胃肠道癌的腹腔加温灌注化疗

胃肠道癌手术后复发和肝转移是导致病人死亡的主要原因。术后经外周静脉所给的化疗药物在腹腔内浓度很低，不仅疗效差，且全身毒副作用很大。术中术后针对切除部位、腹膜及肝脏等常见复发、转移部位进行腹腔内加温灌注化疗则可提高疗效，减少毒副反应，新近临床实践中取得了令人鼓舞的成绩。本文就近年来以日本为主开展的这方面工作作一简要综述。一、理论依据及基础研究胃肠道癌腹膜播散及术后腹膜复发的机理可归纳为“种子──土壤”学说，一旦癌细胞突破浆膜层，就有可能发生腹膜种植，且随着受累浆膜面积的扩大，这种危险性越高。手术中…     

进展期胃肠道恶性肿瘤术后早期腹腔内化疗

进展期胃肠道恶性肿瘤术后早期腹腔内化疗陈军（综述），林言箴，尹浩然（审校）上海第二医科大学附属瑞金医院普外科（上海·２０００２５）直接向腹腔内灌注化疗药物治疗癌症的历史已二十余年。术后早期腹腔内化疗（ｅａｒｌｙｐｏｓｔｏｐｅｒａｔｉｖｅｉｎｔｒａｐｅ...     

胃肠道恶性肿瘤术后早期腹腔内化疗

浆膜受侵的胃肠道恶性肿瘤即使施行了肿瘤根治术,术后仍有超过半数的病人死于肿瘤复发,腹腔内复发源于腹腔内游离癌细胞的种植,是最常见的复发类型。术后早期腹膜内化疗是一种治疗及预防腹腔内复发的新方法,具有药理学方面的优越性,并被动物实验所证实。     

腹腔热灌注化疗联合静脉化疗治疗晚期胃肠道肿瘤的疗效

目的探讨腹腔热灌注化疗联合静脉化疗对晚期胃肠道肿瘤患者的治疗效果。方法选择70例晚期胃肠道肿瘤患者,按照临床试验数字随机法分为治疗组和对照组,每组35例。对照组患者予以静脉化疗进行治疗,治疗组患者在对照组的基础上加用腹腔热灌注化疗进行治疗,比较两组患者的治疗效果、生存时间、不良反应以及免疫功能变化。结果治疗组患者的治疗有效率为68.6%,显著优于对照组的40.0%(P<0.05)。治疗组患者生存期显著高于对照组(P<0.05)。治疗组患者不良反应发生率低于对照组,但差异无统计学意义(P>0.05)。治疗组患者术后CD3+T细胞、CD4+T细胞水平升高,CD8+T细胞水平降低(P<0.05)。对照组患者CD3+T细胞、CD4+T细胞、CD8+T细胞水平变化不大(P>0.05)。结论与单纯静脉化疗相比,腹腔热灌注联合静脉化疗能有效治疗晚期胃肠道肿瘤患者,治疗有效率高,患者生存率高,不良反应率低。     

进展期胃肠道恶性肿瘤腹腔热灌注化疗的临床应用

进展期胃肠道恶性肿瘤腹腔热灌注化疗的临床应用陈嘉勇张捷谭晶王兴贤我们应用卡铂、５－氟脲嘧啶、丝裂霉素联合的腹腔热灌注化疗，治疗进展期胃肠道恶性肿瘤手术患者２０例，其中男９例，女１１例。年龄３２～７２岁，中位年龄５１．６岁。病理组织学诊断：胃腺癌５例，...     

晚期胃肠道肿瘤时辰化疗的临床观察

为了研究晚期胃肠道癌应用Melodie泵时辰化疗的近期疗效和耐受性,将晚期胃肠道癌患者共64例,应用配对设计,随机分为时辰化疗组和常规化疗组各32例.时辰化疗组:应用Melodie多通道编程输液泵给药.两组中化疗方案和每周期的药物剂量均相同.氟尿嘧啶(5-FU)500mg/(m2·d),醛氢叶酸(CF)130mg/(m2·d),奥沙利铂(L-OHP)130mg/m2.L-OHP给药的浓度高峰时间为16:00,5-FU和CF为4:00.5d为1个周期,休息14d进行下1个周期.常规化疗组:L-HOP 130mg/m2静脉滴入,d1;CF 200mg/m2静脉滴入2h接用5-FU 400mg/m2静脉推注,继以5-FU 1.6g/m2恒速静脉滴入22h,21d为1个周期.化疗>2个周期评定近期疗效及毒副反应.结果:总有效率53.13%(34/64),时辰组65.63%(21/32),常规组40.06%(13/32),疗效差异有统计学意义,P=0.0276.不良反应主要为胃肠道反应、末梢神经炎、骨髓抑制及口腔炎等,时辰化疗组的各种毒副反应均较常规化疗组轻,其中口腔炎的发生率分别为9.37%(3/32)和34.37%(11/32),两组差异有统计学意义,P=0.0133.初步研究结果提示,L-0HP、5-FU和CF3药采用多通道编程输液泵时辰化疗对晚期胃肠道癌的有效率高,耐受性好.     

应用托烷司琼及甲氧氯普胺控制化疗所致胃肠道反应疗效观察

化疗所致的恶心呕吐是癌症病人的一大难题,正确处理化疗所致的胃肠道反应,对改善肿瘤病人的生活质量,提高疗效具有积极作用。托烷司琼(欧必亭)是一种新的5羟色胺(5ＨＴ)受体拮抗剂,可抑制肿瘤患者化疗后引起的恶心呕吐。现就1998年6月～1999年2月对我科住院患者应用欧必亭和甲氧氯普胺(胃复安)控制化疗所致的恶心呕吐,总结如下。资料和方法1病例选择　全部病例均为我科住院患者,诊断明确,符合化疗条件,ＫＰＳ>70分,化疗前无恶心呕吐等胃肠道症状。入院时随机分为两组:欧必亭组70例,男性45例,女性25例,年龄28～80岁,中位58岁。胃复安组42例,…     

胃肠道肿瘤化疗多药耐药的研究进展

胃肠道肿瘤的治疗是以手术为主,辅以化疗等综合治疗,而往往在有明显症状之前已出现转移,故多数失去手术机会,而选择以化疗为主的综合治疗。然而因肿瘤的原发或继发性对化疗药物的不敏感而导致的多药耐药（MDR）常常影响化疗效果,这是临床常见难题。MDR的机制复杂,现综述胃肠道肿瘤MDR产生的机制以及逆转MDR的策略,将对进一步提高化疗效果具有重要意义。     

Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy-induced oral mucositis in non-neutro-penic cancer patients

The aim of this study was to assess prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of chemotherapy-induced oral mucositis in non-neutropenic cancer patients. In a prospective open study, 30 cancer patients with chemotherapy-induced, neutropenia-independent oral mucositis were treated with GM-CSF (Schering Plough Corp, Kenilworth, NJ) prepared as a mouthwash solution (5-10 μg ml^-1). GM-CSF was administered within 24 hours of occurrence of oral mucositis x 4 to 6 times daily. Systemic GM-CSF was not permissible. Oral mucositis was graded according to the modified Radiation Therapy Oncology Group criteria. Six patients were subsequently excluded as they experienced neutropenia during GM-CSF therapy. The remaining 24 patients were all evaluable. Most patients had either Grade 3 or 4 gross (76%) or functional (54%) mucositis. The mean ± SEM gross oral mucositis scores for all 24 patients combined decreased from 3.08 ± 0.18 at baseline to 2.04 ± 0.19(p < 0.0001) after 2 days, 0.92 ± 0.16(p < 0.0001) after 5 days, and 0.25 ± 0.09(p < 0.0001) after 10 days of therapy. Likewise, the mean ± SEM functional oral mucositis scores decreased from 2.71 ± 0.18 at baseline to 1.58 ± 0.19(p < 0.0001) after 2 days, 0.75 ± 0.16(p < 0.0001) after 5 days, and 0.17 ± 0.08(p < 0.0001) after 10 days of therapy. The duration of severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis score) was evident in seven (29%), 20 (83%), and 24 (100%) patients by the 2nd, 5th, and 10th day of therapy, respectively. Similarly, Grade 0 or 1 (functional mucositis score) reported in 13 (54%), 19 (79%), and 24 (100%) by the 2nd, 5th, and 10th day of therapy respectively. It was found that GM-CSF mouthwash as used in this study has a significant recuperative efficacy on the severity, morbidity, and duration of chemotherapy-induced oral mucositis. A large randomized, placebo-controlled study is warranted to ascertain that benefit and determine the optimal dosages and schedule.     

急性白血病化疗后合并口腔粘膜炎的综合治疗

目的:探讨急性白血病(acute leukemia AL)化疗后合并口腔粘膜炎感染相关因素及临床治疗方法。方法:对我院2004年5月~2006年5月住院的212例AL化疗后出现口腔粘膜炎(oraL mucositis OM)的病例进行临床资料分析,在给予全身支持疗法的基础上,使用中药紫草油与氟康唑、利多卡因的混匀液交替进行局部治疗。结果:AL化疗后并发OM占65%,发病率较高,发病率和骨髓受抑、粒细胞缺乏程度呈正相关。积极控制细菌、霉菌混合感染,应用人血丙种球蛋白等提高免疫力,局部紫草油加氟康唑250ml(或者伊曲康唑0.25g配置成250ml溶液代替氟康唑) 2%利多卡因溶液5ml的交替涂敷、漱口治疗,与常规给药对比有显著疗效(P<0.01)。结论:急性白血病(AL)口腔粘膜炎感染相关因素和机体的免疫力、化疗强度、粒细胞缺乏程度相关,紫草油与氟康唑 利多卡因混匀液的交替治疗效果较好。     

Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies

BACKGROUND: The purpose was to evaluate prevention of oral mucositis (OM) using chlorhexidine compared with placebo and with oral cooling (cryotherapy) during fluorouracil (5-FU)-based chemotherapy in gastrointestinal (GI) cancer. METHODS: Patients with previously untreated GI cancer receiving bolus 5-FU/leucovorin chemotherapy were randomized to chlorhexidine mouthrinse 3 times a day for 3 weeks (Arm A), double-blind placebo (normal saline) with the same dose and frequency (Arm B), or cryotherapy with crushed ice 45 minutes during chemotherapy (Arm C). Patients self-reported on severity (CTC-grading) and duration of OM. RESULTS: Among 225 patients randomized, 206 answered the questionnaire (70, 64, and 63 patients in Arms A, B, and C, respectively) and were well balanced with respect to diagnoses, stage, age, sex, smoking habits, and performance status. Mucositis grade 3-4 occurred more frequently in Arm B (33%) than in A (13%, P< .01) and C (11%, P< .005). Duration was significantly longer in B than in both A (P= .035) and C (P= .003). CONCLUSIONS: The frequency and duration of OM are significantly improved by prophylactic chlorhexidine and by cryotherapy. The latter is easy and inexpensive but has limited use, as it is drug- and schedule-dependent. The current study is the first double-blind randomized evaluation of prophylactic chlorhexidine in a large adult patient population with solid tumors receiving highly OM-inducing chemotherapy. A role for chlorhexidine in the prevention of OM is suggested, which should be evaluated further.     

The effectiveness of commonly used mouthwashes for the prevention of chemotherapy-induced oral mucositis: a systematic review

Daily chlorhexidine mouthwash is often recommended for preventing chemotherapy-induced oral mucositis. Povidone-iodine, NaCl 0.9%, water salt soda solution and chamomile mouthwash are also recommended. However, the effectiveness of these mouthwashes is unclear. Therefore, we performed a systematic review to assess the effectiveness of mouthwashes in preventing and ameliorating chemotherapy-induced oral mucositis. Based on study quality, three out of five randomized controlled trials were included in a meta-analysis. The results failed to detect any beneficial effects of chlorhexidine as compared with sterile water, or NaCl 0.9%. Patients complained about negative side-effects of chlorhexidine, including teeth discoloration and alteration of taste in two of the five studies on chlorhexidine. The severity of oral mucositis was shown to be reduced by 30% using a povidone-iodine mouthwash as compared with sterile water in a single randomized controlled trial. These results do not support the use of chlorhexidine mouthwash to prevent oral mucositis.     

Effect of vitamin E on chemotherapy-induced mucositis and neutropenia in leukemic patients undergoing bone marrow transplantation

Aim: This study was conducted to investigate the effect of oral vitamin E on mucositis and neutropenia in patients with leukemia. Methods: This was a randomized double‐blind placebo controlled clinical trial of 60 patients with leukemia (acute lymphoblastic, acute myelogenous leukemia and chronic myelogenous leukemia) who were consecutive recipients of allogenic bone marrow transplantation (BMT), randomly assigned to receive 400 mg vitamin E twice daily (supplemented group) or placebo (control). The incidence and severity of mucositis and the mean duration of neutropenia were compared. Results: The mean duration of neutropenia and the incidence of the mucositis between the two groups was the same (P = 1.0). The difference between the placebo group and mucositis grade 1 (P = 0.31), grade 2 (P = 0.25), grade 3 (P = 0.93) and grade 4 (P = 0.32) was not statistically significant. Moreover the variables of age, sex, BMI and underlying disease had no effect. Conclusion: In this study supplementation with oral vitamin E had no effect on mucositis and neutropenia in patients with leukemia who were recipients of allogenic BMT. More interventional trials are warranted.     

The effect of zinc sulfate in the prevention of high-dose chemotherapy-induced mucositis: a double-blind, randomized, placebo-controlled study

The purpose of this study was to evaluate the effect of oral zinc sulfate in the prevention of chemotherapy-induced mucositis in patients undergoing hematopoietic stem-cell transplantation (HSCT). This study was a double-blind, randomized, placebo-controlled design, with 60 patients undergoing HSCT, divided proportionally in experimental group who received zinc sulfate, and in placebo group. They all had received high-dose chemotherapy conditioning regimen for allogenic transplantation. Oral mucositis assessed was based on World Health Organization (WHO) oral mucositis scale. There were no significant differences in the development of mucositis between the two groups. Severity of mucositis was not significantly different between the two groups either. The same result was obtained regarding the duration of mucositis. Zinc sulfate did not show any significant adverse effects in experimental group. In conclusion, Zinc sulfate did not have any clinical benefits in prevention or reduction of severity, and duration of high-dose chemotherapy-induced mucositis in patients undergoing HSCT.     

胃肠间质瘤内科治疗进展

酪氨酸激酶抑制剂甲磺酸伊马替尼(STI571)是治疗无法手术切除、术后复发及远处转移胃肠间质瘤(GIST)的首选药物,传统放化疗主要用于治疗STI571无效的GIST,苯甲酰星形孢菌素等药物在治疗STI571原发和继发性耐药的GIST方面有着积极的效果。     

肿瘤治疗引起口腔黏膜炎的治疗研究进展

口腔黏膜炎是癌症患者在接受放化疗时常见的并发症,其严重程度关系到患者生活质量和临床疗效,是肿瘤治疗药学监护的重要课题。本文从口腔黏膜炎发生机制、临床表现及临床治疗方案等角度介绍肿瘤治疗诱发的口腔黏膜炎防治现状;探讨“湿性愈合”理论应用于口腔黏膜炎治疗的可能性,以期将这一技术广泛运用于缓解口腔黏膜炎症状,并联合其他治疗药物,促进溃疡高质量愈合。     

Updated clinical practice guidelines for the prevention and treatment of mucositis

Considerable progress in research and clinical application has been made since the original guidelines for managing mucositis in cancer patients were published in 2004, and the first active drug for the prevention and treatment of this condition has been approved by the United States Food and Drug Administration and other regulatory agencies in Europe and Australia. These changes necessitate an updated review of the literature and guidelines. Panel members reviewed the biomedical literature on mucositis published in English between January 2002 and May 2005 and reached a consensus based on the criteria of the American Society of Clinical Oncology. Changes in the guidelines included recommendations for the use of palifermin for oral mucositis associated with stem cell transplantation, amifostine for radiation proctitis, and cryotherapy for mucositis associated with high-dose melphalan. Recommendations against specific practices were introduced: Systemic glutamine was not recommended for the prevention of gastrointestinal mucositis, and sucralfate and antimicrobial lozenges were not recommended for radiation-induced oral mucositis. Furthermore, new guidelines suggested that granulocyte-macrophage-colony stimulating factor mouthwashes not be used for oral mucositis prevention in the transplantation population. Advances in mucositis treatment and research have been complemented by an increased rate of publication on mucosal injury in cancer. However, additional and sustained efforts will be required to gain a fuller understanding of the pathobiology, impact on overall patient status, optimal therapeutic strategies, and improved educational programs for health professionals, patients, and caregivers. These efforts are likely to have significant clinical and economic impact on the treatment of cancer patients. Cancer 2007;109:820-31. (c) 2007 American Cancer Society.     

放化疗所致口腔黏膜炎的干预治疗

口腔黏膜炎是放化疗治疗头颈部肿瘤的常见并发症,发病率高,影响肿瘤治疗效果.其干预治疗方法有三维适形放疗、调强放疗,以尽量减少正常组织受照面积减轻症状;药物治疗方法如生长因子类药物、氨磷汀、硫酸锌、抗炎症药物、谷氨酰胺等的使用能降低黏膜炎严重程度,缩短黏膜炎病程,一定程度上改善了患者生活质量.