腹腔热灌注化疗的研究进展

【摘要】〓随着对腹腔肿瘤的治疗技术不断发展,世界上众多医疗中心已经把腹腔热灌注化疗作为治疗腹腔肿瘤的治疗方式。腹腔热灌注化疗对治疗腹腔内肿瘤的优势已经逐渐为医学界所认同。其兼有化疗和腹腔灌注疗法的优点,并且能使两者相互协同。把腹腔热灌注化疗和减瘤术结合起来对腹腔肿瘤有良好疗效。本文就近年来有关IHPC的发展历史、治疗作用机制,临床应用及疗效等方面进行探讨,旨在阐明腹腔热灌注化疗的研究现状及存在问题。     

恒温腹腔热灌注化疗治疗结直肠癌并恶性腹水临床疗效观察

【摘要】目的 探讨恒温腹腔热灌注化疗对结直肠癌并恶性腹水的临床疗效。方法 42例结直肠癌并腹水患者行肿瘤切除术后,使用BR-TRG-Ⅰ型体腔热灌注治疗系统进行腹腔恒温热灌注化疗,水温恒定保持在42±0.5℃,化疗液为生理盐水3000ml＋5-FU 2.0,灌注时间为60分钟。结果 42例患者均顺利完成热灌注化疗,未发生需要终止治疗的严重不良反应,其中腹水完全缓解24例（57.15%）,部分缓解12例（28.57%）,稳定4例（9.52%）,无效2例（4.76%）,有效率达到85.71%。结论 恒温腹腔热灌注化疗是治疗结直肠癌并恶性腹水的有效方法。     

消化道恶性肿瘤腹腔热灌注化疗的护理

腹腔热灌注化疗是将腹腔局部用药与全身用药、热疗与化疗结合起来 ,以寻求治疗腹腔恶性肿瘤的新途径。 1 998年 5月至 1 999年 1 2月 ,我科对 30例消化道恶性肿瘤患者采用腹腔热灌注化疗 ,效果显著。1　资料与方法1 .1　资料30例中男 1 8例 ,女 1 2例 ,年龄 32～ 69岁 ,平均 50 .5岁。贲门癌 7例 ,胃癌 1 2例 ,大肠癌 1 1例 ,所有病例均经病理学检验证实。均表现不同程度腹胀、纳差、腹痛、发热。其中合并腹水 1 1例。1 .2　方法预先将生理盐水 30 0 0～ 40 0 0 ml置恒温水浴箱中加热至 44～ 45℃ ,患者取平卧位 ,选定左或右髂前上棘与脐连…     

进展期腹腔肿瘤的热灌注化疗

我们应用腹腔内热化疗治疗 2 1例进展期腹腔肿瘤 ,总有效率为 4 7 6%。恶心、呕吐及白细胞降低发生率分别为 2 3 8%及 33 3%。现报道如下。1　临床资料2 0 0 0年 5月— 2 0 0 1年 4月本院共收治晚期腹腔肿瘤 2 1例 ,均经ＣＴ、Ｂ超、胃、肠镜检查及病理确诊。均已丧失手术治疗的条件。 2 1例中男性 16例 ,女性 5例 ;年龄 2 9～ 75岁 ,平均年龄 4 5岁。进展期胃癌 7例、大肠癌 5例、胰腺癌 3例、肝癌 6例。病史 2 0～ 34 6ｄ ,平均 78ｄ。瘤体 2 5ｃｍ～ 2 0ｃｍ×1 8ｃｍ～ 15ｃｍ。2　治疗方法治疗前检查血、尿常规 ,肝、肾功能 ,血电解质…     

手术联合腹腔热灌注化疗治疗进展期胃肠癌的研究——临床实验研究

本文报道了27例进展期胃肠癌术中根治或姑息性切除病灶后,施行丝裂霉素(MMC)腹腔或盆腔热灌注化疗的临床和药代动力学研究。方法在术中切除病灶后,以MMC～50mg加入生理盐水500ml中,经NK-1单机电脑型热灌注化疗仪加热后循环灌入腹腔,使腹腔内温度维持在41℃～43℃,持续60分钟,并分别于灌注后10、20、30、40、50、60分钟分别取腹腔液、门静脉血、外周静脉血,以高效液相法测定MMC浓度。 结果:CHPP和PHC全过程顺利,血压、中心静脉压、二氧化碳分压稍上升,肺顺应性和血PH值稍有下降,无明显呼吸、循环障碍。术后无明显化疗症状,白细胞有暂时下降,3～7天恢复正常。无肠瘘、化学性腹膜炎、肠梗阻、腹腔感染出现。二例患者因其它病再次开腹,未发现复发和转移。药代动力学显示CHPP、PHC时,腹腔液MMC浓度最高,峰值浓度为门静脉和外周静脉血的1.6和4.4倍,平均分别为1.7和4.3倍。门静脉血MMC浓度次之,峰值浓度和平均浓度为外周静脉的2.7和2.6倍。外周血浓度最低,三者间保持持久恒定的浓度差。结果表明:CHPP、PHC在腹腔或盆腔提供高浓度MMC,通过热疗与化疗协同作用,直接杀灭腹腔内游离癌细胞和残存微小癌灶,化疗毒副作用小。无手术并发症出现。防止术后复发和肝转移,是防止进展期胃肠癌术后复发肝转移提高患者生存率的     

手术联合腹腔热灌注化疗治疗进展期胃肠癌的研究——体外实验研究

腹腔内恶性肿瘤术后复发和肝转移是其最主要的致死原因。腹腔内游离癌细胞和残余微小病灶的存在,是腹腔内恶性肿瘤术后复发和转移的关键因素,至今尚未有十分有效的防治措施。腹腔热灌注化疗为此提供了新的途径。本文为寻求腹腔热灌注化疗最佳温度、时间、加温方式、渗透压等条件,用MTT法在体外进行了热化疗联合MMC对人大肠癌细胞株LOVO的细胞毒动力学研究。结果表明:单纯热疗,43℃30分钟有较强的细胞毒作用。单纯化疗MMC浓度0.01mg/ml有较强的细胞毒作用。热疗联合化疗,细胞毒作用明显加强,大于单纯热疗和单纯化疗之和,两者具有协同作用。43℃30分钟以上。细胞毒作用很强,随着时间和温度升高,细胞毒指数变化不显著,曲线平坦。单纯热疗或单纯化疗在低渗条件下,CL值大于等渗的CL值(P<0.05)。热疗与MMC联合,同温度、时间、MMC浓度下,等渗状态下CL值大于低渗下CL值(P<0.05)。缓慢加热达处理温度时细胞毒指数小于直接达处理温度的CL值(P<0.01)。以上结果提示:经尽可能短的时间由等渗的MMC化疗液使腹腔内温度达到43℃,持续时间不少于30分钟,MMC浓度不低于0.01mg/ml时,对游离癌细胞和残余微小癌灶有很强的杀灭作用,为临床腹腔内恶性肿瘤术后行腹腔热灌注化疗,防止腹腔内复发和转移提供了理论依据。     

腹腔热灌注化疗在胃肠道肿瘤中的应用

目的对腹腔热灌注与静脉化疗在胃肠道肿瘤患者中的应用情况进行评价。方法选取79例胃肠道肿瘤患者按就诊顺序分为研究组40例和对照组39例。研究组采用腹腔热灌注与静脉化疗;对照组单纯采用静脉化疗。对比两组的临床疗效、不良反应。结果研究组总有效率为67.5%,对照组为41.03%,P0.05;研究组胃肠道反应0、Ⅰ、Ⅱ级分别为77.5%、25%、12.5%,对照组分别为74.36%、17.95%、7.69%,P0.05;研究组骨髓抑制0、Ⅰ、Ⅱ级分别为82.5%、22.5%、4%,对照组分别为79.92%、12.82%、7.69%,P0.05;研究组肝功能异常0、Ⅰ级分别为92.5%、7.5%,对照组分别为89.74%、5.13%,P0.05;研究组肾功能异常0、Ⅰ级分别为95%、2.5%,对照组分别为97.44%、0,P0.05。结论腹腔热灌注与静脉化疗联合能有效的提高对胃肠道肿瘤患者的治疗效果,且不增加不良反应。     

Hyperthermic intraperitoneal chemoperfusion is an option for treatment of peritoneal carcinomatosis in children

Background

Gastrointestinal carcinomas in childhood are rare and frequently present at an advanced stage. Besides lymphatic and distant organ metastasis, peritoneal carcinomatosis may be detected and has a poor prognosis. In addition to surgery and intravenous chemotherapy, hyperthermic intraperitoneal chemoperfusion (HIPEC) may be an option for selected patients. Our aim was to demonstrate the feasibility of the method and to discuss possible indications.

Methods

After treating a series of adult patients, HIPEC for peritoneal carcinomatosis from a signet cell carcinoma of the colon was performed intraoperatively in a 12-year-old boy. We gave mitomycin C at a dose of 30 mg/m² over 90 minutes at maximum temperature of 41.2°C. We performed intraoperative drug level monitoring and daily postoperative liver and kidney function tests and differential blood counts.

Results

Hyperthermic intraperitoneal chemoperfusion was performed according to protocol without complications. Perfusate and venous drug levels were similar to those in an adult case. The patient had an uneventful recovery, and serum chemistry and blood count returned to normal after a week. The boy lived for 36 months after initial presentation. Sixteen months after HIPEC, still with excellent quality of life, an elevated carcinoembryonic antigen (CEA) indicated recurrence. Thirty months after HIPEC, he died of progressive recurrent disease.

Conclusions

Hyperthermic intraperitoneal chemoperfusion as performed in adults may be beneficial to children with peritoneal carcinomatosis and merits further study.     

胰腺肝样腺癌腹腔多发转移1例报告并文献复习

背景与目的 胰腺肝样腺癌（PHC）是一种罕见的易发生于胰腺体尾部的具有肝细胞癌（HCC）样分化特征的特殊类型腺癌,其发病率低,恶性程度高,侵袭性强,早期易发生淋巴转移和远处转移,疾病发展快,预后较差。PHC临床表现和影像学特征缺乏特异性,术前诊断困难,但多数患者可高表达甲胎蛋白（AFP）,为其诊断提供一定依据,而最终疾病的确诊需进行病理学检查。本文回顾性分析总结1例PHC并腹腔多发脏器转移的患者临床资料特点及诊治过程,并对国内外相关文献进行复习,旨在增加临床医生对PHC的认识,并不断完善疾病的治疗方案。方法 回顾性分析昆明医科大学第二附属医院肝胆胰外科收治的1例PHC并腹腔多发脏器转移患者的临床资料及诊治过程,并结合国内外相关文献对该病的发生机制、临床特点、疾病诊断及治疗方案等进行分析总结。结果 患者为63岁男性,因出现腹胀腹痛伴乏力、纳差3个月余入院,检查提示肝脏、胰腺、脾脏、胃等多脏器占位性病变,性质待排,后行姑息性减瘤手术治疗。术后病理结果提示为PHC,实性型,组织学分级3级。术后3个月出现肝内转移灶,行奥沙利铂130 mg+氟尿嘧啶200 mg肝动脉灌注化疗及栓塞治疗,后病灶转移至肺,于术后10个月因多器官功能衰竭死亡。结论 PHC是一种罕见的病因不明的具有HCC样分化特征的特殊类型腺癌,缺乏典型的临床及影像学表现,该病恶性程度高,早期易发生淋巴转移和远处转移,出现症状时多达中晚期,已丧失根治性手术切除机会;PHC发病机制不详,但病变表现为特征性的HCC样分化,可高度表达AFP及HCC免疫组织化学标志物,病理学检查是其诊断金标准;目前国内外尚无PHC的诊治共识,对于有手术切除机会的患者应积极手术治疗,切除病灶,改善预后;而对于无法根治性切除的患者可采取辅助治疗,目前认为放疗对其无效,而化疗是疾病的独立预后因素,但在化疗方案上仍存在争议;因此,有条件者可取材活检明确诊断后选择合适的化疗方案,提高患者治疗的客观缓解率,不能明确诊断者可参照消化道系统疾病治疗方案处理。     

晚期胃癌恶性腹水患者腹腔热灌注化疗期间应用不同营养支持的效果比较

目的：探讨不同营养支持方法在晚期胃癌恶性腹水患者腹腔热灌注化疗（HIPEC）期间的应用效果。 方法：将符合标准的40例患者按照随机对照原则分为肠外营养组（PN组）和肠外联合肠内营养组（PN+EN组）,每组20例,PN组患者行HIPEC同时PN支持,PN+EN 组患者行HIPEC同时PN+EN支持。比较两组患者治疗前后营养指标、免疫学指标的变化、不良反应的发生情况以及胃肠道功能恢复时间、住院时间及治疗费用。 结果：两组患者治疗前的营养指标和免疫学指标比较差异均无统计学意义（均P>0.05）。两组治疗后4、7 d的营养指标与免疫学指标均较治疗前降低,部分指标第7天有恢复趋势,PN组与PN+EN组各项营养指标的变化水平无明显差异（均P>0.05）,但PN+EN治疗后7 d的各项免疫学指标恢复程度均明显优于PN组（均P<0.05）;PN+EN组胃肠功能恢复时间、住院时间均较PN组明显缩短（均P<0.05）,治疗相关费用明显低于PN组（P<0.05）。两组患者不良反应发生率差异均无统计学意义（P>0.05）。 结论：晚期胃癌患者HIPEC期间应用肠外联合肠内营养有助于改善患者免疫功能,促进肠道早日恢复,节约医疗成本。

     

温热灌洗化疗及动脉插管化疗在胃肠道肿瘤中的应用

目的　探讨胃肠道癌手术切除后腹腔及肝转移的防治方法。方法　将 2 82例胃肠道癌切除术后患者分成术中腹腔温热低渗灌洗化疗加术后动脉灌注化疗组 1 69例 (治疗组 )和单纯术后静脉化疗组 1 1 3例 (对照组 ) ,对比两组局部复发率、肝转移率及 3年生存率。结果　治疗组腹腔转移率、肝脏转移率、和 3年生存率依次为 2 1 .9% ,1 2 .4 %和 74.6 % ;对照组依次为 46 .0 % ,2 7.4 %和 46 .8%(均P <0 .0 5)。结论　术中温热低渗灌洗化疗及术后动脉灌注化疗对进展期胃肠道肿瘤术后腹腔复发和肝转移有良好的防治作用。     

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion: The University of Arizona early experience

AIM:To evaluate the safety and effectiveness of our new cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemoperfusion(HIPEC)program.METHODS:Retrospective review of patients with gastrointestinal malignancies who were suitable candidates for CRS and HIPEC between 12/1/2009 and 10/1/2010.All clinicopathologic data were reviewed with a special focus on the surgical outcome and the postoperative morbidity and mortality.RESULTS:Fourteen patients were identified.Median age was 64 years;seven were female.The primary tumors were:colonic(29%),appendiceal(36%),peritoneal mesothelioma(14%),gastric(7%),adenocarcinoma of unknown primary(7%),and gastrointestinal stromal tumor(7%).Eleven patients(79%)received CRS/HIPEC,three for palliation.Three patients that did not undergo CRS/HIPEC had an average peritoneal cancer index(PCI)of 25.The eight patients that underwent curative CRS/HIPEC had an average PCI of 10 and a completeness of cytoreduction score of 0(87.5%) or 1(12.5%).Postoperative morbidity was 36%;the worst adverse event was Grade 3 ileus.Mortality rate was 0%.CONCLUSION:CRS with HIPEC is safe and feasible at tertiary institutions with fledgling programs.PCI is an accurate predictor of surgical outcomes.     

Chylous ascites in colorectal surgery: A systematic review

BACKGROUNDChylous ascites is a rare complication in colorectal surgery with limited evidence. AIMTo systematically review all available evidence to describe the incidence, clinical presentation, risk factors and management strategies.METHODSThe systematic review was performed through PubMed, MEDLINE, EMBASE and Cochrane and cross-checked up to November 2020. The data collated included: Demographics, indications (benign vs malignant), site of disease, surgical approach, extent of lymphadenectomy, day to and method of diagnosis of chylous ascites and management strategies. RESULTSA total of 28 studies were included in the final analysis (426 cases). Patient age ranged from 31 to 89 years. All except one case were performed for malignancy. Of the 426 cases, 195 were right-colonic, 121 left-colonic, 103 pelvic surgeries and 7 others. The majority were diagnosed during the same inpatient stay by recognition of typical drain appearance and increased volume. Three cases were diagnosed during outpatient visits with increased abdominal distention and subsequently underwent paracentesis. Most cases were managed successfully non-operatively (fasting with prolonged drainage, total parenteral nutrition, somatostatin analogues or a combination of these). Only three cases required surgical intervention after failing conservative management and subsequently resolved completely. Risk factors identified include: Right-colonic surgery/ tumour location, extent of lymphadenectomy and number of lymph nodes harvested. CONCLUSIONChylous ascites after colorectal surgery is a relatively rare complication. Whilst the majority of cases resolved without surgical intervention, preventative measures should be undertaken such as meticulous dissection and clipping of lymphatics during lymphadenectomy to prevent morbidity.     

胰腺神经内分泌肿瘤5例报告并文献复习

目的:分析胰腺神经内分泌肿瘤(PNENs)的临床特征与诊治方法。方法:回顾性分析2013年6月—2016年6月收治的5例PNENs患者临床资料。结果:PNENs 5例中,男2例,女性3例;均行B超及CT检查,1例患者行PET-CT;年龄48~75岁;临床表现各异,且无特异性;实验室检查无特异性指标;4例患者行手术治疗,1例仅行穿刺活检。病理(根据2010年WHO分期)结果为G1期2例,G2期1例,G3期2例。5例均随访,1例术后12个月因肝转移死亡,其余均恢复良好。结论:PNENs大多缺乏特征性临床表现,术前诊断困难,主要依靠术后病理组织学检查,治疗方法主要是手术为主的综合治疗,预后较好。     

瘤体周围缝扎加瘤内药物注射治疗肝海绵状血管瘤：附22例临床分析

目的：探讨瘤体周围缝扎加瘤内药物注射治疗肝海绵状血管瘤的效果。方法：对22例肝海绵状血管瘤患者，在剖腹直视下行肝海绵状血管瘤体周围缝扎加瘤内药物注射治疗。结果：全组无并发症及手术死亡。该法治疗肝海绵状血管瘤的显效率为76.19%，有效率达100%。22例获随访3个月至4年均无复发。结论：肝海绵状血管瘤瘤体周围缝扎加瘤内药物注射治疗方法安全可靠，简单易行。     

Respiratory distress due to malignant ascites palliated by hyperthermic intraperitoneal chemotherapy

Malignant ascites is a common symptom in patients with peritoneal cancer. Current assumption is that anincreased vascular permeability and obstruction of lymphatic channels lead to the accumulation of fluid in the abdominal cavity. This case report describes a severely symptomatic patient with malignant ascites. The previously healthy 73-year-old male was presented with abdominal distention causing respiratory distress. Computed tomography revealed large amounts of ascites, a recto-sigmoidal mass with locoregional lymphadenopathy and an omental cake. Biopsy taken during colonoscopy revealed an adenocarcinoma of the colon with signet cell differentiation. A widespread peritoneal carcinomatosis was found during a diagnostic laparoscopy. The extent of peritoneal disease rendered the patient not suitable for cytoreductive surgery with curative intent. The ascites proved to be refractory to ultrasound-guided paracentesis; thus, a decision was made to perform palliative hyperthermic intraperitoneal chemotherapy without cytoreductive surgery. Consequently, ascites production stopped, and the respiratory distress was relieved thereafter. The postoperative recovery was uneventful. Ascites recurred eight months later, and a second hyperthermic intraperitoneal chemotherapy procedure was performed. The patient was still alive at the time of writing, 16 mo after the initial diagnosis.     

原发直肠肛管小细胞癌1例报告并文献复习

背景与目的：原发直肠肛管小细胞癌（SCC）是直肠肛管肿瘤罕见的类型，占比不超过1%。与常见的直肠肛管腺癌相比，直肠肛管SCC的临床症状以及影像学表现不具有特异性，诊断较为困难，术后极易发生复发和远处转移，预后差，其总体病死率极高。由于直肠肛管SCC的罕见性和特殊性，目前国内外文献报道较少，缺乏相关的研究数据和治疗经验，对其认识不够深入，尚无统一的最佳治疗方案，这给临床对其诊治带来了一定的困扰。笔者通过收治1例原发直肠肛管SCC患者，分析诊疗经过，探讨直肠肛管SCC的诊断和治疗方法，以期为该类疾病诊断和治疗提供相应的临床经验和新的思路。 方法：回顾性分析1例原发直肠肛管SCC患者的临床资料，对患者的病史特点、一般情况、影像学检查、病理组织形态和免疫标记物特征进行分析诊断，根据其特点制定相应的治疗策略，并结合相关文献复习。 结果：患者表现出便血的临床特点，影像学检查考虑为直肠肛管恶性肿瘤，经过2次肠镜下组织活检病理提示为SCC，遂行腹腔镜辅助Miles手术，术后病理诊断为直肠肛管SCC。患者术后通过辅以盆腔放疗和“顺铂+依托泊苷”EP化疗方案的综合治疗，定期复查胸部CT、全腹CT、盆腔MRI、结肠镜检查、血清肿瘤标志物等均未发生肿瘤复发和远处转移，已无瘤生存13个月，目前继续随访观察中。 结论：原发直肠肛管SCC是一种罕见的疾病，总体生存率低。直肠肛管SCC的临床症状、影像学表现与常见的直肠肛管腺癌相似，不具有特异性，肠镜下的组织活检取材较为困难，确诊需要结合病理组织形态和多种免疫组化标记物。手术切除是治疗局部进展期直肠肛管SCC最为主要且有效的方法，应尽早的进行手术治疗，术后辅以盆腔放疗和“顺铂+依托泊苷”EP化疗方案的综合治疗，能改善患者的预后，延长生存期。