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.     

Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery

Background We performed hepatectomy without lymph node (LN) dissection for intrahepatic cholangiocarcinoma (ICC) limited to the peripheral region of the liver, and hepatectomy with extrahepatic bile duct resection and regional LN dissection for any types of ICC extending to the hepatic hilum. Surgical outcomes were evaluated to elucidate the prognostic factors that influence patient survival with respect to intrahepatic recurrence. Methods Forty-one patients underwent resection of ICC with no macroscopic evidence of residual cancer. Results Significant risk factors for poorer survival included preoperative jaundice (P = 0.0115), serum CA19-9 levels >37 U/ml (P = 0.0089), tumor diameter >4.5 cm (P = 0.017), ICC extending to the hepatic hilum (P = 0.0065), mass-forming with periductal-infiltrating type (P = 0.003), poorly differentiated adenocarcinoma, portal vein involvement (P = 0.0785), LN metastasis at initial hepatectomy (P < 0.0001), and positive surgical margin (P = 0.023). Intrahepatic recurrence, which was the predominant manner of recurrence, was detected in 20 patients (74.1%). Patients with intrahepatic recurrence had a significantly high incidence of high serum CA19-9 levels (>37 U/ml; P = 0.0006), preoperative jaundice (P = 0.0262), ICC extended to the hepatic hilum (P = 0.0349), large tumors (>4.5 cm; P = 0.0351), portal vein involvement (P = 0.0423), and LN metastasis at initial hepatectomy (P = 0.009) compared with disease-free patients. The multiple logistic regression analysis revealed that preoperative CA19-9 elevation and obstructive jaundice influenced intrahepatic recurrence of ICC. Conclusions Although LN metastasis is a significant prognostic factor, the most obvious recurrence pattern after surgery was intrahepatic recurrence, which could be predicted preoperatively by a combination of elevated serum CA19-9 levels and manifestation of obstructive jaundice.     

Routine lymph node dissection may be not suitable for all intrahepatic cholangiocarcinoma patients: Results of a monocentric series

AIM:To investigate the indications for lymph node dissection(LND)in intrahepatic cholangiocarcinoma patients.METHODS:A retrospective analysis was conducted on 124 intrahepatic cholangiocarcinoma(ICC)patients who had undergone surgical resection of ICC from January 2006 to December 2007.Curative resection was attempted for all patients unless there were metastases to lymph nodes(LNs)beyond the hepatoduodenal ligament.Prophylactic LND was performed in patients in whom any enlarged LNs had been suspicious for metastases.The patients were classified according to the LND and LN metastases.Clinicopathologic,operative,and long-term survival data were collected retrospectively.The impact on survival of LND during primary resection was analyzed.RESULTS:Of 53 patients who had undergone hepatic resection with curative intent combined with regional LND,11 had lymph nodes metastases.Whether or not patients without lymph node involvement had undergone LND made no significant difference to their survival(P=0.822).Five patients with multiple tumors and involvement of lymph nodes underwent hepatic resection with LND;their survival curve did not differ significantly from that of the palliative resection group(P=0.744).However,there were significant differences in survival between patients with lymph node involvement and a solitary tumor who underwent hepatic resection with LND and the palliative resection group(median survival time 12 mo vs 6.0 mo,P=0.013).CONCLUSION:ICC patients without lymph node involvement and patients with multiple tumors and lymph node metastases may not benefit from aggressive lymphadenectomy.Routine LND should be considered with discretion.     

Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node-negative intrahepatic cholangiocarcinoma

1. Download : Download high-res image (289KB)
2. Download : Download full-size image

     

Skip lymph node metastases from a small hepatocellular carcinoma with difficulty in preoperative diagnosis

Recent autopsy studies have clarified the frequency of lymph node (LN) metastases from hepatocellular carcinoma (HCC). However, LN metastases commonly occur in advanced and poorly differentiated HCC and are very rare in small HCC. We encountered a patient with skip LN metastases from a small HCC, 10 mm in diameter. An intra-abdominal tumor adjoining the duodenum was detected by follow-up ultrasonography for viral hepatitis C. Computed tomography showed, in addition to the tumor bordering the duodenum, a small low-density area of the liver (S6), 2 cm in diameter, and a swelling of LN adjacent to the common hepatic artery. Upper gastrointestinal rentogenography revealed a compression of the duodenal second portion without irregularity of the mucosa. Our pre-operative diagnosis was duodenal gastrointestinal stromal tumor with LN metastasis and HCC or liver metastasis. However, laparotomy proved them to be LN metastases from a small HCC and partial hepatectomy and LN dissection were performed. The patient is doing well 22 months after surgery with no signs of recurrence. In the cases of HCC with LN metastases, the prognosis is generally very poor. However, in small HCC, the clinical characteristics are not fully evaluated. In treatment, we have to keep LN metastases, particularly skip LN metastases, in mind, even in cases of small HCC.     

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.     

Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma

Background/Purpose. We retrospectively investigated the clinicopathologic features and outcome of 51 patients who underwent hepatectomy for intrahepatic cholangiocellular carcinoma (ICC) between 1991 and 2000, and we also analyzed the potential prognostic factors for long-term survival. Methods. There were 27 men and 24 women, with a mean age of 63.7 years. The surgical procedures were extended right or left hepatectomy (15 cases), right or left hepatectomy (19 cases), bisegmentectomy (3 cases), segmentectomy (7 cases), and subsegmentectomy (7 cases). The macroscopic findings of the excised tumor showed the mass-forming (MF) type (31 cases), the periductal-infiltrating (PI) type (13 cases), and the intraductal growth (IG) type (7 cases). Results. The patients with the MF type had a significantly higher incidence of lymph node metastasis (44.8%), as compared to those with the PI or IG type (15.0%). Two patients who died of hepatic failure during their hospital stay were excluded from this survival study. The cumulative 1-, 3-, and 5-year survival rates in 49 patients who underwent liver resection were 68.2%, 44.1%, and 32.4%, respectively. The patients with the IG type had the best outcome, followed by those with the PI type and MF type. The survival rates with or without lymph node metastasis were 9.0% and 60.6% at 3 years, and 9.0% and 42.9% at 5 years, respectively (P ? 0.05). The 1-, 2-, and 3-year survival rates in the MF-type patients with lymph node metastasis were 25.4%, 16.9%, and 0%, respectively. Eight patients (15.7%) survived for more than 5 years after operation. The gross appearance of these tumors was the PI type in 5 patients, the IG type in 2, and the IG + MF type in 1. Except for one case with the PI-type tumor, lymph node metastasis was not observed. All of the 5-year survivors underwent curative resection and none of them had any positive surgical margin. Conclusion. Analysis of the clinicopathologic factors influencing the survival after surgical treatment showed that the macroscopic type, surgical curability, lymph node metastasis, tumor size, and cancer-free margin were the most predictive.     

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.     

Hepatic lymph node involvement in resected cases of liver metastases from colorectal cancer

PURPOSE: Lymph node metastasis in the hepatoduodenal ligament is known as one of the most significant prognostic factors after liver resection for colorectal metastasis. However, there have been very few articles on the clinical features of node-positive patients and on detailed distribution of positive nodes. Further, there has been no established strategy on how to handle hepatic lymph nodes during liver resection. To address these subjects, a retrospective study was conducted. METHODS: During the period of 1980 through April 1998, 182 hepatic resections were performed for metastatic colorectal carcinoma. Of these, 78 cases had hepatic lymph node sampling during the operation. Distribution of positive nodes, location of liver metastasis, stage of the primary lesion, and outcome after liver resection were analyzed. RESULTS: Nine cases (12 percent) had secondary lymph node metastases in the hepatoduodenal ligament. The incidence was slightly higher (13.5 percent) in the most recent 44 consecutive cases. There was a tendency for liver metastases in the right lobe to metastasize to No. 12b (or node of the foramen of Winslow, lymph nodes along the common bile duct) and liver metastases in the left lobe to metastasize to No. 8a (anterosuperior group of the lymph nodes along the common hepatic artery). Outcome of node-positive patients (n=9) was extremely poor (P<0.001) compared with that of node-negative patients (n=66), and the most common site of recurrence in the node-positive patients was remnant liver and hepatic lymph nodes. Preoperatively, there were no significant predicting factors for positive hepatic lymph nodes. CONCLUSIONS: No. 8a and No. 12b nodes are principal nodes that should be palpated and sampled during liver resection to check the secondary lymphatic spread from liver metastases. Hepatic nodal involvement indicates the progression of disease beyond simple liver metastases and may not be the indication for simple surgical removal. Further study, including hepatoduodenal dissection and systemic adjuvant chemotherapy, may elucidate the survival benefit, if any, of liver resection in node-positive patients.     

Prognosis after resection for hepatitis B virus-associated intrahepatic cholangiocarcinoma

AIM:To investigate the prognostic factors after resection for hepatitis B virus(HBV)-associated intrahepatic cholangiocarcinoma(ICC) and to assess the impact of different extents of lymphadenectomy on patient survival.METHODS:A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed.The patients were classified into groups according to the extent of lymphadenectomy(no lymph node dissection,sampling lymph node dissection and regional lymph node dissection).Clinicopathological characteristics and survival were reviewed retrospectively.RESULTS:The cumulative 1-,3-,and 5-year survival rates were found to be 60 %,18 %,and 13 %,respectively.Multivariate analysis revealed that liver cirrhosis(HR = 1.875,95%CI:1.197-3.278,P = 0.008) and multiple tumors(HR = 2.653,95%CI:1.562-4.508,P 0.001) were independent prognostic factors for survival.Recurrence occurred in 70 patients.The 1-,3-,and 5-year disease-free survival rates were 36%,3% and 0%,respectively.Liver cirrhosis(HR = 1.919,P = 0.012),advanced TNM stage(stage Ⅲ/Ⅳ)(HR = 2.027,P 0.001),and vascular invasion(HR = 3.779,P = 0.02) were independent prognostic factors for disease-free survival.Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection.Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status.CONCLUSION:The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC,and routine lymph nodedissection is not recommended,particularly for those without lymph node metastasis.     

Major anatomical hepatic resection with regional lymph node dissection for liver metastases from colorectal cancer

Sixty-four patients with liver metastases from colorectal cancer were studied to clarify the characteristics of the regional spread of liver metastases (secondary invasive factors) and the effects of major anatomical hepatic resection with lymph node dissection on reducing liver recurrence. No secondary invasive factors, i.e., lymph node metastasis, portal or hepatic vein involvement, bile duct involvement, micrometastasis, and direct invasion, were observed in patients with liver metastases less than 3 cm in diameter (5-year survival rate; 100%). Secondary invasive factors were seen in 19.2% of the patients with liver metastases from 3 cm to less than 6 cm (5-year survival rate; 28.7%), and in 45.2% of those with liver metastases 6 cm and over (5-year survival rate; 14.6%). Secondary invasive factors were noted in 45% of the patients with recurrence in the remmant liver. Although 31% of all 64 patients exhibited secondary invasive factors, major anatomical hepatic resection with lymph node dissection achieved a low liver recurrence rate of 31.3%. In conclusion, considering the risks attributed to secondary invasive factors, major anatomical hepatic resection with lymph node dissection is an appropriate surgical procedure for patients with liver metastases exceeding 3 cm in diameter.     

肝内胆管细胞癌外科治疗进展

手术切除是肝内胆管细胞癌首选的治疗方法,也是唯一可能的治愈手段。R0切除是影响肝内胆管细胞癌手术预后的重要因素,在保证R0切除和手术安全性的基础上,切缘距离应>10 mm。淋巴结是否转移是肝内胆管细胞癌手术最重要的预后因素之一,淋巴结清扫能改善患者的预后,术后辅以系统治疗可以延长患者的生存期。对于起始不可切除的肝内胆管细胞癌患者,辅助化疗是一个可能获得根治性手术切除机会的有效措施。     

Anatomic and molecular pathology of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor of the liver, and ICC is reportedly increasing recently. ICC is usually adenocarcinoma with variable desmoplastic reaction, although there are several special or unusual histological features. ICC may arise at the large intrahepatic bile duct near the hepatic hilus and also from the bile ductules at the border of the hepatic parenchyma. On the anatomical level, the pathology of ICC differs depending on the region from which the ICC arises. At the large intrahepatic bile duct, ICC presents papillary growth and periductal infiltration. Some cases show extensive papillary growth and intraluminal spread with marked gastroenteric metaplasia. Mucus core protein 1 is expressed in aggressive ICC. ICC arising from ductules shares phenotypes of hepatocellular carcinoma. ICC in chronic biliary diseases, particularly arising in hepatolithiasis, presents precancerous lesions that include biliary epithelial dysplasia, as well as in-situ carcinoma. Chronic advanced hepatitis C is one of the background diseases of ICC. Chronic inflammation, with the upregulation of cyclooxygenase-2 and growth factors, and the formation of reactive oxygen species are one of the causative factors in the DNA damage of biliary epithelial cells. K-ras mutation and aberrant expression of p53 are found in one-third of ICCs. The latter may be due to mdm-2 upregulation. Hepatocyte growth factor/met and interleukin 6 (IL6)/IL6 receptor are involved in cell proliferation/mitoinhibition and apoptosis in ICC. Fibrous stroma formation and invasion involve the proliferation of Α-smooth muscle antigen-positive stromal cells, and cell-to-cell and cell-to-matrix interactions involving E-cadherin/catenin and CD44 and matrix proteinases may be involved in the invasion of ICC. Evasion of immune surveillance involving the Fas/FasL system is important in the malignant progression of ICC. Further molecular and genetic studies are mandatory to evaluate the pathogenesis and progression of ICC.     

Characteristics of intrahepatic cholangiocarcinoma in patients with hepatitis B virus infection: clinicopathologic study of resected tumours

Recent efforts suggest an aetiological role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcomes of patients with HBV‐associated ICC. All patients with chronic HBV infection were identified from a database of patients with ICC that underwent surgical resection between 1 January 2005 and 31 December 2006. Their clinicopathologic and survival characteristics were compared with ICC patients without chronic HBV infection. The age of the HBV‐associated ICC patients tend to be younger than that of ICC patients without chronic HBV infection. HBV‐associated ICC patients tend to have higher abnormal α‐fetoprotein levels and lower abnormal serum carbohydrate antigen19‐9 (CA19‐9), r‐glutamyltransferase (r‐GT) and alkaline phosphatase levels. The pathologic features of the resected specimens revealed that HBV‐associated ICC patients tended to be of the mass‐forming type have a lower prevalence of lymphatic involvement and poorer tumour differentiation, and a higher prevalence of capsule formation and liver cirrhosis. Patients with HBV‐associated ICC had a significantly better survival than patients without chronic HBV infection. The clinicopathological features of HBV‐associated ICC patients showed significant differences from ICC patients without HBV infection. These tumours are characterized by the mass‐forming growth pattern and appeared to have a more favourable prognosis.     

Major hepatectomy for perihilar cholangiocarcinoma

Background/purpose

Hilar cholangiocarcinoma and intrahepatic cholangiocarcinoma involving the hepatic hilus are defined as “perihilar cholangiocarcinoma”. The principle of surgical treatment is hemi-hepatectomy or trisectionectomy of the liver, caudate lobectomy, and resection of the extrahepatic bile duct for complete resection of the tumor. The aim of this study was to review the outcomes of major hepatectomy for perihilar cholangiocarcinoma.

Methods

Using the Kaplan–Meier method and the Cox proportional hazards model, we analyzed the results in 125 patients with perihilar cholangiocarcinoma who had undergone major hepatectomy.

Results

Right hepatectomy, right trisectionectomy, left hepatectomy, and left trisectionectomy were performed in 66, 8, 49, and 2 patients, respectively. Curative resection was achieved in 79 patients (63.2%). Mortality and morbidity rates were 8.0 and 48.7%, respectively. The overall 1-, 3-, and 5-year survival rates of all patients were 73.2, 36.7, and 34.7%, respectively. The median survival was 26.8 months. Multivariate analysis showed that the independent prognostic factors for overall survival were gender, histopathological grading, curative resection, and American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) pT.

Conclusions

Major hepatectomy for perihilar cholangiocarcinoma was acceptable and showed satisfactory outcomes. For long-term survival in these patients, the surgeon should aim for complete resection of the tumor with negative margins.