Prognostic value of platelet-to-lymphocyte ratio in upper tract urothelial carcinoma patients treated with radical nephroureterectomy:A metaanalysis

Objective:To evaluate the prognostic value of platelet-to-lymphocyte ratio(PLR)in upper tract urothelial carcinoma(UTUC)patients treated with radical nephroureterectomy.Methods:This study was pre-registered in PROSPERO(No.CRD42020186645).Two reviewers independently performed a comprehensive literature search on PubMed,Web of Science,EMBASE,Cochrane Library databases,China Biology Medicine disc(CBM),Wanfang database,and China National Knowledge Infrastructure(CNKI)from inception to May 2021 for prospective or retrospective cohort studies evaluating the prognostic value of PLR.Literature was analyzed with inclusion and exclusion criteria.Data and other useful clinicopathological features were extracted and analyzed with fixed or random-effect models when applicable.Heterogeneity was assessed on the basis of Cochran’s Q test and I2 statistic.Publication bias was assessed with funnel plots and precisely assessed by Egger's tests.Results:A total of ten studies involving 3287 UTUC patients were included.Meta-analysis showed that elevated preoperative PLR was associated with worse overall survival(HR=1.51,95%CI 1.17-1.94,P=0.001),cancer specific survival(HR=1.52,95%CI 1.21-1.90,P<0.001),disease free survival(HR=1.32,95%CI 1.12-1.56,P=0.001),and progression free survival(HR=1.88,95%CI 1.41-2.52,P<0.001).Furthermore,the sensitivity analyses validated the stability and reliability of the results.Conclusion:The present meta-analysis demonstrates a significant association between elevated preoperative PLR and poor prognosis of UTUC patients treated with radical nephroureterectomy.Hence,PLR could be helpful as a potential prognostic biomarker to guide clinical decision-making and select individualized treatment strategies for UTUC patients.However,more prospective and large-scale trials are needed to provide more evidence.

Research progress in genomics associated with prognosis of upper tract urothelial carcinoma

Upper tract urothelial carcinoma and bladder urothelial carcinoma both belong to urothelial carcinoma,which is a malignant tumor occurring in the renal pelvis and ureteral urothelium.The incidence rate of UTUC is higher among Asians and it shows various pathogenic factors.Patients of UTUC have a short lifespan,and most of them have shown invasive malignant tumors at the time of initial diagnosis.The treatment of most UTUC patients is limited to surgical resection,radiotherapy and chemotherapy in clinical.Due to its rarity,the studies on targeted therapy are rare.With the development of the targeted therapy and immunotherapy,genomics exploration that affects the prognosis of UTUC becomes particularly important.In this paper,we intend to review the differential expression,clinical significance and some special types of UTUC genomes through the UTUC genome.

Percutaneous resection of upper tract urothelial cell carcinoma:When,how,and is it safe?

Introduction:In the management of upper tract urothelial cell carcinoma(UTUC)endoscopic,nephron sparing procedures like ureterorenoscopy(URS)or percutaneous tumour resection(PCTR)still play a very limited role.This could lead to possible unnecessary radical nephroureterectomies(RNU),still being the gold standard treatment.The risk of chronic kidney disease(CKD)later in life is important.In this study we present the results of 24-year experience with PCTR in a single institution.Methods:We identified 44 patients who underwent PCTR between 1992 and 2015.Radical resection was achieved in 40 patients who were included in this study.Demographic and clinical data,including tumour recurrence,progression to RNU,tumour grade and overall survival(OS)were retrospectively acquired.An outcome analysis was conducted.Results:Median age at diagnosis was 68 years(range 42-94 years).Low grade tumours were found in 37 patients(92.5%)and high grade tumours in three patients(7.5%).Median followup was 53 months during which 20 patients developed upper tract recurrences(50.0%).The longest time to recurrence was 97 months.At follow-up 11 patients(27.5%)underwent an RNU and two patients died from UTUC.RNU could be avoided in 29 patients(72.5%).In this study we found that multifocality is a significant risk factor for recurrence,but not for stage progression to RNU.Conclusion:PCTR is a surgically and oncologically safe procedure.Renal preservation in patients with UTUC who are eligible for percutaneous resection can be achieved in the majority of patients.Selection criteria for PCTR should be further refined,leading to a wider application of PCTR in the future.Follow-up needs invasive procedures and should be long term.

Oncological impact of different distal ureter managements during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma

BACKGROUND The current standard surgical treatment for non-metastatic upper urinary tract urothelial carcinoma(UTUC)is radical nephroureterectomy(RNU)with bladder cuff excision(BCE).Typically,BCE techniques are classified in one of the following three categories:An open technique described as intrasvesical incision of the bladder cuff,a transurethral incision of the bladder cuff(TUBC),and an extravesical incision of the bladder cuff(EVBC)method.Even though each of these management techniques are widely used,there is no consensus about which surgical intervention is superior,with the best oncologic outcomes.AIM To investigate the oncological outcomes of three BCE methods during RNU for primary UTUC patients.METHODS We retrospectively analyzed the data of 248 primary UTUC patients,who underwent RNU with BCE between January 2004 to December 2018.Patients were analyzed according to each BCE method.Data extracted included patient demographics,perioperative parameters,and oncological outcomes.Statistical analyses were performed using chi-square and log-rank tests.The Cox proportional hazards regression model was utilized to identify independent predictors.P<0.05 was considered statistically significant.RESULTS Of the 248 participants,39.9%(n=99)underwent intrasvesical incision of the bladder cuff,38.7%(n=96)EVBC,and 21.4%(n=53)TUBC.At a median followup of 44.2 mo,bladder recurrence developed in 17.2%,12.5%,and 13.2%of the cases,respectively.Cancer-specific deaths occurred in 11.1%,5.2%,and 7.5%of patients,respectively.Kaplan-Meier survival curves with a log-rank test highlighted no significant differences in intravesical recurrence-free survival,cancer-specific survival,and overall survival among these approaches with P values of 0.987,0.825,and 0.497,respectively.Multivariate analysis showed that the lower ureter location appears to have inferior intravesical recurrence-free survival(P=0.042).However,cancer-specific survival and overall survival were independently influenced by tumor stage(hazard ratio[HR]=8.439;95%con
dence interval:2.424-29.377;P=0.001)and lymph node status(HR=14.343;95%CI:5.176-39.745;P<0.001).CONCLUSION All three techniques had comparable outcomes;although,EVBC and TUBC are minimally invasive.While based upon rather limited data,these findings will support urologists in blending experience with evidence to inform patient choices.However,larger,rigorously designed,multicenter studies with long term outcomes are still required.

Conservative management of an early abdominal complication during a Tullio percutaneous endoscopic excision of renal pelvis urothelial carcinoma:A case report

BACKGROUND Upper tract urothelial carcinoma(UTUC)representing only a small fraction of all urothelial tumors.It predominantly affects the renal pelvis in men,often coexisting with bladder carcinoma.UTUC displays a more aggressive genetic profile compared to bladder neoplasms,with the majority of patients presenting with advanced disease.Histologically,about a quarter of UTUC cases exhibit high-grade subtypes,associated with a worse prognosis.Tobacco use and past exposure to aromatic amines are significant risk factors for UTUC.Imaging modalities such as Uro-computed tomography and magnetic resonance imaging play crucial roles in diagnosis.Ureterorenoscopy is vital for direct visualization and biopsy sampling,but its limited sampling capacity presents challenges in determining tumor depth and staging.Traditionally,nephroureterectomy with bladder cuff excision has been the gold-standard treatment for UTUC.Endoscopic conservative treatment has recently emerged as a viable option for selected patients,offering comparable oncological outcomes to radical surgery.Percutaneous access is also feasible for larger intrarenal tumors.CASE SUMMARY We present a case of an 84-year-old woman who underwent percutaneous endoscopic excision of a renal pelvis neoplasm using the Tullio laser.Despite successful tumor removal,the patient experienced a postoperative complication with abdominal fluid leakage.Conservative management effectively resolved the complication.Given the patient's age and refusal for radical surgery,the conservative approach proved to be a valid therapeutic choice.CONCLUSION Overall,UTUC remains a diagnostic and therapeutic challenge due to its rarity.However,advances in endoscopic and percutaneous techniques provide valuable alternatives for selected patients,warranting further exploration in this evolving field.

Impact of surgical management of upper tract urothelial cancer in octogenarians:A population-based study

Background Upper tract urothelial carcinoma(UTUC)is an aggressive disease with a high progression rate.The standardmanagement for this disease is nephroureterectomy.Nephron sparing nonradical surgery is an alternative therapeutic approach.In men with limited life expectancy,the potential harm of UTUC progression must be weighed against surgical morbidity and mortality,and thus,more conservative approaches may be selected.This study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized UTUC.Materials and methods A search was conducted in the Surveillance,Epidemiology,and End Results database for patients older than 80 years who were diagnosed with localized(T1–2N0M0)cancer in the renal pelvis or ureter as the only malignancy from 2004 to 2015.Patients were divided into 3 therapeutic groups:no surgery,local intervention(ie,local tumor excision or segmented ureterectomy),and radical surgery(nephroureterectomy).Demographic and cancer-related parameter data were collected.Logistic regression analysis was conducted to investigate predictors for surgical treatment.Kaplan-Meier curves and Cox regression were used to analyze survival outcomes.Results Data from 774 patients were analyzed,including 205 in the no-surgery group,181 in the local intervention group,and 388 in the radical surgery group.Older,African American patients with T1 stage disease were less likely to receive surgical treatment.Among surgically treated patients,renal pelvic tumors,and high-grade and T2 stage disease were associated with radical resection.Surgically treated patients had a longer median overall survival(OS)than in those treated nonsurgically(13,35,and 47 months in no-surgery,local intervention,and radical surgery groups,respectively;p<0.001).Although surgically treated patients demonstrated higher 5-year OS(8.8%[no surgery],23.2%[local intervention],and 23.5%[radical surgery],p<0.001)and 5-year disease-specific survival(DSS)(41.0%[no surgery],69.1%[local intervention],and 72.9%[radical surgery];p<0.001)than in those treated nonsurgically,no significant differences were found between the local intervention and radical surgery groups(p>0.05).Based on multivariate Cox regression analysis,surgical treatments,including both nonradical and radical resection,were independently associated with improved OS and DSS after controlling for age,marital status,tumor grade,and radiation status.Conclusions Patients older than 80 years with localized UTUC who undergo surgery demonstrate longer survival.Radical and nonradical resections seemto have similar OS and DSS outcomes.Thus,when clinically indicated in this population,a more conservative surgical approach may be reasonable.

Metachronous urothelial carcinoma in the renal pelvis,bladder,and urethra:A case report

BACKGROUND Urothelial carcinoma(UC)is a common malignancy of the urinary system that can occur anywhere from the renal pelvis to the proximal urethra.Most UCs are in the bladder and have multifocal growth.Upper urinary tract UC(UTUC),which occurs in the renal pelvis or ureter,accounts for only 5%to 10%of UCs.CASE SUMMARY In March 2015,a 70-year-old male who initially presented to a local hospital with a complaint of painless hematuria was diagnosed with UTUC of the right renal pelvis.The doctors administered radical nephroureterectomy and bladder cuff excision.Although the doctors recommended intravesical chemotherapy and regular follow-up,he rejected this advice.In December 2016,the patient presented at our hospital with dysuria.We identified UC in the residual bladder and administered radical cystectomy and left cutaneous ureterostomy.In November 2021,he presented again with urethral bleeding.We detected urethral UC as the cause of urethral orifice bleeding and administered radical urethrectomy.Since then,he has visited regularly for 6-mo follow-ups,and was in stable condition as of December 2022.CONCLUSION UTUC is prone to seeding and recurrence.Adjuvant instillation therapy and intense surveillance are crucial for these patients.

Current laser therapy options for endoscopic treatment of upper tract urothelial carcinoma

Endoscopic management via retrograde ureteroscopic laser ablation of upper tract urothelial carcinoma(UTUC)has become the preferred treatment modality for low-risk tumors.The most popular ablative lasers over the past 15-20 years have been the holmium:yttrium-aluminum-garnet(Ho∶YAG)and neodymium(Nd∶YAG)lasers,but recently the thulium(Th∶YAG)laser has emerged as a potential alternative.This review compares the mechanism of action,physiological properties and effects,and oncologic outcomes of Ho∶YAG/Nd∶YAG lasers versus the Th∶YAG laser for UTUC treatment.Potential advantages of the Th∶YAG laser over existing technologies are outlined,followed by a discussion of emerging laser technologies in UTUC management.

Comparison of survival outcomes between laparoscopic versus open radical nephroureterectomy in upper tract urothelial cancer patients:Experiences of a tertiary care single center

Objectives:To test for differences in overall and recurrence-free survival between laparoscopic and open surgical approaches in patients undergoing radical nephroureterectomy(RNU)for upper tract urothelial carcinoma(UTUC).Materials and methods:We retrospectively identified patients treated for UTUC from 2010 to 2020 from our institutional database.Patients undergoing laparoscopic or open RNU with no suspicion of metastasis(cM0)were for the current study population.Patients with suspected metastases at diagnosis(cM1)or those undergoing other surgical treatments were excluded.Tabulation was performed according to the laparoscopic versus open surgical approach.Kaplan-Meier plots were used to test for differences in overall and recurrence-free survival with regard to the surgical approach.Furthermore,separate Kaplan-Meier plots were used to test the effect of preoperative ureterorenoscopy on overall and recurrence-free survival within the overall study cohort.Results:Of the 59 patients who underwent nephroureterectomy,29%(n=17)underwent laparoscopic nephroureterectomy,whereas 71%(n=42)underwent open nephroureterectomy.Patient and tumor characteristics were comparable between groups(p≥0.2).The median overall survival was 93 and 73 months in the laparoscopic nephroureterectomy group compared to the open nephroureterectomy group(p=0.5),respectively.The median recurrence-free survival did not differ between open and laparoscopic nephroureterectomies(73 months for both groups;p=0.9).Furthermore,the median overall and recurrence-free survival rates did not differ between patients treated with and without preoperative ureterorenoscopy.Conclusions:The results of this retrospective,single-center institution showed that overall and recurrence-free survival rates did not differ between patients with UTUC treated with laparoscopic and open RNU.Furthermore,preoperative ureterorenoscopy before RNU was not associated with higher overall or recurrence-free survival rates.

Validation of the Pretreatment Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor in a Large Cohort of Chinese Patients with Upper Tract Urothelial Carcinoma

Background：The pretreatment neutrophil-to-lymphocyte ratio （NLR） has been reported to be a prognostic factor in various types of carcinomas.The aim of this study was to investigate the prognostic value of pretreatment NLR in a large cohort of Chinese patients with upper tract urothelial carcinoma （UTUC）.Methods：We retrospectively analyzed the medical data of 656 UTUC patients who underwent radical nephroureterectomy （RNU） from 2001 to 2011 at Peking University First Hospital.Receiver operating characteristic （ROC） curve analysis was performed to calculate the optimal cutoffpoint of pretreatment NLR.Uni-and multi-variate analyses were used to identify the prognostic factors for cancer-specific survival （CSS） and intravesical recurrence-free survival （IVRFS）.Results：The optimal cutoff point of pretreatment NLR was 2.40 by ROC curves,by which patients with high NLR （NLR 〉2.40） and low NLR （NLR 〈2.40） accounted for 314 （47.9%） and 342 （52.1%） patients,respectively.Patients with a high pretreatment NLR tended to have high tumor grades （x2 =15.725,P〈 0.001）,high tumor stages （x2 =25.416,P〈 0.001）,tumor sizes 〉5 cm （x2 =8.213,P=0.005）,ipsilateral hydronephrosis （x2 =4.624,P =0.033）,and concomitant carcinoma in situ （CIS） （x2 =9.517,P =0.003）.A high pretreatment NLR （hazard ratio [HR] =1.820,P=0.001）,main tumor diameter 〉5 cm （HR =1.789,P =0.009）,lymph node metastasis （HR =1.863,P =0.024）,and high tumor stage （HR =1.745,P 〈 0.001） independently predicted poor CSS after surgery,while only concomitant carcinoma in situ （CIS） （HR =2.164,P =0.034）,ureteroscopy before surgery （HR =1.701,P =0.015）,and high tumor grade （HR =1.645,P =0.018） were independent predictors of IVRFS after RNU.Conclusions：The pretreatment NLR was related to some adverse clinicopathological features and was an independent predictor of CSS,although not IVRFS,in Chinese UTUC patients.

Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma

GATA binding protein 3 (GATA3) and mismatch repair (MMR) deficiency contribute to the development of urothelial carcinoma. However, the combined expression of GATA3 and microsatellite instability (MSI) in upper tract urothelial carcinoma (UTUC) and its prognostic value have not been investigated. Here, we immunohistochemically stained GATA3 and MMR proteins in 108 UTUC samples. GATA3 was positive in 74 cases, and its expression was significantly lower than in adjacent benign urothelium (P<0.001). Loss of GATA3 expression was statistically associated with adverse clinicopathologic parameters, such as advanced stage, lymphovascular invasion, neural invasion, lymph node metastasis, and extensive necrosis. Cancer-specific survival (CSS, P=0.028) and disease-free survival (DFS, P=0.024) were significantly shorter in patients with GATA3 negative tumors than in patients with GATA3 positive tumors. The absence of MMR proteins was observed in 8.3% of the cases, and focal staining was identified in 13.0%. When using “lax criteria” which resulted in counting cases as negative where MMR staining was in fact focally positive (<5%), we found that GATA3 was inversely associated with MSI (P=0.005). Moreover, GATA3−/microsatellite stability (MS) tumors were correlated with advanced pT stage (P<0.001) and poor outcome (P=0.019 for CSS, P=0.016 for DFS) compared with GATA3+/MSI ones. The GATA3−/MSI cases had unfavorable clinical outcomes compared with GATA3+/MSI cases (P=0.008 for CSS, P=0.023 for DFS). This finding raises a question as to whether GATA3 interacts with MSI through the TGF-β signaling pathway and regulates UTUC progression.

Clipping the extremity of ureter prior to nephroureterectomy is effective in preventing subsequent bladder recurrence after upper urinary tract urothelial carcinoma

Background Bladder recurrent disease is still a challenge in the treatment of upper tract urothelial carcinoma （UTUC）. This controlled study aims to investigate the efficacy of early clipping of the distal ureter prior to nephroureterectomy （NU） to prevent bladder recurrence after UTUC.

The interplay of cell cycle and DNA repair gene alterations in upper tract urothelial carcinoma:predictive and prognostic implications

Upper tract urothelial carcinoma(UTUC)is rare but can occur sporadically outside the context of Lynch syndrome.In these cases,knowing whether non-mismatch repair(MMR),DNA damage response and repair(DDR),and cell cycle gene alterationsmay predict responses to chemotherapy orimmunotherapy and survival is of clinical importance.This study examined the germline and somatic mutational landscape of two UTUC patients with differential responses to programmed death 1(PD-1)/PD-ligand 1(PD-L1)immune checkpoint inhibitors and queried three independent UTUC cohort studies for co-occurrence of key cell cycle and DDR genes,as well as for their associations with overall survival(OS).TP53 and RB1 emerged as potential determinants of shorter OS in UTUC cohort patients,regardless of concurrent DDR alterations,and if prospectively assessed in larger studies they might also explain resistance to PD-1/PD-L1 blockade despite PD-L1 expression.

Synchronous renal pelvis carcinoma associated with small lymphocytic lymphoma:A case report

BACKGROUND Chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL) is often associated with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin.Coincidence of CLL/SLL and urothelial carcinoma(UC) is very rare.Herein,we report a case of synchronous renal pelvis carcinoma with SLL.CASE SUMMARY A 78-year-old man presented with the complaint of terminal painless gross hematuria for the past 2 mo.On physical examination,enlarged lymph nodes were palpable in the cervical and axillary regions.The patient’s peripheral blood film was normal.He had a significant smoking history for the past 50 years.Cystoscopy revealed bleeding in the left upper urinary tract.Abdominal computed tomography imaging demonstrated a left renal pelvis tumor.The patient underwent laparoscopic radical nephroureterectomy.Histopathology revealed left renal pelvis high-grade invasive papillary UC and SLL involving the kidney and bone marrow.Renal pelvis lymphatic tissue and lymphocytes were positive for CD5,CD20,and CD23.In addition,the following results were obtained:CD3(-),Ki-67(30%+),Bcl-2(+),Bcl-6(+),CD10(-),and CD79a(+).Moreover,no UC metastasis was observed in the lymph nodes.CONCLUSION This is the first case of coincident CLL/SLL and upper tract UC in the literature.Cancer patients with lymphadenopathies should always be investigated to rule out the possibility of synchronous or metachronous malignancy.

Genitourinary manifestations of Lynch syndrome in the urological practice

Objective:Lynch syndrome(LS)is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM gene.From a clinical perspective,LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general population.We aimed to provide a comprehensive overview of all the genitourinary manifestations of LS,focusing on incidence,diagnosis,clinical features,therapeutic strategies,and screening protocols.Methods:Previous literature was assessed through Medline,Scopus,and Google Scholar data-bases.A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was provided.Results:In the LS tumor spectrum,upper tract urothelial carcinoma(UTUC)represents the third most frequent malignancy,and the first most common cancer in the urological field,with an approximately 14-fold increased risk of developing UTUC compared to general population.LS diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process,including(i)clinical criteria,(ii)molecular testing,and(iii)genetic testing to confirm the hereditary disorder.The current European Association of Urology(EAU)guidelines recommend to perform molecular testing among UTUC patients under 65 years old,or UTUC patients with personal history of LS-related tumor,or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor,or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of onset.Newly diagnosed LS patients should be referred to a multidisci-plinary management,including gastroenterologists and gynecologists.Finally,considering the increased risk of metachronous recurrence,treatments other than radical nephroureterectomy may be a valuable therapeutic alternative.Whether urological malignancies other than UTUC should be included in the LS tumor spectrum is still controversial.Conclusion:Considering the strict association between UTUC and LS,we believe that the urologist should recognize patients at increased risk for hereditary disease according to current EAU clinical criteria and address them to a comprehensive diagnostic algorithm,including molecular evaluationandgenetic testing.To date,literature lacks clear evidence regarding the role of LS in developing bladder cancer,prostate cancer,or renal cell carcinoma,and current data are still inconclusive,highlighting the urgent need for further studies.