卵巢硬化性间质瘤的研究进展

卵巢硬化性间质瘤是一种临床罕见的卵巢良性肿瘤，其发病率低，病因不明确，以年轻女性多见，多为单侧肿块，常因月经不规则出血或体检发现腹部包块而就诊。影像学检查可见“湖岛征”、“快进慢出”和“向心性强化”等改变。病理组织学见单侧类圆形囊实性肿块，“假小叶”为特征性病变。免疫组织化学可见抑制素、波形蛋白和肌动蛋白等阳性表达。确诊主要通过病理组织学诊断，影像学检查具有重要参考价值。术前诊断困难，容易与卵巢纤维瘤、卵泡膜细胞瘤、卵巢库肯勃瘤和颗粒细胞瘤等相混淆。手术治疗为主要治疗手段，多采用患侧肿瘤切除术或附件切除术，术后预后较好，卵巢功能可恢复正常。对于肿瘤细胞出现核分裂象和坏死较多时，需警惕复发风险，建议长期跟踪随访。     

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

经皮对比增强超声在乳腺癌前哨淋巴结术前定位及转移风险评估中的临床应用价值

目的探讨经皮注射对比增强超声(CEUS)在乳腺癌前哨淋巴结(SLN)术前定位及转移风险评估中的临床应用价值。 方法根据纳入及排除标准，选择2019年5～9月在江苏大学附属人民医院乳腺外科行手术治疗的21例女性乳腺癌患者进行前瞻性研究。术前根据经皮CEUS示踪结果，在皮肤表面标记SLN位置及数目，根据其增强模式评估SLN转移风险，并在术中联合亚甲蓝共同确认SLN的位置及数目。以亚甲蓝染色的病理检查结果为金标准，计算经皮CEUS预测SLN状态的敏感度、特异度、阳性预测值、阴性预测值及准确率。用Kappa一致性检验分析CEUS与SLN常规病理检查结果的一致性及2名超声科医师对SLN增强模式判读的一致性。用Fisher精确概率法分析不同临床病理特征患者CEUS评估SLN结果的差异。 结果21例患者中，经皮CEUS共检出32枚SLN，亚甲蓝染色共检出71枚。经皮CEUS体表定位的SLN均为术中亚甲蓝染色的SLN,患者经皮CEUS检出(1.6±0.9)枚SLN,低于亚甲蓝染色检出的(3.4±1.4)枚(t＝5.017, P<0.001)。CEUS预测SLN转移风险：判定有SLN转移患者9例(病理证实SLN有转移7例，无转移2例)，判定无转移患者12例(病理证实SLN无转移11例，有转移1例)。CEUS评估SLN状态的敏感度7/8，特异度11/13，阳性预测值7/9，阴性预测值11/12，准确率85.7%(18/21)。CEUS与病理诊断结果具有较高一致性(Kappa ＝0.704，P＝0.001)。2名超声科医师对CEUS中32枚SLN增强模式的判读结果一致性较好(Kappa＝0.829，P<0.001)。不同组织学分级的患者，其CEUS预测结果比较，差异有统计学意义(P＝0.046)。 结论经皮CEUS是乳腺癌患者SLN术前定位及转移风险评估的一种有效方法。     

Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy

Background/Aim: The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. Methods: The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Results: The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. Conclusion: The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility.     

miRNA-325-3p通过下调细胞角蛋白13 的表达降低鼻咽癌细胞CNE1 的放疗敏感性

目的：探究miRNA-325-3p 及其靶基因细胞角蛋白13（cytokeratin 13，CK13）对鼻咽癌细胞CNE1 的放疗敏感性的影响。方法：通过miRBase、Targetscan 及Microcosm 三大数据库预测miRNA-325-3p 的潜在靶基因，并通过双荧光素酶活性检测实验进行验证，qPCR检测不同放射剂量下鼻咽癌细胞CNE1 中miRNA-325-3p 及其靶基因的表达水平变化，通过克隆形成实验观察不同放射剂量下过表达miRNA-325-3p 及敲低靶基因后CNE1 细胞克隆形成率的变化，流式细胞术验证过表达miRNA-325-3p及敲低靶基因后CNE1 在不同放射剂量下凋亡水平的变化，MTT法检测miRNA-325-3p 过表达和CK13 敲低组鼻咽癌细胞CNE1在不同放射剂量下的细胞存活率以验证其放疗敏感性的变化。结果：CK13 确认为miRNA-325-3p 的潜在靶基因，鼻咽癌细胞CNE1 经放射处理后，miRNA-325-3p 的表达水平显著升高、CK13 的表达水平显著降低（均P<0.05）。miRNA-325-3p 表达量上调和CK13 基因沉默均显著提高CNE1 细胞的存活率[miRNA上调时：（60.14±3.55）% vs（19.23±3.42）%，t=14.37、P<0.01；CK13 沉默时：（76.15±5.13）% vs（28.53±3.68）%，t=13.06、P<0.01]和克隆形成率，降低了凋亡率[miRNA 上调时：（27.95±2.67）% vs（51.68±3.47）%，t=9.39、P<0.01；CK13 沉默时：（20.31±2.62）% vs（38.14±3.83）%，t=6.66、P<0.01]。结论：miRNA-325-3p 能够通过下调靶基因CK13的表达降低鼻咽癌细胞CNE1 对放疗的敏感性。     

Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC-Registry

Non-clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non-clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first- and second-line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC-Registry), 99 patients with papillary mRCC treated with systemic first-line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first-line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression-free survival from start of first-line treatment was 5.4 months (95% confidence interval [CI], 4.1–9.2) and median overall survival was 12.0 months (95% CI, 8.1–20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow-up, and 9% were alive at the end of the individual 3-year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real-world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC.     

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.