Vulvar cancer is a rare malignancy with an incidence of 2.5–4.4 per 100,000 persons per year, making it the fourth most common gynaecological malignancy (Huang et al., 2023). The most common type is vulvar squamous cell carcinoma (VSCC), followed by basal cell carcinoma, extramammary Paget's disease and vulvar melanoma. The median age at diagnosis is 69 years (Bogani et al., 2023). Although vulvar surgery and treatment has become more targeted and less radical over the decades, it may still cause scarring and mutilation of the external genitalia, and it also may affect various nerves and blood vessels involved in sexual, anal and/or urinary functions. Olesen et al. (2023) performed an integrated review to explore the impact of vulvar cancer on women's sexual health from a multidimensional perspective. They concluded that the sexual health of women with vulvar cancer was tabooed and stigmatised for patients and healthcare professionals. Consequently, women received sparse sexual guidance, felt isolated and had unmet needs. We would like to point out some suggestions to improve the paper. First, quantitative research is more convincing than qualitative research, as 28 articles were included, a meta-analysis should be performed to confirm the results. Second, the pathological classification of vulvar cancer differed from each study. Therefore, stratification analysis is required to identify the impact of vulvar cancer on women's sexual health and function. Third, most of the studies use non-validated tools such as clinical interviews or data taken from medical records. While these have made it possible to obtain qualitative insight into patients' experiences, there is less scope for distinguishing between areas and isolating the factors that impact on them. Last, the sample sizes of the included studies were small, which may decrease the statistical power. The importance of the role of psycho-oncologists in the treatment of vulvar cancer should be emphasised for proposing and offering psychological support and psychoeducational interventions. These kinds of interventions could be useful not only for sustaining women's sexual health and their emotional condition but also for supporting the familial network. Moreover, evaluation by a psychiatric specialist may be useful in order to provide possible psychopharmacological therapy in the presence of severe depressive–anxiety symptoms, analysing the risk factors and any pharmacological interactions with chemotherapy treatments. This may be useful in improving the detection and treatment of psychosexual and psychosocial distress. The ideal goal could be the integration of a psycho-oncologist and/or psychiatrist in the multidisciplinary team for the treatment of vulvar cancer with the aim of addressing both the physical and psychosocial needs of these women (Elit & Reade, 2015).

胃癌转移是导致胃癌相关死亡的首要原因,循环肿瘤细胞的形成是实现肿瘤血行转移的最初阶段,为最终形成肿瘤转移病灶提供了可能,循环肿瘤细胞检测对于癌症的早期诊断,疗效与预后的评估,个体化治疗的选择等方面具有重要的临床意义,上皮间质转化促进了肿瘤细胞转移的发生,通过综述胃癌患者外周血循环肿瘤细胞富集检测技术,分析胃癌患者原发灶、循环肿瘤细胞及转移灶发生上皮间质转化及间质上皮转化的上皮间质标志物的表达情况,探究胃癌转移可能的发生途径和模式.

Background:To develop a novel highly accurate circulating tumor cell (CTC) identification method and to validate its application in cancer diagnostics and/or prognostics.Methods:We verified and validated the combined fluorescent probe staining protocol (combination of three fluorescent probes: Dil, Hoechst 33342, and PY) through CTC and non-CTC (white blood cell) morphological comparison of five tumor cell lines (THP-1, HEC, HEPG2, Eca-109, HeLa) in vitro and 32 patient tumor samples from the Shandong Cancer Hospital and Institute. Wright's Giemsa staining and cluster differentiation 45 (CD45) immunocytochemistry (ICC) staining were used as reference control methods. The association between the developed method and clinicopathology was also investigated.Results:We successfully developed and optimized the protocol, and validated the use of combined fluorescent probe staining for the identification of CTCs in the peripheral blood (PB) of tumor cell lines and tumor patients. Comparable CTC and non-CTC morphologies were observed for combined fluorescent probe staining and Giemsa staining methods in vitro. However, in vivo comparison between the three staining methods revealed that the identified CTCs differed in cell diameter and nucleo-cytoplasmic ratio. In addition, a higher CTC detection rate of 14/32, lower standard deviation (SD), and higher area under the receiver operating characteristic (ROC) curve (AUC) value of 0.844 were noted for combined fluorescence staining. Clinicopathological analysis revealed that CTCs were correlated with platelet levels (P=0.031), but not with age, gender, drinking history, or granule ratio.Conclusions:We developed a combined fluorescent probe staining method with higher CTC identification accuracy than Wright's Giemsa staining, and propose this technique as a novel clinical diagnostic/prognostic tool.

Background Circulating tumor cells (CTCs) are considered useful prognostic factors for various cancers, and in 2014, our research group conducted a comparative experiment of CTC detection in patients with renal cell cancer (RCC). However, the reason for the low detection rate of CTCs in cancer patients using the CellSearch® system is still unknown, although it has been hypothesized to be attributed to the likelihood that CTCs undergoing epithelial-mesenchymal transition (EMT) do not express the CTC biomarkers cytokeratin (CK)8/18/19 or epithelial cell adhesion molecule (EpCAM). The overall aim of the current study was to investigate the expression levels of CK8/18/19 and EpCAM in relation to the EMT biomarkers vimentin and E-cadherin in patients with RCC. Methods Patients with RCC who had undergone radical nephrectomy or partial resection between May 2014 and December 2014 were initially recruited. Results Among 34 RCC patients, nine co-expressed EpCAM and CK8/18/19 in primary tumor tissues. The CellSearch® results showed that CK8/18/19 was expressed in 5 of 6 patients (5/6) and EpCAM was expressed in 6 patients (6/6). However, the isolation by size of tumor cells (ISET) technique showed these were co-expressed in only four of the 10. The expression of CK8/18/19, EpCAM, vimentin, and E-cadherin was distributed unequally in different enumeration groups of CTCs (all P>0.05), and the positive expression of CK8/18/19 was correlated with neutrophil number and tumor size (P<0.05). The positive expression of vimentin was correlated with the Karnofsky Performance Status (KPS) score and clinical stage of renal cancer patients (P<0.05). Conclusions Our results indirectly proved the occurrence of EMT in the formation of CTCs by comparing and analyzing the expression of CK8/18/19 and EpCAM in renal cancer tissues and the detection results of CTCs.

目的 探讨CellSearch和CTC-Biopsy系统检测肾细胞癌(又称肾癌)患者外周血循环肿瘤细胞(CTCs)的价值及临床意义.方法 应用CellSearch和CTC-Biopsy系统同时检测山东省肿瘤医院收治的37例肾癌患者外周血CTCs,分析CTCs检测结果与患者临床病理特征和预后之间的关联性.2种检测方法结果比较采用χ2检验及一致性检验.采用Kaplan-Meier法绘制生存曲线,Log-rank检验对生存数据进行分析,Cox比例风险回归模型分析评估影响预后的因素.结果 CellSearch系统在7例患者中检测到外周血CTCs,总检出率为18.92％(7/37),无循环肿瘤细胞团(CTM)检出;CTC-Biopsy系统在13例患者外周血中检测到CTCs/CTM,CTCs/CTM总检出率为35.14％(13/37).CellSearch检测结果与肾癌患者的各项病理因素均无关联性(均P>0.05);CTC-Biopsy检测结果与患者的TNM分期(χ2=8.877,P=0.005)、肿瘤大小(χ2=7.758,P=0.019)和肾癌危险度(χ2=5.106,P=0.042)评分有关联.2种检测方法CTCs检测结果与肾癌患者5年无进展生存期(PFS)和总生存期(OS)无相关性(均P>0.05).结论 在肾癌患者中,CTC-Biopsy系统CTCs检出率高于CellSearch系统;CTC-Biopsy系统CTCs检测结果可以作为肾癌临床病理分期的有益补充.

背景与目的:多聚腺苷二磷酸核糖聚合酶抑制剂[inhibitors of poly(ADP-ribose)polymerase,PARPi]已被多项临床试验证实能使同源重组修复(homologous recombination repair,HRR)基因突变的转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)患者生存获益.氟唑帕利作为新型PARPi,已获批用于卵巢癌、输卵管癌及腹膜癌的治疗,但尚未见在前列腺癌中的研究报道.初步评价氟唑帕利治疗前列腺癌患者的有效性和安全性.?方法:回顾性分析2020年1月1日—2021年2月1日在复旦大学附属肿瘤医院等全国9家医院接受氟唑帕利单药或联合治疗的13例mCRPC患者的临床资料.基因突变数据、生存数据、不良反应等通过门诊随访或电话随访获得.结果:13例患者中,3例行氟唑帕利单药治疗,8例行氟唑帕利联合阿比特龙治疗,2例行氟唑帕利联合雄激素受体拮抗剂SHR3680治疗.单药治疗的3例患者均携带HRR基因突变,且均见前列腺特异性抗原(prostate-specific antigen,PSA)下降,其中2例(66.7％)患者的PSA下降50％以上.氟唑帕利联合阿比特龙治疗的8例患者前期均已阿比特龙耐药,基因检测结果显示,2例患者未携带HRR致病突变,1例患者未接受基因检测,8例患者中仅1例未携带HRR突变的患者接受联合治疗后PSA升高,其余7例(87.5％)患者的PSA下降,3例(37.5％)患者PSA下降50％以上,2例(25.0％)患者PSA下降90％以上.氟唑帕利联合SHR3680治疗的2例患者前期均已阿比特龙及多西他赛耐药,1例患者未接受基因检测且无PSA应答,另1例患者未检测出DNA损伤修复(DNA damage repair,DDR)基因突变但PSA下降50％以上.同时,61.5％(8/13)的患者出现了不同程度的不良反应,主要不良反应为贫血、关节疼痛、食欲下降及乏力;23.1％(3/13)的患者出现了3级贫血,其中1例患者因3级贫血而停止治疗.结论:氟唑帕利单药或联合治疗方案,在mCRPC患者中均显示出一定的疗效和可接受的不良反应,但仍需更大样本量前瞻性临床研究的证实.

Renal cell carcinoma is the second malignant tumors in the urinary system with high mortality and morbidity. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. In the current study, based on the publicly available data obtained from GEO and TCGA database, we identified five prognosis-related lncRNAs with the ability to predict the prognosis of patients with renal cell carcinoma. Among them, the uncharacterized and upregulated lncRNA RCAT1 (renal cancer-associated transcript 1) was identified as the key lncRNA. Our data further revealed that the expression of lncRNA RCAT1 was significantly upregulated in renal cell carcinoma tissues and cells. Gain-of-function and loss-of-function studies showed that lncRNA RCAT1 promoted cell proliferation, migration, and invasion in vitro and in vivo. Furthermore, we verified that lncRNA RCAT1 could abundantly sponge miR-214-5p, which served as a tumor suppressor in renal cell carcinoma. Significantly, miR-214-5p overexpression could attenuate the promotion of cell proliferation and metastasis induced by lncRNA RCAT1. Moreover, we found that E2F2 was a direct target of miR-214-5p, and lncRNA RCAT1 could protect E2F2 from miR-214-5p-mediated degradation. Taken together, our findings suggested that lncRNA RCAT1 could enhance the malignant phenotype of renal cell carcinoma cells by modulating miR‐214‐5p/E2F2 axis, and lncRNA RCAT1 might be a novel prognostic biomarker and a potential therapeutic target for renal cell carcinoma.

目的 观察肾透明细胞癌(CCRCC)组织中程序性细胞死亡受体1(PD-1)表达变化,并分析患者预后影响因素.方法 CCRCC患者67例,术中留取CRCC组织及其癌旁组织各67例份,采用免疫组化检测上述组织PD-1,分析PD-1阳性表达与CCRCC临床病理参数的关系,比较不同PD-1表达的CCRCC患者无进展生存期(PFS)、总生存期(OS)生存率,分析CCRCC患者预后不良的危险因素.结果 CCRCC、癌旁组织中PD-1阳性率分别为38.81％(26/67)、22.39％(15/67),两者比较,P<0.05.PD-1阳性表达与CCRCC Fuhrman分级、TNM分期、淋巴结转移、远处转移相关(P均<0.05).PD-1阳性表达者(26例)、PD-1阴性表达者(41例)PFS生存率分别为42.31％、85.37％,OS生存率分别为53.86％、87.80％,两者比较,P均<0.05.PD-1阳性表达、淋巴结转移、远处转移是CCRCC患者不良预后的危险因素(P均<0.05).结论 CCRCC组织中PD-1表达升高,PD-1阳性表达与高Fuhrman分级、高TNM分期、淋巴结转移、远处转移及患者预后有关,是患者不良预后的危险因素,PD-1有望成为CCRCC预后评估潜在生物学指标.

目的 Survivin和p27在多种肿瘤的临床分期、病理分级以及预后判断中具有重要应用价值.本研究通过检测前列腺癌组织中Survivin和p27表达,及其与临床病理特征的关系,进一步探讨其在预测前列腺癌患者前列腺特异性抗原无进展生存时间(prostate-specific antigen progression-free survival,PSA PFS)中的作用.方法 选取2013-01-012019 08 01山东省肿瘤医院收治的前列腺癌组织99例和前列腺增生组织27例,采用免疫组化法检测Survivin和p27表达并对患者血清PSA值进行随访,计算患者PSA PFS.结果 前列腺癌组织中Survivin阳性率为84.8％(84/99),高于前列腺增生组织的7.4％(2/27),差异有统计学意义,x2=58.716,P＜0.001;前列腺癌组织中p27阳性率为33.3％(33/99),低于前列腺增生组织的77.8％(21/27),差异有统计学意义,x2=17.111,P＜0.001.Survivin表达与前列腺癌的局部T分期(x2 =8.839,P=0.003)、Gleason评分(x2=10.925,P=0.004)以及是否发生骨转移(x2=8.048,P=0.005)具有关联性;而与患者年龄、初始PSA值是否＞100 ng/mL以及最低PSA值是否≤0.1 ng/mL差异无统计学意义,P＞0.05;p27表达与Gleason评分(x2=9.750,P=0.008)、是否发生骨转移(x2=15.240,P＜0.001)以及初始PSA值是否＞100 ng/mL(x2 =7.312,P=0.007)有关联性,而与患者年龄、局部T分期以及最低PSA值是否≤0.1 ng/mL差异无统计学意义,P＞0.05.Log-rank检验分析发现,是否发生骨转移(P=0.04)、初始PSA值是否＞100 ng/mL(P=0.049)、PSA最低值是否≤0.1 ng/mL(P=0.005)、治疗方式(P＜0.001)以及p27表达(P=0.005)是影响PSAPFS的相关因素.Cox回归模型分析结果显示,p27表达(HR=0.344,95％CI:0.141～0.840,P=0.005)、治疗方式(HR=0.218,95％CI:0.115～0.413,P＜0.001)以及最低PSA值是否≤0.1 ng/mL(HR=0.509,95％ CI:0.275～0.943,P=0.032)是PSA PFS的独立保护因素.结论 前列腺癌组织中Survivin阳性率较高,p27阳性表达、内分泌+化疗和PSA最低值≤0.1 ng/mL的患者PSA PFS更长.

目的 循环肿瘤细胞(circulating tumor cell,CTC)在判断临床分期、评估预后、监测疗效、辅助诊断和指导个体化治疗等方面表现出巨大潜力.本研究在完善和优化CTC-Biopsy检测系统的基础上,通过临床试验验证其检测肿瘤患者外周血中CTC的效果,探讨其临床推广应用的价值.方法 使用CTC-Biopsy检测系统,按照中国国家食品药品监督局(China Food and Drug Administration,CFDA)的药物临床试验管理规范(Good Clinical Practice,GCP),对山东大学附属山东省肿瘤医院2014-09-01-2014-12-31收治的150例肿瘤患者及2014-12-12-2014-12-1522名健康志愿者进行了临床试验.结果 CTC-Biopsy检测系统检测的染色标本背景干净,细胞形态清晰,细胞核质分界清楚;除异常细胞外,样片中仅残留少量的单核细胞.CTC-Biopsy检测系统检测不分病种恶性肿瘤灵敏度为51.33％(77/150),特异性为100.00％(77/77),约登指数为0.513.由CTC-Biopsy检测系统的CTC检出率的95％CI下限为43.33％,大于国际ISET法报道的43.06％.胃癌Ⅳ期患者检出率高于Ⅰ～Ⅲ期患者,差异有统计学意义,P=0.002.结论 通过GCP临床试验证实,CTC-Biopsy系统检测肿瘤患者外周血中CTC的灵敏度、特异性等指标均达到国际同类检测系统水平.该系统检测操作简便易行,且高效、稳定和经济,具有良好的临床推广价值.

BACKGROUND/AIMS:Detection of circulating tumor cells (CTCs) in cancer patients has diagnostic and prognostic importance. However, the clinical implications of CTC detection in patients with renal cell carcinoma (RCC) are still unclear. In this study, we investigated the clinical significance of CTCs using two detection systems, the CellSearch system (CSS) and isolation by size of epithelial tumor cells (ISET), among RCC patients.METHODS:We recruited 36 RCC patients and 22 healthy volunteers as controls. Blood was drawn before treatment. Samples were analyzed using the CSS and ISET. We prospectively followed the RCC patients to determine overall and progression-free survival.RESULTS:We did not detect CTCs in the control group using either the CSS or ISET. CTCs were detected in 7/36 patients (19.4%) using the CSS and in 13/36 patients (36.1%) using ISET, while circulating microemboli (CTMs) were detected in three patients (8.3%). The presence of ISET-detected CTCs correlated with clinical tumor node metastasis (TNM) stages, while the CSS-detected CTCs did not. After 36 months (median), CTCs detected by both methods failed to correlate with overall and progression-free survival among RCC patients.CONCLUSION:We discovered that ISET is more suitable than the CSS for detecting CTCs in RCC patients. The presence of CTCs/CTMs in RCC patients correlated with higher TNM stages, suggesting that the presence of CTCs could be a prognostic marker in RCC patients.

Detection of circulating tumor cells (CTCs) has been made to develop reliable assays for early diagnosis of various cancers. Overexpression of survivin in cancer cells is strongly associated with tumor progression. Although upregulation of survivin is observed in various tumors, its expression profile in the peripheral blood of prostate cancer (PCa) patients has not yet been investigated. In this study, we validated the application of survivin as the tumor marker to detect CTC and assessed its utility for diagnosis of PCa distant metastasis. Immunohistochemistry and quantitative real-time PCR (QRT-PCR) were performed to confirm the levels of surviving expression in PCa tissues. In addition, CTC values in 3 mL of peripheral blood from PCa patients, benign prostate hyperplasia (BPH) patients, and normal controls were also measured by the survivin-targeted PCR. Our results showed that surviving was overexpressed in PCa tissues. The median levels of blood surviving mRNA of PCa patients, BPH patients, and normal controls were 5.67 (range from 0 to 12.46), 2.24 (range from 0 to 6.55), and 1.85 (range from 0 to 3.82), respectively. The levels of survivin are positively associated with PCa distant metastasis. Our results concluded that quantitation of CTCs through survivin-PCR could be a promising marker for diagnosis of PCa metastasis.

Detection of circulating tumor cells (CTCs) has been made to develop reliable assays for early diagnosis of various cancers. Overexpression of survivin in cancer cells is strongly associated with tumor progression. Although upregulation of survivin is observed in various tumors, its expression profile in the peripheral blood of prostate cancer (PCa) patients has not yet been investigated. In this study, we validated the application of survivin as the tumor marker to detect CTC and assessed its utility for diagnosis of PCa distant metastasis. Immunohistochemistry and quantitative real-time PCR (QRT-PCR) were performed to confirm the levels of surviving expression in PCa tissues. In addition, CTC values in 3 mL of peripheral blood from PCa patients, benign prostate hyperplasia (BPH) patients, and normal controls were also measured by the survivin-targeted PCR. Our results showed that surviving was overexpressed in PCa tissues. The median levels of blood surviving mRNA of PCa patients, BPH patients, and normal controls were 5.67 (range from 0 to 12.46), 2.24 (range from 0 to 6.55), and 1.85 (range from 0 to 3.82), respectively. The levels of survivin are positively associated with PCa distant metastasis. Our results concluded that quantitation of CTCs through survivin-PCR could be a promising marker for diagnosis of PCa metastasis.

The specificity of circulating tumor cell (CTC) such as epithelial-mesenchymal transition,fusion of bone marrow-derived cells,resistance anoikis determines the necessity of cell cultivating.The produced cell lines can provide good material basis for further research of malignant tumor metastasis,also provide individualized targeted therapy for patients with a new direction.

Combination chemotherapy is emerging in the management of advanced penile cancer. However, evidence-based chemotherapeutic regimens in the current guidelines are lacking. The aim of this study was to evaluate the efficacy of preoperative neoadjuvant chemotherapy combined with a BMP regimen including bleomycin (BLM), methopterin (MTX) and cisplatin (DDP) for treating advanced penile cancer patients.

BACKGROUND:Identifying novel tumor biomarkers to develop more effective diagnostic and therapeutic strategies for patients with ACC is urgently needed. The aim of the study was to compare the proteomic profiles between adrenocortical carcinomas (ACC) and normal adrenocortical tissues in order to identify novel potential biomarkers for ACC.METHODS:The protein samples from 12 ACC tissues and their paired adjacent normal adrenocortical tissues were profiled with two-dimensional electrophoresis; and differentially expressed proteins were identified by mass spectrometry. Expression patterns of three differently expressed proteins calreticulin, prohibitin and HSP60 in ACC, adrenocortical adenomas (ACA) and normal adrenocortical tissues were further validated by immunohistochemistry.RESULTS:In our proteomic study, we identified 20 up-regulated and 9 down-regulated proteins in ACC tissues compared with paired normal controls. Most of the up-regulated proteins were focused in protein binding and oxidoreductase activity in Gene Ontology (GO) molecular function classification. By immunohistochemistry, two biomarkers calreticulin and prohibitin were validated to be overexpressed in ACC compared with adrenocortical adenomas (ACA) and normal tissues, but also calreticulin overexpression was significantly associated with tumor stages of ACC.CONCLUSION:For the first time, calreticulin and prohibitin were identified to be novel candidate biomarkers for ACC, and their roles during ACC carcinogenesis and clinical significance deserves further investigation.VIRTUAL SLIDES:The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1897372598927465.

OBJECTIVE: To compare the proteomic profiling of renal clear cell carcinoma (RCC) and paratumorous tissues, in order to identify novel tumor markers. METHODS: Protein samples from 10 RCC tissues and their paired paratumor tissues were extracted, and isolated by two-dimensional electrophoresis. Differently expressed protein spots were identified by mass spectrometry. RESULTS: About 20 up-regulated and 10 down-regulated proteins in RCC tissues. Most of the up-regulated proteins were involved in response to hypoxia, anti-apoptosis and Glycolysis, Regulation of actin cytoskeleton and PPAR cancer-related pathway. CONCLUSION: The differently identified proteins in this study were novel candidate biomarkers for RCC, and its clinical significance deserves further investigation.

回顾分析2000年9月~2007年11月收治的16例肿瘤患者术后肺栓塞(PE)的临床特点及治疗经过。认为肿瘤患者术后并发下肢深静脉血栓形成是急性PE的主要危险因素,积极的溶栓治疗可显著改善预后。