Yukihiro Okuda

An Experimental Study on the Relationship Among Airway Pressure, Pneumoperitoneum Pressure, and Central Venous Pressure in Pure Laparoscopic Hepatectomy.

Objectives:To determine optimal settings for airway pressure (AWP), pneumoperitoneum pressure (PPP), and central venous pressure (CVP) in pure laparoscopic hepatectomy. Background:High PPP is often employed to control bleeding from the hepatic vein during pure laparoscopic hepatectomy; however, there is a risk of pulmonary gas embolism. We noted that decreases in AWP were often effective. Methods:After establishing carbon dioxide pneumoperitoneum in 6 male piglets and maintaining PPP at 25 mmHg, CVP was measured 3 times at each of 9 levels of airway pressure, which was increased in increments of 5 cmH2O from 0 to 40 cmH2O. CVP was measured in the same manner by maintaining PPP at 20, 15, 10, 5, and 0 mmHg, and in laparotomy. Correlation and regression analyses were performed among airway pressure, CVP, and pneumoperitoneum pressure. Results:Positive correlations were observed between AWP and CVP and between PPP and CVP (P < 0.001). Under high airway pressure, CVP was persistently higher than pneumoperitoneum pressure. Under low airway pressure, CVP did not increase or often decreased when PPP was higher than CVP. Conclusions:By increasing pneumoperitoneum pressure, bleeding from the hepatic vein cannot be controlled under high airway pressure, but can be controlled under low airway pressure. However, under low airway pressure, the risk of pulmonary gas embolism increases when PPP is higher than CVP. We consider that reducing AWP is also effective for controlling bleeding from the hepatic vein and safer than increasing pneumoperitoneum pressure.

Usefulness of operative planning based on 3-dimensional CT cholangiography for biliary malignancies

BACKGROUND The complexity of hepatic hilar anatomy is an obstacle to precise diagnosis of tumor spread and appropriate operative planning for biliary malignancies. Three-dimensional (3D) cholangiography and angiography may overcome this obstacle and facilitate curative resection. The objective of this study was to evaluate the impact of 3D CT cholangiography on operative planning and outcomes of biliary malignancies. METHODS From 2009 to 2014, 3DCT cholangiography was performed on 49 patients with biliary malignancies requiring major hepatic resection and extrahepatic bile duct resection. The 3D cholangiogram was merged with 3D angiography and portography to create an all-in-one 3D image of the hepatic hilum. The cutting line of the bile duct and the type of liver resection were determined based on the spatial relationship between tumor spread and the landmark vessels. The necessity of vascular reconstruction was also evaluated. Preoperative imaging and operative findings were compared. Operative curability was compared with that of the historical cohort before the introduction of 3D cholangiography. RESULTS Histologic examination of the bile duct stump showed a negative margin in 39 (80%), carcinoma in situ in 7 (14%), and invasive cancer (IC) in 3 patients (6%) on the first cutting. The IC-free rate (94%) on the first cutting was superior to that in the historical cohort (80%; P = .02). The necessity for portal and arterial reconstruction was predicted with 98 and 94% accuracy, respectively. CONCLUSION We found 3D cholangiography to provide accurate information about hilar anatomy and plays a role in facilitating adequate operative planning.

Usefulness of Mac-2 Binding Protein Glycosylation Isomer for Prediction of Posthepatectomy Liver Failure in Patients With Hepatocellular Carcinoma.

Objective: The aim of this study was to evaluate the usefulness of the Mac-2 binding protein glycosylation isomer (M2BPGi) for the prediction of posthepatectomy liver failure (PHLF) in hepatocellular carcinoma (HCC) patients. Summary Background Data: M2BPGi is a novel serum marker of liver fibrosis. The usefulness of M2BPGi for the prediction of PHLF has not been evaluated. Methods: Clinicopathological data were analyzed in 138 HCC patients who underwent liver resection between August 2011 and November 2014. PHLF was evaluated according to the definition of the International Study Group of Liver Surgery. Performance of preoperative parameters in predicting PHLF was determined using receiver operating characteristic (ROC) analysis. Results: Serum M2BPGi level correlated with the METAVIR fibrosis score. M2BPGi levels of hepatitis C virus (HCV)-positive patients were significantly higher than those of HCV-negative patients, even in the same fibrosis stage. PHLF ≥ Grade B developed in 19 patients (13.8%). The area under the ROC curve (AUROC) of M2BPGi for the prediction of PHLF ≥ Grade B was 0.71. In multivariate analysis, M2BPGi [odds ratio (OR): 2.08, 95% confidence interval (CI) 1.28–3.55], platelet count (OR: 0.39, 95% CI 0.18–0.80), and resection rate (OR: 2.71, 95% CI 1.46–5.40) were the significant factors associated with PHLF ≥ Grade B. The AUROC of the PHLF index defined by these factors was 0.81. Notably, in patients with HCV infection, the predictive ability of M2BPGi for PHLF (AUROC 0.85) was the best among the preoperative parameters. Conclusions: M2BPGi is a useful predictor of PHLF, especially in patients with HCV infection.

Pancreatic Stellate Cells Have Distinct Characteristics From Hepatic Stellate Cells and Are Not the Unique Origin of Collagen-producing Cells in the Pancreas

Objectives The origin of collagen-producing myofibroblasts in pancreatic fibrosis is still controversial. Pancreatic stellate cells (PSCs), which have been recognized as the pancreatic counterparts of hepatic stellate cells (HSCs), are thought to play an important role in the development of pancreatic fibrosis. However, sources of myofibroblasts other than PSCs may exist because extensive studies of liver fibrosis have uncovered myofibroblasts that did not originate from HSCs. This study aimed to characterize myofibroblasts in an experimental pancreatic fibrosis model in mice. Methods We used transgenic mice expressing green fluorescent protein via the collagen type I &agr;1 promoter and induced pancreatic fibrosis with repetitive injections of cerulein. Results Collagen-producing cells that are negative for glial fibrillary acidic protein (ie, not derived from PSCs) exist in the pancreas. Pancreatic stellate cells had different characteristics from those of HSCs in a very small possession of vitamin A using mass spectrometry and a low expression of lecithin retinol acyltransferase. The microstructure of PSCs was entirely different from that of HSCs using flow cytometry and electron microscopy. Conclusions Our study showed that characteristics of PSCs are different from those of HSCs, and myofibroblasts in the pancreas might be derived not only from PSCs but also from other fibrogenic cells.

Low Preoperative Platelet Count Predicts Risk of Subclinical Posthepatectomy Liver Failure in Right Lobe Donors for Liver Transplantation

Living donor right hepatectomy (LDRH) is a common procedure in adult‐to‐adult living donor liver transplantation, but it is associated with a higher risk of posthepatectomy liver failure (PHLF) compared with left hepatectomy because of a smaller remnant. We identified risk factors for PHLF and other complications in LDRH, verified the appropriateness of the criteria, and explored the possibility of adjusting the minimum remnant liver volume (RLV) based on individual risk. Between October 2005 and November 2017, 254 donors undergoing LDRH at Kyoto University Hospital were enrolled. Clinical data were collected retrospectively. All complications were graded according to the Clavien‐Dindo classification. No donors had grade 4 or 5 complications or clinically significant grade B or C PHLF. Grade A PHLF occurred in 30 donors (11.8%). Male sex (P = 0.01), lower preoperative platelet count (PLT; P = 0.01), higher prothrombin time–international normalized ratio (P = 0.03), higher total bilirubin (P = 0.01), smaller RLV (P = 0.03), and greater blood loss (P = 0.04) were associated with increased risk of PHLF in the univariate analysis, whereas PLT, RLV, and blood loss remained significant in the multivariate analysis. Grade 2 or 3 complications were observed in 32 (12.6%) donors. Higher body mass index (BMI; P = 0.002) and larger blood loss (P = 0.02) were identified as risk factors for complications (Clavien‐Dindo grade ≥ 2) in univariate analysis. Only BMI remained significant in the multivariate analysis. In conclusion, LDRH is performed safely with acceptable morbidity under the current criteria. Minimum RLV may be marginally adjusted by PLT and reducing intraoperative blood loss minimizes PHLF risk. Liver Transplantation 00 000–000 2018 AASLD.

CAAT/enhancer binding protein–homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice

Ischemia/reperfusion injury (IRI) is one of the main causes of liver dysfunction after liver surgery. Involvement of endoplasmic reticulum (ER) stress in various diseases has been demonstrated, and CAAT/enhancer binding protein–homologous protein (CHOP) is a transcriptional regulator that is induced by ER stress. It is also a key regulator of ER stress‐mediated apoptosis. The aim of this study was to investigate the role of CHOP in liver IRI. Wild type (WT) and CAAT/enhancer binding protein–homologous protein knockout (CHOP–/–) mice were subjected to 70% liver warm ischemia/reperfusion for 60 minutes. At different times after reperfusion, liver tissues and blood samples were collected for evaluation. Induction of ER stress including CHOP expression was ascertained. Liver damage was evaluated based on serum liver enzymes, liver histology, and neutrophil infiltration. Hepatocyte death including apoptosis was assessed. Liver warm IRI induced ER stress in both WT and CHOP–/– mice. In addition, CHOP expression was up‐regulated in WT mice. At 6 hours after reperfusion, liver damage was attenuated in CHOP–/– mice. On the basis of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick‐end labeling staining, apoptotic and necrotic cells were significantly reduced in CHOP–/– mice. CHOP deficiency also reduced the cleavage of caspase 3 and expression of the proapoptotic protein B cell lymphoma 2–associated X protein. Liver IRI induces CHOP expression, and CHOP deficiency attenuates liver IRI by inhibiting apoptosis. Elucidation of the function of CHOP in liver IRI may contribute to further investigation for a therapy against liver IRI associated with the ER stress pathway. Liver Transplantation 24 645–654 2018 AASLD.

Effect of mapping biopsy on surgical management of cholangiocarcinoma: YAO et al.

The effect of endoscopic transpapillary mapping biopsy (MB) on decision‐making of surgical indications, selecting surgical procedures, or operative outcomes remains unclear.