Extramural vascular invasion is an adverse prognostic indicator of survival in patients with colorectal cancer

Background/aims  Extramural vascular invasion (EVI) in colorectal cancer is reported to be a stage-independent adverse prognostic factor, and is a core item in the Royal College of Pathologists minimum data set for colorectal cancer histopathology reporting. The detection of EVI is also highly variable amongst pathologists. Our aims were to analyse both the frequency of EVI in colorectal cancer resections, and the effect of EVI on survival, in patients operated on over a 5-year period.
Method  A retrospective analysis of patients having potentially curative surgery for colorectal cancer between January 1999 and December 2004.
Results  Over 5 years, 378 patients underwent a potentially curative resection. One-hundred seven (28.3%) cancers exhibited EVI, of which 104 (97%) were T3 and T4 tumours. Survival curves with and without EVI, unadjusted for nodal status and T stage, were significantly different ( P  =   0.0001) with 5-year survivals of 52% and 73% respectively. Survival curves for T3 and T4 tumours stratified with and without EVI also showed significantly different survival distributions ( P  =   0.007). A significant difference in frequency of EVI year on year was seen ( P  <   0.001), ranging from 8.5% to 46.7%, whereas the number of T3 and T4 tumours in each year was not significantly different ( P  =   0.677).
Conclusions  EVI is an adverse prognostic indicator for survival in patients undergoing potentially curative resection of colorectal cancer, and the routine requirement of EVI in colorectal cancer histopathology reporting is justified. Optimal specimen preparation, meticulous histopathological analysis and regular auditing of EVI detection rates are essential for the accurate staging of colorectal cancer.     

The prognostic impact of pelvic lymph node metastasis and lymphovascular invasion on bladder cancer

Objectives:   To present long-term results of a single-center series of patients undergoing bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer and to analyze the impact of pelvic lymph node metastasis and lymphovascular invasion on clinical outcome.
Methods:   Between 1986 and 2005 833 patients were treated with bilateral pelvic lymphadenectomy and radical cystectomy at our institution. 614 of them with valid clinical follow-up information and no neoadjuvant therapy could be evaluated.
Results:   Disease-free and overall survival in the entire cohort was 56.7% and 49.5% at 5 years and 52.4% and 38.2% at 10 years, respectively. 28.1% of all patients had pelvic lymph node metastasis. We found organ-confined tumor stages (≤pT2) in 43.8%. Patients with non-organ-confined tumor stages (≥pT3) and positive pelvic lymph nodes had a significantly shorter overall survival than those without lymph node metastasis ( P  < 0.0001). In the subgroup of ≤pT2, the presence of pelvic lymph node metastasis did not show a statistically significant effect on overall survival ( P  = 0.618). The presence of lymphovascular invasion was associated with an impaired survival ( P  < 0.0001). In multivariate analysis, pathological tumor stage ( P  < 0.0001), lymph node stage (≥pT3) ( P  = 0.004) and lymphovascular invasion ( P  = 0.001) were independent prognostic parameters.
Conclusions:   According to the present series, survival for patients with ≤pT2 does not depend on the lymph node stage. Lymphovascular invasion is an independent parameter of impaired survival and should be determined routinely in cystectomy specimens to identify patients, who may benefit from adjuvant systemic therapy.     

Growth pattern in the muscular layer reflects the biological behaviour of colorectal cancer

Objective  To determine the clinical value of evaluating the cancer morphology in muscularis propria (MP) for colorectal cancer (CRC) patients.
Method  A total of 994 patients with advanced CRC were reviewed in terms of two distinctive growth patterns in the MP: (i) horizontal spread between the circular and longitudinal muscle layers (H-spread) and (ii) 'streaming' spread between the muscle bundles of the circular muscle layer (S-spread).
Results  The incidence of H-spread ( n  = 153) and S-spread ( n  = 150) showed a positive correlation with tumour-node-metastasis (TNM) stage and both exerted a negative impact on postoperative survival. Adverse morphology in the MP (H-spread and/or S-spread) was consistent with a high grade of vascular invasion and budding in the extramural layer, as also with unfavourable fibrotic stromas in the reactive fibrous zone; the 5-year survival rate in patients with such features was 64.2%, which was lower than that in those without (86.5%, P  < 0.0001). Multivariate analysis demonstrated that adverse morphology was an independent prognostic determinant, along with T- and N -stage. As the mode of H-spread, perineural invasion in the myenteric plexus was found to be predominant over lymphatic spread on the basis of S100 and CD34 immunostaining, but neural cell adhesion molecule expression, whether on cancer cells or on neural cells, was not significant for this growth pattern.
Conclusion  A particular group of CRCs ingeniously utilizes the thin space between muscle fascicles for development in the MP. Although the biological mechanism remains unknown, this distinctive growth pattern could be a useful indicator to identify CRC patients at high risk of recurrence.     

血管内皮生长因子-C和生存素在胃癌组织中的表达及其临床意义

目的 探讨胃癌组织中血管内皮生长因子（vascular endothelial growth factor，VEGF）-C和生存素（sunrivin）蛋白表达及其临床意义。方法 采用免疫组织化学SP法检测97例原发性胃癌组织、癌旁组织及20例正常胃黏膜组织中VEGF-C和survivin蛋白的表达，并分析其与临床病理特征和预后的关系。结果 胃癌组织VEGF-C和survivin蛋白表达阳性率分别为66．0％和57．2％，显著高于癌旁组织和正常胃组织（P〈0．05）；VEGF-C蛋白表达与肿瘤分化程度、肿瘤部位、肿瘤直径、静脉侵犯及远处转移等无关，但与淋巴结转移、淋巴管侵犯、浆膜面受累和肿瘤TNM分期等密切相关；survivin蛋白表达与肿瘤分化程度、肿瘤部位、肿瘤直径、静脉侵犯等无关，但与浆膜面受累、淋巴管侵犯、淋巴结转移、远处转移和肿瘤TNM分期等密切相关；VEGF-C和survivin阳性表达组术后生存率明显低于阴性组；VEGF-C和survivin在胃癌组织中阳性表达呈正相关。结论 VEGF-C及survivin蛋白的阳性表达可作为胃癌预后不良的参考指标。     

Ovarian metastases from colorectal cancer: a clinicopathological analysis of 103 patients

Objective  To improve management of ovarian metastasis through assessment of clinicopathological features and treatment outcomes associated with ovarian metastasis from colorectal cancer.
Method  We recruited 103 subjects who were diagnosed with ovarian metastasis and subjected to surgery between June 1989 and December 2005. Clinical and pathological variables were evaluated. Survival and its associated factors were analysed with a median follow-up of 31 months after ovarian surgery (range 1–129 months).
Results  The mean age at diagnosis was 46 years (range 14–72 years), synchronous ovarian metastasis occurred in 74 patients and metachronous in 29 patients. The primary tumour was more commonly associated with the colon rather than the rectum (84/1608, 5.2% vs 19/1534, 1.2%, P  <   0.001). Combined metastases occurred in 69 patients (67%). Complete resection was achieved in 34 (33%) patients without other metastases. The estimated 5-year disease free survival and overall survival rate were 40.1% and 26.6%, respectively. From univariate analysis, lymphovascular invasion (35.6% vs 12.8%, P  =   0.034), combined metastasis (50.9% vs 15.6%, P  =   0.0035) and bilaterale ovarian metastasis (36.4% vs 10.6%, P  =   0.015) were identified as significant poor prognosis factors, and from multivariate analysis combined metastasis and bilaterale ovarian metastasis were significant ( P  =   0.034 and P  =   0.015, respectively).
Conclusion  This study suggests a role for regular follow-up computed tomography scans within 6 months postoperatively and tumour marker assays for the early detection of ovarian metastasis in premenopausal women after primary surgery, especially in colonic patients with poor prognostic factors.     

Clinical Significance of Serum Carcinoembryonic Antigen,Carbohydrate Antigen 19-9, and Squamous Cell Carcinoma Antigen Levels in Esophageal Cancer Patients

Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and squamous cell carcinoma (SCC) antigen levels were assessed to determine if their levels are useful for staging esophageal cancer preoperatively and for predicting patient survival after esophagectomy. Hence their seropositivity was investigated for a correlation with resectability, clinicopathologic parameters of tumor progression, and treatment outcomes in patients with unresectable esophageal cancer (n = 63) and those undergoing esophagectomy for resectable disease (n = 267). Abnormal elevation of serum SCC antigen levels showed a significant correlation with resectability (p < 0.0001), depth of tumor invasion (p < 0.0001), lymph node status (p = 0.0015), TNM stage (p < 0.0001), lymphatic invasion (p = 0.0019), blood vessel invasion (p = 0.0079), and poor survival after esophagectomy (p = 0.0061). A significant relation (p = 0.0145) was found between elevated serum CEA levels and distant metastasis, whereas the seropositivity of CA 19-9 showed no association with resectability, tumor progression, or patient survival. These results indicate that abnormal elevation of serum SCC antigen is a useful predictor of advanced esophageal cancer associated with poor survival after esophagectomy.     

Immunohistochemical assessment of lymphovascular invasion in stage I colorectal carcinoma: prognostic relevance and correlation with nodal micrometastases

Several studies have suggested that the presence of occult nodal metastases (micrometastases) is related to adverse clinical course in stage I colorectal carcinoma. Herein we analyzed the correlation between nodal micrometastases and lymphovascular invasion (LVI) or lymphatic vessel density (LVD) in a series of stage I colorectal carcinomas; the cohort included cases characterized or not characterized by disease progression during the follow-up. In these cases, LVI and LVD were evidenced through the immunohistochemical detection of the specific marker for lymphatic vessels, D2-40. LVI was significantly more frequent in colorectal carcinomas characterized by the presence of micrometastases (P<0.0001), high peritumoral LVD (P<0.0001), and disease progression (P<0.0001). The analysis for progression risk indicated that nodal micrometastases and LVI were significant, negative, independent prognostic parameters associated with shorter disease-free survival of stage I colorectal cancer (P=0.0001; P=0.0242). In conclusion, in this study we demonstrated for the first time that LVI is significantly associated with nodal occult metastases in stage I colorectal carcinoma. In the light of its significant, independent, prognostic value in this neoplasia, the detection of LVI may represent a faster and cheaper tool compared with the time-consuming evaluation of micrometastases to select high-risk patients who may benefit from adjuvant systemic treatment. Furthermore, the assessment of LVI may be applied to establish the likelihood of nodal involvement from carcinomas treated with conservative local excision techniques, which provide no regional nodes for histologic examination.     

转移淋巴结比值与血清CEA联合检测对预测Ⅱ〜Ⅲ期结肠癌术后远处转移的临床意义

目的探讨转移淋巴结比值(metastatic lymph node ratio,MLNR)与术前血清CEA联合检测对Ⅱ〜Ⅲ期结肠癌根治术后肿瘤远处转移的预测价值。方法回顾性分析2010年1月至2015年1月在兰州大学第二医院行结肠癌根治术的325例Ⅱ〜Ⅲ期结肠癌患者的临床资料。结果结果表明,MLNR与肿瘤最大径、肿瘤组织分化程度、TNM分期及远处转移均有关(均P<0.05);血清CEA与肿瘤最大径、TNM分期、神经或脉管侵犯及远处转移均有关(均P<0.05)。Logistics回归分析结果显示,肿瘤组织分化程度低、TNM Ⅲ期、高MLNR及高血清CEA是结肠癌根治术后发生肿瘤远处转移的独立危险因素。结论MLNR与血清CEA联合检测对Ⅱ〜Ⅲ期结肠癌根治术后患者的肿瘤远处转移有良好的预测价值。     

胆囊癌的临床病理特点及淋巴转移的临床病理危险因素分析

目的:探讨胆囊癌的临床病理特点及淋巴转移的临床病理危险因素。方法:回顾性分析2013年3月—2018年3月收治的50例胆囊癌患者的临床资料,对其临床病理特点进行总结,对患者淋巴转移的临床病理因素进行单因素和多因素分析。结果:50例患者中,女性比例高于男性(男女比例为2:3);7例患者无任何症状,43例有不同程度的上腹痛、恶心呕吐、乏力、体质量或食欲下降等;肿瘤部位以胆囊体底部居多(58.0%),T分期以T3～T4为主(78.0%),多数组织学分级恶性度较高(G3～G4者占64.0%),有淋巴转移者32例(64.0%)。单因素分析显示,肿瘤部位、T分期、组织学分级、远处转移、血管浸润、肝脏侵犯和血清CEA水平与患者淋巴结转移明显有关(均P0.05)。Logistic多元回归模型分析结果显示,肿瘤部位、T分期、组织学分级、远处转移为胆囊癌患者淋巴转移的独立危险因素(均P0.05)。结论:胆囊癌患者中女性较多,淋巴转移常见。多种因素与患者淋巴转移密切相关。临床针对这些患者在术中应仔细清扫淋巴组织,避免局部复发及远处转移,以期延长患者生存时间。     

972例结肠癌患者预后多因素分析

目的 通过对972例结肠癌患者临床病理等因素的分析,探讨影响结肠癌患者术后生存的因素.方法 对972例结肠癌患者的临床资料进行单因素及多因素COX回归分析,生存率采用寿命表法计算,生存率的比较采用Log.rank检验法.结果 单因素分析表明,年龄、围手术期输血、术前血清cEA(癌胚抗原,carcinoembryonie aIltigen)水平、肿瘤大体类型、肿瘤浸润深度、淋巴结转移、肝转移、其他脏器转移、肿瘤局部复发、腹膜种植、病理类型、TNM分期及淋巴结廓清术式均为影响预后的因素.多因素回归分析表明,年龄、术前血清CEA水平、肿瘤大体类型、淋巴结转移、肝转移、其他脏器转移、肿瘤局部复发、腹膜种植、病理类型、淋巴结廓清术式以及TNM分期是影响患者术后生存的独立因素.结论 淋巴结转移是影响结肠癌患者预后最重要的因素.