National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

“Hepatic hilum area priority,liver posterior first”:An optimized strategy in laparoscopic resection for type Ⅲ-Ⅳ hilar cholangiocarcinoma

BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still worthy of further improvement and attention.AIM To summarize and share the application experience of the emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types Ⅲ and IV.METHODS The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed.RESULTS Among the 6 patients,4 were males and 2 were females.The average age was 62.2±11.0 years,and the median body mass index was 20.7(19.2-24.1)kg/m^(2).The preoperative median total bilirubin was 57.7(16.0-155.7)μmol/L.One patient had Bismuth-Corlette type Ⅲa,4 patients had Bismuth-Corlette type Ⅲb,and 1 patient had Bismuth-Corlette type Ⅳ.All patients successfully underwent pure laparoscopic radical resection following the strategy of“hepatic hilum area dissection priority,liver posterior separation first”.The operation time was 358.3±85.0 minutes,and the intraoperative blood loss volume was 195.0±108.4 mL.None of the patients received blood transfusions during the perioperative period.The median length of stay was 8.3(7.0-10.0)days.Mild bile leakage occurred in 2 patients,and all patients were discharged without serious surgery-related complications.CONCLUSION The emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ.This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA,shortens the learning curve,and is worthy of further clinical application.

Accurate resection of hilar cholangiocarcinoma using eOrganmap 3D reconstruction and full quantization technique

BACKGROUND For treatment of hilar cholangiocarcinoma(HCCA),the rate of radical resection is low and prognosis is poor,and preoperative evaluation is not sufficiently accurate.3D visualization has the advantage of giving a stereoscopic view,which makes accurate resection of HCCA possible.AIM To establish precise resection of HCCA based on eOrganmap 3D reconstruction and full quantification technology.METHODS We retrospectively analyzed the clinical data of 73 patients who underwent HCCA surgery.All patients were assigned to two groups.The traditional group received traditional 2D imaging planning before surgery(n=35).The eOrganmap group underwent 3D reconstruction and full quantitative technical planning before surgery(n=38).The preoperative evaluation,anatomical classification of hilar hepatic vessels,indicators associated with surgery,postoperative complications,liver function,and stress response indexes were compared between the groups.RESULTS Compared with the traditional group,the amount of intraoperative blood loss in the eOrganmap group was lower,the operating time and postoperative intestinal ventilation time were shorter,and R0 resection rate and lymph node dissection number were higher(P<0.05).The total complication rate in the eOrganmap group was 21.05%compared with 25.71%in the traditional group(P>0.05).The levels of total bilirubin,Albumin(ALB),aspartate transaminase,and alanine transaminase in the eOrganmap group were significantly different from those in the traditional group(intergroup effect:F=450.400,79.120,95.730,and 13.240,respectively;all P<0.001).Total bilirubin,aspartate transaminase,and alanine transaminase in both groups showed a decreasing trend with time(time effect:F=30.270,17.340,and 13.380,respectively;all P<0.001).There was an interaction between patient group and time(interaction effect:F=3.072,2.965,and 2.703,respectively;P=0.0282,0.032,and 0.046,respectively);ALB levels in both groups tended to increase with time(time effect:F=22.490,P<0.001),and there was an interaction effect between groups and time(interaction effect:F=4.607,P=0.004).In the eOrganmap group,there was a high correlation between the actual volume of intraoperative liver specimen resection and the volume of preoperative virtual liver resection(t=0.916,P<0.001).CONCLUSION The establishment of accurate laparoscopic resection of hilar cholangiocarcinoma based on preoperative eOrganmap 3D reconstruction and full quantization technology can make laparoscopic resection of hilar cholangiocarcinoma more accurate and safe.

Precise mapping of hilar cholangiocarcinoma with a skip lesion by SpyGlass cholangioscopy:A case report

BACKGROUND Cholangiocarcinoma(CC)is a very aggressive cancer with a poor prognosis.As surgery is the only curative therapy,preoperative evaluation of the tumor extent is essential for surgical planning.Although high-quality image modalities such as computed tomography and magnetic resonance imaging have been used extensively in preoperative evaluation,the accuracy is low.To obtain precise localization of tumor spread arising from the hilar region preoperatively,the development of an acceptable imaging modality is still an unmet need.CASE SUMMARY A 52-year-old female presented to our emergency department with jaundice,abdominal pain,and fever.Initially,she was treated for cholangitis.Endoscopic retrograde cholangiopancreatography with the cholangiogram showed long segment filling defect in the common hepatic duct with dilatation of bilateral intrahepatic ducts.Transpapillary biopsy was performed,and the pathology suggested intraductal papillary neoplasm with high-grade dysplasia.After treatment of cholangitis,contrasted-enhanced computed tomography revealed a hilar lesion with undetermined Bismuth-Corlette classification.SpyGlass cholan gioscopy showed that the lesion involved the confluence of the common hepatic duct with one skip lesion in the posterior branch of the right intrahepatic duct,which was not detected by previous image modalities.The surgical plan was modified from extended left hepatectomy to extended right hepatectomy.The final diagnosis was hilar CC,pT2aN0M0.The patient has remained disease-free for more than 3 years.CONCLUSION SpyGlass cholangioscopy may have a role in precision localization of hilar CC to provide surgeons with more information before the operation.

Proposal of a modified classification for hilar cholangiocarcinoma

Hilar cholangiocarcinoma is a malignant tumor that originates from the left and right hepatic ducts and their confluence.It is highly malignant and associated with a poor prognosis.Surgical resection is the only available curative treatment option.A scientific classification system can aid in the preoperative assessment of resectability and guide the development of appropriate surgical strategies.Several classification systems are available,with the Bismuth-Corlette(BC)classification being the earliest and most widely used.Similar to many other classifications,the BC classification relies on the secondary branching of the bile ducts as an important anatomical landmark,making it unsuitable for cases with variations in the bile duct anatomy.With advances in understanding the hepatic plate and anatomical structures at the hilum,the secondary bile ducts are no longer considered important anatomical landmarks.Therefore,modifications to the BC classification are needed to align with modern anatomical improvements and advancements in surgical techniques.Herein,we propose a modification to the BC classification.In this new system,the boundary of the hilar plate is considered as limit of the proximal ductal margin and used as an anatomical landmark,rather than the concept of“secondary bile ducts”in the BC classification.

Hilar Cholangiocarcinoma with Synchronous Metastases to Breast and Skeletal Muscle: A Case Report and Literature Review

Hilar cholangiocarcinoma has been reputed as a slow growth tumor in the past. Skeletal muscle is one of the most unusual sites of metastasis from any malignancy. We report herein a case of hilar cholangiocarcinoma with synchronous metastases to skeletal muscle and breast, and review the literature. The patient was a 48-year-old woman who presented with jaundice and weight loss. An inoperable hilar cholangiocarcinoma was diagnosed. She was treated with a combination of endoscopic plastic stent biloiary drainage and three-dimensional conformal radiotherapy （3DCRT）. Good response was achieved. Ten months later, she exhibited with a painful metastatic mass in the muscle rectus femoris of left thigh and a painless mass in the left breast. She underwent operation to relieve the pain, but died from liver failure after 8 months. The literature only offers isolated cases of cholangiocarcinoma with distant metastases, of which the common sites were cervical lymph node, bone, and portal venous system. Most patients were presented with multiple metastases with extensive local disease.

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 152percutaneous 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.

Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma

AIM： To determine the efficacy of external beam radiotherapy （EBRT）, with or without intraluminal brachytherapy （ILBT）, in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS： We analyzed 64 patients with locally advanced hilar cholangiocarcinoma, including 25 who underwent resection （17 curative and 8 non-curative）, 28 treated with radiotherapy, and 11 who received best supportive care （BSC）. The radiotherapy group received EBRT （50 Gy, 30 fractions）, with 11 receiving an ad- ditional 24 Gy （4 fractions） ILBT by iridium-192 with remote after loading. ILBT was performed using percu-taneous transhepatic biliary drainage （PTBD） route. Uncovered metallic stents （UMS） were inserted into nonresected patients with obstructive jaundice, with the exception of four patients who received percutaneous transhepatic biliary drainage only. UMS were placed endoscopically or percutaneously, depending on the initial drainage procedure. The primary endpoints were patient death or stent occlusion. Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups. Stent patency was compared in the radiotherapy and BSC groups.RESULTS： No statistically significant differences in patient characteristics were found among the resection, radiotherapy, and BSC groups. Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone; cholangitis occurred after endoscopic stenting, and patients were treated with PTBD. A total of 16 patients were administered additional systemic chemotherapy （5-fluorouracil-based regimen in 9, S-1 in 6, and gemcitabine in 1）. Overall survival varied significantly among groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery （P = 0.0076）. Cumulative survival in the radiotherapy group was significantly longer than in the BSC group （P = 0.0031）, but did not differ significantly from those in the non-resection group. Furthermore, the median survival time of patients in the radiotherapy group who were considered for possible resection （excluding the seven patients who were not candidates for surgery due to comorbid disease or age） was 25.9 mo. Stent patency was evaluated only in the 24 patients who received a metallic stent. Stent patency was significantly longer in the radiotherapy than in the BSC group （P = 0.0165）. Biliary drainage was not eliminated in any patient. To determine the efficacy of ILBT, we compared

Preoperative assessment of hilar cholangiocarcinoma:combination of cholangiography and CT angiography

BACKGROUND: Hilar cholangiocarcinoma is one of the most difficult carcinomas to manage because of the location of the main tumor at the hepatic hilus and the complex anatomy of the biliary, arterial, and portal systems. To plan an operation, it is important to acquire accurate information about the relationship between hilar cholangiocarcinoma and adjacent vessels. This study aimed to evaluate the clinical value of cholangiography combined with spiral CT three-dimensional (3D) angiography for a preoperative assessment of hilar cholangiocarcinoma. METHODS: From March 2007 to August 2009, cholangiography was performed in 13 patients with hilar cholangiocarcinoma. Meanwhile, contrast-enhanced abdominal scanning was performed using 16-slice spiral CT, and the 3D images of the hepatic artery and portal vein were acquired. The level and range of invasion of the hepatic artery, the portal vein, and the bile duct, the preoperative Bismuth classification, and T-staging were recorded and compared with those after surgical exploration. RESULTS: The hepatic artery and portal vein were reconstructed successfully in all these patients. Percutaneous transhepatic cholangiography was performed in 9 patients, endoscopic retrograde cholangiopancreatography in 1, and magnetic resonance cholangiopancreatography in 3. The CT angiography records of invasion of the hepatic artery were consistent with the results of explorations in these patients. The data from 5 of the 13 patients were consistent with those on invasion of the portal vein. The results of the Bismuth classification and the T-staging system were consistent with those of surgical exploration in 12 of the 13 patients. Seven of 8 patients who were estimated to be suitable for operation based on images were curatively treated and 5 who were judged to be unsuitable for curative operation by cholangiography and CT angiography were confirmed intraoperatively and underwent palliative procedures. CONCLUSIONS: Cholangiography combined with multi-slice spiral 3D CT angiography can satisfactorily delineate the local invasion of hilar cholangiocarcinoma and accurately evaluate the resectability. This approach, therefore, contributes to the planning of safe operation. (Hepatobiliary Pancreat Dis Int 2010; 9: 186-191)

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) ,hepatolithiasis(adjusted OR=3.278,P=0.018) ,cholecystolithiasis(adjusted OR =4.499,P<0.0001) ,cholecystectomy(adjusted OR =7.012,P=0.004) ,biliary ascariasis(adjusted OR= 7.188,P=0.001) ,liver fluke(adjusted OR=10.088,P =0.042) and liver schistosomiasis(adjusted OR=9.913,P=0.001) was higher in HC patients than in healthy controls. CONCLUSION:Biliary tract stone disease(choledocho-lithiasis,hepatolithiasis,cholecystolithiasis) and parasitic liver disease(biliary ascariasis,liver fluke,liver schistosomiasis) are the risk factors for HC in Chinese population.

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 reporteddue 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.

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

BACKGROUND Postoperative morbidity after curative resection for hilar cholangiocarcinoma(HCCA)is common;however,whether it has an impact on oncological prognosis is unknown.AIM To evaluate the influence of postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA.METHODS Patients 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).RESULTS Postoperative 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 decreasedOS 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 wasindependently 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, majormorbidity 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 forunfavorable prognosis in HCCA patients following curative resection.

Combined vascular resection and analysis of prognostic factors for hilar cholangiocarcinoma

BACKGROUND： Hilar cholangiocarcinoma （HCCA） is a devastating malignancy arising from the bifurcation of the hepatic duct, whether combined vascular resection benefits HCCA patients is controversial. This study was undertaken to assess the effect of combined vascular resection in HCCA patients and to analyze the prognostic factors.

Effect of hepatitis C virus core protein on modulation of cellular proliferation and apoptosis in hilar cholangiocarcinoma

BACKGROUND: Hepatitis C virus (HCV) is believed to be an important human pathogen causing carcinoma. But the effect of HCV infection on the alteration of cellular pro- liferation and apoptosis and the relationship between the effect and the development of hilar cholangiocarcinoma are largely unknown. The aim of this study was to assess the effect of HCV core protein on proliferation and apoptosis of hilar cholangiocarcinoma. METHODS: HCV core protein (HCV C protein) was de- tected by peroxidase-antiperoxidase assay in surgical speci- mens from 48 patients with hilar cholangiocarcinoma. The apoptosis index ( AI) and PCNA index ( PI) in hilar cholangiocarcinoma were detected by in situ end labeling assay and streptavidin-biotin assay respectively. RESULTS: The expression of HCV C protein was observed in 32 (67.7%) of the 48 specimens of hilar cholangiocarci- noma. The mean ± standard deviation for AI and PI was 3.52%±0.64% and 46.24%±11.46% respectively. The AI of hilar cholangiocarcinoma specimens with HCV C protein expression was significantly lower than that of HCV C pro- tein negative specimens (P<0.01), whereas the PI of HCV C protein positive specimens was significantly higher than that of HCV C protein negative specimens (P<0.01). CONCLUSION: HCV C protein may promote the cellular proliferation of hilar cholangiocarcinoma and inhibit its cel- lular apoptosis.

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.

Current therapy of hilar cholangiocarcinoma

BACKGROUND: Hilar cholangiocarcinoma (HC) is an adeno-carcinoma of the extrahepatic biliary tree arising from the main left or right hepatic ducts or their confluence. This tumor is still considered to be difficult to treat or to cure. DATA SOURCES: We reviewed the medical literature on HC. Relevant and updated information on this tumor was analyzed in a concise and easy-to-read manner. The article is not intended to be a systematic review, but an extensive search was conducted on PubMed and MEDLINE using the keywords 'hilar cholangiocarcinoma' and 'Klatskin tumor' until July 2011. RESULTS: The selection and the timing of management options for patients with HC are determined by the degree of certainty of the diagnosis, the general condition of the patients, the underlying liver function and the stage of the disease. Current treatment of HC can be divided into curative and palliative treatment. For the curative treatment, local excision should only be used on small tumors which are confined to the bile duct wall and Bismuth I papillary carcinoma. Partial hepatectomy should be combined with caudate lobe resection and porta-hepatis lymph node dissection. The results of these major resections can be improved with portal vein embolization, and staging laparoscopy and laparoscopic ultrasound. The role of preoperative biliary drainage is controversial. Autotransplantation for HC gave disappointing results while the Mayo Protocol of chemoradiation for selecting patients with unresectable HC for orthotopic liver transplantation has been widely accepted. Palliative treatment included bypass surgery, endoscopic or percutaneous stenting, photodynamic therapy, intraluminal brachytherapy, and external radiation and systemic therapy. CONCLUSIONS: Adequate surgery with R0 resection should be the main goal of treatment. For patients with unresectable HC, treatment aims to improve the quality and quantity of their survival.

Effect of mutated IKBa transfection on multidrug resistance in hilar cholangiocarcinoma cell lines

AIM: To explore the expression effect of mutated IκBα transfection on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells by inhibiting the activity of nuclear transcription factor-κB (NF-κB). METHODS: We used the mutated IicBa plasmid to transfect QBC939HCVC+ cells and QBC939 cells, and electrophoretic gel mobility shift assay (EMSA) to detect the binding activity of NF-κB DNA and the effect of the transfrecting mutated IκBα plasmid on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells and its expression protein (P-GP). RESULTS: Plasmid DNA was digested by restriction enzymes Xbal and Hand III, and its product after electrophoresis showed two bands with a big difference in molecular weight, with a size of 4.9 kb and 1.55 kb respectively, which indicated that the carrier was successfully constructed and digested with enzymes. The radioactivity accumulation of QBC939HCVC+ and QBC939 cells transfected with mutated IκBα plasmid was significantly lower than that of the control group not transfected with mutated IκBα plasmid. Double densimeter scanning showed that the relative signal density between the tansfection group and non-transfection group was significantly different, which proved that the mutated IκBα plasmid could inhibit the binding activity of NF-KB DNA in hilar cholangiocarcinoma cells. Compared to control group not transfected with m IκBα plasmid, the expression level of MDR-1mRNA in the QBC939 and QBC939HCVC+ cells transfected with mutated IκBα plasmid was lower. The expression intensity of P-GP protein in QBC939 and QBC939HCVC+ cells transfected with mutated IκBα was significantly lower than that of the control group not transfected with mutated IκBα plasmid. CONCLUSION: The mutated IκBα plasmid transfection can markedly reverse the multidrug resistance of hilar cholangiocarcinoma cells. Interruption of NF-κB activity may become a new target in gene therapy for hilar cholangiocar-cinogenesic carcinoma.

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 PubMed 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.

The ratio of MMP-2 to TIMP-2 in hilar cholangiocarcinoma:a semi-quantitative study

BACKGROUND: Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases- 2 (MMP-2 ) and its tissue inhibitor of metalloproteinase-2 (TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma. METHODS: The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections ob- tained from 50 patients with human hilar cholangiocarcino- ma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semi- quantitatively determine the ratio of MMP-2 to TIMP-2. RESULTS: The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in pa- tients with hilar cholangiocarcinoma. Significant diffe- rences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS: MMP-2 plays an essential role in tumor invasion and metastasis,while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma.

Postoperative Complications and Survival Analysis of Surgical Resection for Hilar Cholangiocarcinoma:A Retrospective Study of Fifty-Nine Consecutive Patients

Objective Hilar cholangiocarcinoma(HC)is invariably fatal without surgical resection.The primary aim of the current study was to determine the safety of variable surgical resections for patient with HC and their survival after surgical resection.In addition,prognostic factor for the overall survival was also evaluated.Methods The study included 59 consecutive patients who were newly diagnosed with HC and underwent surgical resections with curative intend between February 2009 and February 2017.Patients were followed up at 3-6 months intervals after hospital discharge.Postoperative complications and overall survival were determined.Associations of clinicopathologic and surgeon-related factors with overall survival were evaluated through univariate analysis and Cox regression analysis.Results Of patients with Bismuth and Corlette(B&C)type HI(n=19)and IV(n=25)HC lesions,33(55.9%)were treated with hilar resection combined with major liver resection(MLR),while the other 11 patients with type HI and IV,and those with type I(n=8)and II(n=7)HC lesions were treated with hilar resection.The overall surgical mortality was 5.1%and surgical morbidity was 35.6%.There was no statistical difference in the mortality between MLR group and hilar resection group(6.1%vs.3.8%;X2=0.703,P=0.145).The median follow-up period was 18 months(range,1-94 months).The 1-,3-,5-year survival rate was 59.3%,36.5%,and 17.7%,respectively.The overall survival after resections was 18 months.In HC patients with B&C type III and IV lesions,the median survival was 23 months for hilar resection with MLR and 8 months for hilar resection alone;the 1-,3-,5-year cumulative survival rate was 63.9%,23.3%,and 15.5%,respectively for hilar resection with MLR,and 11.1%,0,and 0,respectively for hilar resection alone,with significant diflerene observed(HR,9.902;95%CI,2.636-19.571,P=0.001).Four factors were independently associated with overall survival:preoperative serum Cal9-9(HR,7.039;95%CI,2.803-17.678,P<0.001),histopathologic grade(HR,4.964;95%CI,1.046-23.552,?=0.044),surgical margins(P=0.031),andAJCC staging(P=0.015).Conclusions R0 resection is efficacious in surgical treatment of HC.MLR in combination with caudate lobe resection may increase the chance of R0 resection and improve survival of HC patients with B&C type IK and IV lesions.Preoperatively prepared for biliary drainage may ensure the safety of MLR in most HC patients.Novel adjuvant therapies are needed to improve the survival of HC patients with poor prognostic factors.