肿瘤包绕型血管在肝细胞癌中的研究进展

早期转移是肝细胞癌（HCC）术后复发及病死率高的主要原因。目前,研究发现一种新的血管转移模式—肿瘤包绕型血管（VETC）,不依赖经典的上皮-间质转化转移方式,其转移程度更高,预后更差,给HCC患者的精准治疗带来更大的挑战。故笔者总结VETC模式在HCC中研究现状、作用机制及临床意义,旨在为HCC的临床与基础研究提供参考。     

胰腺实性-假乳头状瘤的诊断与外科治疗

目的分析胰腺实性-假乳头状瘤（SPTP）的临床特点和治疗方法。方法回顾性分析8例经病理证实为SPTP患者的临床资料。结果8例均为女性,平均年龄26.3岁。5例无临床症状,3例上腹部隐痛。血清CEA、CA199均正常。CT平扫为边缘清晰的囊实性占位,增强扫描病灶囊性部分不强化,实性部分轻至中度强化。8例均行手术切除,7例术后平均随访18.6个月,均未见肿瘤复发或转移。结论多数SPTP结合临床特点和CT表现可在术前作出准确诊断,为治疗方案提供重要依据。SPTP是一种低度恶性的肿瘤,积极手术切除可以获得良好的预后。     

颈椎骨肿瘤的外科治疗讨论

目的：研究颈椎骨肿瘤的手术处理方式。方法：回顾复习１９９０年以后５我科治疗４２例颈椎骨肿瘤（包括肿瘤样变）的临床肿瘤,共归纳为７种外科处理方式。结果：平均２５个月随访结果显示,在２９例原发骨肿瘤患者中,１例Ｃ２居细胞瘤复发导致病人死亡,２例恶性肿瘤死于全身转移,１例巨细胞瘤及１例血管瘤复发再手术成功,其余２４例手术均达到预期结果。在１３例转移癌患者中手术起到了缓解脊髓、神经根压迫及颈部疼痛症状。结     

血清白细胞介素34与肝癌肝移植临床预后的关系及其作用机制

背景和目的：肝移植在肝癌的治疗中发挥了越来越重要的作用。目前移植术后肿瘤复发与转移的临床问题尚未解决。本研究旨在分析白细胞介素34（IL-34）表达与肝癌肝移植受者预后、肿瘤复发与转移的关系,并探讨其在肝癌生长和转移中的作用机制。方法 采用酶联免疫吸附试验（ELISA）法检测93例肝癌肝移植受者术前血清中IL-34表达情况,用统计学方法分析IL-34表达与临床病理特征和预后的关系;用受试者工作特征（ROC）曲线分析IL-34检测肿瘤复发和转移的诊断价值。取雄性5~6周龄NOD/SCID小鼠建立人源性肝癌原位移植瘤模型,并随机分为4组,分别腹腔注射不同浓度的IL-34（5、10、35 μg/kg）（干预组）及等量生理盐水（对照组）,1次/d,共2周。比较10周后各组小鼠总体生存率、移植瘤体积与质量、肺组织转移情况;用Western blot检测各组移植瘤中细胞增殖相关蛋白（Ki-67与PCNA）、肿瘤转移相关蛋白（MMP-2与MMP-9）、上皮-间充质转化（EMT）相关蛋白（E-cadherin、vimentin和snail）的表达。结果 经5年随访,93例肝癌肝移植受者中肿瘤复发27例、转移9例、死亡45例。肿瘤复发和转移患者中IL-34表达水平明显低于肿瘤未复发和未转移患者（均P<0.05）;IL-34低表达与肿瘤复发、转移、血管侵犯呈负相关（均P<0.05）;IL-34低表达患者5年总体生存率和无瘤生存率明显低于IL-34高表达患者（均P<0.05）。IL-34低表达、肿瘤复发与转移是影响总体生存率的独立危险因素（均P<0.05）。血清IL-34检测肿瘤复发与转移曲线下面积（AUC）分别为0.93与0.79,优于甲胎蛋白（AFP）。与对照组比较,3个IL-34干预组小鼠总体生存率增加,移植瘤体积与重量减少,肺组织转移率和转移灶数量降低,移植瘤中Ki-67、PCNA、MMP-2、MMP-9、vimentin、snail蛋白表达水平降低而E-cadherin表达水平增加,且均呈浓度依赖性（均P<0.05）。结论 血清IL-34低表达与肝癌肝移植受者不良预后、肿瘤复发与转移密切相关。IL-34具有对抗肝癌生长与转移的作用,机制可能与抑制细胞增殖和EMT有关。     

314例直肠癌患者术后复发转移形式及其预后

目的 探讨直肠癌术后复发转移的形式、预后及其治疗对策.方法 回顾性研究1979年5月至2006年11月哈尔滨医科大学附属肿瘤医院行直肠癌手术治疗并术后复发转移的314例患者的临床资料.结果 全组患者局部复发168例（53.5%）,复发间隔期为（24.7±1.9）个月;远隔转移146例（46.5%）,远隔转移间隔期为（22.7±1.9）个月;远隔转移时间早于局部复发时间（P〈0.01）.复发时间段较早（P〈0.01）、腹膜反折以下（P=0.043）及术后未行放化疗（P=0.007）的患者发生局部复发的构成比高.局部复发组3年和5年生存率为0.48和0.25,生存期为（24.7±1.9）个月;远隔转移组3年和5年生存率为0.33和0.16,生存期为（22.7±1.9）个月,两组差异有统计学意义（P〈0.01）;Cox回归分析提示,复发早、TNM分期及治疗方式（包括手术方式和术后是否放化疗）是影响患者复发后生存的独立因素（均P〈0.01）.结论 直肠癌术后局部复发者预后优于远隔转移者：根治性切除可使术后复发患者生存显著获益.     

胃肠道平滑肌肿36例临床分析

目的：探讨如何鉴别平滑肌肿瘤的性质以及肿瘤病理分型、大小、浸润和转移之间的关系。方法：1993－1999年经我院治疗的胃肠道平滑肌肿瘤36例，对其临床表现，发生部部位，肿瘤大小、生长方式，淋巴转移、远处转移，辅助检查，组织学人类和外科治疗等进行分析，随访时间为1－5年。结果：平滑肌肿瘤的好发部位是胃（23例），其次是小肠（10例）和食管（2例），在平均25个月的随访中，3例死于转移，3例有局部复发。结论：肿瘤组织学恶性与局部复发和远处转移明显相关，包括（1）大小：2cm以上，尤其是发生于十二指肠的肿瘤；（2）组织学恶性；（3）生长方向；向浆膜生长的肿瘤易侵犯周围组织；（4）与临床脏器关系：已侵犯周围组织的肿瘤。     

以囊性胰岛素瘤为主的多发性内分泌腺瘤病1型：病例报道与文献回顾

目的 通过研究笔者团队诊治的1例以囊性胰岛素瘤为主的多发性内分泌腺瘤病1型（multiple endocrine neoplasia type 1，MEN1），结合文献，探讨MEN1的临床特点、诊疗及预后。方法 回顾性分析内蒙古医科大学附属医院肝胆外科诊治的1例MEN1的临床资料；同时在万方数据库以“多发性内分泌腺瘤病1型”和“胰岛素瘤”为检索词，在Pubmed以“multiple endocrine neoplasia type 1”与“insulinoma”为检索词进行检索，对诊断为胰岛素瘤且有影像学资料提示囊、实性胰腺占位的病例资料汇总分析。结果本组病例共有24例患者纳入分析，其中男11例，女13例，年龄8～55岁。所有患者中，囊性或囊实性患者5例：1例为多发，肿瘤位于胰体、胰尾；其余4例为单发，肿瘤分别位于胰体、胰尾；实性患者19例：8例为多发，11例为单发，钩突、胰头、胰体、胰尾均有肿瘤分布。24例中有18例行手术切除肿瘤治疗，1例药物治疗（二氮嗪），1例行超声引导下无水乙醇消融术，1例经动脉注射聚苯乙烯-马来酸偶联新卡津抑素，1例因胰岛素瘤术后复发行球形聚乙烯醇颗粒栓塞治疗，2例患者未治疗。治疗的22例恢复良好，未治疗的2例死亡，其中1例因肿瘤无法切除行对症治疗，2个月后死于进行性肾功能衰竭，另1例未手术数月后死亡。有随访记录的患者12例，随访期间均存活，有1例患者术后复发，再次手术后恢复良好。结论 MEN1是一种常染色体显性遗传疾病，以囊性或者囊实性胰岛素瘤为表现者较少，容易漏诊和误诊。综合分析临床资料，合理运用基因检测辅以手术等适宜干预措施对MEN1诊疗和预后具有重要意义。     

依据临床循证医学研究探讨晚期胃癌的转化治疗

尽管在化疗、放化疗与生物免疫治疗等已取得了较大发展，但是晚期胃癌的预后仍然欠佳。在多数医学中心，姑息性化疗与最佳支持治疗仍作为治疗晚期胃癌的主要手段。晚期胃癌存在着各种转移形式，其肿瘤特征与预后主要取决于转移的部位与体量。转化治疗主要针对因手术技术或肿瘤学因素等已无法切除或勉强可予切除的晚期肿瘤，通过术前治疗等，争取使肿瘤能达到R0切除。为了能进一步改善晚期胃癌转化治疗的效果，临床上应充分关注如下几个重点因素：（1）首先，应该尽可能筛选出转化治疗潜在的获益者，包括远处“寡转移”或局限性远处转移者，例如N2融合转移（Bulky N2）和（或）腹主动脉旁淋巴结转移（No.16a1或16b2）、潜在可切除的肝转移与非弥漫性腹膜转移；肿瘤内外科医生共同面临的一大挑战即如何能正确地筛选出转化治疗的适宜对象并给予合适的综合治疗。（2）转化治疗的目的是使肿瘤降期，并能达到根治性切除（R0切除），包括完全切除转移灶，尽可能减少手术并发症，使病人术后可按计划接受后续化疗等；由于肿瘤系多途径转移，因此，围手术期全身治疗十分重要，但是R0切除仍然是改善预后的关键；另一方面，对于施行姑息性切除应持非常谨慎的态...     

平均血小板体积和循环肿瘤细胞对结直肠癌术后复发转移的预测价值

目的：探讨平均血小板体积（MPV）和循环肿瘤细胞（CTCs）对结直肠癌患者术后复发转移的预测价值。方法：纳入2016年6月—2017年6月接受根治性手术治疗的100例结直肠癌患者作为研究对象，记录患者一般临床病理资料、肿瘤标志物、术前MPV、术前及术后2周CTCs以及根治术后5年内肿瘤复发转移情况，多因素Cox回归分析获得独立预测因素，重点分析MPV及CTCs与患者术后肿瘤复发转移的相关性，基于MPV及CTCs建立相关Cox复发转移风险得分模型，并绘制MPV及CTCs用于预测结直肠癌患者术后肿瘤复发转移净收益率的决策曲线，进一步验证MPV及CTCs的预测效能。结果：多因素分析结果显示，中分化（β=0.554,HR=1.546）、低分化（β=1.017,HR=2.841）、TNM/T分期（β=1.554,HR=6.552）、淋巴结转移（β=1.215,HR=4.312）、术后CTCs(β=1.235,HR=4.415)以及MPV(β=0.578,HR=1.615)为影响患者术后5年肿瘤复发转移的独立预测指标（P<0.05）。Cox复发转移风险得分模型显示，MPV及CTCs与Cox复...     

肝癌干细胞研究进展

转移、复发是治疗恶性肿瘤过程中遇到的最大难题。传统观点认为，肿瘤的每个细胞都具有无限增殖和形成克隆的能力，但具体由哪些细胞克隆参与肿瘤的复发却是随机的。新近提出的“肿瘤干细胞（Tumor／cancer Stem Ceils，TSCs／CSCs）假说”对此观点提出了挑战，认为肿瘤中只有一小部分具有无限增殖潜力，维持着肿瘤的生长，且可能与肿瘤的转移、复发有密切关系，     

肺转移瘤的转移前微环境与转移微环境

一个多世纪前Paget就肿瘤器官特异性转移现象提出了“种子与土壤”学说。时下研究热点集中在一些特殊因子介导的靶器官环境改造,肿瘤细胞归巢行为。有动物实验证实肺转移瘤形成前,肺部已发生大量炎症因子聚集。宿主靶器官的改变影响转移瘤形成的每一个步骤。BethanPsaila与DavidLyden针对这一土壤变化过程提出转移前微环境（pre-metastaticniche）及转移微环境（metastaticniche）假说,指出土壤的变化是转移瘤形成的保障。该假说提出后迅速引起肿瘤研究界轰动。研究这一系列细胞分子生物学的改变,有助于阐明肿瘤转移这一复杂的过程,为转移干预带来新的思路。     

直肠癌单个转移淋巴结分布情况及临床意义

目的：通过回顾性分析直肠癌单个转移淋巴结的病理情况,预测直肠癌前哨淋巴结（SLN）的分布,为下一步行前瞻性研究提供参考。方法：收集1994年10月—1999年10月行根治性切除的68例直肠癌患者,其病理检查结果均为单个淋巴结转移,分析转移淋巴结的解剖位置,推断直肠癌SLN分布情况。结果：68例患者共计淋巴结720枚,平均每例10.59枚（3～26枚）。单个转移淋巴结分布情况结果显示肠旁淋巴结转移（肠旁组）52例（76.5%）,中间淋巴结转移（中间组）12例（17.6%）,中央淋巴结转移（中央组）4例（5.9%）。非肠旁组织转移的＂跳跃＂转移（SM）共计16例（23.5%）。随着直肠癌组织浸润肠壁深度的增加、肿瘤直径的增大以及分化程度的变差,SM亦呈升高趋势（P〈0.05）,SM与肿瘤位置无明显相关性（P〉0.05）。结论：大部分直肠癌SLN分布于肠旁,极少部分可出现＂跳跃＂转移现象,分布于肠系膜血管周围。     

肝癌复发和转移的新理念

Cancer metastasis is considered as a complex process involving a series of sequential steps and a variety of molecalar signal transduction pathways.Tumor recurrence and metastasis are major obstacles for long-term survival of Liver cancer patients.Although the prognosis after recurrence and metastasis is dismal,the advancement of molecular researches of metastasis of liver cancer seems promising.In studies of origins of metastasis of liver cancer,the primary cancer cell and corresponding metastatic liver cancer cells share similar gene signature,which indicates that genes favoring metastasis progression are initiated in the primary tumors.The metastasis of liver cancer may be an early event in hepatic carcinogenesis and progression.Some molecular signatures have been developed to classify the metastatic potential of liver cancer.Furthermore,a variety of studies demonstrate that the tumor microenvironment instead of tumor cells plays a more important role in liver cancer metastasis.The pre-metastatic niche composed of non-tumoral cells may promote the cancer cell sedimentation and progression.The theory of cancer stem cell speculates that cancer stem cells were the real source of recurrent or metastatic tumors.Cancer stem cells will be one of the main targets of liver cancer treatment.The prevention and treatment of liver cancer recurrence or metastasis are quite difficult because liver cancer is resistant to traditional chemotherapy.Targeting the molecules involved in the metastasis of liver cancer WOuld be promising to cure those diseases.     

如何切实有效地开展胃肠肿瘤的转化医学研究

转化医学作为医学发展的新理念,虽然定义尚未明确,但其作为连接临床医学和实验室之间的桥梁,重要性已日益凸显。胃肠外科的发展始终体现着转化医学的理念。为开展转化医学研究,胃肠外科医师必须学习从临床中寻找研究问题,完整收集临床资料,重视团队协作,特别是跨学科的合作,同时充分利用各种资源。通过转化医学研究,胃肠外科医师能够进一步提高我国胃肠道肿瘤的综合诊治水平,提高患者长期生存率。     

Analysis of organ selectivity in the metastatic behavior of Dunn osteosarcoma

In the current study, the authors established a novel metastatic model to analyze organ selective metastasis by osteosarcoma, using a murine cell line, Dunn osteosarcoma. The lung, liver, kidney, and spleen were resected from syngeneic donor mice, and a tissue fragment of the respective organs was transplanted subcutaneously into a recipient mouse. Two weeks later, tumor cells were injected intravenously and the formation of metastatic deposits in the ectopic transplants was examined. Ectopic lung transplants had a significantly higher incidence of metastasis than either liver or kidney transplants. When enzymatically dispersed organ cells that were embedded in agar gel were transplanted, intravenous injection of tumor cells also resulted in a higher metastatic rate in lung transplants than in either liver or kidney transplants. Photomicrographs and microangiographs of the transplants showed equivalent revascularization of the different organs. Radiolabeled tumor cells were deposited in equivalent amounts in the ectopic transplants of the different organs after intravenous injection. In addition, in vitro growth of tumor cells was stimulated by medium conditioned with lung tissue in a dose-dependent manner. These results suggest that organ selective metastasis by osteosarcoma is not defined anatomically or hemodynamically, but may be caused by tumor cells responding to possible paracrine factors emanating from the lung.     

Molecular insights into prostate cancer progression: the missing link of tumor microenvironment

PURPOSE: Tumor cell genotype and phenotype have been considered the only determinants supporting cancer growth and metastasis. This review focuses on the published literature that suggests that tumor-microenvironment interaction has a decisive role in controlling local cancer growth, invasion and distant metastasis. As this review shows, genetic alterations in prostate cancer cells alone are not enough to confer metastatic status without a supporting tumor microenvironment. Effective therapeutic targeting requires a deeper understanding of the interplay between tumor and stroma. Approaches co-targeting tumor and stroma already show promise over the conventional targeting of tumor cells alone in preventing prostate cancer progression and eradicating preexisting or newly developed prostate cancers in bone and visceral organs. MATERIALS AND METHODS: A literature survey using the MEDLINE database was performed in basic and clinical publications relevant to tumor-host microenvironment interaction. Information pertinent to the biology and therapy of prostate cancer local growth and distant metastases was specifically emphasized. RESULTS: Tumor associated stroma actively fuel the progression of prostate cancer from localized growth to the invasion of surrounding tissues, and the development of distant bone and visceral organ metastasis. In concert with this progression tumor cells recovered from metastatic sites could represent a subpopulation of preexisting tumor cells or could be a newly acquired variant subsequent to tumor-stromal interaction. Experimental data from our laboratory and others suggest that permanent genetic and phenotypic changes occur in prostate cancer cells after 3-dimensional co-culture in vitro or when co-inoculated and grown with inductive stromal cells in vivo. These results support the idea that newly acquired variants are the dominant mechanism of prostate cancer progression. Intercellular communication between prostate cancer cells and organ specific stroma, including prostate and marrow stroma, could involve diffusible soluble and solid matrix molecules as mediators, leading to the development of metastasis. This presents a new opportunity for therapeutic targeting for the treatment of benign and malignant growth of the prostate glands. This review summarizes specific research implicating tumor-microenvironment interaction as the molecular basis of cancer progression, providing a rationale for targeting tumor and the tumor associated microenvironment in the management of androgen independent and bone metastatic prostate cancer progression in patients. CONCLUSIONS: Cancer is not a single cell disease. Aberrant cancer cells and their interactive microenvironment are needed for prostate cancer to progress to androgen independence and distant metastasis. It is highly plausible that newly evolved prostate cancer cell clones dominate cancer metastasis after cell-cell and cell-matrix interaction with the host microenvironment, rather than the selection or expansion of a preexisting prostate cancer cell clone(s). Based on this premise potential molecular targets in the microenvironment are especially emphasized. Further elucidation of the molecular mechanisms underlying tumor-stromal interaction may yield improved medical treatments for prostate cancer growth and metastasis.     

Hemangiopericytomatous meningioma metastasized to the liver: Report of a case and review of the literature

A 54-year-old male was admitted to our hospital for treatment of a liver tumor which was pointed out by screening ultrasonography. Computed tomography revealed a tumor in the right lobe of the liver measuring 7 cm in diameter. Angiography revealed a hypervascular tumor. A hepatocellular carcinoma or hypervascular metastatic tumor was suspected. A right hepatic lobectomy was performed. The patient had previously undergone operations for a hemangiopericytomatous meningioma in the occipital fossa in 1972 and 1977. The histological findings of the liver tumor were identical to those for hemangiopericytomatous meningioma, so the etiology was considered to be liver metastasis from the previous meningioma. Nineteen cases of extracranial metastasis of hemangiopericytomatous meningioma have been reported in the literature, but hepatic resections of this metastasizing tumor have been very rare.     

The molecular biology of pulmonary metastasis

Curing cancer requires the treatment of metastatic disease. Whether this is a patient with advanced disease and clinically apparent metastases, or if the patient with localized disease is at risk for development of dissemination, failure to control metastasis will result in a poor outcome. Here, we have presented a molecular guide to our current understanding of the processes underlying metastasis. Experimental clinical trials designed to further the understanding of metastasis are often limited by selection of patients with advanced disease. Therefore, our understanding of the processes involved in the metastatic cascade is limited by the availability of comprehensive experimental model systems. The study of metastasis relies most heavily on xenografts, tumors using human cell lines, or tumor tissue that can grow in mice. These models present a limited recapitulation of the patients. Xenograft models require some degree of immunosuppression on the part of the host, because mice with native immune systems will reject transplanted human tumors, preventing their growth. As a result, mice with immune defects ranging from depleted T cells (nude mice) to absent T, B, and NK cells (SCID-Beige) are used as hosts. As the evasion of the immune system is a key function demonstrated by the metastatic cancer cell, xenograft models, by necessity, subvert this step. Furthermore, recent studies have established that angiogenesis in transplanted tumors is different than in native tumors, further highlighting the limitations of these models. With these limitations, studies of metastasis may require development of models of autochthonous tumors, that is, tumors originating in the study animals. A number of cell lines of autochthonous murine tumors have been established that generate metastatic disease after implantation into mice. Moreover, some transgenic animals spontaneously develop metastatic tumors that, although occurring in genetically engineered animals, may represent the most complete model from early development to late effects. Finally, a very promising field of autochthonous tumor studies lies in work with companion animals (pets). Some dogs will have cancer, often with striking similarities to those of their human counterparts. These pets may represent an important study group, because they have autochthonous tumors, occurring spontaneously, in an outbred population. In all of these cases, the tumor, new vasculature, and the immune system are syngeneic with the host. In addition to the advances in model systems, advances in technology will further our understanding and ability to combat metastatic disease. As demonstrated, genomics is proving to be a powerful tool in identifying those at risk for metastasis. From these genetic signatures, molecular targets may be deduced from the genes altered in patients with poor prognoses. Furthermore, other molecular tools such as proteomic analysis may provide further information. Clearly, therefore, a synthesis of different technologies and complimentary information will be required to target metastases and improve the outcome for patients affected by them.     

Histologic Characteristics of Renal Cell Carcinomas with Lymph Node Metastasis

Background :
This study was conducted to determine if there are any specific histologic features that are associated with lymph node metastasis in renal cell carcinoma (RCC).
Methods :
TNM classification, histologic grade, mean nuclear volume, cell type, and histologic architecture of the tumors were evaluated in 66 patients who had undergone nephrectomy and lym-phadenectomy for RCC. In the 18 patients with positive lymph node metastasis, both primary lesions and metastatic lymph nodes were evaluated.
Results :
Lymph node status was correlated with primary tumor stage, venous involvement, and distant metastasis. The tumor grade was higher, and the mean nuclear volume was larger, in both primary and metastatic lesions of RCCs with lymph node metastasis than in tumors with no metastasis. In primary lesions of RCCs with lymph node metastasis, clear cell, alveolar, or cystic patterns were observed less frequently, and granular or spindle/pleomorphic cells and papillary or solid patterns, were observed more frequently, as compared to those lesions without metastasis. Comparison between primary and metastatic lesions in individual patients revealed no significant difference in grade or mean nuclear volume. The development of new cell types or histologic architectures, which was not noted in the primary lesions, was also a rare event in the metastatic lesions.
Conclusion :
Several characteristic histologic features, which may reflect the increased metastatic potential of the tumor, were observed in both primary and metastatic lesions in cases of RCC with lymph node metastasis. No substantial difference in histologic features was observed between the primary or metastatic lesions of individual patients.