细胞角蛋白7、18、19在壶腹周围癌淋巴结微转移灶的检测及临床意义

目的探讨细胞角蛋白对壶腹周围癌淋巴结微转移的检出率,并分析淋巴结微转移与临床预后的关系,为提高临床综合疗效提供理论依据。方法应用细胞角蛋白(CK7、CK18、CK19)单克隆抗体,对45例壶腹周围癌根治术后经病理常规HE染色阴性的186枚淋巴结进行免疫组织化学技术(S P法)检测,结合随访资料进行临床预后分析。结果45例壶腹周围癌根治术后HE染色阴性的186枚周围淋巴结中,有9例(20%、9/45)34枚(18.3%、34/186)淋巴结中检出微小转移灶。免疫组化诊断微转移阳性组和阴性组的1年复发率分别是88.9%(8/9)和16.7%(6/36),两组间有显著性差异(P<0.05)。不同单克隆抗体(CK7、CK18、CK19)检测发现,CK19在壶腹周围癌186枚淋巴结的检出率高达15.6%(29/186),CK19与壶腹周围癌淋巴结微转移关系密切(P<0.05)。结论对常规病理检查阴性的壶腹周围癌淋巴结进行CK7、CK18、CK19检测有助于发现微转移灶,为提高淋巴结微转移诊断的准确性、判断临床分期、估计预后及选择辅助治疗提供理论依据。CK系列单抗联合检测可提高淋巴结微转移阳性检出率。     

壶腹及壶腹周围癌51例治疗分析

目的 探讨壶腹及壶腹周围癌的手术治疗措施。方法 对３２例壶腹及壶腹周围癌患者行Ｗｈｉｐｐｌｅ手术。３２例中术前因胆道梗阻合并感染行胆囊造瘘引流１０例;术中胆囊造瘘引流１６例,Ｔ管引流４例。多孔硅胶管插入胰管５ｃｍ支撑,另一端置空肠引流３２例。与同期内未行手术治疗者１９例对比。结果 术后胆瘘１例,胰瘘１例,无手术死亡者,全组平均随访５年,１、３、５年生存者分别为３１例、１７例、１１例,５年生存率为３     

壶腹周围癌某些相关基因表达与预后的关系

胆总管在穿经十二指肠壁时与胰管汇合后略膨大,称胆胰壶腹（简称壶腹）。壶腹及其外周环绕的括约肌向十二指肠腔突出,使二十指肠粘膜隆起形成十二指肠乳头。在壶腹周围（包括壶腹）上述组织结构所发生的肿瘤统称壶腹周围肿瘤,可为良性或者恶性,以恶性居多。恶性肿瘤包括来自壶腹、胆总管下端、十二指肠乳头和胰头的癌肿,临床上把前三者统称壶腹部癌,连同胰头癌统称壶腹周围癌。     

壶腹周围癌胰十二指肠切除术预后因素

胆总管下端、壶腹、十二指肠乳头及胰头的恶性肿瘤因为临床表现相似,临床上统称壶腹周围癌。壶腹周围癌的早期诊断和治疗方面一直存在困难,唯一可能治愈的方法是手术切除,如胰十二指肠切除术（pancreaticoduodenectomy,PD）。肿瘤根治术后整体长期存活率是外科医牛所共同关注的问题。就PD术预后而言,壶蝮部癌及十二指肠乳头部癌最高,远端胆管癌次之,胰头癌最差。对于壶腹周旧癌行PD术后存活率的相关因素,得到公认的包括肿瘤病理来源、细胞分化程度、TNM分期等。而近年国内外在该方而又有了深入研究,现就壶腹周围癌PD术后预后相关因素的研究进展综述如下。     

壶腹周围癌各种切除手术的评价

主持人 :胆胰肠结合部包括胆总管胰后段和壶腹、胰头及其主副胰管 ,十二指肠二、三、四段 ,以及与这些脏器相关的血管、淋巴和神经等结缔组织。这一区域在解剖上复杂多变 ,是连接胆道、胰腺、胃肠道的枢纽 ,且变异多见 ;在功能上较复杂 ,一些功能性的改变亦能引起严重的后果 ;在诊断和治疗上比较棘手 ,直观性、创伤小的诊断方法较少 ,恶性病变的根治范围广、并发症多 ,使该区域恶性肿瘤的根治率低 ,对于性质难以判断的肿块 ,在处理上更是进退维谷。近年来 ,胆胰十二指肠结合部外科取得了较大进展 ,内镜手术在某些疾病的治疗上取代了传统方法 ;各种扩大、改良根治术和区域性切除术在原Whipple手术的基础上得以开展 ,其远期疗效尚有待于进一步探讨。本期特邀国内肝胆胰外科界知名专家撰写笔谈 ,针对该区域较新颖或者有必要重申的手术方法进行详细讲解 ,使之更趋规范化、科学化。同时 ,针对临床工作中经常碰到的难题进行解答与讨论 ,力图能为广大读者在胆胰肠结合部外科疾病的认识上提供一些新颖的或更清晰的思路。     

黄疸前期壶腹周围癌的早期诊断

本文报告我科１９８８年以来收治的１５例上腹隐痛不适、隐痛伴发热，Ｂ超显示胆囊及胆道扩张但无黄疸存在的病人，经十二指肠低张造影、ＣＴ、ＥＲＣＰ等检查，诊断为黄疸前期壶腹周围癌、手术切除率６６．７％，随访５年，５年以上生存４例，本文讨论对上腹隐痛不适，伴发热病例（类似胃炎、胆囊炎）不能忽视Ｂ超筛选，发现胆囊胀大，胆道扩张者，应进一步检查，及时发现那些黄疸前期壶腹周围癌病例，以提高手术切除率和延长生存时     

黄疸前期壶腹周围癌诊治体会

目的：探讨壶腹周围癌早期诊断的相关因素。方法：对我院1988年1月至2002年11月收治的19例黄疸前期壶腹周围癌的临床资料作回顾分析。结果：本组19例,手术治疗18例,切除12例,切除率为66．7％(12／18)。病死率为5．3％(1／19)。全组病人经BUS检查,其阳性率为91．7％(22／24),壶腹周围占位的诊断率为57．9％(11／19)。CT检查15例,阳性发现率为86．7％(13／15),壶腹周围占位的诊断率为73．3％(11／15)。当BUS,CT,ERCP等影像学联合检查时：阳性率达100％,壶腹周围占位的诊断率为94．7％(18／19)。这些阳性发现主要包括胆胰管的扩张以及发现壶腹周围的占位性病变等。结论：壶腹周围癌在黄疸前期是有其临床特点和(或)影像学异常改变的,临床医生应针对可疑病人进行全面细致的检查,才可以减少误漏诊情况的发生。提高早期诊断率和手术切除率,改善疗效。     

壶腹周围癌局部扩大切除术

目的：探讨壶腹周围癌的局部切除术的改进方法，方法：对4例壶腹腺癌和十二指肠乳头腺癌实施局部扩大切除术，将部分十二指肠降段，胆胰管远段，局部1cm厚度的胰腺组织连同壶腹周围癌一并切除，关闭十二指肠两断端，将近段空肠分别与胆胰管，胰头断面和十二指肠上部吻合，结果：标本切缘均无癌组织；术后胰瘘1例，经保守治疗后痊愈；术后4-24个月随访无复发及其他并发症发生。结论：该术式操作简单，对早期壶腹周围癌能够达到根治目的。     

壶腹周围癌的诊断与治疗

本文报告壶腹周围癌１６８例，行胰十二指肠切除术６２例，全胰切除术互例，总切除率为３７．５％，切除率最高者为Ｖａｔｅｒ氏壶腹癌和十二指肠降部癌，分别为８８．０％和８５．０％，而胰头癌切除率仅为１４．９％。术后发生并发症２０例，占１１．９％。手术死亡９例，死亡率为为５．４％。全部获得随诊，切除组３年和５年生存率分别为３２．１％和１２．４％。未切除组均行胆肠内引流术，平均生存时间为５．２月。强调提高壶腹周围癌治疗水平的关键在于早期诊断与早期手术。     

Detection and Prediction of Micrometastasis in the Lymph Nodes of Patients With pN0 Gastric Cancer

Background:The clinicopathologic significance of micrometastasis (MM) and tumor cell microinvolvement (TCM) in regional lymph nodes as identified by immunohistochemical staining for cytokeratin expression was evaluated in patients with node-negative gastric cancer.Methods:MM was defined as tumor cells with stromal reaction, and TCM was defined as individual tumor cells without stromal reaction. We investigated 1761 lymph nodes obtained from 67 gastric cancer patients whose diagnosis showed no lymph node metastasis by routine histological examination. The depth of tumor invasion was T1 (submucosa) in 33 patients and T2 (muscularis propria and subserosa) in 34 patients. The lymph nodes were examined immunohistochemically for the presence of tumor cells using anti-cytokeratin AE1/AE3 monoclonal antibody. Both the biopsy tumor specimens obtained prior to surgery and the resected primary tumors were immunostained with E-cadherin (E-cad) monoclonal antibody.Results:Thirty (1.5%) of the 1761 lymph nodes showed MM and/or TCM. MM with or without TCM was found in 10 patients, and TCM alone was found in 4 patients; 6 (18.2%) of the 33 patients with T1 tumor and 8 (23.5%) of the 34 patients with T2 tumor had occult lymph node metastasis. The 5-year survival rate was worse among those with MM with or without TCM, than among those without MM. Nearly all of the patients with MM and/or TCM had reduced or negative E-cad expression in the primary tumor.Conclusions:We demonstrated that the incidence of MM and/or TCM in the lymph nodes of patients with gastric cancer is quite high, and that such metastasis is associated with the prognosis of patients with pN0. Examination of E-cad expression in biopsy tumor specimens may be useful for predicting MM and/or TCM.     

大肠癌前哨淋巴结微转移的检测及其临床意义

为探讨大肠癌前哨淋巴结（SLN）微转移（MM）的检测方法及其临床意义,我们对64例行根治性手术的DukesB期大肠癌患者SLN进行定位;应用常规HE染色联合免疫组化SIP法染色,对定位成功的122枚SLN中细胞角蛋白20（CK20）及端粒酶进行检测,并分析其表达与I临床病理因素的相关性。结果显示：（1）SLN定位成功61例（95．3％）,共获取SLN122枚。（2）定位成功的61例中,有6例9枚SLN常规HE染色阳性;余55例113枚SLNHE染色阴性,其中免疫组化染色CK20阳性15例（27．3％）,端粒酶阳性12例（21．8％）,两者联合检测SLNMM阳性21例（38．2％）。（3）DukesB期大肠癌患者SLNMM（＋）组癌的复发转移率明显高于同期SLNMM（-）组（P〈0．05）,生存率明显降低（P〈0．05）;而与DukesC期复发转移率及生存率比较,差异无统计学意义（P〉0．05）。（4）SLNMM（-）组患者的复发转移率、生存率与同期DukesC期患者比较,差异有统计学意义（P〈0．05）。（5）DukesB期大肠癌患者SLNMM的发生与患者年龄、性别及肿瘤侵犯肠管周径、生长方式、生长部位均无显著相关,而与肿瘤分化程度及大小、外周血癌胚抗原（CEA）值显著相关。结果表明,应用免疫组化法联合检测CK20和端粒酶,可提高大肠癌SLNMM的检出率;大肠癌SLNMM的检出能精确大肠癌的Dukes分期,有助于指导术后的辅助治疗和预后判断。     

肝癌外周血微转移检测意义及其问题

目的明确外周血微转移检测在肝细胞癌（hepatocellular carcinoma，HCC）转移复发中的诊断价值。方法通过回顾文献分析HCC外周血微转移检测的方法及意义。结果HCC的外周血微转移检测目前主要有播散细胞检测与HCC特异mRNA标记检测两类，从理论上来说都被认为是早期检测转移复发的理想方法，但不同实验研究间普遍存在着相互矛盾的结论，调整改进检测手段与时间亦未能够彻底解决检测结论的冲突。结论外周血微转移检测对于深入理解HCC转移复发机理和完善临床治疗有很大意义，但理论与应用中均存在着有待改进的地方，该技术的不断完善将促进对转移复发的机理研究与检测应用。     

直肠癌淋巴结微转移标志物的比较研究

目的：评价直肠癌淋巴结CK20、CK19、CEA诊断微转移的敏感性、特异性，探讨微转移的临床病理意义。方法：采用免疫组织化学染色方法，以CK20、CK19、CEA为指标，检测36例直肠癌患者手术区域252枚淋巴结的微转移，对照组为淋巴结反应性增生的标本15例。结果：常规HE检测淋巴结转移阳性率7．94％，CK19、CK20、CEA阳性率分别为20．63％、23．02％、17.46％，均高于HE检测结果（P〈0．01）。三种抗体在淋巴结微转移阳性率存在统计学差异。19枚对照组淋巴结CK19阳性率47.37％，CEA阳性率10．53％．CK20表达阴性。CK20、CK19、CEA淋巴结微转移阳性率与3年复发率无统计学差异（P〉0.05）。结论：对常规病理检测未发现区域淋巴结转移的直肠癌，有必要辅以免疫组化方法检测其微转移，CK20是首先标志物。     

胃癌淋巴管生成、淋巴管浸润及淋巴结微转移的临床意义

目的探讨胃癌淋巴管生成、淋巴管浸润及淋巴结微转移的临床意义。方法免疫组化法检测68例胃癌原发灶中D2-40的表达及其中51例胃癌的791枚淋巴结中CK20和CKpan的表达，结合患者的l临床病理特征进行综合分析。结果胃癌HE染色淋巴管浸润（LVI-HE）和D240染色淋巴管浸润（LVI-IM）的阳性率分别为66．2％（45／68）和76．5％（52／68），差异无统计学意义（P=0．118）。LVI-IM阳性率与肿瘤浸润深度（P=0．044）、TNM分期（P=0．003）及存在淋巴结转移（P=0．000）有关。68例胃癌平均淋巴管密度（LVD）为（18．19&#177;7．44）个／HP.LVD升高与LVI-HE阳性（P=0．040）、LVI—IM阳性（P=0．001）、静脉浸润（P=0．037）、TNM分期较晚（P：0．020）及存在淋巴结转移（P=0．001）有关系。LVD值≥15个／HP者近期生存率较LVD值≤14个／HP者明显降低（P=0．032）。51例胃癌HE染色和CK（CK20或CKpan）染色检出淋巴结转移率分别为74．5％（38／51）和88．2％（45／51），791枚淋巴结的转移淋巴结检出率由HE染色的32．0％（253／791）提高到CK染色的41．5％（328／791），P〈0．001。CKpan的微转移检出率明显高于CK20（P=0．003）。微转移淋巴结数量与肿瘤大小（P=0．001）、LVIHE（P=0．040）、肿瘤浸润深度（P=0．018）及TNM分期（P=0．012）有关。微转移淋巴结的检出使淋巴结转移站别及TNM分期迁移：7例N0→N1，6例N1→N2，1例N2→N3；4例Ⅰb→Ⅱ，4例Ⅱ→Ⅲa，3例Ⅲa→Ⅲb，1例Ⅲb→Ⅳ。结论D2-40及CK检测在诊断淋巴管浸润和淋巴结微转移上优于HE检查。CK20和CKpan的联合检查有利于发现微转移淋巴结。肿瘤TNM分期越晚，越易发生淋巴结微转移。LVI-IM、LVD及淋巴结微转移三者都与胃癌淋巴结转移有关。LVD值较高者近期生存率较低。     

Pattern of Lymph Node Micrometastasis and Prognosis of Patients with Colorectal Cancer

Background: Studies of lymph node micrometastases in patients with colorectal cancer have ignored the prognostic significance of the number and level of lymph node micrometastases. The aim of this study was to clarify the prognostic significance of the status of lymph node micrometastases in histologically node-negative colorectal cancer.Methods: We used immunohistochemistry with anti-cytokeratin antibody CAM5.2 to examine 1013 lymph nodes in 42 patients (12 recurrent and 30 nonrecurrent) with histologically determined Dukes B colorectal cancer. Five serial 6-m sections were used for immunohistochemical staining. The frequency, tumor cell pattern, and number and level of lymph node micrometastases were compared between the recurrent and nonrecurrent groups.Results: Micrometastasis was confirmed in 16% (59/373) of lymph nodes in the recurrent group and 12% (77/640) of lymph nodes in the nonrecurrent group, and the frequency of lymph node micrometastases was 92% (11/12) in the recurrent group and 70% (21/30) in the nonrecurrent group. The tumor cell pattern in the metastatic lymph nodes was similar in the recurrent and nonrecurrent groups. Micrometastasis in four or more lymph nodes occurred more frequently in the recurrent group than in the nonrecurrent group (58% vs. 20%, P < .05), and micrometastasis to N2 or higher nodes occurred more frequently in the recurrent group than in the nonrecurrent group (92% vs. 47%, P < .01).Conclusions: The number and level of positive micrometastatic lymph nodes was significantly correlated with postoperative recurrence of histologically determined Dukes B colorectal cancer. This parameter is a useful prognostic indicator in histologically node-negative colorectal cancer and is helpful in planning adjuvant chemotherapy.     

实时荧光定量PCR检测胃癌淋巴结微转移及其临床意义

目的使用实时荧光定量PCR(qRT-PCR)法检测胃癌淋巴结的微转移情况,并探讨微转移的临床意义。方法收集我院2010年1～6月期间40例行胃癌根治术切除的281枚和10例行胃十二指肠溃疡手术切除的39枚,共计320枚淋巴结标本,以CEA、CK-19和CK-20为引物进行qRT-PCR检测其微转移情况,并分析微转移的临床病理特点。结果 40例胃癌患者中有28例(70.00%)、31枚(15.35%,31/202)淋巴结检测出有微转移。10例胃溃疡的39枚淋巴结标本,HE染色检测和qRT-PCR检测均为阴性。淋巴结微转移的阳性率与肿瘤分化程度、浸润深度和临床分期有关(P<0.05)。结论 qRT-PCR是检测胃癌淋巴结微转移敏感且特异的方法,对胃癌临床分期、判断预后以及治疗方案选择具有重要意义。     

CK19表达及其在结肠癌淋巴结微转移诊断中的应用

目的：研究用免疫组化方法检测CK19及其在结肠癌淋巴结微转移诊断中的应用与临床病理意义。方法：取材于50例结肠癌病人肿瘤组织及癌周淋巴结255枚,同时进行HE染色组织学检查和抗角蛋白19抗体的免疫组化检测。结果：50例结肠癌组织中CK19表达均为阳性。255枚淋巴结用HE染色检查阳性者56枚(22．0％),皆同时表达CK19阳性;另20枚淋巴结HE染色阴性,而CK19表达阳性。50例中有12例淋巴结中发现微转移,其中6例常规组织学检查属淋巴结转移阴性而免疫组化染色诊断表现为转移阳性。占常规病理检查淋巴结转移阴性者的21．4％(6／28)。随着肿瘤分期增加,淋巴结CK19表达阳性率亦增加。CK19表达阳性者预后较阴性者为差。结论：CK19免疫组化法是检测结肠癌淋巴结微转移的敏感而便捷的方法,而检测结肠癌微转移有助于判断肿瘤进展程度与预后。特别对在筛选组织学检查淋巴结阴性但存在微转移的病人有实用价值。     

How Many Lymph Nodes Properly Stage a Periampullary Malignancy?

The impact of lymphadenectomy in prognosis and staging in periampullary malignancies remains largely undefined. We examined all pancreaticoduodenectomies for periampullary carcinomas in the SEER cancer registry from 1993 through 2003. Overall, 5465 pancreaticoduodenectomies for nonmetastatic periampullary carcinomas were identified. The cohort was comprised of 62.5% pancreatic, 18.9% ampullary, 11.6% distal bile duct, and 7.0% duodenal cancers. A linear association between the number of lymph nodes (LNs) examined and overall survival was observed overall and for pancreas and ampullary cancers for node-negative (N0) disease. Median survival for all patients with localized, N0 disease improved from 24 to 31 months, with sampling of a minimum of 10 LNs, whereas 2 and 5-year survival improved from 52 and 29%, with <10 nodes examined to 58 and 37% with 10+ nodes examined (P < 0.001). A 1-month median survival advantage was seen in patients with node-positive disease when more than 10 lymph nodes examined (15 versus 16 months, P < 0.001). Significantly better median survival and cure rates are observed after pancreaticoduodenectomy for localized periampullary adenocarcinoma when a minimum of 10 lymph nodes are examined. This benefit likely represents more accurate staging. To optimize the prognostic accuracy and prevent stage migration errors in multicenter trials a minimum of 10 lymph nodes should be obtained and examined before the determination of node-negative disease. This paper was presented at the 2007 American Hepato-Pancreato-Biliary Association Congress in Las Vegas, Nevada, on Saturday, April 21, 2007.     

Micrometastasis to In-Transit Lymph Nodes From Extremity and Truncal Malignant Melanoma

Background: The sentinel lymph node (SLN) is the first lymph node in the regional nodal basin to receive metastatic cells. In-transit nodes are found between the primary melanoma site and regional nodal basins. To date, this is one of the first reports on micrometastasis to in-transit nodes.Methods: Retrospective database and medical records were reviewed from October 21, 1993, to November 19, 1999. At the UCSF Melanoma Center, patients with tumor thickness >1 mm or <1 mm with high-risk features are managed with preoperative lymphoscintigraphy, selective SLN dissection, and wide local excision.Results: Thirty (5%) out of 557 extremity and truncal melanoma patients had in-transit SLNs. Three patients had positive in-transit SLNs and negative SLNs in the regional nodal basin. Two patients had positive in-transit and regional SLNs. Three patients had negative in-transit SLNs but positive regional SLNs. The remaining 22 patients were negative for in-transit and regional SLNs.Conclusions: In-transit SLNs may harbor micrometastasis. About 10% of the time, micrometastasis may involve the in-transit and not the regional SLN. Therefore, both in-transit and regional SLNs should be harvested.Supported in part by a grant from the Eva B. Buck Charitable Trust.