Ureteral Cancer Research Articles

Postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS): a single-center study

ObjectiveThe purpose of this study was to evaluate the efficacy of postoperative adjuvant radiotherapy for patients with upper tract urothelial carcinoma (UTUC) who underwent kidney-sparing surgery (KSS).MethodsWe retrospectively reviewed the clinical records of 31 patients with primary UTUC who underwent kidney-sparing surgery (KSS) and who were treated with adjuvant radiotherapy at our center between October 1998 and May 2017. Statistical analyses were performed with SPSS 23.0. The primary endpoints of this study included overall survival (OS) and local recurrence-free survival (LRFS); the secondary endpoints were disease-free survival (DFS) and treatment-related toxicity.ResultsThe median follow-up was 58.4 months (range, 12.7-185.3 months), and the median local recurrence time was 59.0 months (range, 7.0-185 months). All of the patients completed radiotherapy on schedule, and no grade 3–4 late-stage reaction was observed. The estimated 5-year and 10-year OS, DFS and LRFS rates of the patients were 64.0%, 61.1%, 69.6% and 48.0%, 40.9%, 64.6%, respectively. Univariate analysis showed that age (χ2 = 4.224, P = 0.040), R0 resection (χ2 = 3.949, P = 0.047), and early stage (I + II) (χ2 = 6.515, P = 0.011) were associated with good OS; DFS benefit in early stage patients (χ2 = 6.151, P = 0.013) and age<70 years old (χ2 = 5.091, P = 0.024). Patients with distal ureteral segments had better LRFS than patients with proximal ureteral cancer (χ2 = 5.248, P = 0.022). However, multivariate analysis showed that age was the only factor of OS (χ2 = 4.099, P = 0.043).ConclusionAdjuvant radiotherapy is safe and tolerated, and LRFS was superior in middle and distal ureteral cancer than in proximal ureteral cancer.

Clinical outcomes of intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma

BackgroundWe aimed to evaluate the safety and efficacy of intraluminal iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma.MethodsFrom January 2014 to January 2023, 48 patients with ureteral cancer not suitable for surgical resection were enrolled. Iodine-125 seed strand was inserted in 26 patients under c-arm CT and fluoroscopic guidance (Group A), and 22 patients underwent percutaneous nephrostomy without seed strand (Group B). The clinical outcomes (technical success rate, tumor sizes, hydronephrosis Girignon grade, complications, objective response rate (ORR), disease control rate (DCR), and survival time) were evaluated and compared.ResultsA total of 53 seed strands were successfully inserted and replaced in Group A, with a technical success rate of 100%. No procedure-related death or severe complications occurred in both group. Migration of seed strand or drainage tube was the most common complication. The Girignon grade of hydronephrosis was significantly improved 1, 3 and 6 months after procedure in both groups. DCR in Group A were 96.2%, 80.0%, and 70.0% at 1-, 3-, and 6-month follow up, respectively. At 1 and 6 months later, ORR in Group A were significantly higher than those in Group B (p < 0.05). The median overall survival were 30.0 months in Group A and 16.1 months in Group B, respectively (p = 0.04). The median progression-free survival were 11.1 months in Group A and 6.9 months in Group B, respectively (p = 0.09).ConclusionIntraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy is safe and effective in patients with ureteral carcinoma, with higher ORR and median overall survival than patients underwent percutaneous nephrostomy without seed strand.

Copy number gain of ACTN4 is associated with poor prognosis in patients with upper urinary tract urothelial carcinoma.

α-Actinin4 (ACTN4), an isoform of non-muscular α-actinin, is involved in enhancing cell motility and promoting cancer infiltration and metastasis in various cancers. However, information remains limited regarding the pathological significance of ACTN4 expression in upper urinary tract urothelial carcinomas (UUTUCs). We obtained tumor samples from 168 consecutive patients with newly diagnosed UUTUCs (92 with renal pelvic cancers and 76 with ureteral cancers), who were treated with nephroureterectomy or partial ureterectomy, and analyzed the expression of the ACTN4 protein and the amplification of ACTN4 using immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. The median follow-up duration was 65 months. Among 168 cases, 49 (29%) showed ACTN4 protein overexpression and 25 (15%) showed copy number gain (≥4 copies per cell) of ACTN4. The copy number gain of ACTN4 detected using FISH significantly correlated with ACTN4 protein overexpression and several adverse clinicopathological factors, including higher pathological T stage, lymphovascular invasion, lymph node metastasis, positive surgical margin, concomitant subtype histology, and non-papillary gross finding. Cox univariate regression analyses revealed that both copy number gain of ACTN4 and ACTN4 protein overexpression were significant risk factors for extraurothelial recurrence and death (each p < 0.0001), but multivariate analysis revealed that only copy number gain of ACTN4 was an independent risk factor for extraurothelial recurrence and death (p = 0.038 and 0.027, hazard ratio = 2.16 and 2.17, respectively). This is the first study demonstrating the aberrant expression status of ACTN4 in UUTUC and indicating its putative usefulness as a prognostic indicator in patients with UUTUC.

Duodenal obstruction in a patient with ureteral cancer

Duodenal obstruction in a patient with ureteral cancer

Carbon-ion radiotherapy for inoperable upper tract ureteral cancer.

This study aimed to report initial results of hypofractionated carbon-ion radiotherapy (C-ion RT) for inoperable upper tract ureteral cancer. Retrospective chart review was performed for five consecutive patients with medically inoperable ureter cancer that was treated with radical C-ion RT between December 2013 and December 2014. The median age of the patients was 80 years (range, 68-84 years). The reasons for inoperability were advanced age, post-contralateral nephrectomy, alcoholic cirrhosis, both advanced age and contralateral renal function degeneracy, and pneumonia. The median size of tumor was 2.8cm (range, 2.2-4.0cm). Diagnostic imaging did not identify lymph node metastases or distant metastases in any case. All patients underwent C-ion RT (52.8Gy relative biological effectiveness; 12 fractions in 3weeks). The clinical target volume encompassed the growth tumor volume with a 5-mm margin bilaterally; there was a 40-mm margin craniocaudally but the clinical target volume did not encompass the whole ureter. Within a median follow-up time of 32.9 months (range, 24-36 months), two patients died and three remained alive. Neither local recurrence nor regional lymph node metastases were observed. Secondary bladder tumor was observed in four patients, and one patient had a liver metastasis. Grade 1 hematuria was observed in two patients, and Grade 3 pyelonephritis was observed in one patient as acute toxicity. Ureteral obstruction was observed in two patients. C-ion RT might be a useful treatment option for inoperable ureter cancer.

PD46-01 DETECTION OF INDIVIDUALIZED MUTATIONS AND MONITORING OF POSTOPERATIVE RECURRENCE USING CIRCULATING TUMOR DNA IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023PD46-01 DETECTION OF INDIVIDUALIZED MUTATIONS AND MONITORING OF POSTOPERATIVE RECURRENCE USING CIRCULATING TUMOR DNA IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA Daichi Tamura, Masakazu Abe, Daiki Ikarashi, Renpei Kato, Yoichiro Kato, Shigekatsu Maekawa, Mitsugu Kanehira, Ryo Takata, Yutaka Suzuki, Hidewaki Nakagawa, Satoshi Nishizuka, and Wataru Obara Daichi TamuraDaichi Tamura More articles by this author , Masakazu AbeMasakazu Abe More articles by this author , Daiki IkarashiDaiki Ikarashi More articles by this author , Renpei KatoRenpei Kato More articles by this author , Yoichiro KatoYoichiro Kato More articles by this author , Shigekatsu MaekawaShigekatsu Maekawa More articles by this author , Mitsugu KanehiraMitsugu Kanehira More articles by this author , Ryo TakataRyo Takata More articles by this author , Yutaka SuzukiYutaka Suzuki More articles by this author , Hidewaki NakagawaHidewaki Nakagawa More articles by this author , Satoshi NishizukaSatoshi Nishizuka More articles by this author , and Wataru ObaraWataru Obara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is an aggressive disease which have high recurrence after surgery. Current standard methods for the diagnosis and detection of recurrence are invasive or low sensitivity. Circulating tumor DNA (ctDNA) analysis using digital polymerase chain reaction (dPCR) has demonstrated promising results for monitoring as recurrence in several cancers. The aim of this study was to evaluate the validity of plasma and urinary ctDNA as a tumor biomarker for UTUC among a perioperative period. METHODS: This study included 23 patients who underwent radical nephroureterectomy (RNU) diagnosed as UTUC from January 2019 to December 2020. In each patient, whole exome sequencing (WES) of tumor DNA and corresponding peripheral blood mononuclear cell (PBMC) DNA were performed by next generation sequencer (NGS). To investigate ctDNA by dPCR analysis, we selected tumor specific gene mutations included in our original primer-probe library. We also collected plasma and urine ctDNA from each patient. Longitudinal variant allele frequency (VAF) of ctDNA were plot on a pre- and post-operative period. RESULTS: The median age was 71 years old (range 57-82). 13 cases were renal pelvis cancer, and 10 cases were ureteral cancer. Most frequently mutated genes revealed by tumor DNA analysis using NGS were TERT (43%), KMT2D (35%), TTN (30%), FGFR3 (26%), and TP53 (26%). 17 cases (74%) could be performed ctDNA monitoring by our primer-probe library. Tumor specific mutations were detected in preoperative samples in 15 cases. Tumor specific mutations were not detected in two cases who were ypT0 due to neoadjuvant chemotherapy. Six cases experienced recurrence after RNU, five of which showed increase of VAFs of ctDNA. CONCLUSIONS: ctDNA analysis using dPCR could detect tumor specific mutations in majority of patients with UTUC. Individualized ctDNA monitoring could be a useful biomarker for postoperative recurrence. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1169 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daichi Tamura More articles by this author Masakazu Abe More articles by this author Daiki Ikarashi More articles by this author Renpei Kato More articles by this author Yoichiro Kato More articles by this author Shigekatsu Maekawa More articles by this author Mitsugu Kanehira More articles by this author Ryo Takata More articles by this author Yutaka Suzuki More articles by this author Hidewaki Nakagawa More articles by this author Satoshi Nishizuka More articles by this author Wataru Obara More articles by this author Expand All Advertisement PDF downloadLoading ...

Safety and efficacy of iodine-125 seed strand for intraluminal brachytherapy on ureteral carcinoma.

Our aim is to evaluate the safety and efficacy of iodine-125 seed strand for intraluminal brachytherapy on ureteral carcinoma. From November 2014 to November 2021, 22 patients with ureteral cancer not suitable for surgical resection were enrolled. Iodine-125 seed strand was inserted under c-arm CT and fluoroscopic guidance. The technical success rate, complications, disease control rate, and survival time were evaluated. Hydronephrosis Girignon grade and ureteral cancer sizes before and after treatment were compared. A total of 46 seed strands were successfully inserted and replaced, with a technical success rate of 100% and median procedure time of 62min. No procedure-related death, ureteral perforation, infection, or severe bleeding occurred. Minor complications were observed in eight (36.4%) patients, and migration of seed strand was the most common complication. Six months after seed strand brachytherapy, one complete response, three partial responses, and five stable diseases were evaluated, and the disease control rate was 64.3%. The Girignon grade of hydronephrosis was significantly improved 1 to 3 months after seed strand insertion. Disease control rates were 94.4, 62.5, and 64.3% at 1-, 3-, and 6-month follow-up. Twenty patients were successfully followed up, with a mean follow-up of 18.0 ± 14.5 months. The median overall survival and progress-free survival were 24.7 and 13.0 months, respectively. Iodine-125 seed strand is safe and effective for intraluminal brachytherapy and can be used as an alternative to patients with ureteral carcinoma who are not suitable for surgical resection or systemic combined therapy.

Prognostic analysis of inflammatory response-related genes and biomarkers in patients with urothelial carcinoma of ureter.

Ureteral urothelial carcinoma is a common urinary system tumor, accounting for 40% to 60% of all ureteral diseases. This study attempted to analyze the prognosis of patients with urothelial carcinoma, judging ureteral urothelial carcinoma by genes and biomarkers of inflammatory response. In this paper, co-expression network analysis and gene-based image fusion evaluation methods were proposed to obtain the prognosis results of patients with ureteral urothelial carcinoma. The experimental results showed that the levels of PLR and NLR increased, and the levels of HGB and HCT decreased; high PLR and high NLR levels, low HGB and low HCT levels were all risk factors affecting bladder urothelial carcinoma, and their ratios (OR) were 1.023, 1.611, 0.961, 0.859, 1.015, 1.072, 0.979, and 0.951, respectively. However, high PLR and high NLR levels were independent risk factors for bladder urothelial carcinoma, and their OR values were 1.497 and 1.071, respectively. Through biomarker diagnosis, the area under the curve, sensitivity, specificity and Youden index of hsa-mir-17, hsa-mir-93, hsa-mir-429 and hsa-mir-20a all exceeded 0.9, indicating that this is a potential diagnostic indicators. All in all, during the treatment of ureteral cancer, in order to reduce tumor recurrence, systemic therapy should be combined with ureteral cancer. In addition, this study also analyzed the prognosis of chemotherapy patients, and the results showed that immunotherapy may increase the risk of tumor cell reperfusion during chemotherapy.

Difficulties in Differentiating Osteosclerosis in Patients With Multifocal Micronodular Pneumocyte Hyperplasia and Cancer

A 52-year-old woman with multifocal micronodular pneumocyte hyperplasia in bilateral lungs and multiple sclerotic bone lesions (SBLs) visited our hospital. Tuberous sclerosis complex (TSC) was suspected but did not meet the diagnostic criteria. Ten years later, at age 62, the patient developed ureteral cancer. Cisplatin-containing chemotherapy ameliorated ureteral tumor, concomitant with exacerbation of SBLs. It was difficult to distinguish whether the exacerbation of SBLs was due to exacerbation of TSC or bone metastasis of cancer. The administration of cisplatin made the diagnosis even more difficult because its molecular biological effects can exacerbate the complications of TSC.

Preoperative upper tract invasive diagnostic modalities are associated with intravesical recurrence following surgery for upper tract urothelial carcinoma: A population-based study.

Intravesical recurrence (IVR) after surgery for upper tract urothelial carcinoma (UTUC) is a clinical problem. We investigated if preoperative invasive diagnostic modalities (IDM) such as antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy are associated with IVR after radical surgery for UTUC. Risk of death from urothelial cancer and all causes was investigated as secondary outcomes. We investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015-2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes was assessed using multivariable Cox regression models. The study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03-1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12-2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21-2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81-1.41). Limitations included the observational setting and the lack of variables such as tumour grade, multifocality and preoperative hydronephrosis. Worse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter.

Carcinoma of bladder: A rare case report

Bladder cancer begins after the healthy cells in the bladder wall, the most commonly urothelial cells change and grow out of control, forming a mass called tumor urothelial cells, the urothelial cells that also line the renal pelvis and ureter cancer that develops in the type of urothelial cancer, and it is often called upper tract urothelial cancer. A tumor can be benign or malignant, a cancerous tumor is malignant it can grow and spread to other parts of the body, a benign tumor means the tumor can grow but will not spread, these are very rare. Bladder tumors can be divided into 3 types based on microscopic structure of the tumor cells: Urothelial carcinoma, squamous cell carcinoma, adenocarcinoma and others include sarcoma. These cancers may be of two types based on cell type bladder cancer that can be categorized as NMIBC (Non-muscle invasive bladder cancer) and MIBC (Muscle invasive bladder cancer). Risk factors include tobacco use, age, gender, race, chemicals, chronic bladder problems, cyclophosphamide use and pioglitazone use, personal history, schistosomiasis, arsenic exposure, genetic syndromes. Clinical symptoms are blood clots in the urine, pain or burning micturition, frequent urination, lower back ache on one side of the body in the abdomen region, hematuria. Diagnostic tests include urine test, cystoscopy, biopsy, TURBT, MRI, CT (KUB), and USG. Treatment includes surgical removal by TURBT, BCG vaccination, radiotherapy, chemotherapy, and immunotherapy in addition palliative or supportive care.

Kidney-sparing surgery for distal high-risk ureteral carcinoma: Clinical efficacy and preliminary experiences in 22 patients.

Several groups proved kidney-sparing surgery (KSS) had equivalent oncological outcomes compared with radical nephroureterectomy (RNU) for the low-risk upper urinary tract urothelial carcinoma (UTUC) patients. Whereas, the clinical efficacy of KSS for high-risk UTUC, especially for distal high-risk ureteral carcinoma, remains unclear. To evaluate the feasibility of KSS for patients with distal high-risk ureter cancer. Our study included 22 patients who diagnose the distal high-risk ureter cancer and underwent KSS between May 2012 and July 2021 in the First Affiliated Hospital of Chongqing Medical University. Overall survival (OS), confirmed as the primary endpoint of present study, was assessed by a blinded independent review committee (BIRC). The secondary endpoints included the postoperative SF-36 (the short form 36 health survey questionnaire) score, progression-free survival (PFS), postoperative complications, and so on. Overall, 17 (77.3%) and 5 (22.7%) patients underwent segmental ureterectomy (SU) and endoscopic ablation (EA), respectively. By the cut-off date, the mean OS was 76.3months (95% Cl: 51.3-101.1months) and the mean PFS was 47.0months (95% Cl: 31.1-62.8months), respectively. And the SF-36 score in a majority of patients was >300 (90.9%). This is a daring endeavor to explore the clinical efficacy of KSS in distal high-risk ureter cancer based on the high-risk UTUC criteria, which shows satisfactory results in the long-term prognosis and operation-associated outcomes. However, future randomized or prospective multicenter studies are necessary to validate our conclusions.

Increased urinary B2-microglobulin is associated with poor prognosis of upper tract urothelial carcinoma

BackgroundKidney tubular damage markers are biomarkers of acute or chronic kidney injury. Hypothetically, upper tract urothelial cancer (UTUC), which induces obstructive uropathy or direct invasion of the renal parenchyma, may also induce increased excretion of urinary tubular damage proteins. Therefore, this study aimed to investigate the use of tubular damage biomarker as prognostic markers for UTUC.MethodsThe records of 417 surgically resected patients with UTUC were obtained from the Seoul National University Prospectively Enrolled Registry for urothelial cancer-upper tract urothelial cancer (SUPER-UC-UTUC) between January 2016 and December 2020. Patients with non-urothelial cancer or without urinary tubular injury marker measurement were excluded, and finally, 296 patients were finally included. B2-microglobulin (B2-MG) was an injury marker, and a value higher than 0.3 was considered abnormally elevated, according to previous studies.ResultsThe mean age was 70.9 years, and the male sex was predominant (n = 211, 71.3%). The incidences of renal pelvis and ureter cancer were similar (50.7% vs. 49.3%). Most patients had high-grade diseases (n = 254, 88.8%). The high urine B2-MG group was older, had decreased renal function, and had a higher pathologic T stage than did the low group. Multivariate Cox regression analysis of disease-free survival (DFS), open surgical method (Hazard ratio (HR) 1.52, p = 0.027), large tumor size (HR 1.06, p = 0.017), tumor multifocality (HR 1.90, p = 0.038), lymphovascular invasion (HR 2.19, p < 0.001), and high urine B2-MG (HR 1.57, p = 0.021) were significantly associated with shortened metastasis-free survival (MFS). Kaplan–Meier curve analysis revealed short DFS (median survival 15.5 months vs. unattained, log-rank p = 0.001) and MFS (unattained median survival in both groups, log-rank p = 0.003) for the high urine B2-MG group compared to the low urine B2-MG group.ConclusionPatients with UTUC presenting with increased pre-operative urine B2-MG levels were associated with disease recurrence and metastasis. This biomarker may aid in performing pre-operative risk stratification and in assessing the individual prognosis of patients with UTUC.

Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies.

BackgroundMuscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies, or anti-fibroblast growth factor receptor (FGFR) treatments, these tumors are still of a poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating the molecular heterogeneity of MIBC and UTUC, to facilitate the preclinical identification of therapies.MethodsFresh tumors were obtained from patients and subcutaneously engrafted into immune-compromised mice. Patient tumors and matched PDXs were compared regarding histopathology, transcriptomic (microarrays), and genomic profiles [targeted Next-Generation Sequencing (NGS)]. Several PDXs were treated with chemotherapy (cisplatin/gemcitabine) or targeted therapies [FGFR and epidermal growth factor (EGFR) inhibitors].ResultsA total of 31 PDXs were established from 1 non-MIBC, 25 MIBC, and 5 upper urinary tract tumors, including 28 urothelial (UC) and 3 squamous cell carcinomas (SCCs). Integrated genomic and transcriptomic profiling identified the PDXs of three different consensus molecular subtypes [basal/squamous (Ba/Sq), luminal papillary, and luminal unstable] and included FGFR3-mutated PDXs. High histological and genomic concordance was found between matched patient tumor/PDX. Discordance in molecular subtypes, such as a Ba/Sq patient tumor giving rise to a luminal papillary PDX, was observed (n=5) at molecular and histological levels. Ten models were treated with cisplatin-based chemotherapy, and we did not observe any association between subtypes and the response. Of the three Ba/Sq models treated with anti-EGFR therapy, two models were sensitive, and one model, of the sarcomatoid variant, was resistant. The treatment of three FGFR3-mutant PDXs with combined FGFR/EGFR inhibitors was more efficient than anti-FGFR3 treatment alone.ConclusionsWe developed preclinical PDX models that recapitulate the molecular heterogeneity of MIBCs and UTUC, including actionable mutations, which will represent an essential tool in therapy development. The pharmacological characterization of the PDXs suggested that the upper urinary tract and MIBCs, not only UC but also SCC, with similar molecular characteristics could benefit from the same treatments including anti-FGFR for FGFR3-mutated tumors and anti-EGFR for basal ones and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone.

Prognostic impact of stromal periostin expression in upper urinary tract urothelial carcinoma

BackgroundPeriostin is an extracellular matrix protein that has been known to be implicated in fibrillogenesis and cell migration, including cancer metastasis. Periostin overexpression in cancer cells and/or intervening stroma is usually related to tumor progression and poor patient outcomes in various human cancers; however, its role in urothelial carcinoma, especially upper urinary tract urothelial carcinomas (UTUCs), remains inconclusive.MethodsSamples from 126 consecutive cases of invasive UTUC (69 renal pelvic cancers and 57 ureteral cancers) were histologically reviewed and analyzed for periostin expression using immunohistochemistry. The intensities of immunoreactivity and the fraction of positive cancer cells and stroma (i.e., epithelial and stromal expression, respectively) were classified into four categories each (intensity, 0–3; fraction, 0–25% = 1; 26–50% = 2; 51–75% = 3; and > 75% = 4). The overall score was determined by multiplying both scores, and overall scores ≥ 6 were considered to indicate high periostin expression.ResultsAmong 126 UTUCs, 55 (44%; 27 renal pelvic and 28 ureteral cancers) showed high stromal periostin expression. None of the cases were considered to have high epithelial periostin expression. High stromal periostin expression was associated with non-papillary gross findings, higher pathological T category, lymphovascular invasion, concomitant carcinoma in situ, subtype histology, lymph node metastasis, positive surgical margins, high tumor budding, and high tumor-associated immune cell status. Multivariate analysis revealed that high stromal periostin expression was an independent predictor of overall survival (p = 0.00072, hazard ratio = 3.62), and lymphovascular invasion and high stromal periostin expression were independent predictors of cancer-specific survival (p = 0.032 and 0.020, hazard ratio = 2.61 and 3.07, respectively).ConclusionsStromal periostin expression was often observed in invasive UTUCs with adverse clinicopathological factors and may be a useful predictor of patient outcomes.

PD58-03 DETECTION OF INDIVIDUALIZED MUTATION USING PLASMA AND URINARY CIRCULATING TUMOR DNA IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 May 2022PD58-03 DETECTION OF INDIVIDUALIZED MUTATION USING PLASMA AND URINARY CIRCULATING TUMOR DNA IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA Daichi Tamura, Masakazu Abe, Renpei Kato, Yoichiro Kato, Shigekatsu Maekawa, Mitsugu Kanehira, Ryo Takata, Yutaka Suzuki, Hidewaki Nakagawa, Satoshi Nishizuka, and Wataru Obara Daichi TamuraDaichi Tamura More articles by this author , Masakazu AbeMasakazu Abe More articles by this author , Renpei KatoRenpei Kato More articles by this author , Yoichiro KatoYoichiro Kato More articles by this author , Shigekatsu MaekawaShigekatsu Maekawa More articles by this author , Mitsugu KanehiraMitsugu Kanehira More articles by this author , Ryo TakataRyo Takata More articles by this author , Yutaka SuzukiYutaka Suzuki More articles by this author , Hidewaki NakagawaHidewaki Nakagawa More articles by this author , Satoshi NishizukaSatoshi Nishizuka More articles by this author , and Wataru ObaraWataru Obara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002643.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is an aggressive disease which have high recurrence after surgery. Current standard methods for the diagnosis and detection of recurrence are invasive or low sensitivity. Circulating tumor DNA (ctDNA) analysis using digital polymerase chain reaction (dPCR) has demonstrated promising results for monitoring as recurrence in several cancers. The aim of this study was to evaluate the validity of plasma and urinary ctDNA as a tumor biomarker for UTUC among a perioperative period. METHODS: This study included 23 patients who underwent radical nephroureterectomy (RNU) diagnosed as UTUC from January 2019 to December 2020. In each patient, whole exome sequencing (WES) of tumor DNA and corresponding peripheral blood mononuclear cell (PBMC) DNA were performed by next generation sequencer. Tumor specific mutations were identified by comparing the single nucleotide variants from tumors and PBMCs. To investigate ctDNA by dPCR analysis, we designed primers and probes for each mutation. We also obtained plasma and urine ctDNA from each patient. Longitudinal variant allele frequency (VAF) of ctDNA were plot on a perioperative period. RESULTS: The median age was 71 years old (range 57-82). 13 cases were renal pelvis cancer, and 10 cases were ureteral cancer. The median tumor mutation burden in all cases was 3.02/Mb (range 0.00-15.97). Tumor specific mutations such as TERT, PIK3CA and p53 gene were selected by individualized patient, and performed plasma and urinary ctDNA monitoring by dPCR in 7 patients. Tumor specific mutations were detected in preoperative samples and VAFs of ctDNA decreased quickly after RNU in 5 patients. Tumor specific mutations were not detected in 2 patients who were pT0 due to neoadjuvant chemotherapy. CONCLUSIONS: VAFs in plasma and urinary ctDNA were associated with tumor burden. Individualized ctDNA monitoring could be a useful biomarker for UTUC. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1012 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daichi Tamura More articles by this author Masakazu Abe More articles by this author Renpei Kato More articles by this author Yoichiro Kato More articles by this author Shigekatsu Maekawa More articles by this author Mitsugu Kanehira More articles by this author Ryo Takata More articles by this author Yutaka Suzuki More articles by this author Hidewaki Nakagawa More articles by this author Satoshi Nishizuka More articles by this author Wataru Obara More articles by this author Expand All Advertisement PDF DownloadLoading ...

Is Lymph Node Dissection Necessary During Radical Nephroureterectomy for Clinically Node-Negative Upper Tract Urothelial Carcinoma? A Multi-Institutional Study.

PurposeThis study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU).MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan–Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (−) groups.ResultsA total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.ConclusionsWe found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

Case Report: Good responsiveness of metastatic sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation to immune checkpoint inhibitor after radical surgery and chemotherapy

Background: Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation (SUCCD) in the ureter has a poor prognosis and is a rare histological variant of ureteral cancer. The majority of ureteral cancers are urothelial carcinomas. Clinical case: We present a case of well-controlled metastatic SUCCD treated with an immune checkpoint inhibitor after radical surgery and failed adjuvant chemotherapy. The patient was a 68-year-old male with previous cure history of cT1 staged esophageal squamous cell carcinoma referred to the urology department for a right hydronephroureterosis complicating an intraureteral enhancing mass. After ureteroscopic biopsy and intraureteral urine cytology, atypical pleomorphic cell nests and chondroid tissue consistent with sarcomatoid urothelial carcinoma were observed. The patient underwent a successful radical right nephroureterectomy with bladder cuffing. The final diagnosis was a pT3N0 sarcomatoid urothelial carcinoma (heterologous component: chondrosarcoma &gt; 95%) located at the right distal ureter and right renal calyx with infiltration of the periureteric fat and renal parenchyma of the renal capsule. On the postoperative one-month follow-up computed tomography scan, multiple enlarged lymph nodes and metastatic lung nodules were detected. The initiated three cycles of gemcitabine-carboplatin therapy was marked by disease progression; thus, second-line therapy with atezolizumab was used for treatment. After five cycles of atezolizumab, the tumors showed a partial response without any grade 3 complications. Conclusion: The recurrent metastatic SUCCD showed good response to the immune checkpoint inhibitor after unsuccessful therapy with radical surgery and first line chemotherapy despite the unfavorable outcome of the pathology.

Aristolochic acid and the risk of cancers in patients with type 2 diabetes: Nationwide population-based cohort study

BackgroundBoth aristolochic acid (AA) exposure and diabetic can increase risk of certain cancers,whetherAAexposureincreases cancer risk in diabetic patientsisunknown. The purpose of this study was to investigate the association between the use of Chinese herbal products containing AA and the risk of cancer in diabetic patients. MethodsA cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients older than 18 years who were diagnosed with diabetes between 1997 and 2010 were enrolled in our cohort. The use of Chinese herbal products containing AA was recorded from the beginning of 1997 until the ban of herbs containing AA in November 2003. Patients were individually tracked to identify cancer incidence between 1997 and 2013. Only patients who visited traditional Chinese medicine clinics between 1997 and 1 year before the end of follow-up were included in the cohort to ensure comparability. Cox proportional hazards regression was used to calculate the hazard ratio for the association between the use of Chinese herbal products containing AA and the occurrence of cancer. ResultsAmong the 430 377 male and 431 956 female patients with diabetes enrolled in our cohort, 37 554 and 31 535 cancer diagnoses were recorded during the study period, respectively. The use of AA-containing herbal products was associated with a significantly higher risk of liver, colorectum, kidney, bladder, prostate, pelvis, and ureter cancer in a dose-dependent manner. An increased risk of extrahepatic bile duct cancer in women was also associated with AA exposure at doses of more than 500 mg. ConclusionsAssociation between AA exposure and the risk of some cancers were found in this study. AA exposure might increase risk of kidney,bladder,pelvis, ureter,liver,colorectum,andprostatecancer in all patientsandextrahepatic bile duct cancerin women.

Dermatomiositis amiopática como primera manifestación de cáncer de uréter

Resumen Descripción del caso clínico: Varón de 79 años, consultó por episodio de angioedema facial sin otra sintomatología. A la exploración física presentaba eritema en cara y cuello, angioedema peripalpebral y máculas eritematosas en el dorso de las manos. Se realizó biopsia de lesión cutánea compatible con pápula de Gottron y para descartar enfermedad sistémica urografía por tomografía computarizada observando ureterohidronefrosis izquierda grado III por posible neoplasia ureteral. Estudio de extensión negativo. Se realizó nefroureterectomía izquierda laparoscópica e instilación endovesical de Mitomicina C, con resultados anatomo-patológicos de carcinoma papilar urotelial de alto grado multifocal. El paciente presentó una evolución posquirúrgica favorable, con mejoría de las lesiones dérmicas, pero a los 7 meses desarrolló múltiples metástasis siendo éxitus. Relevancia: La asociación de dermatomiositis con neoplasias es bien conocida, pero son pocos los casos descritos con malignidad urológica. El cáncer ureteral con dermatomiositis amiopática es extremadamente raro. Implicaciones clínicas: Es importante realizar un tamizaje de cáncer en pacientes que cursan con dermatomiositis para así tratarlos y mejorar su pronóstico. Conclusión: La dermatomiositis es un síndrome paraneoplásico raro que se asocia al cáncer ureteral de manera muy infrecuente. El tamizaje de cáncer en estos pacientes es muy importante para mejorar el pronóstico. El tratamiento quirúrgico de este tumor supuso la desaparición de las alteraciones cutáneas.