Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients

In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdr1 gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan–Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further larger studies (validation set as opposed to the training set used in the present study). Due to the complexity of events in cancer, the evaluation of a combination of prognostic factors should be of value to clinicians to make a more objective estimate of the prognosis of individual breast cancer patients.     

右美托咪定联合舒芬太尼术后镇痛对卵巢癌根治术患者细胞免疫功能和炎症应激反应的影响

摘要 目的：探讨右美托咪定联合舒芬太尼术后镇痛对卵巢癌根治术患者细胞免疫功能和炎症应激反应的影响。方法：根据随机数字表法将2020年2月至2023年2月期间陕西省肿瘤医院120例择期行卵巢癌根治术的患者分为对照组（n=60，术后镇痛药物选用舒芬太尼）和研究组（n=60，术后镇痛药物选用右美托咪定联合舒芬太尼）。对比两组镇静（Ramsay镇静评分）、细胞免疫功能[CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺]、镇痛情况[视觉模拟评分法（VAS）]、不良反应、炎症应激反应[白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、皮质醇（Cor）和去甲肾上腺素（NE）]变化情况。结果：与对照组术后6 h、12 h、24 h、48 h 相比，研究组同时间点VAS评分更低，Ramsay镇静评分更高（P<0.05）。与对照组术后24 h相比，研究组同时间点CD3⁺、CD4⁺、CD4⁺/CD8⁺更高，CD8⁺更低（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。与对照组术后24 h相比，研究组同时间点IL-6、TNF-α、Cor、NE更低（P<0.05）。结论：右美托咪定联合舒芬太尼用于卵巢癌根治术患者术后镇痛，镇静、镇痛效果显著，同时还可减轻机体炎症应激反应，缓解免疫抑制。     

地塞米松联合昂丹司琼对胸腔镜术后病人静脉自控镇痛PONV的影响

目的:观察地塞米松联合昂丹司琼对胸腔镜术后病人自控静脉镇痛(PCIA)相关恶心呕吐的防治效果。方法:120例ASAⅠ~Ⅱ接受胸腔镜手术的患者,随机分为两组:地塞米松与昂丹司琼联合组(OD组)和昂丹司琼组(O组)。OD组患者在诱导时给予10 mg地塞米松,O组给予等量生理盐水,在手术结束前10分钟时,患者均给予静脉注射8 mg昂丹司琼,术后均行病人自控静脉镇痛(PCIA:生理盐水将2μg/kg舒芬太尼和8 mg昂丹司琼稀释到100 m L)。观察术后48小时内的恶心呕吐的发生率及严重程度。结果:在术后恶心呕吐整体发生率上OD组(53.3%)与O组(60%),差异无统计学意义(P0.05),但在重度PONV发生率上OD组(10%)要显著低于O组(26.7%),差异有统计学意义(P0.05)。结论:地塞米松联合昂丹司琼能有效地降低胸腔镜手术后以舒芬太尼为主的病人自控静脉镇痛所致严重恶心呕吐的发生率。     

柱状经腹会阴直肠癌切除术后并发症分析及对策

目的:探讨分析柱状经腹会阴直肠癌切除术术后并发症发生的可能原因,并提出解决对策。方法:回顾分析我院自2010年1月至2014年5月采用柱状经腹会阴直肠癌切除术的68例直肠癌患者的临床资料。记录并分析患者发生术后并发症的情况,探讨发生的可能原因及可行对策。结果:68例患者术后出现并发症共9例,占13.2%。切口并发症4例,术后排尿困难2例,术后骶尾部疼痛3例。结论:柱状经腹会阴直肠癌切除术因为手术切除范围大,术后并发症亦随之凸显。但通过精细的术中解剖、重叠缝合腹膜关闭盆底、骶前通畅引流、合理掌握尿管拔管时机等手段,可有效降低术后并发症的发生。     

几丁糖和透明质酸钠对宫腔粘连的防治效果及并发症的影响

目的:探讨几丁糖和透明质酸钠对宫腔防粘连效果及并发症的影响。方法:回顾性分析本院2013年9月~2014年9月收治的150例人工流产患者的临床资料,均实施常规无痛人流手术,按照术前处理方式的不同分为空白对照组(50例)和几丁糖组(50例)、透明质酸钠组(50例)。术后随访6个月,观察两组的阴道流血持续时间和月经复潮时间,以及术后第14 d子宫内膜厚度和术后粘连发生情况、并发症发生情况,并进行比较。结果:术后几丁糖组和透明质酸钠组的阴道流血持续时间和月经复潮时间,以及术后第14 d天子宫内膜厚度和术后粘连发生情况、并发症发生率与空白对照组之间均存在统计学差异,各项指标均显著优于空白对照组,P0.05,但几丁糖组和透明质酸钠组二组间比较差异无统计学意义,P0.05。结论:对人工流产患者予以几丁糖和透明质酸钠处理均可以获得良好的临床效果,有效减少术后粘连以及各种并发症的出现。     

老年患者全身麻醉术后认知功能障碍的影响因素分析

目的：探讨分析老年非心脏手术患者全身麻醉术后认知功能障碍(POCD)的影响因素。方法：选择我院80 例老年行非心脏手 术患者,所有患者均给予全身麻醉手术,于术前及术后1、3 d 分别使用简易智能状态检查法（MMSE）评估患者认知功能,同时记 录行不同手术种类患者POCD 发生率并分析其年龄、麻醉时间、术中出血量、并发症情况及受教育程度等指标与POCD发生的相 关性。结果：80 例患者POCD发生率为30.0%,且不同种类手术中的发生率比较差异无统计学意义（P＞0.05）;POCD 组术后1d MMSE 评分为较术前分明显下降,比较差异具有统计学意义（P＜0.05);POCD组术后3 d及非POCD 组术后1、3 d MMSE 评分与 术前比较差异无统计学意义（P＞0.05）;Logistic 回归分析显示,患者年龄、文化程度、麻醉持续时间≥ 3 h、术中出血量≥ 350 mL及 合并高血压与POCD的发生具有显著相关性（P＜0.05）。结论：行全麻手术患者术后POCD 发病率较高,且患者高龄、文化程度 低、高血压合并症及麻醉持续时间长等是引起POCD发生的重要影响因素。     

Toxicity of a serotonin-derived neuromelanin

Postoperative Cognitive Dysfunction (POCD) is associated with increased mortality in the elderly and may occur from lipid peroxidation in aging. We previously showed that sevoflurane sequesters acrolein, which promotes the formation of a novel species of a putative neuromelanin. The current study examined the properties of this serotonin-derived melanoid (SDM). The interaction of SDM with unilamellar vesicles (ULVs) was examined using lipid membrane probes. Vesicle disruption was investigated by leakage of dye from calcein-loaded ULVs. We observed that SDM decreased diphenyl-hexatriene fluorescence anisotropy and increased the temperature-dependent change in anisotropy. SDM changed the absorbance of merocyanin-bound ULVs. SDM increased detergent-mediated calcein leakage. SDM structure was dramatically altered upon interaction with ULVs. We also observed that SDM enhanced detergent-mediated leakage of loaded ULVs, suggesting that SDM may be neurotoxic. We propose that inhalational agents, which sequester acrolein, may promote the production of certain species of neuromelanin that depletes local serotonin and enhances neuronal vulnerability.     

Postoperative radiotherapy in prostate cancer: Analysis of prognostic factors in a series of 282 patients

Aim

To assess the outcomes of patients treated with postoperative RT in relation to the possible prognostic factors.

Background

Postoperative radiotherapy (RT) has been proved to reduce the risk of biochemical recurrence in high-risk prostate cancer patients. Baseline prostate specific antigen (PSA), pathological Gleason score (GS), positive surgical margins, nodal status and seminal vesicle invasion are independent predictors of biochemical relapse.

Materials and methods

The clinical records of 282 patients who underwent postoperative RT were retrospectively reviewed. The prognostic value of postoperative PSA, preoperative risk class, nodal status, pathological GS, margins status, and administration of hormonal therapy (HT) was analyzed.

Results

Postoperative RT was delivered with a median dose to the prostatic fossa of 66 Gy (range 50–72) in 1.8–2 Gy/fraction. Median follow-up was 23.1 months (range 6–119). Five-year actuarial biochemical disease-free survival (bDFS) and overall survival rates were 76% and 95%, respectively. Higher bDFS was found for patients with postoperative PSA <0.02 ng/ml (p = 0.03), low preoperative risk class (p = 0.01), pN0 (p = 0.003), GS 4–6 (p = 0.0006), no androgen deprivation therapy (p = 0.02), and irrespective of surgical margin status (p = 0.10). Multivariate analysis showed that postoperative PSA and Gleason score had a significant impact on bDFS (p = 0.039 and p = 0.05, respectively).

Conclusions

Postoperative RT with a dose of 66 Gy offers an acceptable toxicity and an optimal disease control after radical prostatectomy in patients with different risk features. A postoperative PSA >0.02 ng/ml could be considered as a prognostic factor and a tool to select patients at risk for progression.     

Intratumoral expression of IL-17 and its prognostic role in gastric adenocarcinoma patients

In this study, we characterized the intratumoral expression of IL-17 and CD8(+) TILs in gastric adenocarcinoma patients after resection and determined the correlation between the survival probability of gastric adenocarcinoma patients and the expression of IL-17 in tumor. Expression of IL-17 and CD8 was assessed by immunohistochemistry, and the prognostic effects of intratumoral IL-17 expression and CD8(+) TILs were evaluated by Cox regression and Kaplan-Meier analysis. Immunohistochemical detection revealed the presence of IL-17 and CD8(+) cells in gastric adenocarcinoma tissue samples (90.6%, 174 out of 192 patients and 96.9%, 186 out of 192 patients, respectively). We have also found that intratumoral IL-17 expression was significantly correlated with age (p=0.004) and that the number of CD8(+)TILs was significantly correlated with UICC staging (p=0.012) and the depth of tumor invasion (p=0.022). The five-year overall survival probability among patients intratumorally expressing higher levels of IL-17 was significantly better than those expressing lower levels of IL-17 (p=0.036). Multivariate Cox proportional hazard analyses revealed that intratumoral IL-17 expression (HR: 0.521; 95% CI: 0.329-0.823; p=0.005) was an independent factor affecting the five-year overall survival probability. We conclude that low levels of intratumoral IL-17 expression may indicate poor prognosis in gastric adenocarcinoma patients.     

LOH at 6p21.3 region and HLA class altered phenotypes in bladder carcinomas

Alterations in HLA class I antigen expression have been frequently described in different epithelial tumors and are thought to favor tumor immune escape from T lymphocyte recognition. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes. Some are structural defects that produce unresponsiveness to treatment with interferons. Others include alterations in regulatory mechanisms that can be switched on by treatment of tumor cells with different cytokines. One important mechanism belonging to the first group is loss of heterozygosity (LOH) at chromosome region 6p21.3, which can lead to HLA haplotype loss. In this investigation, the frequency of LOH at 6p21 chromosome region was studied in 69 bladder carcinomas. Short tandem repeat analysis showed that 35% of cases had LOH in this chromosome region. By considering these results together with immunohistological findings previously published by our group, we identified a distribution pattern of HLA class I altered phenotypes in bladder cancer. The most frequently altered phenotype in bladder carcinomas was total loss of HLA class I expression (17 cases, 25%), followed by phenotype II associated with HLA haplotype loss (12 cases, 17.5%), and HLA allelic loss (ten cases, 14.5%). Nine cases (13%) were classified as having a compound phenotype, five cases (7%) as having HLA locus loss, and in 16 cases (23%) no alteration in HLA expression was detected. An important conclusion of this report is that a combination of different molecular and immunohistological techniques is required to precisely define which HLA alleles are lost during tumor progression and to characterize the underlying mechanisms of these losses. These studies should be performed when a cancer patient is to be included in an immunotherapy protocol that aims to stimulate different immune effector mechanisms.