Partial Liver Resection Research Articles

Central pancreatectomy in portal annular pancreas for metastatic renal cell carcinoma: a case report

BackgroundPortal annular pancreas (PAP) is a rare congenital anatomical abnormality of the pancreas in which the portal vein is encircled by aberrant parenchyma, and special attention is needed for pancreatic resections. This is the first report of central pancreatectomy (CP) in a PAP for metastatic renal cell carcinoma (RCC).Case presentationA 76-year-old man who had a history of left nephrectomy for renal cancer not otherwise specified 36 years earlier and radical cystectomy for bladder cancer 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor. The pancreatic tumor was diagnosed as metastasis of clear cell RCC, and the liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC) on preoperative histological evaluation. Preoperative computed tomography imaging showed a type 3A PAP, in which the main pancreatic duct (MPD) ran ventral to the portal vein (anteportal type), and the aberrant parenchyma was located cranial to the confluence of the portal vein and splenic vein (suprasplenic type). After adhesiotomy and partial liver resection, CP was performed. With intraoperative ultrasound guidance, the aberrant parenchyma of the PAP could be preserved, avoiding additional resection. Thus, two pancreatic transections were performed, creating a single-cut margin that contained the MPD in the distal pancreas. Oncologically safe margins were confirmed by intraoperative pathological diagnosis. The distal pancreas was reconstructed by pancreatojejunostomy in the routine procedures. The pathological diagnosis of the surgical specimens was identical to the preoperative diagnosis. A postoperative pancreatic fistula (POPF) developed from the proximal stump of the head of the pancreas, necessitating no specific treatment other than drainage. The patient showed no signs or symptoms of recurrent RCC or abnormal pancreatic function for 2 years after the operation, although a histologically proven new HCC lesion developed distant from the initial site 8 months after the operation.ConclusionsPrecise preoperative evaluation of the tumor features and PAP allowed adequate surgical strategies to be planned. Intraoperative ultrasound was useful to minimize parenchymal resections of the PAP. CP is still a challenging procedure in terms of the development of POPF.

Laparoscopic anatomical liver resection using indocyanine green fluorescence imaging

Anatomical liver resections guided by a demarcation line after portal staining or inflow clamping of the target area have been established as essential methods for curative treatment of hepatocellular carcinoma (HCC) and have subsequently been applied to other malignancies. However, laparoscopic anatomical liver resection (LALR) procedures are very difficult to reproduce, and the confirmation of demarcation of the hepatic segment on a monitor is also challenging. Recently, indocyanine green (ICG) fluorescence imaging has been used to identify hepatic tumors and segmental boundaries during hepatectomy. Herein, we describe LALR using ICG fluorescence imaging. Three patients underwent pure LALR using ICG fluorescence imaging at our institute. One patient underwent anatomical partial liver resection for HCC, another underwent segmentectomy 3 for metastatic liver cancer, and the third underwent right anterior sectionectomy for HCC. To visualize hepatic perfusion and the demarcation line by negative staining using an optical imaging system, 2.5mg ICG was injected intravenously during surgery following clamping or closure of the proximal Glissonean pedicles. For all three cases, ICG fluorescent imaging clearly delineated the demarcation lines and allowed identification of intersegmental planes to some extent because the tumor-bearing hepatic region became non-fluorescing parenchyma during parenchymal transection. This allowed surgeons to recognize the direction and guide the transection of the liver parenchyma when performing LALR. LALR using ICG fluorescence imaging is a feasible procedure for resection of the tumor-bearing hepatic region and facilitates visualization of the demarcation line and identification of the boundaries of the hepatic sections.

Impact of Percoll purification on isolation of primary human hepatocytes

Research and therapeutic applications create a high demand for primary human hepatocytes. The limiting factor for their utilization is the availability of metabolically active hepatocytes in large quantities. Centrifugation through Percoll, which is commonly performed during hepatocyte isolation, has so far not been systematically evaluated in the scientific literature. 27 hepatocyte isolations were performed using a two-step perfusion technique on tissue obtained from partial liver resections. Cells were seeded with or without having undergone the centrifugation step through 25% Percoll. Cell yield, function, purity, viability and rate of bacterial contamination were assessed over a period of 6 days. Viable yield without Percoll purification was 42.4 × 106 (SEM ± 4.6 × 106) cells/g tissue. An average of 59% of cells were recovered after Percoll treatment. There were neither significant differences in the functional performance of cells, nor regarding presence of non-parenchymal liver cells. In five cases with initial viability of <80%, viability was significantly increased by Percoll purification (71.6 to 87.7%, p = 0.03). Considering our data and the massive cell loss due to Percoll purification, we suggest that this step can be omitted if the initial viability is high, whereas low viabilities can be improved by Percoll centrifugation.

Single Cell RNA‐sequencing (scRNA‐seq) Reveals Reprogramming and Functional Compensation Preceding Cellular Recovery in Multiple Models of Acute Liver Injury

The liver is an essential organ critical for several homeostatic functions. Because of its vital role in detoxificaion, the liver is regularly exposed to toxic insults leading to injury, cell death, and a loss of functional mass. Consequently, the liver has evolved a unique capacity to regenerate in order to maintain function. While numerous studies have focused on the proliferative capacity of the liver to regenerate tissue mass after injury, the ability of the liver to maintain function after massive cell loss has not been explored in detail. Here, we deploy single cell RNA‐sequencing (scRNA‐seq) to define dynamic changes in the transcriptional profile of the liver following different forms of acute injury.Hepatocytes, the major parenchymal cell of the liver, are heterogeneous and arranged in a pattern consistent with their specific function, known as hepatic zonation. Select toxic insults will injure particular zones of the liver depending on zonation‐specific metabolism. One example is acetaminophen (APAP) toxicity, the most common cause of acute liver failure in the U.S. APAP affects a specific group of hepatocytes within an area known as the pericentral zone. In order to elucidate the immediate transcriptional responses of the entire liver after acute injury, we performed scRNA‐seq analysis in murine livers following APAP overdose compared to injury of the periportal zone (allyl alcohol) as well as physical injury that is not specific to a particular zone (partial liver resection). We discover that hepatocytes exhibit the ability to alter their transcriptional identity in order to maintain essential, zone‐dependent liver function, such as glucose metabolism, coagulation, and detoxification, prior to and during proliferative regeneration of liver mass. These findings are further validated and quantified by single‐molecule FISH. Further, our analysis reveals that zonal reprogramming is dependent on the Wnt pathway, which also regulates liver zonation and cellular regeneration. Therefore, we have identified a novel regenerative response that is focused on the preservation of function prior to the onset of cellular regeneration.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Can newly developed device contribute to improve outcome of laparoscopic liver resection?

In the initiation phase of laparoscopic liver resection (LLR), studies from Western countries reported LLR in benign legions of the liver (1,2). In 1993, we experienced laparoscopic partial liver resection for both of primary and metastatic malignancy, with liver cirrhosis occasionally.

Diltiazem Increases the Liver Regeneration in Rats by Inhibiting TGF-β1

Transforming growth factor beta-1 (TGF- β1) is the most important inhibitory cytokine during the hepatic regeneration process. Diltiazem is a Ltype calcium channel blocker that has inhibitory effect on TGF- β1. The aim of the present study was to determine the effect of diltiazem on hepatic regeneration. Sixty female Wistar Albino rats were used. Three groups were created; the control, low dose diltiazem and high dose diltiazem groups, each consisting of 20 rats. After partial liver resection (70% hepatectomy), saline was introduced to control group, 5 mg/kg diltiazem was introduced to low dose group and 15 mg/kg diltiazem to high dose group intraperitoneally. Ten rats in each group were sacrificed on the first postoperative day and the remaining rats on the fifth day. Liver weight, mitotic rate and the Ki-67 ratio were measured for determining hepatic regeneration. Liver regeneration rate on the fifth postoperative day was significantly higher both in the low dose and high dose diltiazem groups than the control group (Low diltiazem vs control: P 0.05). The Ki-67 ratio on the first postoperative day was significantly higher both in the low dose and high dose diltiazem groups than the control group (Low diltiazem vs control: P<0.001; High diltiazem vs control: P<0.001). Diltiazem increases liver regeneration by inhibiting TGF-β1.

Chronological occurrence of PI3KCA mutations in breast cancer liver metastases after repeat partial liver resection

BackgroundLiver metastases of breast cancer are frequent and can recur even after “complete/R0” resection in combination with systemic and hormonal treatments. The aim of this study was to analyze throughout repeat hepatectomies for liver metastases the evolution of PI3KCA gene mutational status.MethodsAll liver metastases nodules (n = 70) from 19 women who underwent at least 2 liver resections were reexamined. DNA extraction from archived tumoral tissue was performed and the major ‘hot spot’ mutations in the helical and catalytic domains of PI3KCA have been analyzed using Massarray platform (Agena Bioscience) based on allelic discrimination PCR amplification followed by sensitive mass spectrometry detection.ResultsThe two major somatic hot spot PI3KCA mutations were found in 27 (38.6%) nodules corresponding to 8 of the 19 patients (42%). The frequency of women whose breast cancer liver metastases (BCLM) carries PI3KCA mutations increased from the first to the third hepatectomy. Tumors carrying PI3KCA mutations are significantly larger and more frequently observed when resections were R0 compared to patients with no PI3KCA mutation.ConclusionPI3KCA mutations are frequently observed in BCLM and persist along with the recurrence. Their identification in circulating tumor cells should become a useful biomarker in the routine practice of breast cancer management to prevent tumor recurrence and overcome the problems of intra- and inter-tumoral heterogeneity of the current biomarkers,

MicroRNA-224 Expression and Polymorphism Predict the Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Liver Resection.

Hepatocellular carcinoma (HCC) is one of the common lethal types of tumors all over the world. Overexpression of mircoRNA-224 (miR-224) has been reported to act as a potential biomarker for HCC patients. The goal of our study was to assess the prognostic impact of the expression and polymorphism of miR-224 in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after liver resection. A total of 62 cases of HBV-positive HCC patients, 17 HCC patients without HBV, and 13 healthy cases were enrolled in this study. Blood leukocyte miR-224 level were determined by qRT-PCR. Genotyping analysis of miR-224 rs188519172 was performed using an allele-specific PCR assay. All patients were undergoing partial liver resection and the prognostic values of miR-224 rs188519172 polymorphism for tumor development, survival rate, and liver injury after liver resection were examined. When we compared the blood leukocyte miR-224 level between HCC patients and healthy cases, we found that it was significantly increased in HCC patients. By subgroup analysis, it demonstrated that miR-224 expression was significantly increased in the HBV positive group compared with the HBV negative group. miR-224 rs188519172 AG + GG phenotype was significantly associated with severe liver injury after liver resection and patients carrying miR-224 rs188519172 AG + GG phenotype have a higher risk of cirrhosis and lower overall and disease-free survival rate. Meanwhile, the combination of miR-224 rs188519172 AG + GG phenotype and AFP value could improve the prognosis assessment of HBV related HCC. miR-224 rs188519172 polymorphism is an indicator of liver injury and a novel prognostic biomarker for tumor development and survival of HBV related HCC patients after liver resection.

Liver resection is safely performed in patients receiving antithrombotic therapy

Background: This study was to assess the safety and feasibility of liver resection in patients with antithrombotic therapy (ATT, including antiplatelet therapy (APT) and anticoagulation therapy (ACT)) for thromboembolic risks. Methods: 344 patients receiving liver resection at our institution between 2005 and 2016 were retrospectively reviewed. ATT was used in 123 patients (35.8%). Our perioperative management included maintenance of preoperative aspirin monotherapy for APT and bridging heparin for ACT in patients at high thromboembolic risks. Outcomes variables were compared between the patients with ATT and those without ATT . Results: This series included 202 partial liver resection, 66 sectionectomy and 76 lobectomy. Patients with ATT showed high frequency of history of acute coronary syndrome and cerebral infarction, though the type of operation was similar. There were 14 bleeding complications (4.1%) and 6 thromboembolic events (1.7%). No significant differences were found between the groups in operative blood loss and blood transfusion rate. Multiple analysis showed that increased bleeding complications were independently associated with high-risk liver resection (HR 6.125, p=0.004). Poor performance status (HR 14.945, p=0.020) was the significant prognostic factor for thromboembolic events. Neither ACT nor preoperative aspirin continuation affected bleeding or thromboembolism. Conclusion: In patients undergoing ATT, liver resection is safely performed under the relevant perioperative management of ATT.

Precoagulation with microwave ablation for hepatic parenchymal transection during liver partial resection

Purpose: To evaluate the feasibility of precoagulation with microwave ablation (MWA) for hepatic parenchymal transection during liver partial resection.Methods: A total of 66 eligible patients were enrolled in this double-blind, randomized, controlled study. Patients were randomized to receive either the traditional clamp-crushing method (Control group) or the MWA precoagulation method (MWA group) for hepatic parenchymal transection during liver partial resection. The operative time, hepatic portal occlusion time, intraoperative blood loss and transfusion, postoperative complications and recovery outcomes were compared.Results: Compared to the Control group, the MWA group had significantly less intraoperative blood loss. Fewer red blood cell transfusions were observed in the MWA group but without statistical significance. The MWA group showed significantly higher serum alanine aminotransferase and aspartate aminotransferase levels at day 1 postoperatively, but no differences between the MWA and Control groups were found at days 3 and 7. There were no significant differences in terms of operative time, hepatic portal occlusion time, postoperative total bilirubin levels, human albumin solution consumption or length of hospital stay. Postoperative complications such as impaired renal function, pyrexia, admission to ICU, abscess, biliary leakage, intrahepatic and distant tumor recurrence and in-hospital mortality were comparable between the two groups.Conclusion: Precoagulation with MWA reduced intraoperative blood loss with similar postoperative complications, providing a safe, effective, novel alternative for hepatic parenchymal transection during liver partial resection. Additional results from larger series are recommended to confirm these findings.

FXR agonist obeticholic acid induces liver growth but exacerbates biliary injury in rats with obstructive cholestasis

Cholestasis impairs liver regeneration following partial liver resection (PHx). Bile acid receptor farnesoid X-receptor (FXR) is a key mediator of liver regeneration. The effects of FXR agonist obeticholic acid (OCA) on liver (re)growth were therefore studied in cholestatic rats. Animals underwent sham surgery or reversible bile duct ligation (rBDL). PHx with concurrent internal biliary drainage was performed 7 days after rBDL. Animals were untreated or received OCA (10 mg/kg/day) per oral gavage from rBDL until sacrifice. After 7 days of OCA treatment, dry liver weight increased in the rBDL + OCA group, indicating OCA-mediated liver growth. Enhanced proliferation in the rBDL + OCA group prior to PHx concurred with a rise in Ki67-positive hepatocytes, elevated hepatic Ccnd1 and Cdc25b expression, and an induction of intestinal fibroblast growth factor 15 expression. Liver regrowth after PHx was initially stagnant in the rBDL + OCA group, possibly due to hepatomegaly prior to PHx. OCA increased hepatobiliary injury markers during BDL, which was accompanied by upregulation of the bile salt export pump. There were no differences in histological liver injury. In conclusion, OCA induces liver growth in cholestatic rats prior to PHx but exacerbates biliary injury during cholestasis, likely by forced pumping of bile acids into an obstructed biliary tree.

Experimental Evaluation of a New Tissue Factor-Based Topical Hemostat (TT-173) for Treatment of Hepatic Bleeding

Background: Excessive blood loss is a relevant complication of partial liver resection. Topical hemostatic agents have proven useful to improve the control of the bleeding in this among other surgical indications. Until now all of these products have been based on the action of thrombin. In contrast TT-173 is a new topical hemostatic agent based on recombinant tissue factor naturally incorporated into membrane vesicles. This work sought to assess the efficacy and toxicity of TT-173 in an animal model of liver resection.Materials and Methods: Procoagulant activity of 0.15, 0.41, and 1 mg of TT-173 was evaluated in pigs subjected the resection of hepatic lobe margins. The most effective of these doses was also compared against thrombin. In addition, the toxicity, local tolerance, systemic absorption, and immunogenicity of the product were investigated in rats subjected to liver biopsy lesion.Results: The three doses of TT-173 evaluated significantly reduced the bleeding time in liver lesions. The highest dose of product was significantly more effective than the others and thrombin. Application of high doses of TT-173 in rats did not cause any local or systemic alterations. Absorption into blood stream was negligible and no immunogenic reaction against the product was detected.Conclusions: TT-173 shows favorable pharmacodynamic properties for improving hemostasis in partial liver resection which support further investigation of the product in this surgical indication.

Identification of a Novel Bone Marrow Cell-Derived Accelerator of Fibrotic Liver Regeneration Through Mobilization of Hepatic Progenitor Cells in Mice.

Granulocyte colony stimulating factor (G-CSF) has been reported to ameliorate impaired liver function in patients with advanced liver diseases through mobilization and proliferation of hepatic progenitor cells (HPCs). However, the underlying mechanisms remain unknown. We previously showed that G-CSF treatment increased the number of bone marrow (BM)-derived cells migrating to the fibrotic liver following repeated carbon tetrachloride (CCl4 ) injections into mice. In this study, we identified opioid growth factor receptor-like 1 (OGFRL1) as a novel BM cell-derived accelerator of fibrotic liver regeneration in response to G-CSF treatment. Endogenous Ogfrl1 was highly expressed in the hematopoietic organs such as the BM and spleen, whereas the liver contained a relatively small amount of Ogfrl1 mRNA. Among the peripheral blood cells, monocytes were the major sources of OGFRL1. Endogenous Ogfrl1 expression in both the peripheral blood monocytes and the liver was decreased following repeated CCl4 injections. An intrasplenic injection of cells overexpressing OGFRL1 into CCl4 -treated fibrotic mice increased the number of HPC and stimulated proliferation of hepatic parenchymal cells after partial resection of the fibrotic liver. Furthermore, overexpression of OGFRL1 in cultured HPC accelerated their differentiation as estimated by increased expression of liver-specific genes such as hepatocyte nuclear factor 4α, cytochrome P450, and fatty acid binding protein 1, although it did not affect the colony forming ability of HPC. These results indicate a critical role of OGFRL1 in the mobilization and differentiation of HPC in the fibrotic liver, and administration of OGFRL1-expressing cells may serve as a potential regenerative therapy for advanced liver fibrosis. Stem Cells 2019;37:89-101.

Preliminary Evaluation of Thulium Doped Fiber Laser in Pig Model of Liver Surgery.

Partial liver resection is a treatment of choice for liver tumors; the range of parenchyma excision varies from a small part of the tissue surrounding the neoplasm up to 70% of the organ. One of the major concerns during liver resection is blood loss. Thulium lasers which are characterized by the length of emission wave corresponding to a peak absorption of water create a new possibility of cutting tissues efficiently with minimal thermal damage and concurrently providing a good hemostasis control. The aim of our study was to evaluate an impact of liver transection with thulium doped fiber laser on an intraoperative bleeding and histopathological changes during postoperative period in swine model. Ten animals were subjected to open surgery partial liver resection and an incision of liver tissue with an all-fiber, diode-pumped, and continuous-wave Tm3+-doped fiber laser emitting 37.4 W of output power at ~1.94 μm wavelength. The macroscopic and histopathological evaluation was performed intraoperatively as well as 7 and 14 days after surgery. Macroscopically almost no bleeding was observed during surgery and no signs of bleeding were stated after 7 and 14 days. Histopathological analysis of the transection margin revealed a thermal damage area ranging in depth from 620.23 ± 23.82 μm on the day of surgery to 1817.70 ± 211.98 μm after 7 days. In the samples taken intraoperatively and after 7 days a superficial zone of carbonization was visibly separated from the deeper changes. After 14 days one 765.35 μm deep zone characterized by a granulation was present. In conclusion, thulium doped fiber laser is efficacious in cutting with a narrow zone of thermal injury and provides a good hemostasis during liver transection, thus being a potential tool for oncotic liver surgery.

Locoregional Therapy With Transarterial Chemoembolization (TACE) for Stage 1A Intrahepatic Cholangiocarcinoma (ICC) Before Surgical Resection: A Case Report

Intrahepatic cholangiocarcinoma is usually treated by hepatic resection to achieve negative resection margins but only minority of patients present with early stage disease. Hepatic artery based therapies such as radioembolization (TACE) is used for locally advanced unresectable disease. We present a case of stage 1A localized ICC treated with TACE followed by radiotherapy with possible liver resection in the future. A 42 year old male with history of alcohol use disorder, diabetes mellitus and hypertension came in with right upper quadrant abdominal pain. Abdominal examination was significant for distended abdomen with epigastric tenderness. Labs revealed alanine transaminase (ALT) 72 U/L, aspartate transaminase (AST) 79 U/L, platelet count 132 k/uL, and INR of 1.0. He had a sonogram of the liver which revealed a complex left hepatic lobe lesion with peripheral vascularity, so magnetic resonance imaging (MRI) of abdomen was done which showed cirrhosis with portal hypertension and 2.6 x 2.3 cm lesion involving segment II and III (Figure 1). His viral hepatitis panel was negative, and CA 19-9 was 36.8 U/ml. He underwent EGD and colonoscopy which revealed no mass. Interventional radiology (IR) guided liver biopsy of mass ICC. Patient underwent IR guided TACE with 75 mg of Doxorubicin beads administered into segmental branch of right hepatic artery the tumor (Figure 2) followed by split beam radiation therapy (SBRT). Repeat CT scan of abdomen done 7 months post TACE has not shown recurrent disease (Figure 3).2328_A Figure 1. MRI abdomen showing 2.6 x 2.3 cm lesion involving segment II and III of liver (red arrow) before TACE procedure2328_B Figure 2. Cone beam CT imaging (right) during TACE procedure showing chemotherapy beads being administered near tumor site by catheter (red arrow) & contrast enhancement of tumor site (left) on digital subtraction angiography (DSA) imaging.2328_C Figure 3. CT abdomen showing post treatment tumor with surrounding peripheral region of hyper density representing post TACE changes (red arrow).Intrahepatic tumors derive blood supply from hepatic artery rather than portal vein. This has led to development of TACE which involves elimination of tumor's blood supply by particle embolization and/or cytotoxic chemotherapy infusion into the branch of hepatic artery that feeds the tumor. Such therapies, particularly radioembolization, appear promising for patients with locally advanced unresectable ICC. Partial hepatectomy is the treatment of choice for small peripheral ICC. In our case due to patient's current heavy alcohol use and compensated cirrhosis, partial hepatectomy was thought to confer a very high risk for hepatic decompensation postoperatively. So, he was successfully treated with TACE followed by radiotherapy, with plan of left hepatic resection once he is abstinent from alcohol. Our case demonstrates the effectiveness of TACE for ICC which cannot undergo partial liver resection due to his alcoholic cirrhosis.

MiR-155 Aggravates Liver Ischemia/reperfusion Injury by Suppressing SOCS1 in Mice

Liver ischemia/reperfusion injury (IRI) occurs during partial liver resection and liver transplantation. Activation of Toll-like receptors (TLRs) is a key event triggered by a range of proinflammatory cytokines during liver I/R. Although it has been reported that miR-155 takes part in both innate and adaptive immune responses, the potential role of miR-155 in liver IRI remains unknown. In this study, we found that expression of miR-155 was upregulated during liver I/R by many inflammatory cytokines, and forced expression of miR-155 aggravated hepatocyte injury following liver I/R both in vivo and in vitro. Mice transfected with Ago-miR-155—a chemically modified miR-155—showed enhanced liver severity compared to those transfected with negative control miRNA by inhibiting the expression of SOCS1, the target of miR-155. Thus by the inhibition of SOCS1, the overexpression of miR-155 promoted activation of NF-κB, and elevating the production of proinflammatory cytokines, such TNF-α and IL-6. In conclusion, miR-155 aggravates liver I/R injury in vivo and hepatocyte hypoxia/reoxygenation injury by suppressing the expression of SOCS1.

Brg1 positively regulates liver regeneration after partial hepatectomy in mice

Introduction: Brahma-related gene-1 (Brg1) is the specific ATPase of switch/sucrose nonfermentable chromatin-remodeling complex. Liver regeneration is activated spontaneously after injury and organized based on a strong proliferation rate. Up to the present, little is known on how Brg1 orchestrates liver regeneration. The aim of the study was to investigate the role of Brg1 in liver regeneration following partial liver resection in mice. Methods: We used a hepatocyte-specific Brg1 gene knockout mouse model performing a 70% partial hepatectomy (PH) to analyse the role of Brg1 in liver regeneration. Liver regeneration was analysed by liver/body weight ratio and cell proliferation rate. Different cellular pathways were analysed by RNA sequencing. Results: It was shown that in wildtype mice the expression of Brg1 was significantly upregulated after PH. Liver/body ratio was significantly lower in hepatocyte-specific Brg1 gene knockout mice 48h post operation. In addition, proliferation rate of the hepatocytes was significantly higher in wildtype mice after PH compared to the proliferation rate of hepatocyte-specific Brg1 gene knockout mice. RNA sequencing showed that the expression of cell cycle genes was significantly modulated by Brg1 in order to regulate liver regeneration. Conclusion: The results of this study underline the important role of Brg1 in liver regeneration by promoting proliferation caused by modulating different cell cycle genes. Particular the new molecular insights improve the understanding of the role of Brg1 in liver proliferation and may provide a potential target for future therapeutic treatments.

Incidental intraoperative multiple bile duct adenomas found in conjunction with hepatocellular carcinoma

Literature reviews from 1999-2016 determined bile duct adenoma (BDA) to be a very rare benign tumor. BDA usually presents as a single nodular lesion, most often found incidentally and is very difficult to distinguish from hepatocellular carcinoma (HCC) on imaging. We present a case of multiple BDAs in a patient with a known HCC. Patient is a 65-year-old male, non-cirrhotic, cured hepatitis C after Harvoni treatment, with one 4.0 cm lesion found on CT in segment 6. Due to the difficulty of diagnosis based on CT and MRI, biopsy was performed and confirmed HCC. Intra-operatively four other nodular lesions, in addition to the 4.0 cm HCC, were found involving both lobes of the liver surface. Sizes varied from 3 to 7 mm, intraoperative ultrasound did not view other lesions. Intraoperative diagnosis was one HCC with four other small HCCs, possible HCC intrahepatic metastasis. Partial liver resection with several liver wedge resections was performed, all lesions were resected and the patient recovered well. Pathology results showed 4cm HCC in segment 6 and four small (< 1cm) BDAs of segments 2, 3, 6, and 7. BDA is a rare benign liver tumor, usually a small (< 5mm) singular lesion and rarely presents together with HCC. Our case showed multiple BDAs can coexist with HCC. From our literature search, this has never been reported. This is the first case of multiple BDAs in conjunction with HCC. Increased knowledge and awareness is essential to appropriately diagnose and treat patients.

Treatment of hepatocellular carcinoma in the cirrhotic and non-cirrhotic liver

The treatment of hepatocellular carcinoma (HCC) includes surgical, interventional and systemic approaches. This review highlights the importance of surgical treatment approaches in the multimodal treatment of HCC, based on the currently available literature, corresponding German guidelines as well as current developments in organ donation in Germany. Curative treatment options for HCC include liver transplantation, partial liver resection, and local ablative procedures depending on the lesion size. In the case of an early HCC in acirrhotic liver fulfilling the Milan criteria, liver transplantation is the treatment of choice. In view of the organ shortage in Germany and improved results after partial liver resection, surgery can alternatively be performed in patients with asufficient liver function. In selected patients with multinodular HCC, regional lymph node metastases or macrovascular invasion, the possibility of liver resection must be decided on an individual basis; however, the latter two criteria are contraindications for transplantation. Local ablative procedures can be considered as an alternative to resection in selected patients with early solitary HCC. Surgery of HCC in the non-cirrhotic liver with a curative intent is guided by the general principles of oncological liver surgery. Curative treatment options for HCC include liver transplantation, partial liver resection and local ablative procedures. Current developments in the area of organ donation and technical advances in minimally invasive liver surgery should be included in decision-making in tumor boards.

Intercostal and Glissonian Pedicle Approach in Laparoscopic Liver Resection for Bilobar Tumors

BackgroundBilobar liver metastasis is challenging for laparoscopic liver resection. Especially, subphrenic liver tumors in S7 or S8 are technically difficult to be resected out because the space is limited and the angle of instruments to lesions cannot be perpendicular.1,2 Major liver lobectomy is also challenging for laparoscopic liver resection. Glissonian pedicle approach has benefit that any variation of vascular and bile duct elements does not need to be considered in the hepatoduodenal ligament under the hilar plate. Glissonian pedicle approach is simpler and faster than individual dissection of hepatoduodenal ligament. MethodsThis video illustrates a hand-assisted laparoscopic left lobectomy and partial liver resection of S8 in a 48-year-old male with metastatic colorectal carcinoma to the liver. He received 6 cycle of FOLFOX as neoadjuvant chemotherapy. The patient was positioned in semi left lateral decubitus so that a lesion in S8 was easily approached. A tumor in S8 was approached after right lobe mobilization. The liver resection was performed by a harmonic scalpel. A 5-mm balloon port was placed in 6th intercostal space to approach the lesion perpendicular. For left hepatectomy, glissonian pedicle approach was applied to control vascular inflow. Dissections was performed at bifurcation on the right glissonian and left glissonian pedicles. Dissection direction to the left side was above hepatogastric ligament. The tunnel was created including all left glissonian sheath, and a vessel loop was taped. An endovascular stapler was inserted and fired with dividing the left glissonian pedicle as en bloc. Hepatic parenchymal dissection was performed by the harmonic scalpel. Left hepatic vein was divided using an endoscopic vascular stapler. The specimens were removed from a hand-port. ResultsThe operative time was 290 min. Blood loss was 250 ml, and no blood transfusion was required. He resumed a regular diet the next day and was discharged on postoperative day 4. ConclusionsIntercostal approach is useful for subphrenic liver tumors, and glissonian pedicle approach is also useful for major lobectomy for laparoscopic liver resection.