年龄对转移性结直肠癌不同治疗方法的影响及预后研究

目的探讨年龄与转移性结直肠癌（mCRC）的治疗方式选择和预后的相关性。 方法我们从美国国家癌症数据库（NCDB）中选择了2004~2014年mCRC的患者,总数为43 977人,将患者分为三个年龄组：18~49岁、50~75岁和＞75岁。分别描述了每个治疗类别的患者百分比,包括仅原发性肿瘤切除术（PTR）、仅化疗和PTR加化疗。在调整人口统计学和临床因素后,计算并比较不同年龄组和治疗组的限制平均生存时间（RMST）。 结果18~49岁年龄组的大多数患者（61.8%）接受PTR联合化疗,50~75岁年龄组约有53.3%的患者接受PTR联合化疗,＞75岁年龄组大约有34.7%接受PTR联合化疗。在研究期间,所有年龄组的mCRC患者,PTR加化疗组呈下降趋势,而仅化疗组呈上升趋势。与其他治疗方法相比,PTR加化疗在所有年龄组中的生存率最高。除了18~49岁组的患者外,化疗与仅PTR相比具有更高的生存时间。在接受PTR加化疗治疗的患者中,与其他治疗相比,18~49和50~75岁组的围手术期化疗的患者可以获得更长的生存期,但＞75岁组的化疗与否和生存期无关。 结论尽管mCRC患者PTR加化疗呈下降趋势,但是其在所有年龄组中显示出最大的生存获益。不同的年龄组在接受特定的MDT治疗后的获益存在差异。     

结直肠de novo癌的研究概况

近年来，随着内镜技术的发展，已能发现越来越多的微小和早期结直肠病变。部分报道曾描述了一种微小而极具侵袭性的结直肠癌，因其缺乏起源于腺瘤的证据，被称为“de novo癌（de novo carcinoma）”。这类肿瘤由于挑战了经典的腺瘤癌变途径而引起众多争议，但由于其所显示的独特生物学特性，也得到了各国学者的充分重视。本文将对de novo癌的概念、争议及其临床、分子生物学水平的特点进行初步概述。     

结直肠息肉与肠道菌群变化关系

正结直肠息肉虽是肠道良性肿瘤,但少数腺瘤性息肉可癌变,其中腺瘤-癌假说实验已被证实~([2])。据统计,在我国,结直肠癌是第5类最常见癌症,且近年来发病率呈迅速上升趋势~([3])。肠道菌群是人体内最复杂和最大的微生态系统,对维持机体健康有重要作用~([4])。研究发现肠道菌群与结直肠息肉密切相     

结直肠支架的临床应用

自1991年Dhomoto首次报道使用金属支架置入治疗恶性直肠狭窄以来,结直肠支架置入治疗良恶性结直肠梗阻的方法在世界范围内得到广泛应用。结直肠支架的种类很多,最常用的是自膨式金属支架（SEMS）。支架根据表面是否覆膜,还可以分为覆膜支架和非覆膜支架两类,覆膜支架可以阻止组织或肿瘤细胞长入,但容易发生移位。支架置入一般需要在X线造影监测和内镜直视配合下进行。支架的输送系统分为经内镜钳道（TTS）方式和非TTS方式两种。目前结直肠支架主要用于恶性结直肠梗阻的姑息治疗和肿瘤切除手术前的过渡,在良性梗阻中也有应用,覆膜支架还可以用于封堵肠道瘘口。结直肠支架置入处理急性梗阻可以避免急诊手术,减少结肠造口,提高生活质量。结直肠支架置入的主要并发症包括穿孔、移位和再梗阻。目前,结直肠支架置入术的真实效果尚未证实。发展新型支架,改善输送系统,规范实施机构的资质,提高内镜医师的经验技术,谨慎合理选择适应证有助于提高结直肠支架置入的疗效。     

结直肠腺瘤患者血脂及脂蛋白变化的研究

目的　探讨血脂及脂蛋白变化与结直肠腺瘤的关系。方法　结直肠腺瘤患者 180例 ,对照组 5 5例 ,收集清晨静脉血 2ml,分别测定血清总胆固醇 (TC)、甘油三脂 (TG)、高密度脂蛋白胆固醇 (HDL C)和低密度脂蛋白胆固醇 (LDL C) ,并根据腺瘤的部位、大小、数量、组织成分、异型增生的情况进行分组 ,分别比较各组的测定值。结果　腺瘤组TC、TG、LDL C较对照组显著升高 (P <0 .0 1) ,HDL C显著下降 (P <0 .0 1) ,其他各亚组测定值也有相应改变。结论　TC、TG、LDL C与腺瘤的发生及恶变有关 ,HDL C对其有抑制作用。     

血脂异常患者结直肠早期癌发病的危险因素分析

探讨血脂异常患者结直肠早期癌发病的危险因素,以及他汀类药物在其中可能发挥的作用。回顾性分析2018年2月—2021年2月北京友谊医院消化科行内镜治疗合并血脂异常的结直肠肿物患者资料。根据结肠镜及病理结果将266例患者分为结直肠腺瘤组（n=174）和结直肠早期癌组（n=92）。分析两组患者临床资料的差异,采用Logistic回归分析血脂异常患者结直肠早期癌发病的危险因素。结果发现,与结直肠腺瘤组相比,结直肠早期癌组患者的男性比例（64.1%比25.9%）、吸烟比例（41.3%比14.4%）和饮酒比例（37.0% 比17.2%）更高,同时低密度脂蛋白胆固醇［（3.06±0.81） mmol/L比（2.60±0.74） mmol/L］和总胆固醇值更高［（5.27±1.22） mmol/L 比（4.61±1.06） mmol/L］,而他汀用药占比更低（27.2% 比52.9%）,差异均有统计学意义（P均<0.05）。多因素Logistic回归分析显示,男性（OR=3.641, 95%CI：1.694~7.826）、吸烟（OR=2.920, 95%CI：1.159~7.356）以及较高的低密度脂蛋白胆固醇（OR=2.203,95%CI：1.481~3.277）、较高的总胆固醇水平（OR=1.744,95%CI：1.329~2.289）是血脂异常患者结直肠早期癌发生的危险因素,而他汀用药史（OR=0.469,95%CI：0.236~0.932）对避免血脂异常患者结直肠早期癌的发生具有保护作用。应对血脂异常患者进行戒烟宣教,监测低密度脂蛋白胆固醇、总胆固醇水平,必要时使用他汀类药物促进血脂达标,同时积极进行结直肠癌的早期筛查。     

便秘与结直肠息肉及结直肠癌关系的研究进展

目前便秘与结直肠息肉及结直肠癌的发生、发展的相关性仍存在争议.有研究显示便秘可能参与了结直肠息肉和结直肠癌的发生、发展,其机制可能是肠道菌群失调引起菌群代谢产物异常,导致肠道运动功能障碍和(或)免疫微环境异常.便秘可能可以作为结直肠息肉和结直肠癌发病的预警症状.尽早对便秘患者行结肠镜筛查,并定期随访和适时干预,有助于发...     

结直肠侧向发育型肿瘤组织中RNF6蛋白的表达变化及其意义

目的 观察结直肠侧向发育型肿瘤（LST）组织中RNF6蛋白的表达变化,并探讨其意义。方法 LST患者33例、结直肠隆起型腺瘤（PA）患者37例、结直肠癌患者35例均接受手术治疗,手术过程中留取切除的肿瘤组织分别记为LST组、PA组、CRC组,留取结直肠癌患者的癌旁正常组织（距癌组织>5 cm）记为Control组。采用免疫组织化学染色法检测各组织中RNF6蛋白,采用半定量评分法评估蛋白表达情况,包括阳性表达率和阳性程度,并分析RNF6蛋白表达与LST患者临床病理参数的关系。结果 癌旁正常组织多数不染色或染色颜色较浅、阳性面积小,而结直肠癌组织中RNF6蛋白染色较深,多数呈棕黄色颗粒沉积,PA组织及LST组织的染色程度介于癌旁正常组织及结直肠癌组织中间。Control组、PA组、LST组、CRC组RNF6蛋白阳性表达率分别为40%、51.4%、75.8%、91.4%,组间相比,P均<0.05。Control组、PA组、LST组、CRC组RNF6蛋白阳性强度呈递增趋势（P均<0.05）。RNF6蛋白表达与LST患者上皮内瘤变级别有关（P<0.05）,上皮内瘤变级别越...     

重视结直肠腺瘤癌变的精准防治

近年来,结直肠癌发病率持续升高引起广泛重视。结直肠腺瘤是结直肠癌最主要的癌前病变,防治结直肠腺 瘤是减低结直肠癌发病率和死亡率的重要途径。结直肠腺瘤的发生与多种因素相关,如饮食、烟酒摄入、体重、年龄 及家族史等。结直肠腺瘤的治疗包括内镜下切除和手术治疗,术后病理评价至关重要。通过积极开展筛查、生活方 式的改善以及化学预防等方式,可对结直肠腺瘤癌变进行个体化精准防治。     

钙剂预防结直肠癌和结直肠息肉的荟萃分析

目的研究饮食中钙对成人结直肠癌发病率和结直肠息肉复发率的影响及其不良反应。方法应用国际Cochrane协作网的系统评价方法对全世界关于钙剂与安慰剂或空白对照比较的随机对照试验进行系统评价,选用固定效应模型。结果3组共37 628例患者的随机对照研究(Jadad评分≥5分)经荟萃分析显示．钙剂有预防结直肠息肉复发的作用(Peto OR:0．74,CI:0．58～0．95,P=0．02),但无证据支持长期使用钙剂可减少结直肠癌发生的危险性(Peto OR:1.07,CI:0．86～1．33,P> 0．05)。未发现补钙组和安慰剂组间有不良反应(Peto OR:1．05,CI:0．91～1．22)及失访率(Peto OR: 1．11,CI:0．88～1．40)的差异。结论结直肠息肉患者长期使用钙剂可预防结直肠息肉复发,但尚无减少结直肠癌发生的证据。     

Role of cetuximab in first-line treatment of metastatic colorectal cancer

The treatment of metastatic colorectal cancer(mCRC)has evolved considerably in the last decade,currently allowing most mCRC patients to live more than two years.Monoclonal antibodies targeting the epidermal growth factor receptor(EGFR)and vascular endothelial growth factor play an important role in the current treatment of these patients.However,only antibodies directed against EGFR have a predictive marker of response,which is the mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS).Cetuximab has been shown to be effective in patients with KRAS wild-type mCRC.The CRYSTAL study showed that adding cetuximab to FOLFIRI(regimen of irinotecan,infusional fluorouracil and leucovorin)significantly improved results in the first-line treatment of KRAS wildtype mCRC.However,results that evaluate the efficacy of cetuximab in combination with oxaliplatin-based chemotherapy in this setting are contradictory.On the other hand,recent advances in the management of colorectal liver metastases have improved survival in these patients.Adding cetuximab to standard chemotherapy increases the response rate in patients with wild-type KRAS and can thus increase the resectability rate of liver metastases in this group of patients.In this paper we review the different studies assessing the efficacy of cetuximab in the first-line treatment of mCRC.     

KRAS mutation testing in metastatic colorectal cancer

The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers, and KRAS mutational status testing has been highlighted in recent years. The most frequent mutations in this gene, point substitutions in codons 12 and 13, were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies. Therefore, determining the KRAS mutational status of tumor samples has become an essential tool for managing patients with colorectal cancers. Currently, a variety of detection methods have been established to analyze the mutation status in the key regions of the KRAS gene; however, several challenges remain related to standardized and uniform testing, including the selection of tumor samples, tumor sample processing and optimal testing methods. Moreover, new testing strategies, in combination with the mutation analysis of BRAF, PIK3CA and loss of PTEN proposed by many researchers and pathologists, should be promoted. In addition, we recommend that microsatellite instability, a prognostic factor, be added to the abovementioned concomitant analysis. This review provides an overview of KRAS biology and the recent advances in KRAS mutation testing. This review also addresses other aspects of status testing for determining the appropriate treatment and offers insight into the potential drawbacks of mutational testing.     

Impact of KRAS mutation and PTEN expression on cetuximab-treated colorectal cancer

AIM:To investigate the prognostic value of KRAS mutation,and phosphatase and tensin (PTEN) expression in Chinese metastatic colorectal cancer metastatic colorectal cancer (mCRC) patients treated with cetuximab.METHODS:Ninety Chinese mCRC patients treated with cetuximab were evaluated for KRAS mutation and PTEN protein expression by DNA sequencing of codons 12 and 13 and immunohistochemistry,respectively.We then selected 61 patients treated with cetuximab,either in combination with chemotherapy,or alone as a second-line or third-line regimen to assess whether KRAS mutation or PTEN protein expression is associated with the response and the survival time of mCRC patients treated with cetuximab.RESULTS:KRAS mutation was found in 30 (33.3%) tumor samples from the 90 patients,and positive PTEN expression was detected in 58 (64.4%) of the 90 patients.Among the 61 patients who were treated with cetuximab as a second-line or third-line regimen,the resistance to cetuximab was found in 22 patients with KRAS mutation and in 39 patients without KRAS mutation,with a response rate of 4.5% and 46.1% respectively (P=0.001),a shorter median progression-free survival (PFS) time of 14 ± 1.3 wk and 32 ± 2.5 wk respectively (P < 0.001),a median overall survival (OS) time of 11 ± 1.2 mo and 19 ± 1.8 mo respectively (P < 0.001),as well as in 24 patients with negative PTEN expression and in 37 patients with positive PTEN expression respectively (P < 0.001),with a responsive rate of 4.2% and 48.6% respectively,a shorter median PFS survival time of 17 ± 2.0 wk and 28 ± 1.9 wk respectively (P=0.07),and a median OS time of 11 ± 1.3 mo and 18 ± 1.9 mo respectively (P=0.004).Combined KRAS mutation and PTEN expression analysis showed that the PFS and OS time of patients with two favorable prognostic factors were longer than those of patients with one favorable prognostic factor or no favorable prognostic factor (P < 0.001).CONCLUSION:KRAS mutation and PTEN protein expression are significantly correlated with the response ra     

Molecular biomarkers for the detection of metastatic colorectal cancer cells

Approximately half of all patients with colorectal cancer develop local recurrence or distant metastasis during the course of their illness. Recently, the molecular detection of metastatic cancer cells in various types of clinical samples, such as lymph nodes, bone marrow, peripheral blood, and peritoneal lavage fluid, has been investigated as a potential prognostic marker. The prognostic value of molecular tumor cell detection was independent of the type of detection method used. As assays become more sensitive and quantitative, a more thorough assessment of the cancer status of patients will be based on molecular markers alone. At present, it is difficult to conclude that one specific molecular marker is superior to others. Comparative analyses are recommended to assess the prognostic impact of molecular analyses in the same patient and determine the biomarkers that provide the most accurate prognostic information.     

EGFR单抗治疗晚期结直肠癌的疗效预测标志物的研究进展

靶向EGFR的单克隆抗体西妥昔单抗和帕尼单抗的问世大大拓宽了转移性结直肠肿瘤疗效,而当人们意识到使用免疫组织化学技术检测EGFR蛋白表达阳性与应用EGFR单抗治疗的疗效并没有相关性,便致力于可能的疗效预测标志物的研究.EGFR信号转导系统下游的例如K-ras、BRAF、PIK3CA的基因突变,以及肿瘤抑制基因PTEN的失活都成了研究的热点.在结直肠癌中,K-ras基因突变率为35%-45%,已成为EGFR单克隆抗体治疗转移性结直肠癌的主要疗效预测标志物.另外,在K-ras野生型基因的患者中,BRAF、PIK3CA基因突变以及PTEN的缺失表达,都可能与EGFR单克隆抗体的耐药有关,但在这些可能的疗效预测标志物被运用到临床实践中前,还需进一步地研究以明确他们的价值,以期在选择适合接受EGFR单克隆抗体的患者中起到更大的作用.而K-ras基因突变被作为治疗前的疗效预测标志物,则是开创了转移性结直肠癌个体化治疗的第一步.     

遗传性非息肉病性大肠癌6家系临床分析

目的总结遗传性非息肉病性大肠癌(HNPCC)的临床特征,提高其早期诊断和治疗水平。方法对我院6个HNPCC家系进行调查,记录患者性别、发病年龄、肿瘤部位等。结果6个家系有大肠癌患者19例,占同期所有大肠癌的2.7%。其中男性10例,女性9例;发病年龄为26～74岁,中位年龄为53.4岁;共有大肠癌病灶23处,60.9%位于右半结肠,多原发大肠癌有4例。另有大肠腺瘤患者2例,白血病患者1例,原发性肝癌患者1例。结论HNPCC有明显的临床特征,利用这些特征有助于早期诊断和提高防治效果。     

Treatment dilemmas of cetuximab combined with chemotherapy for metastatic colorectal cancer

Although monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR) have largely enriched the available therapeutic choices for colorectal cancer (CRC), the understanding and management of their associated clinical toxicities are limited. In addition, the combined strategies of administering EGFR mAbs and traditional cytotoxic agents, such as 5-fluorouracil, oxaliplatin and irinotecan, have resulted in a more complicated management of CRC treatment-related side effects compared with EGFR mAb monotherapy. We believe that a thorough recognition of the toxicities of EGFR mAb drugs is essential for physicians to increase the therapeutic index in the treatment of CRC. This review aims to summarize the existing information regarding the treatment dilemmas of cetuximab combined with chemotherapy in the management of metastatic CRC.     

A meta-analysis of randomized controlled trials comparing chemotherapy plus bevacizumab with chemotherapy alone in metastatic colorectal cancer

Purpose  Bevacizumab has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients when combined with chemotherapy. Several randomized clinical studies have evaluated bevacizumab in combination with chemotherapy. Meta-analysis was performed to better assess the efficacy and safety of bevacizumab with chemotherapy for mCRC. Materials and methods  Five clinical trials randomizing a total of 3,103 mCRC patients to chemotherapy alone or to the combined treatment of chemotherapy plus bevacizumab were identified. The efficacy data included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), and the safety data contained the 60-day all-cause mortality rate, adverse events (AEs), and specific toxicity such as hypertension, thrombosis, bleeding, proteinuria, gastrointestinal perforation, diarrhea, and leucopenia. Result  There was a significant PFS benefit (P = 0.00; hazards ratio [HR] = 0.66) and OS benefit (P = 0.00; HR = 0.77) in favor of the combined treatment. The ORR was significantly higher on the bevacizumab-containing arm (P = 0.021; relative risk [RR] = 1.5), while CR was comparable between the two arms (P = 0.09). A higher incidence of grade 3/4 AEs, grade 3/4 hypertension, grade 3/4 thromboembolic/thrombotic events, grade 3/4 bleeding, and gastrointestinal perforation was associated with the bevacizumab group. The two treatment groups were similar in terms of grade 3/4 proteinuria, grade 3/4 leukopenia, grade 3/4 diarrhea, and the 60-day all-cause mortality rate. Conclusion  The addition of bevacizumab to chemotherapy confers a clinically meaningful and statistically significant improvement in OS, PFS, and ORR. Its side effects are predictable and manageable and do not compound the incidence or severity of toxicities from chemotherapy.     

I~III期结直肠癌淋巴结转移比率与预后关系

目的评价I~III期结直肠癌淋巴结转移比率与患者预后的关系。 方法回顾性分析中山大学附属第一医院胃肠胰腺外科2004年6月至2008年11月间446例行根治性切除的结直肠癌患者临床病理数据,探讨结直肠癌预后相关危险因素,评估结直肠癌淋巴结转移比率与患者预后的关系。 结果446例结直肠癌I、II、III期患者的5年总体生存率分别约为87.4%,83.1%和64.8%（Log-rank检验,P<0.001）。我们根据淋巴结转移比率（metastatic lymph node ratio, mLNR）将CRC患者分为三组：A组：mLNR为0;B组：mLNR为>0%~14%;C组：mLNR为>14%。A、B、C组三组患者的5年总体生存率分别约为84.3%、79.6%和49.1%（Log-rank检验,χ²=55.959,P<0.001）。就直肠癌患者而言,A、B、C三组5年生存率分别为79.0%、73.5%和43.2%（Log-rank检验,χ²=26.332,P<0.001）。而对于结肠癌患者来说三组的5年生存率分别为87.1%,80.8%和55.5%（Log-rank检验,χ²=21.214,P<0.001）。单因素和多因素Cox分析均显示,mLNR是结直肠癌独立的预后危险因素,随着mLNR的上升,结直肠癌患者的预后变差。 结论淋巴结转移比率（mLNR）是结直肠癌患者预后的独立危险因素,与N分期类似,但更有优势,可作为评估结直肠癌患者预后的指标之一。