Preoperative evaluation with T-staging system for hilar cholangiocarcinoma

AIM： To investigate the clinical value of T-staging system in the preoperative assessment of hilar cholangiocarcinoma. METHODS： From March 1993 to January 2006, 85 patients who had cholangiocarcinoma diagnosed by operative tissue-biopsy were placed into one of three stages based on the new T-staging system, and it was evaluated the resectability and survival correlated with T-staging. RESULTS： The likelihood of resection and achieving tumor-free margin decreased progressively with increasing T stage （P 〈 0.05）. The cumulative 1-year survival rates of T1, T2 and T3 patients were 71.8%, 50.8% and 12.9% respectively, and the cumulative 3-year survival rate was 34.4%, 18.2% and 0% respectively; the survival of different stage patients differed markedly （P 〈 0.001）. Median survival in the hepatic resection group was greater than in the group that did not undergo hepatic resection （28 mo vs 18 mo; P 〈 0.05）. The overall accuracy for combined MRCP and color Doppler Ultrasonagraphy detecting disease was higher than that of combined using CT and color Doppler Ultrasonagraphy （91.4% vs 68%; P 〈 0.05 ）. And it was also higher in detecting port vein involvement （90% vs 54.5%; P 〈 0.05）.CONCLUSION： The proposed staging system for hilar cholangiocarcinoma can accurately predict resectability, the likelihood of metastatic disease, and survival. A concomitant partial hepatectomy would help to attain curative resection and the possibility of longterm survival. MRCP/MRA coupled with color Doppler UItrasonagraphy was necessary for preoperative evaluation of hilar cholangiocarcinoma.（OR = 2.46, 95% CI = 0.98-6.14）, and a significantly elevated risk of developing esophageal cancer among alcohol drinkers among alcohol drinkers （OR = 9.86, 95% CI = 3.10-31.38）. CONCLUSION： ADH2 and ALDH2 genotypes areassociated with esophageal cancer risk. ADH2＊1 allele and ALDH2＊2 allele carriers have a much higher risk of developing esophageal cancer, especially among alcohol drinkers.     

肝门部胆管癌术后生存情况的影响因素分析

目的探讨影响肝门部胆管癌患者(hilar cholangiocarcinoma,HC)术后生存情况的影响因素。方法对在徐州医学院附属医院手术治疗的233例HC患者临床资料和随访结果进行回顾性分析,对可能影响预后的临床病理因素、不同的手术方式进行分析,并将影响因素纳入COX风险回归模型,分析患者生存的危险因素。结果 Kaplan-Meier结果显示,233例患者术后1、2、3年的生存率分别为74.3%、33.1%、14.6%;患者的年龄、性别、总胆红素与预后情况无相关性(P0.05);而肿瘤分型、肿瘤分化程度、淋巴结转移、门静脉浸润、尾状叶浸润和术前减黄与预后有相关性(P0.05);进行R0、R1、R2等不同手术方式和仅进行肿瘤活检的患者生存时间有显著性差异(P0.005);COX风险分析结果显示,手术方式、肿瘤分型、淋巴结转移和门静脉浸润因素对患者生存时间的影响差异有统计学意义(P0.05),是影响HC患者生存的独立危险因素。结论在对HC患者进行临床治疗时应特别注意手术方式、肿瘤分型、淋巴结转移和门静脉浸润等影响预后的独立因素,以提高生存率。     

肝门部胆管癌外科治疗预后影响因素分析*

目的 探讨影响外科治疗肝门部胆管癌（HCCA）患者预后的因素。方法 2010年1月~2014年1月收治的HCCA患者120例,行手术切除者67例【其中行根治性切除30例,姑息性切除（R1,R2）37例】和行胆管引流术53例（内引流术30例,外引流术23例）。结果 120例HCCA患者术后1 a、2 a、3 a生存率分别为67.5%（81/120）、45.8%（55/120）、25.0%（30/120）,其中根治性切除患者1 a、2 a、3 a生存率分别为93.33%、73.33%、60.00%,生存时间为（30.26±5.26） m,显著高于姑息性切除患者的（67.57%、48.65%、32.43%)和（22.14±4.78） m或胆管引流术患者【（52.83%、28.30%、0.0%)和（15.21±3.74） m, P<0.05】,姑息性切除患者上述指标又显著高于胆管引流术患者（P<0.05）;COX多因素分析显示,手术方式、切缘情况、细胞分化程度、TNM分期、淋巴结转移和门静脉侵犯均为影响HCCA患者外科治疗后生存的独立危险因素（P<0.05）。结论 影响HCCA患者治疗后预后的因素较多,应针对性地做出评估,给予合理的治疗,以使患者最大获益。     

Extended lymphadenectomy in hilar cholangiocarcinoma: What it will bring?

Lymph node dissection is always a hot issue in radical resection of hilar cholangiocarcinoma(HCCA). There are still controversies regarding whether some lymph nodes should be dissected, of which the para-aortic lymph nodes are the most controversial. This review synthesized findings in the literature using the Pub Med database of articles in the English language published between 1990 and 2019 on the effectiveness of extended lymphadenectomy including paraaortic lymph nodes dissection in radical resection of HCCA. Hepatobiliary surgeons have basically achieved a consensus that enough lymph nodes should be obtained to accurately stage HCCA. Only a very small number of studies have focused on the effectiveness of extended lymphadenectomy including para-aortic nodes dissection on HCCA. They reported that extended lymphadenectomy can bring some survival benefits for patients with potential para-aortic lymph node metastasis and more lymph nodes can be obtained to make the patient's tumor staging more accurate without increasing the related complications. Extended lymphadenectomy should not be adopted for HCCA patients with intraoperatively confirmed distant lymph node metastases. For these patients,radical resection combined with postoperative adjuvant chemotherapy seems to be a better choice. A prospective, multicenter, randomized, controlled clinical study of regional lymphotomy and extended lymphadenectomy in HCCA should be conducted to guide clinical practice. A standardized extended lymphadenectomy may help to more accurately stage HCCA. Future studies are required to further assess whether extended lymphadenectomy can improve long-term survival in negative celiac, superior mesenteric, and para-aortic lymph node diseases.     

Surgical management of hilar cholangiocarcinoma: the Nagoya experience

Of 400 patients with hilar cholangiocarcinoma who were treated at Nagoya University Hospital from 1977 to 2004, 301 (75%) underwent surgical resection. Most patients underwent major hepatectomy with extrahepatic bile duct resection. The overall mortality rate was 7.6% but had decreased to 2.5% in the last 5 years (p=0.007). The overall survival rates at 5, 10 and 15 years were 22%, 13% and 10%, respectively. The survival rates of 233 patients undergoing R0 resection were 27%, 16% and 13%, respectively. R1 or R2 resection, lymph node metastasis and portal vein involvement were significant negative prognostic factors, although survival was better than in patients with unresected tumours. The results show that aggressive surgical treatment of hilar cholangiocarcinoma offers good outcomes with an acceptable mortality rate.     

Diagnostic and surgical approaches in hilar cholangiocarcinoma

Hilar cholangiocarcinoma is a rare tumor. Surgery remains the only treatment to prolong survival. There is a correlation between the extent of diagnostic work-up and the achieved resection rates. Moreover, diagnostic work-up may contribute to an improvement of the surgical technique. Due to the perihilar fibrosis, the extent of the central lesion may be overestimated, which may lead to exclude the patient from potentially curative surgery. En bloc resection is requested to achieve tumor-free resection margins. The prognosis of the patients treated with surgery is strongly influenced by negative resection margins. According to our experience, 5-year survival of 78/111 patients with tumor resection (resection rate 71%) has been 30%. Forty-eight percent of the patients with curative en bloc resection of tumor and liver survived for more than 5 years. Perioperative mortality was 5.1%. The available data are supposed to reflect the results of centers with high caseload and not the general situation.     

Preoperative biliary drainage in patients with hilar cholangiocarcinoma undergoing major hepatectomy

AIM:To investigate the effect of preoperative biliary drainage(PBD)in jaundiced patients with hilar cholangiocarcinoma(HCCA)undergoing major liver resections.METHODS:An observational study was carried out by reviewing a prospectively maintained database of HCCA patients who underwent major liver resection for curative therapy from January 2002 to December 2012.Patients were divided into two groups based on whether PBD was performed:a drained group and an undrained group.Patient baseline characteristics,preoperative factors,perioperative and short-term postoperative outcomes were compared between the two groups.Risk factors for postoperative complications were also analyzed by logistic regression test with calculating OR and 95%CI.RESULTS:In total,78 jaundiced patients with HCCA underwent major liver resection:32 had PBD prior to operation while 46 did not have PBD.The two groups were comparable with respect to age,sex,body mass index and co-morbidities.Furthermore,there was no significant difference in the total bilirubin(TBIL)levels between the drained group and the undrained group at admission(294.2±135.7 vs 254.0±63.5,P=0.126).PBD significantly improved liver function,reducing not only the bilirubin levels but also other liver enzymes.The preoperative TBIL level was significantly lower in the drained group as compared to the undrained group(108.1±60.6 vs 265.7±69.1,P=0.000).The rate of overall postoperative complications(53.1%vs 58.7%,P=0.626),reoperation rate(6.3%vs 6.5%,P=1.000),postoperative hospital stay(16.5 vs 15.0,P=0.221)and mortality(9.4%vs 4.3%,P=0.673)were similar between the two groups.In addition,there was no significant difference in infectious complications(40.6%vs 23.9%,P=0.116)and noninfectious complications(31.3%vs 47.8%,P=0.143)between the two groups.Univariate and multivariate analyses revealed that preoperative TBIL>170μmol/L(OR=13.690,95%CI:1.275-147.028,P=0.031),Bismuth-Corlette classification(OR=0.013,95%CI:0.001-0.166,P=0.001)and extended liver resection(OR=14.010,95%CI:1.130-     

Risk factors for hilar cholangiocarcinoma: a case-control study in China

AIM:To study the association between hilar cholangiocarcinoma(HC) and pre-existing medical conditions. METHODS:Three hundred and thirteen HC patients admitted to the Eastern Hepatobiliary Surgery Hospital(Shanghai,China) in 2000-2005 and 608 healthy controls were enrolled in this study.Association between HC and pre-existing medical conditions was studied with their adjusted odds ratio(OR) calculated by logistic regression analysis. RESULTS:The prevalence of choledocholithiasis(adjusted OR=2.704,P=0.039) ,h...     

Assessment of clinical outcomes of advanced hilar cholangiocarcinoma

Background: Low resectability and poor survival outcome are common for hilar cholangiocarcinoma(HCCA), especially in advanced stages. The present study was to assess the clinical outcome of advanced HCCA, focusing on therapeutic modalities, survival analysis and prognostic assessment.Methods: Clinical data of 176 advanced HCCA patients who had been treated in our hospital between January 2013 and December 2015 were analyzed retrospectively. Prognostic effects of clinicopathological factors were explored by univariate and multivariate analysis. Survival predictors were evaluated by the receiver operating characteristic(ROC) curve.Results: The 3-year overall survival rate was 13% for patients with advanced HCCA. Preoperative total bilirubin(P = 0.009), hepatic artery invasion(P = 0.014) and treatment modalities(P = 0.020) were independent prognostic factors on overall survival. A model combining these independent prognostic factors(area under ROC curve: 0.748; 95% CI: 0.678–0.811; sensitivity: 82.3%, specificity: 53.5%) was highly predictive of tumor death. After R0 resection, the 3-year overall survival was up to 38%. Preoperative total bilirubin was still an independent negative factor, but not for hepatic artery invasion.Conclusions: Surgery is still the best treatment for advanced HCCA. Preoperative biliary drainage should be performed in highly-jaundiced patients to improve survival. Prediction of survival is improved significantly by a model that incorporates preoperative total bilirubin, hepatic artery invasion and treatment modalities.     

Addition of hepatectomy decreases liver recurrence and leads to long survival in hilar cholangiocarcinoma

AIM： To evaluate hepatic recurrence and prognostic factors for survival in patients with surgically resected hilar cholangiocarcinoma in a single institution over the last 13 years. METHODS： From 1994 to 2007, all patients with hilar cholangiocarcinoma referred to a surgical clinic were evaluated. Demographic data, tumor characteristics, and outcome were analyzed retrospectively. Outcome was compared in patients who underwent additional liver resection with resection of the tumor. RESULTS： Of the 69 patients submitted to laparotomy for tumor resection, curative resection （Ro resection） was performed in 40 patients, and palliative resection in 29. Thirty-one patients had only duct resection, and 38 patients had combined duct resection with liver resection including 34 total or part caudate lobes. Curative rates with the combined hepatectomy were significantly improved compared with those without additional hepatectomy （27/38 vs 13/31; X^2 = 5.94, P 〈 0.05）. Concomitant liver resection was associated with a decreased incidence of initial recurrence in liver one year after surgery （11/38 vs 23/31; X^2 = 13.98, P 〈 0.01）. The 3-year survival rate after Ro resection was 30.7% and was 10.5% for palliative resection. R0 resection improved the 3-year survival rate （30.7% vs 10.5%; X^2 = 12.47, P 〈 0.01）.CONCLUSION： Hepatectomy, especially including the caudate lobe combined with bile duct resection should be considered standard treatment to cure hilar cholangiocarcinoma.     

Operative considerations in resection of hilar cholangiocarcinoma

This article reviews the preoperative evaluation and operative considerations in patients with hilar cholangiocarcinoma. The preoperative evaluation is based on the imaging evaluation of the longitudinal and radial extent of the tumour along and around the hepatic duct confluence. The use of portal vein embolization to increase the safety of extended hepatectomy and the extent of surgical resection (caudate lobe and portal vein) are discussed within the context of recently published series.     

Long-term survival after intraluminal brachytherapy for inoperable hilar cholangiocarcinoma： A case report

Surgical resection with a tumor-free margin is the only curative treatment for hilar cholangiocarcinoma (Klatskin tumor). However, over half of the patients present late with unresectable tumors. Radiotherapy using external beam irradiation or intraluminal brachytherapy (ILBT) has been used to treat unresectable hilar cholangiocarcinoma with satisfactory outcome. We reported a patient with unresectable hilar cholangiocarcinoma surviving more than 6 years after combined external beam irradiation and ILBT.     

Laparoscopy in the management of hilar cholangiocarcinoma

The use of minimally invasive surgery has become widely accepted in many gastrointestinal fields, even in patients with malignancy. However, performing laparoscopic resection for the treatment of hilar cholangiocarcinoma is still not universally accepted as an alternative approach to open surgery, and only a limited number of such procedures have been reported due to the difficulty of performing oncologic resection and the lack of consensus regarding the adequacy of this approach. Laparoscopy was initially limited to staging, biopsy and palliation. Recent technological developments and improvements in endoscopic procedures have greatly expanded the applications of laparoscopic liver resection and lymphadenectomy, and some reports have described the use of laparoscopic or robot-assisted laparoscopic resection for hilar cholangiocarcinoma as being feasible and safe in highly selected cases, with the ability to obtain an adequate surgical margin. However, the benefits of major laparoscopic surgery have yet to be conclusively proven, and carefully selecting patients is essential for successfully performing this procedure.     

Hepatic mucormycosis mimicking hilar cholangiocarcinoma:A case report and literature review

Mucormycosis is a rare but invasive opportunistic fungal infection associated with a high mortality rate,and normally occurs in immunocompromised patients. In this report,we describe an immunocompetent patient suffering from hepatic mucormycosis secondary to adrenal mucormycosis,which masquerades as hilar cholangiocarcinoma. After surgical procedure and treatment with amphotericin B and itraconazole,the patient recovered well and had a 2-year infection-free survival. To our knowledge,this special clinical m...     

Postoperative morbidity adversely impacts oncological prognosis after curative resection for hilar cholangiocarcinoma

BACKGROUNDPostoperative morbidity after curative resection for hilar cholangiocarcinoma (HCCA) is common; however, whether it has an impact on oncological prognosis is unknown.AIMTo evaluate the influence of postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA.METHODSPatients with recently diagnosed HCCA who had undergone curative resection between January 2010 and December 2017 at The First Affiliated Hospital of Army Medical University in China were enrolled. The independent risk factors for morbidity in the 30 d after surgery were investigated, and links between postoperative morbidity and patient characteristics and outcomes were assessed. Postoperative morbidities were divided into five grades based on the Clavien-Dindo classification, and major morbidities were defined as Clavien-Dindo ≥ 3. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence-free survival (RFS) and overall survival (OS).RESULTSPostoperative morbidity occurred in 146 out of 239 patients (61.1%). Multivariate logistic regression revealed that cirrhosis, intraoperative blood loss > 500 mL, diabetes mellitus, and obesity were independent risk factors. Postoperative morbidity was associated with decreased OS and RFS (OS: 18.0 mo vs 31.0 mo, respectively, P = 0.003; RFS: 16.0 mo vs 26.0 mo, respectively, P = 0.002). Multivariate Cox regression analysis indicated that postoperative morbidity was independently associated with decreased OS [hazard ratios (HR): 1.557, 95% confidence interval (CI): 1.119-2.167, P = 0.009] and RFS (HR: 1.535, 95%CI: 1.117-2.108, P = 0.008). Moreover, major morbidity was independently associated with decreased OS (HR: 2.175; 95%CI: 1.470-3.216, P < 0.001) and RFS (HR: 2.054; 95%CI: 1.400-3.014, P < 0.001) after curative resection for HCCA.CONCLUSIONPostoperative morbidity (especially major morbidity) may be an independent risk factor for unfavorable prognosis in HCCA patients following curative resection.     

The role of liver transplantation in the treatment of hilar cholangiocarcinoma

Surgical resection or liver transplantation (LTx) are the only available treatments that offer a potential for long-term survival or cure in cases of hilar cholangiocarcinoma. Hilar resection in combination with partial hepatectomy and caudate lobectomy is regarded as the current treatment of choice. Overall 5-year survival rates range from 9% to 28%, and reach as high as 24-43% in R0 resections. Five-year survival rates in the very limited experience with LTx in hilar cholangiocarcinoma are not dramatically worse than those after resection. However, hilar cholangiocarcinoma is not at present an accepted indication for LTx given both the good results of LTx for benign diseases and the dramatic organ shortage. When compared with the prognosis of other gastrointestinal tumours, these survival rates are encouraging in the setting of an otherwise unresectable malignancy. As such, and considering the fact that it may represent the only possibility for cure, the general exclusion of patients with cholangiocarcinomas as candidates for LTx does not seem to be justified. Furthermore, recent advances in multimodal tumour therapy seem to be most promising in combination with LTx. Prospective studies are required to elucidate the influence of better patient selection and the role of multimodal treatments on the outcome of LTx in hilar cholangiocarcinoma. If the encouraging data achieved with neoadjuvant therapy prior to LTx are confirmed by further studies, we foresee that renewed interest in LTx for hilar cholangiocarcinoma could arise.     

Management of hilar cholangiocarcinoma in the North of England： Pathology, treatment, and outcome

AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center. METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed. RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152 percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these, 36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively. The 5-year survival rate was 4.2% for all patients, 21% for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P<0.05). Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions. CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality. Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.     

Solitary recurrence of hilar cholangiocarcinoma in a mediastinal lymph node two years after curative resection

We recently encountered an unusual case of hilar cholangiocarcinoma in which a solitary recurrence in a mediastinal lymph node occurred two years after curative resection of the primary tumor. A 64-year old woman was admitted to our hospital with a complaint of right hypochondrial discomfort. After imaging studies demonstrated a hilar cholangiocarcinoma in the left hepatic duct, a curative resection of the tumor was performed, consisting of a left hepatic lobectomy along with caudate lobectomy, regional lymph node dissection, and resection of the extrahepatic bile duct. No nodal metastasis was observed histologically. Two years after surgery, the patient was found to have a nodule in the posterior mediastinum, which was thoracoscopically resected. No other swollen lymph nodes, local recurrence, or distant metastasis were noted. Histologically, the nodule proved to be a metastatic lymph node, and adjuvant chemoradiation therapy was initiated. The patient remained well for the four years following her first operation and had no evidence of disease recurrence 28 mo after her second operation. To our knowledge, this case is the first report of solitary recurrence in a mediastinal lymph node after curative resection of hilar cholangiocarcinoma.     

Microvessel density correlates with lymph node metastases and prognosis in hilar cholangiocarcinoma

Background  Neovascularization was shown to be critically involved in the progression of multiple cancers, and treatment approaches targeting tumor-associated neovascularization provide convincing results in recent years in some tumor entities. However, little is known about the tumor-associated neovascularization in hilar cholangiocarcinoma. The present study was conducted to analyze tumor-associated neovascularization in hilar cholangiocarcinoma and to determine its influence on tumor growth, metastasis, recurrence, and prognosis. Methods  We analyzed tissue specimens of hilar cholangiocarcinoma (n = 60) by immunohistochemistry using the endothelial-specific antibody CD31 and subsequently quantified the microvessel density (MVD). The MVD was correlated with clinicopathological characteristics and recurrence pattern of the tumors as well as survival of patients. Results  Hilar cholangiocarcinoma revealed a high degree of vascularization, with a calculated mean MVD of 28.1 ± 14.5 vessels. Tumors with a high MVD had a significant higher incidence of lymph node involvement (P = 0.009) and local recurrence (P < 0.001). Furthermore, a high MVD was identified to be a significant overall survival disadvantage (3-year, 28% vs. 93%; 5-year, 8% vs. 78%; P < 0.001) as well as disease-free survival disadvantage (3-year, 7% vs. 88%, 5-year, 7% vs. 72%; P < 0.001), with MVD representing an independent prognostic factor for survival. Conclusions  Neovascularization is associated with nodal spread as well as local recurrence and serves as an independent prognostic factor for survival after curative resection of hilar cholangiocarcinoma. Therefore, tumor-associated neovascularization seems to be critically involved in the progression of this tumor entity. In addition, neovascularization may represent a potential target in he development of new therapeutic approaches in hilar cholangiocarcinoma.