Preoperative risk stratification models after radical cystectomy for bladder cancer: A multi-center study.

OBJECTIVE: We investigated preoperative patient factors associated with prognosis in 263 bladder cancer (BC) patients undergoing radical cystectomy (RC). We also developed new risk stratification models for prognosis. METHODS: This retrospective study included patients treated at Tottori University Hospital and affiliated hospitals between January 2010 and December 2019. The relationship between preoperative patient factors and overall recurrence-free and cancer-specific survival (CSS) was analyzed. The modified Glasgow prognosis score (mGPS) was calculated using serum albumin and C-reactive protein (CRP) levels. Statistical analyses included the log-rank test and Cox proportional hazards regression. RESULTS: Eastern Cooperative Oncology Group performance status (ECOG-PS), mGPS, and clinical tumor stage independently predicted CSS in multivariate analysis. A new risk stratification model included ECOG-PS ≥2, clinical tumor stage ≥3, serum albumin <3.5 g/dL, and serum CRP >0.5 mg/dL. Risk groups were defined as 0 factors (low risk), 1-2 factors (intermediate risk), and 3-4 factors (high risk). High-risk patients showed significantly poorer 3-year cancer-free survival: 86.9% (low risk), 76.7% (intermediate risk), and 50.0% (high risk). CONCLUSIONS: ECOG-PS, clinical tumor stage, and mGPS are predictive of poor cancer-free survival post-RC for BC. Our model offers the potential for prognostic prediction in these patients.

Prognostic impact of preoperative hematological disorders and a risk stratification model in bladder cancer patients treated with radical cystectomy.

OBJECTIVES: The present study investigated prognostic indicators, including clinicopathological and preoperative hematological factors, and developed a prognostic factor-based risk stratification model in bladder cancer patients treated with radical cystectomy. METHODS: Data were collected from 249 consecutive bladder cancer patients treated with radical cystectomy without neoadjuvant therapy. Prognostic values of the preoperative hematological parameters, along with the patients' clinicopathological parameters were evaluated. A risk stratification model was developed to predict disease-specific survival after radical cystectomy using the regression coefficients of multivariate analysis. RESULTS: In the multivariate analysis, preoperative hemoglobin and C-reactive protein levels, as well as the pathological factors of T stage, positive surgical margin and lymph node metastasis, were independently predictive of disease-specific survival. Low hemoglobin (<10.5 g/dL), a high C-reactive protein (>0.5 mg/dL), extravesical T stage (≥pT3a) and positive surgical margin were independent predictors of poor disease-specific survival. The risk stratification model showed significant differences in disease-specific survival between the three subgroups. CONCLUSIONS: This is the first report to show the significance of combining preoperative hemoglobin with the pathology of radical cystectomy specimens as an independent predictor for disease-specific survival, and it also represents the largest contemporary series to date demonstrating that two types of preoperative hematological disorders, assessed by hemoglobin and C-reactive protein, are independent predictors in bladder cancer patients treated with radical cystectomy. Our risk stratification model could provide physicians with useful prognostic information for identifying patients who might be candidates for multimodal treatments.

The Benefits of Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma Require at Least Three Cycles.

Background: Upper urinary tract urothelial carcinoma (UTUC) is uncommon. In advanced cases, radical nephroureterectomy (RNU) alone is not curative, and recurrence and metastasis are likely to occur. Adjuvant chemotherapy (AC) is an evidence-based treatment. However, the optimal number of AC cycles is not clear. This multicenter study investigated the number of cycles required for the beneficial effects of AC in Japanese patients with UTUC. Methods: Patients who were diagnosed with UTUC and underwent RNU at our hospital and affiliated hospitals from January 2010 to September 2020 were included in the study. Patients with pathological T3 or higher or lymph node metastasis were observed or given AC, and their responses were compared. The AC regimens included gemcitabine and cisplatin or carboplatin. Patients were also classified into two groups: the observation and two cycles of AC group and the three to four cycles of AC group. The survival curves for recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses. Results: Of the 133 patients enrolled in the study, 24 received 2 cycles of AC, 37 received 3-4 cycles, and 72 were observed only. The 5-year RFS was 67.1% for the 3-4 cycles of AC group and 41.7% for the observation and two cycles of AC group. The 5-year CSS was 72.2% for the 3-4 cycles of AC group and 35.9% for the observation and two cycles of AC group. RFS and CSS were significantly longer in the 3-4 cycles of AC group compared to the observation and 2 cycles group (P = 0.048 and P = 0.005 respectively). Conclusion: AC prolonged RFS and CSS in the real-world setting. However, at least three cycles of AC are required to achieve beneficial effects in patients with UTUC.

Coexistence of elastic fibers with hyaluronic acid in the human urethral sphincter complex: a histological study.

PURPOSE: To promote the prevention and treatment of urethral sphincteric dysfunction, we examined the distribution of elastic fibers around the urethral sphincter complex and the histological localization of hyaluronic acid in relation to elastic fiber architecture. MATERIALS AND METHODS: Using elastica-Masson staining as well as biotinated hyaluronic acid binding protein, we examined specimens of the urethral sphincter complex obtained from 14 elderly Japanese cadavers, including 10 men and 4 women. As a control, we also observed other striated muscles in male cadavers. RESULTS: Elastic fibers were densely distributed throughout the submucosal and smooth muscle layers along the entire length of the male urethra, including the prostatic urethra. The levator ani fascia and rhabdosphincter also contained abundant elastic fibers. An intramuscular elastic net was seen in the rhabdosphincter but not in other striated muscles. Strong staining for hyaluronic acid was evident in the submucosa and smooth muscle sphincter of the urethra but not in the levator ani fascia or rhabdosphincter, suggesting that elastic fibers and hyaluronic acid might interact at the former sites. Gender related differences in the distribution of elastic fibers and hyaluronic acid were noted with a much lower density of elastic fibers and hyaluronic acid staining in women than in men. CONCLUSIONS: Urethral sites where elastic fibers and hyaluronic acid coexist could be targeted for the prevention and treatment of urethral sphincteric insufficiency. These findings should improve our understanding of the human urethral sphincter complex.

Oncological and functional outcomes after radical nephrectomy for renal cell carcinoma: a comprehensive analysis of prognostic factors.

OBJECTIVES: To investigate mortality rates and to comprehensively analyze prognostic indicators after radical nephrectomy for renal cell carcinoma. METHODS: Data were collected from 147 patients who underwent potentially curative radical nephrectomy for renal cell carcinoma. The following data were analyzed: tumor pathology, patient demographics and clinical parameters, such as pre- and postoperative estimated glomerular filtration rate, as well as the cause of death. Cause-specific survival rates were calculated including deaths caused by renal cell carcinoma and cardiovascular disease. A Cox proportional hazard model was used for statistical analysis. RESULTS: A univariate analysis showed that age at surgery (≥70 years), postoperative estimated glomerular filtration rate (<45 mL/min/1.73 m(2)), pathological high T stage, grade and venous invasion were significant poor prognostic indicators. The multivariate analysis provided evidence that pathological venous invasion was a significant poor prognostic indicator, whereas age at surgery (≥70 years), pre- (<65 mL/min/1.73 m(2)) or postoperative (<45 mL/min/1.73 m(2)) estimated glomerular filtration rate and pathological high grade were significant poor prognostic indicators in T1 tumor cases. CONCLUSIONS: Post-radical nephrectomy renal function insufficiency can lead to a poor prognostic outcome, especially in patients with T1 renal cell carcinoma. Physicians should consider a comprehensive follow up focusing on possible causes of death, including those related to both renal cell carcinoma and cardiovascular disease events after radical nephrectomy.

Dry box training with three-dimensional vision for the assistant surgeon in robot-assisted urological surgery.

We analyzed whether three-dimensional vision, practice or previous laparoscopic experience improves the surgical performance of the bedside assistant during robot-assisted surgery. Six experienced laparoscopic surgeons and 15 novices carried out three skills drills imitating an assistant's maneuvers in robot-assisted surgery, and times for completing the tasks were recorded. Both the novice and experienced groups showed significantly shorter manipulation times for each drill with three-dimensional vision compared with two-dimensional or glassless three-dimensional vision. The experienced group showed significantly shorter manipulation times than the novice group for all types of vision. A significant improvement was observed 14 out of 18 times in the novice group, but only one out of 18 times in the experienced group. We can conclude that the use of three-dimensional visualization facilitates the performance of the assistant surgeon, especially if a novice, during robot-assisted surgery. Laparoscopic experience also improves the performance, whereas training is beneficial for novice assistant surgeons before carrying out actual operations.

Impact of Hyper- and Hypo-Uricemia on Kidney Function.

Uric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic mutations or polymorphism. Hyperuricemia increases urinary UA concentration and is frequently associated with urolithiasis, which is augmented by low urinary pH. Renal hypouricemia (RHU) is associated with renal stones by increased level of urinary UA, which correlates with the impaired tubular reabsorption of UA. Hyperuricemia causes gout nephropathy, characterized by renal interstitium and tubular damage because MSU precipitates in the tubules. RHU is also frequently associated with tubular damage with elevated urinary beta2-microglobulin due to increased urinary UA concentration, which is related to impaired tubular UA reabsorption through URAT1. Hyperuricemia could induce renal arteriopathy and reduce renal blood flow, while increasing urinary albumin excretion, which is correlated with plasma xanthine oxidoreductase (XOR) activity. RHU is associated with exercise-induced kidney injury, since low levels of SUA could induce the vasoconstriction of the kidney and the enhanced urinary UA excretion could form intratubular precipitation. A U-shaped association of SUA with organ damage is observed in patients with kidney diseases related to impaired endothelial function. Under hyperuricemia, intracellular UA, MSU crystals, and XOR could reduce NO and activate several proinflammatory signals, impairing endothelial functions. Under hypouricemia, the genetic and pharmacological depletion of UA could impair the NO-dependent and independent endothelial functions, suggesting that RHU and secondary hypouricemia might be a risk factor for the loss of kidney functions. In order to protect kidney functions in hyperuricemic patients, the use of urate lowering agents could be recommended to target SUA below 6 mg/dL. In order to protect the kidney functions in RHU patients, hydration and urinary alkalization may be recommended, and in some cases an XOR inhibitor might be recommended in order to reduce oxidative stress.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dL, and the Uur/Ucr and Cur/Ccr were 0.56±0.14% and 45.7±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.

Detailed histological investigation of the female urethra: application to radical cystectomy.

PURPOSE: We histologically examined the urethral anatomy to assess whether the surgical procedure for radical cystectomy should be modified in females. MATERIALS AND METHODS: Anatomical and histological studies were performed on 20 adult female cadavers. Semiserial sections were processed for histological examination and immunohistochemistry. To assess the clinical value of the antegrade approach we examined blood loss and function in 12 consecutive patients who underwent radical cystectomy by this approach. RESULTS: Vaginal wall smooth muscle contributed to urethral wall formation, in addition to a thin layer of proper urethral smooth muscle, particularly when the bladder detrusor was poorly developed or degenerated. The middle urethra was attached tightly to the vaginal smooth muscles with abundant veins running at the interface. The urethral sphincter and its inferoposterior continuation (urethrovaginal sphincter) were embedded in the elastic fiber rich perineal membrane. The membrane was U shaped, wrapping around the anterior aspect of the middle urethra and extending posterior along the distal vagina to end at the lateral extension of the perineal body near the external anal sphincter. Mean estimated blood loss was 965 ml. Of patients who received a neobladder hypercontinence was observed in 14.3% and 57.1% achieved continence. CONCLUSIONS: There is topographical variation in the anatomy of tissues surrounding the female urethra. Care should be taken when dissecting the tissues dorsal or lateral to the urethra. The antegrade approach is useful since the urethra can be dissected under direct vision and traction can be applied to these structures.

Fas expression in renal cell carcinoma accurately predicts patient survival after radical nephrectomy.

OBJECTIVES: To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). PATIENTS AND METHODS: mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. RESULTS: A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. CONCLUSIONS: The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis.

Spontaneous regression of metastatic renal cell carcinoma after cytoreductive nephrectomy: A case report.

We herein report a case involving a 59-year-old man with right lung and mediastinal lymph node metastases from renal cell carcinoma. After cytoreductive nephrectomy without neoadjuvant therapy, he achieved spontaneous regression. The regression was maintained 3 years after the operation. We immunohistochemically examined the surgical specimens and considered the possible mechanism underlying this phenomenon.

Villous adenoma of the urachus obscuring urachal adenocarcinoma: A case report.

We report a case of a 78-year-old woman with a urachal tumor of the bladder wall. We performed a biopsy and revealed the tumor as a villous adenoma. We excised the tumor by partial cystectomy together with the umbilical ligament, because it was possible there was a co-existing malignancy. The tumor turned out to be villous adenoma and a urachal adenocarcinoma. Because the superficial section of the tumor consisted only of adenoma, a biopsy could not identify the malignant component. Villous adenoma of the urinary tract or the urachus is very rare, and it is considered as an intestinal premalignancy.

Xp11.2 translocation renal cell carcinoma with TFE3 gene fusion in the elderly: case report and literature review.

A 68-year-old man was followed up with chronic kidney disease. Follow-up CT incidentally detected a tumor at the left kidney and multiple small nodular shadows in the lungs bilaterally. The patient underwent needle biopsy and was diagnosed with Xp11.2 translocation renal cell carcinoma (RCC) pathologically. Hence, laparoscopic nephrectomy was performed. Fluorescence in situ hybridization analysis revealed a break-apart of the transcription factor E3 (TFE3) genes in the left tumor. After 2 months postoperatively, nivolumab and ipilimumab were administered thrice intravenously, considering the intermediate risk by the IMDC risk classification. However, pleural effusion occurred but was removed adequately. Lung metastasis decreased, but new metastasis occurred at the left iliopsoas muscle. Target therapy was performed with axitinib. Unfortunately, he died 6 months later postoperatively. These tumors commonly occur in children than in adults, and very rare in elderly patients. Xp11.2 translocation RCC in the elderly has a poorer prognosis than that in children. To date, no effective treatment for Xp11.2 translocation RCC has been established.

Effect of Intravesical Bacilli Calmette-Guerin Therapy After Second Transurethral Resection in Stage Ta T1 High-Grade Bladder Cancer.

BACKGROUND: To evaluate the efficacy of Bacilli Calmette-Guerin (BCG) induction instillation therapy after second transurethral resection (TUR) in stage Ta T1 high-grade bladder cancer. METHODS: We performed a retrospective analysis of 49 consecutive new onset Ta T1 high-grade bladder cancer patients treated with second TUR at our affiliated institutions. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors related to RFS were evaluated by univariate and multivariate Cox proportional hazard model analyses. RESULTS: Thirty-one patients received BCG therapy after the second TUR (BCG group), and 18 patients were treated with second TUR alone (no BCG group). There were statistically significant differences in the RFS rates between the two groups, (P = 0.037). BCG therapy was the only factor predictive of intravesical recurrence after second TUR in both univariate and multivariate analyses. After the second TUR, BCG therapy significantly decreased intravesical recurrence in the patients with residual tumors (P = 0.014). However, there was no significant difference in intravesical recurrence in the patients with no residual tumors between the two groups (P = 0.359). CONCLUSION: BCG therapy after second TUR significantly decreased intravesical recurrence of residual tumors found at the second TUR.

HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor.

Hyaluronidases degrade hyaluronic acid, which promotes metastasis. HYAL1 type hyaluronidase is an independent prognostic indicator of prostate cancer progression and a biomarker for bladder cancer. However, it is controversial whether hyaluronidase (e.g., HYAL1) functions as a tumor promoter or as a suppressor. We stably transfected prostate cancer cells, DU145 and PC-3 ML, with HYAL1-sense (HYAL1-S), HYAL1-antisense (HYAL1-AS), or vector DNA. HYAL1-AS transfectants were not generated for PC-3 ML because it expresses little HYAL1. HYAL1-S transfectants produced < or = 42 milliunits (moderate overproducers) or > or = 80 milliunits hyaluronidase activity (high producers). HYAL1-AS transfectants produced <10% hyaluronidase activity when compared with vector transfectants (18-24 milliunits). Both blocking HYAL1 expression and high HYAL1 production resulted in a 4- to 5-fold decrease in prostate cancer cell proliferation. HYAL1-AS transfectants had a G2-M block due to decreased cyclin B1, cdc25c, and cdc2/p34 expression and cdc2/p34 kinase activity. High HYAL1 producers had a 3-fold increase in apoptotic activity and mitochondrial depolarization when compared with vector transfectants and expressed activated proapoptotic protein WOX1. Blocking HYAL1 expression inhibited tumor growth by 4- to 7-fold, whereas high HYAL1 producing transfectants either did not form tumors (DU145) or grew 3.5-fold slower (PC-3 ML). Whereas vector and moderate HYAL1 producers generated muscle and blood vessel infiltrating tumors, HYAL1-AS tumors were benign and contained smaller capillaries. Specimens of high HYAL1 producers were 99% free of tumor cells. This study shows that, depending on the concentration, HYAL1 functions as a tumor promoter and as a suppressor and provides a basis for anti-hyaluronidase and high-hyaluronidase treatments for cancer.

Estimation of mortality and morbidity risk of radical cystectomy using POSSUM and the Portsmouth predictor equation.

INTRODUCTION: The Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) and the Portsmouth predictor equation (P-POSSUM) are simple scoring systems used to estimate the risk of complications and death postoperatively. We investigated the use of these scores to predict the postoperative risk in patients undergoing radical cystectomy (RC). MATERIAL AND METHODS: In this retrospective study, we enrolled 280 patients who underwent RC for invasive bladder cancer between January 2003 and December 2011. Morbidity and mortality were predicted using the POSSUM and P-POSSUM equations. We further assessed the ability of the POSSUM and P-POSSUM to predict the mortality and morbidity risk in RC patients with a Clavien-Dindo classification of surgical complications of grade II or higher. RESULTS: The observed morbidity and mortality rates were 58.9% (165 patients) and 1.8% (5 patients), respectively. Predicted morbidity using POSSUM was 49.2% (138 patients) compared to the 58.9% (165 patients) observed (P <0.0001). Compared to the observed death rate of 1.8% (5 patients), predicted mortality using POSSUM and P-POSSUM was 12.1% (34 patients) and 3.9% (11 patients), respectively (P <0.0001 and P = 0.205). The mortality risk estimated by P-POSSUM was not significantly different from the observed mortality rate. CONCLUSIONS: The results of this study supported the efficacy of POSSUM combined with P-POSSUM to predict morbidity and mortality in patients undergoing RC. Further prospective studies are needed to better determine the usefulness of POSSUM and P-POSSUM for a comparative audit in urological patients undergoing RC.

Hydronephrosis after retroperitoneal laparoscopic dismembered Anderson-Hynes pyeloplasty in adult patients with ureteropelvic junction obstruction: A longitudinal analysis.

OBJECTIVE: We evaluated the improvement of hydronephrosis longitudinally after laparoscopic dismembered Anderson-Hynes pyeloplasty in adult patients with ureteropelvic junction obstruction. MATERIAL AND METHODS: Sixteen patients underwent laparoscopic pyeloplasty at our institution between January 2006 and June 2012. Hydronephrosis was assessed by ultrasound and intravenous pyelography at 3, 6, 12, 18, and 24 months after pyeloplasty. RESULTS: The mean follow-up time was 24 months. Preoperative hydronephrosis was diagnosed as grade 2 and grade 3 in 8 patients each. Postoperative improvement of the hydronephrosis by one grade was observed in 56%, 73%, 67%, 50%, and 40% of patients at 3, 6, 12, 18, and 24 months, respectively. Improvement of the hydronephrosis by two grades was observed in 6%, 27%, 33%, 50%, and 60% of patients at 3, 6, 12, 18, and 24 months, respectively. In 5 of 12 patients (42%), hydronephrosis was still improving even after 12 months postoperatively. CONCLUSIONS: Adult patients demonstrate relatively rapid improvements in the degree of hydronephrosis after laparoscopic pyeloplasty and continue to improve for a long time.

Preoperative prognostic factors after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

PURPOSE: To evaluate the clinical significance of preoperative biomarkers such as laboratory data, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and clinicopathological factors in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: Between 1995 and 2011, a total of 99 patients treated at our institution for upper urinary tract urothelial carcinoma were enrolled in this study. The prognostic significance of various preoperative data and clinicopathological factors were analyzed. Univariate and multivariate analyses were performed using the Kaplan-Meier method with the log-rank test and a Cox proportional hazards regression model. RESULTS: Median patient age was 73 years (range 44-86 years), and the median follow-up period after radical nephroureterectomy was 37.9 months (range 6.6-171.4 months). The 5-year intravesical recurrence-free survival and cancer-specific survival estimates were 47.1 and 70.0 %, respectively. On multivariate analysis, concomitant bladder carcinoma was an independent predictor of intravesical recurrence (hazard ratio 3.689; P = 0.002), and infiltration (hazard ratio 14.842; P = 0.002), preoperative serum creatinine level (hazard ratio 9.992; P = 0.005), preoperative serum hemoglobin level (hazard ratio 6.370; P = 0.018) and ECOG PS (hazard ratio 4.326; P = 0.037) were associated with worse cancer-specific survival. This study is limited by biases associated with its retrospective design. CONCLUSIONS: This study indicates that not only clinicopathological factors, but also preoperative biomarkers, such as serum creatinine and hemoglobin levels and ECOG PS, predict a poor survival in patients with upper urinary tract urothelial carcinoma.

The significant immunological characteristics of peripheral blood neutrophil-to-lymphocyte ratio and Fas ligand expression incidence in nephrectomized tumor in late recurrence from renal cell carcinoma.

OBJECTIVE: In order to characterize the significance of immune system function in patients with advanced renal cell carcinoma (RCC), we investigated the interactive relationships among the following parameters: metastatic characteristics, expression of Fas ligand (FasL) in nephrectomized specimens, immunological parameters, and patient's prognosis. MATERIALS AND METHODS: Thirty-five patients with advanced RCC were stratified into 3 groups according to the characteristics of metastasis timing, at first presentation (mFP), within 5 years of nephrectomy (early-recurrence), after 5 years (late-recurrence). Immunological parameters [hemoglobin, lymphocyte count, neutrophil/lymphocyte ratio (NLR), serum albumin, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and Charlson Comorbidity Index], FasL expression in RCC, and patient prognosis from occurrence of metastasis were compared among the groups. Thirty-five patients were also stratified into 2 groups according to FasL positivity and individual parameters. Patient's prognosis and the remaining immunological parameters were compared between groups. RESULTS: The NLRs of the late-recurrence group were significantly lower than those of the mFP (P = 0.0004) and early-recurrence (P = 0.013) groups. The FasL mRNA positivity of the late-recurrence group was significantly lower than those of the mFP (P = 0.001) and early-recurrence (P = 0.0277) groups. The prognosis of the late-recurrence group was significantly better than that of the early-recurrence group (P = 0.0255). NLRs were significantly lower in the FasL-negative group than in the -positive group (P = 0.0182). The cause-specific survival rates of the ECOG PS 0 group were significantly higher than that of the ECOG PS > 0 group (P < 0.0001). CONCLUSIONS: Our results suggest the associations of the prognosis in advanced RCC with peripheral blood NLR and FasL expression in nephrectomized tumor. The characteristics of lower values of NLR and FasL expression positivity in late-recurrence compared with other metastatic timings suggest strong host immune activity, and may imply relatively long survival. On the other hand, elucidation of the patient's general condition obtained not only by chemical data but also by ECOG PS is crucial in the management of patients with advanced RCC.

Fas expression in nephrectomized, non-cancerous specimens predicts post-nephrectomy chronic kidney disease progression in patients with renal and upper urinary tract malignancies.

OBJECTIVES: Despite the surgical curability of renal cell carcinoma (RCC) and upper urinary tract urothelial carcinoma (UUT-UC), post-nephrectomy chronic kidney disease (CKD) continues to be a cause of concern. We investigated the correlation between the expression of apoptotic regulatory molecules in the nephrectomized, noncancerous cortex, as well as CKD progression and CKD-related mortality. MATERIALS AND METHODS: Fas and Bcl-2 mRNA and protein expression in surgically resected specimens from 100 patients with RCC and UUT-UC were determined. The estimated glomerular filtration rates (eGFR) were determined sequentially before surgery and up to 5 years after surgery. The relationships between CKD progression, the expression of these molecules in the renal cortex, and the clinical characteristics were analyzed. RESULTS: The mean 1-year postoperative percent eGFR decrease was 30.2 (Standard deviation [SD]: 15.2). The 1-year postoperative percent eGFR decrease greater than the approximate value of mean ± SD (45) was categorized as severe renal functional deterioration (SRFD). Glomerular Fas protein expression and a Fas/ß-actin mRNA ratio >0.3 were independent predictors for SRFD. Significantly increased mortality rates due to cardiovascular events were indicated by glomerular Fas protein expression, Fas mRNA levels >0.3, and SRFD. No significant change in Bcl-2 levels was observed. CONCLUSIONS: This study is the first report to demonstrate the significance of Fas expression in the nephrectomized normal cortex as a predictor of post-nephrectomy CKD progression. The results from nephrectomized kidney showed that the natural course of renal function in the remaining kidney may be affected not only by Fas-induced glomerular cell apoptosis but also by the total amount of Fas mRNA in cortical cells.