Lymph node micrometastasis in node negative early gastric cancer

Aims

The clinical significance of lymph node micrometastasis for histologically node negative gastric cancer is not well documented. This study was to assess the incidence and to clarify the risk factors of lymph node micrometastasis in patients with node negative early gastric cancer (EGC).

Methods

We investigated the lymph node micrometastasis with using an anticytokeratin immunohistochemical stain in 90 patients with node negative EGC who underwent curative resection between 1991 and 2000.

Results

Among 3526 nodes from 90 patients, there were 17 cytokeratin immunohistochemical stain positive nodes from nine patients. The incidence of micrometastasis was higher in patients with lymphatic invasion (p = 0.012), venous invasion (p = 0.026) and larger tumor (p = 0.003). The independent risk factors for lymph node micrometastasis were lymphatic invasion (p = 0.004, RR = 22.915, 95% CI = 2.709 ∼ 193.828) and tumor size (p = 0.029, RR = 1.493, 95% CI = 1.042 ∼ 2.138). Although there were 10 deaths during the follow-up period of mean 67.6 months (1 month ∼ 147 months), there was no death from a cancer recurrence.

Conclusions

The incidence of lymph node micrometastasis in patients with node negative early gastric cancer was 10%, and the independent risk factors for micrometastasis were lymphatic invasion and tumor size.     

Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer

Background. E-cadherin has been recognized as an impor-tant factor associated with tumor metastasis. However, the relationship between micrometastasis in the lymph nodes and the expression of E-cadherin in the primary tumor in gastric cancer remains unclear. Methods. Two consecutive sections of 4522 lymph nodes from 162 patients with early gastric cancer were prepared for simultaneous hematoxylin and eosin (H&E) and cytokeratin (CK) staining. Sections of primary tumors from 135 of these patients were prepared for E-cadherin immunostaining. Results. The incidence of lymph node involvement was significantly increased, from 6.8% (11/162 patients) by H&E staining, to 27% (43/162 patients) by CK immunostaining ( P < 0.0001). Micrometastasis in the lymph node was found in 32 of 151 (21%) patients who had no lymph node metastasis evidenced by H&E staining. Micro-lymph node metastasis was frequently found in tumors with a diameter more than 1.0 cm, of those that were poorly differentiated, deeply invaded, showed lymphatic on vascular invasion, and in those that showed reduced expression of E-cadherin. Loss of expression of E-cadherin in the primary tumor was closely correlated with micro-lymph node metastasis. Patients with tumors with micro-lymph node metastasis detected by CK immunostaining had a significantly lower 5-year survival rate ( P < 0.01) than those without such metastases. Conclusion. Tumors more than 1.0 cm in diameter and those that exhibit poor differentiation, deep invasion (i.e., to the submucosa), lymphatic or vascular invasion, and reduced expression of E-cadherin are risk factors for lymph node metastasis in early gastric cancer. Thus, it is recommended that cancers confined to the mucosa (m-cancers) that are more than 1.0 cm in diameter should not be treated with limited surgery without lymphadenectomy. Received: March 27, 2001 / Accepted: May 10, 2001     

免疫功能对食管癌淋巴结微转移的影响

Objective： To explore the effect of immune function on lymph node micrometastasis in esophageal cancer patients by the research on the correlation between immune function and micrometastasis. Methods： Ratios of T-lymphocyte subsets CD3＋, CD4＋, CD8＋ and CD4＋/CD8＋ in peripheral blood were examined by flow cytometry, but no lymph node with metastatic cancer cells was observed in middle thoracic esophageal squamous carcinoma patients by routine pathological examination. The patients were divided into 2 groups with or without micrometastasis to detect micrometastasis by immunohistochemical method, and T-lymphocyte subsets levels were compared between the 2 groups. Results： CD3＋ and CD4＋ T-lymphocytes levels of the group with micrometastasis were significantly lower than those of the group without micrometastasis, while CD8＋ level of the group with micrometastasis was significantly higher than that of the group without micrometastasis. Conclusion： T-lymphocyte subset is closely relative with micrometastasis, and prognosis of the patients with low CD3＋ and CD4＋ levels but high CD8＋ T-lymphocytes is comparatively poor.     

宫颈癌前哨淋巴结微转移的研究进展

宫颈癌主要的转移途径为淋巴结转移, 前哨淋巴结是肿瘤发生淋巴结转移的第一站。淋巴结转移是由淋巴结微转移发展而来, 然而淋巴结微转移通常被传统的病理组织学检测忽略, 未能发现的微转移有可能导致复发。本文将介绍近年来宫颈癌前哨淋巴结微转移的研究进展。     

食管早癌内镜黏膜下剥离术后狭窄预防研究进展

内镜黏膜下剥离术(Endoscopic submucosal dissection, ESD)已被广泛接受为食管早癌及癌前病变的一线治疗方法。然而,大面积食管病变ESD术后往往会造成严重的食管狭窄,从而极大地降低患者的生活质量。目前有多种预防ESD术后食管狭窄的方法,包括药物预防、机械性扩张、组织屏蔽法和再生医学等,临床上取得了一定的疗效,但存在狭窄容易复发、操作复杂等问题,更加有效且易于临床应用的预防狭窄的治疗方案有待进一步研究。本文就目前食管早癌ESD术后狭窄的预防研究进行综述。     

Sentinel lymph node micrometastasis in human breast cancer: an update

Introduction

The advent of sentinel lymph node biopsy (SLNB) and advances in histopathological and molecular analysis techniques have been associated with an increase in micrometastasis (MM) detection rate. However, the clinical significance of sentinel lymph node micrometastasis (SLN MM) continues to be a subject of much debate. In this article we review the literature concerning SLN MM, with particular emphasis on the prognostic significance of SLN MM. The controversies regarding histopathological assessment, clinical relevance and management implications are also discussed.

Methods

Literature review facilitated by Medline and PubMed databases. Cross referencing of the obtained articles was used to identify other relevant studies.

Results

Published studies have reported divergent and rather conflicting results regarding the clinical significance and implications of axillary lymph node (ALN) MM in general and SLN MM in particular. Some earlier studies demonstrated no associations, however most recent studies have found SLN MM to be an indicator of poorer prognosis and to be associated with non-SLN involvement.The use of adjuvant chemotherapy and/or hormonal manipulation therapy is associated with an improved survival in patients with SLN MM. Complete ALND may be safely omitted provided that adjuvant systemic therapy recommendations are equal to patients with node-positive disease. However, optimal management of SLN MM is yet to conclude.Furthermore, the identification of MM remains largely dependant on the analytical technique employed and the use of immunohistochemistry (IHC) increases the detection rate of SLN MM. Discrepancies in the histopathological interpretation of TNM classification of SLN tumour burden do exist. Published studies were non-randomized and have significant limitations including a small sample size, limited follow-up period, and lack of standardization and reproducibility of pathological examination of the SLN.

Conclusion

Patients with SLN MM have a poorer prognosis than those who are SLN negative. Therapeutic recommendations regarding patients with SLN MM should be taken in the context of multidisciplinary team setting and in selected cases of SLN MM, complete ALND may be safely omitted. A better reproducibility of pathological interpretation of the TNM classification is required so that future therapeutic guidelines can be applied without confusion.     

检测胃癌患者外周血微转移端粒酶hTERT-mRNA的意义

目的 探讨检测胃癌血液微转移的新方法，评价端粒酶hTERT-mRNA作为检测微转移标志物的价值。方法 提取42例胃癌病人外周血有核细胞RNA，采用RT-PCR方法检测其端粒酶hTERT-mRNA的表达，半定量分析，并与25名健康者作对照。结果 42例胃癌病人外周血端粒酶hTERT-mRNA的表达显著高于25例健康者；I期癌与Ⅱ～Ⅳ期癌之间存在显著性差异；不同细胞学类型胃癌之间无显著性差异；不同病理学类型的胃癌之间不存在显著性差异。结论 RT-PCR检测外周血端粒酶hTERT-mRNA可用来观察胃癌微转移，半定量分析更具价值。     

Prognostic significance of differentially expressed miRNAs in esophageal cancer

Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let‐7g, miR‐21 and miR‐195p were expressed in all 10 cell lines, miR‐9 and miR‐20a were not expressed in any of the cell lines, and miR‐16‐2, miR‐30e, miR‐34a, miR‐126 and miR‐200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR‐34a inhibited c‐Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR‐16‐2 suppressed RAR‐β₂ expression and increased tumor cell proliferation. Furthermore, we found that miR‐126 expression was associated with tumor cell dedifferentiation and lymph node metastasis, miR‐16‐2 was associated with lymph node metastasis, and miR‐195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan‐Meier analysis showed that miR‐16‐2 expression and miR‐30e expression were associated with shorter overall and disease‐free survival in all esophageal cancer patients. In addition, miR‐16‐2, miR‐30e and miR‐200a expression were associated with shorter overall and disease‐free survival in patients with esophageal adenocarcinoma; however, miR‐16‐2, miR‐30e and miR‐200a expression were not associated with overall or disease‐free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR‐30e and miR‐16‐2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR‐34a in esophageal cancer also warrants further study.     

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer

Aim Recent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes’ A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion. Methods The original histology of 168 consecutive patients with Dukes’ A or B tumours who had undergone curative resection was reviewed. Immunohistochemical staining was performed using CK antibodies, AE1/AE3 and MNF116 on all (n=898) lymph nodes. Survival analysis was performed on 105 cases that had been followed up until death or for at least 5 years. Results IHM were detected in 17.3% of lymph nodes analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%) patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM. IHM was not associated with adverse outcome on either univariate (p=0.540) or multivariate analyses (p=0.673). There was no correlation of IHM with age, gender, site, size and grade of tumour, depth of tumour invasion or perineural and vascular invasion. Vascular invasion was the only independent prognostic factor identified. Discussion We have shown that isolated CK-positive epithelioid cells are commonly found in morphologically benign pericolic lymph nodes of patients with localised (Dukes’ A or B) CRC. These cells may represent occult micrometastasis but are not clinically significant. Vascular invasion identifies patients with localised CRC likely to develop recurrences or die of disease. Presented to Royal Australasian College of Surgeons annual meeting, Adelaide (2002) and Association of Coloproctology of GB and Ireland, annual meeting, Manchester, UK (2002)     

Sentinel node micrometastasis and distant failure in breast cancer patients

BACKGROUND: Lymphatic mapping and sentinel lymph node (SN) biopsy has rapidly replaced axillary lymph node dissection for clinically node-negative breast cancers. Because of a short follow-up period when the procedure was new, there were few reports of the clinical recurrence rate in breast cancer patients treated with SN biopsy. The present study attempts to clarify the occurrence of distant failure after SN biopsy, especially in breast cancer patients with SN micrometastasis. METHODS: The subjects consisted of 375 cases with clinically node-negative breast cancer, who had undergone SN biopsies. Chemotherapy and/or hormonal therapy was recommended based on the pathological primary tumor characteristics. The patients with SN micrometastasis also received adjuvant therapy equal to node-positive patients. RESULTS: Examinations of lymph nodes indicated metastases in 73 cases. Among the invasive cancers, 54 cases had macrometastasis, 19 cases had micrometastasis and 241 cases had a tumor free SN. The median follow-up period ws 30 months (range 6 to 66 months). Distant relapse rates per person-years were 0.3% in the cases with tumor free SN and 3.3% among the macrometastatic cases. However, systemic disease was not observed in the cases with SN micrometastasis. CONCLUSIONS: These results may show that upstaging due to SN investigation increases the number of cases who should receive anti-cancer drugs, and consequently reduces the distant relapse rate. Further studies in a large number of cases as well as longer follow-up are needed to determine the prognostic significance of SN micrometastasis.     

肿瘤微转移研究的临床意义

微转移是肿瘤患者一个独立的预后因素,无瘤生存率和整体生存率都与微转移有关.微转移还可用于判断肿瘤转移和复发,评估肿瘤患者对于辅助治疗的效果,预测患者预后以及提高肿瘤患者肿瘤分期,对指导临床综合治疗均具有重要价值.对微转移的研究还存在一些问题,如缺少回顾性分析,研究的病例过少,以及随访时问过短等都限制了目前对微转移临床意义的研究.     

胃癌淋巴结微转移的多种抗体联合检测及其临床价值

免疫组化法检测胃癌淋巴结中的微转移灶方法简便,但敏感性差。同时应用多种抗体联合检测淋巴结的微转移情况,是否能提高其敏感性,克服免疫组化法的弱点尚有一些争议。本研究应用细胞角蛋白20(CK20)、上皮膜抗原(EMA)及肿瘤相关糖蛋白72-4(CA72-4)抗体对胃癌阴性淋巴结的微转移情况进行联合检测,旨在评价多种抗体联合检测微转移的应用价值。     

食管癌淋巴结微转移的研究

目的探讨食管癌术后常规病理检查无转移性淋巴结微转移的发生率、类型及临床意义。方法选择食管癌术后≥3年的患者,常规病理检查淋巴结转移阴性患者68例,采用抗角蛋白抗体免疫组化染色查找癌细胞,免疫组化染色阳性癌细胞每个视野不超过5个就确定为微转移。结果16例患者22个淋巴结检出微转移1.8%(22/1246)存在微转移的患者术后复发率为50.0%(8/16),不存在微转移的复发率为11.5%(6/52),两者差异有统计学意义,P=0.008;存在微转移的患者术后生存率低于无微转移的患者,P<0.05。结论检测淋巴结微转移对于常规病理检查阴性患者的治疗及预后具有重要的临床意义。     

乳腺癌外周血微转移与远处转移的相关性

背景与目的:乳腺癌是一种全身性疾病,早期就可发生血行转移.本研究采用流式细胞仪定量检测乳腺疾病患者外周血肿瘤细胞含量,探讨外周血肿瘤细胞含量与远处脏器转移的相关性.方法:以人细胞角蛋白抗体和CD45抗体双色免疫标记,应用多参数流式细胞仪方法检测65例乳腺癌患者术前和10例乳腺良性病变及8例健康献血者外周血标本中肿瘤细胞含量.结果:65例乳腺癌患者中,57例检测出肿瘤细胞,阳性率为87.7%;乳腺良性病变、健康献血者外周血中未检测到肿瘤细胞.外周血肿瘤细胞阳性率与肿瘤T分期及N分期具有相关性(r=0.271,P=0.017;r=0.393,P=0.002).除2例失访外,63例患者经过5年随诊,25例出现远处脏器转移,5年转移率为39.7%.所有远处转移病例均为外周血检测阳性患者,8例术前外周血检测阴性的患者均未发现远处转移,两组比较差异有统计学意义(P=0.014);而远处转移与肿瘤T分期、N分期均无明显相关性.结论:术前外周血肿瘤细胞数量与远处转移具有明显相关性,多参数流式细胞术检测乳腺癌患者外周血肿瘤细胞,对指导乳腺癌的个体化治疗具有潜在的应用价值.     

Prognostic factors in early esophageal cancer

During the period from 1975 through 1988, 405 thoracic esophageal carcinoma were resected in our department. Among them, superficial carcinoma was proved in 50 cases. The prognosis of these 50 patients with superficial carcinoma has been analyzed in regard to the prognostic factors. As for the clinico-pathological findings, there were no evident differences in mean age, sex distribution and main location of the lesions between superficial cases and overall resected cases. The distribution of depth of invasion was as follows; ep 4 cases, mm 7 cases and sm 39 cases. The number of patients with invasion to submucosal layer had included the majority of the superficial cases. Lymph node metastasis was proved in 17 cases, and 16 of them had the invasion to the submucosal layer. On the other hand, neither patient with invasion to ep layer had lymph node metastasis, however, in one of seven cases with invasion to mm layer, lymph node metastasis to second group node was proved. The lesions have been resected through thoracotomy in 48 patients out of 50 cases. Blunt dissection has been carried out upon only two cases. The 5-year survival rate of superficial carcinoma was 61.7%, which was clearly better than that of all patients resected in the same period (31.6%). The prognosis distinctly correlated with the depth of invasion; 5-year survival rate of ep, mm and sm cases were 100%, 83.7% and 54.3%, respectively. We experienced no recurrence in case of ep or mm. As for sm cases, lymph node metastasis and/or vessel invasion were most dominant prognostic factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

食管支架在食管癌治疗中的应用进展

食管支架置入广泛用于临床解决进食困难的病人,本文就食管支架在食管癌治疗中的应用作一综述。     

结直肠癌淋巴结微转移对预后影响的意义

背景与目的:淋巴结微转移的预后价值尚无一致意见,本研究旨在探讨结直肠癌淋巴结微转移的预后意义。方法:收集江汉大学附属医院1988年～2001年结直肠癌根治性手术切除、有完整淋巴结检查资料的标本80例,其中直肠癌30例,结肠癌50例。经过溶脂法检查淋巴结共3869枚,平均每例48.36枚,经4μm间断连续切片、常规HE染色和免疫组化染色,确定有无淋巴结转移与微转移(微转移灶为瘤团直径<0.2mm或瘤细胞数<50个)。数据经SAS8.1统计学软件进行Cox模型回归分析及Spearman等级相关分析。结果:共检出转移淋巴结232枚(6%),微转移淋巴结39枚(1.01%)。直肠癌中淋巴结转移数与患者生存时间有关(χ2=9.94,P=0.0016);淋巴结微转移与淋巴结转移数(r=0.44,P=0.016)等病理学指标有关。结肠癌中淋巴结转移数(χ2=9.52,P=0.002)、AJCC淋巴结分期(χ2=5.73,P=0.0167)与患者生存时间有关,淋巴结微转移与Dukes’淋巴结分期(r=0.314,P=0.008)有关。结论:淋巴结微转移与结直肠癌预后相关,但不能作为独立的预后指标。     

A nomogram predictive of non-sentinel lymph node involvement in breast cancer patients with a sentinel lymph node micrometastasis

Purpose

Predictive factors of non-sentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) have been studied in the case of sentinel node (SN) involvement, with validation of a nomogram. This nomogram is not accurate for SN micrometastasis. The purpose of our study was to determine a nomogram for predicting the likelihood of NSN involvement in breast cancer patients with a SN micrometastasis.

Methods

We collated 909 observations of SN micrometastases with additional ALND. Characteristics of the patients, tumours and SN were analysed.

Results

Involvement of SN was diagnosed 490 times (53.9%) with standard staining (HES) and 419 times solely on immunohistochemical analysis (IHC) (46.1%). NSN invasion was observed in 114 patients (12.5%), whereas 62.3% (71) had only one NSN involved and 37.7% (43) two or more NSN involved. In multivariate analysis, significant predictive factors were: tumour size (pT stage ≤10 mm or >11 and ≤20 or >20 mm [odds ratio (OR) 2.1 and 3.43], micrometastases detected by HES or IHC [OR 1.64], presence or absence of lymphovascular invasion (LVI) [OR 1.76], tumour histological type mixed or not [OR 2.64]. The rate and probability of NSN involvement with the model are given for 24 groups, with a representation by a nomogram.

Conclusion

One group, corresponding to 10.1% of the patients, was associated with a risk of NSN involvement of less than 5%, and five groups, corresponding to 29.8% of the patients, were associated with a risk ≤10%. Omission of ALND could be proposed with minimal risk for a low probability of NSN involvement.     

Ⅲ期非小细胞肺癌患者骨髓微转移与新辅助化疗及预后的关系

目的　研究Ⅲ期非小细胞肺癌患者骨髓中微转移与新辅助化疗及预后的关系。方法　选取Ⅲ期非小细胞肺癌患者 65例 ,随机分为新辅助化疗组 ( 3 2例 )及直接手术组 ( 3 3例 ) ,两组患者均于术中切取肋骨获得骨髓 ,应用RT PCR技术检测CK19mRNA及CEAmRNA的表达 ,并进一步分析两指标表达情况与生存期的关系。结果　新辅助化疗组及直接手术组患者骨髓中CK19阳性率分别为 18.8% ( 6/ 3 2 )、45 .5 % ( 15 /3 3 ) (P =0 .0 3 3 ) ,CEA阳性率分别为 2 5 .0 % ( 8/ 3 2 )、5 1.5 % ( 17/ 3 3 ) (P =0 .0 41)。CK19与CEA的表达具有正相关关系 (rs=0 .671,P <0 .0 0 1)。CK19及CEA共同阳性者化疗有效率为 0 % ( 0 / 5 ) ,共同阴性者为 5 6.5 % ( 13 / 2 3 ) (P =0 .0 44 )。CK19及CEA共同阳性者及共同阴性者中位生存期分别为 11和 2 7个月 (P =0 .0 0 0 6)。Cox模型分析提示 ,新辅助化疗组中化疗疗效、CK 19及CEA的阳性表达是影响患者预后的独立因素。无效的化疗较有效的化疗死亡风险增加 (P =0 .0 43 ) ,CEA及CK 19阳性表达者较阴性者死亡风险增加 (P =0 .0 2 1,P =0 .0 2 0 )。结论　新辅助化疗能降低Ⅲ期非小细胞肺癌患者骨髓微转移的发生率。骨髓微转移提示患者预后不良。