Impact of lymphatic and/or blood vessel invasion in stage Ⅱ gastric cancer

AIM： To determine the prognostic value of lymphatic and/or blood vessel invasion （LBVI） in patients with stage 11 gastric cancer. METHODS： From January 2001 to December 2006, 487 patients with histologically confirmed primary gas- tric adenocarcinoma were diagnosed with stage 11 gas- tric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node （LN） dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathologicalfindings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure （subtotal resection vs total resection）, and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS： The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years （range： 23-88 years）. The 5-year overall survival rates were 50.7% and the median survival time was 62 too. Stage Ⅱ a cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three TIN2, and stage Ⅱb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one TIN3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% （51/269） and 42.5% （71/167） in LN-negative and LN- positive patients, respectively. In 218 patients （50.0%）, there was neither a histopathologically detectable LBVI nor LN metastases （LBVI-/LN-, group I）; in 51 patients （11.7%）, LBVI with no evidence of LN me- tastases was detected （LBVILN-, group 11）. In 167 patients （38.3%）, LN metastases were found. Among those patients, LBVI was not determined in 96 patients （22.0%） （LBVI-γLN, group Ⅲ）, and was determined in 71 patients （16.3%） （LBVI＋LN＋, group Ⅳ）. Correla- tion analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI （P 〈 0.001）. The overall 5-year sur- vival was significantly longer in LN-negative patients compared with LN-positive patients （56.1% vs 42.3%, P = 0.015）. There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI- negative tumors （39.6% vs 54.8%, P = 0.006）. Overall 5-year survival rates in each group were 58.8% （ Ⅰ）, 45.8% （Ⅱ）, 45.7% （Ⅲ） and 36.9% （Ⅳ）, and there was a significant difference in overall survival between the four groups （P=-0.009）. Multivariate analysis in stage 11 gastric cancer patients revealed that LBVI in- dependently affected patient prognosis in LN-negativepatients （P = 0.018） but not in LN-positive patients （P = 0.508）. CONCLUSION： In LN-negative stage 11 gastric cancer patients, LBVI is an additional independent prognostic markeF, and may provide useful information to identify patients with poorer prognosis.

Prognostic values of chromosome 18q microsatellite alterations in stage Ⅱ colonic carcinoma

AIM: To investigate the prognostic value of chromosome 18q microsatellite alterations (MA) in stage Ⅱ colon cancer. METHODS: One hundred and six patients with sporadic stage Ⅱ colon cancer were enrolled in this study. DNA was extracted from formalin-fixed, paraffin-embedded tumor and adjacent normal mucosal tissue samples. MA, including loss of heterozygosity (LOH) and microsatellite instability (MSI), was analyzed by polymerase chain reaction, polyacrylamide gel-electrophoresis and DNA sequencing at 5 microsatellite loci on chromosome 18q (D18S474, D18S55, D18S58, D18S61 and D18S64).RESULTS: Among the 102 patients eligible for MA information, the overall frequencies of LOH, high and low frequency MSI/microsatellite stable were 49.0%, 17.6% and 82.4%, respectively. The high frequency of 18q-LOH was signif icantly associated with the poor 5-year overall survival (OS) (P=0.008) and disease free survival (P=0.006). High levels of MSI were significantly associated with a longer 5-year OS (P=0.045) while the higher frequency of 18q-LOH at the loci of D18S474 and D18S61 was significantly associated with a poorer 5-year OS (P=0.010 and 0.005, respectively). But multivariate analysis showed that only the frequency of 18q-LOH was significantly associated with the prognosis of the disease. CONCLUSION: High frequency of 18q-LOH is an independent prognostic factor indicating poor prognosis of the patients with stage Ⅱ colon cancer.

Prognostic and predictive significance of MSI in stages Ⅱ/Ⅲ colon cancer

In colon cancer,classic disease staging remains the key prognosis and treatment determinant.Although adjuvant chemotherapy has an established role in stageⅢcolon cancer patients,in stageⅡit is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features.Patients with stageⅡtumors form a highly heterogeneous group,with five-year relative overall survival rates ranging from 87.5%(ⅡA)to 58.4%(ⅡC).Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging,and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed.The stronger candidate in this category seems to be microsatellite instability(MSI).The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stageⅡcolorectal cancer patients in order to contribute in treatment decisionmaking regarding chemotherapy administration.Thehypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address.Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature,and the matter is far from being settled.In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stageⅡand stageⅢcolon cancer patients.

Macroscopic appearance of TypeⅣand giant Type Ⅲ is a high risk for a poor prognosis in pathological stage Ⅱ/Ⅲ advanced gastric cancer with postoperative adjuvant chemotherapy

AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.

Different strategies of treatment for uterine cervical carcinoma stage ⅠB2-ⅡB

Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.

Ⅰ-ⅡA期肺腺癌根治术后复发转移危险因素分析及预测模型构建

目的分析Ⅰ-ⅡA期肺腺癌根治术后复发转移的危险因素,构建Ⅰ-ⅡA期肺腺癌根治术后复发转移的预测模型。方法行肺癌根治术并经病理确诊为Ⅰ-ⅡA期LUAD患者205例,收集患者的临床资料,包括性别、年龄、吸烟史、术前肺功能、肿瘤位置、肿瘤最大直径、淋巴结清扫数目、术后病理见微乳头结构、胸膜侵犯、脉管癌栓、辅助化疗情况、术前血清癌胚抗原(CEA)水平、术前中性粒细胞计数与淋巴细胞比值(NLR)、术前预后营养指数(PNI),统计患者术后复发转移情况;采用Kaplan-Meier法绘制生存曲线,联合log-rank法分析Ⅰ-ⅡA期LUAD术后复发转移的相关因素;采用COX比例风险模型分析Ⅰ-ⅡA期LUAD术后复发转移的独立危险因素。使用R语言软件构建Ⅰ-ⅡA期LUAD根治术后复发转移风险预测列线图。采用Bootstrap法对列线图进行内部验证,计算该列线图的C-index值;绘制列线图的ROC曲线,评价列线图的区分度;采用校准曲线评价列线图的一致性。结果肿瘤最大直径、术后病理见微乳头结构、术前肺功能、术前血清CEA水平、术前NLR、术前PNI与Ⅰ-ⅡA期LUAD根治术后复发转移有关(P均<0.05),其中肿瘤最大直径>3 cm、术前血清CEA>5 ng/mL、术前NLR>2.285、术前PNI≤46.625是Ⅰ-ⅡA期LUAD根治术后复发转移的独立危险因素(P均<0.05)。构建了Ⅰ-ⅡA期LUAD根治术后复发转移风险预测列线图。列线图的C-index值为0.814(95%CI为0.751~0.877),该列线图预测Ⅰ-ⅡA期LUAD根治术后2年、3年、5年复发转移的ROC的AUC分别为0.757(95%CI为0.641~0.874)、0.696(95%CI为0.595~0.797)、0.675(95%CI为0.589~0.762),Ⅰ-ⅡA期LUAD根治术后复发转移风险预测列线图的校准曲线均接近参考线。结论Ⅰ-ⅡA期LUAD根治术后复发转移的独立危险因素为肿瘤最大直径>3 cm、术前血清CEA>5 ng/mL、术前NLR>2.285、术前PNI≤46.625。成功构建了Ⅰ-ⅡA期LUAD根治术后复发转移风险预测模型,且模型的区分度与一致性均较好。

信迪利单抗联合射频消融治疗Ⅱa期肝癌临床研究

目的 探讨信迪利单抗联合射频消融(RFA)治疗Ⅱa期肝癌的临床疗效。方法 选取衡水市第三人民医院2020年6月至2021年12月收治的Ⅱa期肝癌患者102例,按随机数字表法分为对照组和观察组,各51例。两组患者均予RFA治疗,观察组患者加用信迪利单抗注射液静脉滴注。两组均治疗6个月。结果 观察组客观缓解率和疾病控制率为70.59%和86.27%,明显高于对照组的49.02%和68.63%(P <0.05)。与对照组比较,观察组患者治疗后的CD_(4)^(+)CD_(25)^(+)FOXP_(3)^(+)Treg水平明显降低(P <0.05),CD_(4)^(+)/CD_(8)^(+)明显升高(P <0.05);甲胎蛋白、糖类抗原199和细胞角蛋白19片段抗原21-1水平均明显降低(P <0.05);健康调查简表各领域评分均明显升高(P <0.05)。观察组与对照组不良反应发生率相当(31.37%比21.57%,P> 0.05)。结论 信迪利单抗联合RFA治疗Ⅱa期肝癌疗效较好,可改善细胞免疫和肿瘤标志物水平,提高患者的生活质量。

The path toward prognostication and prediction in stage Ⅱ colon cancer

Currently,there are several newer biomarkers that may be clinically useful in colon cancer. This paper focuses on a few of these biomarkers,namely microsatellite instability,loss of heterozygosity at chromosome 18q(LOH18q) and multi-gene assays,and discusses the clinical evidence behind their predictive or prognostic abilities. The results show that although there have been several newer prognostic factors identified,such as LOH18 q and multi-gene assays,none of these factors can predict benefit from treatment. Therefore,ongoing prospective clinical trials are still needed to further assess the role and optimal use of these tests.

癌胚抗原在ⅡA期结肠癌中的预后意义:一项基于严格倾向性得分匹配的大样本量回顾性研究

目的:探讨癌胚抗原(CEA)升高在ⅡA期结肠癌中的预后意义。方法:通过美国SEER数据库搜集2004年1月—2010年12月确诊为结肠癌且病理分期为ⅡA期、记录有CEA数据的患者共21910例,运用Cox回归分析和Kaplan-Meier曲线确定CEA升高在ⅡA期结肠癌中的预后。结果:倾向性得分匹配前的多因素Cox分析结果显示,CEA升高组的病因特异性死亡风险相对于CEA正常组升高了71.6%(HR:1.716,95%CI:1.589~1.852,P<0.001)。倾向性得分匹配后,CEA升高组和正常组各产生7282例患者。CEA升高组和正常组的5年病因特异性生存率分别为84.7%和91.3%。黏液腺癌或印戒细胞癌、黑种人、女性、年龄>70岁及肿瘤原发灶的直径>3 cm更易出现术前CEA的升高。结论:CEA升高是ⅡA期结肠癌患者的预后不良因素,有可能被用作IIA期结肠癌中需要辅助化疗的高危因素之一。

Postoperative chemotherapy use and survival in non-high-risk young and high-risk old-aged patients with stageⅡcolon cancer

Purpose Intensive postoperative chemotherapy treatment use in early-onset colon cancer and late-onset colon cancer remains to be defined and their effects on prognosis were unclear.This study aims to investigate whether intensive adjuvant chemotherapy for stageⅡcolon cancer would result in matched survival improvement in young patients(<50 years)without risk factors and old-aged(70–85 years)patients with risk factors defined by guidelines.Methods We extracted eligible patients with pathologically confirmed TNM stageⅡcolon cancer from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Patients aged<50 years old without risk factors were defined as non-high-risk early-onset colon cancer(non-HREOCC),and those aged 70 to 85 years with risk factors were defined as high-risk late-onset colon cancer(HRLOCC).Kaplan–Meier(KM)method with log-rank test was performed to calculate the overall survival(OS)and cancer-specific survival(CSS).Multivariate Cox model was used to estimate the association of adjuvant chemotherapy with CSS by adjusting potential confounding factors.Results Of 55,366 eligible stageⅡcolon cancer patients,3341 non-HREOCC patients and 11,722 HRLOCC patients were included.37.68%and 16.8%of patients received adjuvant chemotherapy among non-HREOCC and HRLOCC patients,respectively.For non-HREOCC patients,there was no significant association between adjuvant chemotherapy and CSS(HR=1.09,95%CI0.83–1.44).For HRLOCC patients,adjuvant chemotherapy was associated with a better CSS(HR=0.88,95%CI0.79–0.99).Conclusion Our findings suggested that potential overuse of adjuvant chemotherapy among non-high-risk young patients with stageⅡcolon cancer did not lead to survival improvement,and caution should be called when using chemotherapy in these patients.However,chemotherapy can be used appropriately for high-risk stageⅡcolon cancer patients aged 70 to 85 years.

A multivariate analysis of prognostic determinants for stages Ⅱ and Ⅲ colorectal cancer in 141 patients

Background Previous prognosis analyses of colorectal cancer （CRC） patients with stage Ⅱ and Ⅲ disease were done as separate categories. The purpose of this study was to analyze prognostic factors associated with survival in a group of patients who underwent radical resection of stages Ⅱ and Ⅲ CRC.Methods A retrospective review was performed for 141 consecutive stages Ⅱ and Ⅲ patients who had undergone radical resection of coloractal adenocarcinoma between May 2003 and November 2003. Univariate and multivariate analyses were performed to assess the effect of record variables on disease free survival and overall survival.Results The median follow-up time was 59 months, and the 3-and 5-year survival rates were 76% and 68%,respectively. Four factors were independently associated with a worse disease-free survival： diabetes （hazard ratio （HR） 2.338; 95% confidence interval （CI） 1.011-5.407）, expression of cyclooxygenase-2 （Cox-2） （HR 0.335; 95% CI 0.126-0.888）, expression of matrix metalloproteinases 2 （MMP-2） （FIR 0.233; 95% CI 0.101-0.541）, expression of vascular endothelial growth factor （VEGF） （HR 0.295; 95% CI 0.088-0.996）. Four factors were independently associated with a worse overall survival： lymph nodes metastasis （HR 1.67; 95% CI 1.29-2.14）, Cox-2 positive （HR 0.056; 95% CI 0.247-0.731）, MMP-2 positive （HR 0.398; 95% CI 0.190-0.836）, VEGF （HR 0.364; 95% CI 0.090-0.716）.Conclusions Diabetes, expression of Cox-2, MMP-2 and VEGF were independently associated with a worse diseasefree survival. Lymph nodes metastasis, expression of Cox-2, MMP-2 and high level of VEGF predicted a poor overall survival.

FIGO 2018子宫颈癌中ⅡA期分期合理性探讨

目的通过对比ⅡA期各亚分期之间的肿瘤学结局,探讨子宫颈癌FIGO 2018新分期中ⅡA期分期的合理性。方法纳入接受开腹手术的FIGO 2009分期ⅡA期子宫颈癌开腹手术病例,以FIGO 2018新分期标准重新分期,并将淋巴结转移的病例设为ⅢC-ⅡA期。通过KM生存分析和Cox多因素分析比较FIGO 2018标准下ⅡA1/ⅡA2/ⅢC-ⅡA期的5年总生存率(OS)和无瘤生存率(DFS)。结果(1)纳入2004-2018年于47家医院住院治疗的FIGO 2009分期ⅡA期病例共4691例,按照FIGO 2018标准进行重新分期后,ⅡA1/ⅡA2/ⅢC-ⅡA期及无法明确分期的病例分别为2279、962、1213及237例。(2)KM生存分析发现,ⅡA1、ⅡA2期的肿瘤学结局均优于ⅢC-ⅡA期(ⅡA1 vs.ⅡA2 vs.ⅢC-ⅡA:OS:91.9%vs.91.3%vs.72.8%,P<0.001;DFS:87.3%vs.87.2%vs.61.6%,P<0.001),但ⅡA1期与ⅡA2期的OS及DFS差异无统计学意义(OS:P=0.294,DFS:P=0.570)。(3)COX多因素分析得出,ⅢC-ⅡA期是ⅡA1、ⅡA2期病例死亡或死亡/复发的独立危险因素。而ⅡA2期不是影响ⅡA1期病例死亡或死亡/复发的独立危险因素。结论从肿瘤学结局的角度分析,FIGO 2018分期ⅡA1、ⅡA2期肿瘤学结局无差异,但淋巴结转移病例的生存结局明显差于ⅡA1和ⅡA2。

超声凝胶阴道填充后MRI在早期宫颈癌分期中的价值研究

目的探讨超声凝胶阴道填充后MRI在早期宫颈癌分期中的价值。方法前瞻性纳入经宫颈活检确诊为宫颈癌行MRI检查的患者158例,先行常规MRI检查,超声凝胶填充阴道后再行一次MRI检查。两名医师采用双盲法对凝胶填充前后宫颈癌MRI分期进行判定,以术后病理为金标准,比较同一患者前后2次检查对于鉴别Ⅱa期病例的阳性预测值、阴性预测值,及在判断宫颈癌Ⅱa期中的敏感度、特异度及准确度。结果两名医师采用双盲法对常规MRI图像进行分期,得到的一致性中等(κ=0.680);而运用超声凝胶填充后对MRI图像进行分期时,结果一致性高(κ=0.932)。常规MRI检查图像在鉴别宫颈癌Ⅱa期中的阳性预测值为66.67%,阴性预测值为76.74%;灵敏度、特异度及准确度分别为70.59%、73.33%和72.15%;超声凝胶填充阴道后MRI检查图像的阳性预测值为90.91%,阴性预测值为91.30%;灵敏度、特异度及准确度分别为88.24%、93.33%和91.14%,两者对比灵敏度、特异度及准确度差异有统计学意义(P<0.05)。结论超声凝胶阴道填充后行MRI检查在鉴别宫颈癌Ⅱa期中具有更高的诊断价值,其方法简便易行,可运用于宫颈癌的常规MRI检查中。