淋巴管在肿瘤转移中的作用

恶性肿瘤的局部及远处转移是导致患者死亡的根本原因,淋巴管形成以及结构改变的作用与淋巴转移途径密不可分.本文主要针对淋巴管在肿瘤转移过程中发挥的作用进行讨论,并且主要从近几年国际上关于淋巴管上皮细胞分子水平上的机制研究进展作一综述.     

Gastrointestinal cancer metastasis and lymphatic advancement

The role of angiogenesis in the growth of solid tumors is well established, but the role of lymphatic vessels and the relationship between lymphangiogenesis and tumor spread are less clear. Recently, the molecular pathway that signals lymphangiogenesis and specific markers for lymphatic endothelium have been discovered; however, the lymphatic pathway of cancer metastasis is only partly clarified. Several investigators from the mid 20th century indicated the existence of lymphatico-venous communications, and some observed the retrograde filling of lymph flow and lymphatico-venous communication in obstructive lymphopathy. In the 1960s Burn reported the importance of lymphovenous communication in his clinical and animal experimental data. Thus, the role of potential peripheral lymphatico-venous communication must be considered in the mechanism of cancer metastasis. We observed the lymphatico-venous (portal) communication, as well as lymph retention and reflux, in a rat model of mesenteric lymph vessel obstruction. Based on the phenomenon of lymphatico-venous communication and lymph flow reflux by lymphatic obstruction, we speculate that tumor cell obstruction in the lymph system will lead to the establishment of liver and/or peritoneal metastasis. Clinically, we observed extranodal cancer invasion in a model of lymphatic obstruction, and noted a strong relationship between extranodal invasion and liver or peritoneal metastasis. Thus, the existence of peritoneal and liver metastasis via a lymphatic pathway should be considered.     

大肠癌淋巴转移规律与手术范围的关系

目的 研究进展结肠直肠癌淋巴结转移规律,指导手术根治范围,方法 分析７４例结肠直肠癌行Ｄ３式根治术切除的淋巴结６２３个,按肿瘤旁,肠管纵轴和中枢方向行淋巴结分组,分站计算淋巴结转移率和转移度。结果 肿瘤旁淋巴结转移率为４７．２％,转移度为３８．６％,阳性淋巴结占６１．２％,肠管纵轴方向淋巴结转移率为２２．８％,转移度为１８．６％,阳性淋巴结占１７．１％,并与距肿瘤的距离和方向有关。中枢方向阳性淋巴     

Gastric perforation secondary to metastasis from ovarian cancer: Case report

INTRODUCTIONMetastasis from ovarian cancer occurs frequently through the peritoneal cavity in the form of peritoneal carcinomatosis; isolated gastric metastasis is rarely reported in literature.PRESENTATION OF CASEWe present a case of 43-year-old infertile lady, who developed a picture of acute abdomen four days post total abdominal hysterectomy and salpingoopherectomy for ovarian cancer. Further contrast-enhanced CT scan demonstrated massive free gas and fluid in the abdomen. She underwent antrectomy with truncal vagotomy due to 3 cm × 4 cm prepyloric gastric ulcer. Final pathology proved the presence of metastatic serous cystadenocarcinoma of ovarian origin.DISCUSSIONOur patient had a gastric perforation secondary to ovarian metastasis. Being isolated, the absence of ascites and the transmural nature of the gastric metastasis suggest haematogenous spread .To the best of our knowledge perforated gastric metastasis secondary to ovarian cancer was not reported in literature before.CONCLUSIONGastric metastasis should be kept in mind in patients with a well-known ovarian cancer who present with gastric lesions, ulcers, bleeding or perforation.     

淋巴管生成及其内皮特异性标志物在结直肠癌肝转移中作用的研究进展

淋巴管内皮细胞特异性标志物的出现使淋巴管生成及淋巴管转移的分子机制成为肿瘤转移的研究热点。以往认为结肠癌肝转移的途径主要通过血道途径,而近期一些研究表明,淋巴管生成及淋巴结转移可能在结直肠癌肝转移的过程中同样发挥着至关重要的作用。笔者就淋巴管生成及其内皮特异性标志物在结直肠肝转移中的作用机制作一综述。     

膀胱癌早期淋巴转移机理的研究

目的探讨膀胱癌及癌周淋巴管形态学特征与盆腔淋巴结转移的机理。方法应用５′ＮａｓｅＡＬＰ双重组织化学及透射电镜观察２４例膀胱癌组织和癌旁膀胱壁组织内淋巴管的细微分布、形态和结构。结果发现膀胱癌组织内有较多新生的毛细淋巴管、癌周组织中毛细淋巴管的分布明显高于正常组织,随着癌的浸润发展,癌周组织毛细淋巴管数量增多、密度增高、形态结构变异,内皮细胞间连接呈开放状态,且可见到癌栓经开放之通道侵入毛细淋巴管内。结论膀胱癌及癌周组织淋巴管增生、形态结构变异是癌细胞淋巴道转移的可能原因     

淋巴结清扫数目对无淋巴结转移胃癌患者预后的影响

目的 探讨胃癌根治术中淋巴结清扫数目对无淋巴结转移患者预后的影响.方法 回顾性分析1995年1月至2004年12月期间221例施行D2根治术、术后经病理证实无淋巴结转移的胃癌患者的临床资料.对本组患者预后因素进行单因素及多因素分析,分析淋巴结清扫数目与术后5年生存率及术后并发症发生率的关系.结果 221例无淋巴结转移胃癌患者术后5年生存率为83.5%.淋巴结清扫数目是影响本组患者预后的独立因素之一.相同浸润深度患者的术后5年生存率有随淋巴结清扫数目的 增加而增高的趋势(P<0.05).淋巴结清扫数目pT1.2期≥15枚、pT3期≥20枚时,患者术后5年生存率较高(P<0.05).本组患者术后并发症发生率为10.8%,淋巴结清扫数目与术后并发症发生率的无显著相关性(P>0.05).结论 淋巴结清扫数目是无淋巴结转移胃癌患者的独立预后因素,应积极争取清扫足够的淋巴结,以提高疗效;合理的淋巴结清扫数目并不增加患者术后并发症的发生率.     

Penile cancer: relation of extent of nodal metastasis to survival

A retrospective review of 199 patients with penile cancer revealed that the extent of inguinal nodal metastasis was related to survival after radical ilioinguinal dissection. Patients with unilateral inguinal nodal involvement had a 56 per cent median 5-year survival rate, whereas those with bilateral inguinal nodal metastasis, extranodal tumor extension or iliac nodal involvement had a 9 per cent median 5-year survival rate.     

微血管密度与胃癌复发转移相关性研究

目的　探讨微血管密度（ ＭＶＤ） 与胃癌复发转移及预后的相关性。方法　４５ 例手术切除标本应用ＦⅧ相关抗原抗体免疫组化染色，观察癌灶、癌旁及正常组织中ＭＶＤ，分析其与复发转移及预后的关系。结果　ＭＶＤ 在癌组织为３８－１２ ±１２－８７ ，癌旁为２４－６７ ±１１－０９，正常组织为１３－１１ ±７－５６（ Ｐ＜ ０－０５） 。复发转移组和无复发转移组的ＭＶＤ 分别为３８－３１ ±９－６７ 和２１－９８ ±１２－２３（ Ｐ＜ ０－０１） 。两组在淋巴结转移、浸润深度、肿瘤分期三方面差异也有显著性（ Ｐ＜ ０－０５） 。结论　微血管的生长与肿瘤的血行和淋巴结转移有关。除淋巴结转移、浸润深度、肿瘤分期具有预后意义外，胃癌组织中ＭＶＤ 也具有判断预后价值。     

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目的 探讨早期胃癌的淋巴结转移规律及其对预后的影响。方法 对161例有癌病人术后进行长期随访，对24例伴有淋巴结转移的早期胃癌与137例无淋巴结转移的早期胃癌的临床病理特征及3、5年生存率进行比较。结果 早期胃癌的淋巴结转移与肿瘤大小、浸润深度及淋巴、静脉侵犯有关，伴有淋巴结转移的早期胃癌3、5年生存率分别为82.8%和80.5%，明显低于无淋巴结转移者，后者分别为96.1%和92.4%。结论 术前或术中正确评估早期胃癌的淋巴结转移状态是选择合理的治疗方案和改善预后的重要条件。     

无淋巴结转移的乳癌的预后分析

目的　探讨辅助化疗在无淋巴结转移乳癌病人的治疗效果。方法　随访１１２ 例无淋巴结转移乳癌病人,观察其５ ,１０ 年生存率和复发转移情况。结果　辅助化疗组１０ 年转移率低于单纯手术组（ Ｐ ＜ ０ ．０５） ,１０ 年生存率高于单纯手术组（ Ｐ ＜ ０ ．０５） 。结论　对无淋巴结转移乳癌病人应常规行辅助化疗;而手术范围与生存率无关。     

血管内皮生长因子C和微淋巴管密度与胆管癌淋巴结转移及预后的关系

目的:探讨胆管癌组织中血管内皮生长因子C(VEGF-C)的表达及微淋巴管密度(MLVD)与胆管癌临床病理特征及预后的关系。方法:应用免疫组化法分别检测47例胆管癌、40例近癌的非癌胆管及15例正常肝外胆管组织中VEGF-C的表达和D2-40标记的MLVD。分析两者间的相关性,及其与临床病理特征和预后的关系。结果:胆管癌组织中VEGF-C的阳性表达率明显高于近癌的非癌胆管和正常胆管组织(均P<0.05),胆管癌和近癌的非癌胆管组织中MLVD明显高于正常胆管组织(均P<0.05);VEGF-C的表达以及MLVD与胆管癌浸润深度、TNM分期、淋巴结转移密切相关(P<0.05),且MLVD还与胆管癌分化程度有关(P<0.05);VEGF-C阳性胆管癌组织MLVD明显大于其阴性胆管癌组织(P<0.05),且VEFG-C表达与MLVD呈正相关(r=0.615,P<0.05);VEFG-C阴性表达患者预后明显优于其阳性表达患者,复发者胆管癌组织中的MLVD明显高于无复发者(P<0.05),且MLVD与患者生存期呈负相关(r=-0.542,P<0.05)。结论:VEGF-C的表达和MLVD与管癌淋巴结转移、预后密切相关,VEGF-C可能是预测胆管癌淋巴结转移的有效指标之一。     

肝细胞生长因子与胃癌淋巴管生成及淋巴转移的关系

目的明确肝细胞生长因子（HGF）与胃癌淋巴管生成的相互关系及其可能途径，进一步探索HGF在肿瘤淋巴转移中的作用。方法对60例胃癌组织及其邻近正常胃组织和20例胃溃疡组织标本作免疫组织化学染色，并记数血管内皮生长因子-C（VEGF-C）、HGF、c-Met和淋巴管内皮透明质酸受体-1（Lyve-1），结合胃癌的临床病理资料作相关统计学分析。结果胃癌组织中VEGF-C、HGF、c-Met表达明显上调，其微淋巴管密度（MLD）也明显高于正常胃组织和胃溃疡组织（P〈0．001），有无淋巴转移和远处转移差异有统计学意义（P〈0．05）；胃癌和胃溃疡边缘淋巴管内皮有c-Met表达，HGF和肿瘤MLD之间有明显的正相关系（P〈0．001）和多元线性回归关系（P=0．001）。结论HGF与VEGF．C一样是胃癌的淋巴管生成刺激因子，它可以通过直接或间接途径刺激淋巴管的增生，促进肿瘤淋巴转移。     

A novel in vitro model of lymphatic metastasis from colorectal cancer

INTRODUCTION: For many types of cancers, successful metastasis is critically dependent on tumor cell survival under flow conditions in the lymphatic system as well as attachment to the lymphatic endothelium at distal sites. In the lymphatic system, tumor cells are exposed to dynamic forces of laminar shear stress; however, there are currently no models to study the effects of these dynamic fluid forces on colorectal cancer metastasis. This study aims to establish the rudiments of an in vitro flow system that mimics the conditions to which tumor colorectal cancer cells (CRCCs) are exposed during lymphatic spread. METHODS: Human CRCCs (RKO and HCT-8) were cultured on collagen-1 coated glass slides in 10% fetal bovine serum, and grown until 50% confluence under static conditions. Subconfluent cells were then treated with laminar shear stress (1.2 dynes/cm(2)) using a Flexcell Streamer (Flexcell International Corp., Hillsborough, NC) parallel plate chamber for up to 48 h, in the continued presence of serum. Control conditions consisted of cells maintained under static conditions (0 dynes/cm(2)). Cells were examined with digital microscopy. Cell number was determined directly by cell count. Poly (ADP-ribose) polymerase-1, caspase-3, matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor C levels were measured by Western blot. RESULTS: CRCCs survived under conditions of lymphatic flow (1.2 dynes/cm(2)), and were confluent by 48 h. Although a small number of cells (10% to 15%) initially detached upon exposure to shear stress, the majority of cells remained attached, and mitotic cells were observed. Cells demonstrated increased attachment and spreading under lymphatic flow compared with cells kept under control conditions. Cell number increased in cells treated with both lymphatic flow and static conditions by similar amounts until confluence was achieved. Cleaved products of poly (ADP-ribose) polymerase-1 and caspase-3 were not observed. MMP-2, MMP-9, and vascular endothelial growth factor C were expressed to similar degrees at all time points in cells exposed to lymphatic flow. CONCLUSIONS: Using a novel in vitro model of lymphatic flow, we describe colorectal tumor cell proliferation and expression of peptides critical to lymphatic spread under flow conditions. The ability to model lymphatic spread in vitro will allow additional studies to determine mechanisms of tumor cell survival in the lymphatic system.     

Inguinal lymphatic metastasis of cancer of the testis: staging and therapeutic approach]

Inguinal lymph node metastases from testicular tumors are reported in 2% of cases. Between 1980 and 1990, two patients in a series of 54 testicular tumors, presented with inguinal node metastases. In there two cases and in the cases in the literature, it is well known, that testicular tumors in patients who have had the lymphatics disrupted by prior scrotal or inguinal surgery, or tumor-contaminated scrotum, can metastasize primarily to the ipsilateral inguinal nodes. Even in the absence of other retroperitoneal metastases, these testicular tumors must be considered to be stage IIA. Owing to the efficacy of primary or secondary chemotherapy, ipsilateral inguinal node dissection is not necessary in nonseminomatous testicular tumors. For testicular seminoma, an additional inguinoscrotal radiotherapy is necessary. Survival rate for testicular tumors with isolated metastatic inguinal nodes, particularly in tumor-contaminated scrotum, is not significantly different, compared to a group of patient without inguinal nodes.