Upper Tract Treatment of Urogenital Fistulas at the National Fistula Treatment Center (CNTF)

Introduction: Urogenital fistula is the existence of an abnormal pathway between a urinary organ and a genital organ. It is a public health problem because of its frequency and social aspect. The aim of this study was to analyse the management of urogenital fistulas by the upper route at the National Fistula Treatment Centre in N’Djamena. Material and Methods: This was a 10-year retrospective descriptive and analytical study from May 2011 to April 2021. The records of all patients who had received fistula treatment during this period were identified and analysed. Results: During the study period 2369 patients were managed for cure of urogenital fistula including 84 by the upper route, i.e. 3.5%. The mean age was 28.5 ± 8.13 years. Loss of urine was the most common reason for consultation (71.4%). Primigravida were represented in 50% (n = 42). The average gestational age was 3.2 ± 2.8 with extremes of 0 to 9 pregnancies. Obstetric aetiology was the most common (92.8%). Ureterovaginal fistulas were the most common anatomoclinical type (36.9%). Uretero-vesical reimplantation was the main surgical procedure (41.7%). Late postoperative follow-up was successful in 85.7% of cases. Conclusion: Urogenital fistulas are common in our practice. The only way to combat this scourge is through prevention through information, education and communication.

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.

Laparoscopic nephroureterectomy for upper tract urothelial carcinoma-Update

Upper urinary tract urothelial carcinomas(UTUCs)are uncommon and account for only 5%e10%of urothelial carcinomas.Pyelocaliceal tumors are about twice as common as ureteral tumors.Sixty percent of UTUCs are invasive at diagnosis.Radical nephroureterectomy,including the excision of the distal ureter and bladder cuff is standard of care for treatment of localized UTUCs,because of the high potential for recurrence,multifocality,and progression.Since first laparoscopic nephroureterectomy(LNU)was introduced by Clayman et al.in 1991 and improvement of laparoscopic technique and equipment,LNU has been reported to be equivalent to conventional open method.We reviewed the current literature of patients with UTUCs treated by LNU focusing on technical aspects,peri-operative and oncological outcomes.Laparoscopic radical nephroureterectomy offers the advantages of minimally invasive surgery without deteriorating the oncological outcome for treatment of UTUCs.Indications tend to increase as operator skills increase.Indications for laparoscopic or open nephroureterectomy are in principle the same.The basic requirement for laparoscopic surgery in UTUCs is to achieve benefits of minimal invasive surgery and maintain oncologic principles.

Upper tract urothelial carcinoma: Paradigm shift towards nephron sparing management

Upper tract urothelial carcinoma(UTUC) is relatively rare compared to urothelial carcinoma of the lower tract, comprising only 5%-10% of all urothelial cancers. Although both entities share histologic properties, UTUC tends to be more invasive at diagnosis and portend a worse prognosis, with a 5 year overall mortality of 23%. To date, the gold standard management of UTUC has been radical nephroureterectomy(RNU), with nephron sparing techniques reserved for solitary kidneys or cases where the patient could not tolerate radical surgery. Limited data from these series, as well as select series where nephron-sparing endoscopic management has been offered to a broader patient base, suggest that minimally invasive, nephron sparing techniques can offer comparable oncologic and survival outcomes to RNU in appropriately selected patients. We review the current literature on the topic and discuss long term outcomes and sequelae of the gold standard treatment, RNU. We also discuss the oncologic outcomes of minimally invasive, endoscopic management of UTUC. Our goal is to provide the reader a comprehensive overview of the current state of the field in order to inform and guide their treatment decisions.

Prognostic Factors and Oncological Outcomes after Radical Nephroureterctomy for Upper Tract Urothelial Carcinoma: Review of Contemporary Multi-Center Series

Upper tract urothelial cancers (UTUC) are uncommon and the information guiding their management used to be driven from small single center studies. Multi-center international collaborations should provide clinicians with best management practices as well as prognostic factors guiding treatment decisions and outcomes. We reviewed literature from the largest multicenter collaborations for radical nephroureterctomy (RNU) performed for management of UTUC. Our review included over 50 recent manuscripts from 2009-2012 that were published from multi-center UTUC collaboration groups. Our review aims to determine of the prognostic factors predicting oncological outcomes after RNU and to provide insights about possible maximization of cure with utilization of multimodal treatment approaches. Application of approaches comprising RNU including lymphadenectomy and systemic chemotherapy;particularly in neoadjuvant settings;might have implications on improvement of oncological outcomes in high risk patients.

Follow-Up Upper Tract Imaging Post-Nephroureterectomy for TCC: Need for a Protocol Driven Approach?

Objectives: We present a retrospective analysis of follow-up strategy adapted by different clinician in managing UTUC cases. Methods: Case notes of 83 patients undergoing nephroureterectomy for UTUC at our institute were selected. Their follow-up pattern and any imaging protocols for upper tract surveillance were studied retrospectively. Results: Our study highlighted diversity in clinicians’ overall approach at a time when no approved guidelines or standardised protocols were available. Conclusions: This study clearly highlighted the need for a protocol driven approach;which has lately been addressed with the introduction of EAU guidelines on this subject matter and majority of practising Urologists will adhere to it.

Contemporary management of upper tract urothelial cell carcinoma

Upper tract urothelial cell carcinoma(UTUCC),formerly known as transitional cell carcinoma of the upper urinary tract,is a rare oncologic disease in Western countries.Thus its disease process and its management are not as well defined as other urologic cancers. We are reviewing the current evidence based literature available to develop a plan for the treatment of UTUCC. A Pub Med search was completed using the key words "upper tract urothelial cell carcinoma","epidemiology","risk factor","treatment" and "prognosis". Six hundred fifty two articles were found. We narrowed our search to articles published between January 2004 and June 2016 for a more contemporary review of the topic. Four hundred seventy articles were then available for review. Further detailed search was performed for relevance on the topic and hundred one articles were selected for the review. Many risk factors have been found to be associated with the development of UTUCC,including tobacco use. Patients are often asymptomatic and may only present with microscopic or gross hematuria. Tumor grade and stage are pivotal in determining the treatment options for UTUCC. Advancements in endoscopic techniques have aided in the diagnosis,grading and treatment of this disease. Treatment options include topical therapy,with combinations of methotrexate,vinblastine,doxorubicin and cisplatin or gemcitibine or cisplatin,endoscopic resection,segmental ureterectomy and ureteral implantation,and nephroureterectomy,including bladder cuff. Treatment recommendations depend on tumor grade and stage,renal function,tumor location and the patient's prognosis. There are currently no tissue or blood-based biomarkers available to accurately monitor the disease. Further studies of gene expression and biomarkers may hopefully improve the management of this disease. Although rare in many countries,UTUCC is becoming more prevalent due to exposure to carcinogenic herbal remedies and other identifiable risk factors. Numerous treatment modalities,both surgical and chemotherapeutic,have been utilized to treat both low and high grade UTUCC tumors. Additional clinical trials are necessary to further develop methods for screening,treatment,and surveillance to improve management.

Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

Applications of gastric peroral endoscopic myotomy in the treatment of upper gastrointestinal tract disease

Gastric peroral endoscopic myotomy(G-POME)is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tun-nel around the pyloric sphincter.In 2013,Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy,prov-iding a new direction for the treatment of gastroparesis.With the recent and rapid development of G-POME therapy technology,progress has been made in the treatment of gastroparesis and other upper digestive tract diseases,such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture,with G-POME.This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.

Prognostic value of T cell immunoglobulin and mucin-domain containing-3 expression in upper gastrointestinal tract tumors:A meta-analysis

BACKGROUND There is a lack of robust prognostic markers for upper gastrointestinal(GI)tract cancers,including esophageal,gastric,and esophagogastric junction cancers.T cell immunoglobulin and mucin-domain containing-3(TIM3)plays a key immunomodulatory role and is linked to the prognosis of various cancers.However,the significance of TIM3 in upper GI tract tumors is still uncertain.AIM To investigate the prognostic value of TIM3 expression in upper GI tract tumors.METHODS A literature search was conducted on the PubMed,Embase,and Web of Science databases for relevant studies published until June 2023.After screening and quality assessment,studies that met the criteria were included in the metaanalysis.Statistical methods were used for the pooled analysis to assess the association of TIM3 expression in upper GI tract tumors with the prognosis and clinicopathological parameters.The results were reported with the hazard ratio(HR)and 95%confidence interval(CI).RESULTS Nine studies involving 2556 patients with upper GI tract cancer were included.High TIM3 expression was associated with a worse prognosis in upper GI tract cancer(HR:1.17,95%CI:1.01-1.36).Positive expression of TIM3 in gastric cancer was correlated with the T and N stage,but the difference was not statistically significant.However,TIM3 overexpression was significantly correlated with the TNM stage(odds ratio:1.21,95%CI:0.63-2.33;P<0.05).TIM3 expression showed no association with the other clinicopathological parameters.CONCLUSION High expression of TIM3 in the upper GI tract cancer is associated with a worse prognosis and advanced T or N stages,indicating its potential value as a prognostic biomarker.These findings may provide a basis for the personalized treatment of upper GI tract cancers.

Risk factors of concurrent urinary sepsis in patients with diabetes mellitus comorbid with upper urinary tract calculi

BACKGROUND Urinary sepsis is frequently seen in patients with diabetes mellitus(DM)complicated with upper urinary tract calculi(UUTCs).Currently,the known risk factors of urinary sepsis are not uniform.AIM To analyze the risk factors of concurrent urinary sepsis in patients with DM complicated with UUTCs by logistic regression.METHODS We retrospectively analyzed 384 patients with DM complicated with UUTCs treated in People’s Hospital of Jincheng between February 2018 and May 2022.The patients were screened according to the inclusion and exclusion criteria,and 204 patients were enrolled.The patients were assigned to an occurrence group(n=78)and a nonoccurrence group(n=126).Logistic regression was adopted to analyze the risk factors for urinary sepsis,and a risk prediction model was established.RESULTS Gender,age,history of lumbago and abdominal pain,operation time,urine leukocytes(U-LEU)and urine glucose(U-GLU)were independent risk factors for patients with concurrent urinary sepsis(P<0.05).Risk score=0.794×gender+0.941×age+0.901×history of lumbago and abdominal pain-1.071×operation time+1.972×U-LEU+1.541×U-GLU.The occurrence group had notably higher risk scores than the nonoccurrence group(P<0.0001).The area under the curve of risk score for forecasting concurrent urinary sepsis in patients was 0.801,with specificity of 73.07%,sensitivity of 79.36%and Youden index of 52.44%.CONCLUSION Sex,age,history of lumbar and abdominal pain,operation time,ULEU and UGLU are independent risk factors for urogenic sepsis in diabetic patients with UUTC.

Association of plant-based diets with the risk of upper gastrointestinal tract cancers:A systematic review and meta-analysis

Background:Diets rich in red or processed meat have been linked to an increased risk of cancers within the digestive system.It has been suggested that a plant-based diet may have protective effects against digestive system cancers.This study aimed to determine the association between plant-based diets and upper gastrointestinal tract cancers(UGTC).Methods:We conducted a systematic review and meta-analysis of observational studies.We searched the PubMed,Medline,Embase,and Web of Science databases for articles published up to September 30,2023.We pooled the risk ratios(RR)with the corresponding 95%confi-dence intervals(CI)using fixed or random-effects models.Results:Our meta-analysis included 16 studies(30 results).The data revealed a strong inverse association between a high intake of plant-based diets and UGTC(RR=0.60,95%CI=0.49-0.72),specifically gastric cancer(GC,RR=0.53,95%CI=0.42-0.67)and esophageal can-cer(EC,RR=0.63,95%CI=0.42-0.96).This relationship was not significant for gastric cardia cancer(GCA)or esophagogastric junctional cancer(EGJC,RR=0.76,95%CI=0.47-1.22).A subgroup analysis showed the association was significant in studies from Asia and Europe,as well as in studies utilizing indices such as a vegetarian diet,Mediterranean diet,the plant-based diet index,and principal component analy-sis(PCA)dietary patterns.There was no indication of publication bias among the analyzed studies.Conclusions:This meta-analysis highlights the potential health benefits of plant-based diets in preventing UGTC,particularly regarding esophageal squamous cell carcinoma(ESCC)and GC.Nevertheless,additional research is required to validate these results and explore the un-derlying mechanisms.

A Meta-Analysis of the Effectiveness of Vitamin C in the Prevention and Treatment of Childhood Upper Respiratory Tract Infections

Background:The effectiveness of vitamin C in the prevention and treatment of pediatric upper respiratory tract infections was evaluated in a meta-analysis.Methods:A total 2,573 children with upper respiratory tract infections were included in the meta-analysis,1,280 of whom received vitamin C and 1,293 who received control medication.The analysis of findings related to the studies included was done through random or fixed effects model to determine whether vitamin C supplementation could stop and control upper respiratory tract infections in children using mean difference(MD)with 95%confidence intervals(CIs).Results:On average,vitamin C-treated children had fewer upper respiratory tract infection bouts,their illness lasted shorter(MD-0.84;95%CI-1.47 to-0.20,P=0.009),and they were less contagious than the control.Conclusions:The number of episodes and illness duration of upper respiratory tract-infected pediatric subjects were considerably reduced in the intervention group(vitamin C)compared to the control.Due to the small sample size in four of 11 studies and the limited number of studies included for comparison,the outcomes should be carefully examined.

The Effect of Comfort Nursing on the Compliance and Efficacy of Treatment for Children with Acute Otitis Media Caused by Upper Respiratory Tract Infection

Objective:To explore and analyze the clinical effect of comfort nursing on children with acute otitis media.Methods:62 children with acute otitis media caused by upper respiratory tract infection who visited the outpatient clinic of our hospital from June 2022 to June 2023 were selected for this study.They were divided into a study group(n=31)and a control group(n=31).Children in the control group received basic care,while children in the study group received comfort nursing along with basic care.The hearing thresholds,body temperature,treatment compliance,and nursing satisfaction of the two groups of children were compared.Results:After the nursing intervention,the hearing threshold and average body temperature of the children in the study group were lower than those in the control group(P<0.05);the treatment compliance of the children in the study group was higher than that in the control group(P<0.05);the nursing satisfaction of the study group was higher than that of the control group(P<0.05).Conclusion:Comfort nursing can improve the treatment effect,treatment compliance,and nursing satisfaction of children with children with acute otitis media caused by upper respiratory tract infection.

Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions:Clinical significance

Transoral endoscopic resections in treating upper gastrointestinal submucosal lesions have the advantages of maintaining the integrity of the gastrointestinal lumen,avoiding perforation and reducing gastrointestinal fistulae.They are becoming more widely used in clinical practice,but,they may also present a variety of complications.Gas-related complications are one of the most common,which can be left untreated if the symptoms are mild,but in severe cases,they can lead to rapid changes in the respiratory and circulatory systems in a short period,which can be life-threatening.Therefore,it is important to predict the occurrence of gas-related complications early and take preventive measures actively.Based on the authors'results in the prepublication of the article“Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions,”and in conjunction with our evaluation and additions to the relevant content,radiographs may help screen patients at high risk for gas-related complications.Controlling blood glucose levels,shortening the duration of surgery,and choosing the most appropriate surgical resection may positively impact the prognosis of patients at high risk for gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions.

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.

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.