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Background: Hilar cholangiocarcinoma (HCCA) is a common type of cholangiocarcinoma (CHOL) that originates from the right and/or left hepatic duct near the biliary tract confluence. The objective of this study is to investigate the impact of miR-182-5p on the proliferation and invasion of HCCA cells and identify a potential target for HCCA treatment. Methods: HCCA tissues were collected and HCCA cells were cultured. miR-182-5p and F-box and WD repeat domain containing 7 (FBXW7) were detected. After transfection of miR-182-5p inhibitor into HCCA cells, cell proliferation and invasion were detected by cell counting 8-kit and Transwell assay. FBXW7 expression was detected by Western blot. The targeted relationship between miR-182-5p and FBXW7 3’UTR was verified by dual-luciferase report assay. si-FBXW7 and miR-182-5p inhibitor were transfected into cells for combined experiments. HCCA cells with lowly-expressed miR-182-5p were injected into nude mice to establish the xenograft tumor model, and subsequent observations were made on tumor growth and gene expression changes. Results: miR-182-5p exhibited high expression levels in both HCCA tissues and cell lines. Inhibiting miR-182-5p effectively suppressed the proliferation and migration of HCCA cells. miR-182-5p bounded to FBXW7 3 ‘UTR and inhibited FBWX7 expression. Suppressing FBXW7 expression partially reversed the inhibitory effect of miR-182-5p inhibitor on HCCA cell proliferation and invasion. Silencing miR-182-5p could inhibit the HCCA growth in vivo. Conclusion: miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression. [ABSTRACT FROM AUTHOR]

Purpose: Recently introduced hybrid 2-[18 F]-fluoro-2-deoxy-D-glucose (18 F-FDG) Positron Emission Tomography (PET) combined with Magnetic Resonance Imaging (MRI) may aid in proper diagnosis and staging of perihilar cholangiocarcinoma (pCCA). The aim of this study is to assess the effect of 18 F-FDG PET/MRI on diagnosis and clinical decision making in the pre-operative work up of pCCA. Methods: In this single-centre pilot study patients with presumed resectable pCCA underwent state-of-the-art 18 F-FDG hybrid PET/MRI using digital silicone photomultiplier detectors integrated within a 3-Tesla bore. Data were collected on several baseline and imaging characteristics. The primary outcome measure was the added diagnostic information and the effect on clinical decision making. Secondary aim was to correlate quantitative PET signal intensity to patient- and tumour characteristics. High and low SUVmax subgroups related to the mean value were made. Significance of lesion- and patient characteristics with the high and low SUVmax subgroups, as well as TLR and TBR, was evaluated with Fisher's exact test or Mann-Whitney-U test. Results: In total 14 patients were included (mean age 62.4 years, 64% male). Final diagnosis was pCCA in 10 patients (71.4%), follicular lymphoma in one patient (7.1%) and benign disease in the remaining three patients. FDG-PET/MRI added valuable diagnostic information in six (43%) patients and affected clinical decision making in two of these patients (14%) by increasing confidence for malignancy which lead to the decision for surgery on short term. High SUVmax values were seen in half of cases with pCCA and half of cases with non-cancerous lesions. In addition, high SUVmax values were directly associated with primary sclerosing cholangitis when present (p = 0.03). Conclusion: Simultaneous 18 F-FDG-PET/MRI added diagnostic information in six of fourteen patients and influenced clinical decision making in two patients (14%) with presumed resectable pCCA. [ABSTRACT FROM AUTHOR]

The liver requires careful handling intra‐operatively owing to its vital functions and complexity. Traditional open hepatectomy, while standard, is invasive and requires long recovery periods. Laparoscopic hepatectomy is a less invasive option, with its own challenges. The rise of robotic surgery, such as the da Vinci® system, improves precision and control, addressing the limitations of conventional methods, but brings new concerns, such as costs and training. This review focuses on the latest advancements in robotic hepatectomy from 2022/23 articles, delving into topics like "robotic surgery in liver transplantation," "robotic hepatectomy for hilar cholangiocarcinoma," "robotic vascular reconstruction following hepatectomy," "robotic repeat hepatectomy," and "prospective trials in robotic hepatectomy." To retrieve articles, a focused literature search was conducted using PubMed for articles from 2022/23 with a 5‐year filter, excluding reviews. Initially, abstracts were screened, and relevant articles on robotic surgery were examined in full for inclusion in this review. Although all the above items are cutting‐edge, and many of the references are necessarily at the level of case reports, recent articles are still accompanied by surgical videos, which are useful to readers, especially surgeons who are considering imitating the procedures. In summary, we examined the recent advancements in robotic liver resection. The inclusion of videos that present new techniques aids in knowledge transfer. We anticipate the continued growth of this field of research. [ABSTRACT FROM AUTHOR]

Background: The management of Bismuth–Corlette type IV hilar cholangiocarcinoma typically necessitates extensive hepatectomy, resection of the extrahepatic bile ducts, regional lymph node dissection, and reconstruction of the biliary tract; however, there is a high incidence of postoperative liver dysfunction and failure. Methods: A 64-year-old male patient was admitted to our department after 1 month of escalating jaundice and abdominal discomfort. Upon admission, his total bilirubin was 334 μmol/L and his direct bilirubin was 221 μmol/L. His carbohydrate antigen 19-9 was > 1200.00 U/mL, his carcinoembryonic antigen was 98.90 U/mL, and his α-fetoprotein was normal. Enhanced computed tomography (CT) and magnetic resonance imaging scans revealed a thickened and enlarged biliary tree extending from the common hepatic duct to the orifices of the left and right hepatic ducts. Results: The patient underwent total laparoscopic radical resection of S1 + S4, accompanied by radical lymphadenectomy with skeletonization and biliary reconstruction. The surgery was successfully conducted within 450 min, with a minimal blood loss of 200 mL. The histological grading was T2bN1M0 (stage III). CT on postoperative day 5 showed satisfactory postoperative recovery. The patient was discharged from the hospital on postoperative day 10 without complications, following which the patient underwent a regimen of single-agent capecitabine chemotherapy. Over a 20-month follow-up period, no recurrence was observed. Conclusions: Resection of hepatic segments S1 + S4 is a viable surgical option for hilar carcinoma in cases with poor liver function or when the carcinoma is confined to both hepatic ducts without invasion of the hepatic artery and portal vein. [ABSTRACT FROM AUTHOR]

Abstract The liver requires careful handling intra‐operatively owing to its vital functions and complexity. Traditional open hepatectomy, while standard, is invasive and requires long recovery periods. Laparoscopic hepatectomy is a less invasive option, with its own challenges. The rise of robotic surgery, such as the da Vinci® system, improves precision and control, addressing the limitations of conventional methods, but brings new concerns, such as costs and training. This review focuses on the latest advancements in robotic hepatectomy from 2022/23 articles, delving into topics like “robotic surgery in liver transplantation,” “robotic hepatectomy for hilar cholangiocarcinoma,” “robotic vascular reconstruction following hepatectomy,” “robotic repeat hepatectomy,” and “prospective trials in robotic hepatectomy.” To retrieve articles, a focused literature search was conducted using PubMed for articles from 2022/23 with a 5‐year filter, excluding reviews. Initially, abstracts were screened, and relevant articles on robotic surgery were examined in full for inclusion in this review. Although all the above items are cutting‐edge, and many of the references are necessarily at the level of case reports, recent articles are still accompanied by surgical videos, which are useful to readers, especially surgeons who are considering imitating the procedures. In summary, we examined the recent advancements in robotic liver resection. The inclusion of videos that present new techniques aids in knowledge transfer. We anticipate the continued growth of this field of research.

Abstract Background The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy. Methods A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb. Results Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190–450), and the median estimated blood loss was 360 mL (range, 260–1200). The postoperative hospital stay duration was 14.3 ± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3–43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years. Conclusion Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

Abstract Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation’s success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People’s Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50–500) vs 310 (100–850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience.

Background: The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy. Methods: A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb. Results: Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190–450), and the median estimated blood loss was 360 mL (range, 260–1200). The postoperative hospital stay duration was 14.3 ± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3–43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years. Conclusion: Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation. [ABSTRACT FROM AUTHOR]

Objective: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post‐hepatectomy liver failure (PHLF) among surgically‐treated jaundiced patients with hilar cholangiocarcinoma (HCCA). Methods: We retrospectively reviewed surgically‐treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. Results: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic‐pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly‐acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. Conclusion: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi‐center studies for training and validation are required for further validation. [ABSTRACT FROM AUTHOR]

Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation's success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People's Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50–500) vs 310 (100–850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience. [ABSTRACT FROM AUTHOR]

Background: For patients with hilar cholangiocarcinoma (HC) undergoing hemihepatectomy, there are controversies regarding the requirement of, indications for, and timing of preoperative biliary drainage (PBD). Dynamic threedimensional volume reconstruction could effectively evaluate the regeneration of liver after surgery, which may provide assistance for exploring indications for PBD and optimal preoperative bilirubin value. The purpose of this study was to explore the indications for PBD and the optimal preoperative bilirubin value to improve prognosis for HC patients undergoing hemi-hepatectomy. Methods: We retrospectively analyzed the data of HC patients who underwent hemi-hepatectomy in the First Affiliated Hospital of China Medical University from 2012 to 2023. The liver regeneration rate was calculated using threedimensional volume reconstruction. We analyzed the factors affecting the liver regeneration rate and occurrence of postoperative liver insufficiency. Results: This study involved 83 patients with HC, which were divided into PBD group (n=36) and non-PBD group (n=47). The preoperative bilirubin level may be an independent risk factor affecting the liver regeneration rate (P=0.014) and postoperative liver insufficiency (P=0.016, odds ratio=1.016, b=0.016, 95% CI=1.003--1.029). For patients whose initial bilirubin level was >200 mmol/L (n=45), PBD resulted in better liver regeneration in the early stage (P=0.006) and reduced the incidence of postoperative liver insufficiency [P=0.012, odds ratio=0.144, 95% confidence interval (CI)=0.031--0.657]. The cut-off value of bilirubin was 103.15 mmol/L based on the liver regeneration rate. Patients with a preoperative bilirubin level of ≤103.15 mmol/L shown a better liver regeneration (P<0.01) and lower incidence of postoperative hepatic insufficiency (P=0.011, odds ratio=0.067, 95% CI=0.008--0.537). Conclusion: For HC patients undergoing hemi-hepatectomy whose initial bilirubin level is >200 mmol/L, PBD may result in better liver regeneration and reduce the incidence of postoperative liver insufficiency. Preoperative bilirubin levels ≤103.15 mmol/L maybe recommended for leading to a better liver regeneration and lower incidence of postoperative hepatic insufficiency. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the efficacy and safety of sequential treatment of continuous transcatheter hepatic artery infusion chemotherapy (HAIC) with systemic capecitabine monotherapy and camrelizumab for treating unresectable hilar cholangiocarcinoma (HCCA). Methods: This study retrospectively analyzed patients with unresectable HCCA admitted to Linyi Cancer Hospital in Shandong Province from October 2019 to December 2021. All enrolled patients were treated with HAIC (mFOLFOX7) + camrelizumab for 2-6 cycles and administered systemic therapy with capecitabine and camrelizumab. The objective response rate (ORR), disease control rate (DCR), and adverse reactions of patients were assessed. The Kaplan-Meier method was used to describe overall survival (OS), and univariate and multivariate Cox regression models were utilized to analyze the influencing factors of OS. Results: This study included 34 patients, ORR was 61.76% (21/34), and DCR was 97.06% (33/34) after two HAIC cycles. The median follow-up time was 17.5 months, with an average of 18.32 ± 8.06 months, and the median OS was 20.0 months. HAIC-related adverse reactions included mainly gastrointestinal symptoms and hematological toxicity caused by chemotherapy drugs, all of which were grades 1-2. Further, adverse events for camrelizumab treatment included fatigue, skin rash, and hypothyroidism, all of which were grade <3. Cox regression analysis revealed that the periductal infiltrating type of growth pattern indicated a worse OS, whereas more HAIC cycles (5 ~ 6) were a protective factor for OS. Conclusion: HAIC sequentially combined with systemic capecitabine chemotherapy and a programmed death-1 inhibitor displayed favorable effects for unresectable HCCA, with controllable adverse reactions. [ABSTRACT FROM AUTHOR]

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37–3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11–17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01–2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24–2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21–2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a neoplasm of the biliary tract that has become increasingly prevalent throughout the world. Common risk factors for developing CCA include cirrhosis, primary sclerosing cholangitis, and trematode fluke infestation, although there are no set screening guidelines in high-risk groups. Lesions are typically identified via cross-sectional imaging and/or elevated serum carbohydrate antigen 19-9 levels, often followed by cytology or brushings with fluorescence in situ hybridization for confirmation. Treatments can vary among CCA subtypes but frequently involve systemic therapies such as gemcitabine and cisplatin with durvalumab or pembrolizumab. Targeted therapies may also be effective (eg, ivosidenib, pemigatinib, infigratinib, futibatinib) depending on the molecular alterations present. Resection is the most common surgical treatment for CCA, although liver transplantation is also an option in highly selected patients with liver-limited unresectable disease. Radiotherapy may also be a treatment option, as well as transarterial radioembolization (eg, yttrium-90), which is often utilized in combination with systemic therapy. Although patients with CCA have traditionally had a poor prognosis, recent advances in treatment, including new systemic therapies and increased utilization of liver transplantation, have improved expected survival. This article reviews screening modalities, pros and cons of diagnostic techniques, and therapies that are currently available to treat patients with CCA. [ABSTRACT FROM AUTHOR]

Abstract Objective Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post‐hepatectomy liver failure (PHLF) among surgically‐treated jaundiced patients with hilar cholangiocarcinoma (HCCA). Methods We retrospectively reviewed surgically‐treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. Results A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic‐pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly‐acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p

Abstract Background/purpose This study compared the clinical efficacy and safety of laparoscopic versus open resection for hilar cholangiocarcinoma (HCCA) and analyzed potential prognostic factors. Methods The study included patients who underwent HCCA resection at our center from March 2012 to February 2022. Perioperative complications and postoperative prognosis were compared between the laparoscopic surgery (LS) and open surgery (OS) groups. Results After screening 313 HCCA patients, 68 patients were eligible for the study in the LS group (n = 40) and OS group (n = 28). Kaplan-Meier survival curve analysis revealed that overall survival > 2 years and 3-year disease-free survival (DFS) were more common in the LS than OS group, but the rate of 2-year DFS was lower in the LS group than OS group. Cox multivariate regression analysis revealed age (< 65 years), radical resection, and postoperative adjuvant therapy were associated with reduced risk of death (hazard ratio [HR] = 0.380, 95% confidence interval [CI] = 0.150–0.940, P = 0.036; HR = 0.080, 95% CI = 0.010–0.710, P = 0.024 and HR = 0.380, 95% CI = 0.150–0.960, P = 0.040), whereas preoperative biliary drainage was an independent factor associated with increased risk of death (HR = 2.810, 95% CI = 1.130–6.950, P = 0.026). Perineuronal invasion was identified as an independent risk factor affecting DFS (HR = 5.180, 95% CI = 1.170–22.960, P = 0.030). Conclusions Compared with OS, laparoscopic HCCA resection does not significantly differ in terms of clinical efficacy. Age (

Rong Yin, Shasha Xu, Jing Zhu, Haiou Zhu, Chao He Department of Hepatobiliary Center Ward II, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Rong Yin, Department of Hepatobiliary Center Ward II, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email y13851709399@163.comBackground: Hilar cholangiocarcinoma (HCCA) is a common malignant tumor of the biliary system. Factors such as limited physical function, intractability, and high mortality caused by the tumor lead to negative emotions, such as anxiety and depression in patients. In this study, we investigated the risk factors for negative emotions in patients undergoing radical resection of HCCA during the perioperative period and its effect on prognosis to provide strategies for alleviating the negative emotional disorders of patients and improving prognosis.Methods: From September 2016 to August 2021, we retrospectively examined 205 patients with HCCA who underwent radical resection in our hospital. The incidence of negative emotions and the clinical parameters of patients were compared using Chi-square tests and t-tests. The independent risk factors for unfavorable feelings in patients during the perioperative period were determined using binary logistic regression. The key variables influencing the postoperative survival status of HCCA patients were identified using the log-rank univariate analysis and Cox proportional risk regression analysis.Results: The results of the binary logistic regression analysis showed that perioperative negative emotions were independently influenced by family monthly income (OR = 0.069), medical insurance (OR = 0.089), family care (OR = 0.013), sleep quality (OR = 0.071), TNF-α (OR = 5.851), and bile leakage (OR = 29.412) (P < 0.05). The age of the patient (OR = 2.003), preoperative CA19– 9 (OR = 2.038), lymph node metastases (OR = 2.327), and negative mood (OR = 3.054) were independent risk variables that affected the survival status of patients, as determined by the results of Cox regression analysis (P < 0.05).Conclusion: In this study, we found that anxiety and depression in patients undergoing radical operation of HCCA are related to family monthly income, medical insurance, sleep quality, family care, TNF-α, and bile leakage; also, negative emotions have adverse effects on prognosis.Keywords: hilar cholangiocarcinoma, radical resection, depression, anxiety, risk factors, prognosis

Background/purpose: This study compared the clinical efficacy and safety of laparoscopic versus open resection for hilar cholangiocarcinoma (HCCA) and analyzed potential prognostic factors. Methods: The study included patients who underwent HCCA resection at our center from March 2012 to February 2022. Perioperative complications and postoperative prognosis were compared between the laparoscopic surgery (LS) and open surgery (OS) groups. Results: After screening 313 HCCA patients, 68 patients were eligible for the study in the LS group (n = 40) and OS group (n = 28). Kaplan-Meier survival curve analysis revealed that overall survival > 2 years and 3-year disease-free survival (DFS) were more common in the LS than OS group, but the rate of 2-year DFS was lower in the LS group than OS group. Cox multivariate regression analysis revealed age (< 65 years), radical resection, and postoperative adjuvant therapy were associated with reduced risk of death (hazard ratio [HR] = 0.380, 95% confidence interval [CI] = 0.150–0.940, P = 0.036; HR = 0.080, 95% CI = 0.010–0.710, P = 0.024 and HR = 0.380, 95% CI = 0.150–0.960, P = 0.040), whereas preoperative biliary drainage was an independent factor associated with increased risk of death (HR = 2.810, 95% CI = 1.130–6.950, P = 0.026). Perineuronal invasion was identified as an independent risk factor affecting DFS (HR = 5.180, 95% CI = 1.170–22.960, P = 0.030). Conclusions: Compared with OS, laparoscopic HCCA resection does not significantly differ in terms of clinical efficacy. Age (<65 years), radical resection, and postoperative adjuvant therapy reduce the risk of death, and preoperative biliary drainage increases the risk of death. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor in the treatment of unresectable hilar cholangiocarcinoma. Methods The clinical data of 34 patients of unresectable hilar cholangiocar⁃ cinoma admitted to Linyi Cancer Hospital from October 2019 to October 2021 were retrospectively analyzed. All patients received hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor. The patient received 2-6 cycles of mFOLFOX7⁃hepatic arterial infusion chemotherapy (HAIC) and PD⁃1 inhibitor arterial infusion therapy, and then received capecitabine monotherapy and intravenous drip with PD⁃1 inhibitor. The objective response rate (ORR) and disease control rate (DCR) as well as adverse reactions of patients were observed, and the overall survival (OS) and its influencing factors were analyzed. Results A total of 155 interventional treatments were performed in 34 patients, with an average of (4.56±1.61) times. After 2 cycles of intervention treatment, the ORR and the DCR were 61.76% (21/34) and 97.06% (33/34), respectively. After the whole intervention treatment, the overall ORR was 82.35% (28/34), and the DCR was 100.00% (34/34). The median follow⁃up time was 17.5 months, and the median OS was 20.0 months (95%CI: 15.0-25.0 months). The adverse reactions related to HAIC mainly included fever, abdominal pain, nausea and vomiting, and hematological toxicity caused by chemotherapy drugs, all of which were grade 1-2. The adverse reactions related to PD⁃1 inhibitor treatment mainly included fatigue, rash, body surface capillary hyperplasia, all of which were≤grade 3. Multivariable Cox regression analysis showed that periductal infiltrating was a risk factor for OS (HR=2.051, 95%CI: 1.039-4.407, P=0.038), and 5-6 cycles of intervention treatments was a protective factor for OS (HR=0.465, 95%CI: 0.219-0.853, P=0.006). Conclusions Hepatic arterial infusion therapy sequential capecitabine and PD⁃1 inhibitor are effective in the treatment of unresectable hilar cholangiocarcinoma with controllable adverse reactions, in which the growth pattern classification and the number of intervention treatments may affect the survival rate of patients. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICC) constitutes a group of heterogeneous malignancies within the liver. We sought to subtype ICC based on anatomical origin of tumors, as well as propose modifications of the current classification system. Methods: Patients undergoing curative-intent resection for ICC, hilar cholangiocarcinoma (CCA), or hepatocellular carcinoma (HCC) were identified from three international multi-institutional consortia of databases. Clinicopathological characteristics and survival outcomes were assessed. Results: Among 1264 patients with ICC, 1066 (84.3%) were classified as ICC-peripheral subtype, whereas 198 (15.7%) were categorized as ICC-perihilar subtype. Compared with ICC-peripheral subtype, ICC-perihilar subtype was more often associated with aggressive tumor characteristics, including a higher incidence of nodal metastasis, macro- and microvascular invasion, perineural invasion, as well as worse overall survival (OS) (median: ICC-perihilar 19.8 vs. ICC-peripheral 37.1 months; p < 0.001) and disease-free survival (DFS) (median: ICC-perihilar 12.8 vs. ICC-peripheral 15.2 months; p = 0.019). ICC-perihilar subtype and hilar CCA had comparable OS (19.8 vs. 21.4 months; p = 0.581) and DFS (12.8 vs. 16.8 months; p = 0.140). ICC-peripheral subtype tumors were associated with more advanced tumor features, as well as worse survival outcomes versus HCC (OS, median: ICC-peripheral 37.1 vs. HCC 74.3 months; p < 0.001; DFS, median: ICC-peripheral 15.2 vs. HCC 45.5 months; p < 0.001). Conclusions: ICC should be classified as ICC-perihilar and ICC-peripheral subtype based on distinct clinicopathological features and survival outcomes. ICC-perihilar subtype behaved more like carcinoma of the bile duct (i.e., hilar CCA), whereas ICC-peripheral subtype had features and a prognosis more akin to a primary liver malignancy. [ABSTRACT FROM AUTHOR]

Background: In Bismuth type III and IV Hilar Cholangiocarcinoma (III–IV HC), surgical resection is the only chance for long-term survival. As the surgical procedure is complex and Robotic-Assisted Surgery (RAS) may be particularly suitable in this setting, the aim of this study is to evaluate the potential benefits of RAS in III–IV HC in terms of post-operative outcomes. Methods: We conducted a systematic review using the PRISMA checklist for article selection. We searched the PubMed database and included only studies with clinical data about the treatment of III–IV HC using RAS. Results: A total of 12 papers involving 50 patients were included. All cases were Bismuth IIIa (n = 18), IIIb (n = 27) or IV type (n = 5) and underwent hepatectomy with biliary confluence resection and reconstruction. The mean operative time was 500 minutes with a conversion rate of 4%. The mean hospital stay was 12.2 days, and the morbidity and 30-day mortality rate were 61.9% and 2%, respectively. Over a mean follow up period of 10.1 months, 9/18 cases experienced recurrence (50%). Conclusions: RAS for III–IV HC is safe and feasible, at least if performed by experienced surgeons on selected cases. The oncological outcomes appear acceptable, given the aggressiveness of this pathology, but further studies are needed to fully elucidate the exact role of robotics in this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Upfront surgery with adjuvant capecitabine is the only curative treatment for hilar cholangiocarcinoma. Unfortunately, most patients do not present with resectable disease and are treated with a combination of locoregional therapy and systemic therapy. This review will summarize existing literature and ongoing clinical trials focused on the multidisciplinary care of hilar cholangiocarcinoma. Cholangiocarcinoma (CCA) is a rare malignancy of the intrahepatic and extrahepatic biliary ducts. CCA is primarily defined by its anatomic location: intrahepatic cholangiocarcinoma versus extrahepatic cholangiocarcinoma. Hilar cholangiocarcinoma (HC) is a subtype of extrahepatic cholangiocarcinoma that arises from the common hepatic bile duct and can extend to the right and/or left hepatic bile ducts. Upfront surgery with adjuvant capecitabine is the standard of care for patients who present with early disease and the only curative therapy. Unfortunately, most patients present with locally advanced or metastatic disease and must rely on systemic therapy as their primary treatment. However, even with current systemic therapy, survival is still poor. As such, research is focused on developing targeted therapies and multimodal strategies to improve overall prognosis. This review discusses the work-up and management of HC focused on the most up-to-date literature and ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Hilar cholangiocarcinoma (HCCA) is widely considered to have a poor prognosis. In particular, combined caudate lobe resection (CLR) as a strategy for radical resection in HCCA is important for improving the R0 resection rate. However, the criteria for R0 resection, necessity of CLR, optimal extent of hepatic resection, and surgical approach are still controversial. This review aimed to summarize the findings and discuss the controversies surrounding CLR. Numerous clinical studies have shown that combined CLR treatment for HCCA improves the R0 resection rate and postoperative survival time. Whether surgery for Bismuth type I or II is combined with CLR depends on the pathological type. Considering the anatomical factors, total rather than partial CLR is recommended to achieve a higher R0 resection rate. In the resection of HCCA, a proximal ductal margin greater than or equal to 10 mm should be achieved to obtain a survival benefit. Although there is no obvious boundary between the right side (especially the paracaval portion) and the right posterior lobe of the liver, Peng's resection line can serve as a reference marker for right-sided resection. Laparoscopic resection of the caudate lobe may be safer, more convenient, accurate, and minimally invasive than open surgery, but it needs to be completed by experienced laparoscopic doctors. [ABSTRACT FROM AUTHOR]

The significance of peri-neural invasion (PNI) in resected patients with hilar cholangiocarcinoma (HCCA) has been rarely explored. Our study was performed to evaluate the significance of PNI in resected HCCA patients in terms of tumor biological features and long-term survival. We retrospectively reviewed surgically-treated HCCA patients between June, 2000 and June 2018. SPSS 25.0 software was used for statistical analysis. A total of 239 resected HCCA patients were included (No. PNI: 138). PNI indicated more aggressive tumor biological features. Major vascular reconstruction was more frequently performed in patients with PNI (34.8% vs 24.8%, P = 0.064). Patients with PNI shared a significantly higher percentage of surgical margin width <5 mm (29.0% vs 16.8%, P = 0.02). The proportion of patients with T1-2 disease (31.2% vs 40.6%, P = 0.085) or I-II disease (21% vs 34.7%, P = 0.014) was significantly lower in patients with PNI. The overall morbidity rate was significantly higher in patients with PNI (P = 0.042). A much worse overall survival (OS) (P = 0.0003) or disease-free survival (DFS) (P = 0.0011) in patients with PNI. Even after matching vital prognostic factors, a significantly worse OS (P = 0.0003) or DFS (P = 0.0002) was still observed in patients with PNI. PNI was an independent prognostic factor in both OS (P = 0.011) and DFS (P = 0.024). PNI indicated more aggressive tumor biological features and more advanced tumor stage in patients with resected HCCA. PNI can be an independent prognostic factor in both OS and DFS. Future multi-center studies covering various races or populations are required for further validation. [ABSTRACT FROM AUTHOR]

Many liver surgeons have updated their understanding of the liver in recent years because of detailed studies on the liver anatomy and the rapid advances in laparoscopic liver surgery. Despite newer approaches, concepts and methods, research on the caudate lobe continues to be based on case reports and several persistent challenges concerning caudate lobe surgery that are worth discussing. Based on the literature and the author's experience, this study considers and addresses the challenges associated with caudate lobectomy encountered by most liver surgeons. We searched PubMed for relevant articles in English for 'caudate lobe', 'cholangiocellular carcinoma', 'laparoscopic caudate resection', 'right-side boundary of the caudate lobe' and 'assessment of hepatic functional reserve' published up to May 2022. This study reviewed the anatomical history of the caudate lobe, focusing on the challenges associated with caudate lobe-related surgical resection. Due to the unique anatomical position of the caudate lobe, surgical strategy for caudate lobe resection is particularly important, and the technical requirements for hepatobiliary surgeons are also extremely strict. Therefore, understanding the anatomical history of the caudate lobe and discussing the challenges associated with caudate lobectomy is essential. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis, and high recurrence rate. Immortalized cancer cell lines are the best and easiest models for in vitro cancer research. Here, we established a naturally immortalized highly tumorigenic hilar cholangiocarcinoma (hCCA) cell line, CBC3T-1. The CBC3T-1 cell line was cultured for over 60 passages. Thorough analysis showed that CBC3T-1 cells share characteristics similar to original tumor cells from patients with cholangiocarcinoma and display a stable phenotype, including features of epithelial origin, stem cell-like properties, as well as a high invasive and migratory capability and tumorigenicity in mice. Furthermore, this cell line showed the best sensitivity to paclitaxel, followed by gemcitabine. RNA sequencing and whole‑exome sequencing showed that cancer-associated pathways and somatic mutations played a dominant role in the development of CCA. We established and characterized a new hCCA cell line, CBC3T-1, which contributes to a better understanding of bile duct cancer, and can be used to study tumorigenesis and progression and the role of anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: Surgery represents the only cure for hilar cholangiocarcinoma (HC). However, laparoscopic radical resection remains technically challenging owing to the complex anatomy and reconstruction required during surgery. Therefore, reports on laparoscopic surgery (LS) for HC, especially for types III and IV, are limited. This study aimed to evaluate the safety and feasibility of laparoscopic radical surgery for Bismuth types III and IV HC. Methods: The data of 16 patients who underwent LS and 9 who underwent open surgery (OS) for Bismuth types III and IV HC at Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, between December 2017 and January 2022 were analyzed. Basic patient information, Bismuth-Corlette type, AJCC staging, postoperative complications, pathological findings, and follow-up results were evaluated. Results: Sixteen patients underwent LS and 9 underwent OS for HC. According to the preoperative imaging data, there were four cases of Bismuth type IIIa, eight of type IIIb, and four of type IV in the LS group and two of type IIIa, four of type IIIb, and three of type IV in the OS group (P>0.05). There were no significant differences in age, sex, ASA score, comorbidity, preoperative percutaneous transhepatic biliary drainage rate, history of abdominal surgery, or preoperative laboratory tests between the two groups (P>0.05). Although the mean operative time and mean intraoperative blood loss were higher in the LS group than in OS group, the differences were not statistically significant (P=0.121 and P=0.115, respectively). Four patients (25%) in the LS group and two (22.2%) in the OS group experienced postoperative complications (P>0.05). No significant differences were observed in other surgical outcomes and pathologic findings between the two groups. Regarding the tumor recurrence rate, there was no difference between the groups (P>0.05) during the follow-up period (23.9 ± 13.3 months vs. 17.8 ± 12.3 months, P=0.240). Conclusion: Laparoscopic radical resection of Bismuth types III and IV HC remains challenging, and extremely delicate surgical skills are required when performing extended hemihepatectomy followed by complex bilioenteric reconstructions. However, this procedure is generally safe and feasible for hepatobiliary surgeons with extensive laparoscopy experience. [ABSTRACT FROM AUTHOR]

Objective To investigate the risk factors of surgical complications of grade ≥Ⅲa and the overall survival rate of hilar cholangiocarcinoma (HC) after resection. Methods The clinical data of 62 patients with HC who underwent surgical resection in the Guangxi Medical University Cancer Hospital from June 2010 to March 2022 were retrospectively analyzed. The risk factors of postoperative complications of grade ≥Ⅲa were analyzed by virtue of logistic regression analysis, and Cox regression model was used to analyze the factors influencing overall survival. Results The incidence of postoperative complications in HC patients was 73.5%(36/49), among which the incidence of ≥Ⅲa complications and the perioperative mortality accounted for 46.9%(23/49) and 10.2%(5/49), respectively. Intraoperative blood loss >500 mL and AJCC stage Ⅲ/Ⅳ were independent risk factors for postoperative complications grade ≥Ⅲa in HC patients (all P<0.05). The median survival of HC patients was 24.0 months, and the 1⁃year, 3⁃year and 5⁃year overall survival rates were 73%, 49% and 20%, respectively. Preoperative CA19⁃9≥150 U/L and total caudate lobed resection were independent factors affecting the overall survival rate (all P<0.05). Conclusions AJCC stage Ⅲ/Ⅳ and intraoperative blood loss >500 mL are risk factors for perioperative complications ≥ grade Ⅲa after HC resection. Preoperative CA19⁃9≥150 U/L is a risk factor for postoperative overall survival, and total caudate lobectomy is a protective factor for postoperative overall survival. [ABSTRACT FROM AUTHOR]

To screen potential metabolites and significantly altered metabolic pathways of liver lesions by central carbon pathway metabolites. Methods 32 healthy volunteers (HC), 23 patients with biliary cysts (CYST), 19 patients with biliary stones (Stone), 45 patients with hepatocellular carcinoma (HCC), and 50 patients with hilarcholangiocarcinoma (HCCA) were recruited. Their serum samples were collected for UPLC-QQQ-MS analysis and further MPP statistical analysis. Pattern recognition was further used to discovery the differences in metabolome between groups, and to explore the significantly altered metabolic pathway and possible pathogenic mechanism of liver diseases. Results A total of 15, 7, 7, and 3 metabolites and a total of 8, 4, 4, and 1 metabolic pathway that were significantly different in serum between CYST, Stone, HCC, HCCA and healthy controls were identified and enriched through serum metabolomics analysis, respectively. Conclusion According to the above identified differential metabolites and enriched metabolic pathway results, it is shown that liver lesions mainly involved in the energy metabolism and amino acid metabolism & transport, in addition, inositol phosphate metabolism were significantly changed both in CYST, Stone, HCC and HCCA. [ABSTRACT FROM AUTHOR]

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

Abstract Background The main surgical procedure for Bismuth‒Corlette III–IV hilar cholangiocarcinoma (HCCA) is hemihepatectomy/extended hemihepatectomy. However, many patients have no opportunity for surgery due to having an insufficient remnant liver volume. Preservation of more liver volume on the premise of ensuring R0 resection is the goal. Mesohepatectomy with caudate lobectomy may be a new method to meet these requirements. Methods The clinical data of 41 patients with Bismuth‒Corlette III–IV HCCA, including 18 patients who underwent mesohepatectomy with caudate lobectomy (the mesohepatectomy group) and 23 patients who underwent hemihepatectomy or extended hemihepatectomy (the hemihepatectomy group), were analyzed retrospectively. The perioperative indicators and prognostic survival time between the two groups were analyzed. Results The mesohepatectomy group was compared with the hemihepatectomy group, and the operation time was 7.95 ± 1.2 vs. 7.15 ± 1.5 h (P > 0.05); the intraoperative blood loss was 600.0 ± 153.4 vs. 846.1 ± 366.8 mL (P 0.05). The postoperative complications of the two groups included bile leakage (22.2% vs. 21.7%), pleural effusion (11.1% vs. 8.7%), and fever (16.7% vs. 8.7%), with no significant differences in the incidences (P > 0.05). The 1-, 3-, and 5-year survival rates of the two groups were 87.5%, 55.7%, 27.8% and 83.5%, 56.1%, 24.5%, respectively, with no significant differences (P > 0.05). Conclusions Mesohepatectomy with caudate lobectomy can preserve more functional liver volume while ensuring the bile duct margin. It can be applied as the surgical treatment of Bismuth‒Corlette III–IV HCCA.

Objective Hilar cholangiocarcinoma (HCCA) is a highly aggressive biliary tract tumor. microRNAs (miRs) exert dual actions in various cancers. This paper seeks to expound on the functional mechanisms of miR-25-3p/dual specificity phosphatase 5 (DUSP5) in HCCA cell proliferation and migration. Methods HCCA-related data were downloaded from GEO database to screen out differentially-expressed genes. The potential target miR (miR-25-3p) and its expression in HCCA were analyzed on Starbase. The binding relation between miR-25-3p and DUSP5 was confirmed by dual-luciferase assay. Levels of miR-25-3p and DUSP5 in FRH-0201 cells and HIBEpics were determined by RT-qPCR and Western blot. miR-25-3p and DUSP5 levels were intervened with to explore their effects on FRH-0201 cells. The apoptosis, proliferation, migration, and invasion of FRH-0201 cells were evaluated by TUNEL, CCK8, scratch healing, and Transwell assays. Flow cytometry was conducted to assess FRH-0201 cell cycle. Levels of cell cycle-related proteins were determined by Western blot. Results DUSP5 was weakly-expressed and miR-25-3p was highly-expressed in HCCA samples and cells. miR-25-3p targeted DUSP5. miR-25-3p suppressed FRH-0201 cell apoptosis and increased cell proliferation, migration, and invasion. DUSP5 overexpression partially abrogated miR-25-3p overexpression-exerted effects on FRH-0201 cells. miR-25-3p stimulated G1/S phase transition of FRH-0201 cells by targeting DUSP5. Conclusion miR-25-3p regulated HCCA cell cycle and facilitated cell proliferation and migration by targeting DUSP5.

Abstract Background To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). Methods The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). Results The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P

Abstract Background Hepatitis B core antibody (HBcAb) positivity is considered a prior hepatitis B virus (HBV) infection. However, little is known about the effect of HBcAb positivity on surgical safety for hilar cholangiocarcinoma (hCCA). The present study aims to investigate the role of HBcAb positivity on postoperative complications of hCCA. Methods A retrospective analysis was performed on the status of HBcAb positivity, liver fibrosis, perioperative surgical complications, and long‐term outcomes of hCCA patients with Hepatitis B surface antigen (HBsAg) negativity who underwent surgical treatment in Tongji Hospital from April 2012 to September 2019. Results HBcAb positivity with negative HBsAg occurs in 137 hCCA patients (63.1%). A total of 99 hCCA patients with negative HBsAg underwent extended hemihepatectomy, of whom 69 (69.7%) and 30 (30.3%) were HBcAb‐positive and HBcAb‐negative, respectively. Significant fibrosis was detected in 63.8% of the patients with HBcAb‐positive, which was markedly higher than those with HBcAb‐negative (36.7%) (p = 0.016). The postoperative complications and 90‐day mortality rates were 37.4% (37/99) and 8.1% (8/99), respectively. The incidence of postoperative complications in HBcAb‐positive patients (44.9%) was significantly higher than that in HBcAb‐negative patients (20.0%) (p = 0.018). All the patients who died within 30‐day after surgery were HBcAb‐positive. Multivariate analysis showed that the independent risk factors for complications were HBcAb positivity, preoperative cholangitis, portal occlusion >15 min, and significant fibrosis. There were no significant differences in recurrence‐free survival (RFS) and overall survival (OS) between HBcAb‐positive and HBcAb‐negative patients (p = 0.642 and p = 0.400, respectively). Conclusions HBcAb positivity is a common phenomenon in hCCA patients from China, a country with highly prevalent HBcAb positivity. The status of HBcAb‐positive markedly increases the incidence of postoperative complications after extended hemihepatectomy for hCCA patients.

Laparoscopic radical resection of hilar cholangiocarcinoma was complex because of the tumor near to hepatic hilum. The resection of hilar cholangiocarcinoma increased in recent years in large medical centers with safety of surgery improved. The current status of laparoscopic radical resection of hilar cholangiocarcinoma was discussed in this article including contraindication of surgery, precision evaluation and obstructive jaundice treated with preoperative biliary duct drainage, coordination among operative team and their experience. The key technology involved both blood vessels and lymphatic nodes dissected and separated which included resection of caudal lobe combined with hepatic lobes and hepatic segments, and then reconstruction of digestive tract. Lastly, there is consideration and prospect of laparoscopic radical resection of hilar cholagiocarcinoma.

Radical resection is the only option of curative treatment for hilar cholangiocarcinoma. Microscopically negative resection margin of bile duct (R0 resection) is critical for long-term survival of patients. However, both portal vein and hepatic artery invasions from hilar cholangiocarcinoma were often found, the negative resection margin could not be gotten. Combined vascular resection and reconstruction provide a possible way to solve this problem. At present, the clinical value of resection of portal vein and hepatic artery combining with reconstruction has been fully recognized. The technique of reconstruction for both portal vein and hepatic artery combined with the clinical significance, preoperative evaluation of imaging and postoperative complications for hilar cholangiocarcinoma were included in this article.

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

The differences between Bismuth IIIa and IIIb types of hilar cholangiocarcinoma are unclear. Thus, this study aimed to compare the clinical characteristics of the Bismuth IIIa and IIIb types of hilar cholangiocarcinoma. A case series analysis was designed to explore the clinical and pathological findings and survival of 144 patients with hilar cholangiocarcinoma who underwent curative hepatectomy between 2007 and 2018. The patients in the IIIa group received portal vein embolization and transfusion more frequently than those in the IIIb group (18.3% vs. 0.0%, P < 0.05 and 36.6% vs. 25.0%, P < 0.05). The incidence of posthepatectomy liver failure and serious surgical complications (≥ grade B) was significantly higher in the IIIa group than in the IIIb group (12.2% vs. 4.5%, P < 0.01 and 32.9% vs. 9.1%, P < 0.01). Tumors of the patients in the IIIa group had more advanced T and N stages than those of the patients in the IIIb group (P < 0.01). The patients in the IIIa group had poorer disease-free and overall survival rates than those in the IIIb group (P = 0.014 and P = 0.048). N stage and lymphovascular invasion were independently correlated with disease-free survival, whereas T and N stages were independently correlated with overall survival in the IIIb group. Meanwhile, T stage, N stage, and lymphovascular invasion were independently correlated with disease-free survival, whereas posthepatectomy liver failure, complication, and T stage were independently correlated with overall survival in the IIIa group. Hepatic and portal vessel metastasis occurred more frequently in the IIIa group than in the IIIb group (7.3% vs. 0.0%, P < 0.05). In our centers, patients with Bismuth IIIb hilar cholangiocarcinoma exhibited better disease-free and overall survival rates with more favorable clinicopathological characteristics than those with IIIa hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: 18F-FDG PET/MR has been applied to the diagnosis and preoperative staging in various tumor types; however, reports using PET/MR in hilar cholangiocarcinoma (HCCA) are rare. We investigated the value of PET/MR for preoperative staging and compared it with PET/CT in HCCA. Methods: Fifty-eight patients with HCCA confirmed by pathology were retrospectively analyzed. 18F-FDG PET/CT imaging was performed first, followed with whole-body PET/MR imaging. SUVmax of tumor and normal liver tissue were measured. Paired T test was used to compare SUVmax of tumor and normal liver tissue of PET/CT and PET/MR. In addition, McNemar test was used to compare the accuracy of TNM staging and Bismuth-Corlette typing between PET/CT and PET/MR. Results: There was no significant difference in SUVmax between PET/CT and PET/MR in primary tumor lesions (6.6 ± 5.5 vs. 6.8 ± 6.2, P = 0.439). SUVmax of PET/CT and PET/MR in normal liver parenchyma was significantly different (3.0 ± 0.5 vs. 2.1 ± 0.5, P < 0.001). The accuracy of PET/MR in diagnosing T staging and N staging was significantly higher than those of PET/CT (72.4% vs. 58.6%, P = 0.022 and 84.5% vs. 67.2%, P = 0.002). There was no significant difference between PET/CT and PET/MR in M staging (94.8% vs. 98.3%, P = 0.5). The classification accuracy of PET/MR in Bismuth-Corlette was significantly higher than that of PET/CT (89.7% vs. 79.3%), P = 0.031. Conclusions: The diagnostic accuracy of 18F-FDG PET/MR was superior to that of PET/CT in preoperative T staging, N staging, and Bismuth–Corlette classification of HCCA. In M staging, the diagnostic accuracy of PET/MR was similar to that of PET/CT. [ABSTRACT FROM AUTHOR]

Background: The main surgical procedure for Bismuth‒Corlette III–IV hilar cholangiocarcinoma (HCCA) is hemihepatectomy/extended hemihepatectomy. However, many patients have no opportunity for surgery due to having an insufficient remnant liver volume. Preservation of more liver volume on the premise of ensuring R0 resection is the goal. Mesohepatectomy with caudate lobectomy may be a new method to meet these requirements. Methods: The clinical data of 41 patients with Bismuth‒Corlette III–IV HCCA, including 18 patients who underwent mesohepatectomy with caudate lobectomy (the mesohepatectomy group) and 23 patients who underwent hemihepatectomy or extended hemihepatectomy (the hemihepatectomy group), were analyzed retrospectively. The perioperative indicators and prognostic survival time between the two groups were analyzed. Results: The mesohepatectomy group was compared with the hemihepatectomy group, and the operation time was 7.95 ± 1.2 vs. 7.15 ± 1.5 h (P > 0.05); the intraoperative blood loss was 600.0 ± 153.4 vs. 846.1 ± 366.8 mL (P < 0.05); the postoperative hospital stay was 9.9 ± 2.2 vs. 13.8 ± 3.0 days (P < 0.05); and the R0 resection rate was 100% vs. 87.0% (P > 0.05). The postoperative complications of the two groups included bile leakage (22.2% vs. 21.7%), pleural effusion (11.1% vs. 8.7%), and fever (16.7% vs. 8.7%), with no significant differences in the incidences (P > 0.05). The 1-, 3-, and 5-year survival rates of the two groups were 87.5%, 55.7%, 27.8% and 83.5%, 56.1%, 24.5%, respectively, with no significant differences (P > 0.05). Conclusions: Mesohepatectomy with caudate lobectomy can preserve more functional liver volume while ensuring the bile duct margin. It can be applied as the surgical treatment of Bismuth‒Corlette III–IV HCCA. [ABSTRACT FROM AUTHOR]

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Summary: Backgroud: The aim was to compare perioperative outcomes of hilar cholangiocarcinoma (HCCA) radical resection performed through the laparoscopic route or by open surgery in single-center cohort study. Methods: A retrospective study included all patients undergoing HCCA radical resection in our center from January 2018 to November 2019. Short-term outcomes of patients with laparoscopic and open surgery were compared demographic characteristics, intraoperative and postoperative parameters and extent of resection. Results: Among 64 patients included, 34 were performed with laparoscopic route and 30 were with open surgery. Laparoscopic versus open group was associated with a longer operation duration [475.50(219.00–630.00) vs. 375.00(220.00–557.00) min, P = 0.031], similar intraoperative bleeding volume [300.00(50.00–3500.00) vs. 350.00(100.00–1500.00) ml, P = 0.426]. No significant differences in tumor diameter [2.00(1.50–3.00) vs. 2.00(1.50–3.00) cm, P = 0.965], the number of lymph nodes retrieved [9.50(6.00–15.00) vs. 8.50(5.00–12.00), P = 0.706], and resection margins (94.1% vs. 86.7%, P = 0.407) between the two approaches were found. The LOS [20.00(10.00–44.00) vs. 21.00(6.00–27.00) d, P = 0.622], bile leakage (23.5% vs. 26.7%, P = 0.781), and liver failure (8.80% vs. 6.70%, P>0.99) were similar in the two groups. There was one patient in open surgery group developing liver failure and finally expired. Conclusion: The safety and radicality of laparoscopic resection for HCCA are similar to open surgery and can be technically improved by rational trocar distribution, total caudate lobectomy and appropriate cholangioenteric anastomosis strategy.

Abstract Background Biliary fistula is a common but serious complication after radical resection of hilar cholangiocarcinoma. We aimed to evaluate the influencing factors of biliary fistula after radical resection, to provide insights to the clinical treatment of hilar cholangiocarcinoma. Methods Patients undergoing radical resection of hilar cholangiocarcinoma from January 1, 2015 to March 31, 2022 were selected. Patients’ personnel characteristics and laboratory test results of patients with and without biliary fistula were collected and compared. Logistic regression analyses were conducted to evaluate the associated risk factors of biliary fistula. Results 160 patients undergoing radical resection of hilar cholangiocarcinoma were included, the incidence of postoperative biliary fistulas was 20.63%. There were significant differences in the age, preoperative cholangitis and number of biliary anastomosis between biliary fistula and no biliary fistula patients (all p

Background: To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). Methods: The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). Results: The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9–4.7) months and 2.8 (95% CI 2.5–3.1) months and 13.5 (95% CI 10.7–16.3) months and 8.8 (95% CI 7.8–9.8) months, respectively, with significant differences (P < 0.05). Conclusion: PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B core antibody (HBcAb) positivity is considered a prior hepatitis B virus (HBV) infection. However, little is known about the effect of HBcAb positivity on surgical safety for hilar cholangiocarcinoma (hCCA). The present study aims to investigate the role of HBcAb positivity on postoperative complications of hCCA. Methods: A retrospective analysis was performed on the status of HBcAb positivity, liver fibrosis, perioperative surgical complications, and long‐term outcomes of hCCA patients with Hepatitis B surface antigen (HBsAg) negativity who underwent surgical treatment in Tongji Hospital from April 2012 to September 2019. Results: HBcAb positivity with negative HBsAg occurs in 137 hCCA patients (63.1%). A total of 99 hCCA patients with negative HBsAg underwent extended hemihepatectomy, of whom 69 (69.7%) and 30 (30.3%) were HBcAb‐positive and HBcAb‐negative, respectively. Significant fibrosis was detected in 63.8% of the patients with HBcAb‐positive, which was markedly higher than those with HBcAb‐negative (36.7%) (p = 0.016). The postoperative complications and 90‐day mortality rates were 37.4% (37/99) and 8.1% (8/99), respectively. The incidence of postoperative complications in HBcAb‐positive patients (44.9%) was significantly higher than that in HBcAb‐negative patients (20.0%) (p = 0.018). All the patients who died within 30‐day after surgery were HBcAb‐positive. Multivariate analysis showed that the independent risk factors for complications were HBcAb positivity, preoperative cholangitis, portal occlusion >15 min, and significant fibrosis. There were no significant differences in recurrence‐free survival (RFS) and overall survival (OS) between HBcAb‐positive and HBcAb‐negative patients (p = 0.642 and p = 0.400, respectively). Conclusions: HBcAb positivity is a common phenomenon in hCCA patients from China, a country with highly prevalent HBcAb positivity. The status of HBcAb‐positive markedly increases the incidence of postoperative complications after extended hemihepatectomy for hCCA patients. The present study aims to evaluate the prevalence of HBcAb positivity in hCCA patients and explore the effect of HBcAb positivity on postoperative complications of hCCA patients after curative resection. Among all the 217 patients, 160 (73.7%) patients were HBcAb positive. Data of 99 HBsAg negative patients who underwent curative resection were analyzed, and the HBcAb positivity markedly increased the risk of postoperative complications and mortality after curative resection for hCCA. Surgeons should pay more attention to HBcAb status in hCCA patients with negative HBsAg, which could help them to select optimal surgical modalities. [ABSTRACT FROM AUTHOR]

Simple Summary: Biliary tract cancers (BTCs) are a rare pathology. In the era of precision oncology, the development of next-generation sequencing (NGS) allowed a better understanding of molecular differences between each tumor. Alterations in genes such as the FGFR, HER2, IDH1, and BRAF, result in cancer development, growth, and proliferation. Recent drug development allowed for the use of medications that can target these alterations and inhibit cancer progression. Additionally, the understanding of how the immune system interacts with cancer cells also resulted in the use of immunotherapy in this difficult scenario, although we still do not know how to select the patients with a higher chance of response. Here, we review the most recent data regarding targeted treatment and immunotherapy in the scenario of BTC treatment, discussing not only the role that these medications have in modern oncology, but also the future perspectives for this challenging disease. Biliary tract cancers (BTCs) are a rare pathology and can be divided into four major subgroups: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and gallbladder cancer. In the era of precision oncology, the development of next-generation sequencing (NGS) allowed a better understanding of molecular differences between these subgroups. Thus, the development of drugs that can target these alterations and inhibit the abnormal pathway activation has changed the prognosis of BTC patients. Additionally, the development of immune checkpoint inhibitors and a better understanding of tumor immunogenicity led to the development of clinical trials with immunotherapy for this scenario. The development of biomarkers that can predict how the immune system acts against the tumor cells, and which patients benefit from this activation, are urgently needed. Here, we review the most recent data regarding targeted treatment and immunotherapy in the scenario of BTC treatment, while also discussing the future perspectives for this challenging disease. [ABSTRACT FROM AUTHOR]

Introduction: Hilar cholangiocarcinoma (HC) is the leading cause of hilar biliary obstruction. Radioactive stent insertion has been utilized extensively for inoperable HC patients. Aim: To assess the relative clinical outcomes of inoperable HC patients who underwent either normal or radioactive stent insertion. Material and methods: This single-center, prospective, randomized, open-label study enrolled 90 inoperable HC patients from April 2021 to March 2022 and randomly assigned them to normal or radioactive stent groups (n = 45/group), with clinical data then being compared between these groups. Results: Technical success rates in the normal and radioactive stent insertion groups were 93.3% and 97.9%, respectively (p = 1.000), and clinical success rates were similarly consistent in both groups (95.3% vs. 97.7%, p = 0.983). Individuals in the radioactive stent group exhibited significantly longer median stent patency as compared to the normal stent group (195 days vs. 115 days, p < 0.001), and median overall survival (OS) was also significantly increased in the normal stent group (242 days vs. 125 days, p = 0.002). In the normal stent insertion group, 6 (14.3%) and 5 (11.9%) patients experienced early and late postoperative complications, respectively. Additionally, early and late postoperative complications impacted 7 (16.3%) and 8 (18.6%) patients in the radioactive stent insertion group, respectively. Complication rates were comparable in these 2 patient groups. Conclusions: Radioactive stent insertion represents a safe and effective strategy for patients with inoperable HC, potentially contributing to prolonged stent patency and OS relative to normal stent insertion. [ABSTRACT FROM AUTHOR]