前列腺癌骨转移的疼痛管理

在老年男性中前列腺癌发病率日益增高,晚期骨转移可产生顽固性骨痛,严重影响治疗效果和患者生活质量。对前列腺癌骨转移患者的疼痛管理需要从抗肿瘤治疗和镇痛治疗两方面入手,并防止长期治疗过程中的并发症,全程给予心理治疗。本文从前列腺癌骨转移的治疗入手,对疼痛管理现状作一综述。     

412例前列腺癌患者血清前列腺特异抗原游离与总量比值及骨转移的分析

目的分析前列腺癌(Pca)患者血清前列腺特异抗原游离(FPSA)与总(TPSA)比值(F/T)的结果及骨转移的特点。方法对412例Pca患者术前血清TPSA、FPSA含量和F/T比值及99mTC-MDPECT全身骨骼显像分为二组进行分析。结果无骨转移组为25.5%(105/412例);有骨转移组为74.5%(307/412)。307例Pca骨转移组患者,共有2907个转移病灶,97.5%(2834/2907)显示为"热区"病灶,2.5%显示为"冷区"病灶(73/2907)。有Pca骨转移组血清TPSA、FPSA和F/T分别是97.9±59.4μg/L,10.2±8.1μg/L和0.09±0.04;无ca骨转移组29.6%(16/54),分别是24.8±23.0μg/L,4.4±3.4μg/L和0.12±0.05;二组有显著性差异(P0.01)。TPSA与骨转移程度呈负相关(r=-0.487,P0.05)。当PSA10μg/L,骨转移率为2.6%;当PSA 10～20μg/L,为10.5%;PSA 21～50μg/L,为52.6%;PSA 51～100μg/L,为92.7%;PSA100μg/L,为100%。F/T比值与骨转移程度呈负相关(r=-0.641,P0.05)。F/T0.15者,有84%的Pca患者有骨转移;F/T0.10者,100%的患者有骨转移。结论血清F/T比值小于0.15者,必要时行ECT全身骨骼显像。骨转移的好发部位依次是盆骨、椎骨和肋骨。     

转移性激素敏感性前列腺癌研究进展

在过去的七十多年,转移性激素敏感性前列腺癌（mHSPC）的标准治疗一直都是单独使用雄激素剥夺治疗（ADT）。直到近几年研究显示,多西他赛（DOC）联合ADT可显著提高mHSPC患者的生存率,引起了mHSPC治疗标准的改变。近期研究证实,ADT结合醋酸阿比特龙（AA）和泼尼松（P）同样可以改善mHSPC的生存率。因此,本文将结合近期临床试验,综述mHSPC治疗的新进展。     

血清PSA和BALP测定在前列腺癌骨显像诊断中的应用

目的：探讨血PSA和BALP的测定在前列腺癌骨显像诊断中的应用。方法：对96例前列腺癌患者的核素骨显像结果、血清PSA和BALP结果进行回顾性研究。结果：①血清PSA和BALP的值随着骨转移分期的增高而逐步升高,且差异显著（P〈0.01）;②血清PSA和BALP与骨转移的数目呈正相关,相关系数（r）分别为0.582（P〈0.01）和0.768（P〈0.01）;③血清PSA〉20ng/ml时,骨转移的阳性率为65.4%,血清PSA〈20ng/ml时,骨转移的阴性预测值为92.6%;血清BALP〉20u/L时,骨转移的阳性率为58.9%时,骨转移的阴性预测值为76.5%;当血清PSA〈20ng/ml同时BALP〈20u/L时,骨转移的阴性预测值为100%。结论：血清PSA和BALP测定在前列腺癌骨显像诊断中具有重要的应用价值。     

Metastatic Progression of Pancreatic Cancer: Changes in Antioxidant Enzymes and Cell Growth

Pancreatic cancer has a dismal prognosis due to the fact that patients present late when metastatic disease is already present. Previous studies have demonstrated that pancreatic cancer cells have decreased levels of MnSOD, which correlates well with increased rates of tumor cell proliferation. Recently, we have found that nude mice injected with MIA PaCa-2 human pancreatic cancer cells in the flank occasionally develop ascites and intra-abdominal metastatic deposits. Mice that developed ascites were sacrificed and the ascites cultured. Necropsy demonstrated metastatic tumors in the retroperitoneum, which were excised, digested, and cultured. Western blots, enzyme activity and enzyme activity gels were performed for manganese superoxide dismutase (MnSOD), copper/zinc (CuZnSOD), catalase, and glutathione peroxidase (GPx) in the ascites cell line, metastatic tumor cell line, MIA PaCa-2 primary pancreatic cancer cell line, and the Capan-1, a metastatic pancreatic cancer cell line. Cell growth, plating efficiency, growth in soft agar and growth in nude mice were determined in the ascites, metastatic tumor, and MIA PaCa-2 cell lines. MnSOD, CuZnSOD, and GPx protein and activity were increased in the ascites, metastatic tumor, and Capan-1 cell lines compared to MIA PaCa-2. The ascites and metastatic tumor cell lines had decreased cell growth, plating efficiency, and growth in soft agar, but the ascites cell line had increased cell growth in 4 and 1% O₂ concentrations in vitro and more rapid growth in vivo. Metastatic disease is associated with changes in the content and activity of antioxidant enzymes with an associated change in growth characteristics depending on the O₂ concentrations.     

Effectiveness of Adding Docetaxel to Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer in Korean Real-World Practice

PurposeEvidence in favor of adding docetaxel in treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has led to docetaxel in conjunction with androgen deprivation therapy (ADT) as standard therapy. The aim of this study was to examine the effectiveness of docetaxel with ADT for Korean patients with mHSPC in real-world practice.Materials and MethodsA retrospective cohort study was performed at six Korean hospitals for patients with mHSPC treated with docetaxel plus ADT. Patients were treated every 3 weeks for up to six cycles with 75 mg/m² of docetaxel. The primary endpoint was time to castration resistant prostate cancer (CRPC).ResultsThis study included 46 eligible patients from June 2016 to February 2021. Median age was 68.5 years (range, 52–84) and all patients present with de novo M1 with high-volume disease. The median prostate-specific antigen (PSA) level at ADT initiation was 205.4 (7.7–1933) ng/mL, and time from ADT to docetaxel was 2.4 months (0–5.3). All six planned cycles of docetaxel were delivered in 36 patients (78%), 7 patients (15%) discontinued treatment due to adverse events, and 3 patients (7%) discontinued due to progression. At the time of the analysis, CRPC had developed in 34 patients (74%), and the median time to CRPC was 18.0 (95% confidence interval, 14.1–21.9) months. PSA <0.2 ng/mL was achieved in 11 patients (24%) after 6 months of ADT and in 10 patients (22%) after 12 months. At last follow-up, 35 patients (76%) were alive; the median overall survival was not reached.ConclusionThe effect of docetaxel combined with ADT for Korean patients with mHSPC is comparable with prior results in Western studies.     

血清PSA与PAP检测在前列腺癌诊断中的应用价值

目的：探讨血清前列腺特异性抗原（PSA）及酸性磷酸酶（PAP）对前列腺癌患者的辅助诊断价值。方法：采用免疫放射分析法（IRMA）对98例前列腺癌患者,45例前列腺良性疾患及40例正常健康人进行血清PSA,PAP测定。结果：前列腺癌组PSA,PAP水平均显著高于前列腺良性疾患组及正常对照组（P＜0．01）,PSA对前列腺癌的灵敏性为93．9％）,特异性为93．3％,PAP对前列腺癌的灵敏性为71．％,特异性为91．1％。结论：血清PSA与PAP检测对前列腺癌的早期诊断有较高的临床价值,是临床分期, 效监测及判断预后的重要参考指标。     

Interaction of TLK1 and AKTIP as a Potential Regulator of AKT Activation in Castration-Resistant Prostate Cancer Progression

Prostate cancer (PCa) progression is characterized by the emergence of resistance to androgen deprivation therapy (ADT). AKT/PKB has been directly implicated in PCa progression, often due to the loss of PTEN and activation of PI3K>PDK1>AKT signaling. However, the regulatory network of AKT remains incompletely defined. Here, we describe the functional significance of AKTIP in PCa cell growth. AKTIP, identified in an interactome analysis as a substrate of TLK1B (that itself is elevated following ADT), enhances the association of AKT with PDK1 and its phosphorylation at T308 and S473. The interaction between TLK1 and AKTIP led to AKTIP phosphorylation at T22 and S237. The inactivation of TLK1 led to reduced AKT phosphorylation, which was potentiated with AKTIP knockdown. The TLK1 inhibitor J54 inhibited the growth of the LNCaP cells attributed to reduced AKT activation. However, LNCaP cells that expressed constitutively active, membrane-enriched Myr-AKT (which is expected to be active, even in the absence of AKTIP) were also growth-inhibited with J54. This suggested that other pathways (like TLK1>NEK1>YAP) regulating proliferation are also suppressed and can mediate growth inhibition, despite compensation by Myr-AKT. Nonetheless, further investigation of the potential role of TLK1>AKTIP>AKT in suppressing apoptosis, and conversely its reversal with J54, is warranted.     

PSA、cPSA检测和骨显像对前列腺癌早期骨转移的诊断价值

目的:分析前列腺特异性抗原(PSA)、复合前列腺特异性抗原(cPSA)联检和核素全身骨显像对前列腺癌早期骨转移的诊断价值.方法:选择152例患者(其中74例为临床确诊的前列腺癌患者,78例为良性前列腺疾病患者),全部进行血清PSA、cPSA检测,并同时对74例临床确诊的前列腺癌患者进行核素全身骨显像.另选择正常健康查体男性90例检测血清PSA、cPSA结果作为对照组.并计算cPSA/PSA比值.结果:前列腺癌患者血清PSA、cPSA检测结果及cPSA/PSA比值显著高于良性前列腺疾病患者及正常健康男性.其中,骨转移阳性显像组血清PSA、cPSA水平及cPSA/PSA比值显著高于非骨转移显像组,检测存在显著性差异(P＜0.05).结论:当PSA＞20μg/L、cPSA＞10μg/L、cPSA/PSA＞0.80时,发生前列腺癌骨转移的可能性较大,应常规做核素全身骨显像,可早期、全面地发现前列腺癌骨转移.     

Psychological and Screening Profiles of First-Degree Relatives of Prostate Cancer Patients

The purpose of the present study was to systematically compare the psychological and screening profiles of first-degree relatives (FDRs) of prostate cancer patients versus non-FDRs. FDRs (n = 56) and non-FDRs (n = 100), recruited through prostate cancer index cases and newspaper advertisements, completed questionnaires via mail. FDRs reported feeling at greater risk for prostate cancer, estimated that they were at higher average lifetime risk for the disease, agreed more strongly that prostate cancer is inherited, and that less can be done to prevent the development of the disease. Increased age, but not FDR status, was associated with more frequent screening behavior. Taken together, the results indicate that FDRs are characterized by greater perceived vulnerability to prostate cancer and lower expectations about disease prevention. Yet, they are no more likely to be screened than non-FDRs. These findings underscore the importance of developing, and evaluating, evidence-based health communication protocols to promote screening adherence among at-risk patients.     

Prognostic Factors Influencing Mortality in Cancer Patients with Neutropenia and Bacteremia

 The purpose of this study was to identify risk factors for mortality in neutropenic patients with cancer and bacteremia. A consecutive sample of 438 neutropenic patients (granulocyte count <0.5×10⁹/l) with cancer and bacteremia was studied to identify the clinical characteristics associated with mortality at the onset of bacteremia. The mean age of the subjects was 48 years (range, 15–87 years). Most cases of bacteremia (77%) were hospital-acquired and occurred in patients with acute leukemia (48%). Gram-positive organisms caused 233 (53%) episodes of bacteremia, gram-negative organisms caused 151 (34%) episodes, and 48 (11%) episodes were polymicrobial. The overall mortality within 30 days of the onset of bacteremia was 24.4%. The variables found to be independently associated with increased mortality using logistic regression techniques were as follows: shock at the onset of bacteremia (OR, 10; 95% CI, 4.2–23.8), pneumonia (OR,4.4; 95% CI, 1.9–10), uncontrolled cancer (OR,4.3; 95 %CI, 1.5–12.7), and absence of prophylaxis with norfloxacin (OR,2.4; 95%CI, 1.3–4.5). The prognostic factors ascertained in this study may help to identify those patients at higher risk of death. Medical intervention addressing some of these factors may improve the outcome of bacteremia in neutropenic patients with cancer.     

Prognostic Value of Prostaglandin-endoperoxide Synthase 2 Polymorphisms in Prostate Cancer Recurrence after Radical Prostatectomy

Backgroud: Increasing evidence suggests the involvement of chronic inflammation in the progression of prostate cancer, and prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase-2, catalyzes the rate-limiting steps of the pathway. We hypothesized that genetic variants of PTGS2 can influence the outcome of prostate cancer patients.Methods: We genotyped five haplotype-tagging single-nucleotide polymorphisms (SNPs) to detect common genetic variations across the PTGS2 region in 458 prostate cancer patients treated with radical prostatectomy.Results: One SNP, rs4648302, was associated with disease recurrence. Five-year recurrence-free survival rate increased according to the number of variant alleles inherited (55.6%, 70.7%, and 100.0% for patients with different genotypes; P = 0.037), and the effect was maintained in multivariable analysis. Public dataset analyses also suggested that PTGS2 expression was correlated with prostate cancer prognosis.Conclusion: Our results indicated that PTGS2 could be a potential prognostic marker to improve the prediction of disease recurrence in prostate cancer patients.     

f/t-PSA比值对t-PSA在正常范围内的Pca患者早期诊断的临床意义

目的:研究前列腺特异性抗原游离与总量(f/t-PSA)比值对t-PSA在正常范围内前列腺癌(Pca)早期诊断的价值.方法:采用电化学发光免疫分析技术检测150例正常健康男性,106例t-PSA>4.0μg/L及22例t-PSA<4.0μg/L的Pca患者血清t-PSA和f-PSA并求出f/t-PSA比值,然后进行统计学...     

Depression Impacts the Course of Recovery in Patients with Acute Low-Back Pain

Little is known about the course of recovery of acute low back pain (LBP) patients as a function of depression. In a prospective study, 286 acute LBP patients were assessed at baseline and followed up over 6 months. Recovery was defined as improvement in the Oswestry Disability Index (ODI). Repeated-measures analysis of covariance was employed with ODI as repeated factor, age, sex, and body mass index as covariates, depression and all other potential prognostic factors as between-subject factors. Of study participants, 18% were classified as depressive (>33 points on the Zung Self-Rating Depression Scale). Of 286 participants, 135 were lost to follow-up. In the longitudinal sample of 151 patients the course of recovery was slower in depressive patients. Depression was associated with LBP especially after 6 weeks and should therefore be included in screening instruments for acute LBP patients to identify those at risk of delayed recovery at an early stage.     

Perlecan Knockdown in Metastatic Prostate Cancer Cells Reduces Heparin-binding Growth Factor Responses in vitro and Tumor Growth in vivo

Perlecan (Pln) is a major heparan sulfate proteoglycan (HSPG) of extracellular matrices and bone marrow stroma. Pln, via glycosaminoglycans in domains I and V, acts as a co-receptor for delivery of heparin binding growth factors (HBGFs) that support cancer growth and vascularization. Specifically, glycosaminoglycans bind HBGFs and activate HBGF receptors, including those for FGF-2 and VEGF-A. The contribution of Pln to prostate cancer growth was tested using a ribozyme approach to knockdown Pln expression levels. Transfection into the androgen-independent, bone targeted prostate cancer line, C4-2B, and efficient stable knockdown of Pln was demonstrated by quantitative PCR, immunohistochemistry and immunoblotting. Three individually isolated subclones with 75–80% knockdown in Pln mRNA, protein expression and secretion into ECM were used to study in vitro growth responses to FGF-2 and VEGF-A. While cells with normal Pln levels responded to both HBGFs, knockdown cells responded poorly. All lines responded to serum growth factors and IGF-I. Anchorage-independent growth assays showed reduced colony size and cohesiveness by all Pln deficient subclones compared to parental C4-2B cells. In vivo effects of Pln knockdown were measured by inoculating knockdown and control ribozyme transfected cell lines into athymic mice. A reduced growth rate, smaller tumor size, diminished vascularization and failure to elevate serum PSA characterized mice bearing Pln knockdown C4-2B cells. Poor vascularization correlated with reduced levels of VEGF-A secreted by Pln knockdown lines. We conclude that Pln is an essential ECM component involved in growth responses of metastatic prostate cancer cells to HBGFs deposited in local and metastatic microenvironment.     

The Prevalence of Severe Pain,its Etiopathological Characteristics and Treatment Profile of Patients Referred to A Tertiary Cancer Care Pain Clinic

Pain is the most feared symptom in cancer. About 52–77% patients suffer pain despite World Health Organization (WHO) recommendations. Out of total, one-third patients suffer moderate to severe pain. This study was undertaken to determine the prevalence, etiopathogenesis and characteristics of severe pain and treatment response among pain clinic referrals in a busy tertiary care cancer center. This study found a high prevalence (31.5%) of severe pain. A total of 251 patients who had complete pain data were analyzed for etiopathological characteristics and treatment response. Head and neck cancer contributed the highest prevalence among all regions. Oncologists prescribed non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol with or without mild opioids to 14% patients and pain clinic physicians prescribed opioids and overall 63.7% patients had a better response after pain clinic referral, even then, morphine was not prescribed to many deserving patients. Doctors need pain education about opioids to remove any fear of prescribing opioids in presence of severe pain.     

加巴喷丁联合盐酸羟考酮对晚期癌因性疼痛患者的效果及对其疼痛介质的影响

目的 分析晚期癌因性疼痛患者治疗中加巴喷丁联合盐酸羟考酮的效果、对疼痛介质的影响。方法 选取76例晚期癌因性疼痛患者随机分成参照组37例和观察组39例。参照组给予盐酸羟考酮治疗,观察组给予加巴喷丁联合盐酸羟考酮治疗。比较用药前后两组疼痛评分及疼痛介质水平。结果 用药前两组疼痛数字量表（NRS）评分,5-羟色胺（5-HT）、多巴胺（DA）、去甲肾上腺素（NE）水平比较,差异无统计学意义（P＞0.05）;用药后观察组NRS评分、5-HT、DA、NE分别为（2.30±0.75）分、（682.05±85.93）ng/L、（13254.51±2546.01）ng/L、（468.63±52.74）ng/L,低于参照组的（4.21±0.63）分、（821.17±71.02）ng/L、（15862.01±2634.51）ng/L、（497.30±53.59）ng/L,且两组各项指标均较治疗前降低,差异均有统计学意义（P＜0.05）。结论 晚期癌因性疼痛患者治疗中加巴喷丁联合盐酸羟考酮可减轻疼痛、降低疼痛介质水平。     

Cognitive Behavioral Therapy Techniques for Distress and Pain in Breast Cancer Patients: A Meta-Analysis

This meta-analysis is the first to examine cognitive behavioral therapy (CBT) techniques for distress and pain specifically in breast cancer patients. Twenty studies that used CBT techniques with breast cancer patients were identified and effect sizes were calculated to determine (1) whether CBT techniques have a significant impact on distress and pain, (2) if individual or group treatments are more effective, (3) whether severity of cancer diagnosis influences distress and pain outcomes, and, (4) if there is a relationship between CBT technique efficacy for distress and pain. Results revealed effect sizes of d = 0.31 for distress (p < 0.05) and .49 for pain (p < 0.05), indicating that 62 and 69% of breast cancer patients in the CBT techniques treatment groups had less distress and less pain (respectively) relative to the control groups. Studies with individual treatment approaches had significantly larger effects compared to studies that employed group approaches for distress (p = 0.04), but not for pain (p > 0.05). There were no significant differences in effects between those with or without metastases (p > 0.05). The correlation between effect sizes for distress and pain was not significant (p = 0.07). Overall, the results support the use of CBT techniques administered individually to manage distress and pain in breast cancer patients. However, more well-designed studies are needed.     

雄激素受体异常激活与激素非依赖性前列腺癌的形成机制

前列腺癌进展的晚期常转变为激素非依赖性 ,包括雄激素受体拮抗剂在内的多种细胞外因子能够刺激其增殖。雄激素受体基因突变、多种途径引起的异常磷酸化激活和共激活物的调节失控等是激素非依赖性前列腺癌形成的主要促成因素。以雄激素受体为靶标可能成为晚期前列腺癌的有效治疗途径。