colorectal cancer
结直肠癌(colorectalcancer,CRC)是什么?
结直肠癌(colorectalcancer,CRC)是什么?
结直肠癌(colorectal cancer, CRC),是全球女性中第二常见,男性中第三常见的癌症,也是全球第三大与癌症相关的死亡因素。
CRC的发生是由一些关键基因的突变积累所致,包括CTNNB1、BRAF、PIK3CA、PDGFRL、TP53、APC等[1]。
肿瘤转移(metastasis)是CRC患者死亡的主要原因。
最常见的转移部位是肝脏,此外也有肺和腹膜的转移。
CRC在男性和女性中都很普遍,且50岁后患病风险显著增加[2]。
绝大多数CRC是由结直肠内壁形成的息肉(colorectal polyps)发展而来,因此,做结肠镜筛查十分重要,其能检测出结直肠中有无异常结构(例如息肉),是目前预防CRC最有效的方法。
如果在早期阶段发现CRC,只需手术切除肿瘤即可;但如果在晚期阶段发现,通常需要用到化疗、放疗或靶向药物联合治疗。
三药化疗联合靶向治疗在转移性结直肠癌的临床研究进展
一线治疗的发展历程
1.1 F0 LF0 X 旧丨在m C R C 治疗中的首次亮相 2 0 0 2 年 意 大 利 Falcone教 授 团 队 在 Journal of
Clinical Oncology (JC0 ) 发表 F0 LF0 XIRI 三药双周 化 疗 治 疗 mCRC的 初步研究结果[9],这 是 F0 LF0X IRI三 药 化 疗 方 案 首 次 登 上 历 史 舞 台 。该 研 究 是 一 项 II期临床研究,目的为探究F0 LF0 XIRI三药化 疗抗肿瘤治疗的疗效、安 全 性和药物剂量。试验共 入 组 4 2 名 患 者 ,有 5 例 患 者 (11.9 % ) 治疗后达到 完 全 缓 解 ( complete remission, CR ) ,25 例 患 者 (59. 5 % )部 分 缓 解 ( partial remission,PR) ,客观有 效 率 ( overall response rate,0 RR) 为 71. 4 % ( 9 5 % C/:47% ~ 83% ) , 中 位 无 进 展 生 存 期 ( median progression free survival,mPFS)为 10. 4 个 月 ,中位总生 存 期 ( median overall survival,mOS)达到 26. 5 个 月 。 主要毒副反应包括腹泻和粒细胞缺乏,2 1 % 患者出 现 3 级腹泻,55%患者出现4 级中性粒细胞减少。
[收稿曰期] [基金项目] [通讯作者]
2〇2〇]2-〇2 [ 修 回 曰 期 ] 2〇2丨-〇3-〇5 •国家重点研发计划(编号:2〇l6YFCl3〇3602) 么金永东,E-mail:cccjin@ 163. com
肿瘤各亚专科期刊排名盘点!
肿瘤各亚专科期刊排名盘点!1. 肿瘤放疗International Journal of Radiation Oncology·Biology·Physics,2016年IF:5.13;2017年即时IF:4.57。
俗称“红皮”杂志,肿瘤放疗领域两本顶级杂志之一,发表很难。
Radiotherapy and Oncology,2016年IF:4.33;2017年即时IF:4.54。
俗称“绿皮”杂志,ESTRO会刊,肿瘤放疗领域两本顶级杂志之一,发表很难。
Brachytherapy,2016年IF:2.08;2017年即时IF:2.03。
以粒子植入等短距离放疗文章为主。
2.肿瘤外科2.1大外科综合Annalsof Surgery,2016年IF:8.98;2017年即时IF:7.86。
外科领域绝对的老大,并非仅限于肿瘤领域,而是涵盖外科各领域的老牌权威杂志,今年IF很难超过去年。
JAMA Surgery,2016年IF:7.96;2017年即时IF:6.74。
以前叫Archivesof Surgery,影响力较低。
被JAMA合并之后麻雀变凤凰,去年刚刚有IF就接近8分,目前发展势头良好,但综合影响力目前还不如楼上的Ann Surg。
British Journal of Surgery,2016年IF:5.90;2017年即时IF:5.12。
文章并不仅限于肿瘤领域,以手术方法比较及术式创新为主,很难命中。
2.2 肿瘤外科专刊Annalsof Surgical Oncology,2016年IF:4.04;2017年即时IF:3.70。
美国肿瘤外科学会SSO会刊,三大肿瘤外科王牌期刊之首,同等分数段肿瘤期刊中的影响力数一数二。
EJSO-European Journal of Surgical Oncology,2016年IF:3.52;2017年即时IF:3.45。
三大肿瘤外科王牌期刊之一,IF近两年有所攀升。
结直肠癌干细胞研究进展
结直肠癌⼲细胞研究进展wcjd@/doc/10f17e13a2161479171128d5.html⽂献综述 REVIEW结直肠癌⼲细胞研究进展杨治⼒, 王志刚, 郑起杨治⼒, 王志刚, 郑起,上海交通⼤学附属第六⼈民医院外科上海市 200233作者贡献分布: 本⽂综述由杨治⼒与王志刚完成, 郑起审校.通讯作者: 郑起, 教授, 200233, 上海市, 上海交通⼤学附属第六⼈民医院外科.zhengqi1957@/doc/10f17e13a2161479171128d5.html收稿⽇期: 2009-12-16 修回⽇期: 2010-01-09接受⽇期: 2010-01-26 在线出版⽇期: 2010-03-28Advances in research on colorectal cancer stem cells Zhi-Li Yang, Zhi-Gang Wang, Qi ZhengZhi-Li Yang, Zhi-Gang Wang, Qi Zheng,Department of Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China Correspondence to:Professor Qi Zheng, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong Univer-sity, Shanghai 200233, China.zhengqi1957@/doc/10f17e13a2161479171128d5.html Received: 2009-12-16 Revised: 2010-01-09 Accepted: 2010-01-26 Published online: 2010-03-28AbstractColorectal cancer is a worldwide enormous cancer burden and a major therapeutic chal-lenge as other solid tumors. The cancer stem cell hypothesis provides a cellular mechanism to account for the development, progression, recurrence and metastasis of colorectal can-cer. The aim of this paper is to review the ad-vances in research on colorectal cancer stem cells.Key Words: Colorectal cancer; Cancer; Stem cellYang ZL, Wang ZG, Zheng Q. Advances in research on colorectal cancer stem cells. Shijie Huaren Xiaohua Zazhi 2010;18(9): 913-919摘要结直肠癌与其他实体肿瘤⼀样是我国乃⾄世界范围的重要疾病负担, 其治疗也⾯临许多挑战. 近⼏年, ⽇益受到重视的癌症⼲细胞理论似乎可以解释结直肠癌的发⽣发展、复发转移的细胞学机制. 本⽂就结直肠癌⼲细胞的研究进展作⼀综述.关键词: 结直肠癌; 癌症; ⼲细胞杨治⼒, 王志刚, 郑起. 结直肠癌⼲细胞研究进展. 世界华⼈消化杂志 2010; 18(9): 913-919 /doc/10f17e13a2161479171128d5.html/1009-3079/18/913.asp0 引⾔结直肠癌与其他实体肿瘤⼀样是我国乃⾄世界范围的重要疾病负担, 其治疗也⾯临许多挑战. 近⼏年, ⽇益受到重视的癌症⼲细胞(cancer stem cell, CSC)理论似乎可以解释结直肠癌的发⽣发展、复发转移的细胞学机制, 可能为改进结直肠癌的治疗策略提供理论依据, 从⽽改善结直肠癌患者的预后.1 CSC理论的提出与初步证据同⼀组织的恶性肿瘤存在不同的病理学分类, 且表达不同的⽣物标志. 随着基因芯⽚与蛋⽩组学技术的进展, 对同⼀组织的恶性肿瘤分类已达到分⼦⽔平. 这些肿瘤⽣物学现象可以理解为不同亚型的肿瘤起源于不同的细胞. 然⽽, 同⼀细胞来源的肿瘤经常显⽰出细胞在功能上的异质性(functional heterogeneity), 表现为不同的增殖与分化能⼒[1,2]. ⽬前, 能解释此现象的CSC模型(图1)越来越被⼤多数学者所接受. CSC是指具有⾃我更新及产⽣组成肿瘤不同细胞能⼒的肿瘤细胞亚群[3-5]. 这些细胞显⽰出⼲细胞样特性与持续维持致瘤的能⼒. Lapi d ot等对急性粒系⽩⾎病细胞的研究⾸次证实CSC的存在[6]: ⼤约占⽩⾎病细胞总数的0.01%-1%的细胞移植⼊免疫缺陷⼩⿏后能诱导形成⽩⾎病. 尤其值得关注的是在实体肿瘤中也被证实CSC的存在. Al-Hajj 等从乳腺癌组织中分离出CD44+CD24-/low的细胞亚群, 并发现他们具有起始肿瘤的能⼒[7]. Singh等利⽤CD133作为分选标志分离并鉴定出脑肿瘤中的CSC[8]. 此后, ⽇益增加的证据显⽰⼏乎所有的实体肿瘤包括结肠、肝[9]、胰[10]、前列腺[11]、卵巢[12]、肺[13]、⿊⾊素瘤[14]等都被特有的CSC亚群按等级组织与维持. ⾄今, 乳腺癌与脑恶性肿瘤的CSC研究更为深⼊. 已有证据显⽰CSC的⽣物学⾏为随/doc/10f17e13a2161479171128d5.html ?■背景资料近⼏年,⽇益受到重视的癌症⼲细胞(C S C)理论似乎可以解释结直肠癌的发⽣发展、复发转移的细胞学机制, 可能为改进结直肠癌的治疗策略提供理论依据, 从⽽改善结直肠癌患者的预后.■同⾏评议者王晓艳, 副教授,湖南长沙中南⼤学湘雅三医院消化内科; 朴云峰,教授,吉林⼤学第⼀临床医院消化科整个肿瘤⽣长进展或经受临床⼲预过程⽽变化(图2), Barabe 等[15]研究显⽰⽩⾎病⼲细胞具有随时间积累⽽出现进化潜能, 表现为从最初细胞类型到含有重分配的免疫球蛋⽩H 基因, 这⼀研究提⽰CSC 本⾝可能出现克隆进化(clonal evolution); Clark 等[16]报道肿瘤细胞体内系列移植可产⽣更多的侵袭性肿瘤; Creighton 等[17]对经历常规内分泌与化学治疗后残余乳腺癌的研究显⽰其中CD44+CD24-/low 表型的CSCs 出现更多间质标志基因表达. 这些研究报道均提⽰CSCs受其所处⼩境(niche)的影响可能出现⽣物学特性的变化.2 结直肠癌⼲细胞存在的实验证据⾸次报道结直肠癌⼲细胞存在的两个研究⼩组是O'Brien 等[18]与Ricci-Vitiani 等[19], 前者在17例原发与转移结肠癌组织中⽤FACS 分析显⽰原发结肠癌组织中CD133+细胞占7.5%-15.9%, 转移结肠癌中CD133+细胞占3.2%-24.5%, 分选出CD133+与CD133-细胞后, 分别植⼊NOD/SCID⼩⿏肾囊内鉴定肿瘤起始细胞(colon cancer-initiating cell, CC-IC), 结果显⽰262个CD133+肿瘤细胞中有1个CC-IC; 后者的19例结肠癌组织中有16例含有C D133+细胞, 约占总细胞的0.7%-6.1%, 另3例未检出CD133+细胞, 通过体内外实验显⽰⼀⼩群未分化的C D133+细胞⽪下植⼊NOD/SCID ⼩⿏能产⽣与⽗代相似的结肠癌. 随后, To d aro 等[20]报道在21例结肠癌组织中CD133表达为0.3%-3%, 裸⿏⽪下移植结果显⽰2×106 CD133-细胞在15 wk 的观察期间⽆肿瘤⽣长, ⽽2.5×103 CD133+细胞⽣成肿瘤体积在1.5 cm 3左右; 进⼀步分析显⽰CD133+细胞能通过⾃分泌IL-4保护这些细胞免于凋亡以及抵抗常规治疗. ⾄此, CD133作为结直肠CSC 的标志已被⼤多数学者所认可.除了C D133作为结直肠C S C 的标志外,CD44与结直肠CSC 的研究也有报道. Dalerba等[21]对⼈类结肠C S C s 的表型研究显⽰:(EpCAM)high /CD44+表型的结肠癌细胞为CSC,914 ISSN 1009-3079 CN 14-1260/R 世界华⼈消化杂志 2010年3⽉28⽇第18卷第9期同时对此表型的细胞表⾯标志谱分析发现CD166也能作为CSC 的表型; 此外, 作者还发现CD44+细胞代表了CD133+细胞群中的⼩部分亚群细胞. 即与CD133+结肠癌细胞⽐较, CD44+结肠癌细胞中更有效地富集了CSCs. Du 等[22]利⽤慢病毒R N A ⼲扰技术敲出结直肠癌细胞中的CD44或CD133基因后显⽰: 仅CD44基因敲出能明显阻⽌癌细胞克隆形成以及抑制移植模型中细胞的致瘤性. 该研究提⽰CD44在结直肠CSC 中具有很重要的功能意义. 为了验证再⽣⼀个异质性结直肠癌的能⼒是否存在于⼀个单克隆结直肠癌细胞群体或依靠多个不同的CSCs, 也即按⽬前研究所定义的单个结直肠C S C 是否确实具有多向分化潜能. Vermeulen 等[23]对原发与肝转移结直肠癌细胞⾏结肠球培养, 这些球能在免疫缺陷⼩⿏中成瘤, 从球分离成单个癌细胞培养结果显⽰20个细胞中⼤约有1个细胞能形成克隆, 同时在球培养中⼤约16个CD133+细胞中有1个细胞能形成球, ⽽CD133-细胞需250个中有1个细胞能形成球; 在与CD133共表达的标志如CD44、CD166、CD24、CD29中, 以CD133+CD24+细胞有更⾼的克隆形成能⼒(约20%); 通过对单细胞克隆的结肠CSCs 的体内外研究显⽰CSCs 具有多向分化潜能, PI3K 信号通路参与了CSCs 分化的决定. 该研究⽀持了拥有多向分化潜能的CSC 导致了组成肿瘤的细胞层级的假说. 为了解决单⽤免疫⽅法检测C D133表达的不确定性, Shmelkov 等[24]建⽴了在CD133基因的启动区域敲进报道基因lacZ 的遗传⼩⿏模型, 结果发现CD133⼴泛表达在成年⼩⿏结肠上⽪细胞;⽤CD133抗体检测成年⼈正常结肠上⽪显⽰其表达在绝⼤多数分化的上⽪细胞; 在原发的⼈结肠癌标本中免疫染⾊也显⽰CD133⼴泛表达在所有恶性上⽪细胞中; 随后的Il10-//doc/10f17e13a2161479171128d5.html CSC克隆进化CSC2图 1 CSC模型.图 2 CSC⽣物学特征的变化.■研发前沿⽬前所有的结直肠CSC 的研究, 尽管在分选标志上的差异, 甚⾄有⽭盾的结果, 但仍可认为在结直肠癌中存在⼲细胞样的细胞亚群, 其特异性细胞表型还需深⼊研究.⼀、⾷道癌早期症状1.咽下梗噎感最多见,可⾃⾏消失和复发,不影响进⾷。
晚期大肠癌时间化疗的研究
Cure, H. et al. J Clin Oncol; 20:1175-1181 2002
时间化疗对5-FU剂量与疗效的影响?
5-FU 第1周期:900mg/m2/d 第2周期:10 00mg/m2/d 第3周期:1100mg/m2/d,连续4天 如果出现≥3度的毒性,则每天剂量降低100mg/m2/d
Cattel L, et al. Pharmacokinetic study of oxaliplatin iv chronomodulated infusion combined with 5-fluorouracil iv continuous infusion in the treatment of advanced colorectal cancer. Il Farmaco,2003,58:1333-1338
Qvortrup C, Yilmaz M, Ogreid D,et al.Chronomodulated capecitabine in combination with short-time oxaliplatin: a Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil[J]. Ann Oncol,2008,9(6):1154-1159.
⊙由黑暗期向光照期的过渡预示小鼠休息期的开始,大 约相当于人类的21~24点
氟尿嘧啶(5-fluorouracil, 5-FU)
Harris BE, et al. Relationship between Dihydropyrimidine Dehydrogenase Activity and Plasma 5-FluorouraciI Levels with Evidence for Orcadian Variation of Enzyme Activity and Plasma Drug Levels in Cancer Patients Receiving 5-Fluorouracil by Protracted Continuous Infusion1. Cancer Res.1990,50:197-201.
蓝色癌症科普知识PPT
FOUR
由于癌细胞不断倍增,癌症越往晚期发展得越快。 癌细 胞的内外潜藏着自身无法克服和无法排除的逆转因素,这 是它的特点,也是它的缺点,造就了它的不稳定性
癌症的原因、发展和分类
ONE
TWO
THREE
FOUR
什么导致了癌症
导致癌症最重要的因素是什么?基因?污染?饮食?抽烟?
和癌症发生率最相关的因素是年龄! 流行病学的统计表明,癌症的发病率随年龄的增长而提高,而且是几何级数 提高,癌症的发病率是年龄的3次方、4次方甚至5次方。
癌症的原因、发展和分类
ONE
TWO
THREE
FOUR
癌症为啥那么难搞?
第一个原因是癌症是 “内源性疾病”: 癌 细胞是病人身体的一部 分。
第二个原因是癌症不是 单一疾病,而是几千几 万种疾病的组合。
第三个原因是癌症的突 变抗药性。
03
癌症治疗 方法
癌症治疗方法
ONE
TWO
THREE
FOUR
癌症为什么难以治疗?
01
从癌症病人身上 分离免疫T细胞。
02
癌症和肿瘤
ONE
TWO
THREE
FOUR
那癌症到底是怎么致命的呢?
• 往往和器官衰竭有关,或是某一器官衰竭,或是系统性衰竭。
• 癌症如果转移以后,危险性大大增加,一个原因是一个肿瘤转移就成了N个肿瘤,另一个原 因是转移的地方往往是很重要的地方。比较要命的地方是脑转移,肺转移,骨转移和肝转移。
癌症的严重性和肿瘤的大小没有相 关性。
癌症治疗方法
ONE
TWO
THREE
FOUR
溶瘤病毒,以毒攻毒还是毒上加毒
溶瘤病毒(Oncolytic Virus),所谓溶瘤病毒,并不是特定的一种病毒,而是指一类倾向于感染 肿瘤细胞,同时在癌细胞里面能够大量繁殖,最终让肿瘤细胞裂解,破碎,死亡的一类病毒。
常见的肿瘤缩写词
ABC Advanced Breast Cancer 晚期乳腺癌ACC Adenoid Cystic Carcinoma 腺囊癌ACC Adrenal cortical carcinoma 肾上腺皮质瘤ACC Advanced ColorectalCarcinoma 晚期大肠癌ALCL Anaplastic Large-cellLymphoma 间变大细胞淋巴瘤ALL Acute LymphoblasticLeukemia 急性淋巴细胞白血病AMKL Acute megakaryoblasticleukemia 急性原巨核细胞白血病AML Acute myelogenousleukemia 急性髓细胞性白血病ARMS Alveolarrhabdomyosarcoma 腺泡横纹肌肉瘤BCC Basal Cell Carcinoma 基底细胞癌CGL Chronic GranulocyticLeukaemia慢性粒细胞性白血病CIN Cervical IntraepithelialNeoplasm宫颈上皮内瘤CLL Chronic LymphocyticLeukemia 慢性淋巴细胞白血病CML Chronic MyelogenousLeukemia 慢性髓细胞性白血病CMML chronic myelomonocyticleukemia 慢性粒单核细胞白血病CRC Colorectal carcinoma 结直肠癌CTCL Cutaneous T-CellLymphoma 原发性皮肤T 细胞淋巴瘤DCIS Ductal Carcinoma In Situ 乳腺导管内原位癌DLBCL Diffuse Large B-cellLymphoma 弥漫性大B 细胞淋巴瘤DLCL Diffuse large-celllymphoma弥漫性大细胞淋巴瘤EMC Extraskeletal MyxoidChondrosarcoma 骨外黏液样软骨肉瘤FMTC Familial MedullaryThyroid Carcinoma 家族性甲状腺髓质癌GIST Gastrointestinal StromalTumors 胃肠道间质瘤HCC Hepatocellular Carcinoma 肝细胞癌HCLHairy Cell Leukaemia 毛细胞白血病HD Hodgkin's Disease(lymphoma)霍奇金淋巴瘤HNPCC Hereditary NonPolyposisColorectal Cancer 遗传性非息肉病性大肠癌HNSCC Head and Neck SquamousCell Carcinoma 头颈部鳞状细胞癌LMM Lentigo MalignaMelanoma 恶性黑色素瘤MM Malignant Melanoma 恶性雀斑样痣样黑素瘤 MM Malignant Myelanoma 恶性黑色素瘤 MM Multiple Myeloma 多发性骨髓瘤 MPNST Malignant PeripheralNerve Sheath Tumour 恶性外周神经鞘瘤MRT Malignant RhabdoidTumour 恶性横纹肌样瘤NHL non Hodgkin's lymphoma 非霍奇金淋巴瘤NM Nodular Melanoma 结节性黑素瘤 NMSC Non Melanoma SkinCancer 非黑色素瘤皮肤癌NPC NasopharyngealCarcinoma 鼻咽癌NRSTS Non-RhabdomyosarcomaSoft Tissue Sarcoma 非横纹肌肉瘤软组织肉瘤NSCLC Non-Small Cell LungCancer 非小细胞肺癌ONB Olfactory Neuroblastoma 嗅神经母细胞瘤OS Osteogenic sarcoma 成骨性肉瘤PET Pancreatic EndocrineTumor胰腺内分泌肿瘤PLB Primary Lymphoma ofBone 原发性骨淋巴瘤PNET Primitive neuroectodermaltumour 原始神经外胚层肿瘤RCC Renal Cell Carcinoma 肾细胞癌RMS rhabdomyosarcoma 横纹肌肉瘤SCC Squamous Cell Carcinoma 鳞状细胞癌SCLC Small cell lung cancer 小细胞肺癌SSM Superficial SpreadingMelanoma 浅表扩散性黑素瘤TCC Transitional CellCarcinoma 移行细胞癌TNBC Triple-Negative BreastCancer 三阴性乳腺癌WM Waldenstrom'sMacroglobulinemia 华氏巨球蛋白血症YSTYolk sac tumour 卵黄囊瘤。
铁死亡诱导剂在结直肠癌中的研究进展
- 180 -end-expiratory pressure alone minimizes atelectasis formation in nonabdominal surgery:a randomized controlled trial[J].Anesthesiology,2018,128(6):1117-1124.[39] KIM N,LEE S H,CHOI K W,et al.Effects of positive end-expiratory pressure on pulmonary oxygenation and biventricular function during one-lung ventilation:a randomized crossover study[J].J Clin Med,2019,8(5):740.[40] KATZ J A,LAVERNE R G,FAIRLEY H B,et al.Pulmonaryoxygen exchange during endobronchial anesthesia:effect of tidal volume and PEEP[J].Anesthesiology,1982,56(3):164-171.[41] SENT ÜRK N M,DILEK A,CAMCI E,et al.Effects ofpositive end-expiratory pressure on ventilatory and oxygenation parameters during pressure-controlled one-lung ventilation[J]. J Cardiothorac Vasc Anesth,2005,19(1):71-75.[42] KANG W S,KIM S H,CHUNG J parison of pulmonarygas exchange according to intraoperative ventilation modes for mitral valve repair surgery via thoracotomy with one-lung ventilation:a randomized controlled trial[J].J Cardiothorac Vasc Anesth,2014,28(4):908-913.(收稿日期:2023-03-03) (本文编辑:田婧)*基金项目:安溪县科技计划项目(2022S002)①福建省安溪县医院 福建 安溪 362400通信作者:许永鹏铁死亡诱导剂在结直肠癌中的研究进展*陈伟鸿① 苏小苹① 苏宇超① 黄栋钦① 许永鹏① 【摘要】 结直肠癌(colorectal cancer,CRC)是全球第三大常见癌症,传统治疗方案对CRC 晚期患者的疗效不佳,因此,发现新的治疗策略可能有助于改善CRC 患者的治疗和预后。
二甲双胍在结直肠癌治疗中的研究进展
结直肠癌(colorectal cancer,CRC )是世界范围内第三大常见恶性肿瘤,严重威胁着人类的健康。
根据世界卫生组织GLOBOCAN 数据库统计,2018年CRC 有180万新发病例和88.1万死亡病例[1]。
目前CRC 的主要治疗方式有手术、化疗、放疗、靶向治疗及免疫治疗等,但总体治疗效果仍不容乐观。
因此,亟待一种新的治疗手段为CRC 提高治疗效果。
CRC 的发病机制极其复杂,有多种因素影响CRC 的发生发展,包括吸烟、饮酒、遗传因素、肥胖及糖尿病等。
2型糖尿病是罹患CRC 的独立危险因素[2]。
二甲双胍作为2型糖尿病的一线用药,因其低成本、易耐受及安全性强等优点,越来越被关注。
它除了可以降血糖外,还可以降低恶性肿瘤的发病风险以及延缓肿瘤进展等[3]。
研究显示,二甲双胍可以抑制CRC 细胞的增殖、迁移及侵袭,促进其凋亡,并在治疗CRC 上有一定的作用[4]。
本文就此展开综述。
1二甲双胍与结直肠癌流行病学研究临床研究发现,2型糖尿病患者应用二甲双胍12个月后与未口服二甲双胍的糖尿病患者相比,CRC 发病风险降低了12%[5]。
此外,CRC 的发病风险可随着二甲双胍使用剂量的累积而逐渐降低[6]。
一项关于2型糖尿病与CRC 关系的荟萃分析提示,服用二甲双胍的糖尿病患者与未服二甲双胍的糖尿病患者相比,结直肠腺瘤的发病率降低了25%[7]。
二甲双胍除了可以降低CRC 发病风险外,还可显著改善CRC 患者的预后。
Deng 等[8]研究发现,口服二甲双胍的CRC 患者的总体生存率(HR =0.73,95%CI :0.63~0.84)与癌症特异性生存率(HR =0.60,95%CI :0.50~0.73)均显著提高。
另有研究显示,相较于其他降糖药联合化疗组,二甲双胍联合化疗后的CRC 患者总体生存期延长了14个月[9,10]。
Ng 等[11]认为二甲双胍还可降低CRC 的复发率(HR =0.65,95%CI :0.56~0.76),延缓肿瘤进展。
肠镜检查指南说明书
C o LYour day-to-day guide for your colonoscopy test using CoLyte ®Please prepare yourself ahead of timePlease read through all of these instructions before starting to get ready for the procedure. If you have any questions about the instructions please call the ‘Ask a Question’ telephone number listed above.Before your colonoscopy Tell the doctor or nurse about any drug allergies or health issues you have.Write down all of the medications you take. Your list should includeprescriptions, over the counter medicine, such as Advil®, Aspirin®, iron supplements and herbal supplements. Be sure to include medicalmarijuana, strong painkillers (opioids), and tranquillizers such as Valium® and Xanax®. Make sure your nurse or doctor sees this list.Tell the nurse or doctor if you have any medical devices such as hearing aids, insulin pumps, pacemakers, defibrillators, home oxygen, and sleep apnea machines.Most medicine can be taken up to and on the day of your test. Do not take any medicine within the 2 hours before or after drinking the bowel prep solution.General points about your upcoming colonoscopyC o LDiabetic pills and or insulin, blood thinners, and antithrombotics (e.g.,Coumadin®, Plavix®, Pradaxa® and Xarelto®) are examples of medicinesthat might need to be adjusted or stopped .If you take these medicines talk to the nurse or doctor before your test.They will tell you if you need to stop or adjust any medicine before yourtest.If you start a new medicine between your pre-colonoscopy visit andthe date of your colonoscopy, it may make it unsafe for the test to bedone. Call the ‘Ask a Question’ telephone number listed on the firstpage before the day of your test to make sure it is OK to take.• You may choose whether or not you want to have sedation. Colonoscopies can be comfortable without medicine to help you relax(sedation). Some people can get cramps (pain). Many people do chooseto have sedation for the procedure.• If you do not want sedation, talk to your nurse or doctor on the day of your test. Make plans to have someone drive you home after the test,in case you end up asking for sedation so you can be more comfortable.• If you have sedation, you may not drive for at least 8 hours after you were given sedation. Sedation might make you sleepy. A responsibleadult is required to take you home after the test. The driver will needto come into the department where you are having your colonoscopydone to pick you up. Do not drive, or take a taxi or bus by yourself toget home.• If you don’t have plans for someone to go home with you, you can eitherreschedule your test by calling the ‘Ask a Question’ telephone numberlisted on the first page or choose to have the test without sedation.Make arrangements for getting home after the testC o LThe most important thing you can do for your colonoscopy to be asuccess is to have your bowel prepared properly. The colon must becleaned out so that the bowel wall and any polyps or growths can beseen. If the bowel is not cleaned out, polyps or other growths mightnot be seen. Then the test will have to be done again.The bowel is prepared by drinking a bowel preparation (prep) solutionthat is a very strong laxative. Drinking it will cause you to have looseand watery stool (diarrhea). Be sure to drink plenty of clear fluids aswell as the bowel prep solution , so that your body doesn’t lose a lot of water and become dehydrated.If you need to travel more than 2 hours to get to the facility ask abouthaving your appointment later in the day.Buy at a pharmacy or drugstore:• A 4 litre bottle of the bowel preparation (prep) solution CoLyte®. The drugstore may have other solutions in 4 litre bottles named PegLyte®or GoLYTELY®. You can use any of these.• Clear fluids such as Gatorade® or clear broth. Do not drink anything that is red, purple or blue. Do not drink only water . Read page 5 fora list of what you can drink.• You may want to get baby wipes and or barrier cream for anysoreness you get from repeated trips to the bathroom.• CoLyte® does not require a prescription, but you will have to ask thepharmacist for it.Preparing your bowel No later than 5 days before your testC o LPlease start eating low-fibre foods and keep eatingthem until 1 day before your colonoscopy test.4 days before your testKeep eating the low-fibre diet.2 days before your testDo not eat • Nuts and seeds.• Popcorn.• Oatmeal.• Dried fruit.• Raw fruits and vegetables. • Beans, lentils, and quinoa.• Whole wheat or high fibre bread. • Whole wheat or whole grain cereal or pasta.• Cooked orsteamedvegetables.• White bread,white pasta and white rice.• Canned fruit.• Dairy products like plain yogurt or cheese.• Eggs.• Chicken, beef,pork, fish, tofu, or smooth nut butters.Low-fibre foods that are OK to eat:C o L y t e ®Things to do “1 day before your test” continue on next page1 day Before 10 am • Red, purple, or blue fluids• Milk products or substitutes such as soy, almond, or goat’s milk• Meal replacements like Boost® or Ensure®• AlcoholPlease do not drink Iced tea, tea or coffee without milk or milk substitutes like Coffee-mate®Clear pulp-free fruit juices like apple, white grape, white cranberry or lemonade Sports drinks: Gatorade®, Powerade®Clear broth or bouillonJell-O®,juice popsicles Kool-Aid®ginger ale, Sprite®, 7-Up®, water, and coconut water Clear fluids that are OK to drinkC o LContinues from previous page: 1 day before your testC o L1 2 3 4 5 6 7 8 The day of your test5 hours before the time you were told to be at the facility Drink the last 2 litres of the CoLyte® solution within 2 hours. Drink 1 glass, about 250 mL (8 ounces) every 15 minutes. Depending on the time you need to arrive for your test, you might have to get upearly to do this. For example, if you were told to come at 10 am, startdrinking the solution at 5 am.If you have loose, watery stools after drinking 2 to 3 litres, it doesn’tmean that you can stop drinking the solution. There could still besolid stool in your large bowel. Make sure you drink all 4 litres of thesolution .Keep drinking clear fluids before and after drinking the solution sothat you do not become dehydrated.12 3 4 5 6 7 8Keep track of the CoLyte® you drink the day of your test by checking off each glass after you drink it.•••Do not eat anythingC o L2 hours before the time you were told to be at the facilityWhen the last 2 litres of the solution is working, your stool should beliquid. It should be yellow and clear, like urine. If it does not look like this, call the ‘Ask a Question’ telephone number listed on the first page as they may give your further instructions.Check your stool Stop drinking anything 2 hours before the time you were told to be at the facility.If you have to take any prescription medicine within the 2 hoursbefore arriving at the facility, you can take it with a sip of water, unless you have been told something different.Please be at the reception desk at the time written on the first page of these instructions.You should plan to be at the facility for about 2 to 3 hours. Do not make plans for the rest of the day in case your test is delayed. Your patience is appreciated as sometimes these delays are unexpected. A nurse will take you into another area, where you will change into a hospital gown. The nurse will review the medicine you take, any allergies you have, and check your blood pressure and pulse.If you have questions about your colonoscopy ask the nurse or doctor before your procedure.An intravenous (IV) will be started in a vein in your hand or arm.If you are having sedation medicine it will be given through the IV. The colonoscopy is done by your doctor and usually takes 20 to 45 minutes.•••••••When you arrivefor your colonoscopyC o LThe results of your colonoscopy will be reviewed with you after yourtest. If no polyps are found you will be told when to have your next screening test.If polyps are found it is important that you make an appointment with your family doctor to review the results and find out what follow up is needed.You will be given colonoscopy discharge instructions after your procedure.You can go back to work the next day.You can start to eat your normal diet after the colonoscopy.It is not a good idea to plan air travel or long-distance travel within 2 weeks of your colonoscopy. You may not be covered by your travel insurance if you have a complication from your colonoscopy and are out of the province or country. Please check with your travel insurance provider.•••After the test At home •••C o LC o LSummaryRead all instructions before starting to get ready for the procedureC o L Facilities may use this page to attach additional patient information such as maps。
奥曲肽治疗化学疗法导致的腹泻直肠癌病人:一篇综述翻译参考模板
Octreotide in chemotherapy induced diarrhoea in colorectalcancer: a review article奥曲肽治疗化学疗法导致的腹泻直肠癌病人:一篇综述Abstract摘要Background: Chemotherapy-induced diarrhea(CID)is well known in cancer management. The risk is greater when the primary cancer is colorectal. The article aims towards assessing the role of octreotide in CID through an extensive literature search.背景:化学疗法导致的腹泻(CID)在癌症治疗中比较常见。
当原发癌是直肠癌时风险更大。
这篇综述的目的在于通过大量广泛的文献调查评价奥曲肽在治疗CID的作用。
Methods:After searching through PUBMED,MEDLINE and the Cochrane library, only those studies which were published over the last 20 years in English and where at least the majority of the cohort were colorectal patients, were included. Two randomized trials, four non-randomized studies and two case-series publications were thus considered.方法:在通过PUBMED,MEDLIN和循证医学文库搜索之后,仅挑选出在近20年用英文发表的,并且所选的队列为结肠病人的研究论文。
结直肠癌相关英文词汇
83.The goal of treatment depends on the stage of disease 治疗目标由疾病的分期决定
84.Stages I, II, and III are potentially curable I、II、III 期病人是潜在可治愈的人群
85.the intent is to eradicate micrometastatic disease. 治疗的目标是根除微转移
86.Twenty to thirty percent of patients with metastatic disease may be cured if their metastases are resectable 如果转移灶可切除的话,20%-30%肿瘤转 移的病人可获得治愈。
63.identifying metastatic or recurrent disease in patients with rising CEA levels CEA 持续升高的患者,确定是否存在转移 或复发
64.Stage of colorectal cancer should be determined at diagnosis 结直肠癌确诊时应做分期检查
28.average-risk individuals 中风险人群
43.personal and family history 个人史和家族史
29.annual occult fecal blood testing 粪便隐血检查
44.physical examination 体格检查
30.Signs and symptoms of colorectal cancer 结直肠癌的体征和症状
结直肠癌(colorectal cancer, CRC)
结直肠癌(colorectal cancer, CRC)结直肠癌(colorectal cancer, CRC)是起源于结直肠黏膜上皮的恶性肿瘤,是临床最为常见的恶性肿瘤之一。
我国每年结直肠癌新发病例超过25万,死亡病例约14万,新发和死亡病例均占全世界同期结直肠癌病例的20%。
因此,降低我国结肠癌的发病率和死亡率是刻不容缓的重大临床科学问题。
结直肠癌的转归及预后与病变的分期紧密相关。
局部进展期结直肠癌5年癌症相关生存率为70%,而发生远处转移的晚期结直肠癌患者5年生存率仅12%;且患者生活质量低。
然而,大部分早期结直肠癌可获得良好预后,5年生存率超过90%,部分可行内镜微创治疗获得根治。
但是目前我国结直肠癌的早期诊断率较低,明显低于欧美国家。
因此,逐步普及结直肠癌筛查和推广内镜下早诊早治是提高我国结直肠癌早期诊断率、降低结直肠癌相关死亡率的有效途径。
为规范我国结直肠癌诊疗方案,我国卫生部先后颁布了《结直肠癌诊疗规范(2010年版)》和《结直肠癌诊疗质量控制指标(试行)》,中华医学会消化内镜学分会肠道学组和中华医学会消化病学分会也相继发布了相关指南。
但目前我国尚缺乏侧重于结直肠癌内镜早期诊治且兼顾筛查等方面内容的综合性共识意见。
因此由中华医学会消化内镜学分会和中国抗癌协会肿瘤内镜专业委员会组织我国的消化、内镜、外科、肿瘤、病理等多学科专家、并邀请澳大利亚谭达恩教授及新加坡霍光明教授共同制定本指南意见。
一、定义和术语1.早期结直肠癌:根据1975年日本结直肠癌研讨会上的讨论意见,目前我国普遍将局限于结直肠黏膜层及黏膜下层的癌定义为早期结直肠癌,其中局限于黏膜层的为黏膜内癌,浸润至黏膜下层但未侵犯固有肌层者为黏膜下癌。
而2000年版的WHO肿瘤分类则规定结肠或直肠发生的上皮恶性肿瘤,只有穿透黏膜肌层、浸润到黏膜下层时才被认为是恶性的。
鉴于我国实际情况,推荐使用WHO推荐术语,但也可暂时沿用原位癌、黏膜内癌等术语。
晚期结直肠癌抗血管生成靶向治疗研究进展
晚期结直肠癌抗血管生成靶向治疗研究进展王伟林(综述);闻浩(审校)【摘要】Colorectal cancer is one of the most common malignant tumors , and targeted therapy plays vital roles in its treatment.As tumor angiogenesis plays a critical role in the process of tumor growth ,invasion and metastasis,drugs targeted angiogenesis have become more and more important in the comprehensive ther-apy of cancer.Three antiangiogenic agents are currently approved in the clinical treatment of advanced color-ectal cancer:bevacizumab,ziv-aflibercep,and regorafenib.Here is to make a review of the progression of anti-angiogenesis drugs in the targeted therapy of advanced colorectal cancer .%结直肠癌是最常见的恶性肿瘤之一,靶向治疗在其治疗模式中发挥着重要作用。
肿瘤血管生成是肿瘤生长、浸润和转移中的关键环节,针对新生血管的靶向药物在肿瘤综合治疗中扮演越来越重要的角色。
目前在临床中被批准用于晚期结直肠癌的抗血管药物主要有贝伐单抗、阿柏西普、瑞格非尼等。
该文就抗血管生成靶向药物在晚期结直肠癌靶向治疗中的研究进展进行综述。
【期刊名称】《医学综述》【年(卷),期】2015(000)013【总页数】3页(P2366-2368)【关键词】晚期结直肠癌;抗血管生成;贝伐单抗;瑞哥非尼;阿柏西普【作者】王伟林(综述);闻浩(审校)【作者单位】南京医科大学第二附属医院普外科,南京210011;南京医科大学第二附属医院普外科,南京210011【正文语种】中文【中图分类】R735.34结直肠癌是常见的恶性肿瘤之一,其发病率呈逐年上升趋势,已跃居全球恶性肿瘤发病率的第3位[1]。
结直肠癌(英文版)
*Signs and symptoms *Radiological techniques *Endoscopy *Tumor markers(CEA, CA199…) *Pathologic assessment
27
The extent of the disease is usually determined by a CT scan of the chest,abdomen and pelvis. There are other potential imaging test such as PET and MRI which may be used in certain cases. Colon cancer staging is done next and based on the TNM system which is determined by how much the initial tumor has spread, if and where lymph nodes are involved, and the extent of metastatic disease.
1
Colorectal cancer occurs in the colon and the rectum
2
Risk factors for colorectal cancer include lifestyle, older age, and inherited genetic disorders. Other risk factors include diet, smoking, alcohol, lack of physical activity, family history of colon cancer and colon polyps, presence of colon polyps, race, exposure to radiation, and even other diabetes, obesity.
与结直肠癌相关的粪菌移植研究现状
Journal of Colorectal&AnalSurgery结直肠肛门外科2020年12月第26卷第6期与结直肠癌相关的粪菌移植研究现状*崔曼曼1,马晓飞1,胡家丽1,胡丽霞1,张磊昌2△1江西中医药大学临床医学院江西南昌3300042江西中医药大学附属医院肛肠科江西南昌330006DOI:10.19668/ki.issn1674-0491.2020.06.037结直肠癌(colorectal cancer,CRC)为常见恶性肿瘤之一,在恶性肿瘤中发病率及死亡率均较高[1]。
CRC的发生、发展与多种因素相关,包括遗传因素、精神压力、饮食结构等[2]。
也有研究表明,结直肠癌患者肠道菌群的数量及种类均发生了变化[3-6]。
正常情况下,肠道菌群对维持肠道内环境稳态有重要作用,对机体进行正常生命活动具有重要的影响,肠道菌群失调可能引发一系列的不适或疾病,而粪菌移植(fecal microbiota transplantation,FMT)可以通过将健康供体的粪便作用于受体消化道来达到治疗目的,是调节肠道菌群失衡的方法之一。
本文围绕与CRC相关的FMT研究现状综述如下。
1FMT的应用与发展在东晋医学家葛洪编写的《肘后备急方》中已有“野葛芋毒、山中毒菌欲死者:并饮粪汁一升,即活”的描述[7],这是我国医学史上对粪汁应用的已知的最早记载。
1958年Eiseman等报道,对4例伪膜性肠炎患者进行治疗时将患者各自健康家属的粪便制成粪水用来灌肠[8],此为现代早期报道FMT参与治疗获得成功的案例。
2013年,Van Nood等[9]的研究证实,FMT对复发性艰难梭菌肠炎的治疗效果优于万古霉素,这一研究结果使得FMT得到了医学界更为广泛的关注[10]。
经过多年的发展与临床应用,目前复发性艰难梭菌感染(Clostridium difficile infec⁃tion,CDI)成为其公认适应证,FMT已经被列入CDI的治疗指南[11]。
微卫星不稳定:这个肿瘤指标你绝对不能忽视
微卫星不稳定:这个肿瘤指标你绝对不能忽视“很多结直肠癌(colorectal cancer, CRC)患者需要做 MSI/MMR 检测来选择后续治疗。
2017 年,FDA 批准 K 药用于「MSI-H/dMMR」实体瘤治疗,K 药也成为首个「不看部位看 marker」的抗肿瘤免疫药物。
我们就来了解一下什么是MSI/MMR,以及哪些患者应该接受检测。
”MSI/MMR 简介MMR 的中文名叫做「错配修复」(mismatch repair),系统成员包括 MLH1,MSH2,MSH6 和 PMS2 等蛋白。
DNA 复制过程中偶尔会出现小 DNA 错配错误,可以被这些蛋白识别后剪切,并合成新链进行修复。
整个基因组有超过100000 个被叫作「微卫星」的短串联重复序列区域,复制过程中易于滑动出现错误,因此非常依赖于MMR 系统修复。
上面4 个蛋白出现异常时,引起MMR 缺陷(deficient MMR, dMMR),不能发现和修改微卫星复制错误而造成弥漫的微卫星不稳定(microsatellite instability, MSI)。
虽然大部分微卫星位于非编码区,但是错置的突变会导致移码突变,引起肿瘤相关基因出现异常,进而诱导癌症发生。
高度 MSI(MSI-H)在大约 15% 的 CRC 中起决定作用,此外,MSI-H 也可导致子宫内膜癌,卵巢癌,胃癌等其他肿瘤。
dMMR 常见于两种情况:一种是 MMR 基因的胚系突变,这种情况叫做林奇综合征(Lynch Syndrome),常在一个家族中恶性肿瘤遗传性聚集发生[1];更常见的则是MMR 基因表观修饰失活引起的散发病例,通常伴有CpG 岛甲基化表型(CpG island methylation phenotype, CIMP),50% 的病例同时具有 BRAFV600E 活化突变。
反过来说,具有 CIMP 和 BRAFV600E 突变通常可排除林奇综合征[2,3]。
- 1、下载文档前请自行甄别文档内容的完整性,平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益,请联系客服反馈,我们会尽快为您处理(人工客服工作时间:9:00-18:30)。
Liver
Criteria for resection of metastases
Complete resection must be feasible based on anatomic of disease, maintenance of normal hepatic function is required. There should be no unresectable extrahepatic sites of Hepatic resection is the treatment of choice for resectable liver metastases from colorectal cancer. Ablative techniques should be considered in conjunction with resection in unresectable patients.
Stage description
Tis :carcinoma in situ T1:invasion of the submucosa(黏膜下) T2:invasion of the muscularis propria(肌层) T3: invasion through the muscularis propria in to subserosa(浆 膜下) or the nonperitonealized pericolic or prirectal tissues T4:perforation of visceral peritoneum or direct invasion into adjacent organs or tissyes N0:no regional lymph node metastases N1:metastases in 1-3 pericolic or perirectal lymph node N2:metastases in 4 or more lymph node N3: :metastases in lymph node along a named vascular trunk node; tumor invasion of adjacent organs M0: no distant metastases M1 :distant metastases disease
Lymphadenectomy(淋巴结切除术)
Lymph nodes at the origin of feeding vessel should be identified for pathologic exam. Lymph nodes outside the field of resection considered suspicious should be biopsied or removed. Positive nodes left behind indicate an incomplete (R2) resection. A minimum of 12 lymph nodes need to be examined to clearly establish stage II (T 3-4, N0) colon cancer. Even for Stage III disease, the number of lymph nodes correlates with survival.
TNM grouping
Stage TNM
0 Ⅰ
Ⅱ
Ⅲ
Ⅳ
5-year survival Tis N0M0 100% T1N0M0 95 T2N0M0 90 T3N0M0 80 T4N0M0 75 AnyTN1M0 72 AnyTN2M0 60 AnyTN3M0 40 AnyTanyN 5
M1
Dukes’ grouping A A B B C C C D
Laparoscopic(腹腔镜)-assisted colectomy may be considered based upon the following
Surgeon with experience performinlaparoscopically-assisted colorectal operations. No disease in rectum or prohibitive abdominal adhesions. No advanced local or metastatic disease. Not indicated for acute bowel obstruction or perforation from cancer. Thorough abdominal exploration is required Consider preoperative marking of small lesions. Resection needs to be complete to be considered curative. Best results are seen with solitary lesions when resecting metastatic liver disease6
Colorectal cancer
Wuhan university Cao chuanhua
Epidemiology
Peak
incidence : USA, New Zealand , Australia Lowest incidence: India, South America, Arab Israelis The incidence and mortality rates declined since they peaked in 1985
Principles of adjuvant radiation therapy
Radiation therapy fields should include the tumor bed, which should be defined by preoperative radiological imaging and/or surgical clips. Radiation doses should be: 45-50 Gy in 25-28 fractions. Small bowel dose should be limited to 45 Gy. 5-fluorouracil based chemotherapy should be delivered concurrently with radiation. IORT, if available, should be considered for patients with T4 or recurrent cancers as an additional boost. Preoperative radiation is preferred for these patients to aid resectability. If IORT is not available, low dose external beam radiation could be considered, prior to adjuvant chemotherapy.
Pathology and natural history
Histology
:adenocarcinoma (98%) basaloid(基 底细胞的) carcinoma (anal) Location: left colon (2/3) right (1/3) Clinical presentation Clinical course :rectal cancers are three times more likely to reoccur than colonic cancers ;rectal cancers often reoccurs first in the lungs ,colon cancer more reoccurs first in the liver
Prognosis studies
Biopsy
confirmation General evaluation Carcinombryonic antigen (CEA) screening CT or MRI Endoscopy or barium enema EUS
Clinical presentation of colorectal cancer
Acute large bowel obstruction Anaemia and palpable mass Rectal irritation and bleeding Change in the bowel habit Left-sided tumor Right side tumor Rectal cancer
Principles of adjuvant chemotherapy
Capecitabine
appears to be equivalent to bolus 5-FU/leucovorin in Stage III patients. This is anextrapolation from data available. FOLFOX appears to be superior for Stage III patients but data do not support statisticalsuperiority for Stage II patients. Bolus 5-FU/leucovorin/irinotecan should not be used in adjuvant therapy. Data are not yet available using infusional 5-FU/ leucovorin/irinotecan (FOLFIRI) or capecitabine combination regimens.