Clinical and pathologic features correlated with rare favorable survival in patients with BRAFV600E mutated colorectal cancer

BackgroundBRAF^V600E mutations occur in fewer than 10% of all patients with metastatic colorectal cancer (CRC) and arise from sessile serrated adenomas. Despite efficacy with targeted therapies against MAPK signaling and with immunotherapies in this population, survival outcomes for patients with BRAF^V600E mutated metastatic CRC in general are poor. Characteristics distinguishing patients with BRAF^V600E mutated metastatic CRC with favorable versus unfavorable outcomes have not been well annotated.MethodsRecords of 187 patients with BRAF^V600E mutated metastatic CRC evaluated at MD Anderson Cancer Center between 2005–2020 were reviewed. Patients with the shortest and longest metastatic survival (N=25 for each group) were compared. Associations between prognostic group and clinical/pathologic features were measured by odds ratio and for median survival by log-rank testing.ResultsMedian metastatic survival differed between the 2 BRAF^V600E mutated metastatic CRC populations (8.6 vs. 83.9 months, hazard ratio 32; P<0.0001). Patients with poor survival more commonly had hepatic involvement [75% vs. 28%, odds ratio (OR) 8.1, 95% confidence interval (CI): 2.3–29; P=0.001]. Patients with favorable survival were more likely to develop metachronous metastases (52% vs. 16%, OR 5.7, 95% CI: 1.5–21; P=0.01) and undergo definitive locoregional therapy to metastatic disease (40% vs. 0%, OR 34.5, 95% CI: 1.9–630; P=0.01). Microsatellite instability (36% vs. 4%, OR 19.8, 95% CI: 2.2–180; P=0.008) and prior tobacco exposure (44% vs. 16%, OR 4.1, 95% CI: 1.1–15.6, P=0.04) were associated with a favorable prognosis. Durable responses to MAPK-targeted therapies and immunotherapy were noted in the favorable group.ConclusionsA small fraction of patients with BRAF^V600E mutated metastatic CRC can achieve excellent long-term survival which belies conventional context and is driven by either surgical metastectomy or by systemic treatment options. While poor overall prognosis remains the recognized outcome for most patients with BRAF^V600E mutated metastatic CRC, it is possible that few may achieve exceptionally favorable survival.     

A cross-sectional study of obstructive sleep apnea in patients with colorectal cancer

BackgroundThe association between colorectal cancer (CRC) and obstructive sleep apnoea (OSA) has been attracting increasing attention. several studies had confirmed that OSA increases the risk of CRC onset. However, the findings of studies on the morbidity of OSA in patients with CRC were unclear. Therefore, this study aimed to investigate the morbidity of OSA in patients with CRC as well as the association between the clinicopathological characteristics of OSA and CRC.MethodsA total of 414 patients with a pathological diagnosis of CRC from 1 January, 2020 to 30 December, 2020 were included in this study. Demographic characteristics, clinical information, and tumor characteristics of participants were collected; sleep was monitored using a wearable oximeter and via sleep quality questionnaire. The oxygen desaturation index (ODI) was used to classify OSA severity so that the diagnostic criteria for OSA were set based on the ODI as 0–5 (normal) and ≥5 (abnormal). After correcting for confounding factors, a logistic regression analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for the factors affecting the tumor lymph node stage (N stage).ResultsA total of 402 patients with CRC were included in this study, including 225 (55.97%) men and 177 (44.03%) women. The mean ODI value of participants was 3.40±8.17. The morbidity of OSA among the patients with CRC having ODI ≥5 was 16.17%. A comparison between the normal and abnormal ODI value groups revealed that the high proportion of abnormal ODI was related to higher N stage (P<0.05). Logistic regression analysis revealed a correlation of ODI values and age to the N stage. Specifically, CRC patients with an abnormal ODI had a higher risk of lymph node metastasis compared to those with normal ODI (OR =1.915, 95% CI: 1.025 to 3.579). Moreover, patients with CRC aged ≥65 years had a higher risk of lymph node metastasis compared to those aged <65 years (OR =2.190, 95% CI: 1.163 to 4.125).ConclusionsCRC patients with abnormal ODI are susceptible to OSA. Additionally, abnormal ODI and age ≥65 years are relevant factors for the N2 stage.     

FBXW7α对结直肠癌细胞中热休克转录因子1表达和定位的影响

目的 探讨FBXW7对结直肠癌细胞中热休克转录因子1（HSF1）表达和定位的影响。方法 Western blot法检测敲除FBXW7及WT的结直肠癌细胞系HCT116和DLD1中HSF1及pHSF1^Ser326蛋白的表达;免疫荧光和Western blot检测在热休克及恢复期细胞中pHSF1^Ser326的核蛋白表达和定位。结果 过表达FBXW7α的DLD1细胞中HSF1蛋白表达显著降低（P<0.01）;敲除FBXW7的HCT116和DLD1细胞中HSF1和pHSF1^Ser326总蛋白表达显著升高（均P<0.05）。与WT组比较,敲除FBXW7的细胞中HSF1和pHSF1^Ser326主要累积在细胞核,而胞质表达较弱;温热刺激后,WT细胞中HSF1及pHSF1^Ser326表达恢复至未刺激水平,而敲除FBXW7的细胞中HSF1及pHSF1^Ser326在核中有较强表达（均P<0.01）。结论 敲除FBXW7的结直肠癌细胞热刺激后,细胞核HSF1水平恢复受阻,可能与缺失FBXW7不能降解胞核HSF1有关。     

肿瘤大小分类对0~Ⅲ期结直肠癌预后的影响

目的探讨肿瘤大小分类对0~Ⅲ期结直肠癌（CRC）预后的影响。方法选择538例0~Ⅲ期CRC患者进行研究,术后随访5年。对术后大体标本肿瘤按3种大小分类方法（a：≤1、＞1~≤3、＞3~≤5、＞5;b：≤2、＞2~≤5、＞5;c：≤2、＞2~≤4、＞4;单位：cm）进行分类,根据美国癌症协会第6版TNM分期（合并亚分期）进行0~Ⅲ分期。分析以上3种分类方法与TNM分期的关系,并就3种分类方法对5年总生存率（OS）作单因素和多因素分析,以探讨哪种分类方法更有优越性。结果3种肿瘤大小分类方法与TNM分期均相关,差异均有统计学意义（均P＜0.01）;且分类方法a、b、c与TNM分期均呈正相关（rs=0.436、0.379和0.415,均P＜0.01）。采用log-rank检验对肿瘤大小分类与5年OS作单因素分析,发现差异均有统计学意义（均P＜0.01）;进一步作Cox比例风险回归模型分析,结果显示肿瘤大小分类方法a的风险系数及95%CI为0.401（0.025~6.412）,差异有统计学意义（P＜0.05）;肿瘤大小分类方法b、c的风险系数及95%CI分别为4.586（0.523~40.181）、1.121（0.816~1.541）,差异均无统计学意义（均P＞0.05）。结论3种肿瘤大小分类方法均与TNM分期、预后相关,其中分类方法a是影响预后的独立因素,对预后的意义优于其他2种分类方法。     

MCRS1、MCRS2基因在结直肠癌中的表达研究

目的检测微球蛋白MCRS1、MCRS2基因在结直肠癌（CRC）中的表达情况,探讨其与临床指标的相关性及临床意义。方法选取32例CRC患者手术切除的肿瘤组织和癌旁正常组织为研究材料,RT-PCR检测MCRS1、MCRS2基因在肿瘤、癌旁正常组织中的表达水平,分析基因表达水平与多项临床指标间的相关性。结果（1）MCRS1基因在肿瘤组织中的表达阳性率高于在癌旁正常组织中的表达阳性率（93.75%vs68.75%,P＜0.05）,而MCRS2基因在肿瘤组织中的表达阳性率低于在癌旁正常组织中的表达阳性率（71.88%vs93.75%,P＜0.05）。（2）MCRS1基因在肿瘤组织中的表达水平高于在癌旁正常组织中的表达水平（P＜0.05）,且其在晚期肿瘤组织内的表达水平较在早期肿瘤组织内表达水平高（P＜0.05）,其在侵透外膜的肿瘤组织内的表达水平也高于未侵及外膜者（P＜0.05）。（3）MCRS2基因在肿瘤组织中的表达水平低于在癌旁正常组织中的表达水平（P＜0.05）,且其在晚期肿瘤组织内的表达水平较在早期肿瘤组织内表达水平低（P＜0.05）,其在侵透外膜的肿瘤组织内的表达水平也低于未侵及外膜者（P＜0.05）。（4）MCRS1、MCRS2基因在肿瘤组织中的表达水平呈负相关（r=-0.4656,P＜0.05）,MCRS1基因在肿瘤组织中的表达水平与患者血清癌胚抗原（CEA）水平呈正相关（r=0.5045,P＜0.05）,而MCRS2基因在肿瘤组织中的表达水平与血清CEA水平无明显相关性（r=-0.0139,P＞0.05）。结论MCRS1、MCRS2基因在CRC肿瘤组织中的表达水平显著不同,MCRS1基因可能是促癌基因,而MCRS2基因可能是抑癌基因。     

武汉地区1998例结直肠癌临床病理特征分析

目的分析武汉地区结直肠癌的临床病理特征及发病特点。方法回顾性分析1998年至2013年在武汉市第八医院收治的1 998例结直肠癌临床及病理资料,比较其主要症状、性别、年龄、肿瘤部位、组织类型、病理分级及临床病理分期的差异。结果本组最常见症状为血便及大便次数增多,好发部位主要位于直肠,组织学类型以管状腺癌腺癌为主,淋巴结转移与肿瘤的分化程度、侵袭程度及TNM分期有关。结论武汉地区男性结直肠癌的发病率显著高于女性,老年人仍是结直肠癌的高发人群,但青壮年也占相当大的比例。大部分患者就诊时已是中晚期。     

Modifiable Failures in the Colorectal Cancer Screening Process and Their Association With Risk of Death

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Impact of the supine position versus left horizontal position on colonoscopy insertion: a 2-center,randomized controlled trial

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