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BackgroundLimited studies have reported the actual learning process of laparoscopic liver resection (LLR). This study aimed to chronologically evaluate our 15 years’ experience of LLR.MethodsAll consecutive LLRs between 2006 to 2020 were retrospectively analyzed. The time period was divided into three groups; first (2006–2010), second (2011–2015), and third (2016–2020) period. The primary endpoint of this study was a composite of overall (Clavien–Dindo grade ≥ II) or major (grade ≥ IIIa) postoperative complications within 30 days. Using the IWATE criteria (four difficulty levels based on six indices), LLR was categorized as basic (< 7 points) and advanced (≥ 7 points) one. All analyses were performed based on the intention-to-treat principles.ResultsDuring the study period, a total of 382 LLRs were gradually performed (first period, n = 54; second period, n = 114, and third period, n = 214). Low incidences of overall and major complications were maintained (9.3, 10.5, and 7.0%, p = 0.514, and 1.9, 2.6, and 2.3%, p = 1.000). Meanwhile, pure LLRs (i.e., LLRs without hand-assisted or hybrid approach) and advanced LLRs were increasingly performed in 25 (46.3%), 71 (62.3%), and 205 (95.8%) patients (p < 0.001) and 3 (5.6%), 18 (15.8%), and 58 (27.1%) patients (p < 0.001), respectively.ConclusionsThis study suggests that stepwise approach from basic to advanced procedures and use of hand-assisted or hybrid approach during the early phases for starting LLR practice may allow for maintaining low morbidity in specialized center.

Background Nonalcoholic fatty liver disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Kupffer cells play a central role in promoting hepatic inflammation, which leads to the development of NASH. We investigated the anti-inflammatory effect of hepatic vagus-mediated stimulation of the α7 nicotinic acetylcholine receptor (α7nAChR) on Kupffer cells in NASH pathogenesis. Methods Wild-type (WT) mice undergoing hepatic vagotomy (HV) were fed a methionine- and choline-deficient (MCD) diet for 1 week. α7nAChR knockout (α7KO) chimeric mice were generated by transplanting α7KO bone marrow cells into irradiated and Kupffer cell-deleted WT recipients. Kupffer cells were isolated from WT mice and treated with α7nAChR agonist under stimulation by lipopolysaccharide and/or palmitic acid. Results HV aggravated MCD diet-induced NASH in both steatosis and inflammation. The hepatic inflammatory response, including the upregulation of tumor necrosis factor alpha (TNFα), interleukin (IL)-12, and monocyte chemoattractant protein 1 (MCP-1), was accelerated in HV mice, accompanied by the downregulation of PPARα pathway genes. Kupffer cells were highly activated via the phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-κB) in MCD diet-fed HV mice. The α7nAchR agonist suppressed the inflammatory response of primary Kupffer cells induced by lipopolysaccharide and palmitic acid by attenuating the NF-κB cascade. α7KO chimeric mice fed an MCD diet for 1 week developed advanced NASH with highly activated Kupffer cells. The hepatic expression of TNFα, IL-12, and MCP-1 was upregulated in α7KO chimeric mice, accompanied by abnormal lipid metabolism. Conclusions Hepatic vagus activity regulates the inflammatory response of Kupffer cells via α7nAChR in NASH development.

Background In laparoscopic anatomic liver resection, an increasingly common procedure, the hepatic vein-guided approach is widely used although the hepatic vein tributaries can be a major source of bleeding in the event of inadvertent injury. This report describes the anatomy of the middle hepatic vein (MHV) including its tributaries based on reconstructed three-dimensional computed tomography images and provides anatomic data to enable safe middle hepatic vein-guided liver resection. Methods Following simulation modeling of the hepatic vasculatures, reconstructed MHV data was pooled from 35 healthy liver donors. Yields of the MHV tributaries were analyzed to enable MHV-guided liver resection. Results A total of 252 tributaries were identified in the 35 donors. The MHV yielded fewer tributaries from its anterior and posterior aspects than from its right-side and left-side aspects (40 [15.9%], 13 [5.2%], 93 [36.9%], and 106 [42.1%], respectively). The MHV tributaries from the anterior and posterior aspects were smaller in diameter than those from the right-side and left-side aspects (median, 3.0, 2.0, 4.8, and 4.0 mm, respectively). Discussion Our simulation revealed that MHV dissection from the anterior or posterior aspect poses a lower risk of injury to the MHV tributaries compared to dissection from either lateral aspect. In addition, MHV dissection from the anterior or posterior aspect allows for safer identification and isolation of the thick MHV tributaries originating from the lateral aspects. Ideally, the anterior or posterior aspect of the MHV should be accessed and exposed before the lateral aspects are dissected to minimize the risk of MHV tributary injury.

Background: Multidisciplinary treatment of hepatocellular carcinoma (HCC) has made notable advancements with the emergence of novel agents for systemic therapies, including receptor tyrosine kinase inhibitors (TKIs) and cancer immuno-oncology therapy (IO) utilizing immune checkpoint inhibitors. Although each of these regimens is effective as monotherapy for advanced HCCs, combining them with local treatments (LRT), such as transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and radiotherapy (RT), provides an additional antitumor effect. The emergence of novel systemic therapies has given rise to anticipation for the development of multidisciplinary treatments with a combination of systemic therapy and LRT, which aim to achieve curative-intent resection and improve long-term prognosis after resection. Summary: Perioperative combination therapy, a combination of multiple treatment modalities including systemic therapy (TKI and/or IO) and LRT (TACE, HAIC, or RT), is attracting attention as a potentially useful approach for multidisciplinary curative-intent surgical resection or ablation. Currently, there is no evidence-based guidance regarding selection criteria and optimal regimens for perioperative combination therapy. The definition of oncological resectability for HCC is being pursued to establish the indication and protocol for perioperative combination therapy, which broadly encompasses conversion as well as neoadjuvant and adjuvant therapy for intermediate-to-advanced HCC. Key Messages: Perioperative combination therapy, which positions curative-intent surgical resection or ablation within the combination of multiple modalities including systemic therapy and LRT, provides perspectives for improving the long-term prognosis of patients with initially unresectable HCC and borderline resectable HCC with a high risk of recurrence.

Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of hepatectomy‐related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. The definition of PHLF proposed by the International Study Group for Liver Surgery has gained acceptance as a standard grading criterion. Liver function can be estimated using a variety of parameters, including routine blood biochemical examinations, clinical scoring systems, dynamic liver function tests, liver stiffness and fibrosis markers, and imaging studies. The Child–Pugh score and model for end‐stage liver disease scores are conventionally used for estimating liver decompensation, although the alternatively developed albumin‐bilirubin score shows superior performance for predicting hepatic dysfunction. Indocyanine green clearance, a dynamic liver function test mostly used in Japan and other Asian countries, serves as a quantitative estimation of liver function reserve and helps determine indications for surgical procedures according to the estimated risk of PHLF. In an attempt to improve predictive accuracy, specific evaluation of liver fibrosis and portal hypertension has gained popularity, including liver stiffness measurements using ultrasonography or magnetic resonance elastography, as well as noninvasive fibrosis markers. Imaging modalities, including Tc‐99m‐labeled galactosyl serum albumin scintigraphy and gadolinium‐enhanced magnetic resonance imaging, are used for preoperative evaluation in combination with liver volume. This review aims to provide an overview of the usefulness of current options for the preoperative assessment of liver function in predicting PHLF. Posthepatectomy liver failure remains a major cause of hepatectomy‐related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. Multiple studies have evaluated the predictive performance of various preoperative parameters, which are broadly categorized as clinical scores based on routine blood tests, dynamic liver function tests, liver stiffness and noninvasive fibrosis markers, liver function imaging, and biomarkers for portal hypertension. This review aims to provide an overview of the utility of current options for preoperative assessment of liver function and the performance of each parameter in predicting PHLF.

Recently, non‐B non‐C chronic liver diseases, including alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), have markedly increased worldwide. Liver transplantation (LT) is an effective curative therapy for hepatocellular carcinoma (HCC) as well as decompensated liver cirrhosis. In Japan, where the source of liver grafts is strongly dependent on living donors, efforts have been made to unify the indications for eligibility of HCC patients for LT, leading to the development of 5‐5‐500 criteria. Along with the expansion of eligibility for LT, the current changing trends in underlying liver diseases of LT recipients, which are related to the rising tide of non‐B non‐C cirrhosis and HCC, are highlighting the importance of peri‐transplant management of patients with various comorbidities. The post‐LT prognosis of patients with ALD is significantly affected by de novo malignancies and metabolic syndrome‐related complications as well as posttransplant alcohol relapse. NAFLD/NASH patients often suffer from obesity, type 2 diabetes mellitus, and other metabolic syndrome‐related disorders, and nonneoplastic factors such as cardiovascular events and recurrence of NAFLD/NASH have a significant impact on post‐LT outcomes. Patient management in the peri‐transplant period as well as risk assessment for LT are key to improving post‐LT outcomes in the era of a growing number of cases of LT for non‐B non‐C liver diseases. Recently, the cases of LT for non‐B non‐C cirrhosis and HCC have been increasing in Japan as well as worldwide. Perioperative management of non‐B non‐C liver disease is problematic due to various risk factors, including alcohol consumption and metabolic syndrome‐related risks, such as obesity and diabetes mellitus. This article aims to review the current status and issues of LT focusing on non‐B non‐C liver diseases, including HCC.\" cd_value_code=\"text

INTRODUCTION: Most splenic tumors are benign; however, it is essential to differentiate them from malignant tumors, such as malignant lymphoma and metastatic tumors. Sclerosing angiomatoid nodular transformation (SANT) is a relatively rare benign tumor that has been reported recently. Splenectomy is performed in most cases of SANT because of the challenges associated with a definitive diagnosis. However, in some cases, SANT can be diagnosed through endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and these cases are subsequently followed up. In this report, we present 2 cases of splenic SANT that underwent laparoscopic resection. In Case 1, atypical imaging findings required EUS-FNA for further evaluation. Case 2 exhibited typical imaging findings of SANT, and therefore, EUS-FNA was not performed.CASE PRESENTATION: Case 1: A 47-year-old female was found to have a 26 mm tumor in the spleen on abdominal ultrasonography during follow-up for gallbladder polyps. Abdominal computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-CT were performed. EUS-FNA was performed because of the high surgical risk associated with pulmonary hypertension and because hemangioendothelioma, an intermediate malignancy, was suspected. Subsequently, laparoscopic splenectomy was performed, and SANT was diagnosed. Case 2: A 46-year-old female had an incidental detection of a tumor in the spleen on CT. SANT was suspected based on CT and MRI findings. Malignancy could not be completely ruled out owing to the gradual growth of the mass; therefore, the patient was referred to our hospital for surgery. Laparoscopic splenectomy was performed, and SANT was subsequently diagnosed.CONCLUSION: SANT is a benign tumor that is difficult to diagnose; however, in some cases, it can be diagnosed using EUS-FNA. We report 2 cases of SANT of the spleen that underwent laparoscopic resection. In cases where the diagnosis is confirmed through imaging or histological examination, disease management with follow-up and without surgery is a possible alternative.

Backgrounds In the era of multidisciplinary treatment strategy, resectability for hepatocellular carcinoma (HCC) should be defined. This study aimed to propose and validate a resectability classification of HCC. Methods We proposed following the three groups; resectable-(R), borderline resectable-(BR), and unresectable (UR)-HCCs. Resectable two groups were sub-divided according to the value of indocyanine green clearance of remnant liver (ICG-Krem) and presence of macrovascular invasion (MVI); BR-HCC was defined as resectable HCCs with MVI and/or ICG-Krem≥0.03–<0.05, and R-HCC was the remaining. Consecutive patients with HCC who underwent liver resection (LR) and non-surgical treatment(s) (i.e., UR-HCC) between 2011 and 2017 were retrospectively analyzed to validate the proposed classification. Results A total of 361 patients were enrolled in the study. Of these, R-, BR- and UR-HCC were found in 251, 46, and 64 patients, respectively. In patients with resected HCC, ICG-Krem≥0.05 was associated with decreased risk of clinically relevant posthepatectomy liver failure ( p =0.013) and the presence of MVI was associated with worse overall survival (OS) ( p <0.001). The 3–5-years OS rates according to the proposed classification were 80.3, and 68.3% versus 51.4, and 35.6%, in the R and BR groups, respectively (both p <0.001). Multivariate analysis showed BR-HCC was independently associated with poorer OS ( p <0.001) after adjusting for known tumor prognostic factors. Meanwhile, BR-HCC was associated with benefit in terms of OS compared with UR-HCC ( p <0.001). Conclusion Our proposal of resectability for HCC allows for stratifying survival outcomes of HCC and may help to determine treatment strategy.

Background Primary biliary cholangitis (PBC) is a chronic, progressive liver disease associated with dyslipidemia. There is a consensus that PBC does not accelerate coronary artery disease despite high cholesterol levels, so the screening test for the coronary artery is not routinely performed before liver transplantation (LT). To date, no report has described the potential risk of PBC-related dyslipidemia for developing acute coronary syndrome (ACS) after LT. Case presentation A 40-year-old Asian female with a known history of PBC underwent ABO-incompatible living-donor LT, with her husband as the donor. Although she had high cholesterol and triglyceride levels that were refractory to medications, she passed all routine preoperative examinations, including cardiopulmonary function tests and infection screenings. One week after LT, she developed ACS with 90% stenosis of both the left anterior descending artery and left circumflex artery. Emergent stent implantation was successfully performed followed by dual antiplatelet therapy. The long history of PBC and associated severe dyslipidemia for 10 years would have accelerated the atherosclerosis, causing latent stenosis in the coronary artery. Inapparent stenosis might have become apparent due to unstable hemodynamics during the acute phase after LT. Conclusions PBC-related dyslipidemia potentially brings a risk for developing ACS after LT. This experience suggests that the preoperative evaluation of the coronary artery should be considered for high-risk patients, especially those who have drug-resistant dyslipidemia.