肝门部胆管癌病理学及分子生物学特征的研究

目的探讨肝门部胆管癌的病理学和分子生物学特征。方法分析68例肝门部胆管癌病例的病理学类型、神经和淋巴结浸润发生率；比较不同分化程度组患者血清CA19-9和CEA含量；免疫组织化学法观察肿瘤预后相关基因产物Her-1、Her-2、p170、血管内皮生长因子（VEGF）及突变型p53蛋白；细胞角蛋白CK7、CK18、CK19、CK20；增殖相关蛋白Ki-67、Top-Ⅱ的表达情况。结果68例患者肿瘤病理学类型全部为腺癌，中、低分化腺癌占85．29％；神经浸润发生率为91．18％、淋巴结浸润率为27．94％。高、中、低分化腺癌组，患者血清CA19-9、CEA含量之间的差异元统计学意义（P〉0．05）。Her-1、Her-2、p170、VEGF和突变型p53阳性表达率分别为26．1％、21．7％、51．2％、36．O％和48．8％。CK7、CK18、CK19阳性表达率均为100％。Ki-67、Top-Ⅱ阳性率分别为93．3％、83．7％；Kappa检验显示，Ki-67与Top-Ⅱ对胆管癌细胞增殖程度的检验效果一致性较好（P〈0．01）。结论肝门部胆管癌以中、低分化腺癌为主；肿瘤具有很高的神经浸润发生率；血清CA19-9、特异性角蛋白检测有助于肝门部胆管癌的鉴别诊断；Ki-67与Top-Ⅱ对肿瘤增值程度的检测效果相当。     

肝门部胆管癌外科治疗策略

肝门部胆管癌（hilar cholangiocarcinoma）由Klatskin在1965年首次描述,是指发生在左肝管、右肝管、左右肝管分叉部和肝总管上段的胆管黏膜上皮恶性肿瘤。其男女发病率相近,约占全身恶性肿瘤的2．0％,占所有肝内外胆道肿瘤的60％。中位生存期12～24个月,5年的生存率为10．0％-45．0％。肝门部胆管癌解剖位置特殊．肿瘤易侵袭、浸润,外科手术治疗颇为棘手。然而,目前根治性切除仍然是肝门部胆管癌唯一可能获得治愈希望的方法。     

肝门部胆管癌预后因素分析

目的 探讨影响肝门部胆管癌的预后因素.方法 回顾性分析1996年1月至2007年5月中国医科大学附属第一医院收治的204例肝门门部胆管癌患者的临床资料.生存时间用中位数表示,生存分析采用Kaplan-Meier法,行Log-rank检验,对17个可能影响预后的因素进行单因素分析,有统计学意义的单因素再采用Cox回归模型进行多因素分析.结果 根治性切除中位生存时间为37个月,姑息性切除为18个月,胆道探查置管引流为11个月,剖腹探查为5个月,肝移植为25个月,五者比较差异有统计学意义(χ2=58.300,P<0.05).肿瘤最长径、门静脉或肝动脉侵犯、局部浸润、残端情况、肿瘤分化程度、淋巴结转移、手术方式对预后有影响(χ2=6.541,8.159,5.837,4.365,13.748,5.346,9.472,P<0.05).Cox回归模型多因素分析表明手术方式、肿瘤细胞分化程度是影响预后的独立因素(b=0.287,0.320,P<0.05).结论 根治性切除是肝门部胆管癌最重要的预后因素,合理的围手术期处理能提高患者的生存率.     

肝门部胆管癌预后因素分析

Objective To investigate the prognostic factors of hilar cholangiocarcinoma. Methods The clinical data of 204 patients with hilar cholangiocarcinoma who were admitted to The First Affiliated Hospital of China Medical University from January 1996 to May 2007 were retrospectively analyzed. The survival rate was calculated using the Kaplan-Meier method and Log-rank test. Seventeen factors that may have influenced prognosis were analyzed by univariate analysis. Factors that were statistically significant were further analyzed by the Cox regression model. Results The median survival times of patients who received radical resection, palliative resec-tion, bile duct exploration and catheter drainage, exploratory laparotomy, and liver transplantation were 37, 18, 11,5 and 25 months, respectively, and there was a significant difference between the 5 groups (χ2 = 58. 300, P < 0. 05). The prognostic factors included tumor size, portal vein or hepatic artery invasion, local invasion, resection margin, tumor grading, lymph node metastasis and surgical procedure (χ2 =6. 541, 8. 159, 5. 837, 4. 365, 13.748, 5.346, 9.472, P <0.05). Multivariate analysis demonstrated that surgical procedure and tumor grading were independent prognostic factors (6=0.287, 0. 320, P <0.05). Conclusions Radical resection is the most important prognostic factor of hilar cholangiocarcinoma. Appropriate perioperative care can improve the survival rate.     

肝门部胆管癌预后因素分析

Objective To investigate the prognostic factors of hilar cholangiocarcinoma. Methods The clinical data of 204 patients with hilar cholangiocarcinoma who were admitted to The First Affiliated Hospital of China Medical University from January 1996 to May 2007 were retrospectively analyzed. The survival rate was calculated using the Kaplan-Meier method and Log-rank test. Seventeen factors that may have influenced prognosis were analyzed by univariate analysis. Factors that were statistically significant were further analyzed by the Cox regression model. Results The median survival times of patients who received radical resection, palliative resec-tion, bile duct exploration and catheter drainage, exploratory laparotomy, and liver transplantation were 37, 18, 11,5 and 25 months, respectively, and there was a significant difference between the 5 groups (χ2 = 58. 300, P < 0. 05). The prognostic factors included tumor size, portal vein or hepatic artery invasion, local invasion, resection margin, tumor grading, lymph node metastasis and surgical procedure (χ2 =6. 541, 8. 159, 5. 837, 4. 365, 13.748, 5.346, 9.472, P <0.05). Multivariate analysis demonstrated that surgical procedure and tumor grading were independent prognostic factors (6=0.287, 0. 320, P <0.05). Conclusions Radical resection is the most important prognostic factor of hilar cholangiocarcinoma. Appropriate perioperative care can improve the survival rate.     

46例肝门胆管癌的诊断和治疗

目的总结7年肝门胆管癌的外科诊断和治疗经验。方法对5年间收治的46例肝门胆管癌患者的临床表现、影像学特征、肿瘤标志物和手术方式进行分析。结果肝门胆管癌的主要临床表现为黄疸、腹痛、发热、陶土色大便、呕吐、纳差、呃逆;血清糖链抗原CA19-9的阳性率较高;B超、CT、PTC、ERCP、MRCP和肝动脉造影在影像学表现上各有其特点;治疗:5例行肝动脉灌注化疗;25例行手术治疗,其中11例行根治性切除,4例行胆管内引流术,6例行外引流术,4例行姑息性手术。术后并发症为肺部感染2例,胆道感染2例,脓毒症1例,切口感染1例,住院期间死亡3例。结论肝门胆管癌诊断应根据其临床表现、实验室检查、联合应用多种影像学和免疫组化检查进行,根治切除肝门胆管癌应做到切缘无癌残留,对不能切除的患者可以进行胆道引流术或外科旁路手术,不能手术的患者可以选择肝动脉灌注化疗。     

肝门部胆管癌的外科治疗和预后相关因素分析

目的 探讨肝门部胆管癌的外科治疗策略及预后相关因素.方法 对1990年1月至2005年12月144例行手术切除治疗的肝门部胆管癌患者的临床资料进行回顾性分析.144例患者中,男性102例,女性42例;年龄36～74岁,平均63岁.根治性切除(R0组)86例(59.7%),镜下切缘阳性(R1组)34例(23.6%),肉眼切缘阳性(R2组)24例(16.7%).R0组和R1组的120例患者中,Bismuth-Corlette分型Ⅰ型28例(23.3%),Ⅱ型49例(40.8%),ⅢA型10例(8.3%),ⅢB型19例(15.8%),Ⅳ型14例(11.7%);TNM分期Ⅰ期19例(15.8%),Ⅱ期80例(66.7%),Ⅲ期16例(13.3%),Ⅳ期5例(4.2%);组织病理学分级:高分化(G1)41例(34.2%),中低分化(G2、G3、G4)79例(65.8%);无淋巴结转移者(N0)62例(51.7%),有淋巴结转移者(N1、N2)58例(48.3%);T1分期42例,T2～3分期78例;无血管侵犯者86例,有血管侵犯者34例.R0组和R1组120例患者均施行伴部分肝切除+区域淋巴结清扫术.结果 中位生存期:R0组46.8个月,R1组18.3个月,R2组11.2个月.生存率:R0组和R1组的120例患者术后1、3、5年总生存率分别为60.2%、36.1%、29.4%,R0组预后好于R1组(P<0.01),R1组预后好于R2组(P=0.031);高分化癌患者预后较好(P=0.003);有淋巴结转移患者预后极差(P<0.01);T1期患者的预后好于T2～3分期患者(P=0.030).有血管侵犯者预后较差(P=0.047).结论 肝门部胆管癌的病理类型、临床分期以及是否行根治性切除是影响预后的主要因素.联合不同范围的肝切除及淋巴结清扫术对提高肝门部胆管癌的根治率和生存率有重要的意义.     

Resection of lung metastases. Results and prognostic factors

249 thoracotomies for lung-metastases were performed in 202 patients at the 2nd Dept. of Surgery of the Vienna University Clinic till 1989. Age ranged from 2 to 78 years, 14 patients were younger than 18 years. The primary tumour was a carcinoma in 143 cases, a sarcoma in 45 cases and a melanoma in 14 patients. The primary tumour in the young patients was osteosarcoma in 8 cases, Ewing sarcoma in 2 cases and Wilms tumour in 2 patients. With a minimal follow up period of 2.5 years the 5-years-survival after metastasectomy was 42% for patients with carcinoma and 29% for the sarcoma patients. None of the patients with melanoma survived 5 years. A significant difference was found between the carcinoma and sarcoma groups with respect to survival rate. A prognostic factor was the disease-free interval in carcinoma patients. Actuarial post-thoracotomy survival in patients with osteogenic sarcoma was 34% at 5 years and 18% in the soft-tissue sarcoma group. Size of lesion, vitality of the metastases and the disease free interval correlated with survival in the osteogenic group, whilst the number of lesions was of importance in the soft-tissue group. On account of the lesser functional morbidity and the enablement to assess both lungs for treatment, the median sternotomy is recommended for cases with bilateral lung metastases. The results justify an aggressive surgical approach for the treatment of lung metastases.     

Liver resection for hilar and peripheral cholangiocarcinomas: a study of 62 cases.

OBJECTIVE: To analyze a single center's 14-year experience with 62 consecutive patients with hilar (HCCA) and peripheral (PCCA) cholangiocarcinomas. SUMMARY BACKGROUND DATA: Long-term survival after surgical treatment of HCCA and PCCA has been poor. METHODS: From March 1981 until December 1994, 62 consecutive patients with HCCA (n = 28) and PCCA (n = 34) underwent surgical treatment. The operations were individualized and included local excision of the tumor and suprapancreatic bile duct, lymph node dissection, vascular reconstruction, and subtotal hepatectomy. Clinical and pathologic risk factors were examined for prognostic influence. RESULTS: Patients were followed for a median of 25 months (12-102 months). Postoperative morbidity and mortality (at 30 days) were 32% and 14%, respectively, for HCCA and 24% and 6% for PCCA. The survival rates for HCCA and PCCA were 79% (+/-8%) and 67% (+/-8%) at 1 year; 39% (+/-10%) and 40% (+/-9%) at 3 years; and 8% (+/-7%) and 35% (+/-10%) at 5 years, respectively. The median survival was 24 (+/-4) months for HCCA and 19 (+/-8) months for PCCA. The disease-free survival rates for HCCA and PCCA were 85% (+/-10%) and 77% (+/-9%) at 1 year; 18% (+/-11%) and 41% (+/-12%) at 3 years; and 18% (+/-11%) and 41% (+/-12%) at 5 years, respectively. Nearly 80% of these patients had TNM stage IV tumors. With HCCA, no risk factors were associated with patient survival. For PCCA, multiple tumors (relative risk [RR] = 3.5; 95% confidence interval [CI] = 1.2-10.5) and incomplete resection (RR = 8.3; 95% CI = 2.3-29.6) were independently associated with a worse prognosis. For HCCA, there was a trend for lower disease-free survival in females (p = 0.056; log rank test). For PCCA, tumor size >5 cm was the only factor associated with disease recurrence (p = 0.024; log rank test). CONCLUSIONS: Even though rare, 5-year survival by resection can be achieved in both HCCA and PCCA, but new adjuvant treatments are clearly needed.     

Major hepatectomy for hilar cholangiocarcinoma type 3 and 4: prognostic factors and longterm outcomes

BACKGROUND: Radical operation for hilar cholangiocarcinoma, including major hepatectomy with vascular resection, seems to improve longterm survival. This study retrospectively evaluates several prognostic risk factors that can influence survival after resection of types 3 to 4 Klatskin tumors. STUDY DESIGN: Between 1984 and 2003, 59 patients (36 men and 23 women) with types 3 to 4 hilar cholangiocarcinoma underwent liver resection with curative intent. Medical records and pathologic findings were reviewed to assess prognostic risk factors and survival. Disease-free and overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Survival rates at 1, 3, and 5 years were 82%, 45%, and 20% respectively. In-hospital mortality was 5% and morbidity was 42%. In multivariable analysis, male gender (relative risk [RR] = 5.4; 95% CI, 2.2 to 13.5), absence of preoperative chemotherapy (RR = 4; 95% CI, 1.5 to 10.7), R1 biliary tract margin (RR = 2.6; 95% CI, 1.1 to 4.4), and metastatic celiac lymph nodes (RR = 19.9; 95% CI, 4 to 71.4) were found to be independent factors for overall survival. Pedicular metastatic lymph nodes were not associated with poorer overall survival. If biliary positive-margin is the only risk factor, the 5-year estimated overall survival is 70%. CONCLUSIONS: Major hepatectomy can improve outcomes of hilar cholangiocarcinoma. Compared with nonoperative treatment or R0 hepatectomy, R1 resection in patients with no other risk factor can offer longterm survival.     

原位肝移植治疗肝门胆管癌

目的总结原位肝脏移植(OLT)治疗肝门胆管癌的适应证及临床疗效。方法回顾性分析2003年3月至2006年2月对6例肝门部胆管癌患者施行OLT的临床资料。结果6例患者的手术切除率和根治切除率均为100%,除1例因并发症于术后9d死亡外,其余均健康存活,现已分别存活22,16,15,10和1个月,生活质量良好,未见肿瘤复发和转移。结论常规无法根治切除的肝门胆管癌可作为原位肝移植的适应证。     

Resection of hepatic hilar liver cancer

From January 1970 to January 1987, hepatic hilar liver cancer (or central type of hepatic cancer) resection was done in 51 cases. The resection was often extremely difficult, and sometimes complete occlusion of the hepatic blood supply was needed when the tumor lied close to, or already invaded the great blood vessels. The 1-, 3-, and 5- year postoperative survival rates were 65.7%, 45.3%, and 38.8%, respectively, in contrast to 93.8%, 86.1%, and 80.1% (P less than 0.001) obtained in 51 cases of peripheral type liver cancer of similar tumor size during the same period. It is considered that the difficulty involved in the resection of such a cancer, the limited extent of resection, and the easy entrance of tumor cells into the blood stream may explain the poor prognosis.     

Surgical approach to bismuth Type I and II hilar cholangiocarcinomas: audit of 54 consecutive cases

OBJECTIVE: To clarify the optimal surgical strategy for Bismuth type I and II hilar cholangiocarcinomas. SUMMARY BACKGROUND DATA: Local or hilar resections is often performed for Bismuth type I and II tumors; however, reported outcomes have been unsatisfactory with a high recurrence and low survival rate. To improve survival, some authors have recommended right hepatectomy. However, the clinical value of this approach has not been validated. METHODS: Records of 54 consecutive patients who underwent resection of a Bismuth type I or II hilar cholangiocarcinoma were analyzed retrospectively. Through 1996, bile duct resection or the smallest necessary hepatic segmentectomy was performed. Beginning in 1997, choice of resection was based on the cholangiographic tumor type. For nodular or infiltrating tumor, right hepatectomy was indicated; for papillary tumor, bile duct resection with or without limited hepatectomy was chosen. RESULTS: Right hepatectomy was performed in 5 (20.8%) of 24 patients through 1996 and was done in 22 (73.3%) of 30 patients from 1997 (P = 0.0003). In patients without pM1 disease, R0 resection was achieved more frequently in the later period than in the earlier period (23 of 24 = 95.8% vs. 13 of 21 = 61.9%, P = 0.0073), which lead to better survival (5-year survival, 44.3% vs. 25.0%, P = 0.0495). In the 31 patients with nodular or infiltrating tumor, who tolerated surgery and did not have pM1 disease, survival was better in the 18 patients who underwent right hepatectomy than in those who did not (5-year survival, 62.9% vs. 23.1%, P = 0.0030). In cases of papillary tumor, bile duct resection with or without limited hepatectomy was sufficient to improve long-term survival. CONCLUSIONS: The surgical approach to Bismuth type I and II hilar cholangiocarcinomas should be determined according to cholangiographic tumor type. For nodular and infiltrating tumors, right hepatectomy is essential; for papillary tumor, bile duct resection with or without limited hepatectomy is adequate.     

Results of surgical treatments and prognostic factors for hepatic hilar bile duct cancer

Results of surgical treatments for 57 patients who underwent resection for hepatic hilar bile duct cancer between 1984 and 1997 were studied. Bile duct resection was performed in eight patients, and combined resection of bile duct and liver was performed in 49 patients, of whom vascular reconstruction was added in 15 patients and pancreatoduodenectomy (PD) in six patients. All the operations of bile duct resection that were not combined with hepatectomy were non-curative. In the patients who underwent combined resection of the bile duct with liver, outcomes of the patients with well-differentiated adenocarcinoma were better than those with other lower-grade tumors. The factors related to the degree of tumor extension, such as serosal invasion, lymph node metastasis, lymphatic vessel invasion, perineural invasion, venous vessel invasion, and vascular involvement, were other factors which significantly influenced the survival. Curative resection yielded significantly better results than non-curative resection. Of all these variables, good tumor differentiation and vascular involvement were recognized as important prognostic factors by multivariate analysis. Most of the postoperative deaths were encountered in patients who underwent additional operations to hepatectomy, such as vascular reconstruction or PD. Improvement of surgical techniques and perioperative care has yielded better outcomes of vascular reconstruction. However, the application of hepatopancreatoduodenectomy should be limited due to poor outcomes of widespread bile duct cancer of which the histological grade is usually low. Whereas prognosis of bile duct cancer involving the hepatic hilus is mainly determined by the biologic characteristics of the tumor, surgeons should consider the fact that most patients die of local recurrence regardless of the biologic character of the tumor when curative resection is not performed. Received for publication on April 10, 1998; accepted on July 27, 1998     

Univariate and multivariate analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma

Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival.     

Resection of the inferior vena cava and tumor of the excretory duct: diagnostic and prognostic problems

The authors present a case of transitional cell carcinoma of the renal pelvis with inferior vena cava involvement. Two types of vena cava involvement are discussed: thrombus or nodes. The CT scan appears to be the best examination to preoperatively diagnose the type of invasion in order to be able to select the optimal treatment. However, these two types of involvement have a poor prognosis and surgery abstention may be justified. Chemotherapy may be useful in these cases.     

Resection of hilar cholangiocarcinoma--a European and United States experience

Improvements in preoperative imaging, patient selection, and refined operative techniques have allowed a more radical surgical approach to hilar cholangiocarcinoma. A total of 269 patients with histologically proven cholangiocarcinoma were treated during a 20-year period under the direction of one surgeon (LHB) over three separate time periods in different institutions: 131 patients at the Hepatobiliary Unit of Hammersmith Hospital, London, England, from January 1977 to September 1985; 48 patients at Inselspital, University of Bern, Switzerland, between October 1986 and October 1990; and 90 patients at Memorial Sloan-Kettering Cancer Center, New York, between March 1991 and April 1997. An increase in the use of concomitant hepatectomy was noted over these time periods, paralleled by an increase in achieving negative margins and in survival. Hilar cholangiocarcinoma should not be considered an incurable disease, but patients should be aggressively evaluated for possible curative resection before any intervention is performed. Good long-term results can be achieved and cure is possible provided a complete tumor resection with negative margins is obtained. Received for publication on May 25, 1998; accepted on June 1, 1998