Search

The prognostic value of serum lipid-profile in renal cell cancer (RCC) remains unknown. The purpose of the study is to explore the association between the serum lipid-profile and RCC patients.The levels of preoperative serum lipid-profile (including cholesterol, triglycerides, high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoA-I], and apolipoprotein B [ApoB]) were retrospectively performed in 786 patients with RCC. The cutoff values of the lipids were determined by the receiver-operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum lipids in RCC.Combined ROC analysis and univariate and multivariate Cox regression analyses, for overall survival (OS), revealed patients with low ApoA-I (

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. Human papillomavirus (HPV) infection may result in improved treatment efficacy and disease prognosis in patients with advanced penile squamous cell carcinoma (PSCC) receiving first‐line programmed cell death protein 1 inhibitor–based combination therapy. The antitumor immune microenvironment is stimulated by HPV infection in advanced PSCC tissues. [ABSTRACT FROM AUTHOR]

Although high body mass index (BMI) was reported to associate with a better prognosis for metastatic renal cell cancer (mRCC) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, it is an imperfect proxy for the body composition, especially in Asian patients with a lower BMI. The role of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and perirenal fat thickness (PRFT) in mRCC patients was still unknown. Therefore, a multicenter retrospective study of 358 Chinese mRCC patients receiving anti-VEGF therapy was conducted and their body composition was measured via computed tomography. We parameterized VAT, SAT and PRFT according to their median value and BMI according to Chinese criteria (overweight: BMI ≥ 24). We found VAT, SAT, and PRFT (all p < 0.05) but not BMI, significantly associated with overall survival (OS) and progression-free survival (PFS). Multivariate Cox analysis identified PRFT was the independent predictor of OS and PFS, and IMDC expanded with PRFT showed the highest C-index in predicting OS (OS:0.71) compared with VAT, SAT, and BMI. PRFT could increase the area under the curve of the traditional International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in OS (70.54% increase to 74.71%) and PFS (72.22% increase to 75.03%). PRFT was introduced to improve the IMDC model and PRFT-modified IMDC demonstrated higher AIC in predicting OS and PFS compared with the traditional IMDC model. Gene sequencing analysis (n = 6) revealed that patients with high PRFT had increased angiogenesis gene signatures (NES = 1.46, p = 0.04) which might explain why better drug response to anti-VEGF therapy in mRCC patients with high PRFT. The main limitation is retrospective design. This study suggests body composition, especially PRFT, is significantly associated with prognosis in Chinese mRCC patients receiving anti-VEGF therapy. PRFT-modified IMDC model proposed in this study has better clinical predictive value. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to explore whether complete eradication of tumor burden with stereotactic body radiotherapy (SBRT) would affect the outcomes of oligometastatic renal cell carcinoma (RCC). Materials and methods: Patients diagnosed with extracranial oligometastatic RCC (no more than five metastases) between 2007 and 2019 were reviewed. Those without nephrectomy were excluded. SBRT to all, some and no lesions were defined as complete, incomplete, and no SBRT. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed using Kaplan–Meier method, Cox regression model and the Fine and Gray method. Result: A total of 101 patients were included, 51.5% of whom had < 3 metastases. Forty (39.6%) patients received complete SBRT, and 61 (60.4%) received no or incomplete SBRT. The 1-year LC rate was 97.3%. The complete SBRT group had significantly longer PFS (26.0 vs 18.8 months; p = 0.043) and CSS (not reached vs. 55.3 months; p = 0.012) compared with the no or incomplete SBRT group. In multivariate analysis, ECOG 0–1 (HR 0.389, 95% CI 0.167–0.906, p = 0.029) and complete SBRT were prognostic factors for CSS (HR 0.307, 95% CI 0.108–0.876, p = 0.027). Complete SBRT was associated with improved CSS in the subgroups of patients with age < 55 years, ECOG 0–1, clear-cell histology, IMDC intermediate/poor risk, metachronous metastasis, and < 3 lesions. Conclusion: Complete eradication of tumor burden with SBRT was associated with better survival in patients with oligometastatic RCC. The recommendation of SBRT to all lesions should be individualized. [ABSTRACT FROM AUTHOR]

Objectives: Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC. Methods: All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. Results: The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile. Conclusions: The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiation therapy (SBRT) and tyrosine kinase inhibitors (TKIs) are effective treatments for metastatic renal cell carcinoma, but data on combining these two modalities are scarce. We aimed to investigate the survival outcomes of SBRT plus TKIs. Methods: Data of patients treated with TKIs from December 2007 to June 2019 were collected. Patients received SBRT plus TKIs (TKI + SBRT group) or TKIs alone (TKI alone group). Local control (LC), time to change of systemic therapy (TTS), and overall survival (OS) were assessed. Results: A total of 190 patients were included, and 85 patients received TKI + SBRT. The 2-year LC rate was 92.8%. The median OS in the TKI + SBRT group was significantly longer than that of the TKI alone group (63.2 vs 29.8 months; P < 0.001). In multivariate analysis, IMDC intermediate (HR 1.96; 95% CI 1.10–3.48; P = 0.022) and poor risk (HR 2.43; 95% CI 1.25–4.75; P = 0.009), oligometastasis (HR 0.41; 95% CI 0.26–0.65; P < 0.001), and the addition of SBRT (HR 0.48; 95% CI 0.31–0.75; P = 0.001) were prognostic factors for OS. Patients with oligometastasis (P = 0.009) and those with IMDC favorable (P = 0.044) or intermediate (P = 0.002) risk had significantly longer OS with TKI + SBRT. The median TTS were 21.5, 6.4, and 9.0 months in patients receiving SBRT before first-line TKI failure, SBRT after first-line TKI failure, and first-line TKI alone (P < 0.001). Five patients (5.9%) experienced SBRT-related grade 3 toxicities. Conclusions: Combining SBRT with TKIs is tolerable and associated with longer OS in selected patients, such as those with oligometastasis and favorable or intermediate risk. [ABSTRACT FROM AUTHOR]

Background Acute ischemic injury in the operated kidney after partial nephrectomy (PN) is often masked by a functional contralateral kidney; however, there is no practical method to assess this and its prognostic significance has not been defined. Objective We propose a spectrum score to reflect the degree of ischemic insult in the ipsilateral kidney and study its relationship to subsequent functional recovery. Design, setting, and participants From 2007 to 2014, 243 patients with a functional contralateral kidney underwent PN with necessary studies for detailed analysis of function and parenchymal mass before and after surgery in the ipsilateral kidney. Based on split function and percent parenchymal mass preserved in the ipsilateral kidney, we determined: serum creatinine (SCr) ideal-peak : expected peak SCr presuming no ischemic injury; and SCr worstcase-peak : expected peak SCr presuming temporary complete nonfunction of the ipsilateral kidney. The acute ipsilateral renal dysfunction spectrum score was defined: (observed peak SCr – SCr ideal-peak )/(SCr worstcase-peak – SCr ideal-peak ). Subsequent functional recovery was defined: (percent function preserved)/(percent mass saved). Intervention PN. Outcome measurements and statistical analysis Factors associated with spectrum score and relationship between spectrum score and subsequent functional recovery were evaluated by linear regression. Results and limitations Median duration of warm ischemia ( n = 152) was 21 min (interquartile range [IQR] = 15–27) and hypothermia ( n = 91) 26 min (IQR = 23–30). Median parenchymal mass preservation was 83% (IQR = 74–91%). Warm ischemia and longer ischemia duration associated with higher spectrum score (both p < 0.05). Increased spectrum score (<25%, 25–50%, 50–75%, and >75% quartiles) had decreased functional recovery (98%, 94%, 90%, and 89%, respectively, p < 0.001). However, this trend was not observed in the hypothermia cohort. On multivariable analysis spectrum score and ischemia type significantly associated with functional recovery (both p < 0.01), while age and comorbidities failed to associate ( p = 0.3–0.7). Conclusions Acute ipsilateral renal dysfunction spectrum score unmasks the degree of ischemic insult in the operated kidney after PN and associates with functional recovery. While increased spectrum score associates with suboptimal recovery, even patients with a high spectrum score reached 89–90% recovery. Patient summary Acute functional decline after partial nephrectomy is difficult to evaluate in patients with two kidneys, but a proposed spectrum score can be used to evaluate this. Increased spectrum score reflects increased ischemia and may impact the functional recovery of the kidney. [ABSTRACT FROM AUTHOR]

Background: In the current Tumour-Node-Metastasis (TNM) classification system for renal cell carcinoma (RCC), both renal sinus fat invasion (SFI) and perinephric fat invasion (PFI) are defined as T3a, suggesting that the prognosis should be similar for the two pathologic findings. Several studies, however, have reported a worse prognosis for SFI in patients with a T3a tumor. In order to compare the prognosis of these two pathologic findings (SFI versus. PFI) in a more comprehensive way, this meta-analysis was performed. Methods: To identify relevant studies, Medline, Embase, Cochrane Library, and Scopus database were searched from the inception until October 2014. A meta-analysis was performed using Review Manager 5.2 and STATA 11. Pooled Odds ratio (OR) and/or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association. Results: A total of 6 studies including 1031 patients qualified for analysis. T3a RCC patients with SFI were significantly associated with poor cancer specific survival(CSS) (HR: 1.47, 95% CI: 1.19–1.83; P<0.001) compared to those with PFI. In T3aNx/N0M0 subgroup, SFI patients also showed a worse prognosis than those with PFI (CSS, HR: 1.94, 95% CI: 1.21–3.12; P = 0.006). T3a RCC patients with SFI had higher Furhman grade, greater possibility of lymph node metastasis, sarcomatoid differentiation and tumour necrosis. Main limitation is the relatively small number of included studies. Conclusion: The present meta-analysis suggested that SFI is associated with worse CSS in patients with pT3a RCC. However, due to the small number of included studies, future studies with a large sample size are required to further verify our findings. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prognostic value of histological parameters in patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) undergoing active surveillance post-orchiectomy. Methods: Prognoses and recurrence patterns were investigated in 78 patients with CSI NSGCT who underwent orchiectomy. Immediately following orchiectomy, patients participated in active surveillance between 1999 and 2013 at Sun Yat-sen University Cancer Center, Guangzhou, China. Results: 23.1 % of the 78 investigated patients with CSI NSGCT relapsed, within a median time of 5.6 months It was determined using multivariate analysis that lymph vascular invasion (LVI) (OR 6.521; 95 % CI 1.872-22.721; p = 0.003) and the predominant presence of yolk sac tumor (greater than 50 %) (OR 3.537; 95 % CI 1.076-11.628; p = 0.038) independently correlated with relapse-free survival (RFS). Patients were categorized accordingly into three risk groups: low risk [<50 % presence of yolk sac tumor and LVI (−); n = 41], intermediate risk [50 % or greater presence of yolk sac tumor and LVI (+); n = 29], and high risk [50 % or greater presence of yolk sac tumor and LVI (+); n = 8]. Relapse rates of the low-risk, intermediate-risk, and high-risk groups were 7.3, 31.0, and 75.0 %, respectively. Conclusions: LVI and a predominant presence of yolk sac tumor are crucial risk factors for relapse of CSI NSGCT. For patients without either of these risk factors, active surveillance post-orchiectomy is a safe and effective approach for the initial management of CSI NSGCT. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The objective of this study was to assess the clinical outcome after removal of a broken file from root canal by using ultrasonic techniques and to evaluate various factors that might influence the outcome. Methods: One hundred two patients with 102 teeth with a broken file in the root canal, treated between 2004 and 2008, were contacted for follow-up examination 12–68 months after treatment (median, 28 months). Outcome was assessed on the basis of clinical and radiographic criteria by calibrated examiners and dichotomized as healed or disease. The result was analyzed statistically by Pearson or Fisher exact test and multivariate logistic regression. Results: Of 66 teeth examined (64.7% recall), 81.8% were healed. Stepwise logistic regression analysis revealed that inadequate root canal filling was a statistically significant factor in predicting failure of successful healing. The cases with removal of broken files had a higher healing rate than those with broken files left in the root canal, but the difference was not statistically significant (P > .05). There was no significant difference in outcome related to presence or absence of perforation, although the rate of healing was greater in teeth without perforation. Other factors including age, sex, tooth type, apical status, position of segment, and type of restoration did not affect prognosis. Conclusions: Treatment outcome after the use of ultrasonics for removal of broken files was favorable. Adequate root filling has a more substantial impact on treatment outcome than the other factors. [Copyright &y& Elsevier]

A correction to the article "Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-кB mediated matrix metalloproteinase-1 gene regulation" that was published on March 28, 2017 is presented.