Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection

AIM: To assess blood chitinase 3-like 1 (CHi3L1) levels for 2 mo after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC). METHODS: CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative (PreOp), early postoperative (PostOp), and 1 or more late PostOp samples [postoperative day (POD) 7-27] available were included. Plasma CHi3L1 levels (ng/mL) were determined in duplicate by enzyme linked immunosorbent assay. RESULTS: PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL (n = 80). Significantly elevated (P < 0.001) median plasma levels (ng/mL) over PreOp levels were detected on POD1 (667.7 CI: 495.7, 771.7; n = 79), POD 3 (132.6 CI: 95.5, 173.7; n = 76), POD7-13 (96.4 CI: 67.7, 136.9; n = 62), POD14-20 (101.4 CI: 80.7, 287.4; n = 22), and POD 21-27 (98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. CONCLUSION: Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.     

Academic hospital staff compliance with a fecal immunochemical test-based colorectal cancer screening program

AIM: To measure the compliance of an Academic Hospital staff with a colorectal cancer (CRC) screening program using fecal immunochemical test (FIT). METHODS: All employees of “Attikon” University General Hospital aged over 50 years were thoroughly informed by a team of physicians and medical students about the study aims and they were invited to undergo CRC screening using two rounds of FIT (DyoniFOB^® Combo H, DyonMed SA, Athens, Greece). The tests were provided for free and subjects tested positive were subsequently referred for colonoscopy. One year after completing the two rounds, participants were asked to be re-screened by means of the same test. RESULTS: Among our target population consisted of 211 employees, 59 (27.9%) consented to participate, but only 41 (19.4%) and 24 (11.4%) completed the first and the second FIT round, respectively. Female gender was significantly associated with higher initial participation (P = 0.005) and test completion - first and second round - (P = 0.004 and P = 0.05) rates, respectively. Phy sician’s (13.5% vs 70.2%, P < 0.0001) participation and test completion rates (7.5% vs 57.6%, P < 0.0001 for the first and 2.3% vs 34%, P < 0.0001 for the second round) were significantly lower compared to those of the administrative/technical staff. Similarly, nurses participated (25.8% vs 70.2%, P = 0.0002) and completed the first test round (19.3% vs 57.6%, P = 0.004) in a significant lower rate than the administrative/technical staff. One test proved false positive. No participant repeated the test one year later. CONCLUSION: Despite the well-organized, guided and supervised provision of the service, the compliance of the Academic Hospital personnel with a FIT-based CRC screening program was suboptimal, especially among physicians.     

Systematic review of laparoscopic vs open surgery for colorectal cancer in elderly patients

AIM: To verify the safety and validity of laparoscopic surgery for the treatment of colorectal cancer in elderly patients. METHODS: A meta-analysis was performed of a systematic search of studies on an electronic database. Studies that compared laparoscopic colectomy (LAC) in elderly colorectal cancer patients with open colectomy (OC) were retrieved, and their short and long-term outcomes compared. Elderly people were defined as 65 years old or more. Inclusion criteria were set at: Resection of colorectal cancer, comparison between laparoscopic and OC and no significant difference in backgrounds between groups. RESULTS: Fifteen studies were identified for analysis. LAC was performed on 1436 patients, and OC performed on 1810 patients. In analyses of short-term outcomes, operation time for LAC was longer than for OC (mean difference = 34.4162, 95%CI: 17.8473-50.9851, P < 0.0001). The following clinical parameters were lower in LAC than in OC: Amount of estimated blood loss (mean difference = -93.3738, 95%CI: -132.3437 to -54.4039, P < 0.0001), overall morbidity (OR = 0.5427, 95%CI: 0.4425-0.6655, P < 0.0001), incisional surgical site infection (OR = 0.6262, 95%CI: 0.4310-0.9097, P = 0.0140), bowel obstruction and ileus (OR = 0.6248, 95%CI: 0.4519-0.8638, P = 0.0044) and cardiovascular complications (OR = 0.4767, 95%CI: 0.2805-0.8101, P = 0.0062). In analyses of long-term outcomes (median follow-up period: 36.4 mo in LAC, 34.3 mo in OC), there was no significant difference in overall survival (mean difference = 0.8321, 95%CI: 0.5331-1.2990, P = 0.4187) and disease specific survival (mean difference = 1.0254, 95%CI: 0.6707-1.5675, P = 0.9209). There was also no significant difference in the number of dissected lymph nodes (mean difference = -0.1360, 95%CI: -4.0553-3.7833, P = 0.9458). CONCLUSION: LAC in elderly colorectal cancer patients had benefits in short-term outcomes compared with OC except operation time. The long-term outcomes and oncological clearance of LAC were similar to that of OC. These results support the assertion that LAC is an effective procedure for elderly patients with colorectal cancer.     

Risk of second primary malignancies in a population-based study of adult patients with essential thrombocythemia

AIM: To determine the risk of second primary malignancy (SPM) and survival of patients with essential thrombocythemia (ET). METHODS: We identified all patients with ET diagnosed during 2001 to 2011 from the Surveillance, Epidemiology and End Results (SEER) 18 database. Actuarial and relative survival methods were used to calculate the survival statistics. We utilized the SEER 13 database to calculate SPM. We used multiple primary standardized incidence ratio (SIR) session of the SEER*Stat software (version 8.1.5) to calculate SIR and excess risk of SPM for ET patients. RESULTS: Age standardized five-year cause-specific survival was greater for patients < 50 years vs those ≥ 50 years (99.4% vs 93.5%, P < 0.01). Five-year cause-specific survival was lower for men vs women (70.2% vs 79.7%). A total of 201 patients (2.46%) developed SPM at a median age of 75 years. SPMs occurred at an observed/expected (O/E) ratio of 1.26 (95%CI: 1.09-1.45, P = 0.002) with an absolute excess risk (AER) of 37.44 per 10000 population. A significantly higher risk was noted for leukemia (O/E 3.78; 95%CI: 2.20-6.05, P < 0.001; AER 11.28/10000). CONCLUSION: ET patients have an excellent cause-specific five-year survival but are at an increased risk of SPM, particularly leukemia, which may contribute to excess deaths.     

1980—2018年上海市金山区结直肠癌死亡水平及其所致早死概率的趋势分析

目的掌握1980—2018年上海市金山区结直肠癌死亡水平及其所致早死概率的变化趋势,为制订结直肠癌防控策略和措施提供依据。方法通过死因登记信息系统采集1980—2018年金山区结直肠癌死亡病例,计算不同时期结直肠癌粗死亡率,标化死亡率、年龄组死亡率、早死概率及年度变化百分比等指标。结果 1980—2018年,金山区结直肠癌粗死亡率呈上升趋势(APC=2.14%,P<0.001),标化死亡率呈下降趋势(APC=-1.21%,P<0.001)。39年间,30～69岁组结直肠癌死亡率在男性无升降趋势(APC=-0.73%,P=0.070),女性呈下降趋势(APC=-1.80%,P<0.001),但女性在2000—2009年和2010—2018年期间未呈现明显升降趋势(APC=-3.36%、2.19%,P=0.266、0.465)。39年间,男性结直肠癌早死概率呈下降趋势(APC=-1.71%,P<0.001),但在2000—2009年和2010—2018年期间无明显升降趋势(APC=-2.90%、-2.36%,P=0.150、0.286);同期,女性结直肠癌早死亡概率...     

右美托咪定对腹腔镜胃癌根治术患者氧化应激、糖代谢及术后镇痛的影响

  目的  评价超声引导低位前锯肌平面阻滞对腹腔镜胃癌根治术患者术后镇痛效果的影响。  方法  选取2022年5月至2023年10月在天津医科大学肿瘤医院择期全麻下行腹腔镜胃癌根治术患者60例,按随机数字表法分为全身麻醉组（C组）和全身麻醉联合超声引导低位前锯肌平面阻滞（serratus anterior plane block,SAPB）组（S组）。术毕均行舒芬太尼自控静脉镇痛泵,记录患者术后1、6、12、24、48 h静息时视觉模拟评分（visual analogue scale,VAS）,术后VAS≥4分时静脉注射舒芬太尼0.1 μg/kg补救镇痛,记录镇痛泵有效按压次数、补救镇痛次数、术后首次排气时间、首次下床时间、首次进食时间和住院时长。  结果  与C组比较,S组术后1、6、12 h静息状态下VAS评分明显降低（P<0.05）,S组术后镇痛泵有效按压次数、补救镇痛次数明显减少C组［（6.1±0.4）次 vs. （18.6±1.4）次,2次 vs. 17次;P<0.001］,术后首次排气时间、首次下床时间、首次进食时间和住院时间缩短（P<0.05）。两组患者其余指标比较差异无统计学意义（P>0.05）。  结论  超声引导低位前锯肌平面阻滞可有效减轻腹腔镜胃癌根治术患者术后疼痛,有助于促进患者术后快速康复。     

lncRNA BLACAT1靶向LEMD1促进结直肠癌细胞的增殖和转移

目的 研究长链非编码RNA(lncRNA)BLACAT1在结直肠癌细胞发生发展过程的作用机制。方法 starBase分析TCGA数据库中lncRNA BLACAT1分别在结直肠癌组织和癌旁组织中的表达水平,采用qPCR分别检测10例结直肠癌患者癌组织和癌旁组织中lncRNA BLACAT1的表达水平;检测结直肠癌细胞系SW620、SW480、HT-29、LoVo、HCT116和正常结直肠上皮细胞FHC中lncRNA BLACAT1的mRNA表达水平,筛选lncRNA BLACAT1高表达细胞系;敲低lncRNA BLACAT1验证对高表达细胞系增殖、迁移和侵袭的影响;starBase在线预测与lncRNA BLACAT1靶向作用的基因,qPCR和Western blot实验验证结果;starBase分析lncRNA BLACAT1与作用基因相关性,双荧光素酶报告基因实验验证lncRNA BLACAT1的靶基因;检测lncRNA BLACAT1作用靶基因对结直肠癌细胞的增殖、迁移和侵袭的影响。结果 TCGA数据库分析和结直肠癌患者检测结果均表明癌组织中lncRNA BLACAT1表达明显高于癌旁组织(P＜0.001);结直肠癌细胞系SW620中lncRNA BLACAT1的mRNA表达水平最高(P＜0.001);敲低lncRNA BLACAT1能够抑制SW620细胞的增殖(P＜0.001)、迁移(P＜0.001)和侵袭能力(P＜0.001);qPCR和Western blot实验及数据库分析结果表明lncRNA BLACAT1与LEMD1的表达存在正相关关系(r=0.778,P＜0.001),双荧光素酶报告基因实验证明LEMD1是lncRNA BLACAT1的靶基因;lncRNA BLACAT1上调LEMD1的表达,促进SW620细胞的增殖(P＜0.001)、迁移(P＜0.001)和侵袭(P＜0.001)。结论 lncRNA BLACAT1靶向LEMD1促进结直肠癌细胞SW620的增殖和转移。     

Plasma MMP-2 and MMP-7 levels are elevated first month after surgery and may promote growth of residual metastases

BACKGROUNDMMP-2 also known as gelatinase A and MMP-7 (matrilysin) are members of the zinc-dependent family of MMPs (Matrix metalloproteinase). MMP-2 and MMP-7 are remodeling enzymes that digest extracellular matrix; MMP-2 is extensively expressed during development and is upregulated at sites of tissue damage, inflammation, and in stromal cells of metastatic tumors. MMP-7 is expressed in the epithelial cells and in a variety of cancers including colon tumors. Plasma MMP-2 and MMP-7 levels were assessed before and after minimally invasive colorectal resection for cancer pathology.AIMTo determine plasma MMP-2 and MMP-7 levels before and after minimally invasive colorectal resection for cancer pathology.METHODSPatients enrolled in a plasma bank for whom plasma was available were eligible. Plasma obtained from preoperative (Preop) and postoperative blood samples was used. Only colorectal cancer (CRC) patients who underwent elective minimally invasive cancer resection with preop, post-operative day (POD) 1, 3 and at least 1 late postop sample (POD 7-34) were included. Late samples were bundled into 7 d blocks (POD 7-13, 14-20, etc.) and treated as single time points. Plasma MMP-2 and MMP-7 levels were determined via enzyme-linked immunosorbent assay in duplicate.RESULTSTotal 88 minimally invasive CRC resection CRC patients were studied (right colectomy, 37%; sigmoid, 24%; and LAR/AR 18%). Cancer stages were: 1, 31%; 2, 30%; 3, 34%; and 4, 5%. Mean Preop MMP-2 plasma level (ng/mL) was 179.3 ± 40.9 (n = 88). Elevated mean levels were noted on POD1 (214.3 ± 51.2, n = 87, P < 0.001), POD3 (258.0 ± 63.9, n = 80, P < 0.001), POD7-13 (229.9 ± 62.3, n = 65, P < 0.001), POD 14-20 (234.9 ± 47.5, n = 25, P < 0.001), POD 21-27 (237.0 ± 63.5, n = 17, P < 0.001,) and POD 28-34 (255.4 ± 59.7, n = 15, P < 0.001). Mean Preop MMP-7 level was 3.9 ± 1.9 (n = 88). No significant differences were noted on POD 1 or 3, however, significantly elevated levels were noted on POD 7-13 (5.7 ± 2.5, n = 65, P < 0.001), POD 14-20 (5.9 ± 2.5, n = 25, P < 0.001), POD 21-27 (6.1 ± 3.6, n = 17, P = 0.002) and on POD 28-34 (6.8 ± 3.3, n = 15 P < 0.001,) vs preop levels.CONCLUSIONMMP-2 levels are elevated for 5 wk and MMP-7 levels elevated for weeks 2-6. The etiology of these changes in unclear, trauma and wound healing likely play a role. These changes may promote residual tumor growth and metastasis.     

Utility of different serum fibrosis markers in diagnosing patients with chronic pancreatitis and pancreatic adenocarcinoma

AIM: To estimate the levels of serum cytokines in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) patients in order to evaluate their usefulness as possible biomarkers. METHODS: The study included 167 Caucasian patients: 74 with PDAC (28 men and 42 women, aged 30-88 years), 78 with CP (50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor (TGF)-β1, HA and s-Fr were measured in patients with CP (n = 78), PDAC (n = 74) and healthy controls (n = 15) using ELISA (Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification. RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level (1066 ± 582 and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr (2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA (199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course (2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group (986 vs 839, P = 0.043). CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.     

外周血STAT1,STAT3基因启动子CpG岛甲基化状态与大肠癌预后关系的研究

目的 探讨大肠癌(CRC)患者外周血STAT1,STAT3基因启动子CpG岛甲基化状态与大肠癌预后的关系以及影响大肠癌患者预后生存的因素。方法 采用队列研究的方法,对哈尔滨医科大学附属肿瘤医院病理确诊的原发性大肠癌住院患者239例进行生物学采样并随访,通过甲基化特异性高分辨率熔解曲线(MS-HRM)分析STAT1,STAT3基因启动子CpG岛甲基化状态。结果 239例大肠癌患者术后1年、3年和5年的生存率分别为为94.90%、86.00%和67.20%。STAT1,STAT3基因甲基化状态与大肠癌患者术后生存期无关(STAT1:HR=0.85,95% CI:0.55~1.30,P=0.44;STAT3:HR=0.75,95% CI:0.36~1.58,P=0.45),Dukes分期(HR=1.31,95% CI:1.14~1.51,P＜0.01)和术中肠吻合器的使用(HR=1.98,95% CI:1.25~3.14,P＜0.01)是影响大肠癌患者预后的重要因素,Dukes分期为C、D期的患者死亡风险显著高于A、B期(HR=1.31,95% CI:1.14~1.51,P＜0.01),术中使用肠吻合器的患者预后优于没有使用肠吻合器的患者。而性别、年龄、肿瘤位置、肿瘤大体分型、组织学分型、术后化疗与大肠癌的预后无关。结论 Dukes分期是影响大肠癌预后生存的独立因素,术中使用肠吻合器患者预后优于未使用者,外周血STAT1,STAT3基因甲基化状态尚不能作为影响大肠癌患者预后的生物标志物。     

Patient prompting of their physician resulted in increased colon cancer screening referrals

AIM: To determine whether a communication instrument provided to patients prior to their primary care physician (PCP) visit initiates a conversation with their PCP about colorectal cancer screening (CRC-S), impacting screening referral rates in fully insured and underinsured patients. METHODS: A prospective randomized control study was performed at a single academic center outpatient internal medicine (IRMC, underinsured) and family medicine (FMRC, insured) resident clinics prior to scheduled visits. In the intervention group, a pamphlet about the benefit of CRC-S and a reminder card were given to patients before the scheduled visit for prompting of CRC-S referral by their PCP. The main outcome measured was frequency of CRC-S referral in each clinic after intervention. RESULTS: In the IRMC, 148 patients participated, a control group of 72 patients (40F and 32M) and 76 patients (48F and 28M) in the intervention group. Referrals for CRC-S occurred in 45/72 (63%) of control vs 70/76 (92%) in the intervention group (P≤ 0.001). In the FMRC, 126 patients participated, 66 (39F:27M) control and 60 (33F:27M) in the intervention group. CRC-S referrals occurred in 47/66 (71%) of controls vs 56/60 (98%) in the intervention group (P≤ 0.001). CONCLUSION: Patient initiated physician prompting produced a significant referral increase for CRC-S in underinsured and insured patient populations. Additional investigation aimed at increasing CRC-S acceptance is warranted.     

miR-765靶向ARID1A对结直肠癌细胞侵袭及迁移的影响

目的 探讨微小核糖核酸-765(miR-765)靶向AT丰富结合域蛋白1A(ARID1A)对结直肠癌细胞侵袭及迁移的影响。方法 收集35例结直肠癌患者的结直肠癌组织及癌旁组织,体外培养结直肠癌SW480细胞并分为对照组、siRNA NC组、miR-765 siRNA组、mimic NC组和miR-765 mimic组。qRT-PCR法检测miR-765、ARID1A mRNA表达,Transwell法检测SW480细胞迁移和侵袭情况,蛋白印迹法检测ARID1A、基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)蛋白表达,双荧光素酶实验检测miR-765与ARID1A的靶向关系。结果 与癌旁组织相比,结直肠癌组织中miR-765水平显著升高,ARID1A mRNA及蛋白水平显著降低(P＜0.001),且结直肠癌组织中miR-765与ARID1A mRNA呈显著负相关(r=-0.768,P＜0.001);与TNM分期为Ⅰ~Ⅱ期的患者相比,Ⅲ~Ⅳ期的患者结直肠癌组织中miR-765水平显著升高(P＜0.01),ARID1A蛋白水平显著降低(P＜0.001)。敲减miR-765表达后SW480细胞迁移数、侵袭数、miR-765水平及MMP-9、VEGF蛋白水平显著降低,ARID1A水平显著升高(P＜0.05);过表达miR-765后SW480细胞迁移数、侵袭数、miR-765水平及MMP-9、VEGF蛋白水平显著升高,ARID1A水平显著降低(P＜0.05)。miR-765靶向调控ARID1A表达。结论 miR-765可能通过靶向抑制ARID1A表达,促进结直肠癌SW480细胞的侵袭和迁移过程。     

中国人群中XRCC1 Arg194Trp位点多态性和结直肠癌易感性关系的Meta分析

目的: 探讨中国人群中X射线交叉互补修复基因1(XRCC1)的194位点(Arg194Trp)多态性与结直肠癌(CRC)易感性的关系。方法: 检索万方数据知识服务平台、中国生物医学数据库(CBM)、中国知网(CNKI)、维普数据库(VIP)、PubMed、EBASE等数据库,获取有关XRCC1 Arg194Trp位点多态性与结直肠癌易感性关系的文献,应用Meta分析软件Review Manager 5.1对最终纳入的文献进行综合定量评价,并进行异质性分析、敏感性分析、发表偏倚分析及亚组分析。结果: 经过筛选最终纳入10个研究。Meta分析结果示纯合子模型的合并OR=1.40,95%CI(1.13~1.73),P=0.002;显性模型的合并OR=1.22,95%CI(1.01~1.47),P=0.04;隐性模型的合并OR=1.30,95%CI(1.06~1.60),P=0.01;杂合子模型的合并OR=1.19,95%CI(1.00~1.42),P=0.05。在亚组分析中,病例组吸烟者和对照组吸烟者的OR=1.04,95%CI(0.84~1.29),P=0.72;病例组饮酒者和对照组饮酒者的OR=1.08,95%CI(0.81~1.44),P=0.60。结论: XRCC1 Arg194Trp位点多态性和结直肠癌易感性有关系,在纯合子模型、显性模型及隐性模型中携带194Trp基因型个体发生结直肠癌的危险性会增加,吸烟、饮酒与结直肠癌发病率无明显关联。     

血清肿瘤标志物对肺癌患者支气管镜活检病理组织学分型的预测价值

目的 探讨血清肿瘤标志物水平与支气管镜活检组织病理学分型的关系。方法 本研究纳入2013年1月—2018年12月于哈尔滨医科大学附属肿瘤医院行支气管镜下活检病理检查,且完成相关血清肿瘤标志物(SCCA、CYFRA21-1、CEA、CA125、NSE)检测的356例肺癌患者(140例小细胞癌、122例鳞状细胞癌、94例腺癌),对患者进行回顾性分析。结果 在支气管镜活检的肺癌患者中,五种血清肿瘤标志物的组合(SCCA+CYFRA21-1+CEA+CA125+NSE,AUC=0.948,P<0.001)对小细胞肺癌与非小细胞肺癌的辅助诊断价值更高;三种(SCC+CEA+NSE,AUC=0.901,P<0.001)或四种(SCC+CYFRA21-1+CEA+NSE,AUC=0.901,P<0.001)标志物联合鉴别鳞状细胞癌与腺癌准确性更高;而在非小细胞肺癌中鉴别鳞状细胞癌与腺癌,三种标志物组合(SCCA+CEA+CA125,AUC=0.831,P<0.001)的价值更高。结论 对于不同病理分型的肺癌患者,不同血清肿瘤标志物组合对支气管镜下活检病理的分型有一定的辅助诊断...     

241例局部晚期中低位直肠癌术前同步放化疗联合TME根治术长期疗效分析

目的 回顾性分析 241例局部晚期中低位直肠癌行术前同步放化疗联合TME根治性手术的长期疗效以及影响预后因素。方法 2006—2014年中国医学科学院北京协和医学院肿瘤国家癌症中心连续收治经盆腔MRI或腹盆CT确诊的局部晚期中低位直肠腺癌患者 241例进行分析,该组患者术前盆腔放疗剂量 42.0~50.4 Gy (中位数50 Gy),同步化疗采用卡培他滨 ±奥沙利铂,于同步放化疗后 4~15周(中位数7周)接受TME原则的根治性手术(R0切除),术后均建议行辅助化疗,但需考虑患者恢复情况及意愿。Kaplan-Meier法计算DFS、LRR、DM及OS并Logrank法检验,Cox模型多因素分析。结果 全组患者中位随访42个月,3年LRR、DFS、OS和DM分别为3.8%、76.2%、85.9%和20.6%。亚组分析发现ypT0-2、ypN阴性、pCR、TRG4级患者可以获得更高的DFS (ypT0-2∶ypT3-4:86.0%∶69.3%,P=0.002;ypN阴性∶ypN阳性:88.1%∶56.9%,P=0.000;pCR∶非pCR:100%∶72.4%,P=0.001;TRG4级∶TRG2-3级∶TGR0-1级:94.9%∶73.6%∶66.3%,P=0.011),多因素分析结果显示术后ypN状态是影响DFS的因素(P=0.000)。结论 局部晚期中低位直肠癌行术前同步放化疗联合根治性手术局部区域控制较理想,远处转移是治疗失败的主要原因,放化疗后ypN状态是影响DFS的独立预后因素。     

Intravenous lidocaine infusion compared to thoracic epidural analgesia in cytoreductive surgery with or without heated intraperitoneal chemotherapy. A retrospective case-cohort study

BackgroundIntravenous (IV) lidocaine is a proven analgesic therapy but has not been evaluated in extensive procedures such as cytoreductive surgery (CRS). Our aim was to assess the effectiveness and safety of IV lidocaine in this setting.MethodsThis is a retrospective hybrid case-cohort study investigating analgesic effectiveness and complications of perioperative IV lidocaine at 1.5 mg/kg/h for 48 h compared to thoracic epidural anaesthesia (TEA) among patients undergoing CRS in a high-volume centre.ResultsSixty patients were included, 20 received IV lidocaine and 40 underwent TEA. Pain scores were low (median ≤2) and similar in both groups (p = 0.88). At 72 h, the lidocaine group had a lower median pain score (p = 0.03). Overall opioid consumption in the first 48 h was lower in the lidocaine compared to the TEA group (median 0 (IQR 0–9.5) mg vs. 45.4 (0–62.4) MME respectively, p = 0.001). Opioid consumption was also lower in the lidocaine compared to the TEA group during the whole 5-day period (median 1 (IQR 1–13.5) mg vs. 112 (36.6–137.85) MME respectively, p = 0.000). The incidence of PONV was significantly lower in the lidocaine group (27.5% vs 5%, p = 0.047) with no difference in other complications or length of in-hospital stay.ConclusionIntravenous lidocaine infusion may be a safe and effective analgesic approach in CRS and is associated with a significant reduction of opioid use and PONV compared to opioid-containing TEA.     

Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli (E. coli) using optical imaging. METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume (mm³). Inflammation measuring myeloperoxidase (MPO) activity and reactive oxygen species production was monitored by a bioluminescent (BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay (ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells (HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitis-CEABAC10 DSS models, which mimicked Crohn’s disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume (P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group (P < 0.005). ELISA confirmed that MPO levels were significantly higher (1556 ± 313.6 vs 234.6 ± 121.6 ng/mL P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model (CEABAC10/DSS). CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand host-pathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.     

Impact of RAS and BRAF mutations on carcinoembryonic antigen production and pattern of colorectal metastases

AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen (CEA) production. METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer (CRC) were included. Patients’ characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations. RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations (KRAS and NRAS) were more likely to be found in African American patients (87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA (< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis. CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.     

外周血USP1基因甲基化与大肠癌预后风险的关系

目的 探讨外周血中去泛素化酶USP1甲基化及临床特征与大肠癌预后风险的关系。方法 采用队列研究,共纳入286例大肠癌患者。使用高分辨率熔解曲线分析法(HRM)检测基因甲基化水平。应用Cox回归模型评估基因甲基化及临床特征与大肠癌预后风险之间的关联。结果 在男性大肠癌病例中,USP1甲基化增加预后不良风险(HR=2.091,95% CI:1.195~3.661,P=0.010)。临床病理特征中,UICC肿瘤分期4期(HR=2.464,95% CI:1.205~5.039,P=0.014)、肿瘤大小超过50mm(HR=1.610,95% CI:1.016~2.550,P=0.043)和组织学非腺型(HR=5.117,95% CI:1.142~22.930,P=0.033)是大肠癌不良预后风险增加的影响因素。结论 UICC肿瘤分期4期、肿瘤大小超过50mm和组织学分型为非腺型会增加大肠癌不良预后风险。外周血USP1基因启动子区甲基化与男性大肠癌预后不良风险增加有关。     

腹腔镜气腹相关并发症及原因分析

  目的  探讨乳腺良、恶性肿瘤患者在CO₂气体建腔情况下行乳腺腔镜手术过程中CO₂气腔对围手术期血气参数的影响,为乳腺腔镜手术的安全性提供参考。  方法  选取2022年3月至2022年9月就诊于天津医科大学肿瘤医院行乳腺腔镜手术的良、恶性乳腺肿瘤患者35例,于术前（CO₂充气前）、术中（CO₂充气后60 min）、术后（麻醉苏醒后30 min）分别抽取患者桡动脉血,并采用统计学方法对酸碱度（pH值）、动脉二氧化碳分压（pCO₂）、剩余碱正负值（±BE）、碳酸氢根离子（HCO³⁻）血气指标变化情况,及各指标之间的相关性进行分析。  结果  35例患者术中pCO₂均较术前升高,术后均下降至术前水平。t检验显示,术中与术前相比,pCO₂和HCO³⁻显著增加（t=−7.196和t=−4.709,均P<0.05）、pH值显著下降（t=7.069,P<0.05),BE正值增加（t=−1.924,P>0.05）;术后与术前相比,pCO₂、pH值、HCO³⁻均无明显变化（t=0.141、t=1.170、t=1.622,均P>0.05）,BE负值增加（t=1.830,P>0.05)。Pearson相关性分析显示,患者术中pCO₂变化与pH值及HCO³⁻变化具有相关性（r=0.423及r=0.769,均P<0.05）,±BE与HCO³⁻变化亦具有相关性（r=0.678,P<0.05）。  结论  在CO₂气体建腔下,乳腺腔镜手术对患者的围手术期血气分析指标有一定影响,但术后患者麻醉清醒后可恢复至术前水平,安全可靠,值得广泛推广。