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In the recent decade, analysis of circulating tumor DNA (ctDNA) has improved cancer care by allowing for rapid detection of actionable molecular targets. A new generation of circulating DNA tests is now becoming available commercially. These tests are characterized by a superior limit of detection of 0.01% vaF or better, allowing for the detection of radiologically occult molecular residual disease (MRD). MRD tests have the potential to revolutionize neoadjuvant and adjuvant treatment. In addition, these tests can be used as tumor markers to assess disease response. We reviewed the current evidence for the use of high-sensitivity MRD assays with particular focus on the genitourinary tumors. Multiple studies have now been reported in urothelial, renal, and recently testicular carcinoma. We find that the sensitivity varies across tumor types in the adjuvant setting and may reach a high of 100% in urothelial cancer. Specificity in tumor-informed MRD appears to be preserved across tumor types (98%-100%). Several trials are now prospectively validating MRD testing in biomarker integral studies, mainly in urothelial carcinoma., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The prognostic significance of programmed cell death-ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta-analysis to systematically evaluate its prognostic value in human cancers., Methods: Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre-treatment and post-treatment PD-L1 + CTCs with progression-free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD-L1 detection method, cut-off, and specifically the comparison model were performed., Results: We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre-treatment PD-L1 + CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28-1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36-1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non-ICI therapies (PFS: HR = 1.85, 95% CI 1.21-2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69-3.51, p < 0.001). Post-treatment PD-L1 + CTCs predicted markedly worse PFS and OS. The prognostic value was obviously modulated by comparison models. Among patients with detectable CTCs, PD-L1 + individuals had comparable survival to PD-L1 - individuals, except ICI treatment for which PD-L1 + may predict better PFS (HR = 0.42, 95% CI 0.17-1.06, p = 0.067). Patients with PD-L1 + CTCs had worse survival prognosis compared to those without PD-L1 + CTCs in overall analysis (PFS: HR = 2.10, 95% CI 1.59-2.77, p < 0.001; OS: HR = 2.55, 95% CI 1.70-3.81, p < 0.001) and in most subgroups., Conclusions: Our analysis demonstrated that PD-L1 positive expression on CTCs predicted better survival prognosis for ICI treatment but worse survival for other therapies, which thus can be potentially used as a prognostic marker of malignant tumor treatment. However, the prognostic value of PD-L1 + CTCs for ICI treatment needs validation by more large-scale studies in the future., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients., Methods: Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction., Results: Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response., Conclusion: Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.

There is still no conclusion on the potential effect of the rs2295080 and rs2536 polymorphisms of mTOR (mammalian target of rapamycin) gene on different cancers. Herein, we performed a comprehensive assessment using pooled analysis, FPRP (false-positive report probability), TSA (trial sequential analysis), and eQTL (expression quantitative trait loci) analysis. Eighteen high-quality articles from China were enrolled. The pooled analysis of rs2295080 with 9502 cases and 10,965 controls showed a decreased risk of urinary system tumors and specific prostate cancers [TG vs. TT, TG+GG vs. TT and G vs. T; P<0.05, OR (odds ratio) <1]. FPRP and TSA data further confirmed these results. There was an increased risk of leukemia [G vs. T, GG vs. TT, and GG vs. TT+TG genotypes; P<0.05, OR>1]. The eQTL data showed a potential correlation between the rs2295080 and mTOR expression in whole blood samples. Nevertheless, FPRP and TSA data suggested that more evidence is required to confirm the potential role of rs2295080 in leukemia risk. The pooled analysis of rs2536 (6653 cases and 7025 controls) showed a significant association in the subgroup of "population-based" control source via the allele, heterozygote, dominant, and carrier comparisons (P<0.05, OR>1). In conclusion, the TG genotype of mTOR rs2295080 may be linked to reduced susceptibility to urinary system tumors or specific prostate cancers in Chinese patients. The currently data do not strongly support a role of rs2295080 in leukemia susceptibility. Large sample sizes are needed to confirm the potential role of rs2536 in more types of cancer., (© 2020 The Author(s).)

Plasma untargeted metabolomics is a common method for evaluation of the mechanisms underlying human pathologies and identification of novel biomarkers. The plasma proteins provide the environment for transport of hydrophobic metabolites. The current sample preparation protocol relies on the immediate precipitation of proteins and thus leads to co-precipitation of a significant fraction of hydrophobic metabolites. Here we present a new simple procedure that overcomes the co-precipitation problem and improves metabolome coverage. Introducing an additional step preceding the protein precipitation, namely limited digestion with proteinase K, allows release of associated metabolites through the relaxation of the native proteins tertiary structure. The modified protocol allows clear detection of hydrophobic metabolites including fatty acids and phospholipids. Considering the potential involvement of the hydrophobic metabolites in human cardiovascular and cancer diseases, the method may constitute a novel approach in plasma untargeted metabolomics.

Purpose: The main objective of this study was to compare the effect of two anaesthetic techniques (general vs combined) on plasma levels of NGAL (Neutrophil Gelatinase Associated Lipocalin) after robotic urogenital oncosurgery. The secondary objective was to correlate NGAL levels with the incidence of acute kidney injury (AKI)., Methods: This was a longitudinal prospective study. Forty patients were included and randomized in 2 groups: group C (N=16 cases; combined general-epidural anesthesia) and group G (N=24 cases; control group with general anesthesia). Demographic data, Charlson Comorbidity Index, Apache II, SOFA and ASA scores were similar in both groups. Serum creatinine was determined preoperatively and every 24 hrs for 4 postoperative days to identify AKI according to RIFLE and AKIN criteria. Serum NGAL was determined at 6 and 12 hrs after induction of anesthesia., Results: Serum creatinine increased at 24 hrs postoperatively in both groups as compared to baseline, but significant changes were registered only in the G group (p(control) = 0.004). Serum NGAL increased significantly in both groups as compared with baseline levels (pcase=0.0034 vs p(control)=0.0001). The incidence of AKI was 12.50% (95% CI 0.4-34) in the C group and 37.50% (95% CI 17-58) in the G group (p=0.0909), respectively., Conclusion: Impaired renal function and AKI occurred in robot-assisted laparoscopic urogenital oncosurgery under both general and combined anaesthesia. The incidence of AKI was lower in patients undergoing combined anesthesia compared to general anaesthesia after robotic urogenital oncosurgery but the difference did not reach statistical significance. However, plasma levels of NGAL were significantly increased at 6 and 12 hrs in the general anaesthesia group as compared with combined anaesthesia. NGAL may be a better marker in detecting postoperative acute kidney injury. Further studies are needed.

The present investigation was conducted to determine serum levels of basic fibroblast growth factor (FGF) by enzyme immunoassay in patients with various urogenital tumors. Renal cell carcinoma had a higher tendency (28 of 52, 53.8%) toward increased serum levels of basic FGF than any of the other urogenital tumors, and increased serum basic FGF was detected more frequently in patients with advanced renal cell carcinoma. Analysis of histological pattern indicated that renal cell carcinoma with a solid or tubular component is more likely to produce basic FGF. However, no significant difference was seen between the percentage of clear cell type tumor patients with increased serum basic FGF (50.0%) and the percentage of granular cell type tumor patients with increased serum basic FGF (66.7%). Five of 8 patients with renal cell carcinoma who underwent selective renal venous sampling before nephrectomy showed increased serum basic FGF in the renal vein from the affected kidney. After resection of the affected kidney to remove the cancer, serum basic FGF disappeared within 2 weeks. However, residual huge tumor or postoperative disease prolonged the increased levels of basic FGF in 2 patients, indicating that basic FGF is produced from and secreted by tumor tissue itself. These findings suggest that serum basic FGF can be useful in the diagnosis, and in evaluating the prognosis, of patients with renal cell carcinoma.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 micrograms/kg of body weight to 22 patients with transitional cell carcinoma before chemotherapy as part of a Phase I/II study. In all patients, a specific dose-dependent increase in the absolute neutrophil count (ANC) of 1.8-12 fold was seen. In addition, this augmentation in the ANC was accompanied by an increase in leukocyte alkaline phosphatase, a marker of secondary granule formation. In six of eight patients analyzed, an increase in bone marrow myeloid to erythroid cell ratio was seen. Day 14 peripheral blood cell derived colony forming unit granulocyte macrophage were also increased by day 6 of rhG-CSF treatment. Circulating levels of eosinophils and basophils were unchanged; however, a 10-fold increase in monocytes was observed in patients treated at the highest doses. There was also a small increase in CD3+ lymphocytes that was not dose dependent. Hemoglobin, hematocrit, and platelet count remained near baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.