腹腔热灌注化疗治疗腹膜假性黏液瘤的现状

腹腔热灌注化疗(intraperitoneal hyperthermic perfusion chemotherapy,IHPC)可以清除肿瘤切除术后腹腔内残存的病灶,预防与治疗恶性肿瘤腹腔种植性转移,临床应用取得了满意的疗效[1].传统的细胞减瘤术(cytoreductive surgery,CRS)对腹膜假性黏液瘤(pseudomyxoma peritonei,PMP)的疗效不尽人意[2].如何在CRS术后彻底清除腹腔内残存的PMP活性细胞是预防PMP术后复发、提高患者长期生存率、改善患者预后的关键.现将CRS术后应用IHPC治疗PMP的临床应用现状作一综述.     

晚期胃癌的腹腔热灌注联合全身静脉化疗临床疗效的观察

目的探讨合并腹腔和肝脑脏器转移的晚期胃癌患者,腹腔热灌注化疗联合全身静脉化疗的临床疗效。方法 23例晚期胃癌患者分为2组,实验组10例行腹腔热灌注化疗联合全身静脉化疗,对照组13例仅行单纯静脉化疗。比较2组患者的不良反应和并发症、生存情况、KPS评分情况。结果实验组总生存期较对照组延长,差异有统计学意义(P=0.003)。2组治疗前的生存质量KPS评分没有统计学差异(P=0.835),2组患者的不良反应及并发症发生率无统计学差异。结论合并腹腔和肝脑脏器转移的晚期胃癌患者,行腹腔热灌注化疗联合全身静脉化疗较单纯全身静脉化疗,可能有助于改善其生存质量和延长生存期。     

腹腔热灌注化疗治疗卵巢癌的护理

卵巢癌是女性生殖道癌瘤中死亡率最高的一种肿瘤，早期无明显症状，多数病人在就诊时已有腹腔内广泛转移，手术已无法根除。卵巢癌以腹盆腔播散、种植为主要转移途经。手术减瘤合并化疗即使是完全缓解的患者，仍然有50％～70％限于腹盆腔内复发，最终导致死亡。腹腔内化疗使腹腔内较长时间保持高药物浓度，增加药物与肿瘤广泛接触。热疗可有效增加药物对肿瘤的渗透，增加药物的细胞毒作用，提高晚期复发性卵巢癌的疗效。我科自2004年8月采用中心静脉导管留置于腹腔内进行腹腔灌注热化疗，取得了满意的疗效，现报告如下。     

腹腔热灌注化疗联合静脉化疗治疗晚期卵巢癌的疗效及对血清MMP9、VEGF、HE4的影响

目的:探究腹腔热灌注化疗联合静脉化疗治疗晚期卵巢癌的疗效及对血清基质金属蛋白酶(MMP)9、血管内皮生长因子(VEGF)、人附睾蛋白(HE4)的影响.方法:选取2015年3月至2017年3月我院肿瘤接收治64例晚期卵巢癌患者,按信封随机法将其分为对照组31例和观察组33例,对照组采取常规静脉化疗,观察组再对照基础上联合腹腔热灌注化疗,两组均治疗12周后,比较血清MMP-9、VEGF、HE4水平;同时随访36个月,比较两组远期疗效及复发率.结果:观察组总有效率、疾病控制率分别为63.64％、75.76％,均高于对照组的35.48％、51.16％,差异均有统计学意义(P<0.05);两组1年存活率比较,差异无统计学意义(P>0.05),观察组术后3年存活率为72.73％,高于对照组的48.39％,观察组复发率为27.27％,低于对照组的54.84％,差异均有统计学意义(P<0.05);治疗后两组血清MMP-9、VEGF、HE4水平均低于治疗前,观察组低于对照组,差异均有统计学意义(P<0.05).结论:腹腔热灌注化疗联合静脉化疗治疗晚期卵巢癌近期疗效切确,可显著降低患者血清清MMP-9、VEGF、HE4水平,降低复发率,改善远期生存.     

胃癌术后早期腹腔循环热灌注化疗的临床应用分析

目的：观察分析胃癌术后早期腹腔循环热灌注化疗的临床应用效果。方法回顾性分析78例胃癌手术患者临床资料,按术后化疗方法分为研究组(39例)和对照组(39例),两组患者均给予静脉化疗,研究组在此基础上加以早期腹腔循环热灌注化疗,对比观察两组临床应用效果。结果研究组术后不良反应、并发症与对照组对比,无统计学差异意义(P>0.05);研究组复发率、生存率、细胞免疫功能变化对比,具有统计学差异意义(P<0.05)。结论在静脉化疗基础上,给予胃癌术后患者早期腹腔循环热灌注化疗,可取得显著的临床应用效果,能有效降低患者复发率,提高生存率,改善细胞免疫功能,是胃癌术后理想的化疗方法。     

腹腔灌注及静脉化疗配合热疗治疗晚期卵巢癌的临床观察

目的评价腹腔及静脉化疗配合局部热疗治疗晚期卵巢癌的疗效。方法2003年1月～2005年1月收治的48例卵巢癌病人随机分为观察组25例,对照组23例。观察组采用腹腔灌注和静脉化疗,同时局部给予热疗,对照组仅给予腹腔及静脉化疗。结果观察组和对照组有效率分别为56．0％和21．7％。结论腹腔及静脉化疗配合热疗治疗卵巢癌的疗效优于单纯腹腔及静脉化疗,对治疗晚期卵巢癌有一定的临床价值,值得推广应用。     

细胞减瘤术联合腹腔热灌注化疗治疗在结直肠癌腹膜转移的临床应用

结直肠癌腹膜转移是结直肠癌的终末期病变,预后较差,多采用保守治疗。近年来,细胞减瘤术联合腹腔热灌注化疗治疗结直肠癌腹膜转移逐渐被接受,可显著改善患者的预后,但由于其设备的缺乏、手术的复杂、并发症相对较多等原因未得到普遍应用。本文对其理论基础、技术方法、临床研究及风险与安全等方面进行了综述,探索结直肠癌腹膜转移的多模式治疗方案,进一步提高结直肠癌腹膜转移患者的治疗效果。     

腹腔热灌注化疗联合腹部射频热疗对老年晚期卵巢癌患者的疗效分析

目的:通过观察腹腔热灌注化疗联合腹部局部射频热疗对细胞减灭术后的老年晚期卵巢癌患者血清糖类抗原125(CA125)、人附睾蛋白4(HE4)、甲壳质酶蛋白(YKL)及免疫功能指标的变化,探讨其对癌性腹水的影响及抗肿瘤效应。方法:选择72 例老年晚期卵巢癌患者纳入研究,随机分为对照治疗组和联合治疗组,每组36 例。对照治疗组患者给予细胞减灭术后腹腔热灌注化疗治疗,联合治疗组在行对照治疗组治疗基础上联合腹部局部射频热疗。2 个疗程后评价疗效。比较两组的手术情况、临床有效率、腹水控制有效率,测定比较两组治疗前后的CA125、HE4 和YKL 含量及T 细胞亚群水平的变化,评价安全性。结果:两组的手术情况无差异。联合治疗组患者临床总有效率为80.6%,显著优于对照治疗组的55.6% (字2 = 5.175,P<0.01)。联合治疗组的腹水控制有效率80.0% 显著高于对照治疗组的52.4% (字2 =3.962,P<0.05)。治疗后,两组的CA125、HE4、YKL 均较治疗前显著降低,且联合治疗组下降程度较对照治疗组更加显著,差异均有统计学意义(P<0.05)。治疗后,两组的CD3+ 、CD4+ 、CD4+ / CD8+均较治疗前提高,CD8+较治疗前降低,且联合治疗组各指标改善程度较对照治疗组更加显著,差异均有统计学意义(P<0.05)。两组的骨髓抑制、消化道反应及肝肾功能损伤等不良反应的差异无统计学意义(P>0.05)。结论:CRS、IPHC 细胞减灭术联合腹部局部射频热疗能显著改善卵巢癌的免疫抑制,降低CA125、HE4、YKL 水平,提高老年晚期卵巢癌患者的近期临床疗效,可在临床上推广使用。     

腹腔热灌注与顺铂联用增加人卵巢癌细胞系凋亡

目的研究腹腔热灌注(HIPE)和顺铂对人卵巢癌细胞凋亡的影响。方法将人卵巢癌OVCAR-3和A2780细胞各分为对照组、顺铂组、热疗组和热化疗组;显微镜观察卵巢癌细胞形态;AO/GV染色、流式细胞仪检测卵巢癌细胞凋亡细胞比率;荧光定量PCR(q-PCR)检测卵巢癌细胞凋亡相关基因caspase7、caspase9和Bid等。结果 1)顺铂组、热疗组及热化疗组卵巢癌细胞回缩,部分漂浮,其中热化疗组细胞变化最明显;2)顺铂组、热疗组及热化疗组较对照组凋亡细胞增多,其中热化疗组凋亡细胞数量最多(P0.05);3)顺铂组、热疗组、热化疗组较对照组凋亡细胞比率增多,热化疗组凋亡细胞比率最大(P0.05);4)促凋亡相关基因caspase3、caspase6、caspase7、caspase8、caspase9、Bax、Bak和Bid在热化疗组表达明显高于其他各组,凋亡抑制相关基因Bcl-2、Bcl-x L、Mcl-1和c-FLIP表达较其他各组明显下降。结论顺铂和热疗可促进卵巢癌细胞凋亡,且热化疗联合作用效果最明显。     

中晚期肝癌介入治疗及预后分析

目的探讨中晚期肝癌的治疗方法和预后因素.方法将我院323例住院的中晚期肝癌患者,经股动脉穿刺行肝动脉灌注化疗栓塞术(Transcatheterarterialchemoembolization,TACE)的病例资料进行回顾性分析,依据影像学,血生化指标及生存时间判断疗效.结果323例患者术后肿块缩小占60.3%,症状改善,1年生存率48.9%,2年生存率6.2%,3年生存率4.9%,中位生存期14.9个月.结论介入治疗是中晚期肝癌的有效治疗手段,可减轻症状,延长患者寿命,但要注意并发症的发生.     

实用新型腹腔内循环热灌注系统的研制及其应用

目的研制一种新型腔内循环热灌注系统并进行初步临床应用，以解决国内热灌注化疗设备入腔内水温高、灌注流量低的问题。方法利用心脏手术体外循环装置，即人工心肺机的单一滚压泵，变温水箱的升温部分，组合成腔内热灌注机。热灌注系统由一次性腔内热灌注装置和灌注机组成，其中热灌注装置包括热灌注插管、灌注环路、腹腔压力监测管路、储液器、变温器。热灌注机由灌注泵、变温水箱、温度、压力和时间监测仪组成。通过20例腔内循环热灌注化疗的临床应用验证此系统是否达到设计要求。结果该腔内循环热灌注系统人腔内水温≤43℃时腹腔内流出体外的水温41．5～42．7℃，灌注流量2000～3000mL／min。结论该实用新型一次性腔内热灌注化疗装置和热灌注机符合国际热灌注化疗标准，实用、安全、方便、有效，适合临床推广应用。     

Multidrug resistance-associated biomarkers PGP, GST-pi, Topo-II and LRP as prognostic factors in primary ovarian carcinoma

This study aims to investigate the expression of P-glycoprotein (PGP), glutathione S-transferase pi (GST-pi), DNA topoisomerase II (Topo-II) and lung resistance-related protein (LRP) in ovarian carcinoma, thus providing better chemotherapy choice and post-operative prognosis for ovarian carcinoma patients. A total of 80 primary ovarian carcinoma, 16 benign ovarian epithelial neoplasm, and 12 normal ovarian tissue samples were collected. Immunohistochemistry was used to detect the expression of PGP, GST-pi, Topo-II and LRP, and the results were analysed by correlation with clinicopathological parameters. Positive expression rates of PGP, GST-pi, Topo-II and LRP in patients with ovarian carcinoma (57.5%, 58.8%, 76.3% and 73.8%, respectively) were all higher than those found in normal and benign tissue (P<0.05). In clinical stages I/II vs. III/IV, the expression rates of PGP, GST-pi, Topo-II and LRP were 40.7% vs. 66% (P<0.05), 40.7% vs. 67.9% (P<0.05), 66.7% vs. 81.1% (P>0.05) and 55.6% vs. 83.0% (P<0.05), respectively. Carcinoma differentiation ranged from well to poor, and expression levels of each marker were as follows: PGP, 57.9%, 62.1% and 53.1% (P>0.05); GST-pi, 36.8%, 55.2% and 75.0% (P<0.05); Topo-II, 52.6%, 79.3% and 87.5% (P<0.05); and LRP, 84.2%, 69.0% and 71.9% (P>0.05). Ovarian carcinoma patients with PGP-, GST-pi-, Topo-II- and LRP-positive expression had a shorter median survival time than those who were negative for these markers (PGP: 36 months vs. 48 months [P=0.0017]; GST-pi: 36 months vs. 41 months [P=0.0103]; Topo-II: 37 months vs. 39 months [P=0.3811]; LRP: 37 months vs. 55 months [P=0.002]). COX regression analysis demonstrated that the clinical stage of the tumour, and the expression of PGP, GST-pi or LRP, may influence patient survival time after surgery. The relative death risk for patients with clinical stage III/IV tumours increased 9.46-fold compared to those with stage I/II tumours. The relative death risk in the PGP-, GST-pi- and LRP-positive groups increased by 2.049-, 2.452- or 2.609-fold, respectively, compared with the corresponding negative groups. PGP, GST-pi, Topo-II and LRP are all expressed in primary ovarian carcinoma, indicating the presence of multidrug resistance in this disease. Combined evaluation of PGP, GST-pi, Topo-II and LRP expression may enable better chemotherapeutic choice and provide an accurate prognosis for ovarian carcinoma patients.     

Undifferentiated carcinoma of the ovary.

Thirty-five cases of ovarian carcinomas, which had as the predominant histologic component solid areas of epithelial cells without differentiation into müllerian carcinomas, were reviewed. The patients' ages ranged from 39 to 72 years (mean age, 54 years). Two patients had clinical stage I disease, one had stage II, 26 had stage III, and six had stage IV. Microscopically, the malignant cells formed large groups or sheets with desmoplastic stroma around them. Foci of papillary serous carcinoma, unclassified adenocarcinoma, or transitional cell carcinoma were seen in 26 tumors, foci of necrosis were seen in 30 tumors, and vascular invasion was seen in seven tumors. Six of 13 carcinomas tested expressed CA125 reactivity, and 12 of 13 carcinomas reacted to B72.3 monoclonal antibody. The primary tumors were treated by aggressive surgical reduction in 32 patients and by multiple biopsy procedures in three patients. After the first operation, 30 patients had residual disease, smaller than 2 cm in five patients and larger than 2 cm in 23 patients. After surgery, 33 patients received chemotherapy; three of these 33 also received radiotherapy. One patient was treated with postsurgical radiotherapy only, and one patient refused further treatment. Thirty-four patients (97%) died of disease between 8 and 108 months (mean, 27 months) after initial surgery, 29 patients died in less than 32 months. Four patients (11%) survived more than 5 years: two patients with stage I disease who died at 82 and 102 months, one patient with stage II who died at 72 months, and one patient with stage III who has no evidence of disease after 116 months. Five-year survival of patients with undifferentiated ovarian carcinoma is worse than the reported survival of patients with serous carcinoma or ovarian carcinoma with a pattern resembling transitional cell carcinoma. The distinction between these three carcinomas that have solid areas carries prognostic significance.     

Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma

Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The current study was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma. A total of 60 patients, who were surgically treated for primary ovarian clear cell adenocarcinoma, were enrolled. Surgical specimens were examined for ARID1A protein expression by immunohistochemistry. The correlations between the loss of ARID1A expression and clinicopathological characteristics, prognosis, and chemosensitivity were investigated. Loss of ARID1A expression was identified in 9 (15.0%) of 60 ovarian clear cell carcinoma samples. Loss of ARID1A staining intensity (0+) was more frequently found in cells of clear cell carcinomas than in high-grade serous carcinomas (P<0.01). Loss of ARID1A expression was significantly correlated with advanced FIGO stage and high CA125 levels (P=0.02, 0.01). There were no significant correlations between loss of ARID1A expression and patient age, status of residual tumor, Ki-67 labeling index, or the status of endometriosis. Loss of ARID1A correlated with shorter progression-free survival of patients with clear cell carcinomas treated with platinum-based chemotherapy (P<0.01). Loss of ARID1A expression tended to correlate with shorter overall survival in patients with ovarian clear cell carcinomas treated with platinum-based chemotherapy. When data were stratified for the multivariate analysis, only the loss of ARID1A expression remained a significant (P=0.03) predictor of reduced progression-free survival. Of the 60 patients with ovarian clear cell carcinomas, 14 patients had measurable residual tumor after primary cytoreductive surgery. Tumors with loss of ARID1A expression were more likely to be chemoresistant than tumors with positive ARID1A expression (100.0 vs 40.0%, P=0.04). This study demonstrates that loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy. Measurement of ARID1A expression may be a method to predict resistance to platinum-based chemotherapy in patients with ovarian clear cell carcinoma.     

Correlation of serum CA125 with stage, grade and survival of patients with epithelial ovarian cancer at a single centre

To evaluate the relationship between serum CA125 tumour marker level before and after surgery of epithelial ovarian carcinoma and assess its potential role as a prognostic factor. A retrospective review of 87 patients with epithelial ovarian carcinoma at a single centre between January 2001 and December 2005 was performed. Serum CA125 levels were assessed for their relationship to pathological stage, tumour grade, tumour volume and age as well as overall survival. A total of 75 patients, mean age 58.94 years and median follow-up of 24 months were included in the analysis. While the preoperative CA125 level did not correlate significantly with stage, tumour grade or survival, the postoperative CA125 correlated to FIGO stage (p<0.0001), tumour grade (p<0.0001) and overall survival (p=0.01). Reduced survival was noted with increasing age at the time of surgery (p=0.009) and bulk of the residual disease postoperatively (p=0.011).     

Surgical intervention in patients with aplastic anemia.

Eighteen surgical procedures have been performed on 14 cases of aplastic anemia (AA). Of the 10 major surgical procedures, 7 were emergency and 3 elective. The median duration from the diagnosis of AA to major surgery was 0.5 months (3 days-47.3 months), and the median survival after surgery was 12.3 months (4 days-38 months). The hematological status of AA at the time of major surgery were 3 in partial response (PR), 2 with no response (NR) and 5 at diagnosis, respectively; and those after major surgery were 2 with complete response (CR), 2 in PR, 1 with minimal response, and 2 in NR. Three postoperative complications were sepsis, pneumonia and atelectasis encountered in 2 cases. A total of 3 deaths were caused by infection and cancers. Considering the fact that surgery may not only control complications, but offer the opportunity to give effective therapy for AA and therefore improves chances for survival, it is strongly suggested that active surgical intervention should be performed if the patient's status is not terminal.     

Regimens with intraperitoneal cisplatin plus intravenuous cyclophosphamide and intraperitoneal carboplatin plus intravenuous cyclophosphamide are equally effective in second line intraperitoneal chemotherapy for advanced ovarian cancer

PurposeWe compared response, survival and side effects of regiments with intravenous cyclophosphamide followed by intraperitoneal cisplatin versus intravenous cyclophosphamide followed by intraperitoneal carboplatin as second line treatment in one center retrospective study.Material and MethodsInclusion criteria were: relapse or recurrence of the disease after surgery and first line treatment; stage III histologicaly documented serous epithelial ovarian cancer after one or more prior regiments of chemotherapy. Recurrence were confirmed throughout restaging laparotomy or second look laparotomy. Patients from one of the groups received 90mg/m2 cisplatin on the first day and 750mg/m² cyclophosphamide intravenously, while the second group members AUC 6 carboplatin intraperitoneally and 750mg/m² cyclophosphamide intravenously. Four courses were administrated for each patient.ResultsOf the 49 patients in the cisplatin group the response rates were 21 (43%), 10 (20%) and 18 (37%) in the groups of pathologic complete response, pathologic partial response and progressive disease, respectively. The median survival from the initiation of intraperitoneal chemotherapy was 59 months. Of the 25 patients in the carboplatin group the response rates were 10 (40%), 4 (16%) and 11 (44%) respectively. The median survival -51 months. The differences between the groups were not statistically significant p>0.05 either in response or in toxicity.ConclusionsThe results of our research including relatively long survival from intraperotoneal chemotherapy initiation confirm that carboplatin treatment is as good as cisplatin in second line intraperitoneal chemotherapy for ovarian cancer.     

中性粒细胞/淋巴细胞比值对晚期肝细胞癌FOLFOX肝动脉灌注化疗近期疗效的影响

目的:探讨中性粒细胞/淋巴细胞比值（NLR）对晚期肝细胞癌（HCC）动脉灌注化疗近期疗效的影响。方法:回顾性收集分析2017年5月~2019年3月使用FOLFOX肝动脉灌注化疗的晚期HCC患者共92例。通过CT或MR比较患者每个治疗周期后肿瘤局部反应,通过相关检查结果及临床症状观察患者疗效及肝动脉灌注安全性等。结果:根据mRECIST标准对肝内病灶进行评价,NLR＜4.0组患者的客观缓解率显著高于NLR≥4.0组患者（41.5% vs 17.9%, P=0.016）。NLR＜4.0组患者的疾病控制率显著优于NLR≥4.0组（52.8% vs 28.2%;P=0.018）。对于肝内病灶,NLR＜4.0组的中位PFS（月）较NLR≥4.0组更长（6.1 vs 4.1, P=0.013）。针对全身肿瘤病灶进行疗效评估,NLR＜4.0组和NLR≥4.0组之间的中位PFS（月）也有显著差异（4.3 vs 3.1, P=0.022）。结论:使用FOLFOX肝动脉灌注治疗HCC安全性及有效性均较好,且NLR是预测HCC灌注化疗术后疗效的指标,术前高NLR的HCC患者治疗后PFS较短。