Serosal invasion in TNM staging of mass-forming intrahepatic cholangiocarcinoma

Background/Purpose The Liver Cancer Study Group of Japan established a tumor-nodule-metastasis (TNM) staging system for mass-forming intrahepatic cholangiocarcinoma, with T determined by tumor number and size and vascular or serosal invasion. Serosal invasion is not considered in the designation established by the International Union Against Cancer. Methods Sixty-three patients who underwent hepatic resection for mass-forming intrahepatic cholangiocarcinoma were investigated retrospectively, with the investigation including univariate and multivariate analyses of potential prognostic factors. Results By log-rank test, tumor size more than 3.0 cm, vascular invasion, lymph node metastasis, intrahepatic metastasis, and involved resection margin, but not serosal invasion, were associated significantly with poor prognosis. Even in patients with serosal invasion, the postoperative outcome was much better in those without than in those with vascular invasion. Multivariate analysis identified vascular invasion, lymph node metastasis, and an involved resection margin as independent prognostic factors. When serosal invasion was excluded from tumor staging, the 5-year survival rates became more clearly stratified: 100% in those with stage I disease, 62% in those with stage II, 25% in those with stage III, and 7% for patients with stage IV. Conclusions Serosal invasion showed no survival impact after hepatic resection for mass-forming intrahepatic cholangiocarcinoma. When serosal invasion was omitted from the TNM staging proposed by the Liver Cancer Study Group of Japan, stratification of postoperative survival between stages was more effective.     

Aggressive surgical resection for hilar-invasive and peripheral intrahepatic cholangiocarcinoma

Abstract The clinicopathology and surgical outcome of intrahepatic cholangiocarcinomas are not fully understood. The objective of this study was to clarify the clinicopathologic features of intrahepatic cholangiocarcinoma and evaluate prognostic factors influencing survival. Forty consecutive patients with intrahepatic cholangiocarcinomas undergoing surgical resection at Chiba University Hospital between October 1981 and October 1997 were analyzed retrospectively. Intrahepatic cholangiocarcinomas were classified as hilar-invasive type (n = 26) or peripheral type (n = 14). Patients with peripheral-type tumors had a significantly (p = 0.005) better 5-year survival rate (43%) than those with the hilar-invasive type (4%). Hilar-invasive-type tumors had perineural invasion (100%) and nodal involvement (85%) more frequently than did peripheral-type tumors. Despite aggressive surgical resection, the surgical margin was positive in 88% of patients with hilar-invasive type tumors (23/26) and 29% of patients with peripheral-type tumors (4/14). There was no evidence of a survival benefit of vascular resection for patients with a hilar-invasive intrahepatic cholangiocarcinoma. Patients with lymph node metastasis had a significantly worse prognosis (p = 0.0004). No patients with nodal involvement survived more than 38 months. Negative perineural invasion (p = 0.008) and a negative microscopic margin (p = 0.008) were significantly associated with improved survival. Better survival results could be achieved by curative resection with a free margin for hilar-invasive and peripheral intrahepatic cholangiocarcinoma. Electronic Publication     

Significance of Ductal Margin Status in Patients Undergoing Surgical Resection for Extrahepatic Cholangiocarcinoma

OBJECTIVES: The objective of this study was to determine whether carcinoma in situ at the bile duct margin is prognostically different from residual invasive carcinoma in patients with extrahepatic cholangiocarcinoma. Although there are many reports that the ductal margin status at bile duct resection stumps is a prognostic indicator in patients with extrahepatic cholangiocarcinoma, some patients who undergo resection with microscopic tumor involvement of the bile duct margin survive longer than expected. METHODS: A retrospective clinicopathological analysis of 128 patients who had undergone surgical resection for extrahepatic cholangiocarcinoma was conducted. The status of the bile duct resection margin was classified as negative in 105 patients (82.0%), positive for carcinoma in situ in 12 patients (9.4%), and positive for invasive carcinoma in 11 patients (8.6%). RESULTS: Ductal margin status was an independent prognostic indicator by both univariate (p = 0.0022) and multivariate (p = 0.0105) analyses, along with lymph node metastasis. There was no significant difference between patients with a negative ductal margin and those with a positive ductal margin with carcinoma in situ (p = 0.5247). The 5-year survival rate of patients with a positive ductal margin with carcinoma in situ (22.2%) was significantly better (p = 0.0241) than with invasive carcinoma (0%). There was a significant relationship between local recurrence and ductal margin status (p = 0.0401). CONCLUSIONS: Among patients undergoing surgical resection for extrahepatic cholangiocarcinoma, invasive carcinoma at the ductal resection margins appears to have a significant relation to local recurrence and also a significant negative impact on survival, whereas residual carcinoma in situ does not. Discrimination whether carcinoma in situ or invasive carcinoma is present is important in clinical setting in which the resection margin at the ductal stump is positive.     

Clinicopathological factors predicting outcome after resection of mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND: The prognosis for patients with intrahepatic cholangiocarcinoma differs according to macroscopic type. The identification of clinical and pathological features that predict outcome in patients with mass-forming intrahepatic cholangiocarcinoma is required in order to determine optimal surgical strategies for patients with this type of tumour. METHODS: The details of 35 patients with resected mass-forming intrahepatic cholangiocarcinomas were analysed retrospectively. Univariate analysis of potential prognostic factors was performed. RESULTS: The cumulative survival rate at 1, 3 and 5 years after operation was 58, 33 and 33 per cent respectively. Patients with stage II tumours had a better outcome than those with advanced stage tumours. By univariate analysis, lymphatic invasion, lymph node metastasis, intrahepatic satellite lesions and microscopic resection margin involvement were found to be highly significant variables and were identified as possible risk factors for a poor outcome after operation. CONCLUSION: When frozen-section examination of lymph nodes reveals negative nodal metastasis, extensive anatomical hepatic resection is indicated for mass-forming intrahepatic cholangiocarcinomas. Intraoperative frozen-section examination of the resection margin to confirm the absence of cancer cells is recommended.     

Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma

The clinicopathological characteristics relevant to prognosis after surgical treatment of intrahepatic cholangiocarcinoma (ICC) remain unclear. In this study, the clinicopathological features of 19 patients with mass-forming ICC, the most common form of the disease, were reviewed to analyze prognostic determinants. Two or more segmentectomies of the liver with systematic lymphadenectomy were performed in 18 patients. Resection of the extrahepatic bile duct was performed in 14 patients, and reconstruction of the portal vein was accomplished in 5 patients. Stage IVA or IVB tumors were seen in 13 patients, and lymph node (LN) metastasis was present in 14 patients. The estimated 5-year survival rate after surgery for mass-forming ICC was 28%, with median survival time of 18 months. In univariate analysis, five variables were determined to be significantly correlated with poor survival of patients with mass-forming ICC after surgery. These variables include mass-forming ICC with periductal infiltration, perineural invasion, portal vein invasion, presence of intrahepatic metastasis, and two or more LN metastases. Survival rates of 5 patients without LN metastasis and 6 patients with a single LN metastasis were 80% and 33% at 5 years, respectively, while 8 patients with two or more LN metastasis failed to survive beyond 2 years. Multivariate analysis revealed the presence of intrahepatic metastasis to be an independent prognostic factor of poor survival. Hepatectomy with resection of the extrahepatic bile duct and systematic lymphadenectomy yields a good chance for prolonged survival for patients with mass-forming ICC when the lesion is singular and LN metastasis is limited to a regional LN. Because the presence of intrahepatic metastasis was closely related to a poor prognosis in patients with mass-forming ICC, efficacious chemotherapy would be needed to control development of the lesion.     

肝内胆管癌淋巴结转移规律、术中清扫范围及意义

肝内胆管癌（ICC）是起源于肝内小叶间胆管至二级胆管以上的胆管上皮源性恶性肿瘤，约占胆管源性恶性肿瘤的10%。根治性手术切除是ICC惟一可能治愈的手段。而淋巴结转移是影响ICC预后最重要的独立危险因素。对于ICC根治性切除术中是否需要行淋巴结清扫、清扫范围及意义，国际上对此尚有不少争议。多数研究认为对于可手术切除的ICC病人，区域淋巴结清扫是外科治疗的标准部分，有助于术后准确分期及选择有效的辅助治疗方法。同时伴有淋巴结转移的ICC病人都应接受术后系统性治疗。但也有研究表明单纯化疗相对于手术切除能为已有淋巴结转移的ICC病人提供更好的生存获益。     

Surgical Outcome and Prognostic Factors in Intrahepatic Cholangiocarcinoma

BACKGROUND: The clinicopathologic features and surgical outcome of intrahepatic cholangiocarcinoma are not fully understood. METHODS: Fifty-six consecutive patients with intrahepatic cholangiocarcinoma who underwent surgical resection at the National Cancer Center Hospital East between October 1992 and July 2007 were retrospectively analyzed. Intrahepatic cholangiocarcinomas were subdivided into solitary tumors and tumors with intrahepatic metastasis. RESULTS: Complete tumor removal (R0 resection) was performed in 42 patients (75%). The 5-year survival rate for patients with intrahepatic cholangiocarcinoma (n = 56), patients with a solitary tumor (n = 46), and patients with intrahepatic metastasis (n = 10) were 32, 38, and 0%, respectively. There was a significant difference in survival between patients with a solitary tumor and those with intrahepatic metastasis (p < 0.0001). The 5-year survival rate for patients with stage I (n = 3), II (n = 9), III (n = 15), and IV disease (n = 26) was 100, 67, 37, and 0%, respectively. There was a significant difference in survival between stage I and stage IV (p = 0.011), between stage II and stage IV (p = 0.0002), and between stage III and stage IV (p = 0.0015). The most frequent site of recurrence was the liver. Univariate analysis showed that intrahepatic metastasis, portal vein invasion, hepatic duct invasion, lymph node metastasis, perineural invasion, and positive surgical margin (R1) were significantly associated with poor survival. Multivariate analysis confirmed that intrahepatic metastasis was a significant and independent prognostic indicator after surgical resection for intrahepatic cholangiocarcinoma (p = 0.001). No patient with intrahepatic metastasis survived more than 10 months in this study. CONCLUSIONS: Intrahepatic metastasis was the strongest predictor of poor survival in intrahepatic cholangiocarcinoma.     

Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma

BACKGROUND: Mass-forming type cholangiocarcinoma is a distinct from of cholangiocellular carcinoma, with pathologic and biologic behavior different from those of other types. The clinical consequences of these differences have never been clarified. METHODS: Fifty-two consecutive patients (32 men and 20 women, mean age 62 years) with mass-forming type cholangiocarcinoma that had been treated with curative surgical resection between 1980 and 1998 were retrospectively evaluated. Long-term survival and disease-free survival were calculated, and univariate and multivariate analysis of various prognostic factors was conducted. RESULTS: The 30-day postoperative mortality rate was 2%, and the overall and disease-free 5-year survival rates were 36% and 34%, respectively. Univariate analysis identified 5 significant risk factors for overall survival: surgical margin, lymph node metastasis, lymph node dissection, vascular invasion, and left-side location of the main tumor. Two risk factors were identified for disease-free survival: surgical margin and lymph node metastasis. Multivariate analysis confirmed that surgical margin, lymph node metastasis, and vascular invasion were independently significant variables for overall survival. CONCLUSIONS: This is the first reported study on the effectiveness of liver resection for the treatment of mass-forming type cholangiocarcinoma, showing that surgical therapy can prolong survival if local radicality can be achieved and lymph-node metastases are absent.     

Surgical Outcomes of the Mass-Forming plus Periductal Infiltrating Types of Intrahepatic Cholangiocarcinoma: A Comparative Study with the Typical Mass-Forming Type of Intrahepatic Cholangiocarcinoma

Background The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcomes of patients with the mass-forming (MF) plus periductal infiltrating (PI) type of intrahepatic cholangiocellular carcinoma (ICC). Methods Between January 1, 1998, and December 31, 2004, a total of 94 patients with ICC underwent macroscopic curative resection, and the macroscopic type of the tumors was assessed prospectively. Among the 74 patients with the MF type (n = 46) and the MF plus PI type (n = 28) of ICC, multivariate analysis was conducted to identify the potential prognostic factors. The clinicopathologic data of the two groups were compared. Results The results revealed two independent prognostic factors: presence/absence of intrahepatic metastasis and the macroscopic type of the tumor. ICCs categorized macroscopically as the MF plus PI type were significantly associated with jaundice (p < 0.001), bile duct invasion (p < 0.001), portal vein invasion (p = 0.025), lymph node involvement (p = 0.017), and positive surgical margin (p = 0.038). Conclusion Identification of the macroscopic type of the tumor is useful for predicting survival after hepatectomy in patients with ICC. The MF plus PI type of ICC appears to have a more unfavorable prognosis, even after radical surgery, than the MF type of ICC.     

Prognostic factors of surgical resection in middle and distal bile duct cancer: an analysis of 55 patients concerning the significance of ductal and radial margins

BACKGROUND: The surgical outcome of middle and/or distal bile duct cancer remains unsatisfactory. Although the resectional margin is known to be a predictive factor, the prognostic significance of a positive ductal margin and other radial margin has never been evaluated independently. METHODS: The clinicopathologic data of 55 patients who had undergone surgical resection for middle and/or distal bile duct cancer between 1987 and 2003 were reviewed retrospectively. The surgical procedures consisted of pancreatoduodenectomy in 42 patients (76%), extrahepatic bile duct resection in 8 patients (15%), major hemihepatectomy (Hx) in 3 patients (5%), and pancreatoduodenectomy plus Hx in 2 patients (4%). In all the patients, intraoperative diagnosis of the ductal margins was performed using frozen sections. Twenty-one clinicopathologic factors, including the status of the ductal margins and of other radial margins, were evaluated using univariate and multivariate analyses. RESULTS: The overall 5-year survival rate and the median survival time were 24% and 38 months, respectively. There were 4 (7%) postoperative deaths. Fifteen of the remaining 51 patients (29%) were determined to have positive hepatic-side ductal margins during operation, and 14 of them underwent additional resection of the bile duct (1.6[range, 1-3] times, on average). As a result, hepatic-side ductal margin (hm) and duodenal-side ductal margin were found to be positive in 6 and 0 patients on the final pathologic analysis, respectively. Two of the 6 patients (33%) with positive hm have developed ductal recurrence so far, but the status of hm was not found to be a significant predictor. The depth of neoplastic invasion into the bile duct wall, pancreatic invasion, radial margin, and blood transfusion were significant prognostic factors by the univariate analysis. Multivariate analysis revealed that the depth of neoplastic invasion and blood transfusion were the independent prognostic factors. CONCLUSIONS: In the treatment of middle and distal bile duct cancer, it is of importance to secure a negative radial margin, although it may be less beneficial to obtain a negative hm. Surgeons should make efforts to obtain negative radial margins and to avoid blood transfusion.     

中下段胆管癌切除后切缘阳性的意义及预后因素分析

目的 分析中下段胆管癌切除术后切缘阳性的意义,研究影响中下段胆管癌切除术后的预后因素.方法 回顾性分析1990年1月至2006年12月收治的79例中下段且日管癌切除患者的临床病理资料.其中男性53例、女性26例,年龄30～79岁,平均61岁.中段胆管癌34例,下段胆管癌45例.行胰十二指肠切除术46例,行根治性胆总管癌切除术25例,行根治性胆总管癌切除联合肝部分切除术6例,行根治性胆总管癌切除联合门静脉部分切除术2例.5例于术后1个月内死亡,对其余74例患者的15项临床病理特征进行单因素及多因素分析.结果 74例患者总的5年生存率为30.7%,中位生存期为36个月.术后病理榆查为镜下切缘阳性(R1切除)16例(20.3%),其中肝脏端胍管切缘阳性6例,远端胆管切缘阳性3例,双侧胆管切缘阳性2例,环周切缘阳性5例.接受R0和Rl切除的患者的5年生存率分别为34.4%和15.5%.10例(17.2%)R0切除的胆管癌出现局部复发,10例(62.5%)R1切除出现复发,差异有统计学意义(X2=13.024,P<0.01).单因素分析显示术前血红蛋白水平、分化程度、肿瘤浸润深度、淋巴结转移、TNM分期及手术切缘为影响预后的因素.多因素分析显示淋巴结转移状况和切缘癌残留是影响预后的独立因素.结论 中下段胆管癌根治术中冰冻病理检查切缘达R0切除是提高长期生存的重要策略,辅助治疗的效果尚待进一步研究.     

Hilar cholangiocarcinoma—surgical anatomy and curative resection

We have studied the surgical anatomy of the intrahepatic bile duct, hepatic hilus, and caudate lobe based on intraoperative findings and selective cholangiography of surgical patients and resected specimens, and have established the cholangiographic anatomy of the intrahepatic subsegmental bile duct. Thorough knowledge of the three-dimensional anatomy of the subsegmental bile duct, hepatic hilus, and caudate lobe is indispensable for curative surgery of hilar cholangiocarcinoma. We designed and actually performed 15 kinds of hepatic segmentectomies with caudate lobectomy and extrahepatic bile buct resection in 100 consecutive patients, with curative resection being possible in 82 patients. Postoperative survival after curative resection of hilar cholangiocarcinoma was better than expected, and the 5-year survival rates for all 82 patients with curative resection and for 55 patients with curative surgery without portal vein resection were 31% and 43%, respectively. Hepatic segmentectomy with caudate lobectomy and extrahepatic bile duct resection should be designed not only in accordance with the preoperative diagnosis of tumor extension into the intrahepatic bile ducts but also so that curative surgery for advanced hilar cholangiocarcinoma can be performed.     

Role of Hepatectomy in the Treatment of Hilar Bile Duct Carcinoma

Purpose. To clarify the role of hepatic resection in the surgical treatment of hilar bile duct carcinoma.Methods. Between 1980 and 1997, 68 patients underwent surgery for hilar bile duct carcinoma. The patients were divided into a hepatectomy group (n = 40) and a nonhepatectomized group (n = 28) depending on whether they underwent resection of the bile duct confluence in combination with hepatectomy, or alone, respectively. Background data, operative morbidity and mortality, and survival were retrospectively compared between the two groups.Results. There were no significant differences in morbidity and mortality, or in postoperative survival between the two groups (the 5-year survival rates being 20.6% in the hepatectomized group and 7.1% in the nonhepatectomized group; P = 0.0806). However, patients who underwent curative resection had significantly better postoperative survival than those who underwent noncurative resection (P = 0.048). Hepatectomy provided a significantly better cancer-free margin than bile duct resection alone (P = 0.0296).Conclusions. Although a countermeasure must be taken to decrease mortality, the introduction of hepatectomy with bile duct resection would provide a better cancer-free surgical margin than bile duct resection alone for hilar bile duct carcinoma. Curative resection contributed to long-term survival in this series.     

肝门部胆管癌根治性切除中围肝门区手术处理

目的探讨围肝门区手术处理手段在肝门部胆管癌外科治疗中的临床应用。方法回顾性分析我院2002年1月-2007年12月诊治的86例肝门部胆管癌病人的临床资料。其中,实施单纯内引流术38例,姑息性切除术11例,采取联合尾状叶切除、受侵门静脉肝动脉切除重建、肝内胆管断端整形、肝门区淋巴结清扫等技术完成根治性切除37例。结果肝门部胆管癌的根治性切除率由2002年的33．3％,提高到2007年的75．0％。无围手术期死亡发生。结论联合采用尾状叶切除、肝门部胆管断端整形、受侵门静脉切除重建及肝门区淋巴清扫等围肝门区处理手段可提高肝门部胆管癌根治性切除率,降低手术并发症的发生率。     

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     

Clinical Significance of Intraoperative Bile Duct Margin Assessment for Hilar Cholangiocarcinoma

Background  Frozen section analysis of bile duct margins is often used to guide the extent of surgical resection for hilar cholangiocarcinoma (HCCA), but the usefulness of this practice is unknown. Methods  The association between disease-specific survival (DSS) and pathologic margin status determined during and after surgical resection for HCCA was assessed retrospectively for 101 patients between 1992 and 2005. Final histopathology identified three subgroups on the basis of resection margin status: wide margin (bile duct and specimen margins negative for adenocarcinoma), narrow margin (bile duct margin negative but specimen margins positive), and positive margin (bile duct and specimen margins positive). Results  On the basis of frozen section analysis alone, 90 patients were thought to have a disease-negative bile duct margin intraoperatively. Final histopathology showed that eight patients (9%) had invasive adenocarcinoma in the cuff of bile duct submitted for frozen section analysis. Of the 82 patients with negative final bile duct margins, 54 patients were categorized as having wide margins, and 28 patients had narrow margins. The median DSS for patients with wide margins was 56 months compared with 38 months for patients with narrow margins and 32 months for margin-positive patients (P = .01). Conclusion  Frozen section analysis of the proximal bile duct margin is misleading in 9% of patients. Among patients with HCCA who are determined to have negative duct margins intraoperatively, only 60% will have margins adequately wide enough to be associated with an improvement in DSS. Presented in part at the 61st Annual Cancer Symposium of The Society of Surgical Oncology, March 14, 2008, Chicago, IL.     

Prognosis of Perihilar Cholangiocarcinoma: Hilar Bile Duct Cancer versus Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus

Background Clinically hepatobiliary resection is indicated for both hilar bile duct cancer (BDC) and intrahepatic cholangiocarcinoma involving the hepatic hilus (CCC). The aim of this study was to compare the long-term outcome of BDC and CCC. Methods Between 1990 and 2004, we surgically treated 158 consecutive patients with perihilar cholangiocarcinoma. The clinicopathological data on all of the patients were analyzed retrospectively. Results The overall 3-year survival rate, 5-year survival rate, and median survival time for BDC patients were 48.4%, 38.4 %, and 33.7 months, respectively, and 35.8%, 24.5 %, and 22.7 months, respectively, in CCC patients (P = .033). On multivariate analysis, three independent factors were related to longer survival in BDC patients: achieved in curative resection with cancer free margin (R0) (P = .024, odds ratio 1.862), well differentiated or papillary adenocarcinoma (P = .011, odds ratio 2.135), and absence of lymph node metastasis (P < .001, odds ratio 3.314). Five factors were related to longer survival in CCC patients: absence of intrahepatic daughter nodules (P < .001, odds ratio 2.318), CEA level ≤2.9 ng/mL (P = .005, odds ratio 2.606), no red blood cell transfusion requirement (P = .016, odds ratio 2.614), absence or slight degree of lymphatic system invasion (P < .001, odds ratio 4.577), and negative margin of the proximal bile duct (P = .003, odds ratio 7.398). Conclusions BDC and CCC appear to have different prognoses after hepatobiliary resection. Therefore, differentiating between these two categories must impact the prediction of postoperative survival in patients with perihilar cholangiocarcinoma. T. Sano is currently with: Hepato-Biliary and Pancreatic Surgery Division, Aichi Cancer Center Hospital, Nagoya, Japan.     

Resection of Hilar Cholangiocarcinoma

Objective: Morbidity and mortality involved in the resection of hilar cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and laboratory parameters that might influence the patient''s survival also were re-evaluated.Summary Background Data: Although much progress has been made in the diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most patients remains poor. Surgical resection is usually prohibited because of its local invasiveness, and most patients can only be managed by palliative drainage. Recently, many surgeons have adopted a more aggressive resection with varying degrees of success. Several prognostic factors in bile duct carcinoma have been proposed; however, no reports have specifically focused on resected hilar cholangiocarcinoma and its prognostic survival factors using multivariate analysis.Methods: The clinical records and pathologic slides of 49 cases with resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical and laboratory parameters were evaluated for their correlation with postoperative morbidity and mortality, whereas 31 variables were evaluated for their significance with postoperative survival. Variables showing statistical significance in the first univariate analysis were included in the following multivariate analysis using stepwise logistic regression test for factors affecting morbidity and mortality and Cox stepwise proportional hazard model for factors influencing survival.Results: There were 5 in-hospital deaths, and the cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a median survival of 14.0 months. Multivariate analysis disclosed that coexistent hepatolithiasis and lower serum asparate aminotransferase levels (90 U/L) had a significant low incidence of postoperative morbidity, whereas a serum albumin of less than 3 g/dL was the only significant factor affecting mortality. Regarding survival, univariate analysis identified eight significant factors: 1) total bilirubin 10 mg/dL, 2) curative resection, 3) histologic type, 4) perineural invasion, 5) liver invasion, 6) depth of cancer invasion, 7) positive proximal resected margin, and 8) positive surgical margin. However, multivariate analysis disclosed total bilirubin ≥ 10 mg/dL, curative resection, and histologic type as the three most significant independent variables.Conclusions: Surgical resection provides the best survival for bilar cholangiocarcinoma. An adequate nutritional support to increase serum albumin over 3g/dL is the most important factor to decrease postoperative mortality. Moreover, preoperative biliary drainage to decrease jaundice and a curative resection with adequate surgical margin are recommended if longer survival is anticipated. Patients with well differentiated adenocarcinoma seem to survive longer compared to those with moderately or poorly differentiated tumors.     

Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma.

OBJECTIVE; Morbidity and mortality involved in the resection of hilar cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and laboratory parameters that might influence the patient's survival also were re-evaluated. SUMMARY BACKGROUND DATA: Although much progress has been made in the diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most patients remains poor. Surgical resection is usually prohibited because of its local invasiveness, and most patients can only be managed by palliative drainage. Recently, many surgeons have adopted a more aggressive resection with varying degrees of success. Several prognostic factors in bile duct carcinoma have been proposed; however, no reports have specifically focused on resected hilar cholangiocarcinoma and its prognostic survival factors using multivariate analysis. METHODS: The clinical records and pathologic slides of 49 cases with resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical and laboratory parameters were evaluated for their correlation with postoperative morbidity and mortality, whereas 31 variables were evaluated for their significance with postoperative survival. Variables showing statistical significance in the first univariate analysis were included in the following multivariate analysis using stepwise logistic regression test for factors affecting morbidity and mortality and Cox stepwise proportional hazard model for factors influencing survival. RESULTS: There were 5 in-hospital deaths, and the cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a median survival of 14.0 months. Multivariate analysis disclosed that co-existent hepatolithiasis and lower serum asparate aminotransferase levels (<90 U/L) had a significant low incidence of postoperative morbidity, whereas a serum albumin of less than 3 g/dL was the only significant factor affecting mortality. Regarding survival, univariate analysis identified eight significant factors: 1) total bilirubin > or = 10 mg/dL, 2) curative resection, 3) histologic type, 4) perineural invasion, 5) liver invasion, 6) depth of cancer invasion, 7) positive proximal resected margin, and 8) positive surgical margin. However, multivariate analysis disclosed total bilirubin > or = 10 mg/dL, curative resection, and histologic type as the three most significant independent variables. CONCLUSIONS: Surgical resection provides the best survival for hilar cholangiocarcinoma. An adequate nutritional support to increase serum albumin over 3 g/dL is the most important factor to decrease postoperative mortality. Moreover, preoperative biliary drainage to decrease jaundice and a curative resection with adequate surgical margin are recommended if longer survival is anticipated. Patients with well-differentiated adenocarcinoma seem to survive longer compared to those with moderately or poorly differentiated tumors.     

Extended resection for intrahepatic cholangiocarcinoma in Japan

To elucidate surgical outcome after extended sugery for intrahepatic cholangiocarcinoma (ICC), we retrospectively allocated 83 patients who had undergone resection to a standard surgery group (n = 56), in which the patients had undergone hepatectomy alone or hepatectomy with bile duct resection, and an extended surgery group (n = 27), in which the patients had undergone the standard operation combined with vessel resection and/or pancreatectomy. The incidence of mass-forming plus periductal-infiltrating type lesions (P = 0.0129), lymph node metastasis (P = 0.0005), noncurative resection (P < 0.0001), mortality within 30 days and within 1 year after surgery (P = 0.0392, P = 0.0010), local recurrence (P = 0.0439), and peritoneal disseminated recurrence (P = 0.0241) was significantly higher in the extended surgery group than in the standard surgery group. The 5-year survival rate was significantly higher in the standard surgery group (30%) than in the extended surgery group (10%; P = 0.0061). The mortality rate within 1 year after extended surgery was significantly higher in the patients with infiltrating-spread type tumors than in the patients with non-infiltrating spread type tumors (P = 0.0032), and long-term (5-year) survival in the extended surgery group was significantly lower in the patients with infiltrating-spread type tumors than in the patients with non-infiltrating spread type tumors (P = 0.0253). We conclude that extended surgery does not improve the curative resection rate or the surgical outcome of ICC, and that extended surgery is not indicated for patients with infiltrating-spread type tumors. Received for publication on Dec. 14, 1998; accepted on Dec. 15, 1998