The Impact of Variation in Bladder Volume on the Doses of Target and Organ-at-Risk in Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

Intensity-modulated radiation therapy (IMRT) has become the mainstay of treatment for localized prostate cancer. In IMRT, minimizing differences between the conditions used during planning CT and daily treatment is important to prevent adverse events in normal tissues. In the present study, we evaluated the impact of variation in bladder volume on the doses to various organs. A total of 35 patients underwent definitive radiotherapy at Saitama Medical Center. A Light Speed RT16 (GE Healthcare) was used for planning and to obtain examination CT images. Such images were acquired after 4 - 6 days of planning CT image acquisition. The IMRT plans were optimized using the planning CT data to satisfy the dose constraints set by our in-house protocols for the PTV and the OARs. The dose distributions were then re-calculated using the same IMRT beams, and checked on examination CT images. It was clear that bladder volume affected the doses to certain organs. We focused on the prostate, bladder, rectum, small bowel, and large bowel. Regression coefficients were calculated for variables that correlated strongly with bladder volume (p < 0.05). We found that variation in bladder volume [cm3] predicted deviations in the bladder V70Gy, V50Gy, and V30Gy [%];the maximum dose to the small bowel [cGy];and the maximum dose to the large bowel [cGy]. The regression coefficients were -0.065, -0.125, -0.180, -10.22, and -9.831, respectively. We evaluated the impacts of such variation on organ doses. These may be helpful when checking a patient’s bladder volume before daily IMRT for localized prostate cancer.

Does local vaginal estrogen after tension-free transobturator vaginal tape reduce overactive bladder symptoms in postmenopausal women? A prospective randomized, controlled study

Objective:We aimed to evaluate the efficacy of topical estrogen after transvaginal tension-free vaginal tape-obturator(TVT-O)in the treatment of de novo overactive bladder symptoms that appear after surgery.Methods:This is a prospective randomized controlled study performed in the Urology and Gynecology Departments,Kasr Al Ainy Hospital,Cairo University,Cairo,Egypt.Two hundred and ten postmenopausal females presenting during the period between January 2017 and November 2020 with stress urinary incontinence were included in the study.Patients were divided into two groups,105 patients in Group A(treatment group)and 105 patients in Group B(control group).Patients in Group A underwent transvaginal TVT-O followed by local vaginal estrogen treatment for 6 months,while patients in Group B underwent transvaginal TVT-O only.The study included any postmenopausal female with urodynamic stress urinary incontinence.All patients had to fulfill a 3-day bladder diary,overactive bladder symptoms score,urine analysis,urodynamic study,and post-voiding residual urine measurement by abdominal ultrasound preoperatively and at 3-month and 6-month follow-ups.Results:At 6-month follow-up,daytime frequency was reduced to 8%in Group A(increased to 21%in Group B)with a statistically significant difference between both groups(p=0.009).At 6-month follow-up,nocturia was 8%in Group A(11%in Group B)with no statistically significant difference between both groups(p=0.469).There was a statistically significant difference between both groups as regards to urinary urgency at 6-month follow-up(p=0.024).There was a statistically significant difference in postoperative wound healing events as regards to cure,hyperemia,gapping,and wound infection 1 week after intervention between both groups(p=0.008).No local or systemic side-effects were reported from local estrogen use.Conclusion:Local vaginal estrogen treatment given to postmenopausal patients after midurethral sling procedures can reduce the symptoms of daytime frequency and urinary urgency.Long-term follow-up is needed.

TM9SF1 promotes bladder cancer cell growth and infiltration

BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.

Urachal Cancer: Experience of a High-Volume Bladder Cancer Center

Introduction: Primary urachal cancer (UrCa) is rare, with an estimated incidence of 0.2% - 0.5% of all bladder tumors. Although the preferred treatment is surgical, there is no consensus on the best approach. We present our experience managing 14 cases of primary UrCa. Methods: A retrospective analysis was conducted on the clinical records of a high-volume bladder cancer center in the UK to identify patients diagnosed with UrCa between May 2013 and June 2022. Results: 9 males and 6 females, aged between 30 and 85 years, were included. The diagnosis was most commonly made via flexible cystoscopy and CT for haematuria. 3 patients had metastasis at presentation, and while radiologically no patients showed positive lymph nodes, 2 patients were found to have positive lymph nodes on histopathology. 13 patients underwent partial cystectomy, with 1 undergoing radical cystoprostatectomy. 8 patients underwent concurrent umbilectomy and/or lymphadenectomy. The most common histological subtype was mucinous adenocarcinoma. 2 patients experienced local recurrence and underwent transurethral resection, while 6 patients experienced metastasis. Metastasis-free survival rate was 74.1% and 55.6% at 12 and 24 months, respectively. Umbilectomy and lymphadenectomy did not decrease rates of positive surgical margin, local recurrence, metastasis, or mortality. Conclusions: UrCa is a rare and aggressive malignancy that can occur at any age and may be advanced upon presentation. Bladder-sparing surgery is becoming more prevalent, with chemotherapy being reserved for recurrence or metastasis. In our series, routine umbilectomy and lymphadenectomy did not improve oncologic outcomes. However, lymphadenectomy may have a role in cancer staging.

Transurethral resection of bladder tumor: A systematic review of simulator-based training courses and curricula

Objective:Transurethral resection of bladder tumor is one of the most common everyday urological procedures.This kind of surgery demands a set of skills that need training and experience.In this review,we aimed to investigate the current literature to find out if simulators,phantoms,and other training models could be used as a tool for teaching urologists.Methods:A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement and the recommendations of the European Association of Urology guidelines for conducting systematic reviews.Fifteen out of 932 studies met our inclusion criteria and are presented in the current review.Results:The UroTrainer(Karl Storz GmbH,Tuttlingen,Germany),a virtual reality training simulator,achieved positive feedback and an excellent face and construct validity by the participants.The inspection of bladder mucosa,blood loss,tumor resection,and procedural time was improved after the training,especially for inexperienced urologists and medical students.The construct validity of UroSim®(VirtaMed,Zurich,Switzerland)was established.SIMBLA simulator(Samed GmbH,Dresden,Germany)was found to be a realistic and useful tool by experts and urologists with intermediate experience.The test objective competency model based on SIMBLA simulator could be used for evaluating urologists.The porcine model of the Asian Urological Surgery Training and Education Group also received positive feedback by the participants that tried it.The Simulation and Technology Enhanced Learning Initiative Project had an extraordinary face and content validity,and 60%of participants would like to use the simulators in the future.The 5-day multimodal training curriculum“Boot Camp”in the United Kingdom achieved an increase of the level of confidence of the participants that lasted months after the project.Conclusion:Simulators and courses or curricula based on a simulator training could be a valuable learning tool for any surgeon,and there is no doubt that they should be a part of every urologist's technical education.

Metabolomics for the diagnosis of bladder cancer: A systematic review

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.

Potential clinical application of microRNAs in bladder cancer

Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

Current and Potential Roles of Ferroptosis in Bladder Cancer

Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

Inhibition of proliferation,migration,and invasiveness of bladder cancer cells through SAPCD2 knockdown

Introduction:Bladder cancer(BC)has a high incidence and mortality rate worldwide.Suppressor anaphasepromoting complex domain containing 2(SAPCDC2)is over-expressed in a variety of tumors.Objectives:This study investigated the effects of SAPCD2 knockdown on BC cells.Methods:T24 and UMUC3 cell models and the xenografted BC tumor model with SAPCD2 knockdown were established to observe the malignant phenotype of BC cells by cell counting kit-8 assay,colony formation test,wound healing,and Transwell assay,mRNA and proteins expressions were measured with quantitative real-time polymerase chain reaction,western blotting,and tissue immunohistochemistry.Lithium chloride agonist on the Wnt/β-catenin pathway was used to clarify the molecular mechanism of SAPCD2 knockdown.Results:SAPCD2 expression was significantly higher in BC cell lines than in SVHUC-1 cells.SAPCD2 knockdown inhibited viability and cloning,hindered the G0/G1 phase of the cell cycle in UMUC3 and T24 cells,and decreased the migration and invasiveness of BC cells.SAPCD2 knockdown inhibited expression levels of cyclin D1,cyclin B1,N-cadherin,vimentin,Snail,β-catenin,c-Myc,and cyclin-dependent kinase 4,while the P21 and E-cadherin were raised by SAPCD2 knockdown.Furthermore,lithium chloride reversed the effects of SAPCD2 knockdown on the expression levels of the above proteins in UMUC3 and T24 cells.In vivo,SAPCD2 knockdown inhibited the volume,weight,and expression of Ki-67 andβ-catenin in tumors and increased the E-cadherin expression.Conclusion:SAPCD2 knockdown inhibits the malignant phenotype of BC via a pathway involvingβ-catenin.

Epithelioid malignant peripheral nerve sheath tumor of the bladder and concomitant urothelial carcinoma: A case report

BACKGROUND Epithelioid malignant peripheral nerve sheath tumor(EMPNST)of the bladder is a rare entity with devastating features.These tumors are thought to originate from malignant transformation of pre-existing schwannomas of pelvic autonomic nerve plexuses,and unlike the conventional malignant peripheral nerve sheath tumor(MPNST),are not associated with neurofibromatosis.The tumor has dis-tinctive morphological,immunohistochemical and molecular features.Addi-tionally,it tends to be more aggressive and have a higher mortality.This is the first case that presents with a synchronous urothelial carcinoma of the bladder and the epithelioid variant of MPNST in the literature.It’s also the second re-ported case of EMPNST originating from the bladder wall.CASE SUMMARY In this case report,we present the detailed clinical course of a 71-year-old patient with EMPNST of the bladder alongside a literature review.CONCLUSION During the management of EMPNST cases,offering aggressive treatment moda-lities to the patient,such as radical cystectomy,is appropriate for the best chance to contain the disease,regardless of the tumor stage and the extent of local disease at initial diagnosis.

Clinical implications of single cell sequencing for bladder cancer

Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines.We searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February 2023.We included original studies that used at least one single-cell technology to study bladder cancer.Forty-one publications were included in the review.Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy.Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples.The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level.Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management.This nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.

Laparoscopic management of remnant gall bladder with stones: Lessons from a tertiary care centre's experience

Objective:Laparoscopic cholecystectomy is currently the gold standard for treating symptomatic gallstone disease.Despite its success,approximately 10%of patients may experience persistent biliary symptoms,leading to the post-cholecystectomy syndrome.A remnant gallbladder with cystic duct or bile duct stones is one of the causes of this syndrome.The objective of this study was to shed light on the clinical manifestations,evaluation,therapeutic strategies,and outcomes associated with laparoscopic management of symptomatic remnant gallbladders.Methods:This was a retrospective study,conducted over a five-year period(January 2017 to December 2022)at Apollo Hospitals in South India.All patients who underwent laparoscopic completion cholecystectomy for a remnant gall bladder were included.The following data were collected:patient demographics,symptoms,preoperative investigations,intraoperative details and post operative outcomes.Results:In total,36 patients were included and analysed.The majority of patients were male(25,69.4%),with a mean age of 50.7±12.1 years.The most common presentation was pain in the upper abdomen or right upper quadrant region(24,66.7%).The laparoscopic approach was attempted in all patients,with a success rate of 94.4%.Two patients required conversion to open surgery.Cholecystoenteric fistula to the colon was observed in one patient.Choledocholithiasis was observed in 7 patients(19.4%),and stone clearance was successfully achieved using endoscopic retrograde cholangiopancreatography in all patients preoperatively.Conclusion:Incomplete gall bladder removal either intentionally or unintentionally leaves a remnant gall bladder that is at risk for stone formation and infection.Patients who have this clinical entity with symptoms require a redo or complete cholecystectomy,a complex procedure associated with certain risks.This study highlights the feasibility and safety of laparoscopic completion cholecystectomy for the management of remnant gallbladder with cystic duct or bile duct stones.

Three cancers in the renal pelvis,bladder,and colon:A case report

BACKGROUND Multiple primary cancers are rare occurrences that can involve either metachronous or synchronous development.It is particularly rare for an individual to have more than two primary cancers.In this report,we present a case study of an elderly man who was diagnosed with three heterochronous cancers in the renal pelvis,bladder,and colon.CASE SUMMARY On December 30,2014,a 51-year-old Chinese man was admitted to our hospital with complaints of intermittent painless gross hematuria for the preceding week.A computed tomography(CT)scan revealed wall thickening in the left ureter’s upper segment,while a CT urography revealed a left renal pelvis tumor.A successful laparoscopic radical resection of the left renal pelvis tumor was subsequently performed at Shanghai Zhongshan Hospital in January 2015.The pathological findings after the surgery revealed a low-grade papillary urothelial carcinoma of the renal pelvis.The final pathological tumor stage was pT1N0M0.After surgery,this patient received 6 cycles of intravenous chemotherapy with gemcitabine and carboplatin,as well as bladder infusion therapy with gemcitabine.On December 18,2017,the patient was admitted once again to our hospital with a one-day history of painless gross hematuria.A CT scan showed the presence of a space-occupying lesion on the posterior wall of bladder.Cystoscopic examination revealed multiple tumors in the bladder and right cutaneous ureterostomy was performed under general anesthesia on December 29,2017.The postoperative pathological findings disclosed multifocal papillary urothelial carcinoma of the bladder(maximum size 3.7 cm×2.6 cm).The bladder cancer was considered a metastasis of the renal pelvis cancer after surgery.The pathological tumor stage was pT1N0M1.The patient refused chemotherapy after surgery.After another six years,the patient returned on February 28,2023,complaining of periumbilical pain that had lasted six days.This time,a CT scan of the abdomen showed a tumor in the ascending colon,but a subsequent colonoscopy examination indicated a tumor in the descending colon.On March 12,2023,a subtotal colectomy and an ileosigmoidal anastomosis were carried out under general anesthesia.Postoperative pathological findings revealed that all three tumors were adenocarcinomas.The final pathological tumor stage was pT3N0M0.The patient had an uneventful postoperative recovery and was discharged without complications.CONCLUSION The case of this elderly man presents a rare occurrence of metachronous primary cancers in the renal pelvis and colon.Bladder cancer is considered a metastasis of renal pelvis cancer after surgery.Optimal treatment can be implemented by evaluating the patient’s histological features,clinical history,and tumor distribution correctly.

Primary large cell neuroendocrine carcinoma of the bladder:A case report

BACKGROUND Large cell neuroendocrine carcinoma(LCNEC)of the bladder is a rare nonurothelial tumor of the bladder.The treatment of LCNEC of the bladder is different from that of urothelial carcinoma(UC);therefore,early and accurate diagnosis is particularly important.As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors,the clinical diagnosis of the disease remains challenging.CASE SUMMARY We report a 72-year-old female patient who presented with gross hematuria for 3 mo.A solitary tumor located in the anterior wall of the bladder was found by cystoscopy.Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment.The patient underwent partial cystectomy and was finally diagnosed with LCNEC(pT2bN0M0)based on the results of postoperative immunohistochemical examination.During the 10-mo follow-up,no signs of tumor recurrence or metastasis were found.CONCLUSION Immunohistochemical examination is essential for diagnosing LCNEC of the bladder.Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.

Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision

BACKGROUND Bladder cancer is a type of cancer with a high incidence in men.Plasma electrosurgery(PES)is often used in the treatment of bladder cancer.Postoperative complications often cause depression and anxiety in patients after surgery.AIM To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them.METHODS A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups.Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer.RESULTS Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery,economic status,educational level,and marital status.A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer,and the results showed that whether the risk factors were whether or not it was the first surgery,monthly income between 3000 and 3000-6000,secondary or junior high school education level,single,divorced,and widowed statuses.CONCLUSION The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries,economic status,level of education,and marital status.This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.

This pain drives me crazy:Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome

BACKGROUND Interstitial cystitis/bladder pain syndrome(IC/BPS)is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic,abdominal,and/or pelvic pain.Although the term cystitis suggests an inflammatory or infectious origin,no definite cause has been identified.It occurs in both sexes,but women are twice as much affected.AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS.METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS,we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy:("interstitial cystitis"OR"bladder pain syndrome")AND("mood disorder"OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk).RESULTS On September 27,2023,the PubMed search produced 223 articles,CINAHL 62,and the combined PsycLIT/PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36.Search on ClinicalTrials.gov produced 14 studies,of which none had available data.Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS,i.e.63 articles spanning from 2000 to October 2023.These studies identified depression and anxiety problems in the IC/BPS population,along with sleep problems and the tendency to catastrophizing.CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS.Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Effects of OGFOD1 in bladder cancer progression and its prognostic significance:Insights from bioinformatics analysis

Background:Previous studies have established the role of 2-oxoglutarate and Fe(II)-dependent oxygenase domain–containing protein 1(OGFOD1)in oncogenesis.The objective of this investigation was to discern the diagnostic and prognostic relevance of OGFOD1 within the context of bladder cancer(BLCA)using bioinformatics methodologies.Methods:We collected RNA sequencing data from The Cancer Genome Atlas database and verified it using the GSE13507 dataset.Immunohistochemical analysis was based on data from the human protein atlas,and the protein-protein interaction network was constructed using the STRING database.Bioinformatics analysis was performed using the R application,analyzing the correlation between clinical characteristics and OGFOD1 expression,exploring the potential mechanisms of OGFOD1 in BLCA through Kyoto Encyclopedia of Genes and Genomes analysis,and evaluating the diagnostic and prognostic value of OGFOD1 expression in BLCA through receiver operating characteristic curve analysis,Kaplan-Meier analysis,and multivariate Cox analysis.Furthermore,a BLCA prognostic nomogram was constructed.Results:We report higher expression levels of OGFOD1 in BLCA specimens compared with those in noncancerous tissues;this can be used to predict the outcome of the disease.Further,results suggest that OGFOD1 is implicated in the activation of the peroxisome proliferator-activated receptor signaling cascade,potentially interacting with other genes linked to expression in promoting the onset and progression of BLCA.Conclusions:OGFOD1 is a promising candidate as a prognostic indicator in BLCA.