Clinicopathological features and outcome of hepatic resection for intrahepatic cholangiocarcinoma in Japan

As a result of an increasing number of studies on the surgical treatment of intrahepatic cholangiocarcinoma (ICC), knowledge of its biological characteristics has been accumulating. We analyzed the clinicopathological features and outcome of 36 of 48 surgical patients with histologically proven ICC (75.0%) who underwent hepatic resection between March 1979 and July 1998. According to tumor location, 12 patients had the central type and 24, the peripheral type. The incidence of portal vein tumor thrombus and lymph node metastasis was higher in the central type than in the peripheral type. All 12 patients with the central type had stage IV disease, and none of them underwent complete resection, whereas 12 of the 24 patients with peripheral type tumors had stage IV disease; complete resection was achieved in 12 of the 24 patients with peripheral type tumors (50%). Outcome after resection was significantly poorer in the patients with the central type. The macroscopic type of lesion in the resected specimens was the mass-forming type in 15 patients (41.7%), the mass-forming + periductal-infiltrating type in 15 patients (41.7%), the periductal-infiltrating type in 3 patients (8.3%) and the intraductal growth type in 3 patients (8.3%). The macroscopic tumor type was associated with mode of tumor spread and outcome. All 3 patients with the intraductal growth type are alive without tumor recurrence 26–138 months after surgery. The survival rate was much higher in the patients with the mass-forming type than in those with the mass-forming + periductal-infiltrating type. Importantly, the outcome in the 17 patients who underwent resection for stage IV-B disease and who accounted for 47.2% of patients with resection in the present series was very poor, almost the same as that in the 12 patients who did not undergo resection. By selecting patients based on the biological characteristics of the tumor and taking into account patients' quality of life, complete surgical resection can be performed safely and is associated with long-term survival. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

Extended hepatic resection and outcomes in intrahepatic cholangiocarcinoma

Background/Purpose. The aim of this report was to assess the outcome of aggressive surgical treatment for intrahepatic cholangiocarcinoma. Methods. From 1984 to 2001, we encountered 64 patients with intrahepatic cholangiocarcinoma. Of the 64 patients, 50 patients who underwent surgical resection with macroscopically curative objectives (78%) were reviewed for surgical procedures and outcomes. Results. Hemi- or more extensive hepatectomy was required for surgical resection in 40 patients (80%). Overall hospital morbidity and mortality rates were 50% and 8%, respectively. Curative resection with pathological free margins was achieved in 34 patients (68%). The 1-, 3-, and 5-year patient survival and tumor-free survival rates were 61.6%, 37.6%, and 22.5%; and 55%, 11%, and 11%, respectively. Among the macroscopic types, all 9 patients with intraductal growth type are alive 11–75 months after surgery. Survival rates among patients who had undergone curative resection were significantly better than those in patients who had undergone noncurative resection, even when patients with the intraductal growth type were excluded. Nodal status did not affect patient survival. Conclusions. Although the overall survival rate after surgical resection remains unsatisfactory, long-term survival is possible through extended surgical resection with pathological free margins. Patients with the intraductal growth type of intrahepatic cholangiocarcinoma might have the best chance of being cured by surgical treatment.     

Surgical management of intrahepatic cholangiocarcinoma: A 31-year experience

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver. It is, though, a rare tumor and little is known regarding its natural history, clinicopathologic characteristics, or the outcomes of surgical therapy. We reviewed the experience of 61 patients with ICC seen by the surgical service at the Mayo Clinic over a 31-year period. Patient demographic and clinical data were recorded, as were survival statistics. Pathologic data were also obtained and patients stratified according to the TNM classification. Twenty-eight patients were resected for cure. Overall, 45 patients died of ICC. Of the patients resected for cure, survival at 3 years was 60%. No pathologic condition was found to be associated with the development of ICC. Overall survival correlated with stage of the tumor. Among patients resected for cure, stage did not correlate with survival. Prognosis for patients with ICC remains poor; resection, though, appears to prolong survival. Received for publication on May 8, 1997; accepted on July 3, 1997     

肿瘤负荷评分在获得根治性切除肝内胆管癌患者预后预测中的价值

目的 研究肿瘤负荷评分(tumor burden score,TBS)对肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)患者根治性切除术后预后的预测价值。方法 回顾性分析2005年1月至2011年12月在复旦大学附属中山医院肝肿瘤外科连续收治的322例行根治性切除术的ICC患者资料,随访截止至2014年4月。采用ROC曲线评价TBS预测总体生存率(OS)的准确性。多因素Cox回归分析影响ICC患者预后的独立因素。结果 中位随访时间44.0个月(范围2.7～100.5)。TBS将322例ICC患者分为低、中和高三个预后风险组(104例、176例和42例)。TBS与血清CA199(P=0.004)、术前中性粒细胞/淋巴细胞比值(NLR,P=0.001)、淋巴细胞/单核细胞比值(LMR,P<0.001)、肿瘤最大径(P<0.001)、肿瘤数目(P=0.001)、淋巴结转移(P<0.001)及TNM分期(P<0.001)显著相关。TBS预测ICC患者术后5年OS的曲线下面积(AUC)为0.632(P<0.001),高于NLR≥2...     

Extended right hepatic lobectomy with resection of inferior vena cava and portal vein for intrahepatic cholangiocarcinoma

We report a case of intrahepatic cholangiocarcinoma treated by extended right lobectomy and resection of the inferior vena cava (IVC) and portal vein. A 53-year-old man was referred with elevated serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GTP) levels on April 23, 1999. He was not jaundiced and did not have any symptoms. Endoscopic retrograde cholangiopancreatography (ERCP) revealed irregular strictures in both the anterior and posterior segmental ducts. Contrast-enhanced computed tomography (CT) scan demonstrated a low-density tumor with an unclear margin in the right lobe of the liver. The patient underwent extended right hepatic lobectomy and total caudate lobectomy. Partial resection of the IVC (6 cm) was performed under total hepatic vascular exclusion. The main portal trunk and left portal vein were resected and reconstructed with an end-to-end anastomosis. Macroscopically, a 5.0 × 5.0 × 4.5-cm periductal infiltrating-type tumor occupied the right hepatic parenchyma along the posterior and anterior segmental ducts. Histological examination revealed moderately differentiated tubular adenocarcinoma with marked perineural invasion. Lymph node metastasis was observed in the hepatoduodenal ligament and posterior surface of the pancreatic head. The resected margins of the common bile duct and left hepatic duct were free of tumor. The patient's postoperative course was uneventful, and he was discharged from hospital on the 28th postoperative day. Nine months after the operation, he suddenly developed obstructive jaundice, and died with recurrent disease. This is the first reported case of intrahepatic cholangiocarcinoma treated with major hepatectomy and resection of the IVC and portal vein except ex situ procedure. This aggressive surgical approach may offer hope for patients with intrahepatic cholangiocarcinoma involving the IVC. Received: March 27, 2000 / Accepted: August 8, 2000     

淋巴细胞和C反应蛋白比值在肝内胆管癌根治性手术预后中的意义

目的 淋巴细胞和C反应蛋白比值(LCR)是一种炎症评分,本研究旨在分析LCR评分在肝内胆管癌(ICC)患者行根治性切除术预后中的价值.方法 回顾性选取咸阳市中心医院2015年1月至2020年12月经病理确诊为ICC的157例患者为研究对象,收集患者的年龄、性别、白蛋白(ALB)、总胆红素(TBIL)、血管侵犯、肿瘤大小...     

升高的血清中性粒细胞/淋巴细胞比值与肝内胆管癌较差的预后有关

目的探讨术前血清炎症指标与肝内胆管癌预后之间的关系。方法回顾性分析接受R0肝切除治疗的382例肝内胆管癌患者的临床病理资料,应用最小P值法确定炎症指标截断值,将每个炎症指标分为高低两组。应用KaplanMeier法描绘生存和复发曲线,Cox回归模型分析影响其预后的因素。结果 NLR(中性粒细胞数/淋巴细胞数)≥2.30是ICC患者术后总体生存和肿瘤复发的独立危险因素。NLR≥2.30的患者其血清癌胚抗原水平较高,肿瘤直径较大、多发肿瘤比例高、淋巴转移和血管侵犯比例大。结论 NLR≥2.30是肝内胆管癌患者预后的独立危险因素,NLR≥2.30的患者其术后总体生存率较差,肿瘤复发率更高。     

The significance of hepatectomy for primary intrahepatic stones

(Received for publication on Aug. 13, 1998; accepted on Mar. 11, 1999)     

Macroscopic classification and preoperative diagnosis of intrahepatic cholangiocarcinoma in Japan

We reviewed the records of 64 patients with resected intrahepatic cholangiocarcinoma (ICC) according to the macroscopic classification proposed by the Liver Cancer Study Group of Japan, in which ICC is classified into three types based on the macroscopic appearance of the cut sur-face of the tumor: mass-forming, periductal-infiltrating, and intraductal growth types. There were 24 patients with the periductal-infiltrating type, 28 with the mass-forming type, and 12 with the intraductal growth type. The mass-forming type essentially showed expansive growth irrespective of hilar invasion. The periductal-infiltrating type of tumor exhibited diffuse infiltration along the portal pedicle, and preoperative planning of the resection procedure was similar to that for primary bile duct carcinoma of the hepatic confluence. Vascular resection and reconstruction was required in some patients with advanced disease. In the intraductal growth type of tumor, precise determination of tumor extent was difficult because of the ambiguity caused by abundant mucin secreted by the tumor and/or by the superficial mucosal spread of the tumor along the bile duct. Percutaneous transhepatic cholangioscopy provided the most reliable information for designing the operative procedure. The macroscopic classification is useful for preoperative diagnosis of tumor extent and for planning the surgical procedure. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

Intrahepatic cholangiocarcinoma: A diagnostic and therapeutic challenge

Objectives: Intrahepatic cholangiocarcinoma (ICC) is a rare tumor of the liver. The diagnosis and treatment of it are difficult. The present study reviewed the diagnostic pathways and operative results for ICC. Methods: A retrospective analysis was made of the clinical presentation, diagnostic pathways, and operative results of 20 patients with ICC who underwent hepatectomy from 1997 to 2004 in our institute. Results: The patients were predominantly female (female : male = 15:5), and ranged in age from 41 to 74 years (median 59.8). Abdominal pain was the main presenting symptom, and hepatomegaly was the commonest physical sign. Diagnosis relied mainly on ultrasound or computed tomography. Without biopsy, only two patients were correctly diagnosed with ICC before surgery. The median size of the tumor was 6 cm (range 1.6–12 cm). Major hepatectomy was carried out in 80% of patients. The operative mortality and morbidity were 15% and 40%, respectively. The median follow up was 18.3 months. Thirteen patients (65%) had recurrences at one or more sites, including, in decreasing frequency, the liver, abdominal lymph node, lung, bone, or skin. The median survival was 17.3 months and the 1‐year, 3‐year, and 5‐year survival rates were 60%, 45%, and 10%, respectively. Conclusions: The poor survival of patients with ICC was mainly due to the delay in diagnosis and the aggressive nature of the disease. The diagnosis of ICC relies on a high index of suspicion as there is no reliable tumor marker and imaging results are usually inconclusive. Radical hepatectomy remains the only chance of cure for ICC. The role of lymph node dissection, liver transplantation, and adjunctive chemotherapy in the treatment of patients with ICC remains to be determined.     

周围型肝内胆管细胞癌的诊断和治疗

目的 探讨周围型肝内胆管细胞癌(PICC)的诊断及外科治疗，提高其诊治水平。方法 总结分析1991～2000年间我科收治的46例PICC病人诊断、治疗及预后的资料。结果 (1)本病早期无特异性临床表现，部分病例可并存乙型肝炎(20％)、肝硬化(45％)，部分伴有肝内胆管结石(20％)，血清AFP升高(30％)；(2)影像学检查：B超、CT、MRI的诊断率分别为90．0％、95．4％及100．0％；(3)手术切除率为64．0％．全组病例的1、3、5年生存率分别为60．0％、33．0％及26．0％；(4)生存5年以上的12例病人中，直径≤3cm的小肝癌9例，包膜完整的肿块型直径位于3～5cm肝癌3例，术后均辅助性放射治疗和选择性肝动脉灌注化疗。结论影像学检查能在早、中期提供临床线索，但缺乏特异性血清肿瘤标志物，治愈性切除术加辅助治疗可获得良好生存率。     

Recurrence after surgical resection of intrahepatic cholangiocarcinoma

We aimed to assess the patterns of recurrence after surgery for intrahepatic cholangiocarcinoma (ICC) and the outcomes of treatment in patients with recurrence. From 1981 to 1999, 123 patients with ICC underwent hepatectomy. The 3-year and 5-year survival rates were significantly higher in patients after curative resection (n = 56; 53%, 50%) than in patients after noncurative resection (n = 67; 7%, 2%; P < 0.0001). In 54 patients followed-up after curative resection, the rate of recurrence after surgery was 46%. The recurrences were in the liver (56%), abdomen (disseminated; 24%), and lymph nodes (20%). The rates of recurrence were significantly higher in patients with various classifications of mass-forming ICC tumors (P = 0.039) than in those with other types of tumors, and in patients with tumors over 3 cm in greatest diameter than in those with tumors 3 cm or less (P = 0.006). Hepatic recurrence, abdominal dissemination, and intraductal recurrence were significantly related to tumors that included mass-forming ICC (P = 0.002), tumors that included periductal infiltrating ICC (P = 0.009), and tumors that included intraductal growth ICC (P = 0.038), respectively. Seven patients with recurrence underwent radiation, chemotherapy, immunotherapy, or surgical resection. Only 2 patients, with intrahepatic metastasis and intraductal recurrence, respectively, had good outcomes after surgery. The effectiveness of other treatments has not been established.     

末梢型肝内胆管细胞癌的诊断及外科治疗效果分析

目的 探讨末梢型肝内总胆管细胞癌（PIHCC）的诊断及外科治疗结果,以提高其诊治水平。方法 回顾性分析1970－1999年间外科治疗的20例PIHCC患者诊断、治疗及预后的资料。结果 （1）本病缺乏特异性临床表现,部分病例可并发乙型肝炎（35．0％）、肝硬化（45．0％）和血清AFP升高（25．0％）;（2）影像学检查：B超、CT、MRI及ECT的诊断率分别为90．0％（18／20）、94．4％（17／18）、3／3及4／3;（3）手术切除率为60％,全组病例的1、3、5年生存率分别为55．0％（11／20）、35．0％（7／20）及20．0％（4／20）,其中肝切除术病例分别为83．3％（11／12）、58．3％（7／12）、33．3％（4／12）;（4）生存5年以上的4例患者中,直径≤3cm的小肝癌3例、包膜完整的结节型大肝癌1例,且术后均辅助选择性肝动脉灌注化疗,有助于生存率的提高。结论 本病缺乏特异性血清肿瘤标志物,治愈性切除术（包括术后辅助治疗）可获得良好生存率。     

Resection of intrahepatic cholangiocarcinoma: a Western experience

We analyzed the results of an aggressive surgical approach to intrahepatic cholangiocarcinoma. Between 1990 and 1997, 30 of 42 patients with intrahepatic cholangiocarcinoma underwent resection with curative intent. Mean tumor size was 10 ± 5 cm, and the tumors were classified as TNM type III, IVa, and IVb in 63%, 34%, and 3% of the patients, respectively. All patients underwent hepaticoduodenal lymphadenectomy. Fifteen patients received adjuvant radio- and chemotherapy. The overall survival rates at 1, 2, and 3 years were 86%, 63%, and 22%, respectively, and the median survival time was 28 months. Tumor recurrence was the main cause of death. Three patients survived for more than 5 years, including 2 patients with no evidence of recurrence. Factors influencing survival were: presence of satellite nodules (P = 0.007) and lymph node invasion (P = 0.05). The width of the resection margin and the use of an adjuvant therapy had no impact on survival. Complete surgical resection may offer a chance for long-term survival in selected patients and may improve the quality of life of patients with more advanced disease. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

Intrahepatic cholangiocarcinoma in Hong Kong

We retrospectively analyzed the results of hepatic resection for patients with intrahepatic cholangiocarcinoma managed between December 1966 and January 1998 at the University of Hong Kong Medical Center, Queen Mary Hospital. There were 61 men and 40 women (mean age, 61.8 years). The clinical records of these patients were reviewed. A survival analysis was performed on the group of patients who had undergone hepatic resection. Twenty-one patients were treated conservatively. Non-resective (palliative) operations were performed in 32 patients. The median survivals after conservative management and palliative operation were 2.5 and 3.3 months, respectively. The remaining 48 patients underwent hepatic resection. The overall operative morbidity and mortality rates after hepatic resection were 41.7% and 16.7%, respectively. The median survival after hepatic resection was 16.4 months. The overall 1-, 3-, and 5-year survival rates after hepatic resection were 60.3%, 29.4% and 22.0%, respectively. Lymphatic permeation (P = 0.007) and hilar nodal metastases (P = 0.009) were found to be significantly associated with poor survival after hepatic resection. Hepatic resection is the treatment of choice for intrahepatic cholangiocarcinoma when it is resectable. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998     

Comparative clinicopathological study of resected intrahepatic cholangiocarcinoma in northeast Thailand and Japan

Northeast Thailand has a very high incidence of intrahepatic cholangiocarcinoma (ICC), which is closely linked to infestation by the liver fluke, whereas the etiology of ICC in Japan remains to be clarified. This study compared the clinicopathological features, the expression of p53 and c-erbB-2 proteins, and the proliferative activity of ICC in 19 Thai and 23 Japanese patients with ICC who were treated by hepatic resection. The average age of the Thai patients (55.8 years) was lower than that of the Japanese (61.3 years). All Thai patients presented with symptoms, whereas 8 Japanese patients were asymptomatic. There were no significant differences in preoperative liver function test values. Tumors were less likely to be located in the right lobe in the Japanese (34.8%) than in the Thai patients (63.2%). Peribiliary fibrosis and adenomatous hyperplasia in noncancerous hepatic tissues were much more frequently found in the Thai patients (P = 0.0010; P < 0.0001). No significant differences in the expression of p53 protein or c-erbB-2 protein were found between the two series of patients, but proliferative activity, evaluated on the basis of mean MIB1 labeling index, was significantly higher in the Thai patients (P < 0.001). The present study suggested a higher proliferative activity of ICC in Thai patients than in Japanese patients. Received for publication on Dec. 16, 1999; accepted on Jan. 14, 2000     

Clinical significance of intrahepatic biliary stricture in efficacy of hepatic resection for intrahepatic stones

In the Far East, hepatic resection is the definitive treatment for complicated intrahepatic stones (IHS). However, many investigators have reported that the associated intrahepatic biliary stricture is the main cause of treatment failure. A retrospective comparative study was undertaken to clarify the long-term efficacy of hepatic resection for treatment of IHS and to investigate the clinical significance of intrahepatic biliary stricture in treatment failure after hepatic resection performed in 44 patients with symptomatic IHS. The patients were divided into two study groups: group A, with intrahepatic biliary stricture (n = 28) and group B, without stricture (n = 16). Residual or recurrent stones, recurrence of intrahepatic biliary stricture, late cholangitis, and final outcomes were analyzed and compared statistically between the two groups. The patients were followed up for a median duration of 65 months after hepatectomy. The overall incidence of residual or recurrent stones was 36% and 11%, respectively, in groups A and B. The initial treatment failure rate was 50% in group A and 31% in group B. Intrahepatic biliary stricture recurred in 46% of patients in group A, while none of the group B patients had biliary stricture recurrence (P = 0.001). More than two-thirds of the restrictures in group A were identified at the primary site. The incidence of late cholangitis was higher in group A (54%) than in group B (6%) (P = 0.002). Three-quarters of the patients with cholangitis in group A had severe cholangitis, that was recurrent, and related to stones and strictures (n = 11). They and 2 asymptomatic patients in group B required secondary procedures done at a median of 12 months after hepatectomy. Final outcomes after hepatectomy with or without secondary management were good in 80%, fair in 16%, and poor in 4% of our 44 patients. Most recurrent cholangitis after hepatectomy in patients with IHS was related to recurrent intrahepatic ductal strictures. Therefore, to be effective, hepatic resection should include the strictured duct. However, with hepatectomy alone it is difficult to clear the IHS or relieve the ductal strictures completely, particularly in patients with bilateral IHS, so perioperative team approaches that include both radiologic and cholangioscopic interventions should be combined for the effective management of IHS. Received for publication on Oct. 15, 1997; accepted on Feb. 2, 1998     

Aggressive surgical resection for hilar cholangiocarcinoma

BACKGROUND: Surgical treatment of hilar cholangiocarcinoma remains a great challenge to surgeons because of its low resectability, poor survival, and high operative mortality and morbidity. METHODS: The medical and pathological records of 36 patients with a preoperative diagnosis of 'resectable' hilar cholangiocarcinoma operated on by us between January 1998 and December 2002 were studied. The clinical presentations, operative records, and pathology results were retrospectively reviewed. RESULTS: Twenty-six patients (72%) underwent resection with curative intent. Apart from resection of the extrahepatic biliary tree and porta hepatis lymph node dissection, 85% received concomitant en-bloc liver resection and 4% received ex situ liver resection and auto-transplantation. The margin of resection was negative (R0 resection) in 73% of patients, and microscopically positive (R1 resection) in the remaining 27%. The 30-day hospital mortality was 7.6%. Of the patients, 42% had major postoperative complications. The median survival was 20 months, with the longest survival 75 months. The 1-, 3- and 5-year actuarial overall survival rate after resection with curative intent was 77%, 31%, and 12%, respectively. The 1-, 3-, and 5-year actuarial overall survival after R0 resection was 84%, 42%, and 16%, respectively. Tumour recurrence occurred in 58% of patients. CONCLUSIONS: Aggressive surgery increases the resectability of hilar cholangiocarcinoma. R0 resection provides the only chance of long-term survival of these patients.     

Histologic bile duct invasion by a mass-forming intrahepatic cholangiocarcinoma

Abstract. Background/Purpose: Although curative surgical resection provides the best chance of long-term survival for patients with intrahepatic cholangiocarcinoma, the presence of bile duct invasion decreases postoperative survival rates in patients with mass-forming intrahepatic cholangiocarcinoma. We carried out this study to determine a surgical strategy for patients with bile duct invasion of these tumors. Methods: Forty-one patients with mass-forming intrahepatic cholangiocarcinoma were classified as either having bile duct invasion (n= 26) or not having bile duct invasion (n= 15). Clinicopathologic findings, including postoperative outcomes, were compared between these two groups. Results: Perineural invasion, lymphatic invasion, and a positive resection margin were more frequent in patients with ductal invasion. Patients with ductal invasion had lower survival rates than those without ductal invasion. Conclusions: Intraoperative frozen section examination of the bile duct stump to confirm a clear resection margin is required in patients with mass-forming tumors. Resection of the extrahepatic bile duct should be considered when tumor cells are identified at the surgical margin of the resected bile duct. Received: October 30, 2001 / accepted: November 16, 2001