新生期结直肠扩张对发育期大鼠内脏痛觉敏感性影响

目的探讨新生期伤害性结直肠扩张刺激(CRD)对发育期大鼠内脏痛觉敏感性的影响。方法8日龄新生SD大鼠随机分成实验组和对照组,每组16只;实验组新生鼠在出生第8天开始给予结直肠刺激,1次/d,连续7d;对照组则不给予结直肠刺激。随后,两组大鼠常规饲养到6周龄时进行内脏敏感性测定。采用腹壁撤退反射(AWR)评分和痛阈测定作为不同的扩张压力下结直肠疼痛反应指标,评估肠道痛觉敏感性。采用单因素和重复测量方差分析进行统计学分析,α=0.05为显著性检验标准。结果6周时两组大鼠体重差异无统计学意义;两组大鼠降结肠均未见明显病理组织损伤;随CRD压力增加,两组幼鼠AWR评分增加,实验组幼鼠CRD在60mmHg和80mmHg之间评分差异无统计学意义;在20、40、60mmHg范围内,相同压力下,实验组幼鼠评分明显高于对照组,差异有统计学意义,当CRD压力为80mmHg时,两组评分差异无统计学意义;实验组和对照组大鼠痛阈值分别为26.5±4.9mmHg、47.8±5.0mmHg,两组痛阈差异有统计学意义(F=149.753,P<0.01)。结论新生期进行持续的结直肠刺激的确能造成大鼠痛阈下降,出现慢性内脏高敏感性,并且这种高敏感性能持续到幼年期,同时无明显的组织学改变。     

Bioavailability and phase II study of oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer

Purpose: This study was undertaken to address the influence of concurrent administration on the pharmacokinetics of UFT (uracil plus tegafur) and leucovorin (LV), and to measure the antitumor activity of a 28-consecutive-day oral regimen of UFT plus LV in patients with relapsed or refractory colorectal cancer. Methods: Patients with advanced measurable colorectal cancer who had failed previous therapy with intravenous bolus 5-fluorouracil (5-FU) were eligible. Patients were treated with UFT 300 mg/m² per day plus LV 90 mg per day in three divided doses every 8 h for 28 days, repeated at 35-day intervals. In addition, a three-treatment by three-period crossover bioavailability comparison of oral LV 30 mg plus UFT 200 mg versus either LV or UFT alone was scheduled for the 8 days preceding the first cycle of therapy. Results: Of 19 patients enrolled, 18 were assessable for pharmacokinetics and response. When LV was coadministered with UFT, there were no statistically significant effects on tegafur, uracil, or 5-FU C_max, AUC, or T_max, with the exception of a delayed T_max for tegafur (P = 0.03). No statistically significant differences were found in LV and 5-methyltetrahydrofolate plasma levels when LV was administered alone or with UFT. However, wide interpatient variability was observed for all parameters. There were no antitumor responses seen. Conclusions: Although the T_max for tegafur is delayed with the concurrent administration of LV, there were no differences (P > 0.05) in any pharmacologic parameters that are of likely clinical significance. However, the great interpatient variability observed in UFT and LV pharmacology may have obscured true bioavailability effects in this small patient population. Daily oral UFT plus LV is inactive as second-line therapy in patients who have failed bolus 5-FU. Received: 13 March 1998 / Accepted: 1 June 1998     

食管癌APC/MCC、DCC基因杂合丢失的研究

目的研究ＡＰＣ（ａｄｅｎｏｍａｔｏｕｓｐｏｌｙｐｏｓｉｓｃｏｌｉ）、ＭＣＣ（ｍｕｔａｔｉｏｎｉｎｃｏｌｏｒｅｃｔａｌｃａｎｃｅｒ）和ＤＣＣ（ｄｅｌｅｔｅｄｉｎｃｏｌｏｒｅｃｔａｌｃａｎｃｒ）基因在人食管癌组织中的变化。方法采用聚合酶链反应（ＰＣＲ）及限制性片段长度多态现象（ＲＦＬＰ）法检测了４６例食管癌组织中ＡＰＣ、ＭＣＣ和ＤＣＣ基因的杂合缺失。结果ＡＰＣ、ＭＣＣ和ＤＣＣ位点的杂合性丢失的发生频率分别为２９．０％（９／３１）、３３．３％（８／２４）和３２．４％（１２／３７）。然而,这些基因位点的杂合性丢失与肿瘤病理学类型、肿瘤的大小、浸润性及转移性无统计学的显著相关性（Ｐ＞０．０５）。结论ＡＰＣ、ＭＣＣ和ＤＣＣ基因位点的杂合性丢失在一定程度上是食管癌基因改变的普遍现象,并可能在肿瘤的发生中起作用。     

人类错配修复基因在HNPCC家系中的突变研究

目的 了解２９个遗传性非息肉病性结直肠癌（ＨＮＰＣＣ０这 中ｈＭＬＨＩ和ｈＭＳＨ２基因的种系突变状况。方法 ＨＰＣＲ－ＳＳＣＰ和ＤＮＡ测序的方法进行突变筛选。结果 （１）在２９个家系中,ｈＭＬＨ１和ｈＭＳＨ２两个基因的总突变率为３１．０％,与对照组（２％）相比差异有极显著性,其中ＨＭＬＨ１基因是主要的相关基因。（２）１０名患大肠癌的家系成员均含有与先证者相同的突变,反映了突变与在肠癌的主要的相关基     

大肠腺癌中p16、bcl-2异常表达与多药耐药性关系的研究

目的　研究大肠腺癌ｐ１６、ｂｃｌ－２ 表达与多药耐药性的关系。方法　应用Ｓ－Ｐ免疫组化法检测５２例大肠腺癌及３０例癌旁组织中ｐ１６、ｂｃｌ－２、ｐ－ｇｐ 的表达。结果　癌组织中ｐ１６ 阳性率 ６１．５％ （３２／５２）;ｂｃｌ－２ 阳性率７８．８％ （４１／５２）;ｐ－ｇｐ 阳性率８２．６％ （４３／５２）。ｐ１６ 在不典型增生组织的表达高于正常粘膜上皮（Ｐ＜ ０．０５）,癌与不典型增生组织的表达无差异（Ｐ＞ ０．０５）。癌ｐ１６ 表达水平与癌组织分化呈正相关,与肿瘤细胞的浸润深度、淋巴结转移及ｐ－ｇｐ 表达水平呈负相关。ｂｃｌ－２ 在癌旁的正常粘膜上皮无表达,在癌与不典型增生及ｐ－ｇｐ 的表达无差异（Ｐ＞ ０．０５）。ｐ－ｇｐ 在癌旁与癌的表达无差异（Ｐ＞ ０．０５）,与肿瘤的浸润深度及淋巴结转移呈正相关。结论　ｐ１６,ｂｃｌ－２,ｍ ｄｒ－１基因表达对判断病人耐药程度、设计治疗方案、判断预后具有重要的临床意义     

同时多原发大肠癌（附18例临床分析）

目的探讨提高同时多原发大肠癌诊断率及治疗效果。方法回顾分析１８例同时多原发大肠癌的临床病理资料。结果本组同时多原发大肠癌１８例,癌灶３８个,其中腺瘤癌变占２６３％,均行手术治疗,术后三年生存率、五年生存率分别为６４７％和４７０％。结论术前钡灌肠造影、纤维结肠镜检查,术中充分仔细探查全结肠及经结肠切口结肠镜检查,是提高同时多原发大肠癌诊断率的关键。     

Abdominal lymph node recurrence from colorectal cancer: Resection should be considered as a curative treatment in patients with controlled disease

BackgroundLymph node recurrences (LNR) from colorectal cancer (CRC) still represent a therapeutic challenge, as standardized recommendations have yet to be established. The aim of this study was to analyze short- and long-term oncological outcomes following resection of LNR from CRC.MethodsAll patients with previously resected CRC who underwent histopathologically confirmed LNR resection in 3 tertiary referral centers between 2010 and 2017 were reviewed. Short- and long-term outcomes were analyzed, mainly recurrence-free and overall survival. Further recurrences following LNR resection were also analyzed.ResultsOverall, 18 patients were included. Primary CRC was left-sided in 16 (89%) patients, staged T3-4 in 15 (83%), N+ in 14 (78%) and presented with synchronous metastases in 8 (43%). Median time interval between primary CRC and LNR resections was 31 months. Performed lymphadenectomies were aortocaval (n = 10), pelvic (n = 7), in hepatic pedicle (n = 3) and mesenteric (n = 1). Four patients had associated liver metastases resection. Three (17%) presented with postoperative complications, of which one Clavien-Dindo 3. Fourteen (78%) patients presented with further recurrences after a mean delay of 9 months, with 36% of patients presenting with early (<6 months) recurrence. Five (36%) patients could undergo secondary recurrence resection and 3 (21%) patients radiotherapy. Median overall survival following LNR resection reached 44 months.ConclusionsCurrent results suggest that LNR resection is feasible and associated with improved survival, in selected patients. Longer time interval between primary CRC resection and LNR occurrence appeared to be a favorable prognostic factor whereas multisite recurrence appeared to be associated with impaired long-term survival.     

Dpr2、Nodal在结直肠癌组织中的表达与临床意义

目的：探讨Dpr2及Nodal在结直肠癌组织中的表达情况及临床意义。方法采用qRT-PCR检测结直肠癌癌组织及其对应的癌旁正常组织中Dpr2 mRNA、Nodal mRNA的表达情况,应用免疫组化法检测 Dpr2及 Nodal蛋白的表达。生存率统计采用 Kaplan-Meier法,生存曲线比较采用 Log-Rank检验,预后分析采用 Cox回归模型分析。结果结直肠癌组织中 Dpr2 mRNA的表达低于对应的癌旁组织（0.0015±0.008 vs.0.004±0.0004,P＜0.000）,Nodal mRNA表达显著高于癌旁组织（0.0091±0.0014 vs.0.0048±0.0014,P＜0.000）。相对于癌旁正常组织而言,结直肠癌组织中Dpr2蛋白的表达降低（P＝0.001）,而Nodal蛋白表达则增加（P＜0.001）。同时,结直肠癌中Dpr2蛋白的表达与肿瘤分化程度相关（P＜0.05）,而与性别、年龄、肿瘤位置、淋巴结转移、浸润深度及TNM分期无关,结直肠癌中Nodal蛋白的表达与肿瘤分化程度及浸润深度相关（P＜0.05）,而与其他临床病理特征无关（P＞0.05）。经生存分析及 Cox 风险模型显示,Dpr2及Nodal是结直肠癌的独立预后因素。结论 Dpr2/Nodal通路在结直肠癌组织中的异常表达可能在肿瘤形成及进展过程中发挥重要作用。？     

结直肠癌住院患者分阶段药学监护模式的构建与实践

目的 探讨临床药师参与结直肠癌（CRC）住院患者分阶段药学监护模式。方法 制定住院CRC患者分阶段的药学监护模式及监护内容,依据该监护模式对1例使用FOLFIRI方案（伊立替康+左亚叶酸钙+氟尿嘧啶）发生3度迟发性腹泻及2度口腔溃疡的CRC患者进行分阶段药学监护。具体内容包括化疗前的药学监护,如肝肾功能及血常规的评估、既往不良反应程度的评估、化疗药物剂量调整的评估;化疗中的药学监护,如化疗药物预处理的合理性、化疗药物致吐级别的评估与监护;化疗后的药学监护,如不良反应监测、出院带药建议及患者用药教育。结果 通过制定并实施CRC患者分阶段药学监护模式,患者得到了个体化的治疗方案,药品不良反应得到了及时发现与干预。结论 通过制定住院CRC患者分阶段药学监护模式,临床药师可以对该类患者进行有效的用药监护;本模式可为临床药师参与临床药物治疗工作模式提供一定的参考。