Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has great advantages in the treatment of unicompartmental knee osteoarthritis, but its revision rate is higher than that of total knee arthroplasty. AIM: To summarize and analyse the causes of revision after UKA. METHODS: This is a retrospective case series study in which the reasons for the first revision after UKA are summarized. We analysed the clinical symptoms, medical histories, laboratory test results, imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA. RESULTS: A total of 13 patients, including 3 males and 10 females, underwent revision surgery after UKA. The average age of the included patients was 67.62 years. The prosthesis was used for 3 d to 72 months. The main reasons for revision after UKA were improper suturing of the surgical opening (1 patient), osteophytes (2 patients), intra-articular loose bodies (2 patients), tibial prosthesis loosening (2 patients), rheumatoid arthritis (1 patient), gasket dislocation (3 patients), anterior cruciate ligament injury (1 patient), and medial collateral ligament injury with residual bone cement (1 patient). CONCLUSION: The causes of primary revision after UKA were gasket dislocation, osteophytes, intra-articular loose bodies and tibial prosthesis loosening. Avoidance of these factors may greatly reduce the rate of revision after UKA, improve patient satisfaction and reduce medical burden.

Risk factors for postoperative surgical site infections after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

OBJECTIVES: The primary aim was to evaluate risk factors for surgical site infections after anterior cruciate ligament reconstruction (ACLR). The secondary aim was to investigate the surgical site infection incidence rate and the mean time to postoperative surgical site infection symptoms. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase and Web of Science were searched from database inception to September 2021 and updated in April 2022. ELIGIBILITY CRITERIA: Quantitative, original studies reporting potential risk factors for surgical site infections after ACLR were included. RESULTS: Twenty-three studies with 3871 infection events from 469 441 ACLRs met the inclusion criteria. Male sex (OR 1.78, p< 0.00001), obesity (OR 1.82, p=0.0005), tobacco use (OR 1.37, p=0.01), diabetes mellitus (OR 3.40, p=0.002), steroid use history (OR 4.80, p<0.00001), previous knee surgery history (OR 3.63, p=0.02), professional athlete (OR 4.56, p=0.02), revision surgery (OR 2.05, p=0.04), hamstring autografts (OR 2.83, p<0.00001), concomitant lateral extra-articular tenodesis (OR 3.92, p=0.0001) and a long operating time (weighted mean difference 8.12, p=0.005) were identified as factors that increased the risk of surgical site infections (superficial and deep) after ACLR. Age, outpatient or inpatient surgery, bone-patellar tendon-bone autografts or allografts and a concomitant meniscus suture did not increase the risk of surgical site infections. The incidence of surgical site infections after ACLR was approximately 1% (95% CI 0.7% to 1.2%). The mean time from surgery to the onset of surgical site infection symptoms was approximately 17.1 days (95% CI 13.2 to 21.0 days). CONCLUSION: Male sex, obesity, tobacco use, diabetes mellitus, steroid use history, previous knee surgery history, professional athletes, revision surgery, hamstring autografts, concomitant lateral extra-articular tenodesis and a long operation time may increase the risk of surgical site infections after ACLR. Although the risk of surgical site infections after ACLR is low, raising awareness and implementing effective preventions for risk factors are priorities for clinicians to reduce the incidence of surgical site infections due to its seriousness.

Risk Factors for Revision or Rerupture After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The rerupture or need for revision after anterior cruciate ligament reconstruction (ACLR) is a serious complication. Preventive strategies that target the early identification of risk factors are important to reduce the incidence of additional surgery. PURPOSE: To perform a systematic review and meta-analysis to investigate risk factors for revision or rerupture after ACLR. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science from database inception to November 2021 and updated in January 2022. Quantitative, original studies reporting potential adjusted risk factors were included. Odds ratios (ORs) were calculated for potential risk factors. RESULTS: A total of 71 studies across 13 countries with a total sample size of 629,120 met the inclusion criteria. Fifteen factors were associated with an increase in the risk of revision or rerupture after ACLR: male sex (OR, 1.27; 95% CI, 1.14-1.41), younger age (OR, 1.07; 95% CI, 1.05-1.08), lower body mass index (BMI) (OR, 1.03; 95% CI, 1.00-1.06), family history (OR, 2.47; 95% CI, 1.50-4.08), White race (OR, 1.32; 95% CI, 1.08-1.60), higher posterolateral tibial slope (OR, 1.15; 95% CI, 1.05-1.26), preoperative high-grade anterior knee laxity (OR, 2.30; 95% CI, 1.46-3.64), higher baseline Marx activity level (OR, 1.07; 95% CI, 1.02-1.13), return to a high activity level/sport (OR, 2.03; 95% CI, 1.15-3.57), an ACLR within less than a year after injury (OR, 2.05; 95% CI, 1.81-2.32), a concomitant medial collateral ligament (MCL) injury (OR, 1.62; 95% CI, 1.31-2.00), an anteromedial portal or transportal technique (OR, 1.36; 95% CI, 1.22-1.51), hamstring tendon (HT) autografts (vs bone-patellar tendon-bone [BPTB] autografts) (OR, 1.60; 95% CI, 1.40-1.82), allografts (OR, 2.63; 95% CI, 1.65-4.19), and smaller graft diameter (OR, 1.21; 95% CI, 1.05-1.38). The other factors failed to show an association with an increased risk of revision or rerupture after ACLR. CONCLUSION: Male sex, younger age, lower BMI, family history, White race, higher posterolateral tibial slope, preoperative high-grade anterior knee laxity, higher baseline Marx activity level, return to a high activity level/sport, an ACLR within less than a year from injury, a concomitant MCL injury, an anteromedial portal or transportal technique, HT autografts (vs BPTB autografts), allografts, and smaller graft diameter may increase the risk of revision or rerupture after ACLR. Raising awareness and implementing effective preventions/interventions for risk factors are priorities for clinical practitioners to reduce the incidence of revision or rerupture after ACLR.

Comparisons of the Efficacy and Safety of Total Knee Arthroplasty by Different Surgical Approaches: A Systematic Review and Network Meta-analysis.

The purpose of this network meta-analysis was to investigate the efficacy and safety of total knee arthroplasty (TKA) considering seven different surgical approaches. Four databases (PubMed, Cochrane Library, EMBASE, Web of Science) were searched for clinical randomized controlled trials (RCTs) involving TKA with different surgical approaches. STATA 14.0 was used to construct network maps and publication bias graphs and conduct inconsistency tests, network meta-analyses, and surface under the cumulative ranking (SUCRA) calculations. A total of 51 RCTs involving 4061 patients and 4179 knees from 18 countries were included. Among the seven surgical approaches, the midvastus approach (MV) was the top choice to reduce tourniquet use time, the subvastus approach (SV) had the shortest operation time, the mini-midvastus approach (Mini-SV) was associated with the least amount of time to achieve straight leg raise (SLR) after surgery, the mini-medial parapatellar approach (Mini-MP) reduced postoperative pain effects, and the medial parapatellar approach (MP) was the best approach to improve range of motion (ROM). Excluding the quadriceps-sparing approach (QS), which was not compared, the use of the mini-midvastus (Mini-MV) may shorten the hospital stay. There were no significant differences in blood loss, postoperative complications, American Knee Society Score (AKSS) objective, or AKSS functional between the seven surgical approaches (P > 0.05).

Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated With Better Outcomes Than Hyaluronic Acid and Saline in Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To perform a network meta-analysis to evaluate clinical efficacy and treatment-related adverse events (AEs) of intra-articular hyaluronic acid (HA), leukocyte-poor platelet-rich plasma (LP-PRP), leukocyte-rich platelet-rich plasma (LR-PRP), bone marrow mesenchymal stem cells (BM-MSCs), adipose mesenchymal stem cells (AD-MSCs), and saline (placebo) during 6 and 12 months of follow-up. METHODS: Six databases were searched for randomized controlled trials. Outcome assessment included the visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscore, WOMAC score, International Knee Documentation Committee (IKDC) subjective score, and treatment-related AEs. Main inclusion criteria were at least one of the aforementioned outcome measurements, a minimum follow-up period of 5 months, and >80% patient follow-up. Treatments combined with the use of other operations or drugs were excluded. RESULTS: Forty-three studies meeting the eligibility criteria were included. At 6 months, VAS scores and WOMAC pain subscores showed that AD-MSCs were the best treatment option (surface under the cumulative ranking curve [SUCRA] = 96.7%, SUCRA = 85.3%, respectively). According to WOMAC scores and subjective IKDC scores, LP-PRP was the most effective treatment (SUCRA = 86.0%, SUCRA = 80.5%, respectively). At 12 months, only AD-MSCs were associated with improved VAS scores compared with the placebo (weighted mean difference [WMD] = -20.93, 95% credibility interval [CrI], -41.71 to -0.78). Both LP-PRP and AD-MSCs were more beneficial than the placebo for improving WOMAC pain subscores (WMD = -30.08; 95% CrI, -53.59 to -6.25; WMD = -34.85; 95% CrI, -68.03 to -4.86, respectively). For WOMAC scores, LP-PRP and LR-PRP were significantly associated with improved WOMAC scores compared with the placebo after sensitivity analysis was performed (WMD = -35.26; 95% CrI, -64.99 to -6.01; WMD = -38.69; 95% CrI, -76.21 to -2.76). LP-PRP exhibited relatively better efficacy in improving subjective IKDC scores than the placebo (WMD = 13.67; 95% CrI, 4.05-23.39). Regarding safety, all treatments except for LP-PRP (relative risk = 1.83; 95% CrI, 0.89-4.64) increased treatment-related AEs compared with the placebo. CONCLUSIONS: Based on the results of current research findings, during 6 months of follow-up, AD-MSCs relieved pain the best; LP-PRP was most effective for functional improvement. During the 12-month follow-up, both AD-MSCs and LP-PRP showed potential clinical pain relief effects; functional improvement was achieved with LP-PRP. Unfortunately, AD-MSC/LP-PRP functional comparisons were only based on WOMAC scores due to missing IKDC scores. BM-MSCs seem to have potentially beneficial effects, but the wide credibility interval makes it impossible to draw a well-supported conclusion. HA viscosupplementation clinical efficacy was lower than that of biological agents during follow-up, which may be related to the properties of the drugs. Considering the evaluation of treatment-related AEs, LP-PRP is the most advisable choice; although the AEs of these treatments are not serious, they may affect treatment compliance and satisfaction. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

The clinical efficacy of leukocyte-poor platelet-rich plasma in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of platelet-rich plasma (PRP) in the arthroscopic treatment of rotator cuff injury has been reported in the literature. However, conclusions have been inconsistent and more often related to differences in the types of PRP used. Therefore, to minimize these differences, we performed a meta-analysis of only studies investigating leukocyte-poor PRP to evaluate whether PRP promotes and improves the effects of arthroscopic rotator cuff repair. METHODS: A comprehensive search of the PubMed, Embase, and Cochrane Library databases was conducted to evaluate the efficacy of leukocyte-poor PRP in arthroscopic rotator cuff repair. The available data were extracted, and the methodologic quality of the included studies was evaluated by the Cochrane risk-of-bias assessment tool. RESULTS: In total, 10 randomized controlled trials involving 742 patients were included. The results of the meta-analysis showed that treatment with leukocyte-poor PRP performed better than the control treatment in relieving postoperative pain in the short-term (mean difference [MD], -0.57; 95% confidence interval [CI], -0.79 to -0.35; P < .0001) and medium- and long-term (MD, -0.18; 95% CI, -0.34 to -0.03; P = .02) follow-up groups. However, the changes in the MD in the visual analog scale score were below the minimal clinically important difference. Regarding the Constant shoulder (MD, 3.35; 95% CI, 1.68-5.02; P < .0001) and University of California, Los Angeles (MD, 1.73; 95% CI, 0.94-2.52; P < .0001) scores, statistically significant differences were found in favor of leukocyte-poor PRP over the control treatment. However, the changes in the MD in both the Constant and University of California, Los Angeles scores were below the minimal clinically important difference. Moreover, during medium- and long-term follow-up, the retear rate in the leukocyte-poor PRP group was lower than that in the control group regardless of the rotator cuff tear size (small and medium [<3 cm] [risk ratio (RR), 0.64; 95% CI, 0.43-0.97; P = .03] vs. medium and large [>3 cm] [RR, 0.51; 95% CI, 0.34-0.77; P = .001]) and surgical repair method (single-row repair [RR, 0.61; 95% CI, 0.43-0.87; P = .007] vs. double-row suture bridge repair [RR, 0.57; 95% CI, 0.38-0.84; P = .005]). CONCLUSION: According to our study, leukocyte-poor PRP can significantly reduce the postoperative retear rate in the medium and long term regardless of the tear size and the method used for rotator cuff repair. However, the use of leukocyte-poor PRP failed to show clinically meaningful effects in terms of postoperative pain and patient-reported outcomes.

Clinical Characteristics and Treatment of Spontaneous Osteonecrosis of Medial Tibial Plateau: A Retrospective Case Study.

BACKGROUND: In a small proportion of cases, spontaneous osteonecrosis of the knee (SONK) involves the medial tibial plateau (MT). Here, we introduced the clinical characteristics of spontaneous osteonecrosis of the MT and unicompartmental knee arthroplasty (UKA) as the favorable treatment for this situation based on a retrospective case study. METHODS: Patients with spontaneous osteonecrosis of the MT, confirmed by magnetic resonance imaging (MRI) at Guangdong Provincial Hospital of Chinese Medicine (China) from March 2015 to June 2016, were included as a case serial and analyzed retrospectively. All patients underwent Oxford Medial UKA. The characteristics of their lesions, corresponding treatment, and results of follow-up were presented. The lesion scores and grade were determined according to the criteria of Ficat and Arlet. RESULTS: In total, 22 patients (5 men, 17 women; mean age, 64.1 years) with spontaneous osteonecrosis of the MT were analyzed. The lesion stages assessment showed that 3 (14%) were Stage II, 10 (45%) were Stage III, 7 (32%) were Stage IV, and 2 (9%) were Stage V. In the sagittal plane, 7 (32%) were in the anterior region (MTa) and 15 (68%) were central (MTc). The lesion volume averaged 2.24 ± 0.79 cm3 (range: 1.57-3.08 cm3). Seventeen patients (77%) had Level III posterior medial meniscus root tears (MMRTs). All the patients underwent UKA. Average follow-up was 30.0 ± 6.4 months with a range of 23.0-38.0 months. The visual analog scale score was 7.78 ± 0.67 before surgery while decreased to 2.22 ± 1.09 at the final follow-up (P < 0.001). The Hospital for Special Surgery scores of pre-/post-surgery were 65.67 ± 5.45 and 84.10 ± 4.20, respectively (P < 0.001). CONCLUSIONS: SONK often occurs in the anterior and central tibial plateau due to abnormal stresses. Most of the patients had Level III posterior medial meniscus root tears. MRI is recommended for suspected cases to identify SONK at an early stage. The use of the Oxford Medial UKA for SONK of the MT is reliable both immediately and at follow-up.

Are short-stem prostheses superior to conventional stem prostheses in primary total hip arthroplasty? A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Cementless total hip arthroplasty (THA) is associated with reliable clinical results and high patient satisfaction. Short-stem prostheses (SS) were designed to achieve superior preservation of proximal bone stock and stability compared with those of conventional-stem prostheses (CS). This meta-analysis was conducted to determine the proximal bone remodelling, revision rate, Harris Hip Score, radiolucent line and maximum total point motion values of both SS and CS for primary THA. METHOD: Relevant randomised controlled trials (RCTs) involving SS and CS in primary THA were identified from electronic databases, such as EMBASE, PubMed and the Cochrane Library. RESULT: Ultimately, 12 RCTs involving 1130 patients (1387 hips) were included. The results showed that compared with CS, SS resulted in less bone mineral density (BMD) changes in Gruen zone 7 at 1 year and 2 years postoperatively (mean difference (MD)=5.11; 95% CI, 1.61, 8.61; P=0.30; and MD=4.90; 95% CI, 1.01, 8.79; P=0.17, respectively). No difference in BMD changes was found for Gruen zone 1 (MD=2.66; 95% CI, -3.31, 8.64; P<0.00001), and no differences were observed for the revision rate (relative risk (RR)=1.52; 95% CI, 0.71, 3.26; P=0.94), Harris Hip Score (MD=-0.38; 95% CI, -1.02, 0.26; P=0.89) or stem migration (MD=0.02; 95% CI, -0.07, 0.11; P=0.04). CONCLUSION: Our results suggest that compared with CS, SS may provide superior bone remodelling and similar survival rates and clinical outcomes. However, the short-term follow-up of the included studies was inadequate to determine the long-term performance of SS.

Review: Autologous blood transfusion drainage compared with no drainage in total knee arthroplasty: A meta-analysis and systematic review.

This is the first meta-analysis to assess the clinical efficiency, safety and potential advantages regarding the use of ABT drains compared with no drainage which is controversial in total knee arthroplasty (TKA).A comprehensive literature search was carried out in March 2015 using the PubMed, Embase, and Cochrane Library databases. A metaanalysis was carried out on two retrospective comparative studies (RCSs) and five randomized controlled trials (RCTs). The number of patients receiving homologous blood transfusion was the primary outcome of the meta-analysis; the secondary outcome measure was the mean drop in Hb level in comparison to the mean pre-operative HB level, the range of flexion of the knee joint, and infections of the wound after surgery. A total of 868 patients, who were included in two retrospective studies and five RCTs, were distributed into subgroups for the meta-analysis. This pooled data showed no benefit of ABT drainage compared no drainage in the homologous blood transfusion rate (13.05% and 16.91%, OR:0.73[0.47,1.13], Z=1.41, P=0.016; and 3.49% and 6.54%, OR: 0.50[0.12,2.01], Z=0.98,P=0.033,respectively in subgroups), Hb drop (Weight mean differences (WMD): 0.20[-0.28,0.68], Z=0.82, P=0.41; WMD:0.16[-0.41,0.55], Z=0.93, P=0.35, respectively), range of flexion of the knee joint (WMD:-0.82 [-3.35,1.70], Z =0.64,P=0.52)and wound infection (OR:0.25[0.61,10.20]; Z =1.28, p=0.2) after TKA surgery. Our findings do not recommend the routine use of postoperative ABT drainage in total knee arthroplasty. Well-designed RCTs with large sample sizes, longer term measures and extensive follow-up period should be performed in the future to update the findings of this study.

Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.

OBJECTIVE: To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men. PATIENTS AND METHODS: We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence. RESULTS: A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59). CONCLUSION: Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa.

Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort.

To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03-1.11) and HGPCa (OR = 1.14 95%Cl 1.09-1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60-0.72) to 0.71 (95%Cl 0.65-0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection.

Comparison between autologous blood transfusion drainage and closed-suction drainage/no drainage in total knee arthroplasty: a meta-analysis.

BACKGROUND: Autologous blood transfusion (ABT) drainage system is a new unwashed salvaged blood retransfusion system for total knee replacement (TKA). However, whether to use ABT drainage, closed-suction (CS) drainage or no drainage in TKA surgery remains controversial. This is the first meta-analysis to assess the clinical efficiency, safety and potential advantages regarding the use of ABT drains compared with closed-suction/no drainage. METHODS: PubMed, Embase, and the Cochrane Library were comprehensively searched in March 2015. Fifteen randomized controlled trials (RCTs) were identified and pooled for statistical analysis. The primary outcome evaluated was homologous blood transfusion rate. The secondary outcomes were post-operative haemoglobin on days 3-5, length of hospital stay and wound infections after TKA surgery. RESULTS: The pooled data included 1,721 patients and showed that patients in the ABT drainage group might benefit from lower blood transfusion rates (16.59 % and 37.47 %, OR: 0.28 [0.14, 0.55]; 13.05 % and 16.91 %, OR: 0.73 [0.47,1.13], respectively). Autologous blood transfusion drainage and closed-suction drainage/no drainage have similar clinical efficacy and safety with regard to post-operative haemoglobin on days 3-5, length of hospital stay and wound infections. CONCLUSIONS: Autologous blood transfusion drainage offers a safe and efficient alternative to CS/no drainage with a lower blood transfusion rate. Future large-volume high-quality RCTs with extensive follow-up will affirm and update this system review.

Influence of age on predictiveness of genetic risk score for prostate cancer in a Chinese hospital-based biopsy cohort.

BACKGROUND: We investigated whether age influences the predictiveness of genetic risk score (GRS) for prostate cancer (PCa) in a Chinese hospital-based biopsy cohort. METHODS: We included consecutive patients who underwent prostate biopsies in two tertiary centers between 2012 and 2014. GRS was calculated using 24 PCa-associated genetic variants and its predictiveness was assessed by area under curve (AUC). RESULTS: Of 1120 men tested, 724 with prostate-specific antigen (PSA) < 20 ng/ml were selected for further analysis. Patients were divided into 3 groups by age cutoffs at 60 and 70 years. GRS significantly predicted PCa for all patients (AUC: 0.561; 95% CI: 0.514-0.609) and was an independent predictor in multivariate analysis for the 60-70 year-olds (AUC: 0.612, 95% CI: 0.541-0.684), but not for patients aged < 60 years or ≥ 70 years. For PCa with Gleason score ≥ 7, GRS discriminative ability was 0.582 (95% CI=0.527-0.637) for all patients, and 0.647 (95% CI: 0.541-0.684) for the 60-70 year-old group. CONCLUSION: GRS significantly increased clinical prediction of PCa and high-grade disease in Chinese men aged 60-70 years, which implies that men in this age group would benefit most from genetic testing.

Influence of obesity on localized prostate cancer patients treated with radical prostatectomy.

This study aimed to investigate the association between different anthropometric measures of obesity and clinicopathological characteristics in Chinese patients with clinically localized prostate cancer (PCa). A total of 734 patients with clinically localized PCa who underwent radical prostatectomy (RP) were included in this study. Clinical and pathological data from each patient were collected. Anthropometric measures of abdominal adiposity were measured from T2-weighted sagittal localisation images from magnetic resonance imaging (MRI) for 413 (56.3%) patients. Patient clinical and pathological characteristics were compared across body mass index (BMI) groups. Univariable and multivariable logistic regression models were used to address the influence of the preoperative total testosterone level and anthropometric measures of obesity on pathological outcomes. In the multivariate analysis, BMI was not significantly associated with any pathological outcomes. However, the percentage of visceral adipose tissue (VAT%) was an independent predictor of a pathological Gleason score ≥8 (P<0.001), extracapsular extension (ECE; P=0.002) and seminal vesicle invasion (SVI; P=0.007). More importantly, we found that the preoperative total testosterone level was significantly correlated with the VAT% (Pearson's correlation coefficient: -0.485, P<0.001) and subcutaneous adipose tissue (SAT; Pearson's correlation coefficient: 0.413, P<0.001). In conclusion, the results of this study suggest that abdominal fat distribution, and particularly VAT%, is associated with a risk of advanced PCa. Moreover, our present study confirms a significant inverse correlation between visceral adiposity and testosterone. Further studies are warranted to elucidate the biological mechanisms underlying the relationship between abdominal adiposity and the aggressiveness of PCa.

Kinetics of testosterone recovery in clinically localized prostate cancer patients treated with radical prostatectomy and subsequent short-term adjuvant androgen deprivation therapy.

Androgen deprivation therapy (ADT) is a standard treatment for metastatic, recurrent and locally advanced prostate cancer (PCa). The aim of this study is to investigate the timing and extent of testosterone recovery in clinically localized PCa patients treated with radical prostatectomy (RP) and subsequent short-term adjuvant ADT. A total of 95 localized PCa patients underwent RP and 9-month adjuvant ADT were included in this prospective study. Serum testosterone level was measured before adjuvant ADT, at ADT cessation, and at 1, 3, 6, 9 and 12 months after cessation of ADT. A Cox proportional hazards model was used to assess variables associated with the time of testosterone normalization. The results showed that median patient age was 67 years and median testosterone level before adjuvant ADT was 361 (230-905) ng dl(-1). All patients finished 9-month adjuvant ADT and achieved castrate testosterone level. At 3 months after ADT cessation, testosterone recovered to supracastrate level in 97.9% patients and to normal level in 36.9% patients. The percentage of patients who recovered to normal testosterone level increased to 66.3%, 86.3% and 92.6% at 6, 9 and 12 months, respectively. Cox regression model found that higher baseline testosterone level (≥ 300 ng dl(-1)) was the only variable associated with a shorter time to testosterone normalization (hazard ratio: 1.98; P = 0.012). In conclusion, in most patients, testosterone recovered to supracastrate level at 3 months and to normal level at 12 months after 9-month adjuvant ADT cessation. Patients with higher baseline testosterone level need shorter time of testosterone normalization.

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy.

This study aims to evaluate the potential value of patient characteristics in predicting overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time (PSADT), baseline haemoglobin (Hb) concentration, alkaline phosphatase (ALP) concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT <46.3 days and baseline ALP ≥ 110 IU l(-1), all patients were divided into three risk groups: low-risk group (no risk factors), intermediate-risk group (one risk factor) and high-risk group (two risk factors). Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months (95% CI: 23.8-32.2), 21.0 months (95% CI: 18.9-23.1) and 11.0 months (95% CI: 7.6-14.4), respectively (P<0.001). In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

Anti-proliferative effects, cell cycle G2/M phase arrest and blocking of chromosome segregation by probimane and MST-16 in human tumor cell lines.

BACKGROUND: Anticancer bisdioxopiperazines, including ICRF-154, razoxane (Raz, ICRF-159) and ICRF-193, are a family of anticancer agents developed in the UK, especially targeting metastases of neoplasms. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Cytotoxic activities and mechanisms of Raz (+)-steroisomer (ICRF-187, dexrazoxane), Pro and MST-16 against tumor cells were evaluated by MTT colorimetry, flow cytometry and karyotyping. RESULTS: Pro was cytotoxic to human tumor cell lines in vitro (IC50<50 microM for 48 h). Four human tumor cell lines (SCG-7901, K562, A549 and HL60) were susceptible to Pro at low inhibitory concentrations (IC50 values < 10 microM for 48 h). Although the IC50 against HeLa cell line of vincristine (VCR, 4.56 microM), doxorubicin (Dox, 1.12 microM) and 5-fluoruouracil (5-Fu, 0.232 microM) are lower than Pro (5.12 microM), ICRF-187 (129 microM) and MST-16 (26.4 microM), VCR, Dox and 5-Fu shows a low dose-related - high cytotoxic activity. Time-response studies showed that the cytotoxic effects of Pro are increased for 3 days in human tumor cells, whereas VCR, Dox and 5-Fu showed decreased cytotoxic action after 24 h. Cell cycle G2/M phase arrest and chromosome segregation blocking by Pro and MST-16 were noted. Although there was similar effects of Pro and MST-16 on chromosome segregation blocking action and cell cycle G2/M phase arrest at 1- 4 microM, cytotoxicity of Pro against tumor cells was higher than that of MST-16 in vitro by a factor of 3- 10 folds. Our data show that Pro may be more effective against lung cancer and leukemia while ICRF-187 and MST-16 shows similar IC50 values only against leukemia. CONCLUSION: It suggests that Pro has a wider spectrum of cytotoxic effects against human tumor cells than other bisdioxopiperazines, especially against solid tumors, and with a single cytotoxic pathway of Pro and MST-16 affecting chromosome segregation and leading also to cell G2/ M phase arrests, which finally reduces cell division rates. Pro may be more potent than MST-16 in cytotoxicity. High dose- and time- responses of Pro, when compared with VCR, 5-Fu and Dox, were seen that suggest a selectivity of Pro against tumor growth. Compounds of bisdioxopiperazines family may keep up their cytotoxic effects longer than many other anticancer drugs.

[Inhibition of mixture of lucid garoderma and lucid garoderma spore on tumor cell in vitro and in vivo].

BACKGROUND & OBJECTIVE: Garoderma lucidum (lingzhi) is a kind of medicinal fungus with a long history in China as a valuable tonic folk remedy. It has been demonstrated that lingzhi had growth inhibition effect against implanted mice tumors. It is generally regarded that anti-tumor action of lingzhi is induced by promoting function of immune system. Recently, we found that mixture of lucid garoderma and lucid garoderma spore (MLGLGS) could markedly inhibit activities of topoisomerase I and II, so this study was designed to further evaluate the inhibition effects of MLGLGS on tumor cell in vitro and in vivo. METHODS: Inhibition of MLGLGS on tumor cell were detected by MTT or SRB method in vitro study and by human tumor nude mice xenografts as models in vivo study. RESULTS: Among them, the IC50 values were lower than 2 mg/ml in P388, U-937, and HL-60 leukemias, and lower than 4 mg/ml in 2 human lung cancer and 2 human gastric cancer cells, respectively. In vivo study revealed that MLGLGS had certain experimental therapeutic action on human lung tumor xenograft LAX-83 (dose: 1 g/kg, inhibitory rate: 49.47%) and gastric xenograft SGC-7901 (dose: 2 g/kg, inhibitory rate: 43.09%). CONCLUSION: MLGLGS has inhibitory action on tumor cell at high concentration and high dosage.