Postoperative recurrence detection using individualized circulating tumor DNA in upper tract urothelial carcinoma.

Biomarkers that could detect the postoperative recurrence of upper tract urothelial carcinoma (UTUC) have not been established. In this prospective study, we aim to evaluate the utility of individualized circulating tumor DNA (ctDNA) monitoring using digital PCR (dPCR) as a tumor recurrence biomarker for UTUC in the perioperative period. Twenty-three patients who underwent radical nephroureterectomy (RNU) were included. In each patient, whole exome sequencing by next-generation sequencing and TERT promoter sequencing of tumor DNA were carried out. Case-specific gene mutations were selected from sequencing analysis to examine ctDNA by dPCR analysis. We also prospectively collected plasma and urine ctDNA from each patient. The longitudinal variant allele frequencies of ctDNA during the perioperative period were plotted. Case-specific gene mutations were detected in 22 cases (96%) from ctDNA in the preoperative samples. Frequently detected genes were TERT (39%), FGFR3 (26%), TP53 (22%), and HRAS (13%). In all cases, we obtained plasma and urine samples for 241 time points and undertook individualized ctDNA monitoring for 2 years after RNU. Ten patients with intravesical recurrence had case-specific ctDNA detected in urine at the time of recurrence. The mean lead time of urinary ctDNA in intravesical recurrence was 60 days (range, 0-202 days). Two patients with distal metastasis had case-specific ctDNA in plasma at the time of metastasis. In UTUC, tumor-specific gene mutations can be monitored postoperatively as ctDNA in plasma and urine. Individualized ctDNA might be a minimally invasive biomarker for the early detection of postoperative recurrence.

[A Case of Retroperitoneal Bronchogenic Cyst].

A 75-year-old male visited a clinic with the chief complaint of pollakiuria. A computed tomography scan revealed, a left adrenal mass, and the patient was then referred to our hospital. Since a malignant tumor could not be ruled out. We performed laparoscopic left adrenal resection. Postoperative histopathological findings revealed the mass to be a bronchogenic cyst, which had no continuity with the normal adrenal gland. The postoperative course was uneventful, and recurrence has not been observed. Retroperitoneal bronchogenic cysts are rare and often difficult to diagnose preoperatively using imaging studies.

Prognostic outcomes and safety in patients treated with pembrolizumab for advanced urothelial carcinoma: experience in real-world clinical practice.

BACKGROUND: Prognostic outcomes and safety following treatment with pembrolizumab in patients with advanced urothelial carcinoma (UC) have not been fully elucidated in clinical practice. The aim of this study was to evaluate the oncological efficacy and safety of pembrolizumab after failure of platinum-based chemotherapy in Japanese patients with advanced UC in a routine clinical setting. METHODS: This retrospective study included 41 consecutive Japanese patients with advanced UC treated with pembrolizumab as second-line or greater therapy at Iwate Medical University Hospital from January 2018 to April 2019. RESULTS: The mean follow-up period was 6.2 months. The objective response rate, median progression-free survival, and median overall survival were 15%, 2.5 months, and 11.9 months, respectively. Univariate analysis identified poor performance status (> 1), liver metastasis, two or more metastatic organs, low hemoglobin levels, two or more prior regimens, high baseline C-reactive protein levels, higher relative C-reactive protein level change after 6 weeks, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks as significant predictors of overall survival. Among these factors, poor performance status (> 1), two or more metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks were identified as independent predictors of overall survival in multivariate analysis. CONCLUSIONS: The introduction of pembrolizumab can result in favorable cancer control outcomes in Japanese patients with advanced UC, and the prognosis of these patients can be stratified according to three potential parameters, including poor performance status, high number of metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change.

Changes in Renal Function After Nephroureterectomy for Upper Tract Urothelial Cancer in Elderly Patients.

Introduction Decreased renal function after radical nephroureterectomy is one of the most important complications because it contributes to the decision to initiate adjuvant chemotherapy. This study aimed to investigate clinical factors associated with changes in renal function after radical nephroureterectomy in elderly patients. Methodology A total of 145 patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma were evaluated. The renal function was calculated preoperatively, postoperatively, and one month postoperatively, and the long-term change in renal function was investigated once a year. The association between clinical factors and changes in renal function following radical nephroureterectomy in univariate and multivariate analyses was stratified by age ≥75 years and <75 years. Results The median age of the patients was 71 years, with 94 patients (65%) aged <75 years and 51 patients (35%) aged ≥75 years. The median estimated glomerular filtration rates (eGFRs) were 57.1 (21.8-100) preoperatively, 36.1 (9.1-100) postoperatively, and 42.4 (19.5-100) in one month after radical nephroureterectomy. The median eGFRs in elderly patients were 50.8 (21.8-85.4) preoperatively. In the elderly group, only 8% had an eGFR of ≥50 as cisplatin-eligible at one month postoperatively. The long-term renal function in the elderly may decline further than during the stable postoperative periods. In the multivariate analysis, hydronephrosis (HN) was a significant predictor of decreased renal function in patients aged ≥75 years between the pre- and postoperative periods. Conclusions Elderly patients with HN who have upper tract urothelial carcinoma have a lower risk of decreased renal function after radical nephroureterectomy. This result may be useful in determining adjuvant therapy.

Successful treatment of eosinophilia associated with dialysis-related renal cancer with radical nephrectomy.

Introduction: Secondary eosinophilia due to solid tumors is a rare case. This is the first study to report secondary eosinophilia due to renal cancer in a patient on dialysis. Case presentation: A 70-year-old man, on long-term hemodialysis was incidentally detected with right renal cancer, and workup performed revealed eosinophilia. Allergic symptoms caused by hemodialysis were initially considered; however, treatment did not lead to any improvement in eosinophilia. Therefore, nephrectomy for renal cancer was performed. The resolution of symptoms and eosinophilia after surgery suggested renal cancer as the cause of eosinophilia. Conclusion: As demonstrated in this patient with dialysis-related renal cancer, eosinophilia associated with solid tumors may be addressed by treating the tumor.

The Clinical Validity of Urinary Pellet DNA Monitoring for the Diagnosis of Recurrent Bladder Cancer.

The aim of this study was to evaluate the clinical validity of monitoring urine pellet DNA (upDNA) of bladder cancer (BC) by digital PCR (dPCR) as a biomarker for early recurrence prediction, treatment efficacy evaluation, and no-recurrence corroboration. Tumor panel sequencing was first performed to select patient-unique somatic mutations to monitor both upDNA and circulating tumor DNA (ctDNA) by dPCR. For longitudinal monitoring using upDNA as well as plasma ctDNA, an average of 7.2 (range, 2 to 12) time points per case were performed with the dPCR assay for 32 previously treated and untreated patients with BC. Clinical recurrence based on imaging and urine cytology was compared using upDNA variant allele frequency (VAF) dynamics. A continuous increasing trend of upDNA VAF ≥1% was considered to indicate molecular recurrence. Most (30/32; 93.8%) cases showed at least one traceable somatic mutation. In 5 of 7 cases (71.4%) with clinical recurrence, upDNA VAF >1% was detected 7 to 15 months earlier than the imaging diagnosis. The upDNA VAF remained high after initial treatment for locally recurrent cases. The clinical validity of upDNA monitoring was confirmed with the observation that 26 of 30 cases (86.7%) were traceable. Local recurrences were not indicated by ctDNA alone. The results support the clinical validity of upDNA monitoring in the management of recurrent BC.

Detection of anterior prostate cancer using a magnetic resonance imaging-transrectal ultrasound fusion biopsy in cases with initial biopsy and history of systematic biopsies.

Background: Prostate cancer in the anterior region may be missed on a transrectal systematic biopsy (SBx). Therefore, this study aimed to evaluate the performance of magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TBx) in detecting anterior region cancer in patients with a history of SBxs. Methods: Prostate biopsies were performed in 224 patients after multiparametric MRI, among whom 119 patients with prostate imaging reporting and data system (PI-RADS version 2) scores of 3 to 5 underwent MRI-TRUS fusion TBxs. Afterward, cancer detection rates (CDRs) and TBx-positive core regions were compared by categorizing patients into those with or without a history of SBxs. Results: Total CDR was 68.8% (44/64 cases) in the initial biopsy group (Initial-Bx group) and 47.3% (26/55 cases) in the previous-negative-systematic biopsy group (Pre-Neg-SBx group) (P = 0.018). Interestingly, both TBx- and SBx-core positive cases were more common in the Initial-Bx group than in the Pre-Neg-SBx group (Initial-Bx group: 75% [33/44 cases] vs. Pre-Neg-SBx group: 42.3% [11/26 cases], P = 0.006). However, only TBx-core positive cases were more common in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 11.4% [5/44 cases] vs. Pre-Neg-SBx group: 30.8% [8/26 cases], P = 0.043). In addition, the proportion of anterior lesions detected by TBx cores was higher in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 26.3% [10/38 cases] vs. Pre-Neg-SBx group: 52.6% [10/19 cases], P = 0.049). Conclusion: Using MRI-TRUS fusion TBx in the evaluation of previously negative SBx cases improved the detection rate of anterior lesions, which might have been missed in previous SBxs. Especially in patients with a history of SBxs mpMRI should be performed to screen for anterior lesions.

Geriatric nutritional risk index as a risk-factor for Clostridioides difficile infection relapse in elderly Japanese patients.

Objective: Old age is a risk factor for Clostridioides difficile infection (CDI). As the world's aging population increases, identifying risk factors for CDI in elderly patients is a matter of urgency. This study examined the relationship between CDI relapse and nutritional status using the geriatric nutritional risk index (GNRI). Patients and Methods: Between January 2016 and December 2021, 108 patients were diagnosed with CDI. Of the 108 patients, 19 were excluded because of younger age (<65 years), early death within 14 days of the initial CDI diagnosis, and insufficient data. The patients were divided into low- (<75) and high-GNRI groups (≥75) based on the receiver operating characteristic curve analysis. Variables associated with CDI relapse were also analyzed. Results: The median GNRI scores in all patients and in the low- and high-GNRI groups were 74.9, 68.9, and 83.9, respectively. Of the 89 patients, 28 (31.8%) experienced a CDI relapse. The log-rank test showed a significantly better relapse-free survival (RFS) in the high GNRI group (P=0.002). Univariate analysis revealed that low GNRI (P=0.004), chronic kidney disease (CKD) (P=0.004), and beta-lactamase inhibitor administration before the initial diagnosis of CDI (P=0.025) were significantly correlated with RFS. Multivariate analysis revealed that low GNRI (P=0.008) and CKD (P=0.010) were independent prognostic factors for RFS. Conclusion: Among elderly patients, a low GNRI was strongly associated with CDI relapse. Our study may help clinicians to consider therapeutic strategies for elderly patients with CDI.

Concurrent robot-assisted radical prostatectomy and robot-assisted partial nephrectomy for patients with synchronous prostate cancer and small renal tumor: A case series of five patients.

Robotic surgery has become widely used in the field of urology. We experienced concurrent robot-assisted radical prostatectomy (RARP) and robot-assisted partial nephrectomy (RAPN) for the complex cases of synchronous primary cancers. Concurrent RARP and RAPN with horseshoe kidney have not been reported to date. Mean operative time was 398.6 minutes and mean total console time was 259.6 minutes. Total mean estimated blood loss was 313.4 mL. None of the patients required conversion to open surgery, none needed blood transfusion, and no perioperative complications occurred. The mean estimated glomerular filtration rate at 1 month postoperatively was maintained compared to pre-operative value. Positive surgical margin was shown in one patient with RARP. Concurrent RARP and RAPN using reusable ports can be safely performed. This combined surgery may be considered one of the treatment choices for synchronous prostate cancer and small renal tumor.

Influence of Robot-Assisted Partial Nephrectomy on Long-Term Renal Function as Assessed Using 99m-Tc DTPA Renal Scintigraphy.

Background: The long-term split renal function after robot-assisted partial nephrectomy (RAPN) is yet to be elucidated. This study aimed to assess long-term renal function of RAPN, using renal scintigraphy, and to identify clinical factors related to deterioration of renal function on the affected side of the kidney. Patients and Methods: RAPN for small tumors was performed, and split renal function was evaluated using 99m-Tc DTPA renal scintigraphy before and 1 year after surgery. Clinical factors (age, gender, body mass index, tumor side, presence of urinary protein, diabetes, hypertension, and dyslipidemia), perioperative factors (renal nephrectomy score [RNS], tumor diameter, overall surgery duration, console time, warm ischemic time, and amount of bleeding), and renal function (estimated glomerular filtration rate [eGFR] and glomerular filtration rate [GFR] measured using scintigraphy on both the affected and contralateral kidneys) were analyzed. Results: Sixty-six patients were included in the study. The median eGFR decreased from 71.9 to 63.9 mL/min after 1 year (p < 0.001), accounting for a mean loss of 10.1%. In scintigraphy examination, the median GFR on the affected kidney side decreased from 41.1 to 33.7 mL/min after 1 year (p < 0.001), accounting for a mean loss of 16.8%. RNS was significantly associated with renal function. Among RNS factors, the N factor is associated with renal function after RAPN. Conclusion: RNS, particularly the N factor, possibly influences the long-term deterioration of renal function after RAPN.

Dysuria therapeutic agents as an independent prognostic factor for the primary recurrence of non-muscle invasive bladder cancer: a propensity score matching study.

OBJECTIVE: To investigate if the use of therapeutic agents for dysuria is a risk factor for the primary recurrence of non-muscle invasive bladder cancer (NMIBC). METHODS: First, patients with NMIBC were divided into two groups: the non-recurrence group and the recurrence group. Patient characteristics were compared between both groups. The risk factors of recurrence that were statistically different between the two groups were identified by multivariate analysis. Second, we divided the patients into risk and non-risk groups, and differences in the recurrence-free survival (RFS) between the two groups were analyzed before and after propensity score matching (PSM). RESULTS: A total of 162 patients were included, with 84 patients in the non-recurrence group and 78 patients in the recurrence group. In the multivariate analysis, the intake of dysuria agents and bacillus Calmette-Guérin (BCG) therapy were independent factors. The RFS results in terms of the intake of dysuria agents were statistically significant before and after PSM analysis, but no factors were significantly different between the BCG and non-BCG groups after PSM. CONCLUSIONS: Therapeutic agents for dysuria might be at an independent risk factor for NMIBC recurrence. This trial is registered with the UMIN Clinical Trials Registry under the number UMIN000036097 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno = R000041122).

Complete Pathological Response to Neoadjuvant Pembrolizumab in a Patient With Chemoresistant Upper Urinary Tract Urothelial Carcinoma: A Case Report.

Treatment options as second-line therapy for advanced ureteral carcinoma are limited, and patients experiencing recurrence after first-line cisplatin-based chemotherapy have a poor prognosis. Recently, the programmed death-1 (PD-1) inhibitor pembrolizumab provided a better survival benefit with a complete response rate (9.2%) for chemoresistatant urothelial carcinoma. However, the dynamic changes of the cancer microenvironment about the cases of complete response are still unknown. We herein report a case of a 57-year-old man who had been diagnosed with localized, non-muscle-invasive bladder cancer (pT1N0M0, high grade), for which he underwent transurethral resection of the bladder cancer twice. Given that gemcitabine plus carboplatin as first-line neoadjuvant chemotherapy was unable to control left vesico-ureteral junction recurrence with muscle invasion (T3N0M0, high grade), the patient received the PD-1 inhibitor pembrolizumab as second-line neoadjuvant therapy in an attempt to stop tumor growth, which promoted dramatic tumor shrinkage without serious adverse effects and allowed subsequent nephroureterectomy and lymphadenectomy. To the best of our knowledge, this has been the first study to report that pembrolizumab administration before surgery for chemotherapy-resistant ureteral carcinoma promoted a pathological complete response, providing a better understanding of the cancer microenvironment after immunotherapy.

Laparoscopic nephrectomy in a patient with severe scoliosis: A case report.

Although the role of laparoscopic nephrectomy (LN) has been established, few studies have reported cases of LN in individuals with scoliosis. Here we report a case of right LN in a patient with severe right convex scoliosis. A 26-year-old man presented with a fever. His medical history comprised severe right convex lumbar scoliosis. CT revealed right hydronephrosis and right kidney stones. Pyelonephritis requiring nephrectomy was diagnosed. Right LN was feasible with elaborate perioperative care. The postoperative course was uneventful with no relapse of urinary tract infection.