Contributions of endoscopic ultrasonography-guided tissue acquisition (EUS-TA) to the diagnostics of biliary stricture and gallbladder lesions.

Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen.

A case report of pediatric biliary botryoid rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children, and botryoid rhabdomyosarcoma (BRMS) represents a subtype of RMS. BRMS primarily occurs in infants, young children, and adolescent females, with a predilection for mucosa-lined hollow organs such as the bladder, vagina, bile duct, and so on. Its occurrence in the biliary tract is extremely rare. Due to the high malignancy and rapid metastasis of biliary botryoid rhabdomyosarcoma, early diagnosis and treatment are crucial for improving prognosis.

Endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling.

Advances in next-generation sequencing have made comprehensive genomic profiling (CGP) using tumor tissue specimens and liquid biopsy using blood samples feasible in routine clinical practice. In the context of pancreaticobiliary cancer, it is necessary to consider CGP in formulating individualized treatment strategies. Performing CGP with tumor tissue specimens requires a sufficient number of high-quality samples. EUS-guided tissue acquisition (EUS-TA) is expected to play a significant role in this regard, and endosonographers need to address this role. Here, we review the current status of EUS-TA for CGP focusing on pancreatic cancer and biliary tract cancer.

Preoperative Psoas Muscle Thickness to Height Ratio Predicts Poor Survival After Resection of Biliary Tract Cancer.

BACKGROUND/AIM: Accumulating evidence suggests that muscle mass depletion (sarcopenia) has a negative impact on survival in several malignancies, including biliary tract cancer (BTC). Computed tomography (CT)-measured psoas muscle thickness to height ratio (PMTH) has been reported as a surrogate measure for muscle mass that does not require specialized equipment or software. The aim of this retrospective study was to investigate whether preoperative PMTH predicts oncological outcomes of patients undergoing surgical resection for BTC. PATIENTS AND METHODS: PMTH was assessed in 211 patients by analyzing axial CT images at the level of the umbilicus. The most predictive cutoff of PMTH was determined by survival classification and regression tree analysis. Propensity score-based inverse probability weighting (IPW) was used to balance characteristics between the low and high PMTH groups. RESULTS: Applying a PMTH cutoff of 17.5 mm/m, the low PMTH group comprised 114 patients (54%). Low PMTH was associated with female sex, non-obesity, CA19-9 elevation, and lymph node metastasis. After IPW adjustment, the low PMTH group had a significantly shorter disease-specific survival (p<0.001) and relapse-free survival (p<0.001) than the high PMTH group. IPW-adjusted regression analysis revealed that a low PMTH was independently associated with worse disease-specific survival (hazard ratio=2.98, p<0.001) and relapse-free survival (hazard ratio=2.49, p<0.001), in addition to other factors such as tumor differentiation, perineural invasion, and resection margin status. CONCLUSION: Preoperative PMTH may be a simple and feasible index of sarcopenia for predicting poor survival after resection of BTC.

Variation in clinical target volume delineation in postoperative radiotherapy for biliary tract cancer.

We aimed to evaluate the inter-clinician variability in the clinical target volume (CTV) for postoperative radiotherapy (PORT) for biliary tract cancer (BTC) including extrahepatic bile duct cancer (EBDC) and gallbladder cancer (GBC). Nine experienced radiation oncologists delineated PORT CTVs for distal EBDC (pT2N1), proximal EBDC (pT2bN1) and GBC (pT2bN1) patients. The expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) was used to quantify expert agreements. We generated volumes with a confidence level of 80% to compare the maximum distance to each CTV in six directions. The degree of agreement was moderate; overall kappa values were 0.573 for distal EBDC, 0.513 for proximal EBDC, and 0.511 for GBC. In the distal EBDC, a larger variation was noted in the right, post, and inferior direction. In the proximal EBDC, all borders except the right and left direction showed a larger variation. In the GBC, a larger variation was found in the anterior, posterior, and inferior direction. The posterior and inferior borders were the common area having discrepancies, associated with the insufficient coverage of the paraaortic node. A consensus guideline is needed to reduce inter-clinician variability in the CTVs and adequate coverage of regional lymph node area.

Imaging Features of Premalignant Biliary Lesions and Predisposing Conditions with Pathologic Correlation.

Biliary malignancies include those arising from the intrahepatic and extrahepatic bile ducts as well as the gallbladder and hepatopancreatic ampulla of Vater. The majority of intrahepatic and extrahepatic malignancies are cholangiocarcinomas (CCAs). They arise owing to a complex interplay between the patient-specific genetic background and multiple risk factors and may occur in the liver (intrahepatic CCA), hilum (perihilar CCA), or extrahepatic bile ducts (distal CCA). Biliary-type adenocarcinoma constitutes the most common histologic type of ampullary and gallbladder malignancies. Its prognosis is poor and surgical resection is considered curative, so early detection is key, with multimodality imaging playing a central role in making the diagnosis. There are several risk factors for biliary malignancy as well as predisposing conditions that increase the risk; this review highlights the pertinent imaging features of these entities with histopathologic correlation. The predisposing factors are broken down into three major categories: (a) congenital malformations such as choledochal cyst and pancreaticobiliary maljunction; (b) infectious or inflammatory conditions such as parasitic infections, hepatolithiasis, primary sclerosing cholangitis, and porcelain gallbladder; and (c) preinvasive epithelial neoplasms such as biliary intraepithelial neoplasm, intraductal papillary neoplasm of the bile duct, intra-ampullary papillary tubular neoplasm, and intracholecystic papillary neoplasm of the gallbladder. Recognizing the baseline features of these premalignant biliary entities and changes in their appearance over time that indicate the advent of malignancy in high-risk patients can lead to early diagnosis and potentially curative management. An invited commentary by Volpacchio is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Prospective Comparison of 68Ga-FAPI versus 18F-FDG PET/CT for Tumor Staging in Biliary Tract Cancers.

Background Gallium 68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI), an imaging agent for detecting tumors, represents a promising alternative to fluorine 18 fluorodeoxyglucose (18F-FDG). Purpose To compare the potential efficacy of 68Ga-FAPI PET/CT with that of 18F-FDG PET/CT for detecting primary tumor and nodal and distant metastases in biliary tract cancer (BTC) and to explore the impact (tumor staging) of 68Ga-FAPI compared with 18F-FDG on clinical management of BTC. Materials and Methods This single-center prospective clinical study was performed at the Affiliated Hospital of Southwest Medical University between June 2020 and June 2021. Participants with BTC underwent both 68Ga-FAPI and 18F-FDG PET/CT. Histopathologic examination, morphologic imaging, and/or follow-up imaging served as the reference standard. The maximum standardized uptake value (SUVmax) of the primary tumor and nodal and distant metastases between 18F-FDG and 68Ga-FAPI PET/CT were compared using the paired-sample t test. Results Eighteen participants with primary or recurrent BTC were evaluated (mean age, 61 years ± 10 [SD]). The sensitivity of 68Ga-FAPI PET/CT was higher than that of 18F-FDG PET/CT for detecting primary tumors (16 of 16 [100%] vs 13 of 16 [81%]), nodal metastases (41 of 42 [98%] vs 35 of 42 [83%]), and distant metastases (99 of 99 [100%] vs 78 of 99 [79%]). 68Ga-FAPI PET/CT resulted in new oncologic findings in 10 of 18 participants and upgraded tumor staging or restaging in five of 18 participants compared with 18F-FDG PET/CT. 68Ga-FAPI PET/CT demonstrated higher sensitivity than 18F-FDG PET/CT in inflammatory processes secondary to tumor-related obstruction (seven of eight [88%] vs one of eight [13%]). 68Ga-FAPI showed lower average SUVmax in inflammatory processes than in oncologic lesions (4.9 ± 2.6 vs 10.0 ± 4.6, respectively; P = .003). Conclusion Gallium 68-labeled fibroblast-activation protein inhibitor PET/CT for tumor staging showed potential for more accurate staging of biliary tract cancer, thereby improving treatment decision making. Clinical trial registration no. ChiCTR2100044131 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Choyke in this issue.

Preoperative FDG-Positive Lymph Nodes Predict the Postoperative Prognosis in Resectable Biliary Tract Cancers.

BACKGROUND: F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) has been used to diagnose and stage various cancers. In regard to biliary tract cancer (BTC), due to cholangitis it is difficult to evaluate FDG uptake caused by cancer. We previously showed that FDG-positive lymph nodes (LNs) of resectable BTC had a possibility of predicting postoperative prognosis. OBJECTIVE: This study aimed to validate the usability of FDG-PET for LNs using another cohort and to investigate in detail the relationship between FDG-positive LNs and the prognosis of BTC. METHODS: We measured the preoperative maximum standardized uptake value (SUVmax) at each of the 190 surgically dissected LN areas in 67 patients and investigated the prognosis using our previously determined SUVmax cut-off values of ≥ 2.8. RESULTS: Regarding the prognosis of patients with resectable BTC, a LN SUVmax ≥ 2.8 [PET N (+)] was a poor prognostic factor for recurrence-free survival (RFS) compared with a LN SUVmax < 2.8 [PET N (-)]. It was confirmed that the hazard ratio forest plot [PET N (+)/PET N (-)] for RFS indicated a similar tendency among subcategories. Moreover, we investigated patients with pN0 disease and demonstrated that the PET N (+) group also had a significantly worse RFS outcome compared with the PET N (-) group. Recurrence of the PET N (+) group has significantly occurred more often in LNs than that of the PET N (-) group. CONCLUSION: High LN SUVmax was confirmed to be the preoperatively diagnosed prognostic risk factor for RFS in resectable BTC and could be helpful for clinical decision making regarding the perioperative treatment strategy.

Additional Value of Integrated 18F-FDG PET/MRI for Evaluating Biliary Tract Cancer: Comparison with Contrast-Enhanced CT.

OBJECTIVE: To evaluate the value of 18F-fluorodeoxyglucose PET/MRI added to contrast-enhanced CT (CECT) in initial staging, assessment of resectability, and postoperative follow-up of biliary tract cancer. MATERIALS AND METHODS: This retrospective study included 100 patients (initial workup [n = 65] and postoperative follow-up [n = 35]) who had undergone PET/MRI and CECT for bile duct or gallbladder lesions between January 2013 and March 2020. Two radiologists independently reviewed the CECT imaging set and CECT plus PET/MRI set to determine the likelihood of malignancy, local and overall resectability, and distant metastasis in the initial workup group, and local recurrence and distant metastasis in the follow-up group. Diagnostic performances of the two imaging sets were compared using clinical-surgical-pathologic findings as standards of reference. RESULTS: The diagnostic performance of CECT significantly improved after the addition of PET/MRI for liver metastasis (area under the receiver operating characteristic curve [Az]: 0.77 vs. 0.91 [p = 0.027] for reviewer 1; 0.76 vs. 0.92 [p = 0.021] for reviewer 2), lymph node metastasis (0.73 vs. 0.92 [p = 0.004]; 0.81 vs. 0.92 [p = 0.023]), and overall resectability (0.79 vs. 0.92 [p = 0.007]; 0.82 vs. 0.94 [p = 0.021]) in the initial workup group. In the follow-up group, the diagnostic performance of CECT plus PET/MRI was significantly higher than that of CECT imaging for local recurrence (0.81 vs. 1.00 [p = 0.029]; 0.82 vs. 0.94 [p = 0.045]). CONCLUSION: PET/MRI may add value to CECT in patients with biliary tract cancer both in the initial workup for staging and determination of overall resectability and in follow-up for local recurrence.

Factors influencing diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic and biliary tumors.

BACKGROUND AND AIM: Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is influenced by several factors, primarily operator expertise. Formal training in EUS-FNA, as suggested by the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy guidelines, is not always available and is often expensive and time-consuming. In this study we evaluate factors influencing the diagnostic accuracy of pancreatic EUS-FNA. METHODS: In a retrospective study, 557 consecutive EUS-FNAs were evaluated. Several variables relating to the procedures were considered to calculate the EUS-FNA performance over eight years. RESULTS: A total of 308 out of 557 EUS-FNAs were selected. Overall sensitivity of EUS-FNA was 66% (95% CI: 60.8-71.8), specificity 100%, and diagnostic accuracy 69% (95% CI: 64.0-74.4). An increase in diagnostic accuracy was observed to >90% using a new fine-needle biopsy (FNB) needle and in the case of simultaneous sampling of primary and metastatic lesions. Diagnostic accuracy >80% was observed after 250 procedures, in the absence of rapid on-site cytopathological examination (ROSE). Multivariate logistic regression analysis confirmed that the FNB needle, operator skill, and double EUS-FNA sampling are associated with high diagnostic accuracy. CONCLUSIONS: The learning curve for EUS-FNA may be longer and a considerable number of procedures are needed to achieve high diagnostic accuracy in the absence of ROSE. However, the use of FNB needles and the simultaneous sampling of primary and metastatic lesions can rapidly improve the diagnostic accuracy of the procedure.

Intraoperative contrast-enhanced ultrasound can have a crucial role in surgical decision-making during hepato-pancreatico-biliary surgery - Analysis of impact and input.

OBJECTIVE: To assess the impact and procedural input of intraoperative ultrasound (IOUS) with contrast-enhanced ultrasound (CEUS) and ultrasound elastography on surgical decision making during the procedure and consequently the outcome after hepato-pancreatico-biliary (HPB) surgery. MATERIALS AND METHODS: Data of 50 consecutive patients, who underwent HPB surgery from 04/2018 to 07/2018 were prospectively collected for this study. During surgery, IOUS with a high-resolution ultrasound device using CEUS after bolus injection of 2.4-5 ml dulphur hexafluoride microbubbles using a 6-9 MHz probe and a share wave and strain elastography was performed by an experienced examiner. Process and time analysis were carried out using mobile phone timer. RESULTS: The IOUS with CEUS and elastography correctly identified 42 malignant tumors and 4 benign lesions. In 3 cases, the examination provided false positive result (identifying 3 benign lesions as malignant) and in 1 case a malignant lesion was incorrectly assessed as benign (sensitivity 97,7%, specificity 57,1%, PPV 93,3% and NPV 80%).The specific question by the surgeon could be answered successfully in 98% of the cases. In 76% of the cases, there was a modification (42%) or a fundamental change (34%) of the planned surgical approach due to the information provided by the IOUS. Within the last group, the IOUS had a major impact on therapy outcome. In 7 patients an additional tumor resection was required, in 5 patients the tumor was assessed as inoperable, and in total in 5 patients an intraoperative RFA (4/5) or postoperative RITA (1/5) was required.Regarding procedural input, there was only a slight, but significant difference between the transport and set-up times before the intraoperative use (mean: 14 min 22 s) and the return transport (mean 13 min 6 s), (p = 0,038). The average examination time was 14 minutes, which makes only one third of the overall time demand. CONCLUSION: Combination of IOUS with CEUS and elastography in oncological HPB surgery provides valuable information that affects surgical decision-making. The procedural input of about 45 minutes seems to be a good investment considering the improvement of the surgical procedure and a significant modification of the therapy approach in the majority of the cases.

Consensus Guidelines for the Use of Fluorescence Imaging in Hepatobiliary Surgery.

OBJECTIVE: To establish consensus recommendations for the use of fluorescence imaging with indocyanine green (ICG) in hepatobiliary surgery. BACKGROUND: ICG fluorescence imaging has gained popularity in hepatobiliary surgery in recent years. However, there is varied evidence on the use, dosage, and timing of administration of ICG in clinical practice. To standardize the use of this imaging modality in hepatobiliary surgery, a panel of pioneering experts from the Asia-Pacific region sought to establish a set of consensus recommendations by consolidating the available evidence and clinical experiences. METHODS: A total of 13 surgeons experienced in hepatobiliary surgery and/or minimally invasive surgery formed an expert consensus panel in Shanghai, China in October 2018. By the modified Delphi method, they presented the relevant evidence, discussed clinical experiences, and derived consensus statements on the use of ICG in hepatobiliary surgery. Each statement was discussed and modified until a unanimous consensus was achieved. RESULTS: A total of 7 recommendations for the clinical applications of ICG in hepatobiliary surgery were formulated. CONCLUSIONS: The Shanghai consensus recommendations offer practical tips and techniques to augment the safety and technical feasibility of ICG fluorescence-guided hepatobiliary surgery, including laparoscopic cholecystectomy, liver segmentectomy, and liver transplantation.

Efficacy and safety of palliative endobiliary radiofrequency ablation using a novel temperature-controlled catheter for malignant biliary stricture: a single-center prospective randomized phase II TRIAL.

BACKGROUND: Endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative treatment for malignant biliary strictures (MBSs); however, concerns about complications related to thermal injury remain. In this study, we evaluated the efficacy and safety of EB-RFA with a novel catheter for MBS. METHODS: Patients with inoperable cancer causing MBS were randomly assigned to either the radiofrequency ablation (RFA) group or the non-RFA group. The RFA group underwent EB-RFA at the stricture site with a temperature-controlled catheter (ELRA™; STARmed Co., Goyang, Korea) followed by deployment of a self-expanding metal stent (SEMS). For the non-RFA group, only SEMS placement was performed. The duration of stent patency, overall survival (OS), and 30-day complication rate were evaluated. This trial was registered at ClinicalTrials.gov (number NCT02646514). RESULTS: A total of 48 patients were enrolled (24 in each group). During a median follow-up period of 135.0 days (RFA group) and 119.5 days (non-RFA group), the 90-day stent patency rate, median duration of stent patency, and median OS were not different between the groups (58.3% vs. 45.8% [P = 0.386], 132.0 days vs. 116.0 days [P = 0.440], and 244.0 days vs. 180.0 days [P = 0.281], respectively). In the RFA group, procedure-related complications including thermal injury-related complications, such as bile duct perforation or hemobilia, were not reported. The early complication (< 7 days) rates were not different between the groups (4.2% vs. 12.5%, P = 0.609), and there were no late complications (7-30 days) in both groups. CONCLUSION: EB-RFA with a temperature-controlled catheter followed by SEMS placement for patients with inoperable MBS can be safe and feasible with acceptable biliary patency.

[Application and challenge of radiomics technique in the era of precision medicine for hepatobiliary disease].

Radiomics, as an emerging technique of omics, shows the pathophysiological information of images via extracting innumerable quantitative features from digital medical images. In recent years, it has been an exponential increase in the number of radiomics studies. The applications of radiomics in hepatobiliary diseases at present include: assessment of liver fibrosis, discrimination of malignant from benign tumors, prediction of biological behavior, assessment of therapeutic response, and prognosis. Integrating radiomics analysis with machine learning algorithms has emerged as a non-invasive method for predicting liver fibrosis stages, microvascular invasion and post-resection recurrence in liver cancers, lymph node metastasis in biliary tract cancers as well as treatment response in colorectal liver metastasis, with high performance. Although the challenges remain in the clinical transformation of this technique, radiomics will have a broad application prospect in promoting the precision diagnosis and treatment of hepatobiliary diseases, backed by multi-center study with large sample size or multi-omics study.

Impact of breath-hold level on positional error aligned by stent/Lipiodol in Hepatobiliary radiotherapy with breath-hold respiratory control.

BACKGROUND: Respiratory motion management with breath hold for patients with hepatobiliary cancers remain a challenge in the precise positioning for radiotherapy. We compared different image-guided alignment markers for estimating positional errors, and investigated the factors associated with positional errors under breath-hold control. METHODS: Spirometric motion management system (SDX) for breath holds was used in 44 patients with hepatobiliary tumor. Among them, 28 patients had a stent or embolized materials (lipiodol) as alignment markers. Cone-beam computed tomography (CBCT) and kV-orthogonal images were compared for accuracy between different alignment references. Breath-hold level (BHL) was practiced, and BHL variation (ΔBHL) was defined as the standard deviation in differences between actual BHLs and baseline BHL. Mean BHL, ΔBHL, and body-related factors were analyzed for the association with positional errors. RESULTS: Using the reference CBCT, the correlations of positional errors were significantly higher in those with stent/lipiodol than when the vertebral bone was used for alignment in three dimensions. Patients with mean BHL > 1.4 L were significantly taller (167.6 cm vs. 161.6 cm, p = 0.03) and heavier (67.1 kg vs. 57.4 kg, p = 0.02), and had different positional error in the craniocaudal direction (- 0.26 cm [caudally] vs. + 0.09 cm [cranially], p = 0.01) than those with mean BHL < 1.4 L. Positional errors were similar for patients with ΔBHL< 0.03 L and > 0.03 L. CONCLUSION: Under rigorous breath-hold respiratory control, BHL correlated with body weight and height. With more accurate alignment reference by stent/lipiodol, actual BHL but not breath-hold variation was associated with craniocaudal positional errors.

A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer.

Importance: Currently, there is no established second-line systemic treatment for biliary tract cancer (BTC). Preclinical data have demonstrated that the presence of tumor-infiltrating CD8 T cells and programmed cell death 1 ligand 1-expressing tumor cells in the tumor microenvironment of BTC supports the rationale of using programmed cell death 1 protein blockade immunotherapy in BTC. Objective: To evaluate anticancer activity of nivolumab in patients with advanced refractory BTC. Design, Setting, and Participants: In this single-group, multicenter phase 2 study of nivolumab, 54 patients with histologically confirmed BTC whose disease progressed while undergoing treatment with at least 1 line but no more than 3 lines of systemic therapy were enrolled between October 5, 2016, and December 26, 2018. Analysis was performed on an intention-to-treat basis. Interventions: Nivolumab, 240 mg, was delivered intravenously every 2 weeks for 16 weeks, and then 480 mg was delivered intravenously every 4 weeks until disease progression or unacceptable toxic effects occurred. Main Outcomes and Measures: The primary end point was investigator-assessed objective response rate, and the secondary end points were progression-free survival, overall survival, and incidence of adverse events. Results: A total of 54 patients (27 men and 27 women; median age, 65 years [range, 28-86 years]) enrolled, and 46 (22 men and 24 women; median age, 65 years [range, 28-86 years]) were examined for objective response with radiologic imaging. The investigator-assessed objective response rate was 22% (10 of 46), including 1 unconfirmed partial response, with a disease control rate of 59% (27 of 46). Central independent review found an objective response rate of 11% (5 of 46), including 1 unconfirmed partial response, with a disease control rate of 50% (23 of 46). All patients who responded to treated (hereafter referred to as responders) had mismatch repair protein-proficient tumors. The median duration of investigator-assessed response was not reached, with a median follow-up of 12.4 months. Among the intention-to-treat population, median progression-free survival was 3.68 months (95% CI, 2.30-5.69 months) and median overall survival was 14.24 months (95% CI, 5.98 months to not reached). Programmed cell death 1 ligand 1 expression in tumors was associated with prolonged progression-free survival (hazard ratio, 0.23; 95% CI, 0.10-0.51; P < .001). The most common treatment-related grade 3 or 4 toxic effects were hyponatremia (3 of 54 [6%]) and increased alkaline phosphatase (2 of 54 [4%]). Conclusions and Relevance: This study found that nivolumab was well tolerated and showed modest efficacy with durable response in patients with refractory BTC. Further studies are warranted to verify the findings and evaluate biomarkers for improved treatment selection for patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02829918.

Imaging of Pancreaticobiliary Maljunction.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join outside the duodenal wall, usually forming a long common channel. A major issue in patients with PBM is the risk of biliary cancer. Because the sphincter of Oddi does not regulate the pancreaticobiliary junction in PBM, pancreatic juice frequently refluxes into the biliary tract and can cause various complications, including biliary cancer. Most cancers arise in the gallbladder or dilated common bile duct, suggesting that bile stasis is related to carcinogenesis. Early diagnosis and prophylactic surgery to reduce the risk of cancer are beneficial. The diagnosis of PBM is made mainly on the basis of imaging findings. The development of diagnostic imaging modalities such as multidetector CT and MR cholangiopancreatography has provided radiologists with an important role in diagnosis of PBM and its complications. Radiologists should be aware of PBM despite the fact that it is rare in non-Asian populations. In this review, the authors present an overview of PBM with emphasis on diagnosis and management of PBM and its complications. For early diagnosis, the presence of extrahepatic bile duct dilatation or gallbladder wall thickening may provide a clue to PBM with or without biliary dilatation, respectively. The pancreaticobiliary anatomy should be closely examined if imaging reveals these findings. Radiologists should also carefully evaluate follow-up images in PBM patients even years after prophylactic surgery because residual bile ducts remain at risk for cancer.©RSNA, 2020.