Biliary Tumors Research Articles

Deep Learning in Endoscopic Ultrasound: A Breakthrough in Detecting Distal Cholangiocarcinoma

Introduction: Cholangiocarcinoma (CCA) is a highly lethal malignancy originating in the bile ducts, often diagnosed late with poor prognosis. Differentiating benign from malignant biliary tumors remains challenging, necessitating advanced diagnostic techniques. Objective: This study aims to enhance the diagnostic accuracy of endoscopic ultrasound (EUS) for distal cholangiocarcinoma (dCCA) using advanced convolutional neural networks (CCNs) for the classification and segmentation of EUS images, specifically targeting dCCAs, the pancreas, and the bile duct. Materials and Methods: In this retrospective study, EUS images from patients diagnosed with dCCA via biopsy and an EUS-identified bile duct tumor were evaluated. A custom CNN was developed for classification, trained on 156 EUS images. To enhance the model’s robustness, image augmentation techniques were applied, generating a total of 1248 images. For tumor and organ segmentation, the DeepLabv3+ network with ResNet50 architecture was utilized, employing Tversky loss to manage unbalanced classes. Performance evaluation included metrics such as accuracy, sensitivity, specificity, and Intersection over Union (IoU). These methods were implemented in collaboration with the ADAPTED Research Group at the Technical University of Cluj-Napoca. Results: The classification model achieved a high accuracy of 97.82%, with precision and specificity both at 100% and sensitivity at 94.44%. The segmentation models for the pancreas and bile duct demonstrated global accuracies of 84% and 90%, respectively, with robust IoU scores indicating good overlap between predicted and actual contours. The application performed better than the UNet model, particularly in generalization and boundary delineation. Conclusions: This study demonstrates the significant potential of AI in EUS imaging for dCCA, presenting a robust tool that enhances diagnostic accuracy and efficiency. The developed MATLAB application serves as a valuable aid for medical professionals, facilitating informed decision-making and improving patient outcomes in the diagnosis of cholangiocarcinoma and related pathologies.

No communication between the bile duct and intraductal papillary neoplasm of the bile duct on imaging.

As a rare biliary tract tumor, intraductal papillary neoplasm of the bile duct (IPNB) is most common in elderly men and can progress to cholangiocarcinoma- (CCa) if left untreated. It is reported that IPNB usually communicates with the bile duct. As a result, the downstream bile ducts are imaged asymmetrically dilated. However, a case of IPNB that we report here is different. Enhanced MRI revealed a lack of connectivity with the bile duct in this case. Based on this, the purpose of this case study is to suggest that the majority of imaging doctors should widely understand the various imaging manifestations of the disease to avoid misdiagnosis. In addition, although this feature was not indicated by ultrasound in this case, given previous studies and considering the convenience and non-ionizing radiation damage of CEUS, we recommend its use as a screening method for IPNB to improve diagnostic accuracy.

Prognostic factors for intraductal papillary neoplasm of the bile duct following surgical resection: a systematic review and meta-analysis.

Intraductal papillary neoplasm of the bile duct (IPNB) is a biliary neoplasm characterized by intraductal papillary growth and varying degrees of malignant transformation. This study aimed to identify effective prognostic factors (PFs) for predicting the prognosis of IPNB after surgical resection, addressing the gap in the higher level evidence. We systematically searched databases from their inception to October 10, 2023. Data on 12 predetermined PFs were collected and subjected to a meta-analysis. Forest plots were used to summarize the findings. Fifteen studies with a total of 2311 patients were included. Among the PFs examined, extrahepatic tumor location (HR, 2.97; 95% CI 1.68-5.23), subclassification type 2 (HR, 2.62; 95% CI 1.45-4.76), R1 resection (HR, 2.47; 95% CI 1.73-3.51), elevated CA19-9 level (HR, 3.25; 95% CI 1.91-5.54), tumor multiplicity (HR, 2.65; 95% CI 1.40-5.02), and adjacent organ invasion (HR, 3.17; 95% CI 2.01-5.00) were associated with a poorer prognosis. Additionally, the combined HR values indicated that lymph node metastasis and poor tumor differentiation were linked to a worse prognosis, although both exhibited significant heterogeneity. Our study offers valuable insights for enhancing postoperative prognostication and treatment decision-making for IPNB patients with IPNB. These findings warrant further validation in future prospective studies.

The spectrum of pathogens and their resistance in patients with malignant liver and biliary tract tumors with biliary obstruction after extensive liver resections

The spectrum of pathogens and their resistance in patients with malignant liver and biliary tract tumors with biliary obstruction after extensive liver resections

S2444 Biliary Intraductal Papillary Mucinous Neoplasm (IPMN-B) Associated With Actinomyces

S2444 Biliary Intraductal Papillary Mucinous Neoplasm (IPMN-B) Associated With Actinomyces

The Role of Bile Acids in Pancreatic Cancer.

Bile acids are well known to promote the digestion and absorption of fat, and at the same time, they play an important role in lipid and glucose metabolism. More studies have found that bile acids such as ursodeoxycholic acid also have anti-inflammatory and immune-regulating effects. Bile acids have been extensively studied in biliary and intestinal tumors but less in pancreatic cancer. Patients with pancreatic cancer, especially pancreatic head cancer, are often accompanied by biliary obstruction and elevated bile acids caused by tumors. Elevated total bile acid levels in pancreatic cancer patients usually have a poor prognosis. There has been controversy over whether elevated bile acids are harmful or beneficial to pancreatic cancer. Still, there is no doubt that bile acids are important for the occurrence and development of pancreatic cancer. This article summarizes the research on bile acid as a biomarker and regulation of the occurrence, development and chemoresistance of pancreatic cancer, hoping to provide some inspiration for future research.

Effect of silibinin on GAS6/sAXL and JAK/STAT pathways in human cholangiocarcinoma cell line

Abstract Objectives Cholangiocarcinoma (CCA) is a highly heterogeneous biliary malignant tumor. Studies have demonstrated that JAK/STAT signaling is activated in many types of cancer. In addition, JAK/STAT is activated downstream of AXL, and the AXL receptor is activated by its ligand, GAS6. In this study, we investigated the anticarcinogenic effect of silibinin and its relationship with the GAS6/AXL ve JAK/STAT pathway in the human EGI-1 cell line. Methods Cell viability, apoptosis, and cell cycle were measured by Muse Cell Analyzer. All the protein levels were determined by the ELISA method. Results We observed that silibinin significantly reduced cell proliferation and colony formation (p<0.05, p<0.001, respectively). Silibinin also significantly induced total apoptosis and the G0/G1 phase of the cell cycle (p<0.01). We observed that silibinin significantly decreased JAK2 levels while increased STAT1 levels compared to the controls respectively (p<0.001; p<0.001). Besides, silibinin statistically decreased the levels of sAXL; however, numerically, but not statistically, it increased the level of GAS6 (p>0.05). Conclusions Silibinin reduces colony formation, inducing apoptosis and arresting cancer cells in the G0/G1 phase, which is an indicator of its anticancer activity. In addition, silibinin decreased the levels of JAK2 and sAXL, which contributes to the development of cancer, and increased the levels of STAT1, suggesting silibinin’s antiproliferative effects.

Long-Term Survivor of Intrahepatic Cholangiocarcinoma for over 18 Years: Case Study with Longitudinal Histo-molecular and Tumor Immune Microenvironment Characterization and Systematic Review of the Literature

BackgroundIntrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease. In this study, we report the case of a patient affected by intrahepatic cholangiocarcinoma with multiple relapses and still alive for over 18 years. We also provide a systematic review regarding long-survivor (> 60 months) of intrahepatic cholangiocarcinoma.Case PresentationA 41-year-old woman with no pathological history was diagnosed with localized intrahepatic cholangiocarcinoma and surgically treated with left hepatectomy. After the first intervention, the patients underwent three further surgical resections because of locoregional recurrences. Histologically, there were some significant similarities among all neoplasms, including the tubule-glandular architecture, but also morphological heterogeneity. The tumor immune microenvironment remained stable across the different lesions. The molecular analysis with next-generation sequencing demonstrated that all neoplasms shared the same genomic profile, including NBN and NOTCH3 mutations and chromosomes 1 and 3 alterations.ConclusionsThis case study highlights the essential role of a stringent follow-up after resection of intrahepatic cholangiocarcinoma for detecting early relapsing tumors. Moreover, it shows the importance of the molecular characterization of multiple tumors for understanding their real nature. The accurate study of long-surviving patients highlights the features that are critical for outcome improvement.

Distinct phenotypic consequences of cholangiocarcinoma-associated FGFR2 alterations depend on biliary epithelial maturity.

Epithelial cancers disrupt tissue architecture and are often driven by mutations in genes that normally play important roles in epithelial morphogenesis. The intrahepatic biliary system is an epithelial tubular network that forms within the developing liver via the de novo initiation and expansion of apical lumens. Intrahepatic biliary tumors are often driven by different types of mutations in the FGFR2 receptor tyrosine kinase which plays important roles in epithelial morphogenesis in other developmental settings. Using a physiologic and quantitative 3D model we have found that FGFR signaling is important for biliary morphogenesis and that oncogenic FGFR2 mutants disrupt biliary architecture. Importantly, we found that both the trafficking and signaling of normal FGFR2 and the phenotypic consequences of FGFR2 mutants are influenced by the epithelial state of the cell. Unexpectedly, we found that different tumor-driving FGFR2 mutants disrupt biliary morphogenesis in completely different and clinically relevant ways, informing our understanding of morphogenesis and tumorigenesis and highlighting the importance of convergent studies of both.

Establishment of predictive models and determinants of preoperative gastric retention in endoscopic retrograde cholangiopancreatography.

Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography (ERCP) background: With the wide application of ERCP, the risk of preoperative gastric retention affects the smooth progress of the operation. The study found that female, biliary and pancreatic malignant tumor, digestive tract obstruction and other factors are closely related to gastric retention, so the establishment of predictive model is very important to reduce the risk of operation. To analyze the factors influencing preoperative gastric retention in ERCP and establish a predictive model. A retrospective analysis was conducted on 190 patients admitted to our hospital for ERCP preparation between January 2020 and February 2024. Patient baseline clinical data were collected using an electronic medical record system. Patients were randomly matched in a 1:4 ratio with data from 190 patients during the same period to establish a validation group (n = 38) and a modeling group (n = 152). Patients in the modeling group were divided into the gastric retention group (n = 52) and non-gastric retention group (n = 100) based on whether gastric retention occurred preoperatively. General data of patients in the validation group and modeling group were compared. Univariate and multivariate logistic regression analyses were performed to identify factors influencing preoperative gastric retention in ERCP patients. A predictive model for preoperative gastric retention in ERCP patients was constructed, and calibration curves were used for validation. The receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive value of the model. We found no statistically significant difference in general data between the validation group and modeling group (P > 0.05). The comparison of age, body mass index, hypertension, and diabetes between the two groups showed no statistically significant difference (P > 0.05). However, we noted statistically significant differences in gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction between the two groups (P < 0.05). Multivariate logistic regression analysis showed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were independent factors influencing preoperative gastric retention in ERCP patients (P < 0.05). The results of logistic regression analysis revealed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were included in the predictive model for preoperative gastric retention in ERCP patients. The calibration curves in the training set and validation set showed a slope close to 1, indicating good consistency between the predicted risk and actual risk. The ROC analysis results showed that the area under the curve (AUC) of the predictive model for preoperative gastric retention in ERCP patients in the training set was 0.901 with a standard error of 0.023 (95%CI: 0.8264-0.9567), and the optimal cutoff value was 0.71, with a sensitivity of 87.5 and specificity of 84.2. In the validation set, the AUC of the predictive model was 0.842 with a standard error of 0.013 (95%CI: 0.8061-0.9216), and the optimal cutoff value was 0.56, with a sensitivity of 56.2 and specificity of 100.0. Gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction are factors influencing preoperative gastric retention in ERCP patients. A predictive model established based on these factors has high predictive value.

Prevalence of malignant neoplasms in celiac disease patients - a nationwide United States population-based study.

Celiac disease (CeD) is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. Recent research has unveiled a heightened risk of developing specific malignant neoplasms (MN) and various malignancies, including gastrointestinal, lymphomas, skin, and others, in individuals with CeD. To investigate the prevalence of MN in hospitalized CeD patients in the United States. Using data from the National Inpatient Sample spanning two decades, from January 2000 to December 2019, we identified 529842 CeD patients, of which 78128 (14.75%) had MN. Propensity score matching, based on age, sex, race, and calendar year, was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio. Positive associations were observed for several malignancies, including small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis. Conversely, CeD patients exhibited a reduced risk of respiratory and secondary malignancies. Moreover, certain malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers. Our study is unique in highlighting the detailed results of positive, negative, or null associations between different hematologic and solid malignancies and CeD. Furthermore, it offers insights into evolving trends in CeD hospital outcomes, shedding light on advancements in its management over the past two decades. These findings contribute valuable information to the understanding of CeD's impact on health and healthcare utilization.

Laparoscopic Right Hemi-hepatectomy of the Bile Duct-Obstructed Area Guided by Real-Time Fluorescence Imaging.

The regions of the liver with cholestasis caused by biliary tumors or thrombosis can be distinctly identified using indocyanine green (ICG) fluorescence imaging.1 The authors' team reported the application of bile-duct obstructed area imaging (BOAI) to assist open hepatectomy for intrahepatic cholangiocarcinoma (ICC) combined with intrahepatic bile duct obstruction previously.2 This video is the first report of real-time BOAI-guided three-dimensional (3D) laparoscopic hepatectomy using a 3D-4K fluorescence imaging system. A 65-year-old man was admitted to the authors' institution with clonorchiasis. Preoperative computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed an obstruction and diffuse dilation of the right hepatic duct. A 15-min retention of ICG (ICG R15) was performed 5 days before the operation, with a 3.3% result. Preoperative planning involved performing laparoscopic right hemi-hepatectomy with regional lymph node dissection assisted by visualization technology.3 During the procedure, significant fluorescence accumulation in the right liver was shown by fluorescence imaging. With the guidance of real-time BOAI (Fig. 1), the regions of biliary obstruction were precisely resected, and the middle hepatic vein (MHV) was passively and adequately exposed on the cutting plane. Fig. 1 Administration steps for real-time bile duct-obstructed area imaging. A ICG is injected intravenously 3-5 days before operation at a dose of 0.5 mg/kg. B ICG is accumulated in the whole liver within a few minutes after injection. C ICG is selectively absorbed by the liver and excreted into the intestines, whereby it is retained in areas of biliary obstruction RESULTS: The histopathologic diagnosis indicated high-grade intraepithelial neoplasia of the right bile duct tumor without lymph node metastases and clonorchiasis. The duration of the operation was 300 min, with an intraoperative blood loss of 50 ml. No postoperative complications occurred, and the patient was discharged after 7 days. Laparoscopic right hemi-hepatectomy for the bile-duct obstructed area with the guidance of real-time BOAI is feasible and effective.

Imaging of Biliary Tree Abnormalities.

Pathologic conditions of the biliary system, although common, can be difficult to diagnose clinically. Challenges in biliary imaging include anatomic variants and the dynamic nature of the biliary tract, which can change with age and intervention, blurring the boundaries of normal and abnormal. Choledochal cysts can have numerous appearances and are important to diagnose given the risk of cholangiocarcinoma potentially requiring surgical resection. Choledocholithiasis, the most common cause of biliary dilatation, can be difficult to detect at US and CT, with MRI having the highest sensitivity. However, knowledge of the imaging pitfalls of MRI and MR cholangiopancreatography is crucial to avoid misinterpretation. Newer concepts in biliary tract malignancy include intraductal papillary biliary neoplasms that may develop into cholangiocarcinoma. New paradigms in the classification of cholangiocarcinoma correspond to the wide range of imaging appearances of the disease and have implications for prognosis. Accurately staging cholangiocarcinoma is imperative, given expanding curative options including transplant and more aggressive surgical options. Infections of the biliary tree include acute cholangitis or recurrent pyogenic cholangitis, characterized by obstruction, strictures, and central biliary dilatation. Inflammatory conditions include primary sclerosing cholangitis, which features strictures and fibrosis but can be difficult to differentiate from secondary causes of sclerosing cholangitis, including more recently described entities such as immunoglobulin G4-related sclerosing cholangitis and COVID-19 secondary sclerosing cholangitis. The authors describe a wide variety of benign and malignant biliary tract abnormalities, highlight differentiating features of the cholangitides, provide an approach to interpretation based on the pattern of imaging findings, and discuss pearls and pitfalls of imaging to facilitate accurate diagnosis. ©RSNA, 2024 Supplemental material is available for this article.

Study of cases of obstructive jaundice due to biliary and pancreatic tumors

Obstructive jaundice has recently become more common, particularly among malignant cases. The aim was to study, evaluate and compare various operative managements for obstructive jaundice due to biliary and pancreatic tumors. This prospective study was conducted by random selection of 20 cases presenting with obstructive jaundice due to biliary and pancreatic tumors at a tertiary care hospital affiliated with Smt. N.H.L. Municipal Medical College. Majority of patients were in age group 51-60 years (35%) and 61-70 years (20%). Males (70%) were found to be in higher proportion compared to females (30%). Most comm on presenting symptom was jaundice (90%). Most common cause was periampullary carcinoma (60%). It was found that the most common complication following Whipple’s procedure and Triple Bypass Surgery was pancreatic fistula.

Extrahepatic biliary neuroendocrine tumors: A national cancer database analysis

BackgroundExtrahepatic biliary neuroendocrine tumors (EBNETs) are rare. We aimed to characterize EBNETs including factors associated with survival. MethodsThe National Cancer Database was queried for patients with EBNETs from 2004 to 2016. Patients who underwent resection were examined using Cox proportional hazards regression and the Kaplan-Meier method. We compared overall survival (OS) among patients with EBNETs to those with NETs from other primary sites. ResultsOverall, 223 patients with EBNETs were identified. Patients were predominantly male (n = 113, 50.7 %), white (n = 177, 79.4 %) and presented without distant metastasis (n = 182, 81.6 %). The majority underwent operation (n = 127, 57.9 %) with resection of the primary tumor (n = 89, 70 %). Among patients who underwent resection (n = 71), multivariable regression demonstrated older age (HR 1.11, 95 % C.I. 1.04–1.17), lymph node metastases (HR 1.19, 95 % C.I. 1.02–1.38) and poorly/undifferentiated tumors [HR 22.3, 95 % C.I. 3.78–131]) were associated with worse overall survival. Patients with EBNETs experienced abbreviated OS compared to patients with small bowel or pancreas NETs (p < 0.001), but improved OS when compared to patients with gallbladder NETs (p = 0.001). ConclusionsTumor differentiation and lymph node status significantly impact overall survival.

Pathologic characterization of precursors and cholangiocarcinoma referring to peribiliary capillary plexus: a new pathologic approach to bile duct neoplasm.

The peribiliary capillary plexus (PCP) regularly and densely lines the basal side of the lining epithelia of normal bile ducts. To determine the pathology of the PCP in high-grade biliary intraepithelial neoplasms (BilINs) and intraductal papillary neoplasms of the bile duct (IPNBs), a precursor of cholangiocarcinoma (CCA), and CCA. Seventy-six cases of surgically resected high-grade BilIN and 83 cases of IPNB were histopathologically examined using endothelial immunostaining of PCP; all cases of high-grade BilIN and 40 cases of IPNB were associated with invasive CCA. Invasive and preinvasive neoplasms were pathologically examined referring to a two-layer pattern composed of biliary lining epithelia and underlying PCP unique to the bile duct. All high-grade BilIIN cases had an underlying single layer of capillaries, similar to PCP (PCP-like capillaries). In 43% of the 83 cases of IPNB, these capillaries were regularly distributed in almost all stalks and intervening stroma of intraluminal neoplastic components, while in the remaining 57% of IPNB, capillaries were sparsely or irregularly distributed in intraluminal components showing cribriform or solid growth patterns composed of striking atypical neoplastic epithelia. Invasive carcinomas associated with high-grade BilIN and IPNB were not lined with capillaries. The loss of PCP-like capillaries underlying high-grade BilIN and in stalks or stroma of IPNB may be involved in the malignant progression of these precursors. Immunostaining of PCP could be a new pathological tool for the evaluation of malignant progression and vascular supply in CCA and its precursors.

Role of Multi-Detector Computed Tomography (MDCT) in Assessment of Biliary Neoplasms

Abstract Background Biliary neoplasms are commonly encountered in the day-to-day radiological practice and can be benign or malignant. Multidetector CT (MDCT) is a noninvasive imaging modality for evaluation of patients with biliary obstruction, to localize the cause of obstruction, detect the presence of mass lesion, and define its extension and identify remote metastasis. Objective To find out the role of MDCT scan in the evaluation of biliary neoplasms with respect to nature, cause and level of obstruction. Methods During the period from January 2022 to August 2022, the present study included 30 patients with clinically suspected biliary obstruction and previously radiological or laboratory diagnosed cases of biliary malignancy after fulfilling the inclusion and exclusion criteria and taking written /verbal informed consent. 16 patients were males and 14 were females, their ages ranged between 36– 85 years with mean age of 64years old. Results The mean age of participants was 63.73±11.11 years old; and slight male predominance (53.3%). in correlation to histopathological findings, MDCT was 95.2% sensitive in detection of cholangiocarcinoma (20/21*100). It was 100% sensitive in detection of combined cholangiocarcinoma &amp; HCC (1/1*100). Also it was 85.75 sensitive in detection of gall bladder carcinoma (6/7*100). While it was false positive in detection a case of HCC. The sensitivity of MDCT to detect biliary neoplasm is 96.4% (27/28*100) with specificity of 0% (0/2*100), the positive predictive value is 93.1% (27/29*100) while the negative predictive value is 0% (0/1%). We found significant association between MDCT Final outcome with resectability (P-value 0.002) and between resectability and TNM Staging (P-value &amp;lt;0.0001) Conclusion Multidetector computed tomography MDCT can be considered a noninvasive fast with high sensitivity imaging tool in the assessment of patients with biliary neoplasms. The MDCT is satisfactory for staging of biliary neoplasms and for accurate preoperative assessment of the tumor extent.

Second line chemotherapy for advanced biliary cancer: FOLFOX versus FOLFIRI: Analysis of retrospective and prospective data

Aim. To evaluate the efficacy and toxicity of second-line polychemotherapy according to FOLFOX or FOLFIRI regimen in patients with biliary tract tumours after progression during first-line chemotherapy (CT). Materials and methods. The study is based on the analysis of retrospective and prospective data on the examination and treatment of 94 patients with biliary cancer of grades T1-4N0-2M0-1 followed-up and treated at the N.N. Blokhin National Medical Research Center of Oncology from 2015 to 2023. All patients were divided into 2 groups: Group 1 (FOLFOX, n=47) and Group 2 (FOLFIRI, n=47). In Group 1, patients received the recommended FOLFOX second-line CT regimen. Patients in Group 2 received FOLFIRI regimen. The endpoints were overall survival (OS) and incidence of grade 3-4 adverse events. Results. The study included 94 patients. In the FOLFOX group, the median OS was 13.0 months (1-year OS was 57.8±7.4%); for the FOLFIRI group, the median OS was 12.3 months (1-year OS was 54.4±7.3%). The toxicity profiles of FOLFOX and FOLFIRI were acceptable and consistent with those reported for the regimens. According to the grade 3–4 toxicity data, diarrhea was significantly more common in the FOLFIRI group (p=0.014), and neurotoxicity was more common in the FOLFOX group (p=0.006). During the second-line CT, the frequency of grade 1–4 toxicities in the groups did not differ: 18 (38.3%) events in the FOLFOX group and 19 (40.0%) events in the FOLFIRI group. Conclusion. Our results of evaluating the efficacy and toxicity of the second-line polychemotherapy regimens show that the FOLFOX and FOLFIRI CT regimens have equal efficacy in patients with advanced biliary tract cancer with a good performance according to the ECOG scale, who previously received the first-line therapy with a combination of gemcitabine with a platinum agent (cisplatin or oxaliplatin); also, our data demonstrate similar toxicity profiles of these regimens.

Intraductal Implantation of Biliary Neoplasms: A Potential Cause of "Multifocal" Tumors.

Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.

Tubulocystic Carcinoma of Bile Ducts: A Distinct Type of Cholangiocarcinoma Associated With Adenofibroma-type Lesions.

A type of cholangiocarcinoma (CCA) characterized by peculiar histologic patterns and underlying adenofibromatous lesions has been reported in the literature mostly as individual case reports. This study aims to further clarify the defining characteristics of this spectrum of lesions. Clinicopathologic analysis of 8 biliary tumors with tubulocystic architecture arising in the background of adenofibroma-type lesions was performed. Three of these were also investigated with next-generation sequencing with a 174 genes panel. The patients were 5 males and 3 females, with a mean age of 64.6. All tumors were intrahepatic except for one perihilar that protruded into soft tissues. The mean size was 4.4 cm. At histology, all cases showed a peculiar and cytologically bland tubulocystic pattern that closely resembled tubulocystic-type kidney cancers, including back-to-back microcystic units that formed relatively demarcated nodules, and occurring in the background of adenofibromatous lesions. One case showed perineural invasion by otherwise deceptively benign-appearing microcystic structures, one had areas transitioning to intraductal tubulopapillary neoplasm, and 3 cases harbored more conventional small-duct CCA foci. In those 3 cases, both the tubulocystic and conventional CCA components were investigated by next-generation sequencing separately, and they shared the molecular alterations, including recurrent mutations in chromatin remodeling genes, such as ARID1A , BAP1 , and PBRM1 , and the actionable FGFR2-MCU fusion gene. In the limited follow-up, all but one were alive and free of disease after surgical resection. In conclusion, we described a distinct entity of CCA with specific histo-molecular features, for which we propose the designation of tubulocystic carcinoma of bile ducts.