CT Texture Analysis of Perihilar Cholangiocarcinoma-Associations With Tumor Grading, Tumor Markers and Clinical Outcome.

BACKGROUND: Texture analysis derived from computed tomography (CT) may provide clinically relevant imaging biomarkers associated with tumor histopathology. Perihilar cholangiocarcinoma is a malignant disease with an overall poor prognosis. AIMS: The present study sought to elucidate possible associations between texture features derived from CT images with grading, tumor markers, and survival in extrahepatic, perihilar cholangiocarcinomas tumors. METHODS: This retrospective study included 22 patients (10 females, 45%) with a mean age of 71.8 ± 8.7 years. Texture analysis was performed using the free available Mazda software. All tumors were histopathologically confirmed. Survival and clinical parameters were used as primary study outcomes. RESULTS: In discrimination analysis, "S(1,1)SumVarnc" was statistically significantly different between patients with long-term survival and nonlong-term survival (mean 275.8 ± 32.6 vs. 239.7 ± 26.0, p = 0.01). The first-order parameter "skewness" was associated with the tumor marker "carcinoembryonic antigen" (CEA) (r = -0.7, p = 0.01). A statistically significant correlation of the texture parameter "S(5,0)SumVarnc" with tumor grading was identified (r = -0.6, p < 0.01). Several other texture features correlated with tumor markers CA-19-9 and AFP, as well as with T and N stage of tumors. CONCLUSION: Several texture features derived from CT images were associated with tumor characteristics and survival in patients with perihilar cholangiocarcinomas. CT texture features could be used as valuable novel imaging markers in clinical routine.

Unveiling the potential of strain elastography in perihilar cholangiocarcinoma biopsies.

PURPOSE: This study was conducted to investigate the effectiveness of strain elastography in guiding precise and sufficient tissue sampling for perihilar cholangiocarcinoma (CCA) biopsies. METHODS: Our retrospective analysis included 23 liver biopsies conducted between March 2019 and July 2022 for suspected perihilar CCA. An experienced radiologist performed the biopsies via an ultrasound machine with elastography configuration. Tissue stiffness color maps were used for guiding when the biopsies were performed. Strain index value calculations were made by radiologists on recorded images. RESULTS: Patient demographics revealed a mean age of 65.17 ± 9.25 years, with a gender distribution of six females and 17 males. Gray-scale examinations unveiled diverse echogenic characteristics in liver lesions. Elastography-guided biopsies demonstrated no need for repeats, while gray-scale biopsies necessitated re-biopsy in four patients, resulting in cholangiocarcinoma diagnosis (P = 0.037). Strain index values showcased strong inter- and intra-observer agreements (P < 0.001). Notably, no post-biopsy complications emerged in either study group. CONCLUSION: The diagnostic advantage of elastography, particularly in enhancing accuracy in challenging isoechoic lesions, was demonstrated, although the substantial overlap between strain index values of benign and malignant liver masses limits clinical usefulness of this technique.

A case report of perihilar cholangiocarcinoma in a patient with situs inversus totalis.

Situs inversus totalis is a rare congenital malformation in which organs are positioned in a mirror-image relationship to normal conditions. It often presents with vascular and biliary malformations. Only a few reports have pointed out the surgical difficulties in patients with situs inversus totalis, especially in those with perihilar cholangiocarcinoma. This report describes a 66-year-old male patient who underwent left hemihepatectomy (S5, 6, 7, and 8) with combined resection of the caudate lobe (S1), extrahepatic bile duct, and regional lymph nodes for perihilar cholangiocarcinoma with situs inversus totalis. Cholangiocarcinoma was mainly located in the perihilar area and progressed extensively into the bile duct. Surgery was performed after careful evaluation of the unusual anatomy. Although several vascular anomalies required delicate manipulation, the procedures were performed without major intraoperative complications. Postoperatively, bile leakage occurred, but the patient recovered with drainage treatment. The patient was discharged on the 29th postoperative day. Adjuvant chemotherapy with S-1 was administered for approximately 6 months. There was no recurrence 15 months postoperatively. Appropriate imaging studies and an understanding of unusual anatomy make surgery safe and provide suitable treatment for patients with situs inversus totalis.

Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study.

OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: • The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. • Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. • The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.

Impact of EUS in liver transplantation workup for patients with unresectable perihilar cholangiocarcinoma.

BACKGROUND AND AIMS: For a highly selected group of patients with unresectable perihilar cholangiocarcinoma (pCCA), liver transplantation (LT) is a treatment option. The Dutch screening protocol comprises nonregional lymph node (LN) assessment by EUS, and whenever LN metastases are identified, further LT screening is precluded. The aim of this study is to investigate the yield of EUS in patients with pCCA who are potentially eligible for LT. METHODS: In this retrospective, nationwide cohort study, all consecutive patients with suspected unresectable pCCA who underwent EUS in the screening protocol for LT were included from 2011 to 2021. During EUS, sampling of a "suspicious" nonregional LN was performed based on the endoscopist's discretion. The primary outcome was the added value of EUS, defined as the number of patients who were precluded from further screening because of malignant LNs. RESULTS: A total of 75 patients were included in whom 84 EUS procedures were performed, with EUS-guided tissue acquisition confirming malignancy in LNs in 3 of 75 (4%) patients. In the 43 who underwent surgical staging according to the protocol, nonregional LNs with malignancy were identified in 6 (14%) patients. Positive regional LNs were found in 7 patients in post-LT-resected specimens. CONCLUSIONS: Our current EUS screening for the detection of malignant LNs in patients with pCCA eligible for LT shows a limited but clinically important yield. EUS with systematic screening of all LN stations, both regional and nonregional, and the sampling of suspicious lymph nodes according to defined and set criteria could potentially increase this yield.

Preoperative Endoscopic Ultrasound-Guided Hepaticogastrostomy for Definite Biliary Drainage in Hilar Cholangiocarcinoma Laparoscopic Resection: A Hybrid Minimal-Invasive Technique.

BACKGROUND AND STUDY AIMS: Laparoscopic approach of perihilar cholangiocarcinoma (PHC) is still challenging. We report the original use of a endoscopic hepaticogastrostomy (EHG) for definite biliary drainage in order to avoid biliary reconstruction. PATIENTS AND METHODS: A 70-year-old man presenting with jaundice was referred for resection of a Bismuth type IIIa PHC. Repeated endoscopic retrograde cholangiopancreatography failed to drain the future liver remnant, enabling only right anterior liver section drainage. EHG was performed three weeks before surgery. A hepatogastric anastomosis was created, placing a half-coated self-expanding endoprosthesis between biliary duct of segment 2 and the lesser gastric curvature. RESULTS: A laparoscopic right hepatectomy extended to segment 1, common bile duct, and hepatic pedicle lymphadenectomy was performed. The left hepatic duct was sectioned and ligated downstream to the biliary confluence of segment 2-3 and 4 allowing exclusive biliary flow through the EHG. The patient was disease free at 12 months, postoperative outcomes were uneventful except three readmissions for acute cholangitis due to prosthesis obstruction. CONCLUSIONS: EHG may be used as definite biliary drainage technique in laparoscopic PHC resection, at the expense of prosthesis obstruction and cholangitis.

CT Texture Analysis and Node-RADS CT Score of Lymph Nodes in Patients With Perihilar Cholangiocarcinoma.

BACKGROUND/AIM: Texture analysis can provide quantitative imaging markers from computed tomography (CT) images. The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of CT texture analysis and the Node-RADS classification to categorize and stage lymph nodes in patients with perihilar cholangiocarcinoma. PATIENTS AND METHODS: Overall, 25 patients (n=9 females, 36%) with a mean age of 72.4±8.1 years were included. All patients were surgically resected and the lymph nodes were histopathologically analyzed. CT-texture analysis was performed with the Mazda package. All investigated lymph nodes were scored in accordance with the Node-RADS classification. RESULTS: Regarding lymph node discrimination (N- versus N+), Node-RADS classification achieved an area under the curve (AUC) of 0.86 resulting in a sensitivity of 78% and a specificity of 86%. Multiple investigated texture features were different between negative and positive lymph nodes. The "S(0,1)SumVarnc" achieved the best AUC of 0.75 resulting in a sensitivity of 0.91 and a specificity of 0.67. Correlation analysis showed various statistically significant associations between CT texture features and Node-RADS score. CONCLUSION: Several CT texture features and the Node-RADS score derived from preoperative staging CT were associated with the malignancy of the hilar lymph nodes and might aid for preoperative staging. This could change surgical treatment planning in hilar cholangiocarcinoma.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

68 Ga-FAPI PET/CT Provides a Clear Picture of a Klatskin Tumor That 18 F-FDG PET/CT Missed.

ABSTRACT: Klatskin tumor, also known as hilar cholangiocarcinoma, was clearly demonstrated in this case report by contrasting 68 Ga-FAPI and 18 F-FDG PET/CT in the same patient. This instance exemplifies a false-negative 18 F-FDG PET/CT for the main tumor site, despite positive 68 Ga-FAPI uptake at the same location.

Comparison between Suprapapillary and Transpapillary Uncovered Self-Expandable Metallic Stent Placement for Perihilar Cholangiocarcinoma.

PURPOSE: To compare the effectiveness, adverse events (AEs), stent patency, and patient survival with suprapapillary and transpapillary uncovered self-expandable metallic stent placement for perihilar cholangiocarcinoma. MATERIALS AND METHODS: A single-center retrospective study of 54 patients with inoperable perihilar cholangiocarcinoma who underwent percutaneous transhepatic biliary stent placement between January 1, 2019, and August 31, 2021, was conducted. According to stent location, the patients were classified into 2 groups: suprapapillary (S) and transpapillary (T). Demographic data, Bismuth-Corlette classification, type and location of the stent, laboratory data, postprocedural AEs, procedural success, stent occlusion, reintervention rate, and mortality were compared between the groups. RESULTS: Stent placement was suprapapillary in 13 (24.1%) patients and transpapillary in 41 (75.9%) patients. Mean age was higher in Group T (78 vs 70.5 years; P = .046). Stent occlusion rates were similar in the 2 groups (Group S, 23.8%; Group T, 19.5%), as were AE rates, the most common being cholangitis (Group S, 23.1%; Group T, 24.4%). There were no significant differences in revision rate (Group S, 7.7%; Group T, 12.2%) and 30-day mortality rate (Group S, 15.4%; Group T, 19.5%). Ninety-day mortality rate was statistically significantly higher in Group T (46.3% vs 15.4%; P = .046). Preprocedural bilirubin level was higher in Group T, as were postprocedural leukocyte and C-reactive protein (CRP) levels. CONCLUSIONS: Suprapapillary and transpapillary stent placement procedures were similar in terms of procedural success, occlusion rate, revision rate, postprocedural AEs, and 30-day mortality. Ninety-day mortality rate and postprocedural leukocyte and CRP levels were higher in Group T, although these patients were also older and had higher preprocedural bilirubin levels.

Hilar cholangiocarcinoma presenting with hematochezia due to metastases to the rectum.

An 84-year-old female, with history of endometrial and gallbladder adenocarcinomas, both submitted to curative surgeries, was admitted to the emergency room with obstructive jaundice. Computed tomography and subsequent magnetic resonance cholangiopancreatography revealed a common hepatic duct stenosis with intrahepatic biliary dilatation. She underwent percutaneous transhepatic cholangiography with successful biliary drainage. During the same admission, the patient experienced episodes of hematochezia. Rectosigmoidoscopy showed a 20 mm ulcer in the distal rectum and congestion of the rectal mucosa. Computed tomography revealed rectal wall circumferential thickening. Ulcer biopsies were compatible with a neoplasia of biliary origin.

Impact of preoperative muscle mass and quality on surgical outcomes in patients undergoing major hepatectomy for perihilar cholangiocarcinoma.

PURPOSES: This study sought to define the impact of skeletal muscle mass and quality on postoperative outcomes in patients with perihilar cholangiocarcinoma. METHODS: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma were included. The normalized total psoas area (TPA) (psoas muscle index [PMI]) and average Hounsfield units of the TPA (psoas muscle density [PMD]) were measured using preoperative computed tomography images. The cohort was dichotomized using the following indices: sex-specific lowest tertile (low PMI and low PMD) and other (normal PMI and normal PMD). Intraoperative and postoperative outcomes were compared, focusing on PMI and PMD. RESULTS: A total of 456 patients were analyzed. The intraoperative blood loss (IBL) was 21.3 ml/kg in the low PMI group and 17.2 ml/kg in the normal PMI group (P = .008). Patients in the low PMI or PMD group experienced postoperative infectious complications more frequently than those in the other groups. The median survival time was 37.8 months in the low PMI group and 54.2 months in the normal PMI group (P = .027). CONCLUSIONS: PMI and PMD were closely associated with IBL and postoperative infectious complications. Additionally, PMI impacted long-term survival. These results suggest an importance of improving muscle mass and quality before surgery.

Preoperative risk factors for early recurrence after resection of perihilar cholangiocarcinoma.

BACKGROUND: Early recurrence after curative resection of perihilar cholangiocarcinoma (PHCC) often occurs within a year of surgery. Preoperative predictors of early recurrence remain unclear. The aim of this study was to define reliable preoperative predictors of early recurrence. METHODS: Medical records and preoperative multidetector-row CT of patients with PHCC who underwent resection between 2002 and 2018 were reviewed. Clinical findings, tumour markers, and radiological appearances including a 'periductal enation sign' (PES) where there was evidence of soft tissue enhancement appearing to arise from the extrahepatic bile duct, were analysed. RESULTS: Among 261 patients who underwent resection for PHCC, 67 (25.7 per cent) developed early recurrence. Multivariable analysis identified four preoperative risk factors for early recurrence, namely carbohydrate antigen 19-9 (CA19-9) 37 U/ml or higher (OR 2.19, 95 per cent confidence interval (c.i.) 1.08 to 4.46), positive PES (OR 7.37, 95 per cent c.i. 2.46 to 22.10), mass-forming tumour (OR 4.46, 95 per cent c.i. 1.83 to 10.90), and luminal-occlusion tumour (OR 4.52, 95 per cent c.i. 2.11 to 9.68). The OR of preoperative risk factors were used to define four risk subgroups for early recurrence. The early recurrence rates in the low, moderate, high, and very-high risk groups were 0, 9.4 , 39.7, and 65.0 per cent respectively. CONCLUSION: CA19-9, PES, mass-forming tumour, and luminal-occlusion tumour identify patients at higher risk for early recurrence after resection of PHCC.

Preoperative Diagnosis of Lymph Node Metastasis of Perihilar Cholangiocarcinoma Using Diffusion-Weighted Magnetic Resonance Imaging.

INTRODUCTION: Although the prognosis of patients with resected perihilar cholangiocarcinoma (PHC) with histological lymph node metastasis (LNM) is poor, preoperative prediction of LNM is difficult. This study aimed to evaluate the diagnostic performance of diffusion-weighted magnetic resonance imaging (DWI) for LNM of PHC. METHOD: Consecutive patients who underwent surgical resection of PHC between January 2012 and May 2020 were retrospectively reviewed. The lymph node (LN) area (mm2) and apparent diffusion coefficient (ADC) value ( × 10-3 mm2/s) of pericholedochal LNs were measured by DWI. The characteristics of the patients and the LNs were evaluated according to the histological presence or absence of regional LNM. Univariate and multivariate analyses were performed to identify the predictors of LNM of PHC. RESULTS: Of the 93 eligible patients, 49 (53%) were LNM positive and 44 (47%) were LNM negative. Although the characteristics of the patients were similar between the two groups, the mean ADC value was significantly lower in the LNM positive group than in the LNM negative group. On multivariate analysis, mean ADC value ≤1.80 × 10-3 mm2/s was independently associated with LNM of PHC (risk ratio: 12.5, 95% confidence interval: 3.05-51.4; p = 0.0004). The sensitivity, specificity and accuracy of mean ADC values ≤ 1.80 × 10-3 mm2/s for predicting LNM of PHC were 94%, 55% and 75%, respectively. CONCLUSIONS: DWI might be useful for the preoperative diagnosis of LNM of PHC.

Endoscopic management of perihilar cholangiocarcinoma.

Endoscopic management for perihilar cholangiocarcinoma (PHCC) is evolving toward more accurate diagnosis and safer drainage. In imaging, it is important to diagnose the entire lesion using multidetector-row computed tomography to determine resectability and optimal surgical planning, followed by local diagnosis using endoscopic retrograde cholangiopancreatography. Video peroral cholangioscopy and probe-based confocal laser endomicroscopy have been newly introduced as diagnostic imaging methods and are being applied clinically. In transpapillary forceps biopsy for PHCC diagnosis, the location in the bile duct (for mapping biopsy) and the number of biopsy samples should be determined depending on resectability, the morphological type, and future surgical planning. Preoperative drainage has shifted from percutaneous transhepatic biliary drainage to endoscopic nasobiliary drainage given the possibility of seeding metastasis. In addition, considering potential patient discomfort from a nasal tube, the usefulness of the placement of a plastic stent above the papilla (inside stent) as a bridging therapy for surgery has been reported. For drainage of unresectable PHCC, the improved prognosis due to advances in chemotherapy has necessitated a strategy that accounts for reintervention. Thus, in addition to uncovered self-expandable metallic stents (SEMS), exchangeable slim fully covered SEMS and inside stents have started to be used. In addition to the conventional transpapillary approach, an endoscopic ultrasonography-guided approach has been introduced, and a combination of both methods has also been proposed. To improve the quality of life and prognosis of PHCC patients, endoscopists need to understand and be able to use the various methods of endoscopic management for PHCC.