Regional lymph node mapping in patients with penile cancer undergoing radical inguinal lymph node dissection - a retrospective cohort study.

BACKGROUND: Radical inguinal lymph node dissection (rILND) is the most available treatment to cure penile cancer (PC) with limited inguinal-confined disease. However, guidelines regarding acceptable boundaries of rILND are controversial, and consensus is lacking. The authors aimed to standardize the surgical boundaries of rILND with definite pathological evidence and explore the distribution pattern of inguinal lymph nodes (ILNs) in PC. METHODS: A total of 414 PC patients from two centers who underwent rILND were enrolled. The ILN distribution was divided into seven zones anatomically for pathological examination. Student's t test and Kaplan-Meier survival analysis were used. RESULTS: ILNs displayed a funnel-shaped distribution with high density in superior regions. ILNs and metastatic nodes are present anywhere within the radical boundaries. Positive ILNs were mainly concentrated in zone I (51.7%) and zone II (41.3%), but there were 8.7% and 12.3% in inferior zones V and VI, respectively, and 7.1% in the deep ILNs. More importantly, a single positive ILN and first-station positive zone was detected in all seven regions. Single positive ILNs were located in zones I through VI in 40.4%, 23.6%, 6.7%, 18.0%, 4.5%, and 1.1%, respectively, and 5.6% presented deep ILN metastasis directly. CONCLUSIONS: The authors established a detailed ILN distribution map and displayed lymphatic drainage patterns with definite pathological evidence using a large cohort of PC patients. Single positive ILNs and first-station metastatic zones were observed in any region, even directly with deep ILN metastasis. Only rILND can ensure tumor-free resection without the omission of positive nodes.

Extraperitonealization of the ileal conduit decreases the risk of parastomal hernia: A single-center, randomized clinical trial.

Parastomal hernia (PSH) is a common complication in patients receiving ileal conduit urinary diversion after radical cystectomy. In this randomized controlled clinical trial, we validate our previous finding that extraperitonealization of ileal conduit decreases incidence of PSH. In total, 104 consecutive patients undergoing radical cystectomy at Sun Yat-sen University Cancer Center are randomized 1:1 to receive either modified (extraperitonealized) ileal conduit (n = 52) or conventional ileal conduit (n = 52). Primary endpoint is incidence of radiological PSH during follow-up. Incidence of radiological PSH is lower in the modified group than in the conventional group (11.5% vs. 28.8%; p = 0.028) after a median follow-up of 32 months, corresponding to a hazard ratio of 0.374 (95% confidence interval: 0.145-0.965, p = 0.034) in the modified conduit group. The results support our previous finding that extraperitonealization of the ileal conduit is effective for reducing risk of PSH in patients receiving ileal conduit diversion.

Regular gastroscopy and colonoscopy during the evaluation of urachal cancer: do we really need them?

PURPOSE: Urachal cancer is similar to gastrointestinal adenocarcinoma in histology, and gastroscopy/colonoscopy is often administered during perioperative evaluation. However, gastroscopy and colonoscopy have corresponding disadvantages. This study discusses whether gastroscopy/colonoscopy is truly necessary for patients with urachal cancer. PATIENTS AND METHODS: A total of 166 bladder adenocarcinoma cases diagnosed at Sun Yat-sen University Cancer Center were retrospectively reviewed and divided into two groups (urachal cancer and nonurachal cancer), and perioperative evaluations were retrieved. RESULTS: There were 78 patients with urachal cancer, the median age was 48 years, and 59 were male. Perioperative gastroscopy/colonoscopy revealed 5 intestinal polyps and 1 adenoma during these evaluations, and no primary gastrointestinal cancer was found. Meanwhile, preoperative imaging evaluation did not detect significant gastrointestinal lesions. For 88 patients with nonurachal cancer, including primary bladder adenocarcinoma and metastatic tumors from gastrointestinal cancer, the median age was 56 years, and 64 were male. Preoperative imaging evaluation demonstrated 36 cases of gastrointestinal lesions, and 32 were confirmed by gastroscopy/colonoscopy; the other 4 were negative. Another 4 cases of colon cancer were detected by regular colonoscopy for suspected primary bladder adenocarcinoma. In all, 35 cases of colon cancer and 1 case of gastric cancer were identified by endoscopic examination. The diagnostic consistency of imaging and gastrointestinal endoscopy was favorable (P < 0.001), and the negative predictive value and diagnostic efficiency of imaging were 96.9% and 94.6%, respectively. CONCLUSIONS: The vast majority of gastrointestinal cancer cases can be identified by assessment of the patient's clinical symptoms, meticulous physical examination, and imaging evaluation. We recommend that gastroscopy/colonoscopy only be applied to patients with urachal cancer when the above examinations are positive.

Optimal interval timing between transurethral resection of bladder tumors and Bacillus Calmette-Guerin perfusion.

OBJECTIVE: There is no consensus regarding the best interval time between transurethral resection of a bladder tumor and Bacillus Calmette-Guerin (BCG) perfusion. This study was to explore whether the interval time has an impact on the prognosis and adverse effects. METHODS: We retrospectively reviewed the clinical data of patients who received BCG intravesical perfusion at Sun Yat-sen University Cancer Center (SYSUCC) from September 2015 to October 2021. Recurrence-free survival (RFS) and progression-free survival were the primary endpoints. Cox regression was used to explore independent predictors. The association between interval time and adverse effect grade was detected by logistic regression. Propensity score matching (PSM) was performed. RESULTS: A total of 403 patients were enrolled, the median interval time was 24 days (6-163 days), and the follow-up was 28 months (7-82 months). Eighty-eight (20.9%) patients relapsed, and 40 patients (10.0%) suffered progression. The multivariate Cox regression analysis confirmed that interval time was an independent predictor of RFS (p = 0.017). Notably, when the interval time was less than or equal to 26 days, there was a trend toward better RFS, PSM resulted in 65 matched pairs in each group, and Kaplan-Meier analysis showed that there was a significant difference in RFS between groups (p = 0.009). The logistic regression analysis showed that there was no correlation between interval time and adverse effects and their grades (p > 0.05). CONCLUSIONS: We considered that the first BCG perfusion could be performed within 2-4 weeks after surgery.

Prognostic Significance of HER2 Expression in Patients with Bacillus Calmette-Guérin-exposed Non-muscle-invasive Bladder Cancer.

BACKGROUND: Guidelines recommend intravesical instillation of bacillus Calmette-Guérin (BCG) as the first-choice treatment for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, there is no therapeutic biomarker for predicting BCG efficacy, especially in high-risk cases with high failure rates. HER2 expression is considered a prognostic factor for bladder cancer. OBJECTIVE: To elucidate the predictive value and significance of HER2 expression in patients with BCG-exposed NMIBC. DESIGN, SETTING, AND PARTICIPANTS: A total of 454 patients with NMIBC were included. All patients started BCG intravesical instillation (1.2 × 108 CFU, strain D2PB302) 2-6 wk after transurethral resection of bladder tumor and received 19 treatments over a period of 1 yr. HER2 immunohistochemistry (IHC) results available for 314 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes investigated were recurrence-free survival (RFS) and progression-free survival (PFS). Outcome relationships were explored using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: In the IHC population, 35.7% of patients had HER2 overexpression (IHC score 2/3+). This group had a poor 5-yr RFS rate of 16.5%, in comparison to 68.0% in the group with low HER2 expression (p < 0.001). Patients with high-risk NMIBC and HER2 overexpression had the highest risk of BCG treatment failure, with 5-yr RFS and PFS rates of 19.0% and 58.2%, respectively. Conversely, HER2-negative (IHC score 0) patients with high-risk NMIBC experienced a long-term BCG benefit, with 5-yr RFS and PFS rates of 80.8% and 92.1%, respectively. Limitations include the retrospective study design and the limited details regarding BCG use. CONCLUSIONS: HER2 was an independent predictor of poor BCG efficacy in NMIBC. Patients with high-risk NMIBC and HER2 overexpression had the highest risk of disease recurrence and progression after exposure to BCG. Anti-HER2 targeted therapies could be considered for these patients. PATIENT SUMMARY: Measurement of blood levels of the protein HER2 can be used to predict outcomes after BCG (bacillus Calmette-Guérin) bladder therapy for patients with intermediate- or high-risk non-muscle-invasive bladder cancer. Measurement results for HER2 may help in guiding personalized treatment for these patients.

SAVE Testis-sparing score: a multicenter retrospective study of a novel predictive tool for quantifying testicular tumors.

BACKGROUND: Testis-sparing surgery (TSS) is a safe treatment for patients with benign testicular tumors. Presently, assessments for evaluating the suitability of TSS are poorly standardized, partially because testicular anatomical elements cannot be quantitatively described. MATERIALS AND METHODS: The authors developed a scoring method known as the SAVE testis-sparing score based on four critical and accessible anatomical features of a testicular tumor. The SAVE score ranges from 0 to 8 and is divided into four risk classes ( low , medium , high , and extremely high ) to evaluate the feasibility of TSS, wherein low-risk indicates high feasibility and vice versa. This study included 444 testicular tumor patients from eight centers. Among them, 216 patients (model group: 151 patients, validation group: 65 patients) were included in the modeling analysis, and the other 228 patients from children's centers were included in the proportion analysis. Using retrospective data, patient characteristics associated with surgical methods were identified. Furthermore, a multivariate logistic regression model was built quantify the associations between these characteristics and the surgery method. The receiver operator characteristic curve was used to evaluate the classification efficiency of SAVE. RESULTS: The SAVE testis-sparing score includes size (tumor size as maximal diameter), available testicular tissue volume, volume ratio of the tumor to the testis, and the exophytic / endophytic properties of the tumor. The SAVE scoring system accurately classified the suitability of TSS based on the complexity of benign testicular tumors. CONCLUSION: The SAVE score is a reproducible and robust tool for quantitatively describing the anatomical characteristics of benign testicular tumors and guide the preoperative evaluation of TSS.

Perivesical Fat Invasive Pattern as Prognostic Factor and Predictor of Response to Adjuvant Chemotherapy in T3 Stage Bladder Cancer.

BACKGROUND: The prognostic value of the distinction between microscopic (pT3a) and macroscopic (pT3b) perivesical fat invasions remains a subject of debate. To explore whether the pattern of perivesical fat invasion can serve as a prognostic factor to better subgroup T3 stage bladder cancer. MATERIALS AND METHODS: One hundred and forty-nine patients diagnosed with T3 stage bladder cancer at Sun Yat-sen University Cancer Center (SYSUCC) were selected for the experimental cohort in this study. Ninety-seven T3 stage bladder cancer patients with pathological slices at the Cancer Genome Atlas (TCGA) were selected as validation cohort in this study. The perivesical fat invasive pattern was examined with hematoxylin and eosin-stained pathological slides by two pathologists independently. Two different perivesical fat invasive patterns, fibrous-surrounded (FS) pattern, and nonfibrous-surrounded (NFS) pattern were assessed. RESULTS: Perivesical fat invasion pattern had a significant influence on overall survival in T3 stage bladder cancer. Compared to the NFS pattern, the FS pattern was related to a better prognosis in both the SYSUCC cohort and TCGA cohort. The patients with NFS pattern tumor who underwent cisplatin-based adjuvant chemotherapy experienced an obvious improvement compared to observation after radical cystectomy in overall survival in the SYSUCC cohort. CONCLUSION: The perivesical fat invasion pattern could predict prognosis and clinically different chemotherapeutic survival outcomes in patients with T3 stage bladder cancer after radical cystectomy.

Prognostic Value of Inflammation Biomarkers in Penile Squamous Cell Carcinoma Patients Without Distant Metastasis.

BACKGROUND: To investigate the value of the presurgical inflammatory biomarkers including C-reactive protein (CRP), albumin (ALB), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), the modified GPS (mGPS), and the high-sensitivity modified GPS (Hs-mGPS) in penile squamous cell carcinoma (PSCC) without distant metastasis and develop a tool to predict the overall survival (OS) of PSCC patients. METHODS: We retrospectively enrolled 271 PSCC patients without distant metastasis from 2006 to 2021. Patients were divided into 2 cohorts by a 7:3 ratio-a training cohort (n = 191) and a validation cohort (n = 80). We performed cox regression analyses on the training cohort and constructed a nomogram to predict OS over 1, 3, and 5 years. Data from the validation cohort was used to validate the nomogram's predictive power. RESULTS: According to Kaplan-Meier analysis, elevated CRP (P < .001), hypoalbuminemia (P = .008), higher CAR (P < .001), higher GPS score (P < .001), higher mGPS score (P < .001), and higher Hs-mGPS score (P = .015) were associated with a decreased overall survival. GPS score, along with age, pathology N stage, and grade, was found to be an independent risk factor for poor prognosis in the multivariate analysis. We constructed a nomogram based on the prespecified variables predicting 1-, 3- and 5-year OS. The C-indexes of the nomogram in the training and validation cohorts were 0.871 and 0.869, respectively. The decision curve analysis showed that the nomogram had a larger net benefit. The Kaplan-Meier curves showed significant differences between the risk groups categorized according to the nomogram (P < .001). CONCLUSIONS: Inflammation biomarkers of systemic inflammation and nutritional status play an important role in individual OS predictions for PSCC patients without distant monitoring. The establishment of the nomogram provided a tool to predict the survival of 1-, 3-, and 5-year OS in PSCC patients without distant metastasis.

HER2-targeting antibody-drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: a multicenter, real-world study.

BACKGROUND: Phase II trials showed the efficacy of anti-HER2 RC48-ADC (disitamab vedotin) for HER2-positive metastatic urothelial carcinoma (UC). This study evaluated RC48 alone verses in combination with immunotherapy for locally advanced or metastatic UC using real-world data. METHODS: This retrospective, multicenter, real-world study included patients with locally advanced or metastatic UC who received RC48 in five hospitals in China between July 2021 and April 2022. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. RESULTS: Thirty-six patients were included. The patients were 47-87 years, and 26 (72.2%) were male. Eighteen patients received RC48 alone, and 18 received RC48 combined with a programmed death-1 antibody. The median PFS was 5.4 months. The median OS was not reached. The 6-month and 1-year PFS rates were 38.8% and 15.5%, respectively. The 1-year OS rate was 79.6%. Fourteen (38.9%) patients achieved a partial response, and the ORR was 38.9%. Eleven patients had stable disease, and the DCR was 69.4%. The median PFS for patients who received RC48 combined with immunotherapy and those who received RC48 alone was 8.5 and 5.4 months, respectively. The main treatment-related adverse events included anemia, hypoesthesia, fatigue, and elevated transaminase. No treatment-related death occurred. CONCLUSION: RC48 alone or combined with immunotherapy might benefit patients with locally advanced or metastatic UC, regardless of impaired renal function.

Bladder paraganglioma: basic characteristics and new perspectives on perioperative management.

PURPOSE: Paraganglioma and pheochromocytoma are rare neuroendocrine tumors with severe metabolic and cardiovascular complications. Bladder PGLs are rare, and their clinical management is not precise. Here, we discuss the basic characteristics and perioperative management of bladder PGLs. METHODS: We retrospectively reviewed 20 bladder PGL cases diagnosed at Sun Yat-sen University Cancer Center. Case notes were reviewed, clinical presentations, therapies, and outcomes were collected, and data analysis was performed. RESULTS: Ten male and ten female patients with a median age of 47.5 years (range 14-69 years) were included. Most patients (65%) had no symptoms, and PGL was detected incidentally during medical checkups. All patients were treated surgically; 4 (20%) underwent transurethral resection of bladder tumor (TURBT), and 16 (80%) underwent partial cystectomy. Strong intraoperative blood pressure fluctuations were observed in 13 patients (65%). Two patients who were treated preoperatively with α-receptor blockers also experienced severe intraoperative blood pressure fluctuations. Postoperative measurements of troponin I were available for 3 patients, and all were significantly elevated. All patients were diagnosed with bladder PGL on postoperative pathological examination. The median follow-up time was 51 months (range 2-147 months), and 2 patients were lost to follow-up at 1 and 3 months; 16 (88.9%) survived without recurrence, 2 patients (11.1%) experienced recurrence, and 1 patient died. CONCLUSION: Most bladder paragangliomas are easily mistaken for bladder urothelial carcinoma, and robust hemodynamic instability during surgery might be a challenge for urologists. Postoperative monitoring of troponin I, regardless of the presence of clinical symptoms, is recommended for patients with bladder PGL.

RAB20 Promotes Proliferation via G2/M Phase through the Chk1/cdc25c/cdc2-cyclinB1 Pathway in Penile Squamous Cell Carcinoma.

RAB20, a member of the RAS GTPase oncogene family, is overexpressed in several cancers with poor outcomes, promoting tumorigenesis and inducing genomic instability. Here, we performed comprehensive genomic sequencing on eight penile squamous cell carcinoma (PSCC) and normal tissue pairs and found that RAB20 was upregulated in tumors, especially in metastatic lymph nodes. RAB20 overexpression in tumors was further verified by qPCR, Western blotting, and immunohistochemistry of our newly established PSCC cell lines and paired tissues. The clinical significance of RAB20 was validated in 259 PSCC patients, the largest cohort to date, and high RAB20 expression positively correlated with the T, N, M status, extranodal extension, and clinical stage (all p < 0.01). RAB20 was an unfavorable independent prognostic indicator in the survival analysis (p = 0.011, HR = 2.090; 95% Cl: 1.183−4.692), and PSCC patients with high RAB20 expression experienced shorter 5-year cancer-specific survival times (p < 0.001). Furthermore, tumorigenesis assays demonstrated that RAB20 knockdown inhibited cell proliferation, migration, and colony formation in vitro and tumor growth in vivo. RAB20 depletion also induced PSCC cell cycle arrest at G2/M by increasing Chk1 expression and promoting cdc25c phosphorylation to reduce cdc2-cyclinB1 complex formation. Our study revealed an oncogenic role for RAB20 in promoting PSCC cell proliferation at the G2/M phase via the Chk1/cdc25c/cdc2-cyclinB1 pathway. Thus, RAB20 could be a promising prognostic biomarker of advanced PSCC with poor patient survival outcomes and could be a potential therapeutic target.

Extraperitonealization of ileal conduit reduces parastomal hernia after cystectomy and ileal conduit diversion.

OBJECTIVE: Parastomal hernia (PSH) is a common complication of ileal conduit diversion after radical cystectomy. Novel surgical techniques for preventing PSH formation are needed. We aimed to evaluate surgical technique of extraperitonealizing the ileal conduit (modified ileal conduit) for preventing PSH. METHODS: A retrospective analysis of 375 consecutive patients who underwent ileal conduit after cystectomy at the Sun Yat-sen University Cancer Center between January 1, 2000 and June 31, 2019 was conducted. 214 patients had modified ileal conduit diversion and 161 patients conventional ileal conduit (Bricker) diversion. The demographic and clinicopathologic characteristics of patients in the 2 groups were compared using the t test and Chi square test. Univariable and multivariable Cox regression analyses were used to predict the risk of PSH formation. RESULTS: The 2 groups were comparable in regard to all demographic and clinicopathologic variables. The incidence of PSH diagnosed by CT scan was 7.5% in the modified group and 21.1% in the conventional group (P < 0.001). High BMI and history of prior abdominal surgery was identified by univariable analysis as risk factors of PSH formation. Multivariable analyses revealed that technique of extraperitonealizing ileal conduit significantly reduced incidence of PSH in patients with or without risk factors of PSH formation (OR = 0.29, 95% CI 0.16-0.54, P < 0.001). CONCLUSIONS: Technique of extraperitonealizing ileal conduit appeared to be effective in reducing PSH formation after ileal conduit diversion.

Deep Inguinal Lymph Node Metastases Can Predict Pelvic Lymph Node Metastases and Prognosis in Penile Squamous Cell Carcinoma.

OBJECTIVES: To evaluate the relationship between deep inguinal lymph node metastasis (ILNM) and pelvic lymph node metastasis (PLNM) and explore the prognostic value of deep ILNM in penile squamous cell carcinoma (PSCC). MATERIALS AND METHODS: The records of 189 patients with ILNM treated for PSCC were analysed retrospectively. Logistic regression models were used to test for predictors of PLNM. Cox regression was performed in univariable and multivariable analyses of cancer-specific survival (CSS). CSS was compared using Kaplan-Meier analyses and log rank tests. RESULTS: PLNM were observed in 53 cases (28.0%). According to logistic regression models, only deep ILNM (OR 9.72, p<0.001) and number (≥3) of metastatic inguinal lymph nodes (ILNs) (OR 2.36, p=0.03) were independent predictors of PLNM. The incidences of PLNM were 18% and 19% with negative deep ILNM and extranodal extension (ENE); and 76% and 42% with positive deep ILNM and ENE, respectively. The accuracy of deep ILNM, ENE, bilateral involvement and number (≥3) of ILNMs for predicting PLNM were 81.0%, 65.6%, 63.5% and 67.2%, respectively. The CSS was significantly different in patients with positive and negative deep ILNM (median 1.7 years vs not reached, p<0.01). Patients who presented with deep ILNM had worse CSS (median 3.8 years vs not reached, p<0.01) in those with negative PLNs. CONCLUSIONS: Deep ILNM is the most accurate factor for predicting PLNM in PSCC according to our data. We recommend that patients with deep ILNM should be referred for pelvic lymph node dissection. Involvement of deep ILNs indicates poor prognosis. We propose that patients with metastases of deep ILNs may be staged as pN3.

Role of a Modified Urothelium Immune Prognostic Index in Patients With Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1-Based Therapy.

Introduction: The use of antibodies against programmed death receptor-1 (PD-1) and its ligand (PD-L1) has improved survival in metastatic urothelial carcinoma (mUC) patients. However, reliable and convenient biomarkers of early responses and outcomes are still lacking. Materials and Methods: We retrospectively screened mUC patients who received anti-PD-1/PD-L1-based therapy at our institute. A modified urothelium immune prognostic index (mUIPI) based on the neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) was developed to characterize the three groups as good, intermediate, and poor mUIPI. Major observations were progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). Results: We identified 52 mUC patients with a median follow-up time of 29.8 months (95% CI, 26.3-53.2). Low NLR was with improved PFS and OS (hazard ratio [HR], 0.40, 95% CI, 0.18-0.92; HR, 0.27, 95% CI, 0.11-0.69, respectively). Normal LDH was associated with improved PFS but not OS (HR, 0.22, 95% CI, 0.10-0.52; HR, 0.86, 95% CI, 0.34-2.13, respectively). The median PFS for the poor, intermediate, and good mUIPI groups was 1.97 months (95% CI, 1.15 to NR), 3.48 months (95% CI, 1.58 to NR), and 14.52 months (95% CI, 5.75 to NR), respectively (p < 0.001). The median OS for the poor, intermediate, and good mUIPI was 12.82, 18.11, and 34.87 months, respectively (p = 0.28). A good mUIPI was associated with a higher DCR compared to intermediate and poor mUIPI (odds ratio [OR] 7.58, 95% CI, 1.73-43.69; OR, 6.49, 95% CI, 0.14-295.42, respectively). In the subgroup analysis, a good mUIPI was associated with improved PFS in the subgroups of male patients and patients with low urinary tract primary tumors, liver metastases, non-first-line treatment, and monotherapy. Conclusions: mUIPI predicts early responses in mUC patients who received anti-PD-1/PD-L1-based therapy.

Pelvic Lymph Node Dissection in Penile Cancer With Inguinal Lymph Node Extranodal Extension: A Multicenter Experience.

Background: The aim of this study is to determine the necessary extent of penile lymph node dissection (PLND) in penile cancer patients with inguinal lymph node extracapsular extension (ILN-ENE). Methods: Penile cancer patients who underwent PLND in 15 centers from January 2006 to April 2020 were retrospectively analyzed. PLND was performed in patients with ILN-ENE. Results: Sixty-two patients with ILN-ENE were included in the analysis. A total of 51.6% (32/62) of the patients were confirmed to have pelvic lymph node metastasis (PLNM), and 31.3% (10/32) of patients were confirmed to have multiple PLNMs. Of the patients with metastases, 59.4% (19/32) had bilateral inguinal lymph node metastasis (ILNM). According to the anatomical structure, 71.9% (23/32) of the patients had PLNM in the external iliac region, and 56.2% (18/32) had PLNM in the obturator region. Among those with oligo-PLNM, 65.1% (28/43) of the patients had PLNM in the external iliac region and 38.9% (15/43) had PLNM in the obturator region. A significant overall survival difference was observed between patients with the bilateral ILNM and unilateral ILNM (36-month: 21.2 vs. 53.7%, respectively, P = 0.023). Patients with bilateral ILNM had relatively poor metastasis-free survival compared with unilateral ILNM (36-month: 33.0 vs. 13.9%, respectively, P = 0.051). Conclusions: The external iliac and obturator region were the most commonly affected regions in patients with ILN-ENE, and these regions were the only affected regions in patients with oligo-PLNM. Patients with bilateral ILNM had a high risk of PLNM and worse survival.

BMI1 activates P-glycoprotein via transcription repression of miR-3682-3p and enhances chemoresistance of bladder cancer cell.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer.

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l-1 with a sensitivity of 60.0% and a specificity of 67.8%. In the validation set, the optimal cutoff value showed significantly higher sensitivity than that of conventional magnetic resonance imaging (MRI) (0.619 vs 0.238, P < 0.001). The nomogram involving PMC, free prostate-specific antigen (fPSA), clinical T stage, preoperative Gleason score, and monocyte-to-lymphocyte ratio (MLR) was generated, which showed a robust predictive capacity for predicting LNM before the operation. Our results indicated that PMC as a single agent, or combined with other clinical parameters, showed a robust predictive capacity for LNM in PCa. It can be employed as a complementary factor for the decision of whether to conduct pelvic lymph node dissection.

Molecular stratification by BCL2A1 and AIM2 provides additional prognostic value in penile squamous cell carcinoma.

Background: Lymph node metastasis is the most unfavorable prognostic factor of penile squamous cell carcinoma (PSCC). However, patients with the same lymph node status have different outcomes, and molecular classifiers for precise prognostic assessments are lacking. Methods: Comprehensive genomic profiling and high-content proliferation screening were performed in eight PSCC and normal tissue pairs and in cell lines. BCL2A1 and AIM2 were selected and further evaluated by qPCR and Western blot. The clinical relevance and prognostic value of the target genes were validated via immunohistochemistry in a cohort of 220 PSCC patients with a defined pN stage. Finally, the biological functions and molecular mechanisms of BCL2A1 and AIM2 were investigated in vitro and in vivo. Results: BCL2A1 and AIM2 were both upregulated in PSCC tissues and associated mostly with cell proliferation. Staining for either BCL2A1 or AIM2 revealed that both are correlated with pN status, extranodal extension, clinical stage and cancer-specific survival (CSS). Compared to patients who are single-positive or double-negative for BCL2A1 and AIM2, those overexpressing both genes had a higher risk of tumor progression and the poorest survival in the pN0 (5-year CSS: 63.3% vs. 94.9% and 100.0%, respectively, p = 0.000) and pN+ subsets (5-year CSS: 24.1% vs. 45.7% and 55.1%, respectively, p = 0.035). Molecular biofunction and mechanistic studies demonstrated that BCL2A1 and AIM2 knockdown inhibited tumorigenesis via the AIM2/NF-κB/BCL2A1/MAPK/c-Myc signaling pathway. Conclusions: BCL2A1 and AIM2 promote PSCC progression. Integrating BCL2A1 and AIM2 as novel molecular classifiers with pN stage provides additional information for the prognosis and treatment of PSCC patients.

A panel of eight autophagy-related long non-coding RNAs is a good predictive parameter for clear cell renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) carries a variable prognosis. Prognostic biomarkers can stratify patients according to risk, and can provide crucial information for clinical decision-making. We screened for an autophagy-related long non-coding lncRNA (lncRNA) signature to improve postoperative risk stratification in The Cancer Genome Atlas (TCGA) database. We confirmed this model in ICGC and SYSU cohorts as a significant and independent prognostic signature. Western blotting, autophagic-flux assay and transmission electron microscopy were used to verify that regulation of expression of 8 lncRNAs related to autophagy affected changes in autophagic flow in vitro. Our data suggest that 8-lncRNA signature related to autophagy is a promising prognostic tool in predicting the survival of patients with ccRCC. Combination of this signature with clinical and pathologic parameters could aid accurate risk assessment to guide clinical management, and this 8-lncRNAs signature related to autophagy may serve as a therapeutic target.