Biliary Structures Research Articles

Efficacy of Intraoperative vs Preoperative Indocyanine Green Administration for Near-Infrared Cholangiography During Laparoscopic Cholecystectomy: An Open-Label, Non-Inferiority, Randomized Controlled Trial.

Near-infrared fluorescence cholangiography (NIRFC) improves the clinical effects of laparoscopic cholecystectomy. However, the administration of indocyanine green (ICG) remains controversial. Both the intraoperative (IS, 0.05mg) and preoperative (PS, 0.25mg/kg body weight, 1 day before operation) strategies have been shown to be superior to standard strategy (2.5mg, intraoperative). This trial was designed to determine whether IS offers non-inferior visualization of biliary ducts compared to PS. A total of 168 eligible patients undergoing laparoscopic cholecystectomy were enrolled in this non-inferiority, open-label, randomized controlled trial at Zhujiang hospital between August 2023 and November 2023. Participants were randomized in a 1:1 ratio into PS and IS groups after stratification by BMI and inflammation level. The fluorescence visualization of biliary structures was assessed by comparing the signal-to-background ratio (SBR) and surgeon evaluations. The common bile duct-liver SBR did not significantly differ between IS and PS groups (3.0±0.8 vs 3.1±1.2; p=0.636). The liver fluorescence intensity (FI) of the IS group was significantly lower than that of the PS group (46.3±12.9 vs 70.4±26.2; p<0.01). The visualization score of common hepatic ducts was significantly greater in the IS than in the PS group (4.1±0.7 vs 3.7±0.6; p＜0.01). The critical view of safety (CVS) was achieved more rapidly in the IS group compared to the PS group (9.4 vs 11.0 minutes, p<0.01). While IS did not improve the SBR, it significantly reduced the FI of the liver background, potentially enhancing the surgeon's subjective perception and thereby increasing the visualization score. Compared to PS, IS offers greater convenience and is more effective in facilitating CVS exposure.

Cholangioscopy-based convoluted neuronal network vs. confocal laser endomicroscopy in identification of neoplastic biliary strictures.

Background and study aims Artificial intelligence (AI) models have demonstrated high diagnostic performance identifying neoplasia during digital single-operator cholangioscopy (DSOC). To date, there are no studies directly comparing AI vs. DSOC-guided probe-base confocal laser endomicroscopy (DSOC-pCLE). Thus, we aimed to compare the diagnostic accuracy of a DSOC-based AI model with DSOC-pCLE for identifying neoplasia in patients with indeterminate biliary strictures. Patients and methods This retrospective cohort-based diagnostic accuracy study included patients ≥ 18 years old who underwent DSOC and DSOC-pCLE (June 2014 to May 2022). Four methods were used to diagnose each patient's biliary structure, including DSOC direct visualization, DSOC-pCLE, an offline DSOC-based AI model analysis performed in DSOC recordings, and DSOC/pCLE-guided biopsies. The reference standard for neoplasia was a diagnosis based on further clinical evolution, imaging, or surgical specimen findings during a 12-month follow-up period. Results A total of 90 patients were included in the study. Eighty-six of 90 (95.5%) had neoplastic lesions including cholangiocarcinoma (98.8%) and tubulopapillary adenoma (1.2%). Four cases were inflammatory including two cases with chronic inflammation and two cases of primary sclerosing cholangitis. Compared with DSOC-AI, which obtained an area under the receiver operator curve (AUC) of 0.79, DSOC direct visualization had an AUC of 0.74 ( P = 0.763), DSOC-pCLE had an AUC of 0.72 ( P = 0.634), and DSOC- and pCLE-guided biopsy had an AUC of 0.83 ( P = 0.809). Conclusions The DSOC-AI model demonstrated an offline diagnostic performance similar to that of DSOC-pCLE, DSOC alone, and DSOC/pCLE-guided biopsies. Larger multicenter, prospective, head-to-head trials with a proportional sample among neoplastic and nonneoplastic cases are advisable to confirm the obtained results.

Comparative study on a unique architecture of the brook lamprey liver and that of the hagfish and banded houndshark liver.

Although the liver of the lamprey, a group of cyclostomes that diverged the earliest among vertebrates, has abundant bile ducts in the larval stage, which degenerate during metamorphosis, there is no comparative study on its architecture with other early diverged vertebrates in terms of the morphological evolution of vertebrate livers. The present study was undertaken to compare the characteristics of the brook lamprey liver with those of the hagfish and banded houndshark, which have the portal triad type liver architecture, and to discuss its evolution. Although the liver of the brook lamprey had two-cell cords of hepatocytes lined by sinusoids in the ammocoetes larval stage, intrahepatic bile ducts around portal veins penetrated into the liver parenchyma with convolution and gradual reduction in diameter. They also faced dilated sinusoids. The epithelial cells had characteristic intercellular spaces. These characteristics were distinct from those of bile ducts in the hagfish and banded houndshark livers. Although the liver architectures of the hagfish and banded houndshark were similar, the latter penetrated the intrahepatic bile ducts more deeply along the portal veins than the former, in which intrahepatic bile ducts were restricted near the hilum. After metamorphosis, bile ducts degenerated in brook lampreys. These data indicate that the liver architecture of the ammocoetes larva is unique in the parenchymal distribution of bile ducts, their sinusoidal facing, and morphology among extant vertebrates. The periportal distribution of intrahepatic biliary structures may have been established prior to the divergence of the cyclostomes and gnathostomes.

Intragallbladder versus intravenous indocyanine green (ICG) injection for enhanced bile duct visualization by fluorescent cholangiography during laparoscopic cholecystectomy: a retrospective cohort study.

Iatrogenic bile duct injuries (BDIs) prevention during laparoscopic cholecystectomy (LC) relies on meticulous anatomical dissections through direct visualization. Near-infrared fluorescence (NIRF) with indocyanine green (ICG) improves the visualization of extrahepatic biliary structures. Although ICG can be administered either intravenously or intragallbladder, there remains uncertainty regarding the optimal method for different patient populations. This study sought to assess the suitability of each method for specific patient groups. Between October 2021 and May 2022, 59 consecutive patients underwent fluorescence-guided LC at West China Hospital of Sichuan University. Among them, 32 patients received an intravenous injection of ICG (10 mg) 10 to 12 hours prior to surgery (Group A: the intravenous group), while 27 patients received an intragallbladder injection of ICG (10 mg) (Group B: the intragallbladder group). Baseline clinical factors, inclusion criteria, and measurements of parameters and complications were assessed. Data were retrospectively collected and analyzed to evaluate the comparability of the two groups and the clinical outcomes. Groups A and B included 32 patients (18 males, 14 females), and 27 patients (13 men, 14 women), respectively. In our statistical analysis, significant differences were observed in preoperative diagnoses between the two groups (P=0.041), but the majority of other baseline clinical factors were comparable. Notably, no statistically significant differences were found in complication rates. However, Group A had a shorter operative time (60.38±9.35 vs. 66.78±9.88 min, P=0.01) and superior bile duct fluorescence (P=0.04) than Group B. Interestingly, fluorescence was not observed in impacted gallbladder stones in Group B. Additionally, patients with cirrhosis (P=0.008) and fatty liver (P=0.005) in Group B had higher common bile duct-to-liver ratios (BLRs) than those in Group A. ICG fluorescence cholangiography allows to visualize extrahepatic biliary anatomical structures with both administration methods. However, the efficacy of bile duct fluorescence varies with different administration routes in diverse patient populations. Hence, appropriate administration route selection for ICG should be tailored to individual patients.

Real-time segmentation of biliary structure in pure laparoscopic donor hepatectomy

Pure laparoscopic donor hepatectomy (PLDH) has become a standard practice for living donor liver transplantation in expert centers. Accurate understanding of biliary structures is crucial during PLDH to minimize the risk of complications. This study aims to develop a deep learning-based segmentation model for real-time identification of biliary structures, assisting surgeons in determining the optimal transection site during PLDH. A single-institution retrospective feasibility analysis was conducted on 30 intraoperative videos of PLDH. All videos were selected for their use of the indocyanine green near-infrared fluorescence technique to identify biliary structure. From the analysis, 10 representative frames were extracted from each video specifically during the bile duct division phase, resulting in 300 frames. These frames underwent pixel-wise annotation to identify biliary structures and the transection site. A segmentation task was then performed using a DeepLabV3+ algorithm, equipped with a ResNet50 encoder, focusing on the bile duct (BD) and anterior wall (AW) for transection. The model’s performance was evaluated using the dice similarity coefficient (DSC). The model predicted biliary structures with a mean DSC of 0.728 ± 0.01 for BD and 0.429 ± 0.06 for AW. Inference was performed at a speed of 15.3 frames per second, demonstrating the feasibility of real-time recognition of anatomical structures during surgery. The deep learning-based semantic segmentation model exhibited promising performance in identifying biliary structures during PLDH. Future studies should focus on validating the clinical utility and generalizability of the model and comparing its efficacy with current gold standard practices to better evaluate its potential clinical applications.

Frequency of bile duct variant anatomy on MRCP on 3.0t in liver donors.

Objective: To determine the frequency of bile duct variant using magnetic resonance cholangiopancreatography (MRCP) on a magnetic field strength of 3.0 Tesla in liver donors. Study Design: Descriptive Cross-sectional study. Setting: Department of Radiology, Armed Forces Institute of Radiology and Imaging, Military Hospital Rawalpindi. Period: May 2019 to November 2019. Methods: The research comprised people who went to the hospital for magnetic resonance cholangiopancreatography. 85 liver transplant recipients between the ages of 20 and 70 were chosen for the research. According to Yoshida categorization, bile duct variation was noted. The MRCP methodology includes multiplanar imaging, maximum intensity projection pictures, thin slab axial HASTE, thick slab coronal HASTE, and T2 3D sequence. The Siemens Avanto 3 Tesla machine was used for the study. Results: The study's participants ranged in age from 20 to 70, with a mean age of 41.73 ± 10.03 years. The majority of the 54 patients (63.53 percent) were aged 20 to 45. The male to female ratio was 1:1 among the 85 patients, with 43 (50.59 percent) men and 42 (49.41 percent) women. In my research of liver donors, 57 (67.05 percent) showed normal biliary tree structure and 28 (32.95 percent) exhibited abnormalities. Conclusion: This study concluded that normal biliary tree anatomy was seen in 67.05% and 32.95% had variations in biliary anatomy on MRCP on 3.0T in liver donors.

Modern approaches to the management of blunt liver trauma

Relevance. Liver trauma is one of the most common abdominal injuries. The purpose is to review the evidence and present the current level of diagnosis, tactics and treatment of blunt liver trauma.Materials and methods. The results of clinical studies in liver trauma have been analyzed. Literature was searched in PubMed electronic search engines (https://pubmed.ncbi.nlm.nih.gov), eLibrary (https://elibrary.ru) by keywords: "liver trauma", "management liver trauma", "diagnosis liver trauma". 134 publications were selected for analysis.Results. Historically, most patients with liver trauma were cured promptly using techniques such as liver suturing, liver resection, ligation of the hepatic artery, atrioval shunts. Conservative management was practically not used. Consequently, mortality was high and reached almost 90% in patients with severe trauma, including damage to the main hepatic vessels. The introduction of such techniques as perigepathic packaging and direct suturing of damaged vessels significantly improved the prognosis of patients. The widespread use of conservative therapy in patients with stable hemodynamics, the management of which is based on instrumental assessment, carefully selected diagnostic imaging of the nature of liver injury, instrumental dynamic observation using operative X-ray angiology and endoscopy, in a hybrid operating room, contributed to the improvement of treatment results.Conclusion. In recent decades, conservative therapy has been performed in 80–86% of cases in patients with stable hemodynamics. The use of minimally invasive interventions such as angiography and embolization, a combination of percutaneous drainage and endoscopic methods for injury to vascular and biliary structures can be considered as the main method of treating post-traumatic complications.

Efficacy of different indocyanine green doses in fluorescent laparoscopic cholecystectomy: A prospective, randomized, double-blind trial.

Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC. This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups. Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction. In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.

INDURG TRIAL Protocol: A Randomized Controlled Trial Using Indocyanine Green during Cholecystectomy in Acute Cholecystitis

Introduction: Laparoscopic cholecystectomy is one of the most common gastrointestinal surgeries, and bile duct injury is one of its main complications. The use of real-time indocyanine green fluorescence cholangiography allows the identification of extrahepatic biliary structures, facilitating the procedure and reducing the risk of bile duct lesions. A better visualization of the bile duct may help to reduce the need for conversion to open surgery, and may also shorten operating time. The main objective of this study was to determine whether the use of indocyanine green is associated with a reduction in operating time in emergency cholecystectomies. Secondary outcomes are the postoperative hospital stay, the correct intraoperative visualization of the Calot’s Triangle structures with the administration of indocyanine green, and the intraoperative complications, postoperative complications and morbidity according to the Clavien-Dindo classification. Methods: This is a randomized, prospective, controlled, multicenter trial with patients diagnosed with acute cholecystitis requiring emergency cholecystectomy. The control group will comprise 220 patients undergoing emergency laparoscopic cholecystectomy applying the standard technique. The intervention group will comprise 220 patients also undergoing emergency laparoscopic cholecystectomy for acute cholecystitis with prior administration of indocyanine green. Conclusion: Due to the lack of published studies on ICG in emergency laparoscopic cholecystectomy, this study may help to establish procedures for its use in the emergency setting.

3D auto-segmentation of biliary structure of living liver donors using magnetic resonance cholangiopancreatography for enhanced preoperative planning.

This study aimed to develop an automated segmentation system for biliary structures using a deep learning model, based on data from magnetic resonance cholangiopancreatography (MRCP). Living liver donors who underwent MRCP using the gradient and spin echo technique followed by three-dimensional modeling were eligible for this study. A three-dimensional residual U-Net model was implemented for the deep learning process. Data were divided into training and test sets at a 9:1 ratio. Performance was assessed using the dice similarity coefficient to compare the model's segmentation with the manually labeled ground truth. The study incorporated 250 cases. There was no difference in the baseline characteristics between the train set (n=225) and test set (n=25). The overall mean Dice Similarity Coefficient was 0.80±0.20 between the ground truth and inference result. The qualitative assessment of the model showed relatively high accuracy especially for the common bile duct (88%), common hepatic duct (92%), hilum (96%), right hepatic duct (100%), and left hepatic duct (96%), while the third-order branch of the right hepatic duct (18.2%) showed low accuracy. The developed automated segmentation model for biliary structures, utilizing MRCP data and deep learning techniques, demonstrated robust performance and holds potential for further advancements in automation.

Laparoscopic therapy for Mirizzi syndrome: A case report with review of literature

Mirizzi syndrome (MS) is a rare entity and is due to extrinsic biliary compression. It is a rare complication of cholecystitis and chronic cholelithiasis. The impacted calculi at the infundibulum of the gall bladder or cystic duct lead to compression of the adjacent biliary structures, resulting in total or subtotal obstruction of the common hepatic duct (CHD). This leads to liver dysfunction. We, herein, present one such case of a 50-year-old female patient who was diagnosed to have MS. During surgery, at laparoscopy, she was unexpectedly also found to have a cholecysto-duodenal fistula. Both conditions were successfully treated laparoscopically.

Design of an improved percutaneous transhepatic cholangio drainage tube based on MRCP imaging data

Objective: Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube. Methods: 3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length. Results: In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice. Conclusion: MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

The association between KRAS and histopathological growth patterns and the impact on resection margins around vasculature and bile ducts in colorectal liver metastases.

The liver is the most frequent and often the only site of distant disease in colorectal cancer and, of all treatment protocols currently in use, resection is the most likely to result in long-term cure. Within the liver, tumour proximity to major vasculature and biliary structures poses a resection challenge, requiring a balance of achieving negative margins while preserving adequate vascular circulation and biliary drainage. The focus on parenchymal sparing resections are important but just as important may be the 'biological' behaviour of the tumour. In colorectal liver metastases (CRLM), biomarkers such as the Kirsten rat sarcoma oncogene homologue (KRAS) gene and histological growth patterns (HGPs) further improve the prognostication after resection. However, to date, the association between the KRAS status and HGPs in CRLM and their impact on resection margins around major vasculature or biliary structures in terms of overall survival and recurrence rates are unclear. The aim of this review was to explore the available evidence for the association between KRAS and HGPs in CRLM and attempt to define their impact on resection margins near major structures.

Biliary Anatomy Visualization and Surgeon Satisfaction Using Standard Cholangiography versus Indocyanine Green Fluorescent Cholangiography during Elective Laparoscopic Cholecystectomy: A Randomized Controlled Trial

Background: Intraoperative biliary anatomy recognition is crucial for safety during laparoscopic cholecystectomy, since iatrogenic bile duct injuries represent a fatal complication, occurring in up to 0.9% of patients. Indocyanine green fluorescence cholangiography (ICG-FC) is a safe and cost-effective procedure for achieving a critical view of safety and recognizing early biliary injuries. The aim of this study is to compare the perioperative outcomes, usefulness and safety of standard intraoperative cholangiography (IOC) with ICG-FC with intravenous ICG. Methods: Between 1 June 2021 and 31 December 2022, 160 patients undergoing elective LC were randomized into two equal groups: Group A (standard IOC) and group B (ICG-FC with intravenous ICG). Results: No significant difference was found between the two groups regarding demographics, surgery indication or surgery duration. No significant difference was found regarding the visualization of critical biliary structures. However, the surgeon satisfaction and cholangiography duration presented significant differences in favor of ICG-FC. Regarding the inflammatory response, a significant difference between the two groups was found only in postoperative WBC levels. Hepatic and renal function test results were not significantly different between the two groups on the first postoperative day, except for direct bilirubin. No statistically significant difference was noted regarding 30-day postoperative complications, while none of the complications noted included bile duct injury events. Conclusions: ICG-FC presents equivalent results to IOC regarding extrahepatic biliary visualization and postoperative complications. However, more studies need to be performed in order to standardize the optimal dose, timing and mode of administration.

Profiles of biliary microbiota in biliary obstruction patients with Clonorchis sinensis infection.

Clonorchis sinensis (C. sinensis) is a epidemiologically significant food-borne parasite, causing several hepatobiliary diseases. Biliary microbiota community structure might be influenced by infection with pathogens. However, the biliary microbiome of biliary obstruction patients infected with C. sinensis is still an unexplored aspect. A total of 50 biliary obstruction patients were enrolled, including 24 infected with C. sinensis and 26 non-infected subjects. The bile samples were collected by Endoscopic Retrograde Cholangiopancretography. Biliary microbiota alteration was analyzed through high-throughput 16S ribosomal RNA (rRNA) gene sequencing. Our findings revealed that there was significant increase in both richness and diversity, as well as changes in the taxonomic composition of the biliary microbiota of C. sinensis infected patients. At the phylum level, C. sinensis infection induced Proteobacteria increased and Firmicutes reduced. At the genus level, the relative abundance of Pseudomonas and Staphylococcus increased significantly, while Enterococcus decreased prominently in infected groups (P < 0.05). The PICRUSt analysis further showed remarkably different metabolic pathways between the two groups. C. sinensis infection could modify the biliary microbiota, increasing the abundance and changing the phylogenetic composition of bacterial in biliary obstruction patients. This study may help deepen the understanding of the host-biliary microbiota interplay with C. sinensis infection on the background of biliary obstruction and provide new insights into understanding the pathogenesis of clonorchiasis.

Three-dimensional auto-segmentation of biliary structure of living liver donors using magnetic resonance cholangiopancreatography

Three-dimensional auto-segmentation of biliary structure of living liver donors using magnetic resonance cholangiopancreatography

Automated 3D liver segmentation from hepatobiliary phase MRI for enhanced preoperative planning

Recent advancements in deep learning have facilitated significant progress in medical image analysis. However, there is lack of studies specifically addressing the needs of surgeons in terms of practicality and precision for surgical planning. Accurate understanding of anatomical structures, such as the liver and its intrahepatic structures, is crucial for preoperative planning from a surgeon’s standpoint. This study proposes a deep learning model for automatic segmentation of liver parenchyma, vascular and biliary structures, and tumor mass in hepatobiliary phase liver MRI to improve preoperative planning and enhance patient outcomes. A total of 120 adult patients who underwent liver resection due to hepatic mass and had preoperative gadoxetic acid-enhanced MRI were included in the study. A 3D residual U-Net model was developed for automatic segmentation of liver parenchyma, tumor mass, hepatic vein (HV), portal vein (PV), and bile duct (BD). The model’s performance was assessed using Dice similarity coefficient (DSC) by comparing the results with manually delineated structures. The model achieved high accuracy in segmenting liver parenchyma (DSC 0.92 ± 0.03), tumor mass (DSC 0.77 ± 0.21), hepatic vein (DSC 0.70 ± 0.05), portal vein (DSC 0.61 ± 0.03), and bile duct (DSC 0.58 ± 0.15). The study demonstrated the potential of the 3D residual U-Net model to provide a comprehensive understanding of liver anatomy and tumors for preoperative planning, potentially leading to improved surgical outcomes and increased patient safety.

Agenesis of the gallbladder, a rare congenital anomaly that can mimic chronic cholecystitis: case report

Agenesis of the gallbladder is a rare congenital malformation caused by the failure of the cystic bud to develop in the gallbladder, which may or may not be associated with other biliary malformations. It is an anomaly of variable symptomatology, with 50% of patients presenting symptoms mimicking biliary colic; it may be discovered by chance during surgery, while 15% may present fatal fetal malformations. When symptomatic, it is interpreted as chronic cholecystitis, with a narrowed appearance of the gallbladder on abdominal ultrasound, as the biliary structures may resemble those of a gallbladder, demonstrating the need for radiologists and surgeons to be aware of this diagnosis and its management, in order to avoid unnecessary surgery. In this article, we present a case of gallbladder agenesis in a young man who presented with hepatic colic-like symptoms suggestive of cholecystitis. The gallbladder was not well visualized on ultrasound, simulating chronic cholecystitis, and a Bili MRI concluded that the gallbladder was absent, thus avoiding surgery.

Generation and metabolomic characterization of functional ductal organoids with biliary tree networks in decellularized liver scaffolds.

Developing functional ductal organoids (FDOs) is essential for liver regenerative medicine. We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds (DLSs) with primary cholangiocytes isolated from mouse bile ducts. The developed FDOs were dynamically characterized by functional assays and metabolomics for bioprocess clarification. FDOs were reconstructed in DLSs retaining native structure and bioactive factors with mouse primary cholangiocytes expressing enriched biomarkers. Morphological assessment showed that biliary tree-like structures gradually formed from day 3 to day 14. The cholangiocytes in FDOs maintained high viability and expressed 11 specific biomarkers. Basal-apical polarity was observed at day 14 with immunostaining for E-cadherin and acetylated α-tubulin. The rhodamine 123 transport assay and active collection of cholyl-lysyl-fluorescein exhibited the specific functions of bile secretion and transportation at day 14 compared to those in monolayer and hydrogel culture systems. The metabolomics analysis with 1075 peak pairs showed that serotonin, as a key molecule of the tryptophan metabolism pathway linked to biliary tree reconstruction, was specifically expressed in FDOs during the whole period of culture. Such FDOs with biliary tree networks and serotonin expression may be applied for disease modeling and drug screening, which paves the way for future clinical therapeutic applications.

Preoperative planning and intraoperative real-time navigation with indocyanine green fluorescence in robotic liver surgery

PurposeWe aimed at exploring indocyanine green (ICG) fluorescence wide spectrum of applications in hepatobiliary surgery as can result particularly useful in robotic liver resections (RLR) in order to overcome some technical limitations, increasing safety, and efficacy.MethodsWe describe our experience of 76 RLR performed between March 2020 and December 2022 exploring all the possible applications of pre- and intraoperative ICG administration.ResultsHepatocellular carcinoma and colorectal liver metastases were the most common indications for RLR (34.2% and 26.7% of patients, respectively), and 51.3% of cases were complex resections with high IWATE difficulty scores. ICG was administered preoperatively in 61 patients (80.3%), intraoperatively in 42 patients (55.3%) and in both contexts in 25 patients (32.9%), with no observed adverse events. The most frequent ICG goal was to achieve tumor enhancement (59 patients, 77.6%), with a success rate of 94.9% and the detection of 3 additional malignant lesions. ICG facilitated evaluation of the resection margin for residual tumor and perfusion adequacy in 33.9% and 32.9% of cases, respectively, mandating a resection enlargement in 7.9% of patients. ICG fluorescence allowed the identification of the transection plane through negative staining in the 25% of cases. Vascular and biliary structures were visualized in 21.1% and 9.2% of patients, with a success rate of 81.3% and 85.7%, respectively.ConclusionRLR can benefit from the routine integration of ICG fluoresce evaluation according to each individual patient and condition-specific goals and issues, allowing liver functional assessment, anatomical and vascular evaluation, tumor detection, and resection margins assessment.