The Predictive Significance of Prognostic Nutritional Index and Serum Albumin/Globulin Ratio on the Overall Survival of Penile Cancer Patients Undergoing Penectomy.

Objective: To assess the value of using the prognostic nutritional index (PNI) and serum albumin/globulin ratio (AGR) in predicting the overall survival (OS) of patients with penile cancer (PC) undergoing penectomy. Materials and methods: A retrospective analysis of 123 patients who were admitted to our hospital due to PC from April 2010 to September 2021 and who underwent penectomy were included in the study. The optimal cut-off value of the PNI and AGR was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis and the Cox proportional hazard model were used to evaluate the correlation between the PNI, AGR, and OS in patients with PC. Results: A total of 16 of the 123 patients died during the follow-up period, and the median follow-up time was 58.0 months. The best cut-off values of the PNI and AGR were set to 49.03 (95% confidence interval 0.705-0.888, Youden index = 0.517, sensitivity = 57.9%, specificity = 93.7%, p < 0.001) and 1.28 (95% confidence interval 0.610-0.860, Youden index = 0.404, sensitivity = 84.1%, specificity = 56.2%, p = 0.003). The Kaplan-Meier analysis showed that the OS of the patients in the high PNI group and the high AGR group was significantly higher than that of the patients in the low PNI group and the low AGR group (p < 0.001). The univariable analysis showed that the aCCI, the clinical N stage, the pathological stage, and the PNI, AGR, SII, and PLR are all predictors of OS in patients with PC (p < 0.05). The multivariable analysis showed that the PNI (risk rate [HR] = 0.091; 95% CI: 0.010-0.853; p = 0.036) and the AGR (risk rate [HR] = 0.171; 95% CI: 0.043-0.680; p = 0.012) are independent prognostic factors for predicting OS in patients with PC undergoing penectomy. Conclusions: Both the PNI score and the serum AGR are independent prognostic factors for predicting OS in patients with PC undergoing penectomy.

Single-cell transcriptomics reveals a low CD8+ T cell infiltrating state mediated by fibroblasts in recurrent renal cell carcinoma.

PURPOSE: Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments. RESULTS: reRCC had reduced CD8+ T cells but increased cancer-associated fibroblasts (CAFs) infiltration compared with pRCC. Reduced CD8+ T cells and increased CAFs infiltration were significantly associated with a worse response from immunotherapy. Remarkably, CAFs showed substantial expression of LGALS1 (Gal1). In vitro, CAFs could induce CD8+ T cells apoptosis via Gal1. In vivo, knockdown of Gal1 in CAFs suppressed tumor growth, increased CD8+ T cells infiltration, reduced the proportion of apoptotic CD8+ T cells and enhanced the efficacy of immunotherapy. CONCLUSIONS: We delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8+ T cells via Gal1. Targeting Gal1 combined with anti-PD1 showed promising efficacy in treating RCC.

The prognostic nutritional index predicts the biochemical recurrence of patients treated with robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the prognostic nutritional index (PNI) in predicting the biochemical recurrence (BCR) of patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: The clinical data of 136 patients treated with RALP in the Department of Urology, The Third Xiangya Hospital of Central South University were retrospectively analyzed. The endpoint of observation was BCR. The area under the receiver operating characteristic (ROC) curve was evaluated to determine the optimal cutoff value of PNI. The correlation of the PNI with BCR was estimated using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The optimal cutoff value of the PNI was 46.03 according to the ROC curve. (95% confidence interval: 0.604-0.805, Youden index = 0.401, sensitivity = 82.5%, specificity = 57.6%, p < 0.01). Multivariate Cox analysis showed that clinical staging, prostate-specific antigen, and PNI were independent prognostic factors for predicting BCR in patients treated with RALP. CONCLUSION: PNI is an independent prognostic factor for predicting BCR in patients treated with RALP. The incorporation of the PNI into risk assessments may provide additional prognostic information.

LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis.

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.

The reproductive regulation of LPXRFa and its receptor in the hypothalamo-pituitary-gonadal axis of the spotted scat (Scatophagus argus).

Gonadotropin-inhibitory hormone (GnIH) plays a critical role in regulating gonadotropin-releasing hormone (GnRH), gonadotropin hormone (GtH), and steroidogenesis. The Lpxrfa (the piscine ortholog of GnIH) system has been found to regulate fish reproduction. To gain insight into the role of Lpxrfa in the regulation of spotted scat (Scatophagus argus) reproduction, spotted scat Lpxrfa (ssLpxrfa), and its receptor (ssLpxrfa-r) were cloned and analyzed. Tissue distribution and expression patterns at the hypothalamo-pituitary-gonadal axis (HPG axis) of sslpxrfa and sslpxrfa-r mRNA were also investigated during gonadal development of spotted scat. The open reading frame (ORF) of the sslpxrfa was 606 bp encoding 201 amino acids and includes a putative signal peptide and two mature ssLpxrfa peptides with LPXRFamide motif at their C-terminus. The sslpxrfa-r ORF was 1449 bp encoding 482 amino acids and contracted a seven-hydrophobic transmembrane (TM) domain structure. The tissue distribution showe d that the sslpxrfa was highly expressed in hypothalami, gill, and the gonads. In addition, sslpxrfa-r was highly expressed in hypothalami, pituitaries, and the gonads. Quantitative real-time polymerase chain reaction (qPCR) revealed that sslpxrfa had the highest expression in the hypothalami and pituitaries, and the lowest expression in the gonads in stage V. During gonadal development, the expression of sslpxrfa-r was gradually increased in the hypothalami but reduced in the gonads. However, no obvious trend was observed in the pituitaries. The expression of sslpxrfa and sslpxrfa-r decreased significantly after injection with 17ß-estradiol (E2). However, the expression of both sslpxrfa and sslpxrfa-r was not changed after injection with 17α-methyltestosterone(17α-MT) in the hypothalami. In addition, no changes were observed in the expression of fshß and lhß in the pituitaries after injecting ssLpxrfa-1. However, ssLpxrfa-2 could downregulate the expression of sbgnrh and fshß in the hypothalami and pituitaries, respectively. Taken together, these findings suggested that ssLpxrfa may participate in E2 feedback in reproduction and regulate the reproductive axis of spotted scat.

[Neuroendocrine differentiated prostate adenocarcinoma: Report of 23 cases and review of the literature].

OBJECTIVE: To study the clinical features and prognosis of neuroendocrine differentiated prostate adenocarcinoma (NED/AdPC). METHODS: We retrospectively analyzed the clinical data on 23 cases of NED/AdPC treated between 2005 and 2018, among which, 18 had lower urinary tract symptoms (LUTS). RESULTS: All the 23 patients were diagnosed with NED/AdPC, including 2 cases of AdPC initially diagnosed and confirmed with neuroendocrine differentiation in a second pathological diagnosis after androgen deprivation therapy (ADT). In addition to hormonal therapy for all the cases, 3 of the patients were treated by radical prostatectomy combined with adjuvant chemo- and radiotherapy, 13 by palliative transurethral bipolar plasmakinetic resection of the prostate (pTU-PKRP), of whom 2 underwent a second pTU-PKRP and chemotherapy for castration resistance, 2 with chronic renal insufficiency by percutaneous nephrostomy because of extensive pelvic metastasis, and the other 5 by ADT alone or in combination with radiotherapy. During the follow-up of 7 to 60 months, 2 of the patients died of cancer progression and 1 of pulmonary infection, while the others survived with effective control of the tumor. CONCLUSIONS: Long-term ADT may induce neuroendocrine differentiation in AdPC patients. For early-stage NED/AdPC, radical prostatectomy combined with adjuvant therapy is a main therapeutic option, while for advanced NED/AdPC, pTU-PKRP in combination with ADT may relieve LUTS and improve the patients' quality of life.

Primary abdominal cocoon with cryptorchidism: a case report.

BACKGROUND: We report a rare case of primary abdominal cocoon with bilateral cryptorchidism. CASE PRESENTATION: The patient had a history of laparoscopic surgery for bilateral cryptorchidism 6 years earlier. He was admitted to the hospital again due to intestinal obstruction. Surgery was performed on the patient after the failure of conservative treatment. The patient was diagnosed with primary abdominal cocoon. Instead of the greater omentum, many cocoon-like tissues surrounding the bowel were seen during operation. Abdominal surgery can increase the risk of intestinal adhesion, which is one of the main causes of intestinal obstruction, especially in patients with abdominal cocoon. We hypothesize that the surgery 6 years earlier to address transabdominal bilateral cryptorchidism accelerated the patient's intestinal obstruction. CONCLUSION: This case implies that it is important for urologists to evaluate whether their patients exhibit abdominal cocoon before cryptorchidism surgery, to choose better surgical methods and reduce the risks of poor prognosis.

Phoenixin: Expression at different ovarian development stages and effects on genes ralated to reproduction in spotted scat, Scatophagus argus.

Phoenixin (Pnx), a recently discovered neuropeptide, has been implicated in reproduction. Pnx mainly exists in two active isoforms, phoenixin-14 (Pnx-14) and phoenixin-20 (Pnx-20). However, little is known about the functions of Pnx in teleosts. To determine the roles of Pnx in the regulation of reproduction in Scatophagus argus, the physiological characterization of the Pnx was analyzed. During ovary development, the expression of pnx in phase IV was higher than in phase II and III in the hypothalamus. In the pituitary, pnx expression was highest in phase IV, moderate in phase III, and lowest in phase II. When hypothalamus and pituitary fragments were cultured in vitro with Pnx-14 and Pnx-20 (10 nM and 100 nM) for 6 h, the expression of GnRHR (gonadotropin releasing hormone receptor), lh (luteinizing hormone) and fsh (follicular stimulating hormone) in the pituitary increased significantly, except GnRH (gonadotropin releasing hormone) in the hypothalamus. Similarly, the expression of GnRHR, lh and fsh in the pituitary increased significantly after injecting S. argus with Pnx-14 and Pnx-20 (10 ng/g and 100 ng/g body weight (bw)), except GnRHR and fsh treated with 10 ng/gbw Pnx-20 in the pituitary and GnRHs in the hypothalamus. These results indicate that Pnx may not only stimulate the reproduction of the S. argus through the hypothalamic-pituitary-gonadal (HPG) axis, but also directly through the pituitary.

Pretreatment serum albumin/globulin ratio as a prognostic biomarker in metastatic prostate cancer patients treated with maximal androgen blockade.

The pretreatment serum albumin/globulin ratio (AGR) has been used as a prognostic biomarker for various cancer types. However, the prognostic value of the AGR for prostate cancer, especially for metastatic prostate cancer (mPCa) after maximal androgen blockade (MAB), remains unclear. The aim of this study was to evaluate the prognostic value of the pretreatment serum AGR for mPCa treated with MAB. This retrospective study included 214 mPCa patients receiving MAB from October 2007 to March 2017. The correlation of the AGR with survival was estimated using Kaplan-Meier analysis and Cox proportional hazards models. The cutoff value of the AGR was 1.45 according to the receiver operating characteristic curve. Kaplan-Meier analysis demonstrated that patients with a low AGR (<1.45) had poor outcomes in terms of progression-free survival (PFS) and cancer-specific survival (CSS). Multivariate Cox analyses showed that the AGR was an independent predictor of PFS (hazard ratio [HR] = 0.642; 95% confidence interval [CI]: 0.430-0.957; P = 0.030) and CSS (HR = 0.412; 95% CI: 0.259-0.654; P < 0.001). Furthermore, in a subset of 79 patients with normal serum albumin levels (≥40.0 g l-1), the serum AGR remained an independent predictor of CSS (P = 0.009). The pretreatment AGR was an independent prognostic biomarker for PFS and CSS in patients with mPCa receiving MAB. In addition, the AGR remained effective for the prediction of CSS in patients with normal albumin levels (≥40 g l-1). However, further prospective studies are needed to confirm our conclusions.

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway.

BACKGROUND: Constitutively activated nuclear factor kappa B (NF-κB) signalling plays vital roles in bladder urothelial carcinoma (BC) progression. We investigate the effect of receptor-interacting protein kinase 4 (RIPK4) on NF-κB activation and BC progression. METHODS: The expression of RIPK4 was examined in 25 cryopreserved paired bladder samples and 112 paraffin BC specimens. In vivo and in vitro assays were performed to validate effect of RIPK4 on NF-κB pathway-mediated BC progression. RESULTS: High expression of RIPK4 was observed in BC tissues and was an independent predictor for poor overall survival. Up or downregulating the expression of RIPK4 enhanced or inhibited, respectively, the migration and invasion of BC cells in vitro and in vivo. Mechanistically, RIPK4 promoted K63-linked polyubiquitination of tumour necrosis factor receptor-associated factor 2 (TRAF2), receptor-interacting protein (RIP) and NF-κB essential modulator (NEMO). RIPK4 also promoted nuclear localisation of NF-κB-p65, and maintained activation of NF-κB substantially, leading to upregulation of VEGF-A, ultimately promoting BC cell aggressiveness. CONCLUSIONS: Our data highlighted the molecular aetiology and clinical significance of RIPK4 in BC: upregulation of RIPK4 contributes to NF-κB activation, and upregulates VEGF-A, and BC progression. Targeting RIPK4 might represent a new therapeutic strategy to improve survival for patients with BC.

Molecular cloning, characterization and expression analysis of spexin in spotted scat (Scatophagus argus).

Spexin (Spx), a novel neuropeptide, composed of 14 amino acid residues, is evolutionally conserved from fish to mammals. It has been suggested that Spx has pleiotropic functions in mammals. However, reports about Spx are very limited. To clarify the roles of Spx in the regulation of reproduction and food-intake in the spotted scat, the spx (ssspx) gene was cloned and analyzed. Analysis of the tissue distribution by RT-PCR showed that ssspx expression was widespread. During ovary development, expression of ssspx was found to be highest in phase II, moderate in phase III, and at its lowest level in phase IV. Ssspx expression was significantly down-regulated in the hypothalamus after treatment with E2 both in vitro and in vivo. A significant increase of ssspx was observed after 2 and 7 days of food deprivation. However, the ssspx transcript levels in the 7 day fasting group decreased significantly after refeeding 3 h after the scheduled feeding time. This suggests that ssSpx may be involved in the regulation of reproduction and food-intake in the spotted scat.

Laparoscopic versus open nephroureterectomy to treat localized and/or locally advanced upper tract urothelial carcinoma: oncological outcomes from a multicenter study.

BACKGROUND: Many studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T1-4/N0-X). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T1-4/N0-X UTUC. METHODS: We collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T1-4/N0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox's proportional hazards model was used for univariate and multivariate analysis. RESULTS: The mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P < 0.05). The predicted 5-year intravesical recurrence- free survival (RFS) (79% vs. 88%, P = 0.204), overall RFS (47% vs. 59%, P = 0.076), cancer-specific survival (CSS) (63% vs. 70%, P = 0.186), and overall survival (OS) (61% vs. 55%, P = 0.908) rates did not differ between the ONU and LNU groups. Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with intravesical RFS (odds ratio [OR] 1.23, 95% confidence interval [CI] 0.46-3.65, P = 0.622), Overall RFS (OR 0.99, 95% CI 0.54-1.83, P = 0.974), CSS (OR 1.38, 95% CI 0.616-3.13, P = 0.444), or OS (OR 1.61, 95% CI 0.81-3.17, P = 0.17). CONCLUSIONS: The results of this retrospective study showed no statistically significant differences in intravesical RFS, overall RFS, CSS, or OS between the laparoscopy and the open groups. Thus, LNU can be an alternative to the open procedure for T1-4/N0-X UTUC. Further studies, including a multi-institutional, prospective study are required to confirm these findings.

Influence of body mass index on oncological outcomes in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

OBJECTIVE: To investigate the association between body mass index and oncological outcomes in Chinese patients who had undergone radical nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: Between August 1998 and October 2009, 236 consecutive Chinese patients underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma at Sun Yat-sen University Cancer Center (Guangzhou, China). Body mass index data were available for 230 (97.5%) of these patients. All 230 patients were classified into three groups according to the body mass index criteria for Asians, issued by the Asia Cohort Consortium: underweight, body mass index <18.5 kg/m(2) (n = 21, 9.1%); normal weight, body mass index ≥18.5 and <25 kg/m(2) (n = 151, 65.7%); and obesity, body mass index ≥25 kg/m(2), (n = 58, 25.2%). Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Being underweight was significantly associated with lymph node metastasis (P = 0.017) and Eastern Cooperative Oncology Group performance status (P = 0.003). Univariate analysis showed recurrence-free survival and cancer-specific survival were significantly worse in underweight patients than in patients with normal weight or obese patients. After adjustments for other clinicopathological variables, multivariate analysis confirmed that recurrence-free survival and cancer-specific survival were significantly worse in underweight patients than in patients with normal weight or obese patients (recurrence-free survival P = 0.014, cancer-specific survival P = 0.015). CONCLUSIONS: Preoperative underweight is an independent predictor of unfavorable recurrence-free survival and cancer-specific survival in Chinese patients with upper urinary tract urothelial carcinoma treated by radical nephroureterectomy, whereas obesity is associated with superior recurrence-free survival and cancer-specific survival. Further studies, including a multi-institutional, prospective, Asian cohort study, are required to confirm these findings.

PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway.

BACKGROUND: PIN2/TRF1-interacting telomerase inhibitor1 (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Moreover, loss of PinX1 has been detected in many human malignancies. However, the possible involvement of PinX1 and its clinical/prognostic significance in urothelial carcinoma of the bladder (UCB) are unclear. METHODS: The PinX1 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC) in UCB tissues and adjacent normal urothelial bladder epithelial tissues. PinX1 was overexpressed and silenced in UCB cell lines to determine its role in tumorigenesis, development of UCB, and the possible mechanism. RESULTS: PinX1 expression in UCB was significantly down-regulated at both mRNA and protein level as compared with that in normal urothelial bladder epithelial tissues. PinX1 levels were inversely correlated with tumor multiplicity, advanced N classification, high proliferation index (Ki-67), and poor survival (P < 0.05). Moreover, overexpression of PinX1 in UCB cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing PinX1 dramatically enhanced cell proliferation. Overexpression of PinX1 resulted in G1/S phase arrest and cell growth/proliferation inhibition, while silencing PinX1 led to acceleration of G1/S transition, and cell growth/proliferation promotion by inhibiting/enhancing telomerase activity and via the p16/cyclin D1 pathway. CONCLUSIONS: These findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.

Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder.

BACKGROUND: Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear. METHODS: In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of YAP 1 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blotting, when compared with their paired normal bladder tissues. By IHC, positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86 (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was correlated with poorer differentiation, higher T classification and higher N classification (P < 0.05). In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients' survival was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P = 0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P < 0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis. CONCLUSIONS: Our findings provide evidences that positive expression of YAP 1 in UCB may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with UCB.

Age-specific effect of gender on upper tract urothelial carcinoma outcomes.

The research is to evaluate the age-specific differential effects of gender on outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Between August 1998 and October 2010, we retrospectively reviewed the data from 285 (67.7%) men and 136 (32.3%) women treated with RNU for UTUC at our two institutions. Kaplan-Meier survival estimates the age-specific effect of gender on cancer-specific survival (CSS). Cox proportional hazards regression analyses were used to address the effect of gender on CSS. No significant sex-related differences were found in age and diagnosis, clinicopathologic features, and treatment (all P values >0.05). Women had a 18.7% increased risk of death from UTUC than men (hazard ratio [HR] 1.187; 95% confidence interval [95% CI] 1.017-1.893; P = 0.021). The survival disadvantage was only present in patients aged 59 years and older (P < 0.001). Conversely, the survival advantage for women was found in women aged 42 to 58 years (P = 0.011) and in the age group <42 years (P = 0.019). On multivariable Cox regression analyses that adjusted for the effects of clinicopathologic features, the female gender was associated with decreased CSS (P = 0.036). In conclusion, the impact of gender on UTUC outcomes after RNU is age-specific. Females who aged 59 years and older experienced worse outcomes than their male counterparts, while women in the age group <42 years and 42-58 years have better outcomes than men. Further research is needed to elucidate the molecular mechanisms underlying the age-specific differential effect of gender on UTUC outcomes.

Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma.

The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

The risk factors for the presence of pelvic lymph node metastasis in penile squamous cell carcinoma patients with inguinal lymph node dissection.

OBJECTIVE: To evaluate factors in penile squamous cell carcinoma predictive of pelvic lymph node metastasis and survival. MATERIALS AND METHODS: Data were collected and analyzed retrospectively in 146 patients with squamous cell carcinoma of penis who underwent bilateral inguinal lymph node dissection in our center between January 1998 and April 2011. Variables recorded included serum squamous cell carcinoma antigen, primary tumor p53 immunoreactivity, histological grade, pathological tumor stage, lymphatic or vascular invasion, absent/unilateral or bilateral inguinal lymph node involvement, number of metastatic inguinal lymph nodes, presence of extracapsular growth and lymph node density. RESULTS: Seventy patients had inguinal lymph node metastasis (LNM). Of these, 33 (47.1%) had pelvic LNM. Primary tumor strong p53 expression, lymphatic or vascular invasion, involvement of more than two inguinal lymph nodes and 30% or greater lymph node density were significant predictors of pelvic LNM. Primary tumor strong p53 expression (odds ratio [OR] 5.997, 95% confidence intervals [CI] 1.615-22.275), presence of extracapsular growth (OR 2.209, 95% CI 1.166-4.184), involvement of more than two inguinal lymph nodes (OR 2.494, 95% CI 1.086-5.728) and pelvic lymph node involvement (OR 18.206, 95% CI 6.807-48.696) were independent prognostic factors for overall survival. CONCLUSIONS: Primary tumor expression of p53, lymphatic or vascular invasion, number of metastatic inguinal lymph nodes and lymph node density were all predictors of pathologic pelvic lymph node involvement. Patients with pelvic LNM had an adverse prognosis, with a 3-year overall survival rate of approximately 12.1%. Pelvic lymph node dissection should be considered in these cases.

Prognostic significance of tumor location and superficial urothelial bladder carcinoma history in patients with ureteral urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: To investigate the significance of tumor location and superficial urothelial bladder carcinoma (UBC) history on oncological outcomes in patients treated with radical nephroureterectomy (RNU) for ureteral urothelial carcinoma (UC). METHODS: One hundred and thirty-two patients treated with RNU for ureteral UC between January 1999 and July 2010 were retrospectively analyzed. Recurrence probabilities and survival rates were analyzed, stratified by tumor location and superficial UBC history. RESULTS: Comparison of patients with proximal, middle, and distal ureteral UC showed that percentage of bladder recurrence was 13.3, 14.7, and 25.0 %, respectively (P = 0.285); retroperitoneal (tumor bed or lymph node) recurrence was 26.7, 14.7, and 27.9 % (P = 0.319); and contralateral recurrence was 0, 2.9, and 0 % (P = 0.234). Comparison of patients with and without history of superficial UBC revealed that percentage of bladder recurrence was 15.4 and 20.2 %, respectively (P = 0.681); retroperitoneal recurrence was 15.4 and 25.2 % (P = 0.433); and contralateral recurrence was 0 and 0.84 % (P = 0.740). Using multivariable Cox regression analyses, there were no significant differences of recurrence-free survival (RFS) and cancer-specific survival (CSS) with regard to neither tumor location nor superficial UBC history (RFS: P = 0.282 and 0.762, CSS: P = 0.272 and 0.818, respectively). CONCLUSIONS: Tumor location and history of superficial UBC could not be used to predict oncological outcomes of patients who underwent RNU for ureteral UC. Therefore, operative strategies or postoperative surveillance should not be affected by tumor location or history of superficial UBC.

Clipping the extremity of ureter prior to nephroureterectomy is effective in preventing subsequent bladder recurrence after upper urinary tract urothelial carcinoma.

BACKGROUND: Bladder recurrent disease is still a challenge in the treatment of upper tract urothelial carcinoma (UTUC). This controlled study aims to investigate the efficacy of early clipping of the distal ureter prior to nephroureterectomy (NU) to prevent bladder recurrence after UTUC. METHODS: Patients with clinical diagnosis of UTUC were subjected to open trans-peritoneal NU and were randomly divided into two groups. One group received modified NU: clipping the distal ureter prior to NU; while the other group underwent traditional standard NU. Subsequent bladder recurrence was the primary endpoint. RESULTS: From January 2007 to December 2009, 85 eligible cases were enrolled in this study. Modified NU and standard NU were performed on 42 and 43 patients, respectively. Operation time ((215.73 ± 21.26) minutes vs. (220.19 ± 15.35) minutes), blood loss ((105.15 ± 11.32) ml vs. (110.12 ± 9.07) ml), transfusion event (11.20% vs. 9.78%), and the in-patient time (10.0 days vs 9.5 days) were not significant between the two groups. After a median follow-up of 28 months (5 - 60), six (14.3%) cases who received modified NU had bladder recurrence, which was significantly lower compared with 15 (34.9%) patients from the group that underwent standard NU (P = 0.026). In univariate and multivariate analysis, tumor grade (HR 4.33, 95%CI 2.66 - 6.30, P = 0.01) and operation type (HR 2.35, 95%CI 1.53 - 3.48, P = 0.041) were independent risk factors for subsequent bladder recurrence after UTUC. CONCLUSIONS: Clipping the distal ureter at the beginning of NU significantly reduces bladder recurrence after UTUC. It is reasonable to conclude that clipping the distal portion of ureter trans-peritoneal is an effective surgical procedure for the treatment of UTUC.