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Background/aims: Based on their anatomy, cholangiocarcinomas (CCAs) are classified into intrahepatic, hilar, and distal CCAs. Although the diagnosis and treatment of each type of CCA are thought to be different, real-world data studies on the current practice are limited. Therefore, this study was designed to capture the current practice of diagnosing and treating perihilar CCA in Korea., Methods: We conducted a survey using an online platform. The questionnaire consisted of 18 questions designed to evaluate the current practice of diagnosing and treating perihilar CCA in Korea. The targets of this survey were biliary endoscopists who are members of the Korean Pancreatobiliary Association., Results: In total, 119 biliary endoscopists completed the survey. Of the respondents, 89.9% thought that the use of the International Classification of Diseases, 11th Revision (ICD-11) system is necessary to classify CCA. Approximately half of the respondents would recommend surgery or chemotherapy until patients were 80 years of age. For the pathological diagnosis of CCA, endoscopic retrograde cholangiopancreatography with biopsy was the most preferred modality. Routine preoperative biliary drainage was performed by 44.5% of the respondents. For operable CCAs, 64.7% of the respondents preferred endoscopic biliary drainage using plastic stents. For palliative biliary drainage, 69.7% of the respondents used plastic stents. For palliative endoscopic biliary drainage using metal stents, 63% of the respondents preferred the stent-in-stent method., Conclusions: A new coding system using the ICD-11 is needed for classifying CCAs. Guidelines for diagnosing and treating CCA based on the clinical situation in Korea are needed.

Biliary amputation neuroma is a rare benign tumor that develops due to the peribiliary dissection of nerve fibers during cholecystectomy, a common bile duct surgery, or lymph node dissection performed in gastric cancer surgery. We report a case of amputation neuroma that presented a challenging differential diagnosis from perihilar cholangiocarcinoma. A 64-year-old man, who had undergone open cholecystectomy 30 years ago, was incidentally found to have a bile duct tumor during computed tomography (CT) following surgery for renal cell carcinoma. He had no specific symptoms, and blood test results showed only a slight elevation in alkaline phosphatase levels. Contrast-enhanced CT revealed a 10-mm solid tumor with contrast effect in the common bile duct. On cholangiography, the tumor appeared as a protruding lesion with a smooth surface unilaterally. Given the atypical findings suggestive of cholangiocarcinoma, three bile duct biopsies were performed. Pathological examination did not rule out adenocarcinoma. The patient opted for surgery;however, an intraoperative rapid histological examination confirmed a benign disease, thereby avoiding extensive surgery. Consequently, a minimally invasive bile duct resection was performed. Postoperative histopathological examination revealed the tumor to be an amputation neuroma. Biliary amputation neuromas are characterized as unilateral protruding lesions with contrast effect or benign strictures. If such findings are observed in a patient with a history of surgery around the bile duct, the possibility of an amputation neuroma should be considered. However, completely ruling out malignancy preoperatively, even when suspecting amputation neuroma, can be challenging;therefore, considering surgery to achieve a definitive diagnosis is reasonable. During surgery, a rapid intraoperative histological examination is useful to avoid extensive procedures. In conclusion, diagnosing an amputation neuroma before surgery can be difficult, as it can mimic malignant tumors such as bile duct cancers. In this case, although a preoperative diagnosis of amputation neuroma was not feasible, performing a rapid intraoperative pathological examination helped avoid extensive surgery.

The obstruction of the bile duct secondary to non-Hodgkin lymphoma is extremely rare. That's why we present the case of a 63-year-old female patient who sought medical attention due to jaundice, dark urine, acholia, and weakness. Laboratory results showed a cholestatic pattern, and an ultrasound revealed dilation of the intra and extrahepatic bile ducts, for which a cholangio resonance was ordered. It showed an expansive formation with ill-defined borders compromising the common hepatic duct associated with its stenosis. The initial suspicion was a Klatskin tumor, for which a biopsy was performed, which reported infiltration of a double expressor large B-cell lymphoma as a primary neoplasm of the bile duct. The patient underwent chemotherapy treatment with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and went into remission. Due to continuous episodes of cholangitis, a Roux-en-Y hepatic jejunal anastomosis with biliary tract reconstruction was performed. Currently, she remains in remission, seven years after the diagnosis. This case highlights the rarity of large B-cell non-Hodgkin lymphoma in the bile duct and emphasizes the importance of biopsy for effective treatment, combining chemotherapy for the underlying disease and surgery for obstructive complications., (Universidad Nacional de Córdoba)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Jaundice usually occurs in the late stages of hepatocellular carcinoma (HCC). Obstructive jaundice is rarely seen as an initial presentation of HCC, as opposed to cholangiocarcinoma. Various causes of obstructive jaundice in these cases also known as "Icteric HCC" have been described such as tumour thrombi, compression, infiltration or tumours arising from native hepatocytes in the bile duct. We present a case of 74-year-old gentleman with "Icteric HCC" that clinically and radiologically mimicked cholangiocarcinoma for which the patient underwent left hepatectomy with Roux-en-Y hepaticojejunostomy. Histopathology revealed dilated large duct with polygonal sheets of cells of hepatoid morphology which stained diffusely positive for both glypican 3 and Hep-par 1. The epicentre was in the left hepatic duct with no discernible liver lesion and the tumour probably originated from the ectopic hepatocytes within the biliary duct The patient was disease free at 1.5 years of follow up. In conclusion, HCC should be a differential for obstructive jaundice. Patients with such "Icteric HCC" benefit from surgical resection with favourable outcomes. The prognosis in such patients is better than in patients of HCC with jaundice due to hepatic insufficiency.

Background: For some patients undergoing resection under the suspicion of a perihilar cholangiocarcinoma (pCCA), postoperative diagnosis may differ from the preoperative diagnosis. While a postoperative finding of benign bile duct stricture is known to affect 3-15% of patients, less has been described about the consequences of finding other biliary tract cancers postoperatively. This study compared pre- and postoperative diagnoses, risk characteristics, and outcomes after surgery for suspected pCCA., Methods: Retrospective single-center study, Karolinska University Hospital, Stockholm, Sweden (January 2009-May 2017). The primary postoperative outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. Survival analysis was performed by the Kaplan-Meier method., Results: Seventy-one patients underwent resection for suspected pCCA. pCCA was confirmed in 48 patients (68%). Ten patients had benign lesions (14%), 2 (3%) were diagnosed with other types of cholangiocarcinoma (CCA, distal n = 1, intrahepatic n = 1), while 11 (15%) were diagnosed with gallbladder cancer (GBC). GBC patients were older than patients with pCCA (median age 71 versus 58 years, p = 0.015), with a large proportion of patients with a high tumor extension stage (≥ T3, 91%). Median overall survival was 20 months (95% CI 15-25 months) for patients with pCCA and 17 months (95% CI 11-23 months) for patients with GBC (p = 0.135). Patients with GBC had significantly shorter median disease-free survival (DFS), 10 months (95% CI 3-17 months) compared 17 months (95% CI 15-19 months) for patients with pCCA (p = 0.010)., Conclusions: At a large tertiary referral center, 15% of patients resected for suspected pCCA were postoperatively diagnosed with GBC. Compared to patients with pCCA, GBC patients were older, with advanced tumors and shorter DFS. The considerable rate of re-classification stresses the need for improved preoperative staging, as these prognostic differences could have implications for treatment strategies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

It is difficult to directly obtain pathological diagnosis of perihilar cholangiocarcinoma (pCCA). Analysis of bile in the pCCA microenvironment, based on metabolomics and statistical methods, can help in clinical diagnosis. Clinical information, bile samples, blood liver function, blood CA199, CEA, and other indicators were collected from 33 patients with pCCA and 16 patients with gallstones. Bile samples were analyzed using untargeted metabolomics methods. A combination of multivariate and univariate analyses were used to screen for potential differential metabolites Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and differential metabolite remodeling, we explored changes in the pCCA pathway and potential therapeutic targets. There were significant differences in patient blood TBIL, ALT, AST, TBA, CA19-9, and CEA indices (p < 0.05, |log2(fc)| ≥ 1) between two groups. A significant correlation was found between these different indicators by Spearman's analysis. The clinical parameters were correlated with mass-to-charge ratios of 305 (Positive Ion Mode, POS) and 246 (Negative Ion Mode, NEG) in the metabolic group (|r| ≥ 0.7, P ≤ 10 -7 ). The result of this study indicated that bile untargeted metabolomics combined with statistical analysis techniques may be used for diagnose and treatment of pCCA., (© 2023. The Author(s).)

Early and differential diagnosis of perihilar cholangiocarcinoma (PHCCA) is highly challenging. This study aimed to evaluate whether volatile organic compounds (VOCs) in bile samples could be emerging diagnostic biomarkers for PHCCA. We collected 200 bile samples from patients with PHCCA and benign biliary diseases (BBD), including a 140-patient training cohort and an 60-patient test cohort. Gas chromatography-ion mobility spectrometry (GC-IMS) was used for VOCs detection. The predictive models were constructed using machine learning algorithms. Our analysis detected 19 VOC substances using GC-IMS in the bile samples and resulted in the identification of three new VOCs, 2-methoxyfuran, propyl isovalerate, and diethyl malonate that were found in bile. Unsupervised hierarchical clustering analysis supported that VOCs detected in the bile could distinguish PHCCA from BBD. Twelve VOCs defined according to 32 signal peaks had significant statistical significance between BBD and PHCCA, including four up-regulated VOCs in PHCCA, such as 2-ethyl-1-hexanol, propyl isovalerate, cyclohexanone, and acetophenone, while the rest eight VOCs were down-regulated. ROC curve analysis revealed that machine learning models based on VOCs could help diagnosing PHCCA. Among them, SVM provided the highest AUC of 0·966, with a sensitivity and specificity of 93·1% and 100%, respectively. The diagnostic model based on different VOC spectra could be a feasible method for the differential diagnosis of PHCCA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To improve treatment outcomes in patients with Klatskin tumor and obstructive jaundice by using of endoscopic bilioduodenal stenting., Material and Methods: There were 1904 transpapillary interventions between August 2017 and February 2022. Endoscopic bilioduodenal stenting was performed in 250 patients including 25 (10%) ones with Klatskin tumor., Results: Bilioduodenal plastic and self-expanding stents were installed in 19 (76%) and 6 (24%) patients, respectively. In Klatskin tumor type I, 11 patients (44%) underwent bilioduodenal stenting of common hepatic duct with plastic stent; 5 (20%) patients with Klatskin tumor type II received self-expanding stents. In case of tumor type IIIA, 3 (12%) patients underwent stenting of the right lobar duct with plastic stent. Four (16%) patients with Klatskin tumor type III B underwent stenting of the left lobar duct. Two 2 (8%) patients with Klatskin tumor type IV underwent bilateral bilioduodenal stenting with plastic and bifurcation self-expanding stents. Peroral cholangioscopy using the SpyGlass DS system was performed in 4 (16%) patients. No intraoperative complications were identified. One (4%) patient developed gastrointestinal bleeding in 2 postoperative days after retrograde intervention that did not require surgery. Moreover, 1 (4%) patient with distal dislocation of plastic bilioduodenal stent required redo bilioduodenal stenting. Three (12%) patients died from multiple organ failure despite adequate biliary decompression, and 22 (88%) patients were discharged in 8±5 days after retrograde intervention., Conclusion: Bilioduodenal stenting as minimally invasive and physiological method was highly effective for obstructive jaundice in patients with Klatskin tumor. Peroral cholangioscopy using the SpyGlass system provides effective and safe direct visualization of the biliary tract, as well as biopsy for morphological verification and prescription of chemotherapy in patients with intraductal growth of tumor.

Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms of the bile ducts and represents the second most common hepatic cancer after hepatocellular carcinoma; it is sub-classified as intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), the latter comprising both perihilar cholangiocarcinoma (pCCA or Klatskin tumor), and distal cholangiocarcinoma (dCCA). The global incidence of CCA has increased worldwide in recent decades. Chronic inflammation of biliary epithelium and bile stasis represent the main risk factors shared by all CCA sub-types. When feasible, liver resection is the treatment of choice for CCA, followed by systemic chemotherapy with capecitabine. Liver transplants represent a treatment option in patients with very early iCCA, in referral centers only. CCA diagnosis is often performed at an advanced stage when CCA is unresectable. In this setting, systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option, but the prognosis remains poor. In order to ameliorate patients' survival, new drugs have been studied in the last few years. Target therapies are directed against different molecules, which are altered in CCA cells. These therapies have been studied as second-line therapy, alone or in combination with chemotherapy. In the same setting, the immune checkpoints inhibitors targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), have been proposed, as well as cancer vaccines and adoptive cell therapy (ACT). These experimental treatments showed promising results and have been proposed as second- or third-line treatment, alone or in combination with chemotherapy or target therapies., Competing Interests: Conflicts of interest Pietro Invernizzi and Sara Massironi are members of the European Reference Network on Hepatological Diseases (ERN RARE LIVER), and they thank AMAF Monza ONLUS and AIRCS for the unrestricted research funding. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Portal biliopathy refers to the changes in the bile duct caused by portal vein thrombosis or obstruction. It is assumed to be caused by cavernous transformation due to the development of the venous system surrounding the bile duct, but the exact pathology is still unknown. Biliary morphologic abnormalities of portal biliopathy are discovered incidentally on radiographic images, but it is sometimes difficult to differentiate them from cholangiocarcinoma. Given the poor prognosis of cholangiocarcinoma, a surgical approach can be considered when the diagnosis is uncertain. Herein, we report a case of portal biliopathy with bile ductal wall thickening, which was diagnosed after surgical resection was performed due to the presumed diagnosis of cholangiocarcinoma.

Background: Preoperative serum carbohydrate antigen 125 (CA125) is used to judge the diagnosis and prognosis of various tumors. However, the relationship between preoperative serum CA125 and prognosis of hilar cholangiocarcinoma (HCCA) has not been proven. This study aims to evaluate preoperative serum CA125 in predicting the prognosis of HCCA after resection., Methods: A total of 233 patients after radical resection of HCCA were included. The associations between the levels of preoperative serum CA125 and the clinicopathological characteristics of patients were analyzed. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to identify independent risk factors associated with recurrence-free survival (RFS) and overall survival (OS)., Results: Among 233 patients, 198 (84.97%) with normal CA125 levels (≤35 U/mL) had better OS and RFS than 35 (15.02%) patients with higher CA125 levels (>35 U/mL). Preoperative serum CA125 was significantly correlated with tumor size, Bismuth-Corlette classification, microvascular invasion and carcinoembryonic antigen (CEA) (p < 0.001, p = 0.040, p = 0.019 and p = 0.042, respectively). The results of multivariable Cox regression showed that preoperative serum CA125 >35 U/mL (p = 0.002, HR = 1.910 for OS; p = 0.006, HR = 1.755 for RFS), tumor classification (p < 0.001, HR = 2.110 for OS; p = 0.006, HR = 1.730 for RFS), lymph node metastasis (p < 0.001, HR = 1.795 for OS; p < 0.001, HR = 1.842 for RFS) and major vascular invasion (p = 0.002, HR = 1.639 for OS; p = 0.005, HR = 1.547 for RFS) were independent risk factors for both OS and RFS., Conclusions: Preoperative serum CA125 is a good tumor marker for predicting prognosis after radical surgery for HCCA., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The aim of this study was to investigate the incidence and risk factors of primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma., Methods: All patients who underwent a major liver resection for presumed perihilar cholangiocarcinoma between 2000 and 2020 at 2 tertiary-referral hospitals were included. Liver failure was defined according to the International Study Group for Liver Surgery criteria, and only grade B/C was considered clinically relevant. Primary liver failure was defined as failure without any underlying postoperative cause, and secondary liver failure was defined as liver failure with an onset after an underlying postoperative complication as a cause., Results: The incidence of liver failure and 90-day mortality were 20.9% and 17.0% in the 253 included patients, respectively. The incidences of primary liver failure was 9.1% and secondary liver failure was 11.9%. Abdominal sepsis, portal vein thrombosis, and arterial thrombosis were the most frequent causes. The absence of preoperative remnant liver assessment and blood loss were independent risk factors for primary liver failure. Independent risk factors for secondary liver failure were Eastern Cooperative Oncology group performance status, percutaneous biliary drainage, and preoperative cholangitis., Conclusion: Liver failure after major liver resection for perihilar cholangiocarcinoma occurred in 1 of every 5 patients. The proposed subdivision into primary and secondary liver failure could help to understand differences in outcomes between centers and help to reduce liver failure., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Elevated fibrinogen (Fbg) levels contribute to tumor progression and metastasis. However, little is known regarding the association of the clinicopathological characteristics and the prognosis of hilar cholangiocarcinoma (HC) with plasma fibrinogen., Methods: Data on the plasma Fbg levels, clinicopathological characteristics, and overall survival were retrospectively collected. Plasma fibrinogen concentrations over 4.0 g/L were classified as hyperfibrinogen, elevated fibrinogen, or abnormal fibrinogen levels. We then analyzed the relationships among plasma fibrinogen level, clinicopathological features, and patient prognosis., Results: A total of 171 HC patients were included. An elevated plasma fibrinogen level was associated with lymph-node metastasis (P < 0.001), the AJCC stage (P < 0.001), the surgical margin (P = 0.005), and vascular invasion (P = 0.027). Univariate analyses revealed that preoperative plasma fibrinogen (P < 0.001), operative blood loss (P = 0.044), vascular invasion (P < 0.001), CA19-9 (P = 0.003), surgical margin (P < 0.001), T stage (P < 0.001), histologic differentiation (P = 0.007), and lymph-node metastasis (P < 0.001) were associated with OS. The survival time of patients with high Fbg levels was shorter than that of patients with normal fibrinogen levels (P < 0.001). Furthermore, a multivariate analysis showed that fibrinogen was negatively and independently associated with the HC prognosis (P = 0.029)., Conclusions: An elevated plasma Fbg level was associated with lymph-node metastasis, vascular invasion, the surgical margin, and the tumor stage, and the Fbg level might therefore be an independent factor associated with poor outcomes in HC patients., (© 2021. Springer Nature Singapore Pte Ltd.)

Abstract: The purpose of this study was to determine the glucose metabolism at delay phase measured by pretreatment dual-time-point 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/ computed tomography (CT) provides prognostic information independent of well-known prognostic factors in patients with intrahepatic or perihilar cholangiocarcinoma (ICC or PCC).From July 2012 to December 2017, 55 patients (men 27, women 28, mean age 68 ± 11 years) with pathologically proven ICC or PCC were enrolled in this retrospective study. The dual-time-point 18F-FDG PET/CT as part of a staging workup was performed in all patients. The patient's data includes age, sex, serum CA19-9, presence of LN or distant metastasis, early SUVmax (early maximum standardized uptake value [eSUV]), delay SUVmax (delay maximum standardized uptake value [dSUV]), retention index of SUVmax (percent change of maximum standardized uptake values [ΔSUV]), neutrophil to lymphocyte ratio (NLR) and histopathology including pCEA, p53, Ki-67 index. The analysis of the relationship between metabolic parameters and survival was done using the Kaplan-Meier curve and Cox proportional hazards regression model.Median survival for all patients was 357 days. Median early and delay SUVmax was 5.2 (range: 2.0-21.4) and 6.5 (range 2.7-24.5), respectively. The overall survival was found to be significantly related to eSUV, dSUV, ΔSUV, age, serum CA19-9 and NLR in univariate analysis. In multivariate analysis, dSUV (P = .014, 95%CI; 1.30-10.7, HR 3.74) and ΔSUVmax (P = .037, 95%CI; 1.05-6.12, HR 2.5) were independent factors of overall survival. Kaplan-Meier curve analysis clearly showed the significant difference of overall survival between 2 groups (high eSUV, low eSUV + high ΔSUV vs low eSUV and ΔSUV, P < .001) among the comparisons of the SUV parameters on FDG PET. In the receiver operating characteristic analysis using combinations of the SUV parameters, the 2 groups [eSUV + ΔSUV (P = .0001, area under the curve [AUC] 0.68) and dSUV + ΔSUV (P = .0002, AUC 0.71)] showed significantly larger AUC than the other groups applying eSUV or dSUV alone (AUC 0.61 and AUC 0.68).dSUV and ΔSUV on pretreatment dual-time-point 18F-FDG PET/CT can be useful parameters in the prediction of survival in patients with ICC or PCC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hilar cholangiocarcinoma (HCCA), which lacks specific clinical manifestations, remains very difficult to distinguish from benign disease. This distinction is further complicated by the complex hilar anatomy. We conducted the present study to evaluate the differential diagnosis of these conditions. Sixty-five patients underwent resection surgery for suspected HCCA between January 2011 and October 2018. Institutional Review Board of Shengjing hospital agreed this study and all participants sign an informed consent document prior to participation in a research study. Following a postoperative pathology analysis, all patients were divided into two groups: malignant group (54 patients with HCCA) and benign group (11 cases with benign lesions). Compared with the benign group, the malignant group had a significantly higher median age and serum CA19-9, CEA, ALT, BILT and BILD levels (P < 0.05). In contrast, the groups did not differ significantly in terms of the sex distribution, clinical manifestations, serum levels of AST and ALKP, and imaging findings. In a receiver operating characteristic curve analysis, we identified a CA19-9 cutoff point of 233.15 U/ml for the differential diagnosis and CEA cutoff point of 2.98 ng/ml for the differential diagnosis. The differential diagnosis of HCCA and benign hilar lesions remains difficult. However, we found that patients with HCCA tended to have an older age at onset and higher serum levels of CA19-9, CEA, BILT, ALT and BILD. Furthermore, patients with a serum CA19-9 level >233.15 U/ml and CEA level >2.98 ng/ml are more likely to have malignant disease., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The neurofibroma of the bile duct is an extremely rare and generally asymptomatic disease, however, it maybe cause obstructive jaundice and mimic a Klatskin tumor, leading to radical surgical treatment and increased patient morbidity. We present the case of a 62-year-old woman who underwent cholecystectomy 10 years ago, with jaundice and pain in the right upper quadrant, as well as auxiliary tests compatible with cholestasis. Dilation of the bile duct and the presence of a tumor in the left hepatic duct were observed by magnetic cholangioresonance. The preoperative clinical diagnosis was hilar cholangiocarcinoma, but the histopathological study revealed a neoplasm composed of spindle cells without atypia or mitotic activity, whose neurogenic lineage supported by its positivity to protein S100 in immunohistochemistry. We report the case given its infrequency in the literature and its relevance, as it is a benign entity, as a differential diagnosis of cancer.

Background: Approximately 15% of patients undergoing resection for presumed perihilar cholangiocarcinoma (PHC) have benign disease at final pathological assessment. Molecular imaging targeting tumor-specific biomarkers could serve as a novel diagnostic tool to reduce these futile surgeries. Imaging agents have been developed, selectively binding integrin α ν β 6, a cell receptor upregulated in pancreatobiliary malignancies, for both (preoperative) PET and (intraoperative) fluorescent imaging. Here, expression of integrin α ν β 6 is evaluated in PHC, intrahepatic cholangiocarcinoma (ICC), hepatocellular carcinoma (HCC) and benign disease mimicking PHC using immunohistochemistry., Materials & Methods: Three tissue microarrays (TMA) including 103 PHC tumor cores and sixty tissue samples were selected from resection specimens of pathologically proven PHC (n = 20), ICC (n = 10), HCC (n = 10), metastatic PHC lymph nodes (n = 10) and benign disease (presumed PHC with benign disease at pathological assessment, n = 10). These samples were stained for integrin α ν β 6 and quantified using the H-score., Results: Immunohistochemical staining for integrin α ν β 6 showed membranous expression in all twenty PHC whole mount slides (100%) and 93 out of 103 (92%) PHC tumor cores. Mean H-score of PHC samples was 195 ± 71, compared to a mean H-score of 126 ± 57 in benign samples (p = 0.013). In both benign and PHC samples, inflammatory infiltrates and pre-existent peribiliary glands showed integrin α ν β 6 expression. The mean H-score across ten ICC was 33 ± 53, which was significantly lower compared to PHC (p < 0.001) but too weak to consistently discriminate ICC from HCC (H-score 0)(p = 0.062)., Conclusion: Integrin α ν β 6 is abundantly expressed in PHC and associated metastatic lymph nodes. Expression is significantly higher in PHC as compared to benign disease mimicking PHC, ICC and HCC, emphasizing its potential as a target for tumor-specific molecular imaging., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gallbladder carcinoma and extrahepatic cholangiocarcinoma Abstract. In this article, we focus on three entities of malignant biliary tumors: gallbladder carcinoma, distal and perihilar cholangiocarcinoma. Those are rare malignant tumors which require an extensive interdisciplinary expertise in the treatment of hepato-pancreato-biliary conditions in order to provide an appropriate diagnostic work-up, correctly assess resectability and come up with a clear-cut multimodal treatment plan. Perihilar cholangiocarcinoma (Klatskin-tumour) usually requires the most complex evaluation of resectability, which involves not only the assessment of vascular in- and outflow and an adequate biliary drainage, but also aims to ensure that enough functional liver tissue is left after resection. To this end, preoperative portal vein embolization may be used to increase the size the future liver remnant. In highly selected, unresectable cases of perihilar cholangiocarinoma, or if a primary sclerosing cholangitis is present, neoadjuvant chemoradiotherapy followed by liver transplantation can be evaluated as a curative option. Distal cholangiocarcinomas usually are treated by a partial pancreaticoduodenectomy (Whipple operation). The surgical treatment of gallbladder cancer ranges from simple cholecystectomy to major liver resection with complex biliary and vascular reconstruction, dependent on tumour stage. The surgical treatment is usually followed by an adjuvant regimen of Capecitabine which can significantly improve survival, while a combination Cisplatin and Gemcitabine is used in the palliative setting.

On the basis of the conducted literary search, a number of conclusions can be drawn. When performing preoperative biliary drainage (PBD), it is necessary to have a clear understanding: why is this procedure performed (severe liver failure, cholangitis, long preoperative preparation is required due to comorbid status, neoadjuvant chemotherapy is necessary, etc.)? Routine use of PBD is impractical. In the presence of indications for PBB in perihilar cholangiocarcinoma, percutaneous decompression is preferable, in periampullary tumors, endoscopic. Moreover, both methods can be alternative (for example, in case of technical failure of the first priority). There is also no convincing evidence of the superiority of metal stents over plastic ones for PBD (except in cases of long-term preoperative preparation or neoadjuvate treatment) for periampular tumors. To date, a decrease in overall survival and a higher incidence of implantation metastases have not been proven when using the antegrade PBD method. Large multicenter studies are required with differentiation of patients according to the nosological principle in order to more accurately understand the place of each method, as well as to determine clear indications for PBD and those clinical situations when its implementation is impractical.

Cholangiocarcinomas are rare and often diagnosed late. Clear cell histology is a rare variant of such cancers. We report one such case of a man in his late 60s, with a history of excess alcohol intake, who was found to have deranged liver biochemical tests incidentally during an admission for an allergic reaction. Subsequent imaging to investigate this suggested a diagnosis of perihilar cholangiocarcinoma (ultrasound, CT, MRI, cholangiogram). Biopsy confirmed this to be of clear cell type on histology and immunohistochemistry. Diagnosis and further management of this rare entity was conducted in multidisciplinary meetings with the regional hepatobiliary centre. The patient was deemed unsuitable for surgical resection, underwent chemotherapy but died 1 year later., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hilar biliary stricture caused by isolated fungal infections in immunocompetent patients are considered to be extremely rare and difficult to the diagnose from the outset., Case Presentation: We report a unique case of granulomatous cholangitis based on isolated biliary fungal infection manifesting as obstructive jaundice and mimicking hilar cholangiocarcinoma in an immunocompetent woman. A 67-year-old Japanese woman was referred to our hospital for obstructive jaundice. She had been followed up for hypochondroplasia by the referring physician. Her total bilirubin level was 5.4 mg/dL. Viral hepatitis screening was found to be negative, and serum IgG4 was within normal limits; however, her CA19-9 level was high. Abdominal computed tomography revealed dilatation of the intrahepatic bile ducts. Abdominal echogram detected a solid mass in the hilar bile duct. Her magnetic resonance cholangiopancreatography has also revealed an abrupt stenosis of the primary biliary confluence with upstream dilatation of the intrahepatic bile ducts. Endoscopic nasobiliary drainage was then performed to improve the obstructive jaundice. Although biliary cytology did not reveal malignant findings, the bile duct in the hilum showed severe stenosis, and hilar cholangiocarcinoma could not be completely excluded. The patient had a developmental disorder based on chondrodystrophy. To avoid excessive surgical stress, such as hepatic lobectomy, we performed resection of the extrahepatic bile duct and Roux-en-Y hepaticojejunostomy reconstruction. Intraoperative frozen sections of the resection margins were determined to be negative for tumor. The resected specimen showed multiple strictures inside the common bile duct, numerous calculi in the lumen, and little free space. The final pathological diagnosis was granulomatous cholangitis due to fungal infection. The patient's postoperative course was deemed uneventful. She was discharged from our hospital 23 days after surgery without antifungal treatment., Conclusions: For a unique case of granulomatous cholangitis based on isolated biliary fungal infection mimicking hilar cholangiocarcinoma, we were able to avoid excessive invasion and performed appropriate surgical management.

The widespread use of liver biopsies underscores its utility and significance within the field of medicine. Dr. Gerald Klatskin's pioneering work on liver biopsy techniques, as well as his study of liver histopathology, paved the way for its diagnostic and therapeutic applications around the world. His attention to detail as well as meticulous account of hilar cholangiocarcinoma has had a lasting impact on the medical community. Eponymously, the tumor was named after him-Klatskin's tumor. Klatskin was also well known and respected for his commitment and devotion to his fellows who themselves went on to hold prestigious academic positions and make significant contributions of their own. The life and work of Klatskin documents a pioneering hepatologist and devoted teacher.

The biliary system is an uncommon location for neuroendocrine tumours (NETs), and within this system, the common hepatic duct is an even more rare site for NETs. Clinical and radiological presentations are challenging because these tumours may be preoperatively confused with Klatskin-like lesions. Here we report a well-differentiated grade 2 NET arising from the common hepatic duct in a 64-year-old female. Curative surgery was performed, and no evidence of recurrent disease was observed at the 2-months follow-up., (Copyright © 2020 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background and Aims: To prevent stent migration, transpapillary stent placement has been recommended for the endoscopic treatment of malignant hilar biliary stricture. However, recent studies have suggested that placement above the papilla achieves better results, because it is believed to prevent reflux and prolong stent patency. The aim of this study was to compare the efficacy and safety aspects of transpapillary and suprapapillary stent placement. In addition, the success rates of stent revision were evaluated., Materials and Methods: The medical records of 73 patients with hilar cholangiocarcinoma who underwent endoscopic metal stent insertion between January 2005 and December 2015 were retrospectively reviewed. Patients were assigned by stent location to a suprapapillary (S group; N = 44) or a transpapillary (T group; N = 29) cohort. Clinical outcomes, stent patency, adverse events, and revision success rates were compared between the two study groups., Results: Patency periods were similar in the two groups (S; 140 vs. T; 157 days; P = 0.732). Rates of stent obstruction in the S and T groups were 63.4% and 55.2%, respectively (P = 0.470). An adverse event occurred in 15 (20.5%) of total study subjects, with no significant intergroup difference. The endoscopic revision success rate was significantly higher in the T group (P = 0.01), and the time required for revision tended to be shorter in the T group., Conclusions: The effectiveness and safety of suprapapillary and transpapillary stent insertion were found to be similar, but the success rate of endoscopic revision was significantly higher for the T group. Therefore, we recommend that transpapillary stent placement be considered for patients with hilar cholangiocarcinoma and biliary obstruction.

Background: Perihilar cholangiocarcinoma (PHCCA) is the most common type of human cholangiocarcinoma with a very dismal prognosis. Tumor markers and target drugs of PHCCA are desperately needed. Protein phosphatase N3 (PTPN3) has dual roles in the progression of human cancers, but its expression and functions in PHCCA have not been elucidated., Materials and Methods: The expression of PTPN3 in PHCCA was detected with western blotting, qRT-PCR and immunohistochemistry. The clinical significance of PTPN3 was identified by analyzing the correlations between its expression and the clinicopathological variables, and the prognostic value was evaluated by univariate and multivariate analyses. The functions of PTPN3 in the progression of PHCCA were estimated with both in vitro and in vivo experiments., Results: PTPN3 expression was down-regulated in PHCCA compared with normal bile duct. Low PTPN3 expression was markedly associated with large tumor size and unfavorable prognosis. After knocking down PTPN3, the percentages of G2/S phase of PHCCA cells were elevated, and the proliferation increased significantly. Moreover, we demonstrated that the phosphorylation of AKT was elevated by PTPN3 knockdown, and it was required in PTPN3-involved proliferation of PHCCA. Within vivo experiments, PTPN3 and AKT inhibitor MK-2206 were demonstrated to suppress tumor size of PHCCA., Conclusion: PTPN3 was a favorable prognostic biomarker of PHCCA. PTPN3 suppressed the proliferation of PHCCA by inhibiting AKT phosphorylation and arresting cell cycle. Our results suggested thatpost-operative detection of PTPN3 would be a helpful approach to stratify the PHCCA patients with high-risk., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Hilar cholangiocarcinoma (HC), also referred to as Altemeier-Klatskins tumour, is a lethal primary extrahepatic carcinoma of biliary epithelial origin, arising within 2cm of the hilar confluence. Radical surgical excision provides the best chance for a cure; however, the management of patients with HC is challenging not only because of the need for a high level of skill in biliary and hepatic resections, but also because of the difficulty in reaching an accurate diagnosis preoperatively. In fact, the differential diagnosis of HC is a diagnostic dilemma which is currently persisting, as modern, sophisticated diagnostic modalities are not always able to provide a definitive preoperative diagnosis. This difficulty is compounded by the fact that alternative entities that mimic HC may be present in up to 25% of patients with hilar obstruction. This makes precise preoperative characterisation of a hilar stricture extremely important by preventing unnecessary, high-risk, major surgical procedures. Therefore, alternative benign entities masquerading as Altemeier-Klatskins tumour deserve an important place in the differential diagnosis of hilar obstruction., Purpose: Considering the important clinical implications that a precise diagnosis of the aetiological cause of a biliary obstruction at the liver hilum would have, this paper will focus on the differentiation between HC and benign hilar obstructions and will review benign tumours and pseudotumours masquerading as HC along with their specific diagnostic features.

Background: Although there are many studies on technical outcomes of endoscopic nasobiliary drainage (ENBD), no authors reported on preoperative course of patients undergoing ENBD. The aim of this study was to investigate the course of patients with ENBD during the waiting period., Methods: Patients who underwent resection of perihilar cholangiocarcinoma (PHCC) between January 2013 and September 2017 were retrospectively reviewed., Results: During the study period, 191 consecutive patients underwent surgical resection of PHCC after ENBD. Of the study patients, 154 (80.6%) patients were discharged, returned to their home, then re-admitted for surgery. The remaining 37 patients were continuously hospitalized. The number of cholangitis events during the waiting period was 0 in 120 patients, 1 in 59 patients, 2 ≤ in 12 patients. Endoscopic re-intervention was needed in 52 patients. The median length between the first admission and surgery was 37 days (range 12-197 days) in the entire cohort; it was longer in patients with portal vein embolization than in those without (43 vs. 27 days, P < 0.001)., Conclusions: In patients undergoing resection of PHCC, ENBD is widely tolerable with relatively low incidence of cholangitis and thus recommended for preoperative biliary drainage., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Cholangiocarcinomas are heterogeneous biliary tract tumors that cause devastating disease. Perihilar cholangiocarcinoma (PHC) is the most common type of biliary tract cancer and are associated with a high mortality. Diagnoses of PHC depend on the results of its clinical presentation, serum biomarkers and imaging techniques. Pre-operative managements including pre-operative biliary drainage (PBD) and portal vein embolization (PVE) could reduce mortality. The best chance of long-term survival and potential cure is surgical resection with negative surgical margin. Lymph node metastasis over N2 nodes precludes long-term survival. The benefit of concomitant vascular resection remains uncertain. Liver transplantation combined with neoadjuvant chemotherapy with radiotherapy is a promising option in highly selected patients with unresectable tumors. Herein, an overview is provided of developments in diagnosis, peri-operative management and surgical treatment among patients with PHCs., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Prediction of early postoperative recurrence is of great significance for follow-up treatment. However, there are few studies available that focus on high-risk factors of early postoperative recurrence or even the definition the exact time of early recurrence for hilar cholangiocarcinoma. Thus, we aimed to examine the optimal cut-off value for defining the early in patients with R0 resection of hilar cholangiocarcinoma and to investigate prognostic factors associated with early recurrence. Two hundred and fifty-eight patients with R0 resection of hilar cholangiocarcinoma between 2000 and 2015 were included. The minimum P value approach was used to define the optimal cut-off of early recurrence. The prognostic factors associated with early recurrence were investigated. The optimal cut-off value for dividing patients into early and non-early recurrence groups after R0 resection of hilar cholangiocarcinoma was 12 months. Sixty-two patients were recorded as early recurrence, and the remaining 196 patients were labeled as non-early recurrence. Multivariate logistic regression analysis indicated lymph node metastasis (OR = 2.756, 95% CI 1.409-5.393; P = 0.003), poor differentiation (OR = 1.653; 95% CI 1.040-2.632; P = 0.034), increased postoperative CA 19-9 levels (OR = 1.965, 95% CI 1.282-3.013; P = 0.002), neutrophil-to-lymphocyte ratio > 3.41 (OR = 5.125, 95% CI 2.419-10.857; P < 0.001) and age > 60 years (OR = 2.018, 95% CI 1.032-3.947; P = 0.040) were independent determinants of early and non-early recurrence. Poor differentiation (HR = 2.609, 95% CI 1.600-4.252; P < 0.001), Bismuth classification type III/IV (HR = 2.510, 95% CI 1.298-4.852; P = 0.006) and perineural invasion (HR=2.380, 95% CI 1.271-4.457; P = 0.007) were independent factors of overall survival in the subgroup of patients who developed early recurrence. The optimal cut-off value for dividing early recurrence after R0 resection of hilar cholangiocarcinoma was 12 months. Tumor differentiation, Bismuth classification, and perineural invasion were independent factors of overall survival in the subgroup of patients with early recurrence. Patients with risk factors should be monitored closely after curative surgery., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Perihilar cholangiocarcinoma (PHC) often requires extensive surgery which is associated with substantial morbidity and mortality. This study aimed to compare an Eastern and Western PHC cohort in terms of patient characteristics, treatment strategies and outcomes including a propensity score matched analysis., Methods: All consecutive patients who underwent combined biliary and liver resection for PHC between 2005 and 2016 at two Western and one Eastern center were included. The overall perioperative and long-term outcomes of the cohorts were compared and a propensity score matched analysis was performed to compare perioperative outcomes., Results: A total of 210 Western patients were compared to 164 Eastern patients. Western patients had inferior survival compared to the East (hazard-ratio 1.72 (1-23-2.40) P < 0.001) corrected for age, ASA score, tumor stage and margin status. After propensity score matching, liver failure rate, morbidity, and mortality were similar. There was more biliary leakage (38% versus 13%, p = 0.015) in the West., Conclusion: There were major differences in patient characteristics, treatment strategies, perioperative outcomes and survival between Eastern and Western PHC cohorts. Future studies should focus whether these findings are due to the differences in the treatment or the disease itself., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Hilar cholangiocarcinoma is one of the most difficult malignant tumors to treat in the biliary system. In Japan, 5-year survival rate of the disease has increased from 32.5% to 67.1% during the past 30 years. The impressive progress reflects the solid efforts in preoperative endoscopic diagnosis, innovation in surgery such as PTPE as well as hepato-pancreatoduodenectomy and perioperative treatment including replacement of the bile and synbiotic treatment, which have finally formed a set of standardized diagnosis and treatment systems. The present review intends to report the history, current status and remaining bottlenecks of the diagnosis and treatment system of hilar cholangiocarcinoma in Japan as follows.

Background/aim: Platforms using valid molecular targets can provide concurrent diagnostic and treatment (theragnostic) options in perihilar cholangiocarcinoma (PHC). Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker in the biliary secretome of PHC. Its potential as a theragnostic target and its prognostic significance in this cancer was, therefore, explored., Materials and Methods: In-vitro studies were used to determine NGAL localization in several cholangiocarcinoma cell lines. Tissue expression of NGAL was quantified in PHC resection cases from 2000-2010 by immunohistochemistry., Results: NGAL was expressed in the majority of tested cell lines and localized to their membranes. Tissues from 54 patients underwent NGAL immunohistochemistry. Median tumoral NGAL expression was significantly higher than that in matched liver controls (p<0.001). Higher NGAL tumor expression was associated with nodal metastasis (p=0.021), although no significant association with survival was observed., Conclusion: The expression and localization of NGAL in PHC make it a valid candidate biomarker for exploitation in theragnostic platforms., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Irreversible electroporation (IRE) has successfully been used for palliation of pancreatic and liver cancers due to its ability to ablate tumors without destroying nearby vital structures. To date, it has not been evaluated in patients with advanced hilar cholangiocarcinoma (AHC). This study presents a single-institution experience with IRE for management of obstructive jaundice in AHC., Methods: A single-institution database was queried for patients undergoing IRE for AHC after PTBD placement for relief of obstructive jaundice from 2010 to 2017 and compared to a control group treated with standard of care only (No IRE)., Results: Twenty-six patients underwent IRE for AHC after PTBD replacement. Three patients experienced complications, with two experiencing severe (≥ grade 3) complications. After IRE, median time to PTBD removal was 122 days (range 0-305 days) and median catheter-free time before requiring PTBD replacement was 305 days (range 92-458 days). In comparison, the 137 control patients had an admission rate of 59% (N = 80 patients) for PTBD infection, occlusion, or catheter related problem., Conclusion: IRE safely achieves biliary decompression via tumor electroporation and allows PTBD removal for an extended period of time. In appropriately selected patients with obstructive jaundice in the setting of AHC, IRE can be used to increase catheter-free days and optimize overall quality of life., (Copyright © 2018. Published by Elsevier Ltd.)

Magnetic resonance cholangiopancreatography is a non-invasive imaging, highly performant in detecting and locating biliary stenosis and in predicting its malignancy. The combination of two and three-dimensional MRI sequences is recommended to assess a biliary obstacle. Cholangiopathies are the main differential diagnosis of cholangiocarcinomas. In addition to bile duct abnormalities beyond the stenosis, the predictive signs of malignancy are: asymmetric irregular luminal narrowing (longer than 3mm and thicker than 13mm), abrupt discontinuation of stenosis, and enhancement superior to that of the adjacent hepatic parenchyma during arterial and portal acquisitions. Diffusion sequences improve the sensitivity of biliary stenosis detection. Moreover, restriction of diffusion is useful for distinguishing malignant from benign stenosis. Combining Magnetic resonance cholangiopancreatography, late LAVA and diffusion sequences improves the sensitivity of detection of a possible biliary extension without significant specificity. MRI with gadolinium chelate injection is efficient in assessing vascular extension of cholangiocarcinomas. However its accuracy remains lower than that of Ct-scan. To assess hepatic, lymphatic and peritoneal extensions of cholangiocarcinomas, it is fundamental to combine diffusion and dynamic MRI sequences., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Rationale: Primary mucosa-associated lymphoid tissue (MALT) lymphomas rarely originate in the hilar bile duct. Preoperative diagnosis of a primary MALT lymphoma of the hilar bile duct is difficult owing to the rarity of this disease. Differentiating between obstructive jaundice caused by MALT lymphoma of the hilar bile duct and hilar cholangiocarcinoma (the most common form of bile duct cancer) is challenging., Patient Concerns: A 57-year-old man presented to our hospital in August 2012 with fluctuant obstructive jaundice., Diagnoses: Contrast-enhanced abdominal computed tomography and magnetic resonance cholangiopancreatography showed a hilar liver mass measuring 23 × 28 mm along with intrahepatic biliary dilatation indicating hilar bile duct obstruction with a high index of suspicion for hilar cholangiocarcinoma., Interventions and Outcomes: Based on frozen section examination, he was intraoperatively diagnosed with chronic nonspecific inflammation. Histopathological and immunohistochemical examinations confirmed a diagnosis of malignant lymphoma, specifically classified as an extranodal marginal zone B-cell lymphoma of MALT type., Lessons: A primary MALT lymphoma of the bile duct should be considered among the differential diagnosis in patients with a hilar tumor who present with fluctuating jaundice and are preoperatively diagnosed with suspected hilar cholangiocarcinoma, and/or an intraoperative diagnosis of chronic nonspecific inflammation (based on frozen section examination) assessed for stenosis or obstruction of the bile duct.

Background: Mirizzi syndrome is a condition difficult to diagnose and treat, representing a particular "challenge" for the biliary surgeon. The disease can mimic cancer of the gallbladder, causing considerable diagnostic difficulties. Furthermore, it increases the risk of intraoperative biliary injury during cholecystectomy. The aim of this study is to point out some particular aspects of diagnosis and treatment of this condition., Methods: The clinical records of patients with Mirizzi syndrome, treated in the last five years, were reviewed. Clinical data, cholangiograms, preoperative diagnosis, operative procedures, and early and late results were examined., Results: Eighteen consecutive patients were treated in the last five years. Presenting symptoms were jaundice, pain, and cholangitis. Preoperative diagnosis of Mirizzi syndrome was achieved in 11 patients, while 6 had a diagnosis of gallbladder cancer and 1 of Klatskin tumor. Seventeen patients underwent surgery, including cholecystectomy in 8 cases, bile duct repair over T-tube in 3 cases, and hepaticojejunostomy in 4 cases. Two cases (11.1%) of gallbladder cancer associated with the Mirizzi syndrome were incidentally found: a patient underwent right hepatectomy and another patient was unresectable. The overall morbidity rate was 16.6%. There was no postoperative mortality. An ERCP with stent insertion was required in three cases after surgery. Sixteen patients were asymptomatic at a mean distance of 24 months (range: 6-48) after surgery., Conclusions: Mirizzi syndrome requires being treated by an experienced biliary surgeon after a careful assessment of the local situation and anatomy. The preoperative placement of a stent via ERCP can simplify the surgical procedure.

Background: The performances of the American Joint Committee on Cancer staging systems of the 7th and 8th edition were compared using a cohort of patients undergoing surgery for perihilar cholangiocarcinoma at 2 tertiary referral Italian hepatobiliary centers., Methods: The American Joint Committee on Cancer 7th and 8th edition staging systems were used to classify 214 patients who underwent surgery for perihilar cholangiocarcinoma. The performances of the 2 staging systems were compared using the concordance index., Results: Using the American Joint Committee on Cancer 7th edition staging system, we found that the 5-year overall survival for stages I, II, and IVa was 71%, 34%, and 34%, while no patients in stages IIIa, IIIb, and IVb survived 5 years. In comparison, when the American Joint Committee on Cancer 8th edition staging system was used, the 5-year overall survival was 71% and 35% in stages I and II, resulting in 23%, 19%, and 22% in stages IIIa, IIIb, and IIIc, respectively. Of note, no patients in stages IVa and IVb survived 5 years. The American Joint Committee on Cancer 8th edition staging system had a slightly better discriminatory ability with a concordance index of 0.624 compared with 0.619 for the American Joint Committee on Cancer 7th edition., Conclusion: The newly released classification American Joint Committee on Cancer 8th edition staging system demonstrated a poor to moderate ability to predict prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma, which was only slightly better than the previous edition. Further refinements are needed to improve the prognostic ability of the American Joint Committee on Cancer staging system for perihilar cholangiocarcinoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the influence of type of surgery (transplant vs resection) on overall survival (OS) in patients with hilar cholangiocarcinoma (H-CCA)., Background: Outcomes after resection for H-CCA are poor, yet transplantation is currently only reserved for well-selected patients with unresectable disease., Methods: All patients with H-CCA who underwent resection from 2000 to 2015 at 10 institutions were included. Three institutions additionally had active H-CCA transplant protocols with similar selection criteria over similar time periods., Results: Of 304 patients with suspected H-CCA, 234 underwent attempted resection and 70 were enrolled in a transplant protocol. Excluding incomplete/R2 resections (n = 43), patients who were enrolled, but did not undergo transplant (n = 24), and transplants without confirmed H-CCA diagnoses (n = 5), 191 patients underwent curative-intent resection and 41 curative-intent transplant. Compared with resection, transplant patients were younger (52 vs 65 years; P < 0.001), and more frequently had primary sclerosing cholangitis (PSC; 61% vs 2%; P < 0.001) and received chemotherapy and/or radiation (98% vs 57%; P < 0.001). Groups were otherwise similar in demographics and comorbidities. Patients who underwent transplant for confirmed H-CCA diagnosis had improved OS compared with resection (3-year: 72% vs 33%; 5-year: 64% vs 18%; P < 0.001). Among patients who underwent resection for tumors <3 cm with lymph-node negative disease, and excluding PSC patients, transplant was still associated with improved OS (3-year: 54% vs 44%; 5-year: 54% vs 29%; P = 0.03). Transplant remained associated with improved survival on intention-to-treat analysis, even after accounting for tumor size, lymph node status, and PSC (P = 0.049)., Conclusions: Resection for hilar cholangiocarcinoma that meets criteria for transplantation (<3 cm, lymph-node negative disease) is associated with substantially decreased survival compared to transplant for the same criteria with unresectable disease. Prospective trials are needed and justified.

The diagnosis of malignant biliary strictures remains problematic, especially in the perihilar region and in primary sclerosing cholangitis (PSC). Conventional cytology obtained during endoscopic retrograde cholangiography (ERC)-guided brushings of biliary strictures is suboptimal due to limited sensitivity, albeit it remains the gold standard with a high specificity. Emerging technologies are being developed and validated to address this pressing unmet patient need. Such technologies include enhanced visualization of the biliary tree by cholangioscopy, intraductal ultrasound, and confocal laser endomicroscopy. Conventional cytology can be aided by employing complementary and advanced cytologic techniques such as fluorescent in situ hybridization (FISH), and this technique should be widely adapted. Interrogation of bile and serum by examining extracellular vesicle number and cargo, and exploiting next-generation sequencing and proteomic technologies, is also being explored. Examination of circulating cell-free deoxyribonucleic acid (cfDNA) for differentially methylated regions is a promising test which is being rigorously validated. The special expertise required for these analyses has to date hampered their validation and adaptation. Herein, we will review these emerging technologies to inform the reader of the progress made and encourage further studies, as well as adaptation of validated approaches., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Distinguishing perihilar cholangiocarcinoma (PHC) from benign forms of sclerosing cholangitis affecting the hilar bile ducts is challenging, since histological confirmation of PHC is difficult to obtain and accurate non-invasive diagnostic tests are not available. IgG4-associated cholangitis (IAC), an imitator of PHC, may present with clinical and radiographical signs of PHC. IAC can be accurately diagnosed with a novel qPCR test. The aim of this study was to investigate the incidence and long-term activity of IAC in patients resected for PHC in a single tertiary center over a period of 30 years., Methods: All patients with benign disease who underwent surgery for presumed PHC in our institute between 1984 and 2015 were identified. Benign liver and bile duct specimens were re-evaluated by a pathologist and scored according to international consensus pathology criteria for IgG4-related disease (IgG4-RD). Patients with benign disease still alive were followed-up and a clinical diagnosis of IAC was made using a combination of the HISORt group C (response to steroids) criteria and elevated serum IgG4 levels and/or the novel IgG4/IgG RNA ratio. Also, recurrent symptomatic disease at any time after surgery requiring immunosuppression was assessed., Results: Out of 323 patients who underwent surgery for presumed PHC, 50 patients (15%) had benign disease. In 42% (n = 21/50) of these patients a histological (n = 17) or clinical (n = 4) diagnosis of IAC was established. The remaining patients were diagnosed with unclassified sclerosing inflammation, cystadenoma, or sclerosing hemangioma. Nine out of 12 IAC patients who were followed-up showed episodes of recurrent disease requiring immunosuppressive treatment., Conclusions: Liver and bile duct resections for PHC during three decades disclosed in 15% benign biliary disorders mimicking PHC of which 42% were definitely diagnosed as IAC. IgG4-RD remains active in the majority of patients with IAC years after surgery. Novel diagnostic tests for IAC might reduce misdiagnosis, unnecessary surgery, and life-threatening complications.

BACKGROUND A variety of benign etiologies of biliary stricture may initially be mistaken for hilar cholangiocarcinoma. Consequently, many patients undergo surgery for a benign disease that could have been treated medically. Eosinophilic cholangitis (EC) is an uncommon, benign, self-limiting disease that should be considered when approaching a case of obstructive jaundice since it causes biliary stricture formation. Transmural eosinophilic infiltration of the biliary tree is characteristic of EC. It may initially be indistinguishable from hilar cholangiocarcinoma. CASE REPORT We present a rare case of an 84-year-old male who was referred to our hospital for abdominal mass investigation with the provisional diagnosis of cholangiocarcinoma. During the workup, the index of suspicion for malignancy remained high as the typical laboratory and radiological findings for benign causes of biliary stricture were not present. Hence, the patient underwent left hepatectomy with caudate lobe resection and received a retrograde diagnosis of EC. CONCLUSIONS This case demonstrates that EC could present in the elderly with cardinal signs of cancer and absence of the typical findings of EC which was not previously reported. Since only 70% of patients present with peripheral eosinophilia, we stress on the importance of implementing diagnostic criteria for EC in the setting where peripheral eosinophilia is absent. Furthermore, this disorder has been reported to respond well to steroid therapy, hence, diagnostic criteria for EC would provide another treatment option for elderly and/or those who are not fit for surgery.