Case report: A collision tumor of clear cell renal cell carcinoma and clear cell papillary renal cell tumor.

We report the case of a 51-year-old woman who was initially hospitalized in the respiratory department with cough and fever. Urinary computed tomography (CT) showed two different incidental masses in the right kidney. The patient underwent a radical right nephrectomy without lymph node dissection and postoperative adjuvant treatment. The pathological examination of the surgical specimens showed a collision tumor composed of a clear cell renal cell carcinoma (CCRCC) and a clear cell papillary renal cell tumor (CCPRCT). To the best of our knowledge, this is the first such case reported to date. No recurrence of local or distant metastasis was found during routine follow-up 14 months after the operation.

Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor-based combination therapy.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)-associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor-based combination therapy (PCT). METHODS: HPV status was assessed using quantitative polymerase chain reaction in 87 patients with advanced PSCC treated with PCT. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in the HPV+ and HPV- groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC. RESULTS: Among patients receiving first-line PCT, ORR (91.7% vs. 64.6%, p = .014) and DCR (100.0% vs. 79.2%, p = .025) in the HPV+ group were higher compared to the HPV- group. Kaplan-Meier curves demonstrated that the HPV+ group exhibited superior PFS (p = .005) and OS (p = .004) for patients in the first-line setting. However, these advantages of HPV infection were not observed in multi-line PCT (p > .050). HPV status remained an independent prognostic factor for predicting better ORR (p = .024), PFS (p = .002), and OS (p = .020) in the multivariate analyses. Landmark analyses showed that the HPV-induced superiority of PFS occurred at an early stage (within 3 months) and OS occurred at a relatively late stage (within 9 months). Bioinformatic analyses identified potential immune-activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+ tissues. CONCLUSIONS: HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first-line PCT because of the possible stimulation of the antitumor immune microenvironment. PLAIN LANGUAGE SUMMARY: Human papillomavirus (HPV) infection may induce better objective response rate, progression-free survival (PFS), and overall survival (OS) for advanced penile squamous cell carcinoma (PSCC) patients receiving first-line programmed cell death protein 1 inhibitor-based combination therapy (PCT) instead of multi-line PCT. HPV infection-induced PFS advantage occurs at an early stage (within 3 months) whereas OS superiority occurs at a relatively late stage (within 9 months). Antitumor immune microenvironment could be stimulated by HPV infection in advanced PSCC tissues.

Do patients receive any benefit from the addition of perioperative immunotherapy-chemotherapy for solid tumors?

BACKGROUND: Progress in the use of neoadjuvant immunotherapy combined with chemotherapy has become a highlight of cancer research. Our meta-analysis aimed to better elucidate the activity, efficacy and safety of this combination using data obtained from randomized controlled trials (RCTs). METHODS: A systematic search of PubMed, Embase, Web of Science, the Cochrane Library and conference proceedings up to January 31, 2023 was carried out to identify RCTs investigating neoadjuvant immunotherapy combined with chemotherapy for the treatment of solid tumors. Using fixed- and random-effects models, pooled odds ratios (ORs) and hazard ratios with 95% confidence intervals (CIs) were calculated for pathological complete response (pCR, defined as ypT0/is pN0) and immunotherapy treatment-related adverse events. RESULTS: A total of 1876 studies were identified, and 6 RCTs (N = 2558 patients) were included. The pCR was significantly higher with neoadjuvant immunotherapy combined with chemotherapy than with neoadjuvant chemotherapy alone (OR = 2.30, 95% CI: 1.43-3.71, P < .001). The pCR was confirmed to be statistically significant in the PD-L1-positive subgroup (OR = 2.01; 95% CI: 1.55-2.59, P = .012). The pCR was confirmed to be statistically significant in the PD-1 inhibitor subgroup (OR = 4.17; 95% CI: 1.47-11.87, P = .000), while no statistically significant was observed in the PD-L1 inhibitor subgroup (OR = 1.52; 95% CI: 1.12-2.07, P = .308). The pooled ORs of any grade treatment-related or immunotherapy-related adverse events were significant, but the grade 3-4 immunotherapy-related adverse events were not. CONCLUSION: Our study provides comprehensive data that the addition of PD1 blockade to neoadjuvant chemotherapy resulted in better treatment efficacy than neoadjuvant chemotherapy alone in patients with solid tumors and had a similar safety profile.

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.

Prognostic significance and immune correlates of FADD in penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) with a poor prognosis lacks reliable biomarkers for stratifying patients. Fas-associated death domain (FADD) could regulate cell proliferation and has shown promising diagnostic and prognostic significance in multiple cancers. However, researchers have not determined how FADD exerts its effect on PSCC. In this study, we set out to investigate the clinical features of FADD and the prognostic impact of PSCC. Additionally, we also assessed the role of affecting the immune environment in PSCC. Immunohistochemistry was carried out to evaluate the protein expression of FADD. The difference between FADDhigh and FADDlow was explored by RNA sequencing from available cases. The immune environment evaluation of CD4, CD8, and Foxp3 was performed by immunohistochemical. In this study, we found that FADD was overexpressed in 19.6 (39/199) patients, and the overexpression of FADD was associated with phimosis (p=0.007), N stage (p<0.001), clinical stage (p=0.001), and histologic grade (p=0.005). The overexpression of FADD was an independent prognostic factor for both PFS (HR 3.976, 95% CI 2.413-6.553, p<0.001) and OS (HR 4.134, 95% CI 2.358-7.247, p<0.001). In addition, overexpression of FADD was mainly linked to T cell activation and PD-L1 expression combined with PD-L1 checkpoint in cancer. Further validation demonstrated that overexpression of FADD was positively correlated with the infiltration of Foxp3 in PSCC (p=0.0142). It is the first time to show that overexpression of FADD is an adjunct biomarker with poor prognosis in PSCC and could also serve as a tumor immune environment regulator.

Better specificity and less ischemia: three-dimensional reconstruction is superior to routine computed tomography angiography in navigation of super-selective clamping robot-assisted laparoscopic partial nephrectomy.

Background: Available technologies could be used to guide surgeons in controlling highly selective tumor-bearing arteries robot-assisted laparoscopic partial nephrectomy (RALPN). Methods: Patients undergoing RALPN (from September 2018 to January 2020) for intermediate-high complex renal tumor (R.E.N.A.L. score ≥7) who underwent abdominal computed tomography (CT) scan with angiography and hyper-accuracy 3-dimensional reconstruction (H3DR). All patients underwent high-resolution CT scan with angiography and H3DR with special software, based on which two kinds of highly selective arterial clamp protocols were made for each patient and analyzed independently by two urologists and two radiologists to confirm which renal arterial branch was supplying the tumor. We chose the optimized clamping protocol with the principle of the minimized ischemic regions. During the operation, meticulous microdissection and clip ligation of the specific vascular branch was guided by optimized protocol [H3DR or computed tomography angiography (CTA) reconstruction], according to the in vivo anatomy (identified by intraoperative ultrasound). Results: Of 82 patients, the minimum-ischemic regions planning completed rate (MIRPCR) of preoperative planning with H3DR (90.2%) was higher than that with CTA (34.1%) (P<0.01). H3DR identified 78 high-order arteries (70.3%), whereas CTA identified 33 (29.7%) high-order arteries (P<0.001). H3DR detected a more optimal blocking option in 51 cases that were either missed (n=13) or misclassified by CTA (n=38). A total of 18 cases (56.3%) were converted to H3DR-guided occurred in CTA-guided surgery [5 (10.0%) occurred in group H3DR to CTA, P<0.01]. Moreover, in the CTA-guided group, the separation of renal hilum was avoided in 14 of 19 (73.7%) cases, whereas in the H3DR-guided group, it was avoided in 60 of 63 (95.3%) cases. Conclusions: For patients undergoing RALPN, H3DR-guided surgery compared with standard CTA-guided surgery has higher accuracy and feasibility in controlling arterial branches supplying the tumor and intraoperative surgical navigation. Additionally, it reduces the ischemic lesion area and simplifies vascular isolation steps, thus decreasing procedural difficulty.

Feasibility of contrast-enhanced ultrasound and flank position during percutaneous nephrolithotomy in patients with no apparent hydronephrosis: a randomized controlled trial.

PURPOSE: To investigate the puncture accuracy and feasibility of contrast-enhanced ultrasound (CEUS) guided percutaneous nephrolithotomy (PCNL) in flank position for patients with no apparent hydronephrosis. METHODS: Between May 2018 and June 2020, 72 kidney stone patients with no or mild hydronephrosis were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided group. Patients' demographics and perioperative outcomes were compared, including the success rate of puncture via calyceal fornix, the success rate of a single-needle puncture, puncture time, operative time, postoperative hemoglobin loss, stone-free rate, incidence of complications and postoperative stay. RESULTS: The success rate of puncture via calyceal fornix for CEUS-guided group was significantly higher than that for conventional US-guided group (86.1 vs. 47.2%, p = 0.002). Patients performed with CEUS-guided PCNL required shorter renal puncture time than those guided with conventional US (36.5 s vs. 61.0 s, p < 0.001). The median postoperative hemoglobin loss in the CEUS-guided group was significantly lower than that in conventional US-guided group (2.5 vs. 14.5 g/L, p < 0.01). There was no statistically significant difference in the success rate of a single-needle puncture, operative time, stone-free rate, incidence of complications and postoperative stay between the two groups. CONCLUSION: CEUS guidance facilitates identification of the renal calyx fornix, and benefits more precise renal puncture and less hemoglobin loss in PCNL. CEUS-guided PCNL in flank position is a feasible approach to the treatment of kidney stone patients with no apparent hydronephrosis. TRIAL REGISTRATION NUMBER: ChiCTR1800015417.

What Happens to the Preserved Renal Parenchyma After Clamped Partial Nephrectomy?

BACKGROUND: Most partial nephrectomies (PNs) are performed with hilar occlusion to reduce blood loss and optimize visualization. However, the histologic status of the preserved renal parenchyma years after PN is unknown. OBJECTIVE: To compare the histologic chronic kidney disease (CKD) score of renal parenchyma before and years after PN, and to explore factors associated with CKD-score increase and glomerular filtration rate (GFR) decline. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 147 renal cell carcinoma patients who underwent PN and subsequent radical nephrectomy (RN) due to tumor recurrence was performed in 19 Chinese centers and Cleveland Clinic. Macroscopic normal renal parenchyma was evaluated at least 5 mm away from the tumor in PN specimens and at remote sites in RN specimens. INTERVENTION: PN/RN and ischemia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histologic CKD score (0-12) represents a summary of glomerular/tubular/interstitial/vascular status. Predictive factors for a substantial increase of CKD score (≥3) were evaluated by logistic regression. RESULTS AND LIMITATIONS: Sixty-five patients with all necessary data were analyzed. The median interval between PN and RN was 2.4 yr. Median durations of warm ischemia (n = 42) and hypothermia (n = 23) were both 23 min. The histologic CKD score was increased after RN in 47 (72%) patients, with 29 (45%) experiencing more substantial increase (≥3). There was no significant difference in the change of CKD score related to the type and duration of ischemia (p = 0.7 and p = 0.4, respectively) or interval from PN to RN (p > 0.9). However, patients with comorbidities of hypertension, diabetes, and/or pre-existing CKD (hypertension [HTN]/diabetes mellitus [DM]/CKD) demonstrated increased rate and extent of CKD-score increase. On univariate analysis, HTN/DM/CKD was the only predictor of a substantial CKD-score increase (odds ratio: 3.53 [1.12-11.1]). Decline of GFR was modest and similar between patients with/without a substantial CKD-score increase. CONCLUSIONS: Within the context of conventional, limited durations of ischemia, histologic deterioration of preserved parenchyma after PN appears to be primarily due to pre-existing medical comorbidities rather than ischemia. A subsequent decline in renal function was mild and independent of histologic changes. PATIENT SUMMARY: After clamped PN, the preserved renal parenchyma demonstrated histologic deterioration in many cases, which correlated with the presence of comorbidities such as hypertension, diabetes mellitus, or chronic kidney disease. In contrast, the type and duration of ischemia did not correlate with histologic changes after PN, suggesting that ischemia insult had only limited impact on parenchyma deterioration.

Genome-Wide Profiling Reveals HPV Integration Pattern and Activated Carcinogenic Pathways in Penile Squamous Cell Carcinoma.

Human papillomavirus (HPV) is a significant etiologic driver of penile squamous cell carcinoma (PSCC). The integration pattern of HPV and its carcinogenic mechanism in PSCC remain largely unclear. We retrospectively reviewed 108 PSCC cases who received surgery between 2008 and 2017. Using high-throughput viral integration detection, we identified 35 HPV-integrated PSCCs. Unlike cervical cancer, the HPV E2 oncogene was not prone to involvement in integration. Eleven of the 35 (31.4%) HPV-integrated PSCCs harbored intact HPV E2; these tumors had lower HPV E6 and E7 expression and higher expression of p53 and pRb proteins than those with disrupted E2 did (p < 0.001 and p = 0.024). Integration breakpoints are preferentially distributed in or near host genes, including previously reported hotspots (KLF5, etc.) and newly identified hotspots (CADM2, etc.), which are mainly involved in oncogenic signaling pathways (MAPK, JAK/STAT, etc.). Regarding the phosphorylation levels of JNK, p38 was higher in HPV-positive tumors with MAPK-associated integration than those in HPV-positive tumors with other integration and those in HPV-negative tumors. In vitro, KLF5 knockdown inhibited proliferation and invasion of PSCC cells, while silencing CADM2 promoted migration and invasion. In conclusion, this study enhances our understanding of HPV-induced carcinogenesis in PSCC, which may not only rely on the E6/E7 oncogenes, but mat also affect the expression of critical genes and thus activate oncogenic pathways.

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.

Development and Validation of a Nomogram for the Prediction of Inguinal Lymph Node Metastasis Extranodal Extension in Penile Cancer.

PURPOSE: To determine whether a clinicopathologic and laboratory-based nomogram is capable of predicting the risk of lymph node extranodal extension (ENE) in patients with penile cancer. MATERIALS AND METHODS: From June 2006 to January 2021, 234 patients who underwent bilateral inguinal lymph node dissection (ILND) surgery were included in the analysis. A Lasso regression model was utilized to select the most useful predictive features from among 46 laboratory variables. Then, a logistic regression analysis was used to develop the prediction model. Calibration curves, concordance index (C-index) and Areas under the receiver-operating characteristic curves (AUCs) were performed to evaluate the performance of the nomogram. We also investigated model fit using changes in Akaike Information Criteria (AICs). Decision curve analyses (DCAs) were applied to assess the clinical usefulness of this nomograms. Its internal validation was confirmed. RESULTS: Among the 234 patients, 53 were confirmed to have ENE. The platelet-lymphocyte ratio (PLR) and Squamous cell carcinoma antigen (SCC-Ag) were significantly associated with ENE (P<0.05). The individualized prediction nomogram, including the PLR, SCC-Ag, lymphovascular invasion (LVI), and pathologic tumor stage(pT-stage), showed good discrimination, with a C-index of 0.817 (95% CI, 0.745 to 0.890) and good calibration. Clinical-laboratory nomogram (AIC, 180.034) become the best-fitting model. DCA findings revealed that the clinical-laboratory nomogram was more clinically useful than the pT-stage or tumor grade. CONCLUSIONS: This study presents a clinicopathologic and laboratory-based nomogram that incorporates PLR, SCC-Ag, lymphovascular invasion (LVI), and pT-stage, which can be conveniently utilized to facilitate the individualized prediction of lymph node metastasis ENE in patients with penile cancer.

Safety and Activity of Programmed Cell Death 1 Versus Programmed Cell Death Ligand 1 Inhibitors for Platinum-Resistant Urothelial Cancer: A Meta-Analysis of Published Clinical Trials.

BACKGROUND: Programmed death 1/ligand 1 (PD-1/L1) inhibitors have acceptable antitumor activity in patients with platinum-resistant urothelial cancer (UC). However, the reliability and comparability of the antitumor activity, safety profiles and survival outcomes of different immune checkpoint inhibitors are unknown. Our objective was to compare the clinical efficacy and safety of anti-PD-1/PD-L1 therapies in platinum-resistant UC patients. METHODS: We reviewed the published trials from the PubMed, Embase and Cochrane Library databases up to August 2020. A well-designed mirror principle strategy to screen and pair trial characteristics was used to justify indirect comparisons. The primary end point was the objective response rate (ORR). The safety profile and survival outcomes were also evaluated. The restricted mean survival time (RMST) up to 12 months was calculated. RESULTS: Eight studies including 1,666 advanced or metastatic UC patients (1,021 patients with anti-PD-L1 treatment and 645 patients with anti-PD-1 treatment) met the study criteria. The ORRs of anti-PD-1 and PD-L1 therapy were 22% (95% CI, 18%-25%) and 15% (95% CI, 13%-17%) with all studies combined. The proportions of the treated population with a confirmed objective response (I2 = 0; P = 0.966; HR, 1.60; 95% CI, 1.23-2.07; P < 0.001) and disease control (I2 = 30.6%; P = 0.229; HR, 1.35; 95% CI, 1.10-1.66; P = 0.004) were higher with anti-PD-1 therapy than with anti-PD-L1 therapy. The treatment-related adverse events (AEs) (I2 = 78.3%; P = 0.003; OR, 1.09; 95% CI, 0.65-1.84; P = 0.741) and grade 3-5 treatment-related AEs (I2 = 68.5%; P = 0.023; OR, 1.69; 95% CI, 0.95-3.01; P = 0.074) of anti-PD-1 therapy were comparable to those of anti-PD-L1 therapy. The RMST values at the 12-month follow-up were 9.4 months (95% CI,: 8.8-10.0) for anti-PD-1 therapy and 9.3 months (95% CI, 8.8-9.7) for anti-PD-L1 therapy (z = 0.26, P = 0.794). There was no significant difference between patients in the anti-PD-1 and anti-PD-L1 groups (12-month overall survival (OS): 43% versus 42%, P = 0.765. I2 = 0; P = 0.999; HR, 0.95; 95% CI, 0.83-1.09; P = 0.474). CONCLUSIONS: The results of our systematic comparison suggest that anti-PD-1 therapy exhibits better antitumor activity than anti-PD-L1 therapy, with comparable safety profiles and survival outcomes. These findings may contribute to enhanced treatment awareness in patients with platinum-resistant UC.

Corpora Cavernos invasion vs. Corpus Spongiosum invasion in Penile Cancer: A systematic review and meta-analysis.

Objective: Changes were made in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system according to cavernosum invasion for penile squamous cell carcinoma. This study aimed to determine the difference of prognostic validity between corpora cavernosa (CC) invasion and corpus spongiosum (CS) invasion. Methods: In this study, we searched PubMed, Cochrane CENTRAL, and Embase to select English-language articles until July 15, 2020. Pooled analyses of hazard ratios (HRs) and odds ratios (ORs) were performed. Results: Eleven studies including 3692 cases were included in the final ananlysis (1431 cases with CC and 1360 cases with CS). According to the anatomical structure, the pooled results demonstrated that patients with CC invasion had a similar rate of LNM to those with CS invasion (OR 1.34, 95% confidence interval (CI) 0.97-1.86; P=0.076). However, patients with CC invasion had a higher rate of lymph node metastasis (LNM) than those with CS invasion according to the 8th edition tumor stage (OR 1.58, 95% CI 1.14-2.21; P<0.001). Regarding survival, patients with CS invasion obtained a significantly better cancer-specific survival (CSS) (HR, 0.67; 95% CI, 0.46-0.96; P=0.030), but not in overall survival (OS) (HR: 1.30; 95% CI, 0.52-3.20; P=0.585) than those with CC invasion. No a significant publication bias was observed by Begg's and Egger's tests. Conclusions: The systematic comparison suggests that patients with CS invasion had better CSS than those with CC invasion. CC invasion was associated with a high risk of LNM. The conclusions should be validated by large-scale studies.

Can American Joint Committee on Cancer prognostic groups be individualized in patients undergoing surgery for Stage IV invasive upper tract Urothelial Carcinoma?

Purpose: We explored whether the modified American Joint Committee on Cancer tumor-node-metastasis prognostic stage group IV can be individualized in a large population-based cohort of surgically treated invasive upper tract urothelial carcinoma (UTUC) patients. Methods: Invasive UTUC patients from the Surveillance, Epidemiology and End Results database (2004-2015) were screened for inclusion. A total of 10,482 eligible cases were identified. Cancer-specific survival (CSS) after surgery was analyzed using Kaplan-Meier plots. Results: According to the most recent pathological prognostic group classification, the 5-year mortality rates of T4NxM0 (n=493), TxN1M0 (n=597), TxN2M0 (n=424) and pTxNxM1 (n=677) patients were 41.1% (95% CI 35.2% to 47.0%), 38.6% (95% CI 33.1% to 44.1%), 40.4% (95% CI 33.0% to 47.8%) and 14.2% (95% CI 9.9% to 18.5%), respectively (T4N0M0 vs. TxNxM1, P<0.001; TxN1M0 vs. TxNxM1, P<0.001; TxN2M0 vs. TxNxM1, P<0.001). Stage IV tumors were subdivided on the basis of the mortality data (Modification 1): stage IVa tumors were considered nonmetastatic (T4NxM0, TxN1-2M0; 5-year CSS 39.9%), and stage IVb tumors were considered metastatic (pTxNxM1; 5-year CSS 14.2%). Stage IV tumors were also subdivided according to the grade classification (Modification 2): stage IVa tumors were considered low grade (T4NxM0, TxN1-2M0, TxNxM1; G1-2; n=141), and stage IVb tumors were considered metastatic (T4NxM0, TxN1-2M0, TxNxM1; G3-4; n=2050). The 5-year CSS rates for stage IVa and IVb patients were 76.3% (95% CI 68.7% to 83.9%) and 31.4% (95% CI 28.5% to 34.3%), respectively (P<0.001). Conclusions: Stage IV patients were stratified into two prognostically different risk groups depending on metastasis or grade. The subclassification of stage IV can increase the level of prognostic detail and individualize the prediction of survival in invasive UTUC patients.

A novel predictive model for pelvic lymph node metastasis in patients with penile cancer: A multi-institutional study.

PURPOSE: We determined whether a clinicopathological nomogram is able to predict the risk of pelvic lymph node metastasis (LNM) in penile cancer patients after inguinal lymph node dissection (ILND). METHODS: Ninety-eight patients with bilateral ILND who underwent pelvic lymphadenectomy at 10 centers were retrospectively analyzed. The most predictive features in the nomogram were selected by the stepwise logistic regression method and then tested and verified by multivariate logistic regression analyses. The nomogram was assessed using concordance indices and calibration curves. RESULTS: Of the 181 pelvic basins, pelvic LNM was observed in 52 packages (43 patients). Bilateral pelvic LNM was present in 9 patients (9/43, 20.9%). There was no crossover metastatic spread from one inguinal side to the other pelvic side. Age, previous resection, the biopsy procedure for inguinal lymph nodes, vascular invasion, and ipsilateral inguinal lymph node status were all independent risk factors for pelvic LNM (all P < 0.05) in the multivariate logistic regression analysis. The nomogram exhibited a good probability for survival agreement, with a concordance index of 0.868 (95% CI: 0.813-0.922). CONCLUSIONS: A novel nomogram suggests that the risk of pelvic LNM can be effectively predicted in penile carcinoma patients and may provide a useful guide for clinicians. Further external validation is needed.

A Novel Nomogram for Predicting the Survival of Patients with Invasive Upper Tract Urothelial Carcinoma.

Purpose: Available tools for the prediction of the prognosis of patients with upper tract urothelial carcinoma (UTUC) are unified. We determined whether a novel nomogram is effective in estimating the survival of patients with invasive UTUC. Methods: From January 2004 to December 2015, 4796 invasive UTUC patients in the Surveillance, Epidemiology and End Results database underwent radical nephroureterectomy (RNU) for invasive UTUC. The medical records of the patients were randomly (7:3) divided into the training and validation cohorts. The independent factors included in the nomogram were selected by multivariate analyses. The nomogram was developed based on the training cohort. Bootstrap validation was applied to validate the nomogram, whereas external validation was performed using the validation cohort. The accuracy and discrimination of the nomogram were assessed using concordance indices (C-indices) and calibration curves. Results: The multivariate Cox regression model identified that age, tumor stage, node stage, metastasis stage and grade were associated with survival. In the training set, the nomogram, which included the above factors, exhibited discrimination power superior to that of the 8th American Joint Committee on Cancer (AJCC) TNM classification (Harrell's C-index, 0.74 vs. 0.71; P < 0.001). The nomogram showed better probability of survival agreement with the C-index than the AJCC-TNM staging system in the bootstrap validation (0.74 vs. 0.70; P < 0.001) and validation set (Harrell's C-index, 0.77 vs. 0.73; P < 0.001). The validation revealed that this nomogram exhibited excellent discrimination and calibration capacities. Conclusion: An accurate novel nomogram that is superior to the current AJCC-TNM staging system was established for the prediction of CSS after RNU for invasive UTUC.

Radiotherapy plus chemotherapy versus chemotherapy alone in penile cancer patients with extracapsular nodal extension after inguinal lymph node surgery: a multi-institutional study.

PURPOSE: Because there is a lack of evidence, it is not generally recommended to use adjuvant radiotherapy plus chemotherapy to treat lymph node disease in penile cancer. The aim of this study was to determine the benefit of using adjuvant radiotherapy after inguinal surgery for penile cancer. METHODS: Multi-institutional data were obtained from a total of nine centers from April 2003 to April 2015 and retrospectively analyzed. pN3 patients with an extracapsular nodal extension who received adjuvant therapy after inguinal surgery were included. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. The multivariate analysis was performed using a Cox proportional hazards model. RESULTS: A total of 93 pN3 patients met the inclusion criteria. During the study period, 32 (34.4%) and 61 (65.6%) of these patients received adjuvant radiotherapy plus chemotherapy (AR + AC) or adjuvant chemotherapy alone (AC). The median CSS in all patients was 12.0 months (interquartile range [IQR] 7.5-16.5). The Kaplan-Meier estimated 3-year CSS rate was significantly longer in the AR + AC group (28.5%) than the AC group (16.2%) (p = 0.036). AC + AR was associated with an improvement in CSS by 7.7 months (17.7 [IQR 3.8-31.6] vs. 10.0 [IQR 6.6-13.4] months). In the Cox regression analysis, AR + AC was an independent predictor of CSS [model a: HR 0.486 (95% CI 0.258-0.916), model b: HR 0.527 (95% CI 0.286-0.972)]. CONCLUSION: In conclusions, AR + AC was associated with improved CCS in patients with penile cancer who displayed an extracapsular nodal extension after inguinal surgery. This hypothesis requires further confirmation.

Lymph Node Mapping in Patients with Penile Cancer Undergoing Pelvic Lymph Node Dissection.

PURPOSE: A map of pelvic lymph node metastasis in patients with penile cancer helps to clarify the pattern of pelvic spread and define the reasonable limits of dissection, and it has not been established. We aim to provide an accurate map of lymph node metastasis in patients with penile cancer and determine the reasonable extent of pelvic lymph node dissection. MATERIALS AND METHODS: We enrolled patients with penile cancer undergoing pelvic lymph node dissection (128) at our institution from 1999 to 2018. The numbers of removed lymph nodes and positive lymph nodes at 10 distinct regions were recorded. The chi-square and Fisher exact tests were used. RESULTS: The median number of pelvic lymph nodes retrieved was 18 (IQR 10-30), with the majority being from the external iliac package (43.0%) and obturator package (31.9%). Pelvic lymph node metastasis was present in 57/128 (44.5%) patients. The median number of positive pelvic lymph nodes removed was 2 (IQR 1-4), with the majority being from the external iliac package (50.0%) and obturator package (36.6%). Advanced T-stage was related to higher risk of pelvic lymph node metastasis, which was present in 30.3%, 44.2%, 59.0% and 58.3% of patients with pT1, pT2, pT3 and pT4, respectively. Notably, 2 patients had crossover metastasis from 1 inguinal region to the contralateral pelvic region. CONCLUSIONS: We present a detailed map of pelvic lymph node metastasis in patients with penile carcinoma. The external iliac and obturator packages appear to be most commonly involved. Optimal pelvic lymph node dissection may extend to the common iliac artery, including common iliac, external iliac, internal iliac and obturator lymph nodes. Extranodal extension in inguinal nodes may not be as important as previously thought.

Large-scale public venues as medical emergency sites in disasters: lessons from COVID-19 and the use of Fangcang shelter hospitals in Wuhan, China.

Since the COVID-19 outbreak, Wuhan has adopted three methods of admitting patients for treatment: designated hospitals, newly built temporary hospitals and Fangcang shelter hospitals. It has been proven that converting large-scale public venues such as stadiums and exhibition centres into Fangcang shelter hospitals, which serve as hospitals for isolation, treatment and disease monitoring of patients with mild symptoms, is the most effective way to control virus transmission and reduce mortality. This paper presents some experiences learnt from treating COVID-19 in Wuhan, the first city to report the outbreak and which suffered from a shortage of emergency supplies, heavy workload among staff and a shortage of hospital beds during the early stages of the pandemic. The experiences include location, accessibility, spacious outdoor area, spacious indoor space, power supply, architectural layout design and partition isolation, ventilation, sewage, and problems in the construction and management of Fangcang shelter hospitals. During the COVID-19 pandemic, traditional approaches to disaster preparedness have demonstrated intrinsic problems, such as poor economic performance, inefficiency and lack of flexibility. Converting large-scale public venues into Fangcang shelter hospitals is an important means to rapidly improve the function of the city's healthcare system during a pandemic. This valuable experience in Wuhan will help other countries in their battle against the current COVID-19 pandemic and will also contribute to disaster preparedness and mitigation in the future.