Chemotherapy for ovarian clear cell adenocarcinoma with irinotecan hydrochloride and mitomycin C

Background No effective chemotherapy has been established for the treatment of ovarian clear cell adenocarcinomas. Based on the results of a sensitivity test in cultured cells, we investigated combination chemotherapy using irinotecan hydrochloride and mitomycin C. Methods Six patients with ovarian clear cell, adenocarcinoma and evaluative lesions were infused with irinotecan (140 mg/m²) intravenously over 4 hours and mitomycin C (7 mg/m²) was infused over 60 minutes directly into the pleuroperitoneal cavity or intravenously. One course comprised 3 doses of each agent at 2-week intervals and patients received at least 2 courses. Results A complete response was obtained in 1 patient (maintained for 12 months so far) and a partial response in 1 patient (maintained for 3 months and followed by relapse with peritoneal dissemination). In 3 of the 4 patients without tumor regression, carcinomatous effusions decreased or disappeared. Myelosuppression and gastrointestinal side effects were grade II or less in severity and thus were considered tolerable. Conclusion Because no chemotherapy regimens employing cisplatin are effective for ovarian clear cell adenocarcinomas, this regimen warrants further study.     

超声诊断卵巢透明细胞癌

目的 探讨术前超声诊断卵巢透明细胞癌(ovarian clear cell carcinoma,OCCC)的临床价值.方法 回顾性分析14例经手术病理检查证实的OCCC患者资料,观察OCCC的临床特征及术前超声表现.结果 3例病灶位于双侧卵巢,11例病灶位于单侧卵巢.超声表现为类圆形或类椭圆形肿块,边界清,有包膜;实性...     

白蛋白结合型紫杉醇联合奈达铂一线治疗晚期食管癌患者的临床观察

背景与目的：化疗是晚期食管癌患者的主要治疗手段,但目前尚没有标准的一线治疗方案,通过白蛋白结合型紫杉醇联合奈达铂方案治疗晚期食管癌,评价其临床疗效及安全性。方法：收集2016年2月—2019年2月之间在长海医院诊治的晚期食管癌并有可评价病灶的患者31例,一线予以白蛋白结合型紫杉醇联合奈达铂方案化疗,具体用药为：白蛋白结合型紫杉醇130 mg/m ² ,第1、8天;奈达铂70 mg/m ² ,第1天;每3周重复。采用实体瘤疗效评价标准（Response Evaluation Criteria in Solid Tumors,RECIST）1.1标准评估疗效,按照美国国立癌症研究所通用毒性标准（National Cancer Institute Common Toxicity Criteria,NCI-CTC）5.0评估不良反应。结果：全部31例患者均可评价疗效,其中完全缓解（complete response,CR）1例（3.2%）,部分缓解（partial response,PR）20例（64.5%）,疾病稳定（stable disease,SD）9例（29.0%）,疾病进展（progressive disease,PD）1例（3.2%）,客观缓解率（objective response rate,ORR）为67.7%,疾病控制率（disease control rate,DCR）为96.8%,中位无进展生存期（progression-free survival,PFS）为9.4个月。常见不良反应主要包括骨髓抑制、感觉神经病变、关节酸痛、肌肉酸痛、消化道反应及脱发,无毒性相关死亡病例。结论：白蛋白结合型紫杉醇联合奈达铂一线治疗晚期食管癌疗效较好,不良反应患者可耐受,值得进一步推广。     

88例卵巢透明细胞癌临床及预后分析

目的分析卵巢透明细胞癌的临床病理特点,探讨更有效的治疗方法和影响预后的因素。方法回顾性分析1984年1月至2005年5月收治的88例卵巢透明细胞癌患者的临床及随访资料。结果(1)43例患者术后给予以铂类为主的联合化疗,有效率为35.0%,复发率为67.4%,3、5年生存率分别为43.9%和29.3%;33例患者给予紫杉醇(PTX)联合铂类化疗,有效率为73.9%,复发率为45.5%,3、5年生存率分别为57.3%和40.5%;12例患者给予开普拓(CPT-11) 丝裂霉素(MMC)联合化疗,有效率为71.4%,复发率为25.0%,3年生存率为70.7%。(2)88例患者中,复发47例,复发率为53.4%。Ⅰ期患者总的复发率(45.4%)明显低于Ⅱ Ⅲ期患者(75.0%);Ⅰ期行淋巴结清扫术患者的复发率(27.8%)明显低于未行淋巴结清扫术者(51.3%);CA125升高患者的复发率(67.3%)明显高于CA125正常或不详者(38.1%)。(3)88例患者总的3、5年生存率分别为48.7%和40.9%。Ⅰ期患者总的3、5年生存率明显高于Ⅱ Ⅲ期患者(P<0.05);Ⅰ期行淋巴结清扫术患者的3、5年生存率明显高于未行淋巴结清扫术者(P<0.05);Ⅲ期术后残存肿瘤<2cm患者的3、5年生存率明显高于残存肿瘤≥2 cm的患者(P<0.05);CA125升高患者的3、5年生存率与CA125正常或不详者的差异无统计学意义(P>0.05)。结论卵巢透明细胞癌的预后较差,对以铂类为主的联合化疗可能更耐药;临床分期、是否行淋巴结清扫术以及化疗方案的选择等因素可能会影响预后。     

子宫内膜异位症相关性卵巢透明细胞癌和卵巢子宫内膜样癌的临床病理特征研究

目的 研究子宫内膜异位症(EM)相关性卵巢透明细胞癌(CCC)和卵巢子宫内膜样癌(EC)的临床病理特征.方法 选取CCC和EC患者共167例,根据是否为EM恶变将患者分为EM组(n=84)和非EM组(n=83).比较两组患者的年龄、生育史、EM病史、临床表现、凝血功能、血清CA125水平、超声检查结果、术中情况及术后病理特点.结果 EM组患者的发病年龄、初潮年龄均明显小于非EM组(P﹤0.01),未绝经患者所占比例明显低于非EM组(P﹤0.01);EM组患者的孕次、产次明显低于非EM组(P﹤0.001),不孕症患者所占比例明显高于非EM组(P﹤0.001);EM组中既往有EM病史的患者所占比例高于非EM组(P﹤0.05);临床表现方面,EM组患者的痛经、月经紊乱发生率均明显高于非EM组(P﹤0.01);EM组患者的PT、APTT明显短于非EM组(P﹤0.001);术后,EM组患者的血清CA125水平低于非EM组(P﹤0.05);两组患者超声检查结果比较,差异无统计学意义(P﹥0.05);EM组患者的肿瘤直径明显大于非EM组(P﹤0.001);两组患者的FIGO分期比较,差异有统计学意义(P﹤0.05),其中EM组患者中Ⅰ~Ⅱ期患者所占比例高于非EM组.结论 EM相关性CCC和EC与单纯CCC和EC存在明显不同的临床病理特征,具有确诊年龄及初潮年龄小、绝经比例更高、孕产次更低、既往有EM病史患者所占比例更高、痛经和月经紊乱表现更多、PT和APTT更短、血清CA125水平较低和临床病理分期较早等特点.     

奈达铂联合吉西他滨治疗晚期复治肺鳞癌的临床观察

目的 观察奈达铂联合吉西他滨治疗晚期复治肺鳞癌的疗效和毒性反应。方法 26例经病理组织学或细胞学检查确诊的晚期肺鳞癌复治患者,给予奈达铂80mg／m2 d1,吉西他滨1000mg／m2 d1、d8, 21天为1周期。1～2周期后评价疗效及毒性反应,并随访患者无进展生存时间（PFS）。结果 26例患者中23例可评价疗效,无完全缓解（CR）病例,部分缓解（PR） 6例,稳定（SD） 12例,进展（PD） 5例,总有效率（RR）为261％,临床获益率（DCR）为 783％。中位PFS 为4个月。主要毒副反应为骨髓抑制、肝功能损害和胃肠道反应,骨髓抑制明显但可耐受。结论 奈达铂联合吉西他滨治疗晚期复治肺鳞癌疗效确切,毒副反应可耐受,值得进一步推广研究。     

Immune-Hot tumor features associated with recurrence in early-stage ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) is a distinct histotype of ovarian cancer, which usually presages a worse prognosis upon recurrence. Identifying patients at risk for relapse is an unmet need to improve outcomes. A retrospective cohort analysis of 195 early-stage OCCC patients diagnosed between January 2011 and December 2019 at National Taiwan University Hospital was conducted to identify prognostic factors for recurrence, progression-free survival (PFS) and overall survival (OS). Molecular profiling of tumors was performed in a case-controlled cohort matched for adjuvant therapy for biomarker discovery. Multivariate Cox proportional hazard model revealed that paclitaxel-based chemotherapy was associated with better PFS than nonpaclitaxel chemotherapy (HR = 0.19, P = .006). The addition of bevacizumab was associated with better PFS, compared to no bevacizumab (HR = 0.09, P = .02). Neither showed significant improvement in OS. Recurrence is associated with an Immune-Hot tumor feature (P = .03), the CTLA-4-high subtype (P = .01) and increased infiltration of immune cells in general. The Immune-Hot feature (HR = 3.39, P = .005) and the CTLA-4-high subtype (HR = 2.13, P = .059) were associated with worse PFS. Immune-Hot tumor features could prognosticate recurrence in early-stage OCCC.     

Two cases of recurrent ovarian clear cell carcinoma treated with sorafenib

Sorafenib is an oral multikinase inhibitor targeting Raf and other kinases. The anti-tumor effect of sorafenib is thought to be mediated through its inhibition of the RAS–Raf–Erk pathway, as well as its inhibition of VEGFR and PDGFR. Sorafenib has been effective at treating patients with renal cell carcinoma (RCC). Ovarian clear cell carcinoma (OCCC) is a chemoresistant subtype of ovarian cancer. OCCC is represented by cells with clear cytoplasm that resemble those observed in RCC. Using a microarray database, the gene expression profile of OCCC was similar to that of RCC. The effects of sorafenib against human OCCC are unknown. Therefore, we used sorafenib to treat two patients with recurrent chemoresistant OCCC, and observed good effect in both of them without severe side effects. We believe that sorafenib is an effective agent against OCCC. Given the chemoresistant nature of this tumor, this drug appears to be very valuable.     

Venous thromboembolism,interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma

BackgroundWe compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels.MethodsA multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined.FindingsPatients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P < 0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P = 0.006). Advanced OCCC (hazard ratio [HR] 3.38, P < 0.0001), thrombocytosis (HR 1.42, P = 0.032) and elevated IL-6 (HR 8.90, P = 0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P < 0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P < 0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P = 0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P = 0.07).InterpretationAdvanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC.     

奈达铂联合替加氟治疗８６例晚期食管癌的临床观察

目的：观察奈达铂（ＮＤＰ）联合替加氟（ＦＴ-２０７）方案治疗晚期食管癌的近期疗效和毒副作用。方法：观察组４４例采用ＮＤＰ＋ＦＴ-２０７方案：ＮＤＰ８０～１００ｍｇ／ｍ２,静滴,第１天,ＦＴ-２０７５００～６００ｍｇ／ｍ２,静滴,第１～５天,２８天为１周期。对照组４２例采用顺铂（ＤＤＰ）＋氟尿嘧啶（５-ＦＵ）方案：ＤＤＰ８０～１００ｍｇ／ｍ２,静滴,第１天,５-ＦＵ５００～７５０ｍｇ／ｍ２,静滴,第１～５天,２８天为１周期。结果：全部病例均可评价疗效及毒副反应。观察组有效率为５６.８％,对照组５０.０％,两组差异无统计学意义。观察组消化道反应较对照组明显减轻（Ｐ＜０.０５）,血小板减少、白细胞减少、神经毒性、腹泻等两组无明显差异。结论：奈达铂联合替加氟治疗晚期食管癌近期疗效略好于顺铂加氟尿嘧啶方案,且患者耐受性较好。     

Phase II study of nedaplatin and irinotecan followed by gefitinib for elderly patients with unresectable non-small cell lung cancer

PURPOSE: We conducted a phase II study of combination chemotherapy with nedaplatin (NP) and irinotecan (CPT) followed by gefitinib to determine the effects and toxicities in patients 70 years or older with unresectable non-small cell lung cancer (NSCLC). METHODS: Eligible patients were entered to receive 3 courses of 50 mg/m(2) NP and 60 mg/m(2) CPT on days 1 and 8 every 4 weeks and sequential gefitinib 250 mg po once a day was followed until tumor progression. RESULTS: Twenty-eight patients received NP and CPT combination chemotherapy. One patient achieved CR, 10 PR, 14 SD and 3 PD, and the response rate was 39.3%. Twenty-one patients received gefitinib 250 mg per day until tumor progression after completion of the NP and CPT chemotherapy. Two patients with SD after NP and CPT chemotherapy achieved PR. For the 3-drug combination, there were 13 responders and the overall response rate was 42.9%. Of the toxicities associated with NP and CPT chemotherapy, grade 4 neutropenia, and grade 3 febrile neutropenia were observed in 24 (33.8%) and 3 (4.2%) courses, respectively. Of the toxicities associated with gefitinib treatment, grade 3 anemia, and SGOT and SGPT elevation were observed in one patient (4.8%) each, respectively. The median survival time was 8.7 months, and the 1- and 2-year survival rates were 42.9 and 32.1%, respectively. CONCLUSION: NP and CPT followed by gefitinib is feasible for elderly patients with unresectable NSCLC.     

奈达铂联合顺铂体外干预人卵巢癌Ｓｋｏｖ-３细胞生长的实验研究*

目的：研究奈达铂（ＮＤＰ）联合顺铂（ＤＤＰ）对人卵巢癌细胞株Ｓｋｏｖ-３增殖及凋亡的影响,并探讨其抑制增殖及诱导凋亡的机制。方法：采用ＭＴＴ法检测不同浓度ＮＤＰ与ＤＤＰ单独或联合应用对Ｓｋｏｖ-３细胞的增殖抑制率;采用流式细胞术分析早期凋亡细胞比例;采用ＲＴ-ＰＣＲ和Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ法分析增殖相关基因（蛋白）Ｋｉ-６７及凋亡相关基因（蛋白）Ｂａｘ、Ｂｃｌ ２表达的变化。结果：ＮＤＰ、ＤＤＰ单独应用及两者联合使用明显抑制Ｓｋｏｖ-３细胞的生长,且呈剂量依赖性;根据中效原理发现两者联合使用高浓度时呈协同效应;流式细胞术结果表明正常对照组、ＮＤＰ组、ＤＤＰ组和联合组细胞早期凋亡比例依次增加;与单独用药组比较,联合用药组Ｋｉ-６７、Ｂｃｌ-２基因（蛋白）表达率显著降低,而Ｂａｘ基因（蛋白）表达显著增高。结论：ＮＤＰ和ＤＤＰ联合应用与两药单独应用相比,对Ｓｋｏｖ-３细胞增殖的抑制作用和诱导凋亡能力均有明显增强。     

卵巢透明细胞癌脾脏转移并文献回顾

目的：探讨卵巢透明细胞癌脾脏转移的临床特点和治疗策略。方法：报告1例卵巢透明细胞癌脾脏转移的详细临床资料,并进行系统文献回顾。结果：卵巢癌出现脾脏转移以浆液性乳头状囊腺癌多见,卵巢透明细胞癌发生脾脏转移极为罕见。卵巢癌出现脾脏转移时间多在卵巢癌术后,少数出现于首次就诊时,多数表现为同时多发性的大网膜及盆腔转移,个别患者可表现为孤立性脾转移病灶。结论：卵巢癌脾脏转移诊断的确立需要结合肿瘤标志、影像学资料和组织病理;治疗方面需采取综合手段,应在准确评估病情的前提下,及时行减瘤术和脾切除术,以提高患者生存质量。     

Epigenetic determinants of ovarian clear cell carcinoma biology

Targeted approaches have revealed frequent epigenetic alterations in ovarian cancer, but the scope and relation of these changes to histologic subtype of disease is unclear. Genome‐wide methylation and expression data for 14 clear cell carcinoma (CCC), 32 non‐CCC and four corresponding normal cell lines were generated to determine how methylation profiles differ between cells of different histological derivations of ovarian cancer. Consensus clustering showed that CCC is epigenetically distinct. Inverse relationships between expression and methylation in CCC were identified, suggesting functional regulation by methylation, and included 22 hypomethylated (UM) genes and 276 hypermethylated (HM) genes. Categorical and pathway analyses indicated that the CCC‐specific UM genes were involved in response to stress and many contain hepatocyte nuclear factor (HNF) 1‐binding sites, while the CCC‐specific HM genes included members of the estrogen receptor alpha (ERalpha) network and genes involved in tumor development. We independently validated the methylation status of 17 of these pathway‐specific genes, and confirmed increased expression of HNF1 network genes and repression of ERalpha pathway genes in CCC cell lines and primary cancer tissues relative to non‐CCC specimens. Treatment of three CCC cell lines with the demethylating agent Decitabine significantly induced expression for all five genes analyzed. Coordinate changes in pathway expression were confirmed using two primary ovarian cancer datasets (p < 0.0001 for both). Our results suggest that methylation regulates specific pathways and biological functions in CCC, with hypomethylation influencing the characteristic biology of the disease while hypermethylation contributes to the carcinogenic process.     

卵巢透明细胞癌脾脏转移并文献回顾

目的:探讨卵巢透明细胞癌脾脏转移的临床特点和治疗策略。方法:报告1例卵巢透明细胞癌脾脏转移的详细临床资料,并进行系统文献回顾。结果:卵巢癌出现脾脏转移以浆液性乳头状囊腺癌多见,卵巢透明细胞癌发生脾脏转移极为罕见。卵巢癌出现脾脏转移时间多在卵巢癌术后,少数出现于首次就诊时,多数表现为同时多发性的大网膜及盆腔转移,个别患者可表现为孤立性脾转移病灶。结论:卵巢癌脾脏转移诊断的确立需要结合肿瘤标志、影像学资料和组织病理;治疗方面需采取综合手段,应在准确评估病情的前提下,及时行减瘤术和脾切除术,以提高患者生存质量。     

雷替曲塞联合奈达铂同步螺旋断层放疗治疗局部晚期鼻咽癌的临床研究

目的 比较雷替曲塞联合奈达铂与多西他塞联合奈达铂同步螺旋断层放疗（HT）治疗局部晚期鼻咽癌的疗效和安全性。方法 回顾性分析2011年3月至2015年4月84例初治局部晚期鼻咽癌患者的临床资料,其中31例接受雷替曲塞联合奈达铂方案同步HT治疗（RN+HT组）,53例接受多西他赛联合奈达铂方案同步HT治疗（DN+HT组）。HT处方剂量：PGTVnx及PGTVnd 70～72 Gy／33次,PTV1 60 Gy／33次,PTV2 50 Gy／28次,5次／周。RN+HT组：雷替曲塞25 mg／m2静滴,d1;奈达铂共75 mg／m2静滴,d1～d5。DN+HT组：多西他赛35～40 mg／m2静滴,d1、d8;奈达铂共75 mg／m2静滴,d1～d5。两组化疗方案均以21天为1周期,化疗2个周期。比较两组的远期生存情况和不良反应。结果 全组中位随访21.5个月。RN+HT组局部复发1例,远处转移2例,死亡2例;DN+HT组局部复发2例,远处转移3例,死亡3例。RN+HT组和DN+HT组的2年生存率分别为93.5％和94.3％,2年无进展生存率分别为90.3％和90.6％,差异均无统计学意义（P＞0.05）。两组急性不良反应包括口腔黏膜炎、皮肤损伤、腮腺损伤、咽喉炎、白细胞减少、体重减轻及恶心呕吐等,多为1～2级。DN+HT组恶心呕吐的发生率高于RN+HT组,差异有统计学意义（P＜0.05）;其他不良反应发生率的差异均无统计学意义（P＞0.05）。两组晚期损伤主要为皮肤损伤、皮下纤维化和口干症,不良反应发生率的差异无统计学意义（P＞0.05）。结论 RN方案同步HT是局部晚期鼻咽癌的有效治疗方案,且不良反应可耐受。     

New perspectives on molecular targeted therapy in ovarian clear cell carcinoma

Ovarian clear cell carcinomas (OCCCs) account for about 5–13% of all epithelial ovarian carcinomas in Western populations. It is characterised by resistance to conventional platinum-based chemotherapy, and new therapeutic strategies are urgently required. This article will focus on how recent discoveries have enhanced our understanding of the molecular pathogenesis of OCCCs, leading to new therapeutic opportunities. These include mutations in ARID1A, which provides a link to endometriosis, upregulation of the phosphatidylinositol 3-kinase/AKT pathway, particularly through mutations of PIK3CA and inactivation of PTEN, and increased activity of pathways involved in angiogenesis. Targeting HER2, apoptotic escape mechanisms and mismatch repair defects offer additional opportunities for treating this enigmatic tumour subtype.     

The renal clear cell carcinoma immune landscape

A comprehensive evaluation of the clear cell renal cell carcinoma (ccRCC) immune landscape was found using 584 RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), we identified 17 key dysregulated immune-associated genes in ccRCC based on association with clinical variables and important immune pathways. Of the numerous findings from our analyses, we found that several of the 17 key dysregulated genes are heavily involved in interleukin and NF-kB signaling and that somatic copy number alteration (SCNA) hotspots may be causally associated with gene dysregulation. More importantly, we also found that key immune-associated genes and pathways are strongly upregulated in ccRCC. Our study may lend novel insights into the clinical implications of immune dysregulation in ccRCC and suggests potential immunotherapeutic targets for further evaluation.     

奈达铂治疗非小细胞肺癌的Ⅱ期临床研究报告

背景与目的：观察奈达铂治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的疗效及不良反应。方法：本研究为多中心随机对照Ⅱ期临床研究。复治NSCLC病人进入奈达铂单单治疗组,奈达铂100mg/m^2静滴,每3周重复。将初治病人（未接受过化疗）随机分组,试验组化疗方案为奈达铂联合VDS,对照组为DDP联合VDS。结果：共138你病人,其中化疗方案单药组复发病例16例,联合治疗试验组60例,联合治疗对照组62例。单药组病人,既往均接受了DDP或卡铂的治疗,仍然有12.5％的有效率;治疗组与对照组的疗效基本接近,分别为26.7％与25.8％。在不良反应方面,贫血及白细胞下降发生率,奈达铂组与DDP组基本一致,而血小板的抑制率,奈达铂组则明显高于顺铂组,且严重的血小板下降在奈达铂组中有较高的发生率。奈达铂可致轻度恶心、呕吐。结论：奈达铂对晚期的NSCLC有一定的疗效,对于顺铂或卡铂耐药的NSCLC病人,奈达铂仍有一定的有效率。奈达铂单药或联合治疗临床可耐受,不良反应主要为骨髓抑制,特别是血小板下降。