. Overall, compared to patients who did not receive antibiotics, the pooled HRs for OS and PFS in those who received antibiotics were 1.45 [95% CI 1.25-1.68] and 1.40 [95% CI 1.05-1.87], respectively. Subgroup analysis revealed that the types of ICI and timing of antibiotic initiation did not influence the effect of antibiotics on OS and PFS in UC patients (P > 0.05). CONCLUSIONS: Antibiotic use significantly reduced OS and PFS in UC patients receiving ICI. While antibiotics remain crucial for the treatment of infections in UC patients, antibiotics should be prescribed cautiously in UC patients receiving ICI. PATIENT SUMMARY: Antibiotic use is associated with worsened survival in UC patients receiving immune checkpoint inhibitors.

Triple synchronous malignancies of the stomach, bladder and thyroid in a previously treated prostate cancer patient: A Case Report.

Cancers that develop within six months of the first primary cancer are referred to as synchronous malignancies. These malignancies are difficult to diagnose and treat, with treatment primarily based on case reports.

Stromal inflammation, fibrosis and cancer: An old intuition with promising potential.

It is now well established that the biology of cancer is influenced by not only malignant cells but also other components of the tumour microenvironment. Chronic inflammation and fibrosis have long been postulated to be involved in carcinogenesis. Chronic inflammation can promote tumorigenesis via growth factor/cytokine-mediated cellular proliferation, apoptotic resistance, immunosuppression; and free-radical-induced oxidative deoxyribonucleic acid damage. Fibrosis could cause a perturbation in the dynamics of the tumour microenvironment, potentially damaging the genome surveillance machinery of normal epithelial cells. In this review, we will provide an in-depth discussion of various diseases characterised by inflammation and fibrosis that have been associated with an increased risk of malignancy. In particular, we will present a comprehensive overview of the impact of alterations in stromal composition on tumorigenesis, induced as a consequence of inflammation and/or fibrosis. Strategies including the application of various therapeutic agents with stromal manipulation potential and targeted cancer screening for certain inflammatory diseases which can reduce the risk of cancer will also be discussed.

Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review.

BACKGROUND: Gut microbiome (GM) composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy (ICB) and of ICB-related colitis. AIM: To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB. METHODS: The review protocol was registered in PROSPERO: CRD42021228018. From a total of 300 studies, nine studies met inclusion criteria. Two studies were phase I clinical trials, while the remainder were prospective observational studies. All but one study has moderate risk of bias. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). RESULTS: Fecal samples enriched in Firmicutes phylum were associated with good response to ICB, whereas the Bacteroidales family was associated with poor response to ICB. Samples with greater GM diversity were associated with more favorable response to ICB [hazard ratio (HR) = 3.57, 95% confidence interval = 1.02-12.52, P < 0.05]. Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis (P < 0.01) whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis (P < 0.05). Overall, there was limited concordance in the organisms in the GM identified to be associated with response to ICB, and studies evaluating GM diversity showed conflicting results. CONCLUSION: This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.

Anterior pelvic exenteration and synchronous bilateral nephroureterectomy for BK polyoma virus induced urothelial carcinoma of the bladder: A case report.

BK polyoma virus (BKV) is a known risk factor for the development of urothelial carcinoma. There is currently limited data on the management of BKV-induced urothelial carcinoma (BUC) of the bladder, with available data limited to case reports. It remains debatable whether radical cystectomy (RC) with removal of the native urinary tract or RC alone is the most optimal management for BUC of the bladder. BKV-induced urothelial carcinoma is rare, and its management is challenging in immunocompromised patients such as that of post-transplant patients. This case report provides additional insight into a rare disease, the management of which still lacks established guidelines and remains debatable.

Applications of nanoparticles in cardiovascular imaging and therapeutics.

Cardiovascular disease (CVD) is a major health problem afflicting millions of people worldwide. Early detection methods are lacking, and current therapies have significant limitations. Recently, there has been a surge in the number of studies investigating the utilisation of nanoparticles in cardiovascular imaging and therapy. With respect to cardiovascular imaging, previous studies have looked at the role of nanoparticles in thrombus formation, angiogenesis, blood pool and stem cell imaging. Whereas, with respect to therapy, nanoparticles have been studied for delivering drugs and nucleic acids, specifically to the site of interest; in the context of cardiac regeneration; and its potential in refining current therapy guidelines for CVD management. This review aims to extensively summarise the studies that have been conducted investigating the role of nanoparticles in different aspects of cardiovascular imaging and therapy.

Application of extracellular vesicles in the diagnosis and treatment of prostate cancer: Implications for clinical practice.

Extracellular vesicles (EV) are cell-derived lipid bilayer-delimited structures providing an important means of intercellular communication. Recent studies have shown that EV, particularly exosomes and large-oncosomes contain miRNA and proteins crucial in prostate cancer (PCa) progression, metastasis and treatment resistance. This includes not just EV released from PCa cells, but also from other cells in the tumor microenvironment. PCa patient derived EV have a unique composition compared to healthy and benign prostatic diseases. As such, EV show promise as diagnostic liquid biopsy biomarkers, both as an adjunct and alternative to the invasive current gold-standard. EV could also be utilized to stratify patients' risk and predict response to hormonal, chemo, immune- and targeted therapy, which will direct future treatment decisions in PCa. We present a summary of the current evidence on the role of EV in PCa and the application of EV in PCa diagnosis and treatment to optimize patient outcomes.

Adenocarcinoma of the urethra: A rare subtype of urethral cancer.

Urethral adenocarcinoma (UA) is a rare type of urethral cancer with a poor prognosis. We present a case of UA of intestinal subtype in a 57-year-old patient who initially had lower urinary tract symptoms and was subsequently found to have a urethral lesion in a urethral diverticulum on pelvic MRI which was confirmed on biopsy. She had neoadjuvant chemotherapy followed by open anterior pelvic exenteration, complete urethrectomy and ileal conduit urinary diversion. She required adjuvant chemotherapy for local invasion and a metastasis in the uterus but developed progressive metastatic disease and succumbed to the disease 13-months after surgery.

Effect of dimethyl fumarate on renal disease progression in a genetic ortholog of nephronophthisis.

Dimethyl fumarate is an FDA-approved oral immunomodulatory drug with anti-inflammatory properties that induces the upregulation of the anti-oxidant transcription factor, nuclear factor erythroid-derived factor 2. The aim of this study was to determine the efficacy of dimethyl fumarate on interstitial inflammation and renal cyst growth in a preclinical model of nephronophthisis. Four-week-old female Lewis polycystic kidney disease (a genetic ortholog of human nephronophthisis-9) rats received vehicle (V), 10 mg/kg (D10) or 30 mg/kg (D30) ( n = 8-9 each) dimethyl fumarate in drinking water for eight weeks. Age-matched Lewis control rats were also studied ( n = 4 each). Nuclear factor erythroid-derived factor 2 was quantified by whole-slide image analysis of kidney sections. Renal nuclear factor erythroid-derived factor 2 activation was partially reduced in vehicle-treated Lewis polycystic kidney disease rats compared to Lewis control (21.4 ± 1.7 vs. 27.0 ± 1.6%, mean ± SD; P < 0.01). Dimethyl fumarate upregulated nuclear factor erythroid-derived factor 2 in both Lewis Polycystic Kidney Disease (D10: 35.9 ± 3.8; D30: 33.6 ± 3.4%) and Lewis rats (D30: 34.4 ± 1.3%) compared to vehicle-treated rats ( P < 0.05). Dimethyl fumarate significantly reduced CD68+ cell accumulation in Lewis polycystic kidney disease rats (V: 31.7 ± 2.4; D10: 23.0 ± 1.1; D30: 21.5 ± 1.9; P < 0.05). In Lewis polycystic kidney disease rats, dimethyl fumarate did not alter the progression of kidney enlargement (V: 6.4 ± 1.6; D10: 6.9 ± 1.2; D30: 7.3 ± 1.3%) and the percentage cystic index (V: 59.1 ± 2.7; D10: 55.7 ± 3.5; D30: 58.4 ± 2.9%). Renal dysfunction, as determined by the serum creatinine (Lewis + V: 26 ± 4 vs. LPK + V: 60 ± 25 P < 0.01; LPK + D10: 47 ± 7; LPK + D30: 47 ± 9 µmol/L), and proteinuria were also unaffected by dimethyl fumarate treatment. In conclusion, the upregulation of nuclear factor erythroid-derived factor 2 by dimethyl fumarate reduced renal macrophage infiltration in nephronophthisis without adverse effects, suggesting that it could potentially be used in combination with other therapies that reduce the rate of renal cyst growth. Impact statement This is the first study to investigate the effects of dimethyl fumarate in a model of cystic kidney disease. The study assessed the therapeutic efficacy of dimethyl fumarate in upregulating renal nuclear factor erythroid-derived factor 2 expression, reducing macrophage accumulation and cyst progression in a Lewis polycystic kidney disease rat model. This study demonstrates that dimethyl fumarate significantly upregulated renal nuclear factor erythroid-derived factor 2 expression and attenuates renal macrophage infiltration, but had no effect on renal cyst progression, cardiac enlargement, and improving renal function.