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.

Cholangiocarcinoma: Epidemiology and Imaging-Based Review.

Cholangiocarcinoma (CCA) is a rare cancer of the bile duct epithelium, and in the last few decades its incidence rate has been increasing. It is associated with a high mortality rate due to late diagnosis and its aggressive nature. Many risk factors have been identified; some are more common in certain regions than others. CCA can be classified according to its anatomical location or macroscopic growth pattern, the latter being most helpful for imaging interpretation. Clinical features can vary from obstructive-like symptoms to nonspecific symptoms, such as weight loss and malaise. Imaging, specifically MRI/MRCP, is crucial in diagnosing CCA, staging, and treatment planning. Surgery with chemotherapy is the mainstay treatment option, and other palliative treatment options exist for those who have unresectable disease.

Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct.

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Cholangiocarcinoma identified in perforated choledochal cyst in a 3-year-old boy.

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.

Cox model risk score to predict survival of intrahepatic cholangiocarcinoma after ultrasound-guided ablation.

PURPOSE: To explore factors associated with overall survival (OS) and progression-free survival (PFS) of intrahepatic cholangiocarcinoma (iCCA) after ultrasound-guided ablation and establish a model for survival risk evaluation. METHODS: Data from 54 patients with 86 iCCAs between August 2008 and October 2022 were retrospectively analyzed. Cox regression were used to analyze the effects of clinical features on OS and PFS. Based on the variables screened by multivariable analysis, a model was established to predict the survival of the patients. Time-dependent receiver operating characteristic (timeROC) curve was constructed to evaluate the performance of this model. The model was further verified by bootstrap validation. The clinical usefulness of the model was evaluated by the decision curve analysis (DCA). RESULTS: During follow up, 39 patients died and 49 patients developed recurrence. Pre-ablation CA199 level > 140 U/ml was the only independent predictor of poor PFS. Age > 70 years, early recurrence, maximal diameter of tumor size > 1.5 cm and pre-ablation CA199 level > 140 U/ml were significantly associated with poor OS. Then a model was established based on the above four variables. The areas under the timeROC curve (AUC) for 1-year, 2-year, 3-year, 5-year were 0.767, 0.854, 0.791 and 0.848, respectively. After bootstrapping for 1000 repetitions, the AUCs were similar to the initial model. DCA also demonstrated that the model had good positive net benefits. CONCLUSION: The established model in this study could predict the survival outcomes of the patients with iCCA after thermal ablation, but further research was needed to validate the results.

Usefulness of Direct Peroral Cholangioscopy Using a Multibending Ultraslim Endoscope for the Management of Intrahepatic Bile Duct Lesions (with Videos).

Background/Aims: : Peroral cholangioscopy (POC) has been used to assess intrahepatic duct (IHD) lesions but with a limited role. A new multibending (MB) ultraslim endoscope has been designed to improve POC performance. We evaluated the usefulness of POC using the MB ultraslim endoscope for the management of IHD lesions. Methods: : Between March 2017 and March 2020, 22 patients underwent direct POC using the MB ultraslim endoscope for IHD lesions documented by previous imaging or cholangiopancreatography. The primary outcome was technical success of POC, and secondary outcomes were technical success of POC-guided interventions, median procedure time, and POC-related adverse events. Results: : The technical success rate for POC using the MB ultraslim endoscope for IHD lesions was 95.5% (21/22). Free-hand insertion was successful in 95.2% (20/21). The overall technical success rate for POC-guided intervention was 100% (21/21), including nine diagnostic and 12 therapeutic procedures (eight direct stone removal and four intraductal lithotripsies). The median procedure time was 29 minutes (range, 9 to 79 minutes). There were no procedure-related adverse events. Conclusions: : Direct POC using the MB ultraslim endoscope allows direct visualization of IHD lesions and may be useful for diagnosis and therapeutic management in selected patients.

[Air embolism after biliary stent removal during endoscopic retrograde cholangiopancreatography for cholangitis after biliary reconstruction: a case report].

A 62-year-old male patient underwent pancreaticoduodenectomy with modified Child reconstruction for distal cholangiocarcinoma. After eight years, a contrast-enhanced computed tomography (CT) revealed a recurrent lesion at the biliojejunal anastomosis, and a biliary stent was placed for obstructive cholangitis in the right posterior segment of the liver. A right hepatectomy was planned for a local recurrent lesion;thus, percutaneous transhepatic portal embolization was performed on the portal vein's right branch to enlarge the left liver. However, he was referred to our department for endoscopic retrograde biliary drainage for the subsequent cholangitis and liver abscess appearance. A double-balloon enteroscope under CO2 insufflation was used to reach the bile duct-jejunal anastomosis. After removing the bile duct stent with grasping forceps, his general condition suddenly deteriorated, causing cardiopulmonary arrest. He was diagnosed with air embolism based on the findings of air in the heart, aorta, and brain on CT after the return of spontaneous circulation. Treatment for the air embolism and subsequent complications continued in the intensive care unit, but he eventually died 114 days after the onset of the air embolism due to his deteriorating general condition. Pathological autopsy revealed cholangiocarcinoma that extends from the porta hepatis to the posterior segment. Additionally, the proximity between the bile duct and vein extended by the adenocarcinoma and the fibrous obstruction of the vein were revealed, indicating the possibility of a bile duct-vein shunt.

Unique portal venous phase imaging discordance between CEUS and MRI: a valuable predictor of intrahepatic cholangiocarcinoma?

PURPOSE: We have long noted unique portal venous phase (PVP) imaging discordance of focal liver masses between CEUS, showing rapid marked washout, and MRI, showing progressive or sustained enhancement. We postulate association of this unique discordance with intrahepatic cholangiocarcinoma (ICC) and causal relationship to different contrast agent behavior. We investigate this unique discordance, propose its clinical significance for ICC diagnosis, and confirm further histologic associations. METHODS: Cases were collected within our CEUS department and from pathology records over a ten-year interval. This retrospective review includes 99 patients, 73 with confirmed ICC and 26 other diagnoses, showing unique PVP discordance. The CEUS and MRI enhancement characteristics were compared for all patients. RESULTS: Unique discordance is identified in 67/73 (92%) ICC and difference between the PVP appearance on MRI and CEUS is statistically significant (p <  0.0001). Arterial phase enhancement did not show statistically significant difference between CEUS and MRI, p >  0.05. Other diagnoses showing unique discordance include especially lymphoma (n = 7), sclerosed hemangioma (n = 6), HCC (n = 4), metastases (n = 2), and other rare entities. CONCLUSION: ICC shows this discrepant intermodality enhancement pattern in a statistically significant number of cases and should be considered along with other LR-M features in at-risk patients. Discordance is also rarely seen in a number of other liver lesions.

Preoperative MRI features predicting very early recurrence of intrahepatic mass-forming cholangiocarcinoma after R0 resection: a comparison with the AJCC 8th edition staging system.

PURPOSE: This study aimed to establish a nomogram based on preoperative magnetic resonance imaging (MRI) features to predict the very early recurrence (VER, less than 6 months) of intrahepatic mass-forming cholangiocarcinoma (IMCC) after R0 resection. METHODS: This study enrolled a group of 193 IMCC patients from our institution between March 2010 and January 2022. Patients were allocated into the development cohort (n = 137) and the validation cohort (n = 56), randomly, and the preoperative clinical and MRI features were collected. Univariate and multivariate stepwise logistic regression assessments were adopted to assess predictors of VER. Nomogram was constructed and certificated in the validation cohort. The performance of the prediction nomogram was evaluated by its discrimination, calibration, and clinical utility. The performance of the nomogram was compared with the T stage of the American Joint Committee on Cancer (AJCC) 8th edition staging system. RESULTS: Fifty-three patients (27.5%) experienced VER of the tumor and 140 patients (72.5%) with non-VER, during the follow-up period. After multivariate stepwise logistic regression, number of lesions, diffuse hypoenhancement on arterial phase, necorsis and suspicious lymph nodes were independently associated with VER. The nomogram demonstrated significantly higher area under the curve (AUC) of 0.813 than T stage (AUC = 0.666, P = 0.006) in the development cohort, whereas in the validation cohort, the nomogram showed better discrimination performance, with an AUC of 0.808 than T stage (0.705) with no significantly difference (P = 0.230). Decision curve analysis reflected the clinical net benefit of the nomogram. CONCLUSION: The nomogram based on preoperative MRI features is a reliable tool to predict VER for patients with IMCC after R0 resection. This nomogram will be helpful to improve survival prediction and individualized treatment.

A multi-center diagnostic system for intrahepatic mass-forming cholangiocarcinoma based on preoperative MRI and clinical features.

OBJECTIVES: To establish a non-invasive diagnostic system for intrahepatic mass-forming cholangiocarcinoma (IMCC) via decision tree analysis. METHODS: Totally 1008 patients with 504 pathologically confirmed IMCCs and proportional hepatocellular carcinomas (HCC) and combined hepatocellular cholangiocarcinomas (cHCC-CC) from multi-centers were retrospectively included (internal cohort n = 700, external cohort n = 308). Univariate and multivariate logistic regression analyses were applied to evaluate the independent clinical and MRI predictors for IMCC, and the selected features were used to develop a decision tree-based diagnostic system. Diagnostic efficacy of the established system was calculated by the receiver operating characteristic curve analysis in the internal training-testing and external validation cohorts, and also in small lesions ≤ 3 cm. RESULTS: Multivariate analysis revealed that female, no chronic liver disease or cirrhosis, elevated carbohydrate antigen 19-9 (CA19-9) level, normal alpha-fetoprotein (AFP) level, lobulated tumor shape, progressive or persistent enhancement pattern, no enhancing tumor capsule, targetoid appearance, and liver surface retraction were independent characteristics favoring the diagnosis of IMCC over HCC or cHCC-CC (odds ratio = 3.273-25.00, p < 0.001 to p = 0.021). Among which enhancement pattern had the highest weight of 0.816. The diagnostic system incorporating significant characteristics above showed excellent performance in the internal training (area under the curve (AUC) 0.971), internal testing (AUC 0.956), and external validation (AUC 0.945) cohorts, as well as in small lesions ≤ 3 cm (AUC 0.956). CONCLUSIONS: In consideration of the great generalizability and clinical efficacy in multi-centers, the proposed diagnostic system may serve as a non-invasive, reliable, and easy-to-operate tool in IMCC diagnosis, providing an efficient approach to discriminate IMCC from other HCC-containing primary liver cancers. CLINICAL RELEVANCE STATEMENT: This study established a non-invasive, easy-to-operate, and explainable decision tree-based diagnostic system for intrahepatic mass-forming cholangiocarcinoma, which may provide essential information for clinical decision-making. KEY POINTS: • Distinguishing intrahepatic mass-forming cholangiocarcinoma (IMCC) from other primary liver cancers is important for both treatment planning and outcome prediction. • The MRI-based diagnostic system showed great performance with satisfying generalization ability in the diagnosis and discrimination of IMCC. • The diagnostic system may serve as a non-invasive, easy-to-operate, and explainable tool in the diagnosis and risk stratification for IMCC.

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.

Nomogram based on preoperative clinical and MRI features to estimate the microvascular invasion status and the prognosis of solitary intrahepatic mass-forming cholangiocarcinoma.

PURPOSE: To develop a nomogram based on preoperative clinical and magnetic resonance imaging (MRI) features for the microvascular invasion (MVI) status in solitary intrahepatic mass-forming cholangiocarcinoma (sIMCC) and to evaluate whether it could predict recurrence-free survival (RFS). METHODS: We included 115 cases who experienced MRI examinations for sIMCC with R0 resection. The preoperative clinical and MRI features were extracted. Independent predictors related to MVI+ were evaluated by stepwise multivariate logistic regression, and a nomogram was constructed. A receiver operating characteristic (ROC) curve was used to assess the predictive ability. All patients were classified into high- and low-risk groups of MVI. Then, the correlations of the nomogram with RFS in patents with sIMCC were analyzed by Kaplan-Meier method. RESULTS: The occurrence rate of MVI+ was 38.3% (44/115). The preoperative independent predictors of MVI+ were carbohydrate antigen 19-9 > 37 U/ml, tumor size > 5 cm, and an ill-defined tumor boundary. Integrating these predictors, the nomogram exerted a favorable diagnostic performance with areas under the ROC curve of 0.767 (95% confidence interval [CI] 0.654-0.881) in the development cohort, and 0.760 (95% CI 0.591-0.929) in the validation cohort. In the RFS analysis, significant differences were observed between the high- and low-risk MVI groups (6-month RFS rates: 64.5% vs. 78.8% and 46.7% vs. 82.4% in the development and validation cohorts, respectively) (P < 0.05). CONCLUSIONS: A nomogram based on clinical and MRI features is a potential biomarker of MVI and may be a potent method to classify the risk of recurrence in patients with sIMCC.

Systemic Chemotherapy with or without Hepatic Arterial Infusion Chemotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Oligometastasis: A Propensity Score-Matched Analysis.

PURPOSE: To compare the effectiveness of hepatic arterial infusion chemotherapy (HAIC) plus systemic chemotherapy (SYS) with that of SYS alone in patients with intrahepatic cholangiocarcinoma (ICC) with extrahepatic oligometastasis in terms of overall survival (OS) and mortality related to liver failure. MATERIALS AND METHODS: Consecutive patients diagnosed with ICC with extrahepatic oligometastasis who received either HAIC plus SYS or SYS alone between January 2019 and January 2021 were included in this retrospective cohort study. Propensity score matching (PSM) analysis was performed to address potential confounding factors. OS, progression-free survival (PFS), and intrahepatic progression-free survival (IPFS) were analyzed. The occurrence of death due to liver failure was also assessed. RESULTS: The study included a total of 179 patients, with 96 receiving SYS alone and 83 receiving HAIC plus SYS. After PSM, 83 pairs were included for further analysis. The median OS and IPFS were significantly longer in the HAIC plus SYS group compared to the SYS alone group (OS: 15.8 months vs 12.7 months; P = .023; IPFS: 9.7 vs 6.1 months; P < .001). No difference was found in PFS between the 2 groups. The HAIC plus SYS group had a significantly lower rate of mortality due to liver failure compared to the SYS alone group (42% vs 72%; P = .002). CONCLUSIONS: HAIC plus SYS is a promising treatment approach for patients with ICC and extrahepatic oligometastasis with improved OS, IPFS, and freedom from liver failure mortality compared with SYS alone.

Incremental value of volumetric multiparametric MRI over Fudan score for prognosis of unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy.

BACKGROUND: Individualized patient care requires prognostic models customized to a tumor and an individual's disease profile for reliable survival prediction. MRI has prognostic value for intrahepatic cholangiocarcinoma (ICCA). Existing prognostic models for ICCA exclude imaging-based information about an individual's tumor that may reflect important aspects of tumor's biology. Fudan score, a prognostic model applicable to unresectable ICCA, is limited by subjective morphologic imaging parameters. OBJECTIVES: To assess the prognostic value of baseline volumetric multiparametric MRI in unresectable intrahepatic cholangiocarcinoma (ICCA) treated with systemic chemotherapy and the incremental value of MRI over the Fudan score. METHODS: This retrospective study included 114 ICCA patients treated with systemic chemotherapy between 2007 and 2021 after a baseline MRI. The single largest tumor was volumetrically assessed for anatomic (total tumor volume and diameter) and functional parameters (viable tumor volume, percentage-viable tumor volume, viable tumor burden, and ADC). A derivation cohort of 30 patients was utilized to identify MRI parameters associated with overall survival (OS) using Cox regression analysis. The incremental value of MRI over Fudan score was assessed on an independent sub-cohort of 84 patients using Kaplan-Meier analysis and C-index. RESULTS: 114 patients (64 years +/- 11; 61 women) were evaluated. Pre-treatment high (>1350x10-6 mm2/sec) ADC was the only independent predictor of OS (HR, 8.07; P < 0.001). Replacing subjective tumor boundary with objective ADC value, and using modified biochemical thresholds increased the prognostic stratification for the risk groups in the modified ADC-Fudan model compared to the original Fudan model (median survival 12 and 4.5 months; P = 0.055; vs. 11 and 3 months; P < 0.001). The modified ADC-Fudan model demonstrated an 11 % improvement over the original Fudan model (c-index: 0.80 vs. 0.69; P = 0.044) for survival prediction. CONCLUSIONS: High pre-treatment volumetric ADC was associated with unfavorable prognosis in patients with unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy. Supplementing the original Fudan model with ADC and modified serum marker thresholds improved the survival prediction performance by 11% in the resulting modified ADC-Fudan model. CLINICAL IMPACT: Volumetric MRI could improve the survival prediction among ICCA patients prior to receiving potentially toxic and expensive palliative chemotherapies. This could potentially guide individualized therapy for this patient cohort.

Implications of ultrasound-based deep learning model for preoperatively differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

OBJECTIVES: The current study developed an ultrasound-based deep learning model to make preoperative differentiation among hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-ICC). METHODS: The B-mode ultrasound images of 465 patients with primary liver cancer were enrolled in model construction, comprising 264 HCCs, 105 ICCs, and 96 cHCC-ICCs, of which 50 cases were randomly selected to form an independent test cohort, and the rest of study population was assigned to a training and validation cohorts at the ratio of 4:1. Four deep learning models (Resnet18, MobileNet, DenseNet121, and Inception V3) were constructed, and the fivefold cross-validation was adopted to train and validate the performance of these models. The following indexes were calculated to determine the differential diagnosis performance of the models, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), F-1 score, and area under the receiver operating characteristic curve (AUC) based on images in the independent test cohort. RESULTS: Based on the fivefold cross-validation, the Resnet18 outperformed other models in terms of accuracy and robustness, with the overall training and validation accuracy as 99.73% (± 0.07%) and 99.35% (± 0.53%), respectively. Furthers validation based on the independent test cohort suggested that Resnet 18 yielded the best diagnostic performance in identifying HCC, ICC, and cHCC-ICC, with the sensitivity, specificity, accuracy, PPV, NPV, F1-score, and AUC of 84.59%, 92.65%, 86.00%, 85.82%, 92.99%, 92.37%, 85.07%, and 0.9237 (95% CI 0.8633, 0.9840). CONCLUSION: Ultrasound-based deep learning algorithm appeared a promising diagnostic method for identifying cHCC-ICC, HCC, and ICC, which might play a role in clinical decision making and evaluation of prognosis.

Diagnostic performance of magnetic resonance imaging and contrast-enhanced ultrasound in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma: a meta-analysis.

PURPOSE: To compare the diagnostic ability between magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). METHODS: Original studies reporting the diagnostic accuracy of MRI and CEUS in differentiating ICC from HCC were identified in PubMed and EMBASE databases. Histopathological examination was used as the reference standard for tumor diagnosis. Study quality was assessed using QUADAS-2 scale. Data were extracted to calculate the pooled diagnostic sensitivity, specificity, and diagnostic odds ratio (DOR) using a bivariate random-effects model, as well as the area under the curve (AUC). Sensitivity analysis, subgroup analysis, meta-regression, and investigation of publication bias were also performed. RESULTS: A total of 26 studies with 28 data subsets (18 on MRI, 10 on CEUS) were included, consisting of 4169 patients with 1422 ICC lesions and 2747 HCC lesions. Most MRI studies were performed at 3T with hepatobiliary agents, and most CEUS studies used SonoVue as the contrast agent. In MRI, the pooled sensitivity, specificity, DOR, and AUC in distinguishing ICC from HCC were 0.81 (0.79, 0.84), 0.90 (0.88, 0.91), 41.47 (24.07, 71.44), and 0.93 (0.90, 0.96), respectively. The pooled sensitivity, specificity, DOR, and AUC of CEUS were 0.88 (0.84, 0.90), 0.80 (0.78, 0.83), 42.06 (12.38, 133.23), and 0.93 (0.87, 0.99), respectively. Subgroup analysis and meta-regression analysis demonstrated significant heterogeneity among the studies associated with the type of contrast agent in MRI studies. No publication bias was found. CONCLUSION: Both MRI and CEUS showed excellent diagnostic performance in differentiating ICC from HCC. CEUS showed higher pooled sensitivity and MRI showed higher pooled specificity.