The Use of Exome Genotyping to Predict Pathological Gleason Score Upgrade after Radical Prostatectomy in Low-Risk Prostate Cancer Patients

Background

Active surveillance (AS) is a promising option for patients with low-risk prostate cancer (PCa), however current criteria could not select the patients correctly, many patients who fulfilled recent AS criteria experienced pathological Gleason score upgrade (PGU) after radical prostatectomy (RP). In this study, we aimed to develop an accurate model for predicting PGU among low-risk PCa patients by using exome genotyping.

Methods

We genotyped 242,221 single nucleotide polymorphisms (SNP)s on a custom HumanExome BeadChip v1.0 (Illuminam Inc.) in blood DNA from 257 low risk PCa patients (PSA <10 ng/ml, biopsy Gleason score (GS) ≤6 and clinical stage ≤T2a) who underwent radical prostatectomy. Genetic data were analyzed using an unconditional logistic regression to calculate an odds ratio as an estimate of relative risk of PGU, which defined pathologic GS above 7. Among them, we selected persistent SNPs after multiple testing using FDR method, and we compared accuracies from the multivariate logistic model incorporating clinical factors between included and excluded selected SNP information.

Results

After analysis of exome genotyping, 15 SNPs were significant to predict PGU in low risk PCa patients. Among them, one SNP – rs33999879 remained significant after multiple testing. When a multivariate model incorporating factors in Epstein definition – PSA density, biopsy GS, positive core number, tumor per core ratio and age was devised for the prediction of PGU, the predictive accuracy of the multivariate model was 78.4% (95%CI: 0.726–0.834). By addition the factor of rs33999879 in aforementioned multivariate model, the predictive accuracy was 82.9%, which was significantly increased (p = 0.0196).

Conclusion

The rs33999879 SNP is a predictor for PGU. The addition of genetic information from the exome sequencing effectively enhanced the predictive accuracy of the multivariate model to establish suitable active surveillance criteria.     

Pathological Features of Localized Prostate Cancer in China: A Contemporary Analysis of Radical Prostatectomy Specimens

There has been a rapid increase in the incidence of prostate cancer in China, especially in areas with boosted economic development. In this study, we analyzed the pathological features of a contemporary series of radical prostatectomy cases. A total of 230 consecutive, whole-mounted radical prostatectomy specimens collected from 2012 to 2014 were reviewed. The median age of the patients was 68 years, and 64.3% of patients presented with prostate specific antigen alone. Pathological examination indicated that a high proportion (77.4%) of patients had intermediate- or high-risk disease according to the Cancer of the Prostate Risk Assessment Post-Surgical score. After surgery, only 28 patients met the criteria for active surveillance (organ-confined Gleason ≥6 disease). The Prostate Cancer Research International Active Surveillance criteria achieved a sensitivity of 57.1% and a specificity of 98.0% for identifying candidates. The probability of Gleason score upgrading was 24.8% in the entire group and 59.0% in biopsy-confirmed Gleason ≥6 disease. The predominant tumor was located in the transition zone in 14.8% of cases, while only three patients (1.3%) had a predominant tumor located in the anterior region. Patients with transition zone-predominant tumor were likely to have been referred with urinary symptoms and high prostate specific antigen levels. The results of this study highlight the contemporary pathological features of localized prostate cancer in urban China. There was an increased trend towards asymptomatic cases, though most patients had intermediate- or high-risk disease and were suitable for definitive treatment. The low prevalence of dominant cancer in the anterior region may reflect race-based pathological differences.     

CT引导下经皮肺穿刺并发症的高危因素分析

目的:探讨CT引导下经皮肤肺穿刺并发症发生的高危因素.方法:回顾分析93例因肺部肿块行CT引导下经皮肤肺穿刺患者,对其性别、吸烟史、病灶大小、肿块类型、组织学分型、穿刺时体位、进针位置、进针角度和进针深度等因素与穿刺后并发症的相关性进行分析.结果:单因素分析显示吸烟史、病灶大小、肿块类型和进针深度在有并发症患者和无并发症的患者之间存在显著性差异(P＜0.05),多因素分析显示病灶大小、肿块类型和进针深度在两组患者间存在显著性差异(P＜0.05).结论:病灶大小、肿块类型和进针深度为CT引导下经皮肺穿刺并发症出现的高危因素.     

Association between Seminal Vesicle Invasion and Prostate Cancer Detection Location after Transrectal Systemic Biopsy among Men Who Underwent Radical Prostatectomy

Background

Our hypothesis is that the location of the seminal vesicles near the base of the prostate, the more positive cores are detected in the base, the greater the risk of seminal vesicle invasion. Therefore we investigate the clinical outcomes of base dominant prostate cancer (BDPC) in transrectal ultrasound (TRUS) -guided biopsies compared with anteromiddle dominant prostate cancer (AMPC).

Methods

From November 2003 to June 2014, a total of 990 intermediate and high risk prostate cancer (PCa) patients who underwent radical prostatectomy (RP) were enrolled and stratified into two groups according to proportion of positive cores–BDPC group had ≥ 33.3% ratio of positive cores from the prostate base among all positive cores and AMPC group < 33.3% in systemic biopsy. Between two groups, we compared the rate of pathologic outcomes and biochemical recurrence (BCR). We performed multivariate logistic regression model to confirm the significance of BDPC to seminal vesicle invasion (SVI) and Cox proportional hazard analysis to BCR.

Results

Among these 990 PCa patients, the 487 patients in BDPC group had more advanced clinical stage (p<0.001), a higher biopsy GS (p = 0.002), and a higher rate of extracapsular extension (ECE), SVI and BCR (all p<0.001) than AMPC group. The patients in BDPC group had poor BCR free survival rate via Kaplan-meier analysis (p<0.001). The ratio of the base positive cores was a significant predictor to SVI in multivariate analysis (p < 0.001) and significant predictor of BCR in multivariate Cox proportional analysis (hazard ratio: 1.466, p = 0.004).

Conclusions

BDPC in TRUS-guided prostate biopsies was significantly associated with SVI and BCR after adjusting for other clinical factors. Therefore, BDPC should be considered to be a more aggressive tumor despite an otherwise similar cancer profile.     

Clinical Validation of the 2005 ISUP Gleason Grading System in a Cohort of Intermediate and High Risk Men Undergoing Radical Prostatectomy

In 2005, the International Society of Urological Pathology (ISUP) introduced several modifications to the original Gleason system that were intended to enhance the prognostic power of Gleason score (GS). The objective of this study was to clinically validate the 2005 ISUP Gleason grading system for its ability to detect metastasis. We queried our institutional RP database for men with NCCN clinically localized intermediate to high-risk disease undergoing radical prostatectomy (RP) between 1992 and 2010 with no additional treatment until the time of metastatic progression. A case-cohort design was utilized. A total of 333 available RP samples were re-reviewed and GS was reassigned per the 2005 ISUP Gleason system. Cumulative incidence of metastasis was 0%, 8.4%, 24.5% and 44.4% among specimens that were downgraded, unchanged, had one point GS increase and two point GS increase, respectively. The hazard ratio for metastasis raised in GS 8 and 9 compared to GS 7 from 2.77 and 5.91 to 3.49 and 9.31, respectively. The survival c-index of GS increased from 0.70 to 0.80 when samples were re-graded at 5 years post RP. The c-index of the reassigned GS was higher than the original GS (0.77 vs 0.64) for predicting PCSM at 10 years post RP. The regraded GS improved the prediction of metastasis and PCSM. This validates the updated Gleason grading system using an unambiguous clinical endpoint and highlights the need for reassignment of Gleason grading according to 2005 ISUP system when considering comparisons of novel biomarkers to clinicopathological variables in archival cohorts.     

Preoperative Glycemic Control Status as a Significant Predictor of Biochemical Recurrence in Prostate Cancer Patients after Radical Prostatectomy

Background

The effect of diabetes mellitus (DM) on prostate cancer (PCa) outcome remains controversial. Thus, we investigated the association of DM history, glycemic control, and metformin use with oncologic outcomes after radical prostatectomy (RP).

Methods

We reviewed the records of 746 contemporary patients who had hemoglobin A1c (HbA1c) measured within the 6 months preceding RP. The associations between clinical variables and risk of adverse pathological features and biochemical recurrence (BCR) were tested using a multivariate logistic regression and multiple Cox-proportional hazards model, respectively. BCR was defined as prostatic specific antigen (PSA) > 0.2 ng/mL in 2 consecutive tests.

Results

There were no significant differences in the rates of adverse pathologic features and BCR-free survival between patients with (n = 209) and without (n = 537) a history of DM diagnosis (all p > 0.05). In multivariate analyses, high HbA1c level (≥ 6.5%) was significantly related with high pathologic Gleason score (≥ 4+3; odds ratio [OR] 1.704, p = 0.019) and BCR-free survival (OR 1.853, p = 0.007). Metformin use was not associated with BCR-free survival (OR 0.662, p = 0.125).

Conclusions

Poor glycemic control was significantly associated with BCR after RP. Meanwhile, metformin use was not associated with biochemical outcome after RP. Further investigation would be needed to identify exact mechanism underlying the impact of glycemic control on PCa treatment outcome.     

Risk Factors of Pneumothorax after Endobronchial Ultrasound-Guided Transbronchial Biopsy for Peripheral Lung Lesions

Background

The risk of endobronchial ultrasound-guided transbronchial biopsy-related pneumothorax is a major concern and warrants further studies. The aim of our study was to estimate the risk of pneumothorax after this procedure and identify its risk factors.

Methods

From 2007 to 2011, 399 patients who underwent endobronchial ultrasound-guided transbronchial biopsy for peripheral lung lesions were included in this study. The variables analyzed included patient factors, lesion factors and procedure factors. Multivariate logistic regression analysis was used to identify independent risk factors for pneumothorax.

Results

The incidence of pneumothorax was 3.3% (13/399). Chest tube placement was required for 31% (4/13) of pneumothoraces. Independent risk factors for pneumothorax included pulmonary emphysema (OR, 55.09; 95% CI, 9.37–324.03; p<0.001) and probe position adjacent to the lesion (OR, 17.01; 95% CI, 2.85–101.64; p = 0.002). The number of biopsy specimens, age, sex, history of prior lung surgery and lesion size, location and character did not influence the risk of pneumothorax in our analyses.

Conclusions

The risk of pneumothorax after endobronchial ultrasound-guided transbronchial biopsy is low. To further reduce the risk of pneumothorax, every effort should be made to advance the endobronchial ultrasound probe into the bronchus where it is imaged within the target lesion before embarking on transbronchial biopsy.     

Povidone Iodine Rectal Preparation at Time of Prostate Needle Biopsy is a Simple and Reproducible Means to Reduce Risk of Procedural Infection

Single institution and population-based studies highlight that infectious complications following transrectal ultrasound guided prostate needle biopsy (TRUS PNB) are increasing. Such infections are largely attributable to quinolone resistant microorganisms which colonize the rectal vault and are translocated into the bloodstream during the biopsy procedure. A povidone iodine rectal preparation (PIRP) at time of biopsy is a simple, reproducible method to reduce rectal microorganism colony counts and therefore resultant infections following TRUS PNB.All patients are administered three days of oral antibiotic therapy prior to biopsy. The PIRP technique involves initially positioning the patient in the standard manner for a TRUS PNB. Following digital rectal examination, 15 ml of a 10% solution of commercially available povidone iodine is mixed with 5 ml of 1% lidocaine jelly to create slurry. A 4 cm x 4 cm sterile gauze is soaked in this slurry and then inserted into the rectal vault for 2 min after which it is removed. Thereafter, a disposable cotton gynecologic swab is used to paint both the perianal area and the rectal vault to a distance of 3 cm from the anus. The povidone iodine solution is then allowed to dry for 2 - 3 min prior to proceeding with standard transrectal ultrasonography and subsequent biopsy.This PIRP technique has been in practice at our institution since March of 2012 with an associated reduction of post-biopsy infections from 4.3% to 0.6% (p = 0.02). The principal advantage of this prophylaxis regimen is its simplicity and reproducibility with use of an easily available, inexpensive agent to reduce infections. Furthermore, the technique avoids exposing patients to additional systemic antibiotics with potential further propagation of multi-drug resistant organisms. Usage of PIRP at TRUS PNB, however, is not applicable for patients with iodine or shellfish allergies.     

达芬奇机器人辅助腹腔镜下前列腺癌根治术的临床疗效及术后短期尿控恢复的影响因素分析

摘要 目的：观察达芬奇机器人辅助腹腔镜下前列腺癌根治术（RALRP）的临床疗效,并分析术后尿控恢复的影响因素。方法：选取2020年3月~2023年1月期间山东第一医科大学附属省立医院收治的腹腔镜下前列腺癌根治术182例作为研究对象,根据手术方式的不同将患者分为A组（n=81,传统腹腔镜前列腺癌根治术）和B组（n=101,RALRP）。记录两组手术时间、术后1个月的尿控率、术中出血量、住院时间、尿管拔除时间、引流管拔除时间、术后并发症的发生率。针对RALRP患者,多因素Logistic回归分析术后短期尿控恢复的影响因素。结果：B组手术时间、引流管拔除时间、尿管拔除时间、住院时间短于A组,术中出血量少于A组（P<0.05）。B组术后1个月的尿控率高于A组（P<0.05）。B组的术后并发症的发生率低于A组（P<0.05）。多因素Logistic回归分析结果显示,糖尿病、经尿道前列腺电切术（TURP）史是术后尿控恢复的危险因素,而规律提肛锻炼、保留神经血管束（NVB）是术后尿控恢复的保护因素（P<0.05）。结论：RALRP治疗前列腺癌患者,可缩短手术时间、引流管拔除时间、尿管拔除时间、住院时间,减少术中出血量,同时还可提高术后1个月的尿控率,降低并发症发生率。此外,糖尿病、规律提肛锻炼、保留NVB、TURP史等均是RALRP患者术后短期尿控恢复的影响因素,值得引起重视。