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.

Distribution of splenic artery lymph nodes and splenic hilar lymph nodes

BACKGROUND Total gastrectomy with splenectomy is the standard treatment for advanced proximal gastric cancer with greater-curvature invasion.As an alternative to splenectomy,laparoscopic spleen-preserving splenic hilar lymph node(LN)dissection(SPSHLD)has been developed.With SPSHLD,the posterior splenic hilar LNs are left behind.AIM To clarify the distribution of splenic hilar(No.10)and splenic artery(No.11p and 11d)LNs and to verify the possibility of omitting posterior LN dissection in laparoscopic SPSHLD from an anatomical standpoint.METHODS Hematoxylin&eosin-stained specimens were prepared from six cadavers,and the distribution of LN No.10,11p,and 11d was evaluated.In addition,heatmaps were constructed and three-dimensional reconstructions were created to visualize the LN distribution for qualitative evaluation.RESULTS There was little difference in the number of No.10 LNs between the anterior and posterior sides.For LN No.11p and 11d,the anterior LNs were more numerous than the posterior LNs in all cases.The number of posterior LNs increased toward the hilar side.Heatmaps and three-dimensional reconstructions showed that LN No.11p was more abundant in the superficial area,while LN No.11d and 10 were more abundant in the deep intervascular area.CONCLUSION The number of posterior LNs increased toward the hilum and was not neglectable.Thus,surgeons should consider that some posterior No.10 and No.11d LNs may remain after SPSHLD.

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.

Diagnosis and surgical treatment of hepatic hilar cholangiocarcinoma

BACKGROUND: Hepatic hilar cholangiocarcinoma can be diagnosed early with the progress in diagnostic imaging, and thus the rate of resection of the tumor has increased markedly. To assess the effectiveness of resection, we reviewed 185 cases of hepatic hilar cholangiocarcinoma diagnosed and treated at our hospital. METHODS: The clinical data of 185 patients with hepatic hilar cholangiocarcinoma who had been treated surgically from 1972 to 2006 were retrospectively analyzed. RESULTS: The records of the 185 patients were divided into first stage (1972-1986) or second stage (1987-2006) according to the incidence of the tumor and its resection rate. Primary symptoms included upper abdominal discomfort or pain, anorexia, tiredness, weight loss and progressive jaundice. Ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) were first line methods for atraumatic diagnosis. If the patients displayed intrahepatic bile duct dilatation or were diagnosed as suffering from extrahepatic obstructive jaundice, percutaneous transhepatic cholangiography (PTC), MRCP or endoscopic retrograde cholangiopancreatography (ERCP) should be used. In this series, 87 patients underwent resection of the tumor (47.0%). Of the 87 patients, 43 received radical resection and 44 palliative resection. Fifteen patients underwent resection in the first stage and 72 in the second stage. A total of 74 patients were followed up after the resection. The median survival time of the radical resection group was 37 months and that of the palliative resection group was 17 months (P<0.001). The other 62 patients receiving no resection died within 1.5 years. CONCLUSIONS: Once patients are diagnosed with hepatic hilar cholangiocarcinoma, they should undergo exploratory laparotomy. Resection is the most effective method for the treatment of hepatic hilar cholangiocarcinoma.

Laparoscopic liver resection under hemihepatic vascular inflow occlusion using the lowering of hilar plate approach

BACKGROUND： With advances in technology, laparoscopic liver resection is widely accepted. Laparoscopic liver resection under hemihepatic vascular inflow occlusion has advantages over the conventional total hepatic inflow occlusion using the Pringle＇s maneuver, especially in patients with cirrhosis.METHOD： From November 2011 to August 2012, eight consecutive patients underwent laparoscopic liver resection under hemihepatic vascular inflow occlusion using the lowering of hilar plate approach with biliary bougie assistance.RESULTS： The types of liver resection included right hepatectomy（n1）, right posterior sectionectomy（n1）, left hepatectomy and common bile duct exploration（n1）, segment 4b resection（n1）, left lateral sectionectomy（n2）, and wedge resection（n2）. Four patients underwent right and 4 left hemihepatic vascular inflow occlusion. Four patients had cirrhosis. The mean operation time was 176.3 minutes. The mean time taken to achieve hemihepatic vascular inflow occlusion was 24.3minutes. The mean duration of vascular inflow occlusion was54.5 minutes. The mean intraoperative blood loss was 361 mL.No patient required blood transfusion. Postoperatively, one patient developed bile leak which healed with conservative treatment. No postoperative liver failure and mortality occurred. The mean hospital stay of the patients was 7 days.CONCLUSION： Our technique of hemihepatic vascular inflow vascular occlusion using the lowering of hilar plate approachwas safe, and it improved laparoscopic liver resection by minimizing blood loss during liver parenchymal transection.

Revision of bilateral self-expandable metallic stents placed using the stent-in-stent technique for malignant hilar biliary obstruction

Background: Endoscopic biliary decompression using bilateral self-expandable metallic stent(SEMS) placed using the stent-in-stent(SIS) technique is considered favorable for unresectable malignant hilar biliary obstruction(MHBO). However, occlusion of the bilateral SIS placement is frequent and revision can be challenging. This study was performed to investigate the efficacy, the long-term patency and the appropriate approach for revision of occluded bilateral SIS placement in unresectable MHBO. Methods: From January 2011 to July 2016, thirty-eight patients with unresectable MHBO underwent revision of occluded bilateral SIS placement. Clinical data including success rates and patency of revision, were retrospectively analyzed. Results: The technical success rate of revision was 76.3%. The clinical success rate of revision was 51.7% and mean patency of revision was 49.1 days. No significant predictive factor for clinical failure of revision was observed. The cell size of SEMS was not found to have significant effects on clinical success rates or revision patency. Conclusions: Revision of occluded bilateral SIS placement for MHBO showed fair patency and clinical success rate. Revision method and cell size of SEMS were not found to influence clinical outcomes.

Predictive factors for the failure of endoscopic stent-instent self-expandable metallic stent placement to treat malignant hilar biliary obstruction

AIM To investigate the factors predictive of failure when placing a second biliary self-expandable metallic stents(SEMSs). METHODS This study evaluated 65 patients with an unresectable malignant hilar biliary obstruction who were examined in our hospital. Sixty-two of these patients were recruited to the study and divided into two groups: the success group, which consisted of patients in whom a stent-in-stent SEMS had been placed successfully, and the failure group, which consisted of patients in whom the stent-in-stent SEMS had not been placed successfully. We compared the characteristics of the patients, the stricture state of their biliary ducts, and the implemented endoscopic retrograde cholangiopancreatography(ERCP) procedures between the two groups.RESULTS The angle between the target biliary duct stricture and the first implanted SEMS was significantly larger in the failure group than in the success group. There were significantly fewer wire or dilation devices(ERCP catheter, dilator, or balloon catheter) passing the first SEMS cell in the failure group than in the success group. The cut-off value of the angle predicting stent-in-stent SEMS placement failure was 49.7 degrees according to the ROC curve(sensitivity 91.7%, specificity 61.2%). Furthermore, the angle was significantly smaller in patients with wire or dilation devices passing the first SEMS cell than in patients without wire or dilation devices passing the first SEMS cell. CONCLUSION A large angle was identified as a predictive factor for failure of stent-in-stent SEMS placement.

Mutual regulation between microRNA-373 and methyl-CpGbinding domain protein 2 in hilar cholangiocarcinoma

AIM:To investigate the reciprocal modulation between microRNA(miRNA) and DNA methylation via exploring the correlation between miR-373 and methyl-CpGbinding domain protein(MBD)2.METHODS:MiR-373 expression was examined using the TaqMan miRNA assay.Methylation of miR-373 was investigated using methylation-specific polymerase chain reaction,and recruitment of methyl binding proteins was studied using the chromatin immunoprecipitation assay.Mutation analysis was conducted using the QuikChange Site-Directed Mutagenesis kit.The activity of miR-373 gene promoter constructs and targeting at MBD2-three prime untranslated region(3'UTR) by miR-373 were evaluated by a dual-luciferase reporter gene assay.RESULTS:In hilar cholangiocarcinoma,miR-373 decreased and was closely associated with poor cell differentiation,advanced clinical stage,and shorter survival.The promoter-associated CpG island of miR-373 gene was hypermethylated and inhibited expression of miR-373.MBD2 was up-regulated and enriched at the promoter-associated CpG island of miR-373.Methylation-mediated suppression of miR-373 required MBD2 enrichment at the promoter-associated CpG island,and miR-373 negatively regulated MBD2 expression through targeting the 3'UTR.CONCLUSION:MiR-373 behaves as a direct transcriptional target and negative regulator of MBD2 activity through a feedback loop of CpG island methylation.

SURGICAL TREATMENT OF HILAR BILE DUCT CARCINOMA

From June, 1986 to June 1989, 24 cases of hilar bile duct carcinoma were explored in the Surgical Department of General Hospital of PLA, 16/24 cases were resected, a resectability rate of 66%. The increase of resectability rate was due to earlier recognition of this condition and the extension of surgery, including major resection of liver as well as radical dissection of the hepato-duodenal ligament and repairative operations on the blood vessels. Among these 16 cases, major hepatic resection was performed in 10 cases, in which, 3 cases of resections of the middle lobe of the liver were done instead of right or extended right lobectomy. No operative mortality in the 30 days' postoperative period, but the postoperative morbidity rate was still high and most of the complications were related to biliary leakage and infection. Three patients died in the follow up period at 6, 14 and 15 months respectively. All of them died from biliary infection. The remaining 13 patients were still alive, the longest being 40 months and the average living time was 16.1 months. Probably, lowering of the operative mortality rate and morbidity rate are still the most important considerations in the surgical treatment of hilar carcinoma at the present time. Extensive liver resection especially on the right side, carried a high mortality rate in the deeply jaundiced patients. We considered that preoperative PTCD was of much less value than that used in lower bile duct obstruction such as tumors of the periampullary region. Preservation of the superior and posterior portion of the right lobe of the liver may be of advantages as to lowering postoperative hepatic failure and infection of the right subphrenic space as observed in this series of cases.

Liver transplantation benefits selected patients with hilar cholangiocarcinoma and colorectal liver metastases

Hilarcholangiocarcinoma(HCCA)isanaggressivemalignancy with a dismal prognosis. The 5-year survival rate has been reported to range from 39%to 50%if an R0 resection is obtained [1]. Approximately 25%patients with early stage HCCA of all cases can be treated with radical surgical resection [2], while most patients do not have a chance to receive a surgical procedure due to the advanced stage at the time of diagnosis. The poor prognosis is gen-

Safety and efficacy of transpapillary bridged bilateral side-by-side stenting for unresectable malignant hilar biliary obstruction

To the Editor:Biliary drainage is most frequently performed among endoscopic procedures using pancreatobiliary endoscopy.A large-diameter metallic stent can significantly extend the patency period rather than a plastic stent for extrahepatic biliary stricture.;However,the optimal drainage for the hilar biliary obstruction is still controversial.

Percutaneous insertion of a novel dedicated metal stent to treat malignant hilar biliary obstruction

BACKGROUND Percutaneous bilateral biliary stenting is an established method for the management of unresectable malignant hilar biliary obstruction.AIM To evaluate the efficacy and safety of a novel uncovered biliary stent, specifically designed for hilar reconstruction.METHODS This, single-center, retrospective study included 18 patients(mean age 71 ± 11 years;61.1% male) undergoing percutaneous transhepatic Moving cell stent(MCS) placement for hilar reconstruction using the stent-in-stent technique for malignant biliary strictures, between November 2020 and July 2021. The Patients were diagnosed with cholangiocarcinoma(12/18;66.6%), gallbladder cancer(5/18;27.7%), and colorectal liver metastasis(1/18;5.5%). Primary endpoints were technical(appropriate stent placement) and clinical(relief from jaundice) success. Secondary endpoints included stent patency, overall survival, complication rates and stent-related complications.RESULTS The technical and clinical success rates were 100%(18/18 cases). According to Kaplan-Meier analysis, the estimated overall patient survival was 80.5% and 60.4% at 6 and 12 mo respectively, while stent patency was 90.9% and 68.2% at 6 mo and 12 mo respectively. The mean stent patency was 172.53 ± 56.20 d and median stent patency was 165 d(range 83-315). Laboratory tests for cholestasis significantly improved after procedure: mean total bilirubin decreased from 15.2 ± 6.0 mg/d L to 1.3 ± 0.4 mg/d L(P < 0.001);mean γGT decreased from 1389 ± 832 U/L to 114.6 ± 53.5 U/L(P < 0.001). One periprocedural complication was reported. Stent-related complications were observed in 5 patients(27.7%), including 1 occlusion(5.5%) and 1 stent migration(5.5 %).CONCLUSION Percutaneous hilar bifurcation biliary stenting with the MCS resulted in excellent clinical and technical success rates, with acceptable complication rates. Further studies are needed to confirm these initial positive results.

Evaluation of MRI in Diagnosing Hilar Cholangiocarcinoma

Objective： To investigate the clinical application of MRI in the diagnosis and preoperative evaluation of hilar cholangiocarcinoma （HC）. Methods： Thirty-four cases of HC were examined with 1.5T super-conduct MR unit. The plain MRI and MRCP were followed by dynamic Gd-DTPA （0.1 mmol/kg） contrast-enhanced scanning, which was repeated at 30 s intervals in the first 3 min with the patient being remained in the same position. Delayed scanning was done at 5, 8, 10, 12 and 15 min respectively. 3D- DCE-MRA was performed in arterial and portal venous phase with an additional bolus injection of 15-20 mL Gd-DTPA （0.15-0.20 mmol/kg）. The contrast time-signal curve of both the liver and the tumor was drawn from DCE imaging, and both arterial and portal venous phase imaging were reconstructed with MIP. MRI findings were compared with surgical findings and pathology. Results： Hilar lesion, intrahepatic ducts dilatation and disconnect of main hepatic duct were shown in all cases. Thirty-one cases had tumor-delayed enhancement. In 3D-DCE-MRA, spiral artery deformed was displayed in 6 cases, infiltration, encasement or occlusion of portal vein was displayed in 18 cases. The accuracy of assessing tumor unresectability and resectability by preoperative MRI was 95.0% （19/20） and 78.6% （11/14） respectively. The total accuracy rate of MRI assessing was 88.2% （30/34）. Conclusion： All-in-one MR, including plain MR, MRCP, MR DCE and 3D-DCE-MRA, can accurately show the lesions and involvement of neighbouring tissues. It was of great value in diagnosis and preoperative evaluation of HC.

Biliary metal stents should be placed near the hilar duct in distal malignant biliary stricture patients

BACKGROUND Endoscopic biliary drainage using a self-expandable metallic stent(SEMS)has been widely performed to treat distal malignant biliary obstruction(DMBO).However,the optimal position of the stent remains unclear.AIM To determine the ideal position for SEMS placement.METHODS In total,135 DMBO patients underwent SEMS(uncovered or covered)placement over a ten-year period.A total of 127 patients with biliary obstruction between the junction of the cystic duct and Vater’s papilla were enrolled.An SEMS was placed through the upper common bile duct 2 cm from the biliary hilar duct in 83 patients(Hilar group)or near the top of the biliary obstruction in 44 patients(Lower group).Technical and functional success,adverse events,and risk factors for SEMS dysfunction were evaluated.RESULTS The stent patency period was significantly longer in the Hilar group than in the Lower group(P value<0.01).In multivariate analysis,the only statistically significant risk factor for SEMS dysfunction was being in the Lower group(hazard ratio:9.94,95%confidence interval:2.25–44.0,P<0.01).CONCLUSION A longer patency period was achieved by positioning the SEMS near the biliary hilar duct.

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma:A single-institution experience in China

AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival(OS) and disease-free survival(DFS) were evaluated by univariate and multivariate analyses.RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio(HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease(HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation(HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion(HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins(HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease(HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation(HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion(HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins(HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio(OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter(OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures(OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage(OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion(OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumorfree margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin.

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:1.130-173.646,P=0.040)were independent risk factors for postoperative complications.CONCLUSION:Overall postoperative morbidity and mortality rates after major liver resection are not improved by PBD in HCCA patients with jaundice.Preoperative TBIL>170μmol/L,Bismuth-Corlette classification and extended liver resection are independent risk factors linked to postoperative complications.

Risk factors and classifications of hilar cholangiocarcinoma

Cholangiocarcinoma is the second most common primary malignant tumor of the liver.Perihilar cholangiocarcinoma or Klatskin tumor represents more than 50% of all biliary tract cholangiocarcinomas.A wide range of risk factors have been identified among patients with Perihilar cholangiocarcinoma including advanced age,male gender,primary sclerosing cholangitis,choledochal cysts,cholelithiasis,cholecystitis,parasitic infection(Opisthorchis viverrini and Clonorchis sinensis),inflammatory bowel disease,alcoholic cirrhosis,nonalcoholic cirrhosis,chronic pancreatitis and metabolic syndrome.Various classifications have been used to describe the pathologic and radiologic appearance of cholangiocarcinoma.The three systems most commonly used to evaluate Perihilar cholangiocarcinoma are the Bismuth-Corlette(BC) system,the Memorial Sloan-Kettering Cancer Center and the TNM classification.The BC classification provides preoperative assessment of local spread.The Memorial Sloan-Kettering cancer center proposes a staging system according to three factors related to local tumor extent:the location and extent of bile duct involvement,the presence or absence of portal venous invasion,and the presence or absence of hepatic lobar atrophy.The TNM classification,besides the usual descriptors,tumor,node and metastases,provides additional information concerning the possibility for the residual tumor(R) and the histological grade(G).Recently,in 2011,a new consensus classification for the Perihilar cholangiocarcinoma had been published.The consensus was organised by the European Hepato-PancreatoBiliary Association which identified the need for a new staging system for this type of tumors.The classification includes information concerning biliary or vascular(portal or arterial) involvement,lymph node status or metastases,but also other essential aspects related to the surgical risk,such as remnant hepatic volume or the possibility of underlying disease.