Glisson's Sheath Research Articles

A novel image-guided laparoscopic liver resection with integrated fluorescent imaging and artificial intelligence: A preliminary study.

568 Background: Technology innovations improve surgical techniques. ICG fluorescence imaging is beneficial for real time navigation tool during surgery and enables accurate surgery. Recently, the prediction of anatomical structures by artificial intelligence (AI) is expected to support surgeons as navigation tool. We developed a visual-support AI system to perform the laparoscopic liver resection (LLR) using ICG fluorescence imaging and AI technology. Methods: Procedure: ICG fluorescence imaging was used for liver mapping and securing surgical margin. AI model development and evaluation: Over 430 images extracted from 13 videos of LLR for hepatocellular carcinoma and colorectal liver metastasis was used to develop and evaluate the AI algorithm at Anaut Inc. The annotation was performed on video frames capturing a LLR performed by 2 surgeons for hepatic vein and Glisson sheath. The performance of AI on unlearned LH videos was evaluated quantitatively using Intersection-Over-Union (IOU) and Dice coefficients, and qualitatively on a five-point scale (from 1 to 5) by 10 hepato-biliary-pancreatic surgeons using 35 randomly extracted still images from the analyzed videos. Results: ICG fluorescence imaging could visualize the demarcation line and clarified the boundaries of the liver transected surface. The hepatic veins and Glisson sheath were appeared in the parenchymal transection plane during segmentectomy and securing surgical margin, and this AI system enabled to recognize and display these vascular structures through color-coding under bleeding and ICG fluorescent imaging without visual discrepancies. The AI model accurately recognized vascular structures of any size (IoU=0.33, Dice=0.44) in real-time (<0.12 s) In the qualitative evaluation by surgeons, the mean sensitivity score was 4.10 ± 0.92 (range 3.61–4.76). Additionally, this AI system also recognized vascular structures during robot-assisted liver resection. Conclusions: This is the first study demonstrating that AI can precisely identify vascular structures during LLR. Novel image-guided LLR using ICG fluorescent imaging and artificial intelligence is expected to provide safer and more accurate LLR, thereby contributing to reduce complications and improve survival rates.

Macrophage pathology in hepatotoxicity.

The liver is the most important organ that metabolizes and detoxifies chemicals taken into the body. Therefore, there is always a risk of liver damage owing to the toxic effects of chemicals. The mechanisms of hepatotoxicity have been studied extensively and deeply based on toxic effects of chemicals themselves. However, it is important to note that liver damage is variously modified by the patho-biological reactions evoked mainly via macrophages. Macrophages appearing in hepatotoxicity are evaluated by the M1/M2 polarization; M1 macrophages promote tissue injury/inflammation, whereas M2 macrophages show anti-inflammatory action including reparative fibrosis. The "portal vein-liver barrier" regulated by Kupffer cells and dendritic cells in and around the Glisson's sheath may be related to the initiation of hepatotoxicity. In addition, Kupffer cells exhibit the two-sides of functions (that is, M1 or M2 macrophage-like functions), depending on microenvironmental conditions which may be raised in part by gut microbiota-derived lipopolysaccharide. Furthermore, damage-associated molecular patterns (DAMPs) (in particular, HMGB1) and autophagy (which degrades DAMPs) also play roles in the polarity of M1/M2 macrophages. The mutual relation of "DAMPs (HMGB-1)-autophagy-M1/M2 macrophage polarization" as the patho-biological reaction should be taken into consideration in hepatotoxicity evaluation.

Schwannoma in and around the porta hepatis: radiological features in eight cases and literature review.

Schwannomas in and around the porta hepatis (porta hepatic schwannomas) are rare benign tumors easily misdiagnosed as other pathologies, including malignancies. We aimed to evaluate their imaging features on ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT). We performed a multi-institutional retrospective study by reviewing the clinical and imaging findings of pathologically proven eight porta hepatic schwannomas (mean age, 55years; range, 38-80years; one male and seven females). Preoperative imaging included three ultrasonography, eight CT, eight MRI, and two FDG-PET/CT. All patients were asymptomatic. The mean tumor size was 61.9mm (range, 30-180mm), and all tumors demonstrated well-defined lesions on ultrasonography and their solid components showed soft tissue attenuation on non-contrast CT. MRI showed two distinct components in all cases: the component with T1-weighted hypointensities and T2-weighted hyperintensities with poor enhancement (suggestive of Antoni B histology); the component with T2-weighted hypointensities with gradually increasing enhancement (suggestive of Antoni A histology), resulting in a heterogeneous pattern on post-contrast CT or MRI (8/8, 100%). The separated deviation of surrounding bile ducts and vessels without obstruction allowed the recognition of extrahepatic localization and their benign nature. A ginger root-like morphology (2/8, 25%) seemed to be suggestive of extension along the Glisson's sheath, although this finding was not seen frequently. Recognizing imaging features such as extrahepatic location, benign nature with internal structures suggestive of Antoni A/B histology, and characteristic tumor extension may provide key diagnostic clues for porta hepatic schwannomas.

Survival prediction on intrahepatic cholangiocarcinoma with histomorphological analysis on the whole slide images

Intrahepatic cholangiocarcinoma (ICC) is cancer that originates from the liver's secondary ductal epithelium or branch. Due to the lack of early-stage clinical symptoms and very high mortality, the 5-year postoperative survival rate is only about 35%. A critical step to improve patients' survival is accurately predicting their survival status and giving appropriate treatment. The tumor microenvironment of ICC is the immediate environment on which the tumor cell growth depends. The differentiation of tumor glands, the stroma status, and the tumor-infiltrating lymphocytes in such environments are strictly related to the tumor progress. It is crucial to develop a computerized system for characterizing the tumor environment. This work aims to develop the quantitative histomorphological features that describe lymphocyte density distribution at the cell level and the different components at the tumor's tissue level in H&E-stained whole slide images (WSIs). The goal is to explore whether these features could stratify patients' survival. This study comprised of 127 patients diagnosed with ICC after surgery, where 78 cases were randomly chosen as the modeling set, and the rest of the 49 cases were testing set. Deep learning-based models were developed for tissue segmentation and lymphocyte detection in the WSIs. A total of 107-dimensional features, including different type of graph features on the WSIs were extracted by exploring the histomorphological patterns of these identified tumor tissue and lymphocytes. The top 3 discriminative features were chosen with the mRMR algorithm via 5-fold cross-validation to predict the patient's survival. The model's performance was evaluated on the independent testing set, which achieved an AUC of 0.6818 and the log-rank test p-value of 0.03. The Cox multivariable test was used to control the TNM staging, γ-Glutamytransferase, and the Peritumoral Glisson's Sheath Invasion. It showed that our model could independently predict survival risk with a p-value of 0.048 and HR (95% confidence interval) of 2.90 (1.01–8.32). These results indicated that the composition in tissue-level and global arrangement of lymphocytes in the cell-level could distinguish ICC patients' survival risk.

Development of the nervous system in mouse liver

BACKGROUNDThe role of the hepatic nervous system in liver development remains unclear. We previously created functional human micro-hepatic tissue in mice by co-culturing human hepatic endodermal cells with endothelial and mesenchymal cells. However, they lacked Glisson’s sheath [the portal tract (PT)]. The PT consists of branches of the hepatic artery (HA), portal vein, and intrahepatic bile duct (IHBD), collectively called the portal triad, together with autonomic nerves.AIMTo evaluate the development of the mouse hepatic nervous network in the PT using immunohistochemistry.METHODSLiver samples from C57BL/6J mice were harvested at different developmental time periods, from embryonic day (E) 10.5 to postnatal day (P) 56. Thin sections of the surface cut through the hepatic hilus were examined using protein gene product 9.5 (PGP9.5) and cytokeratin 19 (CK19) antibodies, markers of nerve fibers (NFs), and biliary epithelial cells (BECs), respectively. The numbers of NFs and IHBDs were separately counted in a PT around the hepatic hilus (center) and the peripheral area (periphery) of the liver, comparing the average values between the center and the periphery at each developmental stage. NF-IHBD and NF-HA contacts in a PT were counted, and their relationship was quantified. SRY-related high mobility group-box gene 9 (SOX9), another BEC marker; hepatocyte nuclear factor 4α (HNF4α), a marker of hepatocytes; and Jagged-1, a Notch ligand, were also immunostained to observe the PT development.RESULTSHNF4α was expressed in the nucleus, and Jagged-1 was diffusely positive in the primitive liver at E10.5; however, the PGP9.5 and CK19 were negative in the fetal liver. SOX9-positive cells were scattered in the periportal area in the liver at E12.5. The Jagged-1 was mainly expressed in the periportal tissue, and the number of SOX9-positive cells increased at E16.5. SOX9-positive cells constructed the ductal plate and primitive IHBDs mainly at the center, and SOX-9-positive IHBDs partly acquired CK19 positivity at the same period. PGP9.5-positive bodies were first found at E16.5 and HAs were first found at P0 in the periportal tissue of the center. Therefore, primitive PT structures were first constructed at P0 in the center. Along with remodeling of the periportal tissue, the number of CK19-positive IHBDs and PGP9.5-positive NFs gradually increased, and PTs were also formed in the periphery until P5. The numbers of NFs and IHBDs were significantly higher in the center than in the periphery from E16.5 to P5. The numbers of NFs and IHBDs reached the adult level at P28, with decreased differences between the center and periphery. NFs associated more frequently with HAs than IHBDs in PTs at the early phase after birth, after which the number of NF-IHBD contacts gradually increased.CONCLUSIONMouse hepatic NFs first emerge at the center just before birth and extend toward the periphery. The interaction between NFs and IHBDs or HAs plays important roles in the morphogenesis of PT structure.

Immunophenotypic analysis of the distribution of hepatic macrophages, lymphocytes and hepatic stellate cells in the adult rat liver.

The liver consists of parenchymal hepatocytes and non-parenchymal cells. Non-parenchymal cells, Kupffer cells, hepatic stellate cells and cholangiocytes have crucial roles in liver homeostasis and liver pathology. To establish baseline data, this study investigated immunohistochemically the distribution of non-parenchymal cells in perivenular areas (PV), periportal areas (PP) and Glisson's sheath (GS) of adult rat liver. Liver tissues were collected from the left lateral lobe of rats. CD163-positive macrophages were seen along the sinusoid of PV and PP areas, indicating Kupffer cells. Double immunofluorescence showed, Kupffer cells partly co-expressed CD68 and MHC class II antigens in the liver. The numbers of Kupffer cells were significantly high in PP areas as compared with PV or GS areas. CD68-positive exudative macrophages were highly localized in PP and GS areas and a comparatively low PV area. MHC class II-positive dendritic cells (activated macrophages) were localized mainly in GS. Granzyme B-positive NK cells were mainly localized in the Glisson's sheath. CD3-positive T cells and CD20-positive B cells were distributed along the sinusoids of the PP and PV areas of hepatic lobules. Vimentin and glial fibrillary acidic protein (GFAP)-positive hepatic stellate cells were localized along sinusoids in the hepatic lobules of the liver. Cholangiocytes reacting to cytokeratin 19 were seen on interlobular bile ducts in Glisson's sheath of the liver. This study shows that heterogeneous macrophage populations, liver-resident lymphocytes and hepatic stellate cells localized in PP and PV areas or GS areas of the liver with cells specific patterns.

Laparoscopic Anatomic Resection Guided by Indocyanine Green Fluorescence Imaging - A Single Institution Experience -

In laparoscopic anatomic resection, especially in the sub-segmentectomy of segment 8 or 7, it can be difficult to detect and dissect the targeted branch of Glisson sheath from the hepatic hilum. When that is the case, we inject dye into the targeted portal vein to stain the resection area by using an ultrasound-guided vascular access system for laparoscopic surgery. We use the Bk5000/9066 (BK medical) ultrasound machine with a built-in probe for ultrasound-guided vascular access. This system has an advanced laparoscopic ultrasound transducer that has a small hole for the needle on the tip of the probe which can draw a guideline for the needle. We also use the laparoscope Indocyanine Green (ICG) fluorescence imaging camera system (Storz). The dye is a mixture of ICG and Indigo carmine. Under guidance of ultrasonography, we detect the targeted portal vein and percutaneously insert the PTCD needle into the portal vein. Then, we slowly inject the dye observing the dyeing process with the ICG imaging camera. By using ICG together with Indigo carmine we can detect the color contrast between the area to be resected and the rest of the liver more precisely, especially when we cannot get a clear border line with Indigo carmine for whatever reason. The US-guided injecting ICG together with Indigo carmine into the targeted portal vein can draw a demarcation line more efficiently and clearly than was previously possible. This system should be useful, especially in the laparoscopic anatomic resection of the sub-segment or a smaller area.

A case of intrahepatic pancreatic pseudocyst developed as a complication of pancreatitis

Introduction: Pancreatic pseudocyst is located usually in lesser sac and peripancreatic space and is rarely developed in the liver. The intrahepatic pancreatic pseudocyst(IHPP) following acute pancreatitis is extremely rare with very limited number of clinical reports about IHPP. Methods: A 70-year-old woman was referred because of upper abdominal pain of 3 days' duration. An abdominal CT scan revealed 11x10 cm sized cystic mass in the left lateral section of liver. On EUS findings, a huge hypoechoic lesion with internal echogenicity was noted in the lesser sac. EUS-guided gastrocystostomy was performed and analysis of cystic fluid showed a high level of amylase (21,200 U/L). After the endoscopic procedure, severe abdominal pain developed and physical examination showed peritoneal irritation sign. An emergency operation was performed. Results: On operation findings, a huge cystic tumor was located in the left lateral section of liver without direct communication with pancreas. However, mass-like necrotic tissue was filled with in the hepatoduodenal ligament, hepatogastric ligament, and Glisson sheath of the left hepatic lobe. Left lateral sectionectomy was performed. Pathologic examination confirmed the pseudocyst with findings of non-epithelialized granulation tissue of the cystic wall. Conclusion: IHPP should be considered when a huge intrahepatic cystic lesion is found in patients with recent episodes of pancreatitis. The high level of amylase on cystic fluid analysis plays a key role in the diagnosis of IHPP. Drainage procedure or surgical resection can be considered, if necessary, for the treatment of IHPP.

Research progress in the Hepatobiliary Surgery operation of hepatic hilar plate system

An estimate of about 50% of new liver cancer cases worldwide occur in China every year.Surgical resection is still the major treatment choice for longer survival of patients with hepatocellular carcinoma. Blocking hepatic blood flow and reducing intraoperative bleeding ensure the success of the operation. Anatomic separation of hepatic hilar region is the precondition of hepatic inflow occlusion. The hepatic hilar plate system involves a thick layer of connective tissue covering the hepatic inflow ducts of hepatic hilar region. The descending part of hilar plate assists in reducing the anatomical difficulty of the hepatic hilar region. The "forth porta hepatis" that is hidden in the hepatic hilar plate system involves the accumulation area of "short hepatic portal veins" .The communicating branch vessels between the hepatic inflow vessels form the anatomical basis in reducing the indocyanine green fluorescence stain effect.The relatively fixed position of the hepatic portal plate is considered as a positioning marker for accurate liver resection. The intrahepatic Glisson sheath is connected with thick connective tissue of the hepatic portal panel system, and is regarded as the physical barrier in limiting the proliferation and hypertrophy of hepatocytes and continuation of hepatic portal panel system in the liver.This paper summarizes the anatomy and application of hepatic hilar plate system during hepatobiliary surgery.

Histochemical and Immunohistochemical Characterizations of Hepatic Trematodiasis in Odontocetes.

Hepatic trematodiasis is a common condition in a number of free-ranging cetacean species, which occasionally result in severe hepatic and/or pancreatic lesions. However, even the basic pathological information of this disease is unknown for the majority of affected species. The current study describes and compares the histomorphology and immune reaction induced by hepatic trematodes of the family Brachycladiidae in the liver of the harbor porpoise (Phocoena phocoena, n = 8), Dall's porpoise (Phocoenoides dalli, n = 8), and Hubbs' beaked whale (Mesoplodon carlhubbsi, n = 2). Immunohistochemistry for eight antibodies (CK19, CD3, Foxp3, CD20, Iba1, CD68, CD163, and CD204) was conducted to analyze the pathology of these parasitic infections. In all three odontocete species, the changes observed in the trematode-affected biliary epithelium were comparable with marked hyperplasia and goblet cell metaplasia, as well as lymphoplasmacytic and eosinophilic inflammation. Additionally, regions of the Glisson's sheath were diffusely and severely fibrotic in all examined species, regardless of the physical presence of trematodes. Differences among the three species included the presence of characteristic lymphoid follicles formed in the fibrotic bile duct walls of only the two porpoise species. In the Hubbs' beaked whale, the degree of lymphoplasmacytic cholangitis was more severe, and ductular reaction was generally more prominent. In terms of the overall macrophage population among the three species, CD163- and CD204-positive cells (M2 macrophages) outnumbered Iba1- and CD68-positive cells (M1 macrophages), indicating a chronic infection stage in all analyzed individuals. Species-specific differences among the infiltrating macrophages included numbers of CD68-positive cells being significantly more abundant in the harbor porpoises, whereas CD163-positive cells were significantly more numerous in the Dall's porpoises. The numbers of CD204-positive macrophages were higher in the Hubbs' beaked whales compared to those in the porpoises. Trematode species of the harbor and Dall's porpoises were Campula oblonga, while they were Oschmarinella macrorchis in the Hubbs' beaked whales. This study concludes that interspecies differences in the tissue reactions to hepatic trematode infections are present among odontocete species and that the immune reaction varies depending on the species. This information aids in furthering our understanding of the pathogenesis of hepatic trematodiasis in cetaceans.

Perineural invasion of hilar cholangiocarcinoma in Chinese population: One center's experience.

BACKGROUNDHilar cholangiocarcinoma (HCCA) often produces perineural invasion (PNI) extending to extra-biliary sites, while significant confusion in the incidence of PNI in HCCA has occurred in the literature, and the mechanism of that procedure remains unclear.AIMTo summarize the incidence of PNI in HCCA and to provide the distribution of nerve plexuses around hepatic portal to clinical surgeons.METHODSReported series with PNI in HCCA since 1996 were reviewed. A clinicopathological study was conducted on sections from 75 patients with HCCA to summarize the incidence and modes of PNI. Immunohistochemical stains for CD34 and D2-40 in the cancer tissue were performed to clarify the association of PNI with microvessel and lymph duct. Sections of the hepatoduodenal ligament from autopsy cases were scanned and handled by computer to display the distribution of nerve plexuses around the hepatic portal.RESULTSThe overall incidence of PNI in this study was 92% (69 of 75 patients), while the rate of PNI in HCCA in the literature ranging from 38% to 100%. The incidence of PNI did not show any remarkable differences among various differentiated groups and Bismuth-Corlette classification groups. Logistic regression analysis identified the depth of tumor invasion was the only factor that correlated significantly with PNI (P < 0.01). In spite of finding tumor cells that could invade microvessels and lymph ducts in HCCA, we did not find tumor cells invaded nerves via microvessels or lymph ducts. Three nerve plexuses in the hepatoduodenal ligament and Glisson’s sheath were classified, and they all surrounded the great vessels very closely.CONCLUSIONThe incidence of PNI of HCCA in Chinese population is around 92% and correlated significantly with a depth of tumor invasion. It also should be considered when stratifying HCCA patients for further treatment.

Safety and efficacy of reduced-volume hepatectomy for advanced hepatic alveolar echinococcosis

Objective To evaluate the efficacy and safety of reduced volume hepatectomy in treatment of advanced hepatic alveolar echinococcosis. Methods The clinical data of 90 patients with advanced hepatic alveolar echinococcosis treated at the Qinghai Provincial People's Hospital from January 2017 to January 2019 were retrospectively analyzed. There were 41 males and 49 females, with an average age of 32 (range 11 to 58) years. The locations of the lesions, operations, complications and follow-up were analyzed. Results 90 patients were treated with reduced volume focal hepatectomy, 38 with radical resection and 52 with quasi radical resection. The operation time was (361±22) min. The hospital stay was (22±2) day, and the blood loss was (781±37) ml. Red blood cells were transfused in 19 patients and plasma in 39 patients. Pringle’s maneuver was used in 12 patients, regional hepatic blood flow occlusion in 42 patients, and Glisson sheath occlusion in 26 patients. The total bilirubin, alanine aminotransferase and aspartate aminotransferase returned to normal in 3 to 14 days after operation. There were 12 patients who developed bile leakage, 41 pleural effusion and 26 effusion in the operation sites. A total of ninety patients were followed up for 2 to 24 months. There was no recurrence of echinococcosis after radical resection and no enlargement of residual lesions after quasi-radical resection. Conclusion Reduced-volume hepatectomy reduced the risk and difficulty of operation. The follow-up results were good. This approach provides a feasible scheme for treatment of advanced hepatic alveolar echinococcosis. Key words: Echinococcosis, hepatic; Treatment outcome; Reduced-volume focal hepatectomy; Safety

Balloon-Occluded Trans-Arterial Chemoembolization Technique with Alternate Infusion of Cisplatin and Gelatin Slurry for Small Hepatocellular Carcinoma Nodules Adjacent to the Glisson Sheath

Objective It is difficult to control small hepatocellular carcinoma (HCC) nodules adjacent to the Glisson sheath (GS) by trans-arterial chemoembolization (TACE) probably due to multiple small tumor feeders directly branching from the trunk artery. The purpose of this study was to conduct a retrospective evaluation of a new TACE technique called the repeated alternate infusion of cisplatin solution and gelatin slurry distal to balloon occlusion (RAIB-TACE), for the treatment of small HCC nodules adjacent to GS. Materials and Methods Small nodules less than 4 cm attached to proximal portion of the subsegmental to lobar level portal branch were retrospectively selected. Between January 2011 and April 2014, 29 nodules in 29 patients were treated by super-selective lipiodol TACE/balloon-occluded TACE (B-TACE) (Lip-TACE group). Since April 2014, treatment protocols for small nodules adjacent to GS were changed, and 14 nodules in 12 patients were treated by RAIB-TACE (RAIB-TACE group). In RAIB-TACE group, alternate infusion of cisplatin solution and sparse gelatin slurry (mixture of 80 mg of gelatin fragments and 20 mL of contrast medium) were repeated until arterial flow was ceased. In Lip-TACE group, lipiodol was used as drug carrier and dense gelatin slurry (mixture of 80 mg of gelatin fragments and 2 mL of contrast medium) as embolization material. Dynamic CT/MRI was obtained 1-3 months after TACE, and response of each nodule was evaluated basing on modified RECIST criteria. Results In RAIB-TACE group, all 14 nodules (100%) were diagnosed as CR or PR. In Lip-TACE group, 18 of 29 (62.1%) were diagnosed as CR or PR. There was a statistically significant difference in objective response ratio between the groups (p=0.008, Fisher's test). Biloma (n=1) and benign stricture of the right hepatic duct (n=1) were seen in RAIB-TACE group. The biloma shrunk without treatment and the patient had no symptom, but the patient with biliary stricture repeated cholangitis and was treated by administration of antibiotics. Conclusion The study results show that RAIB-TACE is more effective than lipiodol TACE/B-TACE for small hepatocellular carcinoma adjacent to GS. We speculate that one of the reasons to explain why Lip-TACE is inferior to RAIB-TACE is that viscous lipiodol or dense gelatin slurry could not flow into small tumor feeders effectively.

Predicting peritumoral Glisson's sheath invasion of intrahepatic cholangiocarcinoma with preoperative CT imaging.

To investigate the differences of clinicopathological characteristics and computed tomography (CT) features between intrahepatic cholangiocarcinomas (ICC) with and without peritumoral Glisson's sheath invasion (PGSI), and to construct a nomogram to predict PGSI of ICCs preoperatively. The clinicopathological characteristics and CT features of 84 ICCs were retrospectively analyzed and compared between ICCs with (30/84, 35.7%) and without PGSI (54/84, 64.3%). Multivariate logistic regression analysis was used to identify preoperative independent predictors of PGSI in ICCs. A nomogram was constructed to predict PGSI preoperatively. ICCs with and without PGSI differed significantly in the presence of abdominal pain, serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels, TNM and T stages, tumor location, intratumoral calcifications, intrahepatic bile duct dilatation, intrahepatic bile duct calculus, morphologic type and dynamic enhancement pattern on CT images (all P<0.05). Abdominal pain, serum CEA level, intrahepatic bile duct dilatation, and morphologic type were independent predictors of PGSI in ICCs. A nomogram based on those predictors was constructed to predict PGSI preoperatively with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.908 (P<0.001). Clinicopathological characteristics and CT features differed significantly between ICCs with and without PGSI. A nomogram including abdominal pain, serum CEA level, intrahepatic bile duct dilatation, and morphologic type could predict PGSI accurately.

Intrahepatic pancreatic pseudocyst; a rare complication of pancreatitis

Introduction: Pancreatic pseudocyst is located usually in lesser sac and peripancreatic space and is rarely developed in the liver. The intrahepatic pancreatic pseudocyst(IHPP) following acute pancreatitis is extremely rare with very limited number of clinical reports about IHPP. Methods: A 70-year-old woman was referred because of upper abdominal pain of 3 days' duration. An abdominal CT scan revealed 11x10 cm sized cystic mass in the left lateral section of liver. On EUS findings, a huge hypoechoic lesion with internal echogenicity was noted in the lesser sac. EUS-guided gastrocystostomy was performed and analysis of cystic fluid showed a high level of amylase (21,200 U/L). After the endoscopic procedure, severe abdominal pain developed and physical examination showed peritoneal irritation sign. An emergency operation was performed. Results: On operation findings, a huge cystic tumor was located in the left lateral section of liver without direct communication with pancreas. However, mass-like necrotic tissue was filled with in the hepatoduodenal ligament, hepatogastric ligament, and Glisson sheath of the left hepatic lobe. Left lateral sectionectomy was performed. Pathologic examination confirmed the pseudocyst with findings of non-epithelialized granulation tissue of the cystic wall. Conclusion: IHPP should be considered when a huge intrahepatic cystic lesion is found in patients with recent episodes of pancreatitis. The high level of amylase on cystic fluid analysis plays a key role in the diagnosis of IHPP. Drainage procedure or surgical resection can be considered, if necessary, for the treatment of IHPP.

Accumulation of citrullinated glial fibrillary acidic protein in a mouse model of bile duct ligation-induced hepatic fibrosis.

Hepatic stellate cells (HSCs) play pivotal roles in hepatic fibrosis as they synthesize glial fibrillary acidic protein (GFAP), which is increased in activated HSCs. GFAP-expressing HSCs and myofibroblasts accumulate in and around hepatic fibrosis lesions. Peptidylarginine deiminase 2 (PAD2) is responsible for the citrullination of GFAP (cit-GFAP). However, the involvement of PAD2 and cit-GFAP in hepatic fibrosis remains unclear. To determine the expression of PAD2 and cit-GFAP in hepatic fibrosis, C57BL/6 mice underwent bile duct ligation (BDL) or a sham operation. In BDL livers, the expression of PAD2 and its enzyme activity were significantly increased compared with controls. In addition, PAD2-postitive cells were rarely observed in only the portal vein and the small bile duct in sham-operated livers, whereas an increased number of PAD2-positive cells were detected in the bile duct and Glisson’s sheath in BDL livers. Interestingly, PAD2 was colocalized with α-SMA-positive cells and CK19-positive cells in BDL livers, indicating upregulated PAD2 in activated HSCs and portal fibroblasts of the livers of BDL mice. We also found that citrullinated proteins were highly accumulated in the livers of BDL mice compared with controls. Moreover, the expression level of GFAP and the amount of cit-GFAP were higher in BDL livers than in control livers. In correlation with PAD2 localization, cit-GFAP was observed in α-SMA-positive and CK19-positive cells in the livers of BDL mice. These results suggest that the increased expression and activation of PAD2 along with increased citrullinated proteins, specifically cit-GFAP, may play important roles in the pathogenesis of hepatic fibrosis.

A Case of Cholangiolocellular Carcinoma Preoperatively Diagnosed With Typical Imaging Findings

Introduction:Cholangiolocellular carcinoma (CoCC) is a rare primary liver neoplasm. A recent integrative genomic analysis has revealed that CoCC represents a distinct biliary-derived molecular entity. Several cases of CoCC have been reported so far, but accurate preoperative diagnosis was difficult in most cases.Case presentation:We report a case of 70-year-old woman with CoCC. Preoperative imaging findings revealed several typical signs of CoCC (i.e., thick early ring enhancement in the peripheral area of the tumor and its prolongation, vessel penetration through the tumor, no dilatation of the peripheral bile ducts, and dot-/band-like internal enhancement or a target appearance on contrast-enhanced magnetic resonance imaging). We strongly suspected CoCC from these preoperative imaging findings of the tumor and performed extended left hepatectomy. Pathologic diagnosis was CoCC, and the histologic findings such as peripheral highly cellular areas, central abundant hyalinized/edematous fibrotic stroma, and retained Glisson's sheath structures in the tumor, corresponded closely to each preoperative imaging finding. Immunohistochemical study revealed the tumor cells were positive for cytokeratin 7 and epithelial membrane antigen. The postoperative course was uneventful, and the patient is alive without recurrence for 15 months. The prognosis of CoCC is known to be better than that of cholangiocellular carcinoma, indicating the importance of preoperative differential diagnosis of these tumors.Conclusion:Even though preoperative diagnosis of CoCC is difficult because of its rarity, cautious investigation of preoperative typical imaging findings can possibly lead to accurate diagnosis of CoCC.

Transparenchymal glissonean approach: a novel surgical technique for advanced perihilar bile duct cancer.

To increase the surgical opportunities for locally advanced perihilar bile duct cancers that require left-sided hepatectomies, we developed the transparenchymal glissonean approach (TGA); it comprises intra-hepatic exposure and dissection of the Glisson's sheath to gain access to the hepatic artery and portal vein for reconstruction. Following skeletonization of the hepatoduodenal ligament, the proximal portions of invaded vessels are exposed. If extra-hepatic attempts to access the distal portions of the invaded vessels fail, TGA can be used. The distal portion of the invaded right or right posterior Glisson's sheath is exposed following liver transection. The anterior portion of the wall of bile duct is cut and transected circumferentially including the fibrous plate tissue. The non-invaded portal vein and hepatic artery are isolated and dissected towards the hepatic hilum until the invaded distal portion of the vessels, and vascular reconstructions are performed. TGA was performed in 9 patients; 5 patients underwent left hemihepatectomy and 4 underwent left tri-sectionectomy. Eight patients needed vascular reconstruction. Clavien-Dindo classification (CDC) grades IIIa and IIIb were recorded in 6 and 1 patients, respectively. No patients had CDC grades IV and V disease. Pathologically, all cases were pT4; 3 cases were R0, 5 were R1 with microscopic positive margin, and 2 were R1 with microscopic metastasis. The overall median survival time was 25.0months. TGA is feasible with acceptable prognosis and expands the surgical opportunities.

Application of endobronchial ultrasonography in laparoscopic liver segmentectomy in an animal model.

This study investigated whether laparoscopic ultrasound-guided segment staining and real-time ultrasound-guided hepatectomy, with endobronchial ultrasonography equipped with a guide sheath, would be useful for laparoscopic liver segmentectomy in a porcine model. The abdominal cavity (in two pigs) was reached via a 12-mm umbilical trocar. An artificial tumor was created by radiofrequency ablation within the intended resection area. Portal vein puncture and staining were performed by the endobronchial ultrasonography-guided method. The targeted portal branch was successfully visualized and punctured with a needle through an equipped guide sheath. After targeted segment staining, the liver parenchyma was resected with a bipolar energy device; the regional Glisson's sheath was ligated and cut, and a surgical specimen was extracted. Real-time endobronchial ultrasonography from the cut surface provided information vital for preserving the surgical margin. All procedures were performed laparoscopically. This study demonstrated the technical feasibility of laparoscopic ultrasound-guided portal vein staining and safe surgical resection during laparoscopic liver segmentectomy.

Three-Dimensional Liver Surgery Simulation: Computer-Assisted Surgical Planning with Three-Dimensional Simulation Software and Three-Dimensional Printing.

To perform accurate hepatectomy without injury, it is necessary to understand the anatomical relationship among the branches of Glisson's sheath, hepatic veins, and tumor. In Japan, three-dimensional (3D) preoperative simulation for liver surgery is becoming increasingly common, and liver 3D modeling and 3D hepatectomy simulation by 3D analysis software for liver surgery have been covered by universal healthcare insurance since 2012. Herein, we review the history of virtual hepatectomy using computer-assisted surgery (CAS) and our research to date, and we discuss the future prospects of CAS. We have used the SYNAPSE VINCENT medical imaging system (Fujifilm Medical, Tokyo, Japan) for 3D visualization and virtual resection of the liver since 2010. We developed a novel fusion imaging technique combining 3D computed tomography (CT) with magnetic resonance imaging (MRI). The fusion image enables us to easily visualize anatomic relationships among the hepatic arteries, portal veins, bile duct, and tumor in the hepatic hilum. In 2013, we developed an original software, called Liversim, which enables real-time deformation of the liver using physical simulation, and a randomized control trial has recently been conducted to evaluate the use of Liversim and SYNAPSE VINCENT for preoperative simulation and planning. Furthermore, we developed a novel hollow 3D-printed liver model whose surface is covered with frames. This model is useful for safe liver resection, has better visibility, and the production cost is reduced to one-third of a previous model. Preoperative simulation and navigation with CAS in liver resection are expected to help planning and conducting a surgery and surgical education. Thus, a novel CAS system will contribute to not only the performance of reliable hepatectomy but also to surgical education.