Hypertriglyceridemia Is a Potential Preoperative Predictor for Biochemical Recurrence after Radical Prostatectomy

Objectives

Many previous studies have suggested that the outcome of prostate cancer (PCa) may be closely related to abnormal lipid metabolism. Therefore, in this study, we evaluated the preoperative lipid profiles of patients with clinically localized prostate cancer (PCa) who underwent radical prostatectomy (RP), with particular emphasis on the relationship between these profiles and biochemical recurrence (BCR).

Patients and Methods

We evaluated 715 consecutive men with clinically localized PCa who underwent RP at our institution between January 2011 and December 2013. We defined hypertriglyceridemia as a fasting serum triglyceride (TG) level greater than 200 mg/dL. We used the Kaplan—Meier method to predict BCR-free survival and applied the log-rank test to determine the statistical significance between survival curves. Cox proportional hazard ratio (HR) models were used to identify the significant predictors of BCR according to clinicopathological variables.

Results

Of 663 patients who underwent RP for clinically localized PCa, 66 (10.0%) showed BCR during a median follow-up period of 21 months. Patients without BCR had higher levels of serum TG, and patients with hypertriglyceridemia were significantly more likely to achieve BCR-free survival in the Kaplan—Meier analysis (log-rank test, P = 0.009). In the multivariable analysis, the presence of hypertriglyceridemia (HR 0.22), pathologic Gleason score (≥8; HR 2.85), pathologic T stage (≥pT3; HR 3.44), and a positive surgical margin (HR, 2.39) were still significant BCR predictors.

Conclusions

We found that preoperative hypertriglyceridemia was associated with a lower risk of BCR after RP in patients with clinically localized PCa. Our results could help to clarify the currently conflicting evidence on the relationship between serum lipid profiles, particularly the presence of hypertriglyceridemia, and the risk of BCR in PC a patients after surgery.     

Prostate Stem Cell Antigen Expression in Radical Prostatectomy Specimens Predicts Early Biochemical Recurrence in Patients with High Risk Prostate Cancer Receiving Neoadjuvant Hormonal Therapy

We aimed to identify tissue biomarkers that predict early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PC), toward the goal of increasing the benefits of neoadjuvant hormonal therapy (NHT). In 2005–2012, prostatectomy specimens were collected from 134 PC patients who had received NHT and radical prostatectomy. The expression of 13 tissue biomarkers was assessed in the specimens via immunohistochemistry. Time to BCR and factors predictive of BCR were determined by using the Cox proportional hazards model. During the follow-up period (median, 57.5 months), 67 (50.0%) patients experienced BCR. Four (3.0%) patients were tumor-free in the final pathology assessment, and 101 (75.4%) had negative resection margins. Prostate stem cell antigen (PSCA) was the only significant prognostic tissue biomarker of BCR [hazard ratio (HR), 2.58; 95% confidence interval (CI), 1.06–6.27; p = 0.037] in a multivariable analysis adjusted by the clinicopathological variables that also significantly predicted BCR; these were seminal vesicle invasion (HR, 2.39; 95% CI, 1.32–4.34), initial prostate serum antigen level (HR 1.01; 95% CI, 1.001–1.020), prostate size (HR, 0.93; 95% CI, 0.90–0.97), and the Gleason score of preoperative biopsies (HR, 1.34; 95% CI, 1.01–1.79). We suggest that PSCA is a useful tissue marker for predicting BCR in patients with high risk PC receiving NHT and radical prostatectomy.     

前列腺癌根治术治疗不同分级前列腺癌患者的临床研究

目的:探究前列腺癌根治术在不同危险度前列腺癌患者中治疗的临床效果,为临床前列腺癌患者的治疗提供依据。方法:选择2008年1月~2015年12月期间我院94例前列腺癌患者为研究对象,根据D'Amico评分将其分为高危、中危及低危三组,收集患者基线资料、术后随访资料,并比较三组手术并发症;采用Kaplan-Meier分析法计算三组患者生存率,并采用Log-rank检验比较不同危险组的生存率。结果:高危组患者进行开放性手术人数多于中危组和低危组,且中危组多于低危组,差异具有统计学意义(P0.05);高危组患者术前Gleason评分和PAS水平高于中危组和低危组,且中危组高于低危组,差异具有统计学意义(P0.05);术后5年高危组患者完全控尿率显著低于中危组和低危组(P0.05);三组患者间5年无生化复发率比较无统计学意义(P0.05)。结论:前列腺癌根治术治疗高危前列腺患者较中、低危患者疗效较差,但仍可达到较好的疗效,可在临床推广使用。     

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.     

Co-Occurring Gland Angularity in Localized Subgraphs: Predicting Biochemical Recurrence in Intermediate-Risk Prostate Cancer Patients

Quantitative histomorphometry (QH) refers to the application of advanced computational image analysis to reproducibly describe disease appearance on digitized histopathology images. QH thus could serve as an important complementary tool for pathologists in interrogating and interpreting cancer morphology and malignancy. In the US, annually, over 60,000 prostate cancer patients undergo radical prostatectomy treatment. Around 10,000 of these men experience biochemical recurrence within 5 years of surgery, a marker for local or distant disease recurrence. The ability to predict the risk of biochemical recurrence soon after surgery could allow for adjuvant therapies to be prescribed as necessary to improve long term treatment outcomes. The underlying hypothesis with our approach, co-occurring gland angularity (CGA), is that in benign or less aggressive prostate cancer, gland orientations within local neighborhoods are similar to each other but are more chaotically arranged in aggressive disease. By modeling the extent of the disorder, we can differentiate surgically removed prostate tissue sections from (a) benign and malignant regions and (b) more and less aggressive prostate cancer. For a cohort of 40 intermediate-risk (mostly Gleason sum 7) surgically cured prostate cancer patients where half suffered biochemical recurrence, the CGA features were able to predict biochemical recurrence with 73% accuracy. Additionally, for 80 regions of interest chosen from the 40 studies, corresponding to both normal and cancerous cases, the CGA features yielded a 99% accuracy. CGAs were shown to be statistically signicantly () better at predicting BCR compared to state-of-the-art QH methods and postoperative prostate cancer nomograms.     

Salvage Radiotherapy after Radical Prostatectomy: Prediction of Biochemical Outcomes

Introduction

A significant proportion of patients undergoing salvage radiotherapy (RT) for biochemical recurrence (BCR) following radical prostatectomy (RP) may again experience BCR after salvage RT. Thus, we evaluated the clinical significances of different parameters on the biochemical outcome of RT in salvage setting.

Methods

We reviewed the records of 212 patients who underwent salvage RT between November 2003 and December 2012 for BCR following primary RP. BCR-free survivals after salvage RT were estimated using the Kaplan–Meier method. Cox proportional hazard regression models were used to evaluate the impacts of clinicopathologic parameters on BCR following salvage RT.

Results

The overall median follow-up duration was 63.5 months. The BCR-free survival rate after salvage RT was 58.2% at 5 years. Multivariate analysis showed that a pre-RT prostate-specific antigen (PSA) level of ≤0.5 ng/mL, a pre-RT PSA doubling time (PSADT) of >4.5 months, concomitant androgen deprivation therapy (ADT) with salvage RT, and a positive surgical margin were independent predictors of favorable biochemical outcomes after salvage RT (hazard ratios [HR] = 3.012, 1.132, 2.000, and 1.805, respectively, p = less than 0.001, 0.013, 0.005, and 0.036, respectively). In the early (pre-RT PSA ≤0.5 ng/mL) salvage RT setting, concomitant ADT administration was also shown to be significantly associated with higher risk of BCR-free survival following salvage RT (HR = 2.611, p = 0.038).

Conclusion

Lower pre-RT PSA value, longer PSADT before salvage RT, concomitant ADT administration, and a positive surgical margin were significant predictors of favorable biochemical outcomes following salvage RT performed for BCR after primary RP.     

Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy

Purpose

Clinicopathologic features and biochemical recurrence are sensitive, but not specific, predictors of metastatic disease and lethal prostate cancer. We hypothesize that a genomic expression signature detected in the primary tumor represents true biological potential of aggressive disease and provides improved prediction of early prostate cancer metastasis.

Methods

A nested case-control design was used to select 639 patients from the Mayo Clinic tumor registry who underwent radical prostatectomy between 1987 and 2001. A genomic classifier (GC) was developed by modeling differential RNA expression using 1.4 million feature high-density expression arrays of men enriched for rising PSA after prostatectomy, including 213 who experienced early clinical metastasis after biochemical recurrence. A training set was used to develop a random forest classifier of 22 markers to predict for cases - men with early clinical metastasis after rising PSA. Performance of GC was compared to prognostic factors such as Gleason score and previous gene expression signatures in a withheld validation set.

Results

Expression profiles were generated from 545 unique patient samples, with median follow-up of 16.9 years. GC achieved an area under the receiver operating characteristic curve of 0.75 (0.67–0.83) in validation, outperforming clinical variables and gene signatures. GC was the only significant prognostic factor in multivariable analyses. Within Gleason score groups, cases with high GC scores experienced earlier death from prostate cancer and reduced overall survival. The markers in the classifier were found to be associated with a number of key biological processes in prostate cancer metastatic disease progression.

Conclusion

A genomic classifier was developed and validated in a large patient cohort enriched with prostate cancer metastasis patients and a rising PSA that went on to experience metastatic disease. This early metastasis prediction model based on genomic expression in the primary tumor may be useful for identification of aggressive prostate cancer.     

术前中性粒细胞绝对值/淋巴细胞比值联合血清瘦素、睾酮对前列腺癌根治术后生化复发的评估价值

摘要 目的：探讨术前中性粒细胞绝对值/淋巴细胞比值（NLR）联合血清瘦素、睾酮对前列腺癌（PCa）根治术后生化复发的评估价值。方法：选取2018年1月～2020年1月于我院接受根治性切除术治疗的82例PCa患者。术前均检测NLR、血清瘦素、睾酮水平。术后对所有患者均进行2年随访观察,按照是否发生生化复发分为复发组（n=34）以及无复发组（n=48）。比较两组NLR、血清瘦素、睾酮水平差异。收集患者临床资料,采用多因素Logistic回归分析PCa根治术后生化复发的影响因素。采用受试者工作特征（ROC）曲线分析NLR以及血清瘦素、睾酮预测PCa根治术后生化复发的评估价值。结果：复发组术前NLR以及瘦素水平均高于无复发组（P＜0.05）,而睾酮水平低于无复发组（P＜0.05）。复发组术前前列腺特异抗原（PSA）≥10 ng/mL、TNM分期T2期人数占比以及Gleason评分均高于无复发组（P＜0.05）。多因素Logistic回归分析显示,术前PSA≥10 ng/mL、TNM分期T2期、Gleason评分较高、术前NLR较高、瘦素水平较高、睾酮水平较低是PCa根治术后生化复发的危险因素（P＜0.05）。ROC曲线分析显示,联合检测术前NLR、血清瘦素、睾酮水平预测PCa根治术后生化复发的ROC曲线下面积为0.897,高于三项指标单独检测的0.678、0.712、0.733。结论：PCa根治术后生化复发受术前PSA、NLR、血清瘦素、睾酮水平、TNM分期、Gleason评分等因素影响,术前NLR联合血清瘦素、睾酮对PCa根治术后生化复发的预测价值较高。     

Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging

Purpose

The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting and Data System (PIRADS) score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy.

Methods

A total of 223 patients who fulfilled the criteria for “Prostate Cancer Research International: Active Surveillance”, were included. Mp–1.5 Tesla MRI examination staging with endorectal coil was performed at least 6–8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE), unfavorable prognosis (occurrence of both upgrading and ECE), large tumor volume (≥0.5ml), and seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves and Decision Curve Analyses (DCA) were performed for models with and without inclusion of PIRADS score.

Results

Multivariate analysis demonstrated the association of PIRADS score with upgrading (P<0.0001), ECE (P<0.0001), unfavorable prognosis (P<0.0001), and large tumor volume (P = 0.002). ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI.

Conclusions

mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.     

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.     

Transient but Significant Visual Field Defects after Robot-Assisted Laparoscopic Radical Prostatectomy in Deep Trendelenburg Position

Background

Robot-assisted laparoscopic radical prostatectomy (RALP) is a minimally invasive surgical procedure for prostate cancer. During RALP, the patient must be in a steep Trendelenburg (head-down) position, which leads to a significant increase in intraocular pressure (IOP). The association of RALP with visual field sensitivity, however, has not been prospectively studied. The purpose of this study was to evaluate prospectively the visual field, retinal nerve fiber layer (RNFL) thickness, and optic disc morphology in 50 normal eyes of 25 male patients that underwent RALP.

Methods

The subjects were 25 males among 33 consecutive patients who underwent uneventful RALP under general anesthesia in our hospital. Visual field tests using the Humphrey visual field analyzer 30-2 SITA-standard program were performed before, 7 days after, and 1-3 months after RALP. IOP was measured before, during, and after RALP; and ophthalmologic examinations, including slit-lamp, fundus examination, and optical coherence tomography (OCT), were scheduled before and 7 days after surgery.

Results

IOP was significantly increased during RALP up to 29.4 mmHg (P<0.01). Postoperative local visual field defects were detected in 7 eyes of 7 subjects dominantly in the lower hemifield without abnormal findings in the optic nerve head or retina, and the visual field recovered to normal within 3 months after surgery. General factors associated with RALP, IOP, RNFL thickness, or optic disc parameters did not differ significantly between eyes with and without postoperative visual field defects, and parameters of OCT measurements were not altered after surgery.

Conclusion

Transient but significant unilateral visual field defects were found in 28% of the subjects examined. The probable cause are the increased IOP and altered perfusion during surgery and ophthalmologic examinations are therefore suggested before and after RALP.     

Epidural Analgesia during Open Radical Prostatectomy Does Not Improve Long-Term Cancer-Related Outcome: A Retrospective Study in Patients with Advanced Prostate Cancer

Background

A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking.

Methods

In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death.

Results

The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001).

Conclusions

General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.     

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.     

Radiation Therapy after Radical Prostatectomy for Prostate Cancer: Evaluation of Complications and Influence of Radiation Timing on Outcomes in a Large,Population-Based Cohort

PurposeTo evaluate the influence of timing of salvage and adjuvant radiation therapy on outcomes after prostatectomy for prostate cancer.MethodsUsing the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified prostate cancer patients diagnosed during 1995–2007 who had one or more adverse pathological features after prostatectomy. The final cohort of 6,137 eligible patients included men who received prostatectomy alone (n = 4,509) or with adjuvant (n = 894) or salvage (n = 734) radiation therapy. Primary outcomes were genitourinary, gastrointestinal, and erectile dysfunction events and survival after treatment(s).ResultsRadiation therapy after prostatectomy was associated with higher rates of gastrointestinal and genitourinary events, but not erectile dysfunction. In adjusted models, earlier treatment with adjuvant radiation therapy was not associated with increased rates of genitourinary or erectile dysfunction events compared to delayed salvage radiation therapy. Early adjuvant radiation therapy was associated with lower rates of gastrointestinal events that salvage radiation therapy, with hazard ratios of 0.80 (95% CI, 0.67–0.95) for procedure-defined and 0.70 (95% CI, 0.59, 0.83) for diagnosis-defined events. There was no significant difference between ART and non-ART groups (SRT or RP alone) for overall survival (HR = 1.13 95% CI = (0.96, 1.34) p = 0.148).ConclusionsRadiation therapy after prostatectomy is associated with increased rates of gastrointestinal and genitourinary events. However, earlier radiation therapy is not associated with higher rates of gastrointestinal, genitourinary or sexual events. These findings oppose the conventional belief that delaying radiation therapy reduces the risk of radiation-related complications.     

进展期胃癌根治术后早期复发的影响因素分析

目的:分析影响进展期胃癌根治术后早期复发的相关因素,为临床干预工作提供依据。方法:选取2009年6月至2012年7月本院收治的195例进展期胃癌患者作为研究对象,所有患者均接受胃癌根治术治疗,根据患者术后1年内复发与否将上述患者分为早期复发组(n=103)与对照组(n=92)。先后采用x2检验、非条件Logistic回归分析确定影响进展期胃癌根治术后早期复发的独立相关因素。结果:单因素分析发现,两组患者的肿瘤直径、Borrmann分型、Lauren分型、T分期、N分期、TNM分期、新辅助化疗、术后化疗等指标相比差异有统计学意义(P0.05),两组患者的性别、年龄、体质指数、肿瘤位置、分化程度、手术方式、腹腔镜手术等指标相比差异无统计学意义(P0.05)。非条件Logistic回归发现,N分期、TNM分期是影响进展期胃癌根治术后早期复发的独立危险因素,而新辅助化疗是独立保护因素。结论:进展期胃癌的N分期、TNM分期是其术后早期复发的独立危险因素,采取而新辅助化疗可降低进展期胃癌根治术后早期复发率。     

Identification and Validation of a Multigene Predictor of Recurrence in Primary Laryngeal Cancer

Purpose

Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. This study attempts to identify and independently validate gene expression models, prognostic of disease-free survival (DFS) in operable laryngeal cancer.

Materials and Methods

Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 66 patients with laryngeal cancer treated locally with surgery. We applied Cox regression proportional hazards modeling to identify multigene predictors of recurrence. Gene models were then validated in two independent cohorts of 54 and 187 patients (fresh-frozen and formalin-fixed tissue validation sets, respectively).

Results

We focused on genes univariately associated with DFS (p<0.01) in the training set. Among several models comprising different numbers of genes, a 30-probe set model demonstrated optimal performance in both the training (log-rank, p<0.001) and 1^st validation (p = 0.010) sets. Specifically, in the 1^st validation set, median DFS as predicted by the 30-probe set model, was 34 and 80 months for high- and low-risk patients, respectively. Hazard ratio (HR) for recurrence in the high-risk group was 3.87 (95% CI 1.28–11.73, Wald''s p = 0.017). Testing the expression of selected genes from the above model in the 2^nd validation set, with qPCR, revealed significant associations of single markers, such as ACE2, FLOT1 and PRKD1, with patient DFS. High PRKD1 remained an unfavorable prognostic marker upon multivariate analysis (HR = 2.00, 95% CI 1.28–3.14, p = 0.002) along with positive nodal status.

Conclusions

We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. It seems worthy to prospectively validate PRKD1 expression as a laryngeal cancer prognostic marker, for routine clinical applications.     

CD44 and PTGS2 Methylation are Independent Prognostic Markers for Biochemical Recurrence Among Prostate Cancer Patients with Clinically Localized Disease

Up to 30% of men with clinically localized disease who receive radical prostatectomy develop a biochemical recurrence. Gene methylation in tumor tissue may distinguish men with aggressive cancer. This study evaluated methylation of GSTP1, RARβ2, CD44 and PTGS2 with biochemical recurrence among 60 patients who underwent radical prostatectomy using logistic regression and Kaplan Meier time to event analysis. Methylation of GSTP1 and RARβ2 was not associated with recurrence, however, CD44 and PTGS2 methylation were significant predictors. In multivariate models adjusting for Gleason grade, methylation profile of CD44 and PTGS2 combined was an independent predictor of biochemical recurrence (associated with 9-fold increased risk). In addition, Kaplan Meier analysis showed CD44 and PTGS2 methylation was associated with shorter time to recurrence. CD44 and PTGS2 methylation may predict biochemical recurrence in prostate cancer patients undergoing radical prostatectomy and if validated in larger studies, may identify patients with aggressive cancer.     

腹腔镜前列腺癌根治术治疗前列腺癌的疗效及对患者血清激素水平的影响

目的:分析腹腔镜前列腺癌根治术治疗前列腺癌的疗效及其对患者血清激素水平的影响。方法:选择86例前列腺癌患者为研究对象并按抽签法随机分为对照组与观察组,每组43例。对照组行开放前列腺癌根治术治疗,观察组采用腹腔镜前列腺癌根治术,比较两组手术指标,手术前后血清促卵泡激素(FSH)、黄体生成素(LH)、双氢睾酮(DHT)、游离睾酮(FT)、总睾酮(T)、前列腺特异性抗原(T-PSA、F-PSA),CD3~+、CD4~+、CD8~+、CD4~+/CD8~+水平的变化及术后并发症的发生情况。结果:观察组手术时间明显长于对照组,失血量、肠功能恢复时间、住院时间、疼痛评分均明显低于或短于对照组(P0.05)。两组治疗前后血清FSH、LH、DHT、FT、T、T-PSA、F-PSA比较差异均无统计学意义(P0.05)。观察组CD3~+、CD4~+、CD4~+/CD8~+显著高于对照组(P0.05),CD8~+低于对照组(P0.05)。观察组术后并发症的发生率明显低于对照组(P0.05)。结论:腹腔镜前列腺癌根治术可起到与开放手术相似的控瘤效果,提高血清雄激素水平和患者的免疫功能,控制肿瘤进展,且安全性更高。     

根治性前列腺切除术后大体病理较术前穿刺病理升级的危险因素分析

目的:前列腺穿刺病理Gleason评分(GS)和根治性前列腺切除术后病理Gleason评分经常出现差异.本文主要研究肿瘤病理升级的可能影响因素.方法:选择1999-01至2007-11在本院行前列腺穿刺活检确诊并行根治性前列腺切除术的95例前列腺癌患者,考察的临床资料包括患者确诊时的年龄,前列腺特异性抗原水平(PSA),前列腺体积(PV),前列腺特异性抗原密度(PSAD),术前是否接受新辅助内分泌治疗(NHT),穿刺病理GS,手术后病理GS及肿瘤体积(TIV).使用t-检验或卡方检验比较不用组别之间的变量,分别使用单因素和多因素Logistical回归分析引起GS升级的相关因素.结果:患者的平均年龄是67岁,平均PSA水平为24.3 ng/ml,平均前列腺体积是33.1ml.将前列腺体积分为≤25ml(25例),25-50ml(59例),≥50ml(11例)三组,将穿刺病理GS分为4-5(13例),6(35例),7(32例),8-10(15例)四组.前列腺体积较大组(≥50m1)比体积较小组(≤25ml,25-50m1)的肿瘤升级比率明显较低(48% vs 24%,18%,p＜0.05).穿刺病理GS较高组(8-10)比较低组(4-5,6,7)的肿瘤升级比率明显减低(46% vs 34%,25%,13%,p＜0.05).多因素Logistic回归分析显示,PV、穿刺GS及内分泌治疗与病理升级呈负相关(p＜0.05),而肿瘤体积及PSAD与其呈正相关(p＜0.05).结论:较大的前列腺体积,较高的穿刺病理GS,接受内分泌治疗以及较低的PSAD均可降低其肿瘤升级的可能.泌尿外科医师在决定由穿刺活检确诊的前列腺癌患者的治疗方案时应想到上述结论.