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Metabolomics for the diagnosis of bladder cancer: A systematic review

Asian Journal of Urology 2024年第2期11卷 221-241页

作者： Herney Andrés García-Perdomo Angélica María Dávila-Raigoza Fernando Korkes Division of Urology/Urooncology Department of SurgerySchool of MedicineUniversidad del ValleCaliColombia UROGIV Research Group School of MedicineUniversidad del ValleCaliColombia urologic oncology Division of UrologyABC Medical SchoolSao PauloBrazil

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.Methods: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.Results: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.Conclusion: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.

关键词： Metabolite Metabolomics Bladder cancer Metabolomicsprofile

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Nonmuscle invasive bladder cancer: a primer on immunotherapy

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Cancer Biology & Medicine 2016年第2期13卷 194-205页

作者： Mahir Maruf Sam J.Brancato Piyush K.Agarwal urologic oncology branch National Cancer Institute National Institutes of Health

Intravesical Bacillus Calmette-Guérin(BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer.Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer.

关键词：免疫治疗剂膀胱癌浸润性入门肌单克隆抗体上皮细胞免疫反应

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Pain management strategies in penile implantation

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Asian Journal of Andrology 2020年第1期22卷 34-38页

作者： Jeffrey L Ellis Andrew M Higgins Jay Simhan Department of Urology Einstein Healthcare NetworkDivision of Urologic OncologyDepartment of Surgical OncologyFox Chase Cancer CenterPhiladelphiaPA 19141 USA

The opioid epidemic continues to be a serious public health concern.Many have pointed to prescription drug misuse as a nidus for patients to become addicted to opioids and as such,urologists and other surgical subspecialists must critically define optimal pain management for the various procedures performed within their respective disciplines.Controlling pain following penile prosthesis implantation remains a unique challenge for urologists,given the increased pain patients commonly experience in the postoperative setting.Although most of the existing urological literature focuses on interventions performed in the operating room,there are many studies that examine the role of preoperative adjunctive pain medicine in diminishing postoperative narcotic requirements.There are relatively few studies looking at postoperative strategies for managing pain in prosthetic surgery with follow-up past the immediate hospitalization.This review assess the various strategies employed for managing pain following penile implantation through the lens of the current state of the opioid crisis,thus examining how urologists can responsibly treat pain without contributing to the growing threat of opioid addiction.

关键词： analgesia epidemic opioid pain prosthetic

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Adult urological Cancers at Zinder National Hospital

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Open Journal of Urology 2024年第5期14卷 267-276页

作者： Halidou Maazou Manzo M. S. Ousmane Chaibou Soumana Abdoulaye Kodo Idrissa Seriba Abdoulrazak R. H. Zakou Soumana Amadou Department of Urology University of Zinder Zinder Niger Department of Urologie University of Niamey Niamey Niger Department of Mé dicale Oncology National H&#244pital of Zinder Zinder Niger Department of Anatomy Pathology Universit&#233 of Zinder Zinder Niger

The aim of this study was to present the epidemiological, clinical and therapeutic aspects of adult urological cancers in the department of urology at Zinder National Hospital. Patients and Methods: This was a cross-sectional study of adult primary urologic cancers during the period of January 2019 to December 2023. Data were obtained from the record of patients admitted to urology, and the medical oncology department. The parameters studied were;frequency, age, sex, urogenital distribution, anatomopathological type, and therapeutic aspects. Data were recorded on Excel 2013 and analyzed with Epi-info version 7.2.5. Results: Epidemiology: About 289 cancers were diagnosed through 6017 consultations during the period, corresponding to 4.80% of urological pathologies: prostate cancer (n = 221;76.47%), bladder cancer (n = 46;15.92%), kidney cancer (n = 13;04.5%), testis cancer (n = 09;03.11%). Median age of patients was 50.42 years. Prostate cancer: was Adenocarcinoma in 100% (n = 221) with Gleason scores > 7 (77.83%) and prostatique specific antigen (PSA) > 20 ng/ml in 90.04%. Extension evaluation 134 cases (60.63%). Treatment was chirurgical castration in (62.44%) and resistance to castration appeared between 8 and 11 months. Hospital mortality for prostate cancer was 16.29%. Bladder cancer was found in 46 cases with Sex ratio 7/1. Cystoscopy was performed for all. Histology revealed squamous cell carcinoma (n = 41;89.13%), and (n = 5;10.87%) urothelial. Endoscopic resection performed (n = 14;30.43%). Kidney cancers were 13 cases (10 men, 03 women). Nephrectomy was performed in (n = 8;61.54%) cases and Histology revealed renal cell cancer in 76.92%. Testicular cancers were diag 09 cases. History of cryptorchidism was found in 4 cases, 4-year infertility in 3 cases. Orchidectomy was done in all cases. Chemotherapy in 3 cases. Conclusion: urological cancers are frequent, dominated by prostate cancer. The endemicity of bilharziasis has increased squamous cell carcinoma. The majority of patients have advanced form of th

关键词： urologic Cancers Epidemiology Histology Zinder

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The biochemical efficacy of primary cryoablation combined with prolonged total androgen suppression compared with radiotherapy on high-risk prostate cancer： a 3-year pilot study

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Asian Journal of Andrology 2010年第6期12卷 827-834页

作者： Young Hwii Ko Seok Ho Kang Young Je Park Hong Seok Park Du Geon Moon Jeong Gu Lee Duck Ki Yoon Je Jong Kim Jun Cheon Department of Urology MIS ＆ Robotic Urologic Surgery Centre Korea University School of Medicine Seoul 136-705Korea Department of Radiation oncology Korea University School of Medicine Seoul 136-705 Korea

To gain beneficial effects in the management of high-risk prostate cancer, an integrated approach that combines local therapy and androgen deprivation therapy （ADT） was used. We compared biochemical responses between primary cryosurgical ablation of the prostate （CSAP） combined with prolonged ADT and radiation combined with ADT, which is the established modality in high-risk disease. A total of 33 high-risk patients received CSAP combined with ADT for 3 months before and up to 24 months after treatment. This patient group was matched with another 33 patients who had undergone three-dimensional conformal radiation therapy （3D-CRT） with the same protocol for ADT. Biochemical recurrence （BCR） was assessed by the American Society for Therapeutic Radiation oncology （ASTRO） definition, the Phoenix definition and a prostate-specific antigen （PSA） cutoff of 0.5 ng mL^-1. Median follow-up was 61.0 ± 11.9 months for the CSAP ＋ ADT group and 86.0±15.8 months for the 3D-CRT ＋ ADT group. In the CSAP group, major complications including rectourethral fistula and incontinence were not noted. In the CSAP ＋ ADT group, 57.0% had BCR using the ASTRO definition, 21.2% using the Phoenix definition and 54.5% using a PSA cutoff of 0.5 ng mL^-1. In the 3D-CRT ＋ ADT group, 54.5%, 21.2% and 54.5% had BCR using the ASTRO, Phoenix and PSA definition, respectively. In the CSAP ＋ ADT group, the BCR-free survival （BRFS） was 54 ± 10 months using the ASTRO definition, 65 ± 5 months using the Phoenix definition and 51 ± 4 months using a PSA cutoff of 0.5 ng mL-1. In the 3D-CRT ＋ ADT group, the BRFS was 68 ± 12, 93 ± 19 and 70 ± 18 months using the ASTRO, Phoenix and PSA definition, respectively. By the log-rank test, the BRFS values for each group were not statistically different. This intermediate-term result indicated that primary CSAP combined with prolonged ADT offers a parallel biochemical response compared with radiotherapy in high-risk prostate cancer.

关键词： androgen ablation therapy cryoablation for the prostate radiotherapy

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MicroRNA-371a-3p as a blood-based biomarker in testis cancer

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Asian Journal of Urology 2021年第4期8卷 400-406页

作者： Hamed Ahmadi Thomas L.Jang Siamak Daneshmand Saum Ghodoussipour Department of Urology University of Southern California/Norris Comprehensive Cancer CenterLos AngelesCAUSA Section of urologic oncology Rutgers Cancer Institute of New JerseyNew BrunswickNJUSA

MicroRNAs(miRNAs)are small noncoding RNAs involved in the regulation of mRNA transcription and translation,and possess all desirable features of an ideal tumor marker.Of almost 31 different miRNA clusters identified in germ cell tumors(GCTs),miR-371a-3p has shown exceptionally high sensitivity and specificity for both seminomatous and nonseminomatous GCTs.It is easily obtainable and correlates well with tumor burden.Recent multiinstitutional prospective studies have shown promising test characteristics for miR-371a-3p as a diagnostic blood-based biomarker for GCT prior to orchiectomy including 80%e100%sensitivity and 90%e100%specificity.This accuracy may address other unmet needs in the management of patients with GCT.Early studies have suggested the utility of miR-371a-3p in detecting occult nodal metastasis in high-risk clinical stage I and early stage II disease.Ongoing clinical trials including SWOG 1823 and AGCT1531 are specifically designed to confirm the utility of miR-371a-3p in clinical stage I GCT.Despite its strong association with viable GCT after treatment with chemotherapy,miR-371a-3p does not seem to accurately predict the presence of teratoma in residual lesions.Also,standardization of extraction and interpretation methods is a necessary step to assure uniform results across different institutions.

关键词： Biomarker MicroRNA Non Seminoma Seminoma Testis cancer Tumor marker

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Refining the American urological Association and American Society for Radiation oncology guideline for adjuvant radiotherapy after radical prostatectomy using the pathologic Gleason score

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Asian Journal of Andrology 2017年第1期19卷 20-25页

作者： Wan Song Young Suk Kwon Seong Soo Jeon Isaac Yi Kim Section of urologic oncology Rutgers Cancer Institute of New Jersey Rutgers The State University of New Jersey New Brunswick NJ 08903 USA Department of Urology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea.

Recently, it has been suggested that the guideline for adjuvant radiotherapy （ART） following radical prostatectomy （RP） sponsored by the American urological Association and American Society for Radiation oncology （AUA/ASTRO） may result in a significant overtreatment. Thus, the objective of the present study was to refine the AUA/ASTRO guideline for ART in patients at risk for biochemical recurrence （BCR） after RP. To this end, we reviewed our prospectively maintained database and selected 193 patients who met the AUA/ASTRO ART criteria. With a median follow-up of 24.0 months, BCR rate was 17.6% （34/193）. When stratified by the Gleason score, BCR rate in men with Gleason score 6 was 6.8%. There was no significant association between BCR-free survival and surgical margin （P= 0.690） and pathologic stage （P= 0.353） in patients with the Gleason score 6. However, in patients with positive surgical margins （PSMs）/pathologic stage ≥T3, there was a significant difference in BCR-free survival according to Gleason score （≤7 vs8-10, P= 0.047）. Multivariate Cox regression analysis demonstrated that pathologic stage ≥T3 （HR = 2.106; P = 0.018）, PSMs （HR = 2.411; P = 0.003）, and pathologic Gleason score 8-10 （HR = 4.715; P 〈 0.001） were independent predictors of BCR after RP. Therefore, in addition to pathologic stage 〉T3 and PSMs, Gleason score 8-10 predicts 8CR after RP. In patients with Gleason score 6, observation rather than ART may be more appropriate regardless of stage and surgical margin status.

关键词： adjuvant radiotherapy biochemical recurrence radical prostatectomy

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Heterogeneity and renal mass biopsy:a review of its role and reliability

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Cancer Biology & Medicine 2014年第3期11卷 162-172页

作者： Jeffrey J.Tomaszewski Robert G.Uzzo Marc C.Smaldone Division of Urology Department of SurgeryMD Anderson Cancer Center at CooperRowan University School of MedicineCamdenNJ08103USA Division of urologic oncology Department of Surgical OncologyFox Chase Cancer Center-Temple University Health SystemPhiladelphiaPA19111USA

Increased abdominal imaging has led to an increase in the detection of the incidental small renal mass(SRM). With increasing recognition that the malignant potential of SRMs is heterogeneous, ranging from benign(15%-20%) to aggressive(20%), enthusiasm for more conservative management strategies in the elderly and infirmed, such as active surveillance(AS), have grown considerably. As the management of the SRM evolves to incorporate ablative techniques and AS for low risk disease, the role of renal mass biopsy(RMB) to help guide individualized therapy is evolving. Historically, the role of RMB was limited to the evaluation of suspected metastatic disease, renal abscess, or lymphoma. However, in the contemporary era, the role of biopsy has grown, most notably to identify patients who harbor benign lesions and for whom treatment, particularly the elderly or frail, may be avoided. When performing a RMB to guide initial clinical decision making for small, localized tumors, the most relevant questions are often relegated to proof of malignancy and documentation(if possible) of grade. However, significant intratumoral heterogeneity has been identified in clear cell renal cell carcinoma(ccRCC) that may lead to an underestimation of the genetic complexity of a tumor when single-biopsy procedures are used. Heterogeneous genomic landscapes and branched parallel evolution of ccRCCs with spatially separated subclones creates an illusion of clonal dominance when assessed by single biopsies and raises important questions regarding how tumors can be optimally sampled and whether future evolutionary tumor branches might be predictable and ultimately targetable. This work raises profound questions concerning the genetic landscape of cancer and how tumor heterogeneity may affect, and possibly confound, targeted diagnostic and therapeutic interventions. In this review, we discuss the current role of RMB, the implications of tumor heterogeneity on diagnostic accuracy, and highlight promising future directions.

关键词：异质性活检质量审查穿刺可靠性肾诊断准确性

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Alternative polyadenylation:An untapped source for prostate cancer biomarkers and therapeutic targets?

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Asian Journal of Urology 2021年第4期8卷 407-415页

作者： Akira Kurozumi Shawn E.Lupold The James Buchanan Brady urologic Institute and Department of Urology Johns Hopkins School of MedicineBaltimoreMDUSA The Department of oncology Sidney Kimmel Comprehensive Cancer CenterSchool of MedicineJohns Hopkins UniversityBaltimoreMDUSA

Objective:To review alternative polyadenylation(APA)as a mechanism of gene regulation and consider potential roles for APA in prostate cancer(PCa)biology and treatment.Methods:An extensive review of mRNA polyadenylation,APA,and PCa literature was performed.This review article introduces APA and its association with human disease,outlines the mechanisms and components of APA,reviews APA in cancer biology,and considers whether APA may contribute to PCa progression and/or produce novel biomarkers and therapeutic targets for PCa.Results:Eukaryotic mRNA 30-end cleavage and polyadenylation play a critical role in gene expression.Most human genes encode more than one polyadenylation signal,and produce more than one transcript isoform,through APA.Polyadenylation can occur throughout the gene body to generate transcripts with differing 30-termini and coding sequence.Differences in 30-untranslated regions length can modify post-transcriptional gene regulation by microRNAs and RNA binding proteins,and alter mRNA stability,translation efficiency,and subcellular localization.Distinctive APA patterns are associated with human diseases,tissue origins,and changes in cellular proliferation rate and differentiation state.APA events may therefore generate unique mRNA biomarkers or therapeutic targets in certain cancer types or phenotypic states.Conclusions:The full extent of cancer-associated and tissue-specific APA events have yet to be defined,and the mechanisms and functional consequences of APA in cancer remain incompletely understood.There is evidence that APA is active in PCa,and that it may be an untapped resource for PCa biomarkers or therapeutic targets.

关键词： Prostate cancer Polyadenylation Alternative polyadenylation 30-untranslated region microRNA Intronic polyadenylation

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Risk stratification for disease progression in pT3 prostate cancer after robot-assisted radical prostatectomy

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Asian Journal of Andrology 2017年第6期19卷 700-706页

作者： Jeong Hee Hong Young Suk Kwon Isaac Yi Kim Section of urologic oncology Rutgers Cancer Institute of New Jersey Division of Urology Rutgers Robert Wood Johnson Medical School Rutgers The State University of New Jersey New Brunswick NJ 08903 USA Department of Urology Dankook University College of Medicine Cheonan 31116 South Korea.

The aim of this study is to identify optimal patients for adjuvant radiation therapy （ART） in pT3 prostate cancer. The role of ART for patients with adverse pathologic features after radical prostatectomy （RP） has been demonstrated, but over- or under-treatment remains a significant concern. Two-hundred and five patients with pT3NOMO who underwent robot-assisted RP without ART were analyzed. Multivariate Cox proportional regression analyses were used to identify predictors of biochemical recurrence （BCR） and clinical progression （CP）. The estimated 5-year BCR-free survival （BCRFS） and CP-free survival （CPFS） were 52.8% and 85.6%, respectively. Preoperative prostate-specifc antigen （PSA）：〉10 ng m1-1 （hazard ratio [HR]： 3.288-6.027; P = 0.003）, pathologic Gleason score （pGS）：〉8 （HR： 4.146; P = 0.014）, and lymphovascular invasion （LVI）（HR： 2.167; P = 0.026） were associated with BCR. Based on these factors, a risk stratification tool was developed. Patients with no risk factors （PSA 〈10 ng m1-1, pGS 6, and absent LVI） showed excellent BCRFS and CPFS at 5 years （91.9% and 100.0%, respectively）, but those with two or more risk factors （PSA ：〉10 ng ml-1, pGS ≥8, or present LVI） had poor BCRFS and CPFS （12.1% and 54.6%, respectively）. In addition, the multivariate analysis revealed that pathologic stage pT3b （HR： 5.393; P = 0.025） was the only predictor of CP. Our study demonstrated the heterogeneity of oncologic outcomes in patients with pT3 prostate cancer. The proposed risk stratification can be used to identify patients who are at risk for disease progression and may aid in identifying the best patients for ART.

关键词： prostatectomy prostate-specific antigen recurrence survival

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