Utility of total cell-free DNA levels for surgical damage evaluation in patients with urological surgeries.

The evaluation of surgical damage is challenging because of the lack of specific biomarkers. Total cell-free DNA (cfDNA) levels have been reported to increase with external trauma and may be a biomarker for tissue damage. To investigate the utility of perioperative total cfDNA levels in evaluating surgical damage in urological surgeries. This multicenter, prospective, observational study included 196 patients scheduled for urological surgeries between September 2020 and July 2021. The primary outcome was the change in total cfDNA levels before and after urological surgery. The secondary outcome was the effect of surgical type on total cfDNA ratio before and after urological surgery. The postoperative median total cfDNA level of the 196 patients was significantly increased 2.5-fold compared to the preoperative level (185.2 ng/mL vs. 406.7 ng/mL, P < 0.001). The median total cfDNA before/after ratio was greater than four-fold for kidney transplantation, open cystectomy, and open adrenalectomy. The ratio was less than two-fold for laparoscopic adrenalectomy and robot-assisted radical prostatectomy. Major surgery showed a significant postoperative increase in total cfDNA levels, while minor surgery did not. Total cfDNA levels increased 2.5-fold after urological surgery and it can be used as an acute-phase biomarker for surgical damage.

The Impact of Preoperative Severe Renal Insufficiency on Poor Postsurgical Oncological Prognosis in Patients with Urothelial Carcinoma.

BACKGROUND: The impact of preoperative renal impairment severity on prognosis in urothelial carcinoma remains unelucidated. OBJECTIVE: To evaluate the impact of severe preoperative renal insufficiency on oncological outcomes in patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy. DESIGN, SETTING, AND PARTICIPANTS: A total of 1066 patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy at six medical centres from February 1995 to November 2017 were retrospectively examined. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Oncological outcomes, stratified using preoperative estimated glomerular filtration rate (eGFR≥60, 45≤eGFR<60, and eGFR<45ml/min/1.73m2), were investigated. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analysis was performed to evaluate the impact of preoperative eGFR on prognosis. RESULTS AND LIMITATIONS: Of 610 patients with muscle-invasive bladder cancer (MIBC), 80 (13%) had severe renal insufficiency (eGFR<45ml/min/1.73m2). Of 456 patients with upper tract urothelial carcinoma (UTUC), 101 (22%) had severe renal insufficiency. Significant differences were noted in background and prognosis among the patients with preoperative eGFR≥60, 45≤eGFR<60, and eGFR<45ml/min/1.73m2. Findings of IPTW-adjusted Cox regression analysis demonstrated that preoperative eGFR<45ml/min/1.73m2 was significantly associated with poor postsurgical recurrence-free, cancer-specific and overall survival rates in patients with either MIBC or UTUC. CONCLUSIONS: Patients with urothelial carcinoma with preoperative eGFR<45ml/min/1.73m2 had a significantly lower survival probability than those without. PATIENT SUMMARY: In this report, we found that preoperative severe renal insufficiency (estimated glomerular filtration rate<45ml/min/1.73m2) had higher risk for relapse and lower survival probability. Close attention is necessary when urothelial carcinoma patients have severe renal insufficiency before radical cystectomy or nephroureterectomy.

Impact of bacillus Calmette-Guérin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy.

The clinical benefits of bacillus Calmette-Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS) remain unclear. We aimed to compare the efficacy and safety of BCG therapy for upper urinary tract CIS with those of radical nephroureterectomy (RNU). Of 490 patients with upper urinary tract carcinoma, we retrospectively reviewed the post-treatment course of 58 patients with upper urinary tract CIS who underwent either RNU (RNU group) or BCG therapy (BCG group). Efficacy and safety were compared between the RNU and BCG groups. Inverse probability treatment-weighted (IPTW)-adjusted multivariate Cox regression analysis was performed to identify the influence of BCG therapy on prognosis. The RNU and BCG groups included 20 and 38 patients, respectively. No significant difference was found in patients' background, including age, sex, and performance status, between the groups. The reason underlying the selection of BCG therapy was bilateral CIS of the upper urinary tract (50%), solitary kidney (26%), unwillingness to undergo RNU (13%), and ineligibility for surgery (11%). The cytology became negative in 30 (79%) out of 38 patients after a 6-week course of BCG therapy, and 17 (57%) out of 30 patients remained negative. BCG-related adverse events (AEs) were observed in 92% of patients. The most common AE was cystitis (76%), followed by fever (50%). No significant differences were found in the progression-free, cancer-specific, and overall survivals between the RNU and BCG groups. IPTW-adjusted multivariate analysis revealed that BCG therapy did not worsen the prognosis of these patients. The limitations of our study were its retrospective design and small sample size. In conclusion, BCG therapy for upper urinary tract CIS might be a useful alternative for patient ineligible for RNU under careful observation for AEs.

Slow Gait Speed and Rapid Renal Function Decline Are Risk Factors for Postoperative Delirium after Urological Surgery.

OBJECTIVES: The aim of this study was to identify risk factors associated with postoperative delirium in patients undergoing urological surgery. METHODS: We prospectively evaluated pre- and postoperative risk factors for postoperative delirium in consecutive 215 patients who received urological surgery between August 2013 and November 2014. Preoperative factors included patient demographics, comorbidities, and frailty assessment. Frailty was measured by handgrip strength, fatigue scale of depression, fall risk assessment, and gait speed (the timed Get-up and Go test). Postoperative factors included types of anesthesia, surgical procedure, renal function and serum albumin decline, blood loss, surgery time, highest body temperature, and complications. Uni- and multivariate logistic regression analyses were performed to assess pre- and postoperative predictors for the development of postoperative delirium. RESULTS: Median age of this cohort was 67 years. Ten patients (4.7%) experienced postoperative delirium. These patients were significantly older, had weak handgrip strength, a higher fall risk assessment score, slow gait speed, and greater renal function decline compared with patients without delirium. Multivariate analysis revealed slow gait speed (>13.0 s) and rapid renal function decline (>30%) were independent risk factors for postoperative delirium. CONCLUSIONS: Slow gait speed and rapid renal function decline after urological surgery are significant factors for postoperative delirium. These data will be helpful for perioperative patient management. This study was registered as a clinical trial: UMIN: R000018809.

Core 2 ß-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness.

INTRODUCTION: To avoid over-treatment of early stage prostate cancer (PCa), predictive biomarkers for PCa aggressiveness which can be obtained during pre-treatment evaluation are essential. Core 2 ß-1, 6-N-acetylglucosaminyl-transferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans, the expression of which is associated with aggressive potential of prostate cancer. We examined whether GCNT1 expression in prostate biopsy specimen can predict cancer recurrence after radical prostatectomy for the patients with with PCa. We then investigated molecular background for aggressive malignant potential mediated by GCNT1 expression. METHODS: Paraffin-embedded PCa biopsy specimens were immunohisto-chemically tested for GCNT1 expression using an anti-GCNT1 monoclonal antibody. We also examined the role of GCNT1 in PCa progression using cell lines which express high or low levels of GCNT1. RESULTS: GCNT1 expression correlated with D' Amico's recurrence risk classification. The GCNT1-positive rate in organ confined PCa was significantly lower than that in PCa with extra-prostatic extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that GCNT1 expression status was an independent risk factor for PSA recurrence after radical prostatectomy. Subsequent basic study revealed that GCNT1-over-expressing cells produced a significantly larger amount of growth factors when co-cultured with prostate stromal cells compared with GCNT1-knocked down cells and formed larger tumors. CONCLUSIONS: GCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient. Further validation study is necessary to establish clinical implication of GCNT1 in management of PCa.

Detection of Core2 ß-1,6-N-Acetylglucosaminyltransferase in Post-Digital Rectal Examination Urine Is a Reliable Indicator for Extracapsular Extension of Prostate Cancer.

To identify appropriate candidates for aggressive treatment such as radical prostatectomy or radiation therapy of localized prostate cancer (PCa), novel predictive biomarkers of PCa aggressiveness are essential. Core2 ß-1,6-N-acetylglucosaminyltransferase-1 (GCNT1) is a key enzyme that forms core 2-branched O-glycans. Its expression is associated with the progression of several cancers. We established a mouse IgG monoclonal antibody (mAb) against GCNT1 and examined the relationship of GCNT1 expression to the clinicopathological status of PCa. Paraffin-embedded PCa specimens were analyzed by immunohistochemistry for GCNT1 expression using a newly established mouse anti-GCNT1 mAb by ourselves. GCNT1-positive tumor showed significantly higher Gleason score and larger tumor volume. The number of GCNT1-positive cases was significantly lower in cases of organ-confined disease than in cases of extracapsular extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that detection of GCNT1 expression was an independent risk factor for PSA recurrence. We established new methods for GCNT1 detection from PCa specimens. Immunoblotting was used to examine post-digital rectal examination (DRE) urine from PCa patients. Over 90% of GCNT1-positive PCa patients with high concentrations of PSA showed extracapsular extension. In conclusion, GCNT1 expression closely associates with the aggressive potential of PCa. Further research aims to develop GCNT1 detection in post-DRE urine as a marker for PCa aggressiveness.

Preoperative butyrylcholinesterase level as an independent predictor of overall survival in clear cell renal cell carcinoma patients treated with nephrectomy.

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168-470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P = 0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients.

Switching hemodialysis patients from sevelamer hydrochloride to bixalomer: a single-center, non-randomized analysis of efficacy and effects on gastrointestinal symptoms and metabolic acidosis.

BACKGROUND: Bixalomer (BXL) was developed to improve gastrointestinal symptoms and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis patients. We prospectively evaluated the safety and effectiveness of switching maintenance dialysis patients from sevelamer hydrochloride to BXL. METHODS: Twenty-eight patients were switched from sevelamer hydrochloride to BXL (1:1 dose) from July to October 2012, whereas 84 randomly selected patients not treated with sevelamer hydrochloride were enrolled as a control group. The primary endpoint was improvement of gastrointestinal symptoms; secondary endpoints included improvement in metabolic acidosis, changes in blood biochemistry, and safety 12 weeks after the switch. We also surveyed patient satisfaction with switching to BXL 12 weeks after the switch. RESULTS: Before switching, symptoms of epigastric fullness were significantly worse in the switch than in the control group. Twelve weeks after the switch, reflux, epigastric fullness, and constipation had improved significantly in the switch group. Other factors, including stomach ache, diarrhea, and form of stool, did not change significantly. Blood gas analysis showed that metabolic acidosis was significantly improved by switching. Four patients (14%) experienced grade 1 adverse events, all of which improved immediately after stopping BXL. Major adverse events were diarrhea and abdominal discomfort. Mean satisfaction score was 3.1 ± 0.7, with 64% of patients reporting they were "neither satisfied nor dissatisfied" after switching. CONCLUSIONS: A switch from sevelamer hydrochloride to BXL improved symptoms of reflux, epigastric fullness, constipation, and metabolic acidosis in hemodialysis patients. TRIAL REGISTRATION: The study was registered as Clinical trial: (UMIN000011150).

[Testicular tumor arising in intra-abdominal testis which was not detected at prior orchidopexy : a case report].

A 35-year-old man with an intra-abdominal testicular tumor arising from the right unresolved intraabdominal testis is reported. At 10 years old, left orchidopexy was successfully performed for bilateral undescended testes. However, the right testis was not detected during the operation, and it was diagnosed as vanishing testis. Twenty-five years later, he was referred to our hospital with the complaint of right lower abdominal pain. Computed tomography revealed huge pelvic tumors and bulky para-aortic lymph node swellings. Histopathologic examination of the needle biopsy specimen obtained from the pelvic tumor revealed seminomatous germ cell tumor. Taking the results with a tumor marker study into consideration, the patient was tentatively diagnosed with non-seminomatous germ cell tumor NSGCT (stage IIB) arising from the unresolved intra-abdominal testis or extragonadal germ cell tumor. He received 3 courses of bleomycin, etoposide, cisplatin (BEP), and 4 courses of VP-16, ifosfamide, cisplatin (VIP). After chemotherapy, we performed tumorectomy and retroperitoneal lymphadenectomy because tumor markers were normalized and 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)-CT revealed normalization. We identified the pelvic tumor as an intra-abdominal testicular tumor arising from right unresolved intra-abdominal testis. Pathological examination revealed no residual tumor cells. There has been no recurrence 17 months after surgery.