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.

Enzymatic α-Ketothioester Decarbonylation Occurs in the Assembly Line of Barbamide for Skeleton Editing.

The decarbonylation reaction has been developed significantly in organic chemistry as an effective approach to various synthetic applications, but enzymatic precedents for this reaction are rare. Based on investigations into the hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line of barbamide, we report an on-line α-ketothioester decarbonylation reaction that leads to one-carbon truncation of the elongating skeleton. This enzymatic editing reaction occurs in the first round of lipopeptide extension and modification involving the multienzymes BarE and BarF, which successively house an NRPS module to initiate the biosynthesis and a PKS module to catalyze the first round of chain extension. Starting with processing a leucine-derived α-ketoacyl starter, the ketosynthase domain in BarE displays an unusual dual activity that results in net one-carbon chain elongation. It extrudes carbon monoxide from α-keto-isocaproyl thioester and then mediates decarboxylative condenses of the resultant isovaleryl thioester with malonyl thioester to form a diketide intermediate, followed by BarF-based O-methylation to stabilize the enol form of the ß-carbonyl and afford an unusual E-double bond. Biochemical characterization, chemical synthesis, computational analysis, and the experimental outcome of site-directed mutagenesis illustrate the extraordinary catalytic capability of this ketosynthase domain. This work furthers the appreciation of assembly line chemistry and opens the door to new approaches for skeleton editing/engineering of related molecules using synthetic biology approaches.

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.

First-line programmed death receptor-1 (PD-1) inhibitor and epidermal growth factor receptor (EGFR) blockade, combined with platinum-based chemotherapy, for stage IV penile cancer.

OBJECTIVES: To evaluate the anti-tumour activity and safety of anti-programmed death receptor-1 (PD-1) antibody plus epidermal growth factor receptor blockade combined with platinum-based chemotherapy (PEP) as first-line therapy for stage IV penile squamous cell carcinoma (PSCC). PATIENTS AND METHODS: We conducted a retrospective review of 17 patients with stage IV PSCC undergoing first-line PEP at Sun Yat-sen University Cancer Center between January 2018 and September 2021. Clinical responses were assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Of 17 patients who received first-line PEP, 13 were observed to have partial responses. Twelve patients subsequently received consolidated surgery. Nine of these achieved pN0 status, of whom six with locally advanced PSCC achieved pathological complete response. The median (range) follow-up time was 24.87 (3.63-29.40) months. Median PFS and median OS were not reached, with 2-year PFS and OS rates being 68.4% (95% confidence interval [CI] 48.7-96.1) and 62.9% (95% CI 41.6-95), respectively. Eight patients experienced Grade 3 or 4 treatment-related AEs. No Grade 5 AEs or death associated with treatment was observed. CONCLUSIONS: Anti-PD-1 antibody plus epidermal growth factor receptor blockade and platinum-based chemotherapy showed promising anti-tumour activity, acceptable toxicity, and satisfying long-term survival for stage IV PSCC. Larger clinical trials are needed to validate our findings.

Association of computed tomography-based body composition with survival in metastatic renal cancer patient received immunotherapy: a multicenter, retrospective study.

OBJECTIVES: To investigate the association of computed tomography-assessed body composition with survival outcomes of metastatic renal cell carcinoma (mRCC) received immunotherapy. METHODS: In this multicenter, retrospective study, we reviewed 251 mRCC patients who received anti-PD1 from five centers. We analyzed the relationship between BMI, skeletal muscle area (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and subcutaneous adipose percentage (SAT%) with progression-free survival (PFS) and overall survival (OS). The spatial localization T cells was investigated by multiplex immunofluorescence. RESULTS: Among 224 evaluable patients, 23 (10.3%) patients were underweight, 118 (52.7%) had normal weight, 65 (29%) were overweight, and 18 patients (8%) were obese. The median age was 55 years and most patients were male (71%). No significant improvement in PFS (HR, 0.61; 95% CI, 0.27-1.42) or OS (HR, 1.09; 95% CI, 0.38-3.13) was observed for the obese patients. Besides, SM, VAT, and SAT were not associated with survival outcomes (all p > 0.05). Interestingly, SAT% independently predicted PFS (as continuous variable, HR: 0.02; 95% CI, 0.01-0.11) and OS (HR:0.05; 95% CI, 0.01-0.39), which remained significant in multivariate modeling (as continuous variable, adjusted HR for PFS, 0.01; 95% CI, 0.00-0.04; adjusted HR for OS, 0.08; 95% CI, 0.01-0.72). These associations were consistent in subgroup analysis of different gender, BMI, PD-L1 positive, and sarcopenia group. Tumor of high SAT% patients had a higher intratumoral PD1+ CD8+ T cell density and ratio. CONCLUSION: High SAT% predicts better outcomes in mRCC patients treated with anti-PD1 and T cell location may account for the better response. KEY POINTS: • CT-based subcutaneous adipose percentage independently predicted progression-free survival and overall survival. • Patients with a higher subcutaneous adipose percentage had a higher intratumoral PD1+ CD8+ T cell density and ratio.

Effect of Plasticization on Stretching Stability of Poly(Vinyl Alcohol) Films: A Case Study Using Glycerol and Water.

Adding small molecular plasticizers is the most common route to tailor the stretchability of poly(vinyl alcohol) (PVA). However, how the plasticization along with the nature of the plasticizer governs the structural homogeneity during stretching remains an open question to answer. Herein, two representative plasticizers, glycerol (GLY) and water, are chosen to endow the PVA films with ductility. It is found that large strain cavitations cause obvious stress whitening in the PVA/H2 O films; on the contrary, most of the PVA/GLY films maintain transparent undergoing tensile deformation. Through a combination of experimental inspections and molecular dynamic simulation, it is revealed that partial water molecules that behave as free water will aggregate into microdomains, which serve as mechanical defects responsible for yielding voids. Whereas, the GLY plasticizer homogeneously disperses at a molecular level and interacts with PVA chains through strong hydrogen bonds. More interestingly, it is illustrated that the dispersion and bound states of plasticizers are closely related to the mechanical character of the plasticized PVA films. These findings offer new insight into the working mechanism of plasticization on the structural stability during stretching, and guide the design of PVA/plasticizer system to obtain excellent comprehensive mechanics.

The nutritional literacy of breast cancer patients receiving chemotherapy and its association with treatment self-regulation and perceived social support.

PURPOSE: Chemotherapy can lead to malnutrition and post-menopausal recurrence among breast cancer (BC) patients, who need to achieve nutritional literacy (NL) to cope. The objective of this study was to explore the NL level in Chinese BC patients receiving chemotherapy and its predictors including both internal motivation and the external environment. METHODS: A total of 326 BC female patients from three hospitals were enrolled. Participants completed the Nutrition Literacy Measurement Scale for Chinese Adult (NLMS-CA), Chinese version from the Treatment Self-Regulation Questionnaire (TSRQ-C), and the Perceived Social Support Scale (PSSS) to assess NL, treatment self-regulation, and social support. Stepwise multivariate linear regression was used to identify the main factors of NL. RESULTS: The total NL score was 151.31 ± 16.85, the "knowledge understanding" dimension had the lowest score. In the final regression model, patients with higher scores for "autonomous motivation" and "introjected regulation" on the TSRQ-C and "family support" and "other support" on the PSSS, higher educational levels and average monthly household incomes and endocrine therapy had higher NL levels (adjusted R2 = 66.7%, p < 0.05). CONCLUSIONS: The overall NL score among Chinese BC patients receiving chemotherapy was satisfactory, but the knowledge understanding score was low. Higher autonomous motivation, introjected regulation, family support and other support scores, higher educational and household income levels, and endocrine therapy were predictors of NL in female patients. Interventions should be designed according to the specific performances and predictors of NL in female patients.

Formation and Loading of a (2S)-2-Ethylmalonamyl Starter Unit in the Assembly Line of Polyketide-Nonribosomal Peptide Hybrid Sanglifehrin A.

Sanglifehrin A (SFA) is a spirolactam-conjugated, 22-membered macrolide with remarkable immunosuppressive and antiviral activities. This macrolide is a result of a hybrid polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) assembly line that utilizes (2S)-2-ethylmalonamyl as a starter unit. Here, we report that the formation and loading of this starter unit in the SFA assembly line involve two unusual enzymatic reactions that occur on a discrete acyl carrier protein (ACP), SfaO. An amide synthetase, SfaP, catalyzes the amidation of (2S)-2-ethylmalonyl in a SfaO-dependent manner. Then, a ß-ketoacyl-ACP synthase III-like protein, SfaN, transfers resultant (2S)-2-ethylmalonamyl from SfaO onto the loading ACP domain of the hybrid PKS-NRPS assembly line to prime SFA biosynthesis. Both SfaP and SfaN display promiscuous activities. This study furthers the appreciation of assembly line chemistry, as a new paradigm for unusual building block formation and incorporation is provided.

Hydrogen-bond-dominated mechanical stretchability in PVA films: from phenomenological to numerical insights.

Hydrogen bonds (H-bonds) in poly(vinyl alcohol) (PVA) play a crucial role in macroscopic mechanical properties, particularly for stretchability. However, there is still some ambiguity about the quantitative dependence of H-bond interactions on the mechanical performance, mainly attributed to the difficulty in the discrimination of various H-bond types. Herein, small molecular chemicals as plasticizers were incorporated into the PVA matrix to tailor the H-bonding interactions. By altering the PVA molecular weight, plasticizer type and loading, both the stretchability and H-bond content were regulated on a large scale. By a combination of DMA, IR spectroscopy, MD simulation and solid-state 13C-NMR, every sort of H-bond in PVA was assigned, and their relative fractions were ascertained quantitatively. After correlating the elongation ratio with the relative fraction of the different types of H-bonding interaction, it was found that all the pairs of elongation vs. intermolecular H-bond content derived from different series of PVA/plasticizer films could be plotted into a master curve and exhibited good linearity, indicating that intermolecular H-bonds dominate the mechanical stretchability in PVA films. Our efforts contribute towards an in-depth understanding of performance optimization induced by H-bond manipulation from empirical, phenomenological aspects to intrinsic, numerical insights.

Patient-perceived knee enlargement after total knee arthroplasty: prevalence, risk factors, and association with functional outcomes and radiological analysis.

PURPOSE: In clinical practice, many patients complained that their knees became larger after total knee arthroplasty (TKA), yet no studies have described this phenomenon. We named this as "patient-perceived enlargement of knee" (PPEK). This study aimed to investigate the prevalence of PPEK after TKA; assess the association between PPEK and demographics, surgical options, or component size; assess the influence of PPEK on patient satisfaction and functional outcomes; and determine whether there was radiological difference between patients with or without PPEK. METHODS: We reviewed patients that underwent unilateral primary TKA between May 2018 and April 2019. We investigated the prevalence of PPEK and acquired functional scores and satisfaction. Patients were divided into two groups according to whether they complained of PPEK. In radiological evaluation, we measured anterior and posterior condyle offset (ACO and PCO) of the femur, tibial coverage lines, tibial overhanging lines, and femoral overhanging lines. RESULTS: A total of 389 patients were enrolled and 101 patients felt their knee became "larger" after TKA. Patients with PPEK had significantly shorter height and lower weight, yet component size distribution showed no statistical difference. Patients with PPEK had significantly lower functional scores and satisfaction. Patients with PPEK had significantly larger ACO, shorter postoperative PCO, more ACO increase, and less anterior underhang of the tibia. CONCLUSION: PPEK is common in TKA patients, especially in individuals with smaller height and weight. PPEK is associated with poor satisfaction and lower functional scores. In radiology, post-operative ACO, PCO, and anterior underhang of the tibial component were correlated with PPEK.

Overexpression of CEP72 Promotes Bladder Urothelial Carcinoma Cell Aggressiveness via Epigenetic CREB-Mediated Induction of SERPINE1.

A vital constituent of the centrosome involved in regulating the activity of the organelle during the cell cycle is centrosomal protein (CEP)-72, whose function in the case of human cancer yet lacks clarity. The expression dynamics of CEP72 and its clinical impact were examined in a large cohort of bladder tissues. Several experiments at both the in vitro and in vivo levels on urothelial carcinoma of the bladder (UCB) cells were conducted to understand the role of this molecule along with the mechanisms. Overexpression of CEP72 in UCB was linked with the acquisition of an aggressive phenotype, which was associated with poor prognosis. In UCB cell lines, knockdown of CEP72 using shRNA was sufficient to inhibit cell invasiveness/metastasis, whereas ectopic overexpression of CEP72 promoted cell invasiveness and/or metastasis both in vitro and in vivo. CEP72 was demonstrated to induce UCB cell aggressiveness via up-regulation of an important target downstream, the serpin family member 1 gene (SERPINE1) (alias plasminogen activator inhibitor, PAI1), ultimately leading to increased cancer cell invasiveness. Particularly, overexpression of CEP72 was associated with a sizable increase in cAMP response element-binding protein binding at the SERPINE1 promoter, leading to increased SERPINE1 transcription. Such observations are suggestive of the potential use of CEP72 as a therapeutic tool for UCB.

Proposal for reclassification of N staging system in penile cancer patients, based on number of positive lymph nodes.

In the present study, we aim to compare the rationality of proposed N classification based on the number of metastatic lymph nodes (LNs) with the current one. A total of 509 penile cancer patients at our institute were analyzed. Univariable and multivariable statistical analyses were used to assess cancer-specific survival (CSS) in 2 staging systems. Harrell's concordance index was applied to evaluate predictive accuracy of the current and proposed N classification in predicting CSS. We propose a new classification: pN1 (metastasis in 1-2 regional LNs), pN2 (metastasis in 3 regional LNs, or 3 or fewer regional lymph nodes with extranodal extension), and pN3 (metastasis in 4 or more regional LNs). According to the current and proposed N classification, the 5-year CSS of penile cancer patients with pN1, pN2 and pN3 was 85.8%, 39.0%, and 19.7%; and with pN1, pN2 and pN3 was 79.8%, 39.3% and 15.3%, which almost all showed significant difference (P < .001, P = .259) (P < .001, P < .001). Multivariable predictive accuracy of the proposed and current N staging was 76.48% and 70.92% (5.56% gain; P < .001). With a multivariable model of clinical features, both current (hazard ratio [HR], 7.761, 10.612; P < .001, P < .001) and proposed N stages (HR, 3.792, 3.971; P < .001, P < .001) exhibited independent effects on survival. The proposed N classification is superior to the current one, which is simpler and provides more accurate prognosis.

The effects of intra-arterial chemotherapy on bladder preservation in patients with T1 stage bladder cancer.

PURPOSE: To investigate the effects of intra-arterial chemotherapy on T1 stage bladder cancer (Bca) and evaluate patient outcome with bladder-preserving treatment approaches. MATERIALS AND METHODS: A total of 238 patients with T1 stage Bca were retrospectively analyzed. Among them, 35 patients were categorized into the subgroup of highest-risk T1 stage according to the European Association of Urology guidelines and received immediate radical cystectomy (RC group), whereas 62 were classified as being highest-risk T1 patients but were unwilling to undergo RC and were treated with gemcitabine plus cisplatin intra-arterial chemotherapy (GC group). There were 141 T1 patients who had bladder-preserving surgery with intravesical chemotherapy (IVC group). RESULTS: For patients with T1 stage Bca, the GC group had a higher estimated recurrence-free survival rate (44.4 vs. 13.9%, P = 0.087), progression-free survival rate (75.4 vs. 32.8%, P = 0.006), and cancer-specific survival (CSS) rate (78.7 vs. 67.5%, P = 0.399) when compared with the IVC group, respectively. Using the multivariable regression model, the GC intra-arterial chemotherapy was significantly related to bladder preservation (P = 0.004), lower recurrence (P = 0.012), and less progression (P = 0.004). For patients with the highest-risk T1 stage, GC group did not have a poorer CSS rate in comparison with the RC group (P = 0.383). Moreover, immediate RC did not confer a survival benefit in terms of CSS when compared with those who underwent deferred RC after failing GC intra-arterial chemotherapy (P = 0.283). CONCLUSIONS: Gemcitabine plus cisplatin intra-arterial chemotherapy may be an effective bladder-preserving alternative adjuvant treatment for patients with T1 stage Bca with oncologic benefits, good compliance, and low toxicity.

Accuracy of Digital Tomosynthesis With Metal Artifact Reduction for Detecting Osteointegration in Cementless Hip Arthroplasty.

BACKGROUND: Cementless hip arthroplasty is increasingly gaining popularity worldwide. Radiologic identification of osteointegration is key to confirming biologic fixation. We conducted the study reported here to determine the sensitivity and specificity of digital tomosynthesis with metal artifact reduction (TMAR), radiography, and conventional computed tomography in detecting osteointegration in cementless hip arthroplasty. METHODS: We prospectively included data for 24 patients who underwent revision hip arthroplasty in our hospital, with 13 femoral and 14 acetabular cementless components retrieved that contained solid evidence of biologic fixation. All patients underwent 3 examinations before surgery, and evidence of osteointegration on retrieved prostheses was used as the reference standard. Seven orthopedic surgeons evaluated these images independently using uniform criteria. RESULTS: On the femoral side, the sensitivity and specificity of detecting osteointegration were 73.8% ± 4.6% and 94.3% ± 1.5%, respectively, for TMAR; 50.4% ± 5.3% and 87.8% ± 2.1%, respectively, for radiography; and 36.4% ± 5.1% and 90.9% ± 1.9%, respectively, for CT. On the cup side, the corresponding values were 60.2% ± 8.3% and 86.4% ± 5.7%, respectively, for TMAR; 45.9% ± 8.5% and 66.4% ± 7.8%, respectively, for radiography; and 45.1% ± 8.5% and 73.5% ± 7.3%, respectively, by computed tomography. CONCLUSION: TMAR significantly improved the accuracy osteointegration detection in cementless hip arthroplasty (P < .017).

The C-reactive protein/albumin ratio, a validated prognostic score, predicts outcome of surgical renal cell carcinoma patients.

BACKGROUND: The preoperative C-reactive protein/Albumin (CRP/Alb) ratio has been shown to be valuable in predicting the prognosis of patients with certain cancers. The aim of our study is to explore its prognostic value in patients with renal cell carcinoma (RCC). METHODS: A retrospective study was performed in 570 RCC patients underwent radical or partial nephrectomy including 541 patients who received full resection of localized (T1-3 N0/+ M0) RCC. The optimal cutoff value of CRP/Alb was determined by the receive operating characteristic (ROC) analysis. The impact of the CRP/Alb and other clinicopathological characteristics on overall survival (OS) and disease-free survival (DFS) was evaluated using the univariate and multivariate Cox regression analysis. RESULTS: The optimal cutoff of CRP/Alb ratio was set at 0.08 according to the ROC analysis. Multivariate analysis indicated that CRP/Alb ratio was independently associated with OS of RCC patients underwent radical or partial nephrectomy (hazard ratio [HR]: 1.94; 95% confidence interval [95% CI]: 1.12-3.36; P = 0.018), and DFS of localized RCC patients underwent full resection (HR: 2.14; 95% CI: 1.22-3.75; P = 0.008). CONCLUSION: Elevated CRP/Alb ratio was an independent prognostic indicator for poor OS in patients underwent radical or partial nephrectomy and DFS of localized RCC patients underwent full resection. Overall, CRP/Alb may help to identify patients with high relapse risk.

CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression.

PURPOSE: The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. METHODS: A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay. Protein and mRNA levels of full-length AR (AR-FL) and AR-V7 were determined by qPCR and western blot, respectively. The nuclear translocation of p50 and p65 was assessed to reflect the activity of the NF-κB pathway. RESULTS: CX4945 reduced the proliferation of CRPC cells in a dose-dependent and time-dependent manner. AR-V7 rather than AR-FL was downregulated by CX4945 in both the mRNA and protein level. Furthermore, CX4945 could restore the sensitivity of CRPC cells to bicalutamide. The analysis of possible mechanisms demonstrated that the inhibition of CK2 diminished the phosphorylation of p65 at ser529 and thus attenuated the activity of the NF-κB pathway. CONCLUSION: The inhibition of CK2 by CX4945 can repress the viability of CRPC cells and restore their sensitivity to anti-androgen therapy by suppressing AR-V7. This finding presents a potential option for the treatment of prostate cancer, especially CRPC.

Trends of testis-sparing surgery for pediatric testicular tumors in South China.

BACKGROUND: Testis-sparing surgery is not popular in South China. This study aimed to investigate this procedure for pediatric testicular tumors. METHODS: Children with testicular benign tumors were retrospectively analyzed from January 2001 to June 2015 in the Sun Yat-sen University Cancer Center (SYSUCC) and the First Affiliated Hospital (SYSU-1st). Follow-up was performed until June 2016, and the proportions of TSS in the two hospitals during the different periods were compared. RESULTS: Forty-seven children with testicular benign tumors were enrolled, and 16 cases underwent testis-sparing surgery. All patients were cured and discharged, which included mature teratoma (n = 37), testicular adrenal rest tumors (n = 4), epidermal cysts (n = 3), granulomatous inflammation (n = 2) and adenomatoid tumors (n = 1). Inguinal testis-sparing surgery was performed in 16 children, and no recurrence was detected during follow-up. It was performed more frequently in SYSUCC than in SYSU-1st (P = 0.031), and the tumor size of these patients was smaller than those of patients who underwent radical orchiectomy (P = 0.044). Moreover, testis-sparing surgery has become more common in the past 5 years, although differences over time have not reached significance (P = 0.051). CONCLUSIONS: Testis-sparing surgery is reliable, and tumor size and special hospitals affect its success. Additionally, its use has become more popular in recent years. However, advocacy is still needed for the use of this technique in pediatric testicular benign tumors that are small sized.

Location of the Common Peroneal Nerve in Valgus Knees-Is the Reported Safe Zone for Well-Aligned Knees Applicable?

BACKGROUND: Lateral soft-tissue release can jeopardize the common peroneal nerve (CPN) in total knee arthroplasty for valgus knees. Previous studies reporting safe zones to protect the CPN were based on well-aligned knees. We conducted this study to compare the localization of the CPN in well-aligned knees and in valgus knees. METHODS: We conducted a consecutive 3-dimensional radiographic study on magnetic resonance images of 58 well-aligned knees and 39 valgus knees. We measured the distance between the CPN and the tibia, as well as the mediolateral, anteroposterior, and angular location of the CPN. We compared the results between well-aligned knees and valgus knees. RESULTS: We found that there is an increased distance between the CPN and the tibia at the level of the tibial cut, but not at the joint line in valgus knees. It is safer to release the posterolateral capsule at the tibial side than at the level above this. The angular location and the mediolateral or anteroposterior location of the CPN in valgus knees are similar to those of well-aligned knees. CONCLUSION: The location of the CPN in valgus knees is similar to that in well-aligned knees. The previously reported safe zone in well-aligned knees is applicable in valgus knees to protect the CPN.

Digital tomosynthesis with metal artifact reduction for assessing cementless hip arthroplasty: a diagnostic cohort study of 48 patients.

OBJECTIVES: For postoperative imaging assessment of cementless hip arthroplasty, radiography and computed tomography (CT) were restricted by overlapping structures and metal artifacts, respectively. A new tomosynthesis with metal artifact reduction (TMAR) is introduced by using metal extraction and ordered subset-expectation maximization (OS-EM) reconstruction. This study investigated the effectiveness of TMAR in assessing fixation stability of cementless hip arthroplasty components. MATERIALS AND METHODS: We prospectively included 48 consecutive patients scheduled for revision hip arthroplasty in our hospital, with 41 femoral and 35 acetabular cementless components available for evaluation. All patients took the three examinations of radiography, CT, and TMAR preoperatively, with intraoperative mechanical tests, and absence or presence of osteointegration on retrieved prosthesis as reference standards. Three senior surgeons and four junior surgeons evaluated these images independently with uniform criteria. RESULTS: For TMAR, 82 % diagnoses on the femoral side and 84 % diagnoses on the acetabular side were accurate. The corresponding values were 44 and 67 % for radiography, and 39 % and 74 % for CT. Senior surgeons had significantly higher accuracy than junior surgeons by radiography (p < 0.05), but not by TMAR or CT. CONCLUSIONS: By minimizing metal artifacts in the bone-implant interface and clearly depicting peri-implant trabecular structures, the TMAR technique improved the diagnostic accuracy of assessing fixation stability of cementless hip arthroplasty, and shortened the learning curve of less experienced surgeons. LEVEL OF EVIDENCE: Level II, diagnostic cohort study.

Surveillance for patients with clinical stage I nonseminomatous testicular germ cell tumors.

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.