Laparoscopic Resection of the Middle Bile Duct for Cholangiocarcinoma (with Video).

BACKGROUND: Surgical resection remains the sole approach to achieving long-term survival in cholangiocarcinoma cases. The universally recognised standard procedures for such cases include pancreaticoduodenectomy (PD) or hemihepatectomy accompanied by bile duct reconstruction. Nevertheless, some patients may still attain curative intent through bile duct segmental resection (BDR). However, these procedures are still in the experimental stage and should only be recommended for carefully chosen patients. METHODS: A 57-year-old male patient was admitted to our department after two weeks of escalating jaundice and abdominal discomfort. Upon admission, his total bilirubin was recorded at 102 µmol/L, and his direct bilirubin was 87 µmol/L. His carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) levels were normal. Enhanced computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a thickened and enhanced biliary tree extending from the cystic duct junction to the common hepatic duct no vascular invasion indicated by three-dimensional reconstruction. RESULTS: The patient underwent laparoscopic resection of the extrahepatic bile duct, accompanied by radical lymphadenectomy with skeletonisation and biliary reconstruction, was successfully conducted within 320 min, with a minimal blood loss of only 50 ml. The histological grading of the procedure was T2bN0M0 (stage II). The patient was discharged on the sixth postoperative day without complications. Following this, he underwent a regimen of single-agent capecitabine chemotherapy. After an 18-month follow-up period, no recurrence was observed. CONCLUSIONS: Our experience suggests that in selected patients diagnosed with middle bile duct cholangiocarcinoma, laparoscopic resection could potentially reach the standard of lymphadenectomy through skeletonisation.

Total Laparoscopic Radical Resection of S1 + S4 for Bismuth-Corlette Type IV Hilar Cholangiocarcinoma (With Video).

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.

Laparoscopic caudate lobe resections: How I do it: tips and pitfalls (with video).

BACKGROUND: The caudate lobe (S1) of the liver, due to its deep central position, presents a formidable challenge for laparoscopic resection. Historical skepticism about laparoscopic approaches has been overshadowed by advancements in technology and technique, with recent studies showing comparable outcomes to open surgery. METHODS: This paper introduces the "Easy First" technique and the Sextet strategies for laparoscopic hepatic caudate lobectomy. The strategies include meticulous preoperative planning, optimal trocar placement, and team positioning, tailored to the anatomical complexities of the caudate lobe. RESULTS: With a 0% conversion and mortality rate, our series demonstrates the safety of the "Easy First" technique. The Sextet strategies have been instrumental in navigating the technical challenges, emphasizing the importance of patient selection and surgeon expertise. CONCLUSION: The "Easy First" technique, with its structured approach and the Sextet strategies, offers a replicable method for laparoscopic caudate lobectomy. It underscores the need for stringent patient selection, advanced technical skill, and high-volume center expertise to ensure procedural success and patient safety.

DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP.

BACKGROUND: Although disc large associated protein family (DLGAP5) has been reported to be involved in a variety of tumor pathologic processes, its expression and mechanism in gallbladder cancer (GBC) are still uncertain. Macrophages were divided into M1 and M2 macrophages. TAM is more closely defined as M2 polarized macrophages, which plays a key role in cancer progression. OBJECTIVE: To clarify the role of disc large associated protein family (DLGAP5) in gallbladder cancer (GBC) progression and investigate the mechanism. METHODS: Differential genes in 10 normal paracancer tissues and 10 GBC tissues in GSE139682 from NCBI-GEO were analyzed by R language. Bioinformation analysis and clinical sample analysis were performed to detect DLGAP5 expression in GBC and its correlation with prognosis. CCK-8, EDU, transwell, wound closure, and Immunoblot were performed to detect its effects on the function of GBC cells. GST-pulldown showed the direct interact between DLGAP5 and cAMP. Macrophage polarization assay was further conducted to detect the effects of DLGAP5 on macrophage M2 polarization. The tumor growth assays were further conducted to confirm its role in mice. RESULTS: Biological analysis and clinical samples confirmed that DLGAP5 was increased in GBC and strongly related to poor prognosis in patients with GBC. After overexpression of DLGAP5 in GBC cell lines, such as GBC-SD and NOZ cells, cell proliferation and migration were enhanced, and macrophages were polarized to M2. However, after DLGAP5 is knocked down, there is opposite effect. Mechanistically, DLGAP5 promotes the growth and migration of GBC-SD and NOZ cells and the M2 polarization of THP-1-derived macrophages by activating cyclic adenosine monophosphate (cAMP) pathway. In vivo, GBC-SD with DLGAP5 knockdown was subcutaneously injected into nude mice. It was found that after DLGAP5 knockdown, both tumor volume and tumor were reduced, and indicators related to proliferation and M2 polarization decreased. CONCLUSION: Our study shows that DLGAP5 is significantly elevated in GBC and is strongly related to poor prognosis in patients with GBC. DLGAP5 promotes GBC proliferation, migration, and M2 polarization of macrophages through cAMP pathway, which provides a theoretical basis for the treatment of GBC and may become a promising therapeutic target.

Is laparoscopic surgery a preferred option for benign conditions in the caudate lobe of the liver?

BACKGROUND/AIM: Laparoscopic hepatectomy has become a common management strategy for liver tumors owing to its less invasive nature and enhanced visual perspective. Yet, its use in the caudate lobe poses challenges. This study evaluates the experiences of patients who underwent laparoscopic hepatectomy for hepatic tumors in the caudate lobe and aims to propose strategies for performing such procedures. METHODS: We retrospectively analyzed the clinical data of twelve patients who underwent laparoscopic hepatic caudate lobe resection at the Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University. RESULTS: All twelve laparoscopic procedures were successful, with none requiring conversion to open surgery. The surgical methods varied: five cases involved simple resection of the Spiegel lobe, one case involved total caudate lobe resection, three cases involved paravena cava lobe resection, and three cases involved resection of the caudate process. The operation time ranged from 49 to 319 min (mean, 219 min). Intraoperative blood loss ranged from 20 to 500 ml, averaging 194 ml. No patients needed blood transfusions during or after the operation, and there were no instances of postoperative bleeding, bile leakage, or abdominal infection. CONCLUSION: Given adequate control of hepatic inflow, sufficient exposure to the surgical field, and an appropriate approach, laparoscopic hepatectomy in the caudate lobe could potentially become a standard surgical technique.

Laparoscopic hepatectomy for hepatocellular adenoma using the hepatic vein as anatomic markers,How I do it.(with video).

TECHNIQUE: Hepatocellular adenoma (HCA) is a benign monoclonal tumour that originates from mature hepatocytes.Liver resection is recommended in case of overt malignant transformation to hepatocellular carcinoma.However, hepatobiliary surgeries are technically challenging in patients with giant HCA (GHCA) owing to the risk of catastrophic intraoperative bleeding and difficulty with its control during laparoscopic treatment. We present a technical note on the utilization of the hepatic vein as anatomical landmarks for laparoscopic removal of giant hepatic glands, without intraoperative ultrasonography and with the aid of an augmented reality navigation system during surgery. RESULTS: This video shows aA 37-year-old man was recommended treatment for a progressively increasing HCA (from 3 to 10 cm in a year) involving the right hepatic vein (RHV), inferior vena cava (IVC) and middle hepatic vein (MHV), resulting in the invisibility of the above intrahepatic anatomic markers in CT. Laparoscopic hepatectomy was performed using the hepatic vein as anatomic markers in a treatment centre specialising in minimally invasive surgeries. The procedure involved fully mobilising the right liver, transecting the parenchyma along the demarcation line in the caudal-to-cranial direction, exposing the involved caudal MHV, isolating and transecting the involved RHV and preserving the integrity of the involved IVC. CONCLUSIONS: Laparoscopic hepatectomy for intractable GHCA using the involved intrahepatic anatomic markers is feasible and effective. It reduces pre-operative haemorrhage and open conversion rates while maximising postoperative hepatic function.

A comprehensive study and extensive review of the Caudate lobe: The last piece of "Jigsaw" puzzle.

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.

Efficacy and safety of robotic surgery versus open surgery for hilar cholangiocarcinoma: a systematic review and meta-analysis.

OBJECTIVE: The aim is to assess and contrast the effectiveness and safety of employing robotic surgery versus traditional open surgery in managing cases of hilar cholangiocarcinoma. METHODS: Computer searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database to identify case-control studies comparing robotic surgery with traditional open surgery in the treatment of hilar cholangiocarcinoma from inception until July 2023. References from retrieved articles were reviewed to broaden the search. This review was prospectively registered in the PROSPERO database (PROSPERO ID: CRD42024527511) and reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines.The primary outcome measures included operation time, intraoperative blood transfusion rate, R0 resection rate, lymph node metastasis rate, incidence of postoperative complications, and postoperative hospital stay. Data analysis was performed using RevMan 5.4 software, calculating combined odds ratios (OR), mean differences (MD), and 95% confidence intervals (95% CI). RESULTS: A total of 4 studies encompassing 267 patients diagnosed with hilar cholangiocarcinoma (177 males and 90 females, mean age of (58.8±5.7) years) were included in this analysis. Among these, 165 patients underwent open surgery, while 102 patients underwent robotic surgery. The results of the meta-analysis demonstrated comparable outcomes between the two groups. Specifically, the operation time between the robotic surgery and open surgery cohorts did not significantly differ (MD=-103.96, 95% CI: -216.90 to 8.98, P=0.070). Additionally, the intraoperative blood transfusion rate (OR=1.32, 95% CI: 0.43 to 4.07, P=0.630), R0 resection rate (OR=1.41, 95% CI: 0.71 to 2.81, P=0.330), and lymph node metastasis rate (OR=1.62, 95% CI: 0.46 to 5.63, P=0.450) showed no significant differences between the groups. Similarly, there were no statistically significant disparities observed in the incidence of postoperative complications (OR=0.60, 95% CI: 0.28 to 1.31, P=0.200) and postoperative hospital stay (MD=2.17, 95% CI: -11.56 to 15.90, P=0.760). CONCLUSION: In the treatment of hilar cholangiocarcinoma, robotic surgery demonstrates comparable safety and feasibility to traditional open surgery. However, due to the limited quantity and quality of the included studies, these conclusions warrant validation through additional high-quality investigations.

Application of Indocyanine Green Fluorescence Imaging During Laparoscopic Reoperations of the Biliary Tract Enhances Surgical Precision and Efficiency.

BACKGROUND: A history of abdominal surgery is considered a contraindication for laparoscopic procedures. However, the advancements in laparoscopic instruments and techniques have facilitated the performance of increasingly intricate operations, even in patients with prior abdominal surgeries. ICG fluorescence imaging technology offers advantages in terms of convenient operation and clearer intraoperative bile duct imaging, as confirmed by numerous international clinical studies on its feasibility and safety. The application of ICG fluorescence imaging technology in repeat laparoscopic biliary surgery, however, lacks sufficient reports. METHODS: The clinical data of patients who underwent elective reoperation of the biliary tract in our department between January 2020 and June 2022 were retrospectively analyzed. ICG was injected peripherally before the operation, and near-infrared light was used for 3-dimensional imaging of the bile duct during the operation. RESULTS: Altogether, 143 patients were included in this study and divided into the fluorescence and nonfluorescence groups according to the inclusion criteria. Among the 26 patients in the fluorescence group, cholangiography was successfully performed in 24 cases, and the success rate of intraoperative biliary ICG fluorescence imaging was 92.31%. The intraoperative biliary tract identification time was significantly different between the fluorescence and nonfluorescence groups, but no statistical difference was observed in the final operation method, operative time, and intraoperative blood loss between the 2 groups. Although there was no significant difference in the postoperative ventilation rate, incidence of bile leakage, and stone recurrence rate at 6 months postoperatively between the 2 groups (P>0.05), a significant difference in postoperative hospitalization days was observed (P=0.032). CONCLUSION: The application of ICG fluorescence imaging technology in laparoscopic reoperation of the biliary tract is useful for the early identification of the biliary tract during operation, thereby shortening the operative time and reducing the risk of damage to nonoperative areas. This approach also enhances the visualization of the biliary system and avoids secondary injury intraoperatively due to poor identification of the biliary system. This technique is safe for repeat biliary tract surgery and has a good application prospect.

Thermal decomposition and oxidation of CH3OH.

Thermal decomposition of CH(3)OH diluted in Ar has been studied by monitoring H atoms behind reflected shock waves of 100 ppm CH(3)OH + Ar. The total decomposition rate k(1) for CH(3)OH + M → products obtained in this study is expressed as, ln(k(1)/cm(3) molecule(-1) s(-1)) = -(14.81 ± 1.22) - (38.86 ± 1.82) × 10(3)/T, over 1359-1644 K. The present result on k(1) is indicated to be substantially smaller than the extrapolation of the most of the previous experimental data but consistent with the published theoretical results [Faraday Discuss. 2002, 119, 191-205 and J. Phys. Chem. A 2007, 111, 3932-3950]. Oxidation of CH(3)OH has been studied also by monitoring H atoms behind shock waves of (0.35-100) ppm CH(3)OH + (100-400) ppm O(2) + Ar. For the low concentration CH(3)OH (below 10 ppm) + O(2) mixtures, the initial concentration of CH(3)OH is evaluated by comparing evolutions of H atoms in the same concentration of CH(3)OH with addition of 300 ppm H(2) diluted in Ar. The branching fraction for CH(3)OH + Ar → (1)CH(2) + H(2)O + Ar has been quantitatively evaluated from this comparative measurements with using recent experimental result on the yield of H atoms in the reaction of (1,3)CH(2) + O(2) [J. Phys. Chem. A 2012, 116, 9245-9254]; i.e., the branching fraction for the above reaction is evaluated as, φ(1a) = 0.20 ± 0.04 at T = 1880-2050 K, in the 1.3 and 3.5 ppm CH(3)OH + 100 ppm O(2) samples. An extended reaction mechanism for the pyrolysis and oxidation of CH(3)OH is constructed based on the results of the present study combined with the oxidation mechanism of natural gas [GRI-Mech 3.0]; evolution of H atoms can be predicted very well with this new reaction scheme over a wide concentration range for the pyrolysis (0.36-100 ppm CH(3)OH), and oxidation (0.36-100 ppm CH(3)OH + 100/400 ppm O(2)) of methanol.

RNF126 contributes to stem cell-like properties and metastasis in hepatocellular carcinoma through ubiquitination and degradation of LKB1.

Hepatocellular carcinoma (HCC) is one of the malignant tumors with the worst prognosis, and tumor recurrence and metastasis are the main factors leading to poor prognosis of HCC patients. Accumulating studies show that RNF126, ring finger protein 126, is involved in the pathological process of many tumors. However, the biological function and exact molecular mechanism of RNF126 in HCC remain unclear. In this study, we investigated the role of RNF126 in the pathogenesis of HCC. By analyzing database and verifying with our clinical specimens, it was found that RNF126 was highly expressed in HCC tissues, which is associated with shorter overall survival and higher recurrence rate. Overexpressed RNF126 can significantly promote the proliferation, migration, invasion and angiogenesis of HCC cells, whereas knockdown RNF126 can reverse this effect. Mechanically, RNF126 down-regulates liver kinase B1 (LKB1) expression by ubiquitination of LKB1 to weaken its stability, thereby significantly promoting stem-cell-like activity, migration, and angiogenesis of HCC. Notably, consistent with in vitro results, RNF126 was stably transformed in Hep3B and subcutaneously injected into nude mice. In established mouse xenograft models, tumor growth can be effectively inhibited and the occurrence of lung metastasis is reduced. In HCC, RNF126 may down-regulate LKB1 through ubiquitination, thus becoming a powerful prognostic biomarker and a recognized tumor suppressor. Therefore, our study may provide a promising new therapeutic strategy for targeting RNF126 for HCC patients.

RUNX1 regulates SMAD1 by transcriptionally activating the expression of USP9X, regulating the activation of hepatic stellate cells and liver fibrosis.

Liver fibrosis (LF) is a common pathological process with high morbidity and mortality. Runt-related transcription factor 1 (RUNX1) is a transcription factor that could cause nephropathy and renal fibrosis, but its role in LF is unclear. Therefore, this study aimed to investigate the role RUNX1 in LF. Briefly, hepatic fibrosis was detected by Sirius Red staining. Transcript levels were quantified by qPCR, and proteins were assessed by western blotting or immunofluorescence. Cell viability and cell migration were measured by CCK8 assays and wound healing assays, respectively. The binding of RUNX1 and ubiquitin-specific protease 9X (USP9X) promoter was validated by ChIP assays and luciferase report assays, while the binding of USP9X and SMAD1 was confirmed by co-immunoprecipitation (Co-IP). Our studies found that the expression of RUNX1 was upregulated in LF mice, and RUNX1 knockdown alleviated CCl4-induced LF. RUNX1 silencing reduced the viability and migration of HSCs. Besides, RUNX1, as a transcription factor, bound to the promoter of USP9X and regulated the expression of USP9X. USP9X is a deubiquitination enzyme and was found to be up-regulated in LF mice. USP9X silencing reduced the viability and migration of HSCs, thereby inhibiting LF. Further studies showed that USP9X could stabilize downstream Smad1 expression. Furthermore, we also found that RUNX1 regulated the expression of SMAD1 by transcriptionally activating the expression of USP9X, thereby regulating the activation of hepatic stellate cells and liver fibrosis.

Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and occurs in people with chronic liver diseases. Current treatment methods include surgery, transplant, and chemotherapy. Our study demonstrates runt-related transcription factor 1 (RUNX1) as a novel molecule in the initiation and development of HCC, and the role of its interaction with vascular endothelial growth factor A (VEGFA) in HCC. We showed the suppressive role of RUNX1 in the proliferation and migration of hepatocytes. In addition, the repressor RUNX1 functioned as a transcription factor on the promoter of VEGFA to inhibit the expression of VEGFA. Study in the HCC cells demonstrated that the suppression of HCC proliferation and migration was masked in the presence of overexpressed VEGFA. Introduction of RUNX1 into HCC mice model significantly limited the tumor growth. In summary, our study demonstrated that RUNX1 functions as a repressor in the HCC and this suppressive function was dependent on its effect on VEGFA.