Diagnosis and Treatment of Perihilar Cholangiocarcinoma: A National Survey from the Korean Pancreatobiliary Association.

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.

Hepatocellular carcinoma (HCC) masquerading as hilar cholangiocarcinoma: An unusual presentation of jaundice.

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.

[Non-Hodgkin large B-cell lymphoma of the bile duct mimicking a Klatskin tumor: case report]. / Linfoma no Hodgkin de células B grandes de la vía biliar simulando un tumor de Klatskin: relato de caso.

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.

La obstrucción de la vía biliar secundaria a un linfoma no hodgkin es extremadamente raro. Es por esto que presentamos el caso de una paciente femenina de 63 años que consulta por ictericia, coluria, acolia y astenia. Un laboratorio presentando un patrón colestásico y una ecografía con la vía biliar intra y extrahepática dilatadas llevaron a realizar una colangioresonancia de abdomen que evidenció una formación expansiva de limites mal definidos que comprometía el conducto hepático común asociado a estenosis del mismo. La sospecha inicial fue un tumor de klatskin y se llevó a cabo la toma de biopsia, cuyo resultado anatomopatológico informó infiltración de linfoma de células B de células grandes doble expresor como tumor primario de la vía biliar. Realizó tratamiento quimioterápico con esquema R CHOP (rituximab, ciclofosfamida, doxorrubicina, vincristina, prednisona) y entró en remisión. Por continuos episodios de colangitis se optó por realizar una hepático yeyuno anastomosis en Y de Roux con reconstrucción de la vía biliar. Actualmente continúa en remisión a 7 años del diagnóstico. El caso resalta la rareza del linfoma no hodgkin de células B grandes en la vía biliar, y destaca la importancia de la biopsia para un tratamiento eficaz que combina la quimioterapia para la enfermedad de base y la cirugía para las complicaciones obstructivas.

[Endoscopic treatment of obstructive jaundice in patients with Klatskin tumor]. / Endoskopicheskoe lechenie patsientov s mekhanicheskoi zheltukhoi pri opukholi Klatskina.

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.

Gallbladder cancer mimicking perihilar cholangiocarcinoma-considerable rate of postoperative reclassification with implications for prognosis.

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.

Bile metabolites as diagnostic biomarkers for perihilar cholangiocarcinoma.

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.

Identification and validation of volatile organic compounds in bile for differential diagnosis of perihilar cholangiocarcinoma.

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.

Clinical treatment of cholangiocarcinoma: an updated comprehensive review.

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.

[Portal Biliopathy Misdiagnosed as Hilar Cholangiocarcinoma].

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.

[Gallbladder carcinoma and extrahepatic cholangiocarcinoma]. / Gallenblasenkarzinome und Tumore der extrahepatischen Gallenwege.

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.

[Neurofibroma of the bile duct: a rare cause of cholestatic jaundice that mimics Klatskin’s tumor]. / Neurofibroma de la vía biliar: una causa rara de ictericia colestásica que imita el tumor de Klatskin.

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.

Elevated preoperative CA125 levels predicts poor prognosis of hilar cholangiocarcinoma receiving radical surgery.

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.

Primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma.

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.

[Preoperative biliary drainage for malignant biliary obstruction: to drain or not to drain? And if drain, in what way?] / Predoperatsionnaya biliarnaya dekompressiya pri opukholevoi zheltukhe: drenirovat' ili net? I esli drenirovat', to kakim sposobom?

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.

Prognostic value of metabolic parameters measured by pretreatment dual-time-point 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with intrahepatic or perihilar cholangiocarcinoma: A STROBE study.

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 ±â€Š11 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.

Comparison of Inflammation-based Prognostic Scores in Patients With Biliary Tract Cancer After Surgical Resection.

BACKGROUND/AIM: Inflammation-based prognostic scores are proven prognostic biomarkers in various cancers. This study aimed to identify a useful prognostic score for patients with biliary tract cancer (BTC) after surgical resection. PATIENTS AND METHODS: This retrospective study recruited 115 patients with BTC during 2010-2020. The relationship between clinicopathological variables, including various prognostic scores and overall survival (OS), was investigated using univariate and multivariate analyses. RESULTS: BTC included 58 cholangiocarcinoma, 29 gallbladder carcinoma, 16 ampullary carcinoma, and 12 perihilar cholangiocarcinoma cases. A significant difference was detected in OS of patients with a Japanese modified Glasgow prognostic score (JmGPS) 0 (n=62) and JmGPS 1 or 2 (high JmGPS) (n=53). In the multivariate analysis, tumour differentiation (p=0.014) and a high JmGPS (p=0.047) were independent prognostic factors. CONCLUSION: The high JmGPS was an independent prognostic predictor after surgical resection and was superior to other prognostic scores.

The preoperative elevated plasma fibrinogen level is associated with the prognosis of hilar cholangiocarcinoma.

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.

Expression of integrin ανß6 differentiates perihilar cholangiocarcinoma (PHC) from benign disease mimicking PHC.

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 ανß6, a cell receptor upregulated in pancreatobiliary malignancies, for both (preoperative) PET and (intraoperative) fluorescent imaging. Here, expression of integrin ανß6 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 ανß6 and quantified using the H-score. RESULTS: Immunohistochemical staining for integrin ανß6 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 ανß6 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 ανß6 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.