新辅助化疗联合肿瘤细胞减灭术及术后腹腔热灌注化疗在晚期卵巢癌治疗中的应用价值分析

目的 研究新辅助化疗(NACT)联合肿瘤细胞减灭术(CDS)及术后腹腔热灌注化疗(IPHC)治疗晚期卵巢癌的临床疗效.方法 选择86例Ⅲ～Ⅳ期卵巢癌患者,依据随机数字表法将患者分为试验组(n=43)和对照组(n=43).试验组患者行NACT联合CDS及术后IPHC治疗,对照组患者行CDS联合卡铂/顺铂化疗治疗.观察两组患者的术中和术后指标、治疗前后外周血T淋巴细胞因子水平、术后不适和不良反应发生率及临床疗效.结果 试验组患者术中腹腔积液量和失血量明显少于对照组,手术时间、术后化疗疗程和住院时间明显短于对照组(P﹤0.01).试验组患者术后发热率、感染率低于对照组,术后切口Ⅱ期愈合率高于对照组(P﹤0.05).治疗后,试验组患者的CD3+CD56+、CD3+CD4+水平及CD3+CD4+/CD3+CD8+明显高于对照组,差异有统计学意义(P﹤0.01).两组患者恶心呕吐、腹泻腹痛、便秘、肝肾毒性、骨髓抑制不良反应发生率比较,差异均无统计学意义(P﹥0.05).试验组患者的客观有效率为62.79％(27/43),高于对照组的37.21％(16/43),差异有统计学意义(P﹤0.05).结论 NACT联合CDS及术后IPHC可有效清除卵巢癌细胞,改善晚期卵巢癌患者的手术指标,提高机体的免疫能力,且不良反应发生率低,疗效较好,值得临床推广.     

新辅助化疗联合肿瘤细胞减灭术后热灌注化疗治疗晚期卵巢癌疗效观察

目的探讨新辅助化疗联合肿瘤细胞减灭术后热灌注治疗晚期卵巢癌的临床疗效。方法选取2009年4月至2012年7月间收治的60例晚期卵巢癌患者,按收治时间顺序分为两组,观察组患者术前采取新辅助化疗,术后联合腹腔内热灌注辅助化疗1次(顺铂80mg),术后给予TC/TP方案化疗;对照组患者采取常规肿瘤细胞减灭术+术后TC/TP方案化疗,比较两组患者在手术时间、出血量、腹水量、术后化疗疗程、疗效、复发与死亡、生存率等方面的差异。结果观察组患者手术时间为(215.34±32.76)min,腹水量为(678.35±32.32)ml,失血量为(502.89±118.53)ml,对照组患者手术时间为(275.35±42.98)min,腹水量为(1242.24±204.3)ml,失血量为(759.64±153.45)ml,两组比较差异有统计学意义(P<0.05)。观察组患者术后化疗疗程较对照组明显减少(P<0.05)。观察组患者总有效率为83.3%,对照组为33.3%,两组比较差异有统计学意义(P<0.05)。观察组和对照组患者1年生存率比较,差异有统计学意义(P<0.05)。结论晚期卵巢癌患者采取术前新辅助化疗联合肿瘤细胞减灭术、术后热灌注辅助化疗,对患者预后和疗效较常规的方法有较大提高,值得在临床上进行推广。     

先期化疗联合肿瘤细胞减灭术后腹腔热灌注化疗治疗晚期卵巢癌的临床疗效分析

目的 探讨先期化疗联合肿瘤细胞减灭术后腹腔热灌注化疗治疗晚期卵巢癌的临床疗效.方法 将58例卵巢癌患者随机分为对照组和实验组.对照组采用常规肿瘤细胞减灭术联合术后腹腔热灌注化疗(TC/TP方案),实验组在对照组基础上于术前行新型辅助化疗,对比分析2组患者临床治疗效果.结果 实验组手术时间、术中出血量、腹水量以及术后感染率明显优于对照组,差异有统计学意义(P＜0.05),但2组患者在住院时间上差异无统计学意义(P＞0.05).实验组患者治疗疗程结束后外周血免疫相关指标因子CD3+ CD4+、CD3+ CD56+以及CD3+ CD4 +/CD3+ CD8+与对照组相比,上升趋势更明显,差异具有统计学意义(P＜0.05).实验组治疗疗程结束后总有效率为72.4％,显著高于对照组(41.4％),具有统计学意义(P＜0.05);实验组与对照组在癌肿的复发率、死亡率以及1年生存率上差异不具统计学意义(P＞0.05).结论 先期化疗联合肿瘤细胞减灭术后腹腔热灌注化疗对晚期卵巢癌的近期疗效显著,可有效改善患者免疫抑制现象.     

晚期卵巢癌肿瘤细胞减灭术术前选择新辅助化疗的评估

卵巢癌是妇科三大肿瘤之一。因卵巢位于盆腔深部,卵巢癌患者多无明显症状,察觉时已是晚期。晚期卵巢癌恶性程度高,预后差,手术辅以化疗是目前主要治疗手段。手术中尽可能切除肿瘤、缩小残留病灶达到理想肿瘤细胞减灭术以延长生存期、改善预后。对于无法手术的晚期卵巢癌患者,新辅助化疗能够改善手术条件,增加手术满意度,是可行的治疗方案。因此,术前对晚期卵巢癌患者手术可行性进行评估,予以患者正确的首选治疗方案,提高手术满意度,避免不必要的剖腹探查。目前用以晚期卵巢癌肿瘤细胞减灭术术前评估的方法有1)影像学检查,如CT、PET,MRI等;2)CA125值,根据CA125值的高低评估手术可行性;3)腹腔镜探查,根据术中所见评估开腹手术可行性;4)其他各种肿瘤标记物如p53。各研究中探讨的手术评估手段大多局限于某一个方面,未能将有意义的预测因素全部纳入进行综合分析,准确性尚存在不足。探索新的方式方法,或是交叉应用两种或两种以上评估手段对晚期卵巢癌肿瘤细胞减灭术可行性进行综合评估,提高手术满意程度,缩小残留病灶,达到延长晚期卵巢癌患者生存时间和改善晚期预后的目的。本文就晚期卵巢癌肿瘤细胞减灭术可行性的评估和新辅助化疗的选择进行综述。     

细胞减灭术联合腹腔热灌注化疗治疗晚期卵巢癌的疗效分析

目的 探讨细胞减灭术联合腹腔热灌注化疗(IPHC)治疗晚期卵巢癌的疗效.方法 将90例晚期卵巢癌患者按治疗方法不同分为IPHC组(48例)和常规组(42例),两组患者均予以细胞减灭术,常规组术后予以全身静脉化疗,IPHC组术后予以IPHC+全身静脉化疗.比较两组患者临床疗效、肿瘤血清学指标[白细胞介素-1β(IL-1β)、人附睾蛋白4(HE4)、糖类抗原125(CA125)]、免疫功能指标[T细胞亚群(CD3+、CD4+、CD8+)]及不良反应.结果 IPHC组患者总有效率高于常规组,差异有统计学意义(P﹤0.05).治疗后,两组患者IL-1β、HE4、CA125水平均下降(P﹤0.05),且IPHC组患者IL-1β、HE4、CA125水平均明显低于常规组(P﹤0.01).治疗后,两组患者CD3+、CD4+水平均上升,CD8+水平均下降(P﹤0.05),且IPHC组患者CD3+、CD4+水平均明显高于常规组,CD8+水平明显低于常规组(P﹤0.01).两组患者≥3级恶心呕吐、腹泻腹痛、骨髓抑制、肝肾功能不全发生率比较,差异均无统计学意义(P﹥0.05).结论 细胞减灭术联合IPHC治疗晚期卵巢癌疗效肯定,显著改善肿瘤血清学指标水平,改善卵巢癌免疫抑制,且安全可靠.     

肿瘤细胞减灭术加腹腔热灌注化疗治疗卵巢癌的术后不良事件分析

目的 探讨晚期卵巢癌及复发性卵巢癌患者经肿瘤细胞减灭术(CRS)和腹腔热灌注化疗(HIPEC)治疗后围手术期的不良事件情况.方法 回顾性分析2015年4月至2019年7月收治的95例经CRS+HIPEC治疗的晚期卵巢癌或复发性卵巢癌患者的临床病理资料.结果 原发性卵巢癌患者44例,复发性卵巢癌患者51例,死亡率和3～4...     

卵巢癌肿瘤细胞减灭术后腹腔热灌注化疗的不良反应和有效性分析

目的：分析腹腔热灌注化疗治疗卵巢癌肿瘤细胞减灭术后患者的不良反应和有效性。方法：回顾性分析2016年1月至2017年8月于我院妇科肿瘤中心就诊的92例Ⅱ～Ⅳ期卵巢癌患者的病例资料,其中对照组50例,研究组42例,所有患者均行满意的肿瘤细胞减灭术,对照组术后给予6疗程紫杉醇＋卡铂静脉化疗,研究组术后给予2次顺铂腹腔热灌注化疗联合6疗程紫杉醇＋卡铂静脉化疗,所有患者随访24～43个月,观察两组患者不良反应的发生率及治疗的有效性。结果：两组患者腹痛、全身感染、恶心呕吐、骨髓抑制和肝肾功能损伤的发生率比较,差异无统计学意义(P＞0.05)。研究组的中位生存时间较对照组显著延长(42.00个月ｖS36.00个月),研究组的生存情况优于对照组,差异有统计学意义(P＜0.05);研究组的中位无进展生存期较对照组显著延长(16.00个月ｖS13.00个月),差异有统计学意义(P＜0.05);研究组的2年复发率低于对照组,差异有统计学意义(P＜0.05)。结论：顺铂腹腔热灌注化疗能有效改善卵巢癌肿瘤细胞减灭术后患者的预后,延长生存时间,提高生存率,且不增加不良反应的发生率,是一种安全有效的治疗卵巢癌的手段。     

倾向性评分匹配评估肿瘤细胞减灭术联合腹腔热灌注化疗治疗晚期卵巢癌的疗效

  目的  探讨传统减瘤术与肿瘤细胞减灭术（cytoreductive surgery,CRS）联合术中腹腔热灌注化疗（hyperthermic intraperitone-al chemotherapy,HIPEC）治疗上皮性卵巢癌腹膜转移（peritoneal carcinomatosis of epithelial ovarian cancer,EOCPC）的疗效。  方法  收集2004年5月至2019年5月186例于首都医科大学附属北京世纪坛医院行手术切除的卵巢癌患者的临床病理资料,采用倾向性评分匹配（propensity score matching,PSM）2:1匹配后,纳入133例EOCPC患者,分为行传统减瘤术80例为对照组、行CRS+HIPEC53例为研究组,并行亚组分析。比较两组中位生存期（median overall survival,mOS）。  结果  研究组患者mOS显著长于对照组（87.3个月vs.25.2个月,P=0.002）,5年生存率为对照组2.5倍（46.5% vs.18.3%,P=0.003）,3、4年生存率均为对照组1.9倍（70.0% vs.36.7%,P=0.016）。亚组分析显示,达到满意肿瘤细胞减灭研究组mOS较对照组显著延长（118.1个月vs.70.7个月,P=0.024）;未达到满意肿瘤细胞减灭研究组mOS显著长于对照组（87.3个月vs.23.1个月,P=0.028）。  结论  标准化、规范化CRS+HIPEC为治疗EOCPC的必要措施,可为患者带来显著的生存获益。      

新辅助化疗联合肿瘤细胞减灭术治疗Ⅲ～Ⅳ期卵巢癌的疗效分析

目的 探讨新辅助化疗联合肿瘤细胞减灭术治疗Ⅲ～Ⅳ期卵巢癌的疗效.方法 回顾性分析60例Ⅲ～Ⅳ期卵巢癌的临床治疗相关资料,根据采用的治疗方法不同分为对照组30例和化疗组30例,其中对照组患者仅行肿瘤细胞减灭术,观察组患者术前进行新辅助化疗后再行肿瘤细胞减灭术.比较分析两组患者的肿瘤体积、腹腔积液量、术中出血量、手术时间和住院时间等相关指标,并观察疗效.结果 观察组患者的肿瘤体积、腹腔积液量、术中出血量、手术时间和住院时间等指标与对照组相比均显著降低(P＜0.05);观察组患者的临床疗效显优于对照组,观察组的总有效率为73.3％,显著高于对照组(43.4％).结论 Ⅲ～Ⅳ期卵巢癌患者肿瘤细胞减灭术之前,进行2～3个疗程的化疗可减少腹腔积液量和术中出血量,缩短手术时间和住院时间,提高临床疗效.     

Perioperative fast track program in intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery in advanced ovarian cancer

Introduction

Diffuse peritoneal dissemination in advanced ovarian cancer can be treated using optimal effort surgery involving peritonectomy procedures and the administration of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC).

Objective

To report on our experience in the treatment of advanced ovarian cancer using peritonectomy procedures and HIPEC through the fast track program.

Patients and method

From September 2008 until May 2010, forty-six patients with primary advanced (stage III-C) or recurrent ovarian cancer have been included in the fast track protocol if they had optimal cytoreduction CC-0 or CC-1 accompanied by HIPEC and there had no more than one digestive anastomosis.

Results

The mean peritoneal cancer index (PCI) was 12.35 (3-21). The median operation time was 380 min (200-540). Optimal surgery CC-0 was achieved in 38 of the 46 patients and CC-1 in the remaining 8. Mean postoperative hospital stay was 6.94 ± 1.56 days (3-11). Major morbidity rates were 15.3%. Paralytic ileus was the most frequent of these. There was no mortality related to the procedure.

Conclusion

Surgery with peritonectomy procedures and HIPEC in advanced ovarian carcinoma is possible under fast track surgery programs in patients with low volume peritoneal carcinomatosis. Prospective and randomized studies are needed.     

Adjuvant chemotherapy for high-grade appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

IntroductionThere are no available data on the efficacy of adjuvant chemotherapy (ACT) in stage IVA/B high-grade mucinous appendiceal cancer treated with CRS/HIPEC. We evaluated the association between ACT and survival in this cohort.Materials and methodsA single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade mucinous appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1 were included. Survival was compared between ACT and no chemotherapy (NoCT) patients. Subgroup analysis was performed with adjustment for confounding variables.ResultsWe identified 180 patients: 77 ACT and 103 NoCT. ACT regimens included 5-FU/capecitabine (13%), oxaliplatin-based (63%), and irinotecan-based (21%), combined with bevacizumab in 27% of cases. Median number of cycles was 9 (IQR: 6–12). Median overall survival (OS) did not significantly differ between ACT and NoCT (53 vs 75 months, p = 0.566). Multivariable Cox regression showed no OS benefit for ACT vs NoCT in patients with neoadjuvant chemotherapy (HR 1.14; 95%CI: 0.38–3.39) or without it (HR 1.33; 95%CI: 0.69–2.57), with signet ring cell (HR 0.89; 95%CI: 0.38–2.06) or other histologies (HR 1.11; 95%CI: 0.50–2.46), positive lymph nodes (HR 1.60; 95%CI: 0.74–3.49), or peritoneal cancer index ≥20 (HR 1.08; 95%CI: 0.55–2.11) after adjusting for other factors.ConclusionsIn our cohort, colon-type ACT was not associated with better OS in stage IVA/B mucinous appendiceal cancer after CRS/HIPEC, even after adjusting for confounders. This may be due to different tumor biology than colon cancer or small sample size. Prospective collaborative studies are needed.     

腹腔热灌注化疗联合细胞减灭术对胆囊癌腹膜转移的临床疗效研究

目的:探讨腹腔热灌注化疗(hyperthermic intraperitoneal chemtheropy,HIPEC)治疗胆囊癌伴腹膜转移患者的临床疗效研究。方法:本文回顾性分析海军军医大学东方肝胆外科医院2015年1月至2018年1月收治的84例胆囊癌合并腹膜转移患者,31例患者给予HIPEC联合细胞减灭术(cytoreductive surgery,CRS)+术后1个月全身化疗为研究组,53例给予细胞减灭术+术后1个月全身化疗为对照组,观察比较两组临床疗效及不良反应发生情况。结果:研究组中位生存时间为(21.72±2.96)个月,显著长于对照组的(14.93±2.09)个月(P<0.05)。研究组白细胞减少、血红蛋白减少、血小板减少、胃肠道反应、肝功能损伤和肾功能损伤较对照组无显著性差异(P>0.05)。结论:HIPEC治疗进展期胆囊癌临床疗效显著,可延长患者生存时间,不良反应较小,值得推广应用。     

Anastomotic leakage after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer

BackgroundAnastomotic leakage (AL) after colorectal surgery is well-researched, yet the effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) after Cytoreductive Surgery (CRS) is unclear. Assessment of risk factors in these patients may assist surgeons during perioperative decision making.MethodsThis was a single-center, retrospective study of patients who underwent CRS-HIPEC for colorectal peritoneal metastases. Main outcome measures were anastomotic leakage and associated morbidity.ResultsAL was observed in 17 of the 234 (7.3%) anastomoses in 17 of the total of 165 (10.3%) of patients. No association was observed between the number and location of anastomoses and AL, although only one in 87 small bowel anastomoses showed leakage. The only factor associated with AL was administration of bevacizumab within 60 days prior to surgery with an odds ratio (OR) of 6.13 (1.32–28.39), P = 0.03. Deviating stomata were not statistically protective of increased morbidity, although more AL occurred in the patients with colocolic and colorectal anastomoses when no concomitant deviating stoma was created. Deviation stomata were reversed in 52.6%, and no AL was observed after stoma reversal.ConclusionThe overall AL rate of CRS-HIPEC is comparable to colorectal surgery, and there is no cumulative risk of multiple anastomoses – especially in the case of small bowel anastomoses. Deviating stomata should be considered in patients with colocolic or colorectal anastomosis, although there is a significant chance that the stoma will not be reversed in these patients. Due to increased AL-risk surgeons should be aware of previous bevacizumab treatment, and plan the CRS-HIPEC at least 60 days after the treatment-day.     

Morbidity and mortality outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with primary and recurrent advanced ovarian cancer

Background

The aim of this study is to report the perioperative outcomes of CRS and HIPEC from a single institution and review those factors that are associated with a poor perioperative outcome in patients with peritoneal dissemination from primary or recurrent ovarian cancer.

Patients and method

A retrospective cohort study setting was conducted in a third level hospital peritoneal surface malignancy program. Ninety one patients diagnosed with ovarian peritoneal carcinomatosis, primary and recurrent without extraperitoneal metastasis were included for cytoreductive surgery and HIPEC with paclitaxel. We analyzed the postoperative morbidity rates and a univariate and multivariate analysis of factors associated with overall (grade I–IV) and major (grade III–IV) postoperative morbidity were performed.

Results

Peritoneal Cancer Index (PCI) upper than 12 (OR = 2.942 95%: 1.892–9.594 p = 0.044) was an independent factor associated with the occurrence of I–IV postoperative morbidity. Regarding major complications (grade III–IV), on multivariate analysis, in addition to PCI >12 (OR = 6.692, 95% CI: 1974–45, 674, p = 0.032), the need to carry out intestinal resection (OR = 4.987, 95% CI: 1350–27, 620, p = 0.046) was an independent factor related with major morbidity (grade III–IV).

Conclusions

The use of HIPEC after aggressive cytoreductive surgery in patients with ovarian cancer with peritoneal dissemination can be performed with acceptable postoperative morbidity rates. Knowledge of the factors associated with the onset of these postoperative adverse events allows better management of the same and offers the patient a safe procedure.     

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

BackgroundFew prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).Materials and methodsBetween 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.ResultsA complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.ConclusionsA novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.