Non-surgical treatment of hilar cholangiocarcinoma

Cancer of the biliary confluence also known as hilar cholangiocarcinoma (HC) or Klatskin tumor, is a rare type of neoplastic disease constituting approximately 40%-60% of intrahepatic malignancies, and 2% of all cancers. The prognosis is extremely poor and the majority of Klatskin tumors are deemed unresectable upon diagnosis. Most patients with unresectable bile duct cancer die within the first year after diagnosis, due to hepatic failure, and/or infectious complications secondary to biliary obstruction. Curative treatments include surgical resection and liver transplantation in highly selected patients. Nevertheless, very few patients are eligible for surgery or transplant at the time of diagnosis. For patients with unresectable HC, radiotherapy, chemotherapy, photodynamic therapy, and liver-directed minimally invasive procedures such as percutaneous image-guided ablation and intra-arterial chemoembolization are recommended treatment options. This review focuses on currently available treatment options for unresectable HC and discusses future perspectives that could optimize outcomes.     

Long-term survival after multimodal therapy in a patient demonstrating intrahepatic cholangiocarcinoma with hilar invasion and intrahepatic metastases

Cholangiocarcinoma is a therapeutically challenging malignancy. This report describes a case where the patient received multimodal therapy, including surgery, adjuvant chemoradiation therapy, and combination chemotherapy and successfully achieved long-term survival. Specifically, the patient achieved an extended complete response after combination chemotherapy with TS-1 (an orally administered drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine [CDHP], and oteracil potassium [Oxo]) and cisplatin for recurrence. This result suggests that chemoradiation or combination chemotherapy regimens using oral 5-fluorouracil (5-FU) analogues might therefore be helpful in patients with this malignancy. However, further clinical trials are required.     

肝门部胆管癌预后因素分析

目的研究影响肝门部胆管癌预后的因素.方法回顾分析本院自1997年12月～2002年12月收治的200例肝门部胆管癌的临床资料,进行统计学分析.结果200例患者中以黄疸(94.4%)、瘙痒(57.8%)和腹痛(33.0%)为主要症状.获得手术切除126例,手术切除率为63%,根治性切除65例,姑息切除61例,剖腹探查21例,姑息性内外引流53例.统计学处理结果显示术后生存时间与术前血清总胆红素水平、手术方式及AJCC TNM分期三个因素显著相关,与年龄、合并胆石与否、Bismuth-Corlette分型、血管(门静脉或肝动脉)侵犯、肿瘤细胞分级、术后放疗与否和术后化疗与否无显著相关.结论早期诊断和根治切除是改善肝门部胆管癌疗效的重要措施.     

Radiological diagnosis and staging of hilar cholangiocarcinoma

Hilar cholangiocarcinoma is a rare malignant tumor arising from the epithelium of the bile ducts.Surgery is still the only chance of potentially curative treatment in patients with perihilar cholangiocarcinoma.However,radical resection requires aggressive surgical strategies that should be tailored optimally according to the location,size and vascular invasion of the tumors.Accurate diagnosis and staging of these tumors is therefore critical for optimal treatment planning and for determining a prognosis.Multidetector computed tomography(MDCT),magnetic resonance imaging(MRI) and MR cholangiography are useful tools,both to diagnose and stage hilar cholangiocarcinoma.Modern imaging techniques allow accurate detection of the level of obstruction and the longitudinal and radial spread of the tumor.In addition,high-resolution MDCT and MR provide specific radiographic features to determine vascular involvement of anatomic structures,such as the hepatic artery or the portal vein,which are critical to decide the surgical strategy.Finally,radiological staging allows detection of patients with distant metastasis in the liver or peritoneum who will not benefit from a surgical approach.     

肝门胆管癌的外科手术治疗

回顾性分析我院2000-07-2005-07经肝门胆管癌手术治疗的62例患者临床资料和随访结果,总结肝门胆管癌的手术治疗体会.62例手术切除患者中行根治性切除(R0)22例,非根治性切除28例(R1,R2).根治性切除中位生存期34个月,1、3和5年生存率分别为92.0%、40.0%和18.0% ;非根治性切除中位生存期16个月,1、3和5生存率分别为83.0%、22.0%和0.另12例未完成病灶切除,9例行经肿瘤切开放置Y管内支架引流,3例行胆囊桥式肝管一十二指肠吻合,中位生存期10个月,1、3和5年生存率分别为15.0%、0和0.手术切除是治疗肝门胆管癌的有效治疗方法,根治性切除能明显改善预后.     

肝门部胆管癌根治术患者预后的影响因素分析

目的探讨影响肝门部胆管癌根治术患者预后的危险因素。方法回顾性分析2004年1月至2012年2月间陕西省榆林市二院收治的99例接受肝门部胆管癌根治术患者,根据病历记录及术后5年随访结果分为术后生存0~3年组(A组,68例)和术后生存3年以上组(B组,31例)。比较两组患者年龄、性别、病程、手术史、肿瘤直径等临床特征,比较患者的术前糖类抗原19-9(CA19-9)、Bismuth-Corlitte分型、肿瘤分化程度、淋巴结转移情况、门静脉浸润及尾状叶浸润情况;影响预后的多因素分析采用非条件Logistic回归分析。结果 B组患者的肿瘤直径显著小于A组,差异有统计学意义(P<0.05);两组患者在Bismuth-Corlitte分型方面差异无统计学意义(P>0.05)。单因素分析显示,A组患者以术前CA19-9指标>150 U/ml、肿瘤中低分化、淋巴结出现转移、门静脉及尾状叶浸润者居多,与B组患者比较,差异均有统计学意义(均P<0.05)。多因素分析结果显示,肝门部胆管癌根治术后生存期长短与肿瘤直径及术前CA19-9指标呈负相关(均P<0.05),与肿瘤分化程度、淋巴结转移、门静脉浸润及尾状叶浸润呈正相关(均P<0.05)。结论肿瘤直径、淋巴结转移、门静脉浸润、尾状叶浸润、肿瘤分化程度、术前CA19-9等均为影响肝门部胆管癌根治术患者预后的危险因素。     

Multidisciplinary management of hilar cholangiocarcinoma (Klatskin tumor): Extended resection is associated with improved survival

Background

Effective diagnosis and treatment of patients with hilar cholangiocarcinoma (HCCA) is based on the synergy of endoscopists, interventional radiologists, radiotherapists and surgeons. This report summarizes the multidisciplinary experience in management of HCCA over a period of two decades at the Academic Medical Center in Amsterdam, with emphasis on surgical outcome.

Methods

From 1988 until 2003, 117 consecutive patients underwent resection on the suspicion of HCCA. Preoperative work-up included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. More aggressive surgical approach combining hilar resection with extended liver resection was applied as of 1998. Outcomes of resection including actuarial 5-year survival were assessed.

Results

Eighteen patients (15.3%) appeared to have a benign lesion on microscopical examination of the specimen, leaving 99 patients with histologically proven HCCA. These 99 patients were analysed according to three 5-year time periods of resection, i.e. period 1 (1988-1993, n = 45), 2 (1993-1998, n = 25) and 3 (1998-2003, n = 29). The rate of R0 resections increased and actuarial five-year survival significantly improved from 20 ± 5% for the periods 1 and 2, to 33 ± 9% in period 3 (p < 0.05). Postoperative morbidity and mortality in the last period were 68% and 10%, respectively.

Conclusion

Extended surgical resection resulted in increased rate of R0 resections and significantly improved survival. Candidates for resection should be considered by a specialized, multidisciplinary team.     

Predictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survival.

AIMS: Several studies have analyzed the determinants of long-term survival in hilar cholangiocarcinoma (HCCA) patients, but the majority of these have not speculated adjuvant therapy on prognosis. We conduct this study to identify potential predictive factors for prognosis of HCCA focusing on aspects dealing with adjuvant therapy. PATIENTS AND METHODS: Data from 75 consecutive HCCA patients undergoing surgical resection with curative intent were recorded prospectively. The survivals of patients were comparable with respect to different factors followed by a univariate and multivariate analysis. RESULTS: Actual 1-year, 3-year, and 5-year survival rates were 84.0, 44.4 and 12.0%, respectively. By Cox proportional hazards survival analysis, the most powerful predictors of outcome was resection type (Hazard Ratio [HR] 17.4, 95% confidence interval [CI] 16.8-17.8), followed by adjuvant radiotherapy (RT) (HR 4.3, 95% CI 3.6-4.9), regional lymph nodes involvement (HR 2.1, 95% CI 1.7-2.6), and preoperative maximum serum total bilirubin level (HR 2.0, 95% CI 1.5-2.5). CONCLUSIONS: Our study showed overall a highly significant benefit in survival in favor of RT, and the difference was especially significant after R1/R2 resection and in patients with Bismuth III/IV type tumors. Postresection chemotherapy (CTx) did not show any clinical benefits. R0 resection still significantly improves survival. Lower total serum bilirubin level, no regional lymph nodes involvement conferred survival advantage.     

Impact of specialized multi-disciplinary approach and an integrated pathway on outcomes in hilar cholangiocarcinoma

Aims

To assess the outcomes of patients with hilar cholangiocarcinoma following referral to a specialist multi-disciplinary team.

Methods

Over an 11-year period, patients referred with hilar cholangiocarcinoma were identified from a prospectively maintained registry. Collated data included demographics, operative findings and histo-pathological data. Survival differences and prognostic factors were determined.

Results

345 patients were referred with hilar cholangiocarcinoma, of which 57 (16.5%) patients had surgery. Prior to 2008, of 143 patients referred, only 17 (11.9%) patients underwent surgery, compared to 40 (19.8%) of 202 patients referred from 2008 onwards (p = 0.051). In the surgery group, the majority of patients underwent left hemi-hepatectomy (n = 19). In addition, portal vein (n = 5), hepatic artery (n = 2) and inferior vena cava (n = 3) resections were performed. The R0 resection rate was 73.7%. The morbidity and mortality rates were 59.6% and 14.0%, respectively. The median disease-free survival was 16 (4–101) months. The presence of lymph node metastasis (p = 0.002) was the only predictor of poorer disease-free survival. The 5-year overall survival was 39.5% and was significantly better than that of the palliative group (p < 0.001).

Conclusions

Surgery is the optimal treatment option for patients with hilar cholangiocarcinoma and is associated with better overall survival. Prompt referral to tertiary centres with a core team of clinicians to manage this difficult condition may allow more patients to come to potentially curative surgical resections.     

Clinical outcome after resection of early-stage hilar cholangiocarcinoma

BackgroundLiver transplantation in patients with unresectable early-stage (<3 cm, node negative) hilar cholangiocarcinoma has been recently reported to be associated with longer survival compared to liver resection and therefore suggested as potential treatment option also in resectable disease. Here, we investigated the outcome of resection in early-stage tumours as the standard of care in an experienced European centre.MethodsPatients with de novo resectable hilar cholangiocarcinomas who underwent liver resection between mid-2009 and December 2017 were classified as early-stage (<3 cm and node negative) or later-stage tumours (≥3 cm and/or node positive), and were investigated with respect to clinical outcome.ResultsFifty-six patients were analyzed of whom 17 had early-stage tumours and 39 had later-stage tumours. The sex ratio (m:f) was 30:26. The median age was 65 years (range 33–80). The median follow-up was 17.0 months (range 0.7–92.4). 5-year overall survival (OS) rates were 82% in patients with early-stage tumours and 23% in patients with later-stage tumours, respectively. Median OS was 89.9 months and 27.6 months, respectively (HR 0.25 (95% CI 0.08–0.84), P = 0.024).ConclusionsIn an experienced European centre, 5-year survival rates after liver resection for early-stage hilar cholangiocarcinoma are comparable with reported outcomes after transplantation. The results of this study question the value of liver transplantation in this setting, especially with respect to the shortage of transplantable organs worldwide.     

Resection with total caudate lobectomy confers survival benefit in hilar cholangiocarcinoma of Bismuth type III and IV

Purpose

To identify prognostic predictors for overall survival of patients with hilar cholangiocarcinoma of Bismuth type III and IV (HCBT34), and to determine survival benefit and safety of total caudate lobectomy (TCL) in a Chinese centre.

Methods

From January 2001 to December 2010, 171 patients with the diagnosis of HCBT34, who underwent a potentially curative resection, were included in this study. Cox proportional hazards regression models were used to determine the association between possible prognostic variables and survival time. Curative resectability rate, morbidity and mortality were investigated also.

Results

Resection with TCL was significantly associated with more opportunity to achieve curative resection (p < 0.01), did not accompany with more morbidity (p = 0.39) and mortality (p = 0.67). Cox regression analysis demonstrated positive resection margins [Relative Risk (RR) 3.6, 95% CI 3.5–3.7], not well differentiation (RR 2.9, 95% CI 2.7–3.1), higher preoperative serum peak CA19-9 level (RR 1.6, 95% CI 1.5–1.7) and regional lymph nodes involvement (RR 1.5, 95% CI 1.4–1.6) as independent adverse prognostic variables.

Conclusions

Resection with TCL offers a long-term survival opportunity for HCBT34, with high curative resectability rates and an acceptable safety profile.     

Surgery for hilar cholangiocarcinoma: The Leeds experience

Aim

To review the experience with hilar cholangiocarcinoma and to determine the results of a radical surgical approach in a UK centre.

Methods

A 10-year review of all patients treated surgically for proximal bile duct carcinoma at a single surgical unit was conducted. Patient demographics, disease details and histopathology reports were reviewed. From January 1993 through December 2003, 106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61 patients received surgical exploration.

Results

Tumours were staged as follows (UICC 6th edition): stage IB, n = 10 IIA, n = 9; IIB, n = 20; III, n = 8; IV, n = 14. Out of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver resection with bile duct resection), 5 were considered unresectable and 12 underwent liver transplantation (LT). The caudate lobe was excised in 34 of the patients and regional lymphadenectomy was systematically carried out. Para-aortic lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17 and hepatic artery resection was performed in 4 cases. Negative histologic margins (R0) were achieved in 20 patients and microscopic margin involvement (R1) was seen in 16. In the remaining 8 resected patients, localised metastasis were found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic lymph nodes in 2); nevertheless the resection was performed and it was considered R2. Overall survival at 3 and 5 years for patients who underwent a resection was 43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial survival rates for patients who underwent R0 resection were 78%, 64% and 45% respectively, including the postoperative deaths (n = 3). The median survival time was 41.1 months. The 1-, 3- and 5-year actuarial survival rates for R1 resection and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival time for these groups was 15.4 and 6.8 months respectively. The actuarial survival rate at 1, 3 and 5 years for well-differentiated tumours (G1) was 73%, 54% and 40% (median 39.7 months). The figures for G2 were 60%, 48% and 0%. The figures for G3 (poorly differentiated) were 16% and 0% at three years (p = 0.03).The overall survival at 3 and 5 years for those patients who had a liver transplant was 41% and 20% including early postoperative mortality. The tumour grading (presence of poorly differentiated tumour) was found to be the only independent factor affecting the survival time producing a hazard ratio of 4.3 (p = 0.0034, 95% confidence interval 0.1007–6.342).

Conclusions

Radical surgical resection is the best treatment for hilar cholangiocarcinoma. R0 resection provides acceptable 5-year survival, but R1 resection may also provide acceptable palliation. In our experience TNM stage and tumour grade were the main determinants of long-term survival.     

Hilar cholangiocarcinoma

Hilar cholangiocarcinoma(HC) is a rare tumor.It accounts for 2/3 of the tumors of the biliary tract.Untreated,prognosis is very poor.Surgery is the only therapy that offers the possibility of cure but is technically very complex.With recent improvements in the therapeutic strategies applied by multidisciplinary teams,survival rates in the different series currently range from 25% to 45%.A group of experts devoted to HC(pathologists,gastroenterologists,radiologists,surgeons and oncologists) have reviewed and updated every open question in HC in a special issue.     

Long-term morbidity after surgery for perihilar cholangiocarcinoma: A cohort study

BackgroundSurgery for perihilar cholangiocarcinoma (pCCA) offers the only possibility of long-term survival, but remains a formidable undertaking. Traditionally, 90-day post-operative complications and death are used to define operative risk. However, there is concern that this metric may not accurately capture long-term morbidity after such complex surgery.MethodsA retrospective review of a prospective database of patients undergoing surgery for pCCA at a Western centre between January 2009-2020.ResultsEighty-five patients underwent surgical resection for pCCA with a median overall survival of 36.3 months. Post-op (<90day) morbidity rates were high with 46% of patients developing a major complication (Clavien-Dindo grade 3–4). Post-op mortality rate was 13%. In total 38% (28/74) of patients experienced at least 1 episode of delayed morbidity (>90-days of surgery) resulting in 53 separate admissions with a median LOS of 7 days (IQR 2–15). These episodes were predominately secondary to biliary obstruction with the majority requiring radiological intervention (Clavien-Dindo grade 3). The development of long-term morbidity was associated with increased recurrence rates and correlated with poorer OS (27.6 months vs. 65.7 months HR 2.2 CI 1.63-2.77).ConclusionsRoutinely cited 90-day morbidity and mortality does not accurately capture the patient morbidity experienced following surgery for pCCA. Surgery clearly offers a survival benefit and should be pursued in selected patients, but they must be fully counselled on the potential for long-term morbidity before embarking on this strategy.     

Pathological aspects of so called "hilar cholangiocarcinoma"

Cholangiocarcinoma(CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group.However,"hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or,more commonly,the extrahepatic hilar CC.Grossly,a major distinction can be made between papillary and non-papillary tumors.Histologically,most hilar CCs are well to moderately differentiated conventional type(biliary) carcinomas.Immunohistochemically,CK7,CK20,CEA and MUC1 are normally expressed,being MUC2 positive in less than 50% of cases.Two main premalignant lesions are known:biliary intraepithelial neoplasia(BilIN) and intraductal papillary neoplasm of the biliary tract(IPNB).IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma.A series of 29 resected hilar CC from our archives is reviewed.Most(82.8%) were conventional type adenocarcinomas,mostly well to moderately differentiated,although with a broad morphological spectrum;three cases exhibited a poorly differentiated cell component resembling signet ring cells.IPNB was observed in 5(17.2%),four of them with an associated invasive carcinoma.A clear cell type carcinoma,an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.     

肝门部胆管癌手术的历史和发展

随着外科技术和围手术期处理水平的提高,肝门部胆管癌的根治性切除率和生存率近年来明显提高,但仍有部分患者仅能行姑息性手术,因此,提高肝门部胆管癌的根治性切除率在相当长时间内仍是该病外科治疗的首要目标.下面我们结合文献讨论肝门部胆管癌的手术方式,尤其是肝门部胆管癌切除联合肝胰十二指肠切除术(hepatopancreatoduodenectomy,HPD).     

Outcome of surgical resection in Klatskin tumors

Cholangiocarcinomas are the second most frequent primary hepatic malignancy,and make up from 5% to 30% of malignant hepatic tumours.Hilar cholangiocarcinoma(HCC) is the most common type,and accounts for approximately 60% to 67% of all cholangiocarcinoma cases.There is not a staging system that permits us to compare all series and extract some conclusions to increase the long-survival rate in this dismal disease.Neither the extension of resection,according to the sort of HCC,is a closed topic.Some authors defend limited resection(mesohepatectomy with S1,S1 plus S4b-S5,local excision for papillary tumours,etc.) while others insist in the compulsoriness of an extended hepatic resection with portal vein bifurcation removed to reach cure.As there is not an ideal adjuvant therapy,R1 resection can be justified to prolong the survival rate.Morbidity and mortality rates changed along the last decade,but variability is the rule,with morbidity and mortality rates ranging from 14% to 76% and from 0% to 19%,respectively.Conclusion:Surgical resection continues to be the main treatment of HCC.Negative resection margins achieved with major hepatic resections are associated with improved outcome.Preresectional management with biliary drainage,portal vein embolization and staging laparoscopy should be considered in selected patients.Additional evidence is needed to fully define the role of orthotopic liver transplant.Portal and lymph node involvement worsen the prognosis and long-term survival,and surgery is the only option that can lengthen it.Improvements in adjuvant therapy are essential for improving long-term outcome.Furthermore,the lack of effective chemotherapy drugs and radiotherapy approaches leads us to can consider R1 resection as an option,because operated patients have a longer survival rate than those who not undergo surgery.     

腹腔镜与开腹肝门部胆管癌根治术疗效比较的Meta分析

目的:系统评价腹腔镜肝门部胆管癌根治术(laparoscopic radical resection for hilar cholangiocarcinoma, LRRHC)与开腹肝门部胆管癌根治术(open radical resection for hilar cholangiocarcinoma, ORRHC)两种手术方式的临床疗效。方法:以laparoscopy、laparoscopic、laparotomy、open surgery、bile duct neoplasms、hilar cholangiocarcinoma、腹腔镜手术、开腹手术、胆管癌、肝门部胆管癌为检索词,检索PubMed、Embase、the Cochrane Library、CBM、CNKI、VANFUN数据库。检索时间为1960年01月至2020年12月。根据Cochrane系统评价原则,由两名研究者独立筛选文献并提取数据,进行质量评价后使用Review Manager 5.3版进行统计分析。计量资料采用均数差(MD)及其95%可信区间(95%CI)表示,计数资料采用比值比(OR)及其95%CI表示。采...