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.

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.

Summarizing the evidence for robotic-assisted bladder neck reconstruction: Systematic review of patency and incontinence outcomes

Objective:Bladder neck contracture and vesicourethral anastomotic stenosis are difficult to manage endoscopically,and open repair is associated with high rates of incontinence.In recent years,there have been increasing reports of robotic-assisted bladder neck reconstruction in the literature.However,existing studies are small,heterogeneous case series.The objective of this study was to perform a systematic review of robotic-assisted bladder neck reconstruction to better evaluate patency and incontinence outcomes.Methods:We performed a systematic review of PubMed from first available date to May 2023 for all studies evaluating robotic-assisted reconstructive surgery of the bladder neck in adult men.Articles in non-English,author replies,editorials,pediatric-based studies,and reviews were excluded.Outcomes of interest were patency and incontinence rates,which were pooled when appropriate.Results:After identifying 158 articles on initial search,we included only ten studies that fit all aforementioned criteria for robotic-assisted bladder neck reconstruction.All were case series published from March 2018 to March 2022 ranging from six to 32 men,with the median follow-up of 5e23 months.A total of 119 patients were included in our analysis.A variety of etiologies and surgical techniques were described.Patency rates ranged from 50%to 100%,and pooled patency was 80%(95/119).De novo incontinence rates ranged from 0%to 33%,and pooled incontinence was 17%(8/47).Our findings were limited by small sample sizes,relatively short follow-ups,and heterogeneity between studies.

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.

Retraction:miR-203 suppresses bladder cancer cell growth and targets twist1

Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.

Cryoablation techniques in bladder cancer: A review

Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldwide.The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer(NMIBC)is transurethral resection of bladder tumors(TURBT).Currently,the standard of care for muscle-invasive bladder cancer(MIBC)is neoadjuvant chemotherapy followed by radical cystectomy.Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue.This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney,prostate gland,lung,liver,and breast,and is particularly effective for unresectable tumors,offering less trauma,quick recovery,good tolerability,and symptom control.However,cryoablation has its limitations.Over the past few years,cryoablation therapy has emerged as a new method for treating early BC.This treatment is minimally invasive,precise,and offers quick recovery,providing patients with a new treatment option.Although randomized studies are still limited,increasing evidence suggests its potential application in bladder cancer combined with transurethral resection(TURBT)or medication.Cryoablation is not standard therapy for bladder cancer.Treatment decisions should be discussed by a multidisciplinary team of urologists,oncologists,and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.

Chemosensitizing Effect of Monk Fruit Extract on Human Bladder Cancer Cells

The outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive extracts of monk fruit (Siraitia grosvenori) with anticancer activity. We then investigated if these extracts might have chemosensitizing effect to improve the efficacy of drugs clinically used today. Four different drugs, cisplatin (CPL), carboplatin (CBL), mitomycin C (MMC), and gemcitabine (GEM), were used in this study. Human bladder cancer T24 cells were treated with each drug itself or drug combined with either LLE or MOG (two types of monk fruit extracts). Cell viability was determined to assess anticancer effect and also explored the anticancer mechanism of such combinations, focusing on the status of glycolysis, cell cycle, and chromatin structure. Cell viability test showed that all drugs had anticancer activity, reducing cell viability, but only CPL showed the enhanced anticancer effect when combined with LLE (not with MOG). The rest of three drugs had no such effects with LLE or MOG. The CPL/LLE combination was found to disrupt glycolysis, by inhibiting hexokinase activity, resulted in the decreased ATP synthesis. This combination also blocked the cell cycle progression, due to a G1 cell cycle arrest. Moreover, the two epigenetic regulators, DNA methyltransferase and histone deacetylase, were inactivated with the combination, indicating chromatin modifications. Ultimately, these treated cells were found to undergo apoptosis. In conclusion, anticancer activity of CPL can be significantly enhanced with LLE. This chemosensitizing effect is attributed to the glycolysis inhibition, a G1 cell cycle arrest, and chromatin modifications, ultimately leading to apoptosis. Thus, certain natural products such as LLE could be used as an adjuvant agent in current chemotherapy, improving the drug efficacy but minimizing side effects.

Uncovering the epidemiology of bladder cancer in the Arab world: A review of risk factors, molecular mechanisms, and clinical features

Objective:Bladder cancer(BC)is a significant public health concern in the Middle East and North Africa,but the epidemiology and clinicopathology of the disease and contributors to high mortality in this region remain poorly understood.The aim of this systematic review was to investigate the epidemiological features of BC in the Arab world and compare them to those in Western countries in order to improve the management of this disease.Methods:An extensive electronic search of the PubMed/PMC and Cochrane Library databases was conducted to identify all articles published until May 2022,following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.A total of 95 articles were included in the final analysis after title,abstract,and full-text screening,with additional data obtained from the GLOBOCAN and WHO 2020 databases.

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.

High Hydrostatic Pressure Exacerbates Bladder Fibrosis through Activating Piezo1

Objective Bladder outlet obstruction(BOO)results in significant fibrosis in the chronic stage and elevated bladder pressure.Piezo1 is a type of mechanosensitive(MS)channel that directly responds to mechanical stimuli.To identify new targets for intervention in the treatment of BOO-induced fibrosis,this study investigated the impact of high hydrostatic pressure(HHP)on Piezo1 activity and the progression of bladder fibrosis.Methods Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders.Bladder fibroblasts were cultured under normal atmospheric conditions(0 cmH_(2)O)or exposed to HHP(50 cmH_(2)O or 100 cmH_(2)O).Agonists or inhibitors of Piezo1,YAP1,and ROCK1 were used to determine the underlying mechanism.Results The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group.HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts.Additionally,the protein expression levels of Piezo1,YAP1,ROCK1 were elevated,and calcium influx was increased as the pressure increased.These effects were attenuated by the Piezo1 inhibitor Dooku1.The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts,and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro.However,these effects could be partially inhibited by YAP1 or ROCK inhibitors.

A Prognostic Biomarker for Bladder Cancer Correlated with Immune Infiltration Is PAEP

Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.

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.

LncRNA MEG3 Inhibits the Epithelial-mesenchymal Transition of Bladder Cancer Cells through the Snail/E-cadherin Axis

Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Methods Cell invasion,migration,and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells.The expression levels of E-cadherin were measured using Western blotting,RT-qPCR,and dual luciferase reporter assays.RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets.Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin.The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin.Additionally,MEG3 suppressed the phosphorylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinase(JNK),and P38,thereby decreasing the expression of Snail and stimulating the expression of E-cadherin.Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells,indicating its potential as a promising therapeutic target for the treatment of bladder cancer.

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.

Automatic detection method of bladder tumor cells based on color and shape features

Bladder urothelial carcinoma is the most common malignant tumor disease in urinary system,and its incidence rate ranks ninth in the world.In recent years,the continuous development of hyperspectral imaging technology has provided a new tool for the auxiliary diagnosis of bladder cancer.In this study,based on microscopic hyperspectral data,an automatic detection algorithm of bladder tumor cells combining color features and shape features is proposed.Support vector machine(SVM)is used to build classification models and compare the classification performance of spectral feature,spectral and shape fusion feature,and the fusion feature proposed in this paper on the same classifier.The results show that the sensitivity,specificity,and accuracy of our classification algorithm based on shape and color fusion features are 0.952,0.897,and 0.920,respectively,which are better than the classification algorithm only using spectral features.Therefore,this study can effectively extract the cell features of bladder urothelial carcinoma smear,thus achieving automatic,real-time,and noninvasive detection of bladder tumor cells,and then helping doctors improve the efficiency of pathological diagnosis of bladder urothelial cancer,and providing a reliable basis for doctors to choose treatment plans and judge the prognosis of the disease.

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.

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.

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.