Go Oshima

The influence of donor age on liver regeneration and hepatic progenitor cell populations.

BACKGROUND Recent reports suggest that donor age might have a major impact on recipient outcome in adult living donor liver transplantation (LDLT), but the reasons underlying this effect remain unclear. The aims of this study were to compare liver regeneration between young and aged living donors and to evaluate the number of Thy-1+ cells, which have been reported to be human hepatic progenitor cells. METHODS LDLT donors were divided into 2 groups (Group O, donor age ≥ 50 years, n = 6 and Group Y, donor age ≤ 30 years, n = 9). The remnant liver regeneration rates were calculated on the basis of computed tomography volumetry on postoperative days 7 and 30. Liver tissue samples were obtained from donors undergoing routine liver biopsy or patients undergoing partial hepatectomy for metastatic liver tumors. Thy-1+ cells were isolated and counted using immunomagnetic activated cell sorting (MACS) technique. RESULTS Donor liver regeneration rates were significantly higher in young donors compared to old donors (P = .042) on postoperative day 7. Regeneration rates were significantly higher after right lobe resection compared to rates after left lobe resection. The MACS findings showed that the number of Thy-1+ cells in the human liver consistently tended to decline with age. CONCLUSION Our study revealed that liver regeneration is impaired with age after donor hepatectomy, especially after right lobe resection. The declining hepatic progenitor cell population might be one of the reasons for impaired liver regeneration in aged donors.

Increased plasma levels of high mobility group box 1 in patients with acute liver failure

Background: High-mobility group box 1 (HMGB1) is a monocyte-derived late-acting inflammatory mediator, which is released in conditions such as shock, tissue injury and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in patients with acute liver failure (ALF). Patients and Methods: We determined the plasma levels of HMGB1 and aspartate aminotransferase (AST) in 7 healthy volunteers (HVs), 40 patients with liver cirrhosis (LC), 37 patients with chronic hepatitis (CH), 18 patients with severe acute hepatitis (AH), and 14 patients with fulminant hepatitis (FH). The 14 patients with FH were divided into two subgroups depending upon the history of plasma exchange (PE) before their plasma sample collection. The hepatic levels of HMGB1 were measured in tissue samples from 3 patients with FH who underwent living-donor liver transplantation and from 3 healthy living donors. Hepatic tissue samples were also subjected to immunohistochemical examination for HMGB1. Results: The plasma levels of HMGB1 (ng/ml) were higher in patients with liver diseases, especially in FH patients with no history of PE, than in HVs (0.3 ± 0.3 in HVs, 4.0 ± 2.0 in LC, 5.2 ± 2.6 in CH, 8.6 ± 4.8 in severe AH, 7.8 ± 2.7 in FH with a history of PE, and 12.5 ± 2.6 in FH with no history of PE, p < 0.05 in each comparison). There was a strong and statistically significant relationship between the mean plasma HMGB1 level and the logarithm of the mean AST level (R = 0.900, p < 0.05). The hepatic tissue levels of HMGB1 (ng/mg tissue protein) were lower in patients with FH than in healthy donors (539 ± 116 in FH vs. 874 ± 81 in healthy donors, p < 0.05). Immunohistochemical staining for HMGB1 was strong and clear in the nuclei of hepatocytes in liver sections from healthy donors, but little staining in either nuclei or cytoplasm was evident in specimens from patients with FH. Conclusion: We confirmed that plasma HMGB1 levels were increased in patients with ALF. Based on a comparison between HMGB1 contents in normal and ALF livers, it is very likely that HMGB1 is released from injured liver tissue.

Laparoscopic-assisted limited liver resection: Technique, indications and results

BACKGROUND/PURPOSE The purpose of this work was to evaluate the short-term results of laparoscopic-assisted limited liver resection. METHODS We analyzed the clinical outcome in 17 patients (mean age 70 +/- 8 years) who had undergone laparoscopic-assisted limited liver resection from March 2006 to December 2008. Preoperative diagnoses were HCC in 13 patients and metastasis of colon cancer in 4. The operation consisted of laparoscopic mobilization of the target liver lobe, followed by open liver resection through a 7- to 10-cm extraction site. RESULTS Mean tumor size was 3.0 +/- 1.1 cm (range 1.2-5 cm). The mean operative time was 362 +/- 85 min. The mean blood loss was 451 +/- 413 ml, and no blood transfusion was required in any patient. There were no intraoperative complications, and conversion to laparotomy was needed in one case. Postoperative complications developed in 4 cases (4 infections, 24%), all of which were improved by conservative management. However, there was no postoperative mortality. None of the patients had any peritoneal carcinomatosis or port-site or resection site recurrence during a mean follow-up of 18 +/- 9.6 months. According to the analysis of the tumor location, the criterion for an adequate tumor location in the right lobe for this operation was set with the tumor at a distance of more than 5 cm from the inferior vena cava and the root of the hepatic vein (5 cm rule). CONCLUSION Laparoscopic-assisted limited liver resection is feasible and well tolerated. Accumulation of more data may be needed for evaluation of long-term outcome.

Concomitant pancreatic endocrine neoplasm and intraductal papillary mucinous neoplasm: a case report and literature review

We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for mixed-type IPMN for 10 years. Recent magnetic resonance images revealed an increase in size of the branch duct IPMN in the pancreas head, while the dilation of the main pancreatic duct showed minimal change. Although contrast-enhanced computed tomography and magnetic resonance imaging did not reveal any nodules in the branch duct IPMN, endoscopic ultrasound indicated a suspected nodule in the IPMN. A malignancy in the branch duct IPMN was suspected and we performed pylorus-preserving pancreatoduodenectomy with lymphadenectomy. The resected specimen contained a cystic lesion, 10 x 10 mm in diameter, in the head of the pancreas. Histological examination revealed that the dilated main pancreatic duct and the branch ducts were composed of intraductal papillary mucinous adenoma with mild atypia. No evidence of carcinoma was detected in the specimen. Incidentally, a 3-mm nodule consisting of small neuroendocrine cells was found in the main pancreatic duct. The cells demonstrated positive staining for chromogranin A, synaptophysin, and glucagon but negative staining for insulin and somatostatin. Therefore, the 3-mm nodule was diagnosed as a PEN. Since the mitotic count per 10 high-power fields was less than 2 and the Ki-67 index was less than 2%, the PEN was pathologically classified as low-grade (G1) according to the 2010 World Health Organization (WHO) criteria. Herein, we review the case and relevant studies in the literature and discuss issues related to the synchronous occurrence of the relatively rare tumors, PEN and IPMN.

A male case of an undifferentiated carcinoma with osteoclast-like giant cells originating in an indeterminate mucin-producing cystic neoplasm of the pancreas. A case report and review of the literature

We report a rare male case of an undifferentiated carcinoma with osteoclast-like giant cells originating in an indeterminate mucin-producing cystic neoplasm of the pancreas. A 59-year-old Japanese man with diabetes visited our hospital, complaining of fullness in the upper abdomen. A laboratory analysis revealed anemia (Hemoglobin; 9.7 g/dl) and elevated C-reactive protein (3.01 mg/dl). Carbohydrate antigen 19-9 was 274 U/ml and Carcinoembryonic antigen was 29.6 ng/ml. A computed tomography scan of the abdomen revealed a 14-cm cystic mass in the upper left quadrant of the abdomen that appeared to originate from the pancreatic tail. The patient underwent distal pancreatectomy/splenectomy/total gastrectomy/cholecystectomy. The mass consisted of a multilocular cystic lesion. Microscopically, the cyst was lined by cuboidal or columnar epithelium, including mucinous epithelium. Sarcomatous mononuclear cells and multinucleated osteoclast-like giant cells were found in the stroma. Ovarian-type stroma was not seen. We made a diagnosis of osteoclast-like giant cell tumor originating in an indeterminate mucin-producing cystic neoplasm of the pancreas. All surgical margins were negative, however, two peripancreatic lymph nodes were positive. The patient recovered uneventfully. Two months after the operation, multiple metastases occurred in the liver. He died 4 months after the operation.

The superficial precoagulation, sealing, and transection method: A bloodless and ecofriendly laparoscopic liver transection technique

Background: Minimizing blood loss is an important aspect of laparoscopic liver resection. Liver transection is the most challenging part of liver resection, but no standard method is available for this step at present. Herein, we have introduced the superficial precoagulation, sealing, and transection (SPST) method, a potentially “bloodless” and “ecofriendly” laparoscopic liver transection technique involving reusable devices: the VIO soft-coagulation system; VIO BiClamp (bipolar electrosurgical coagulation); Olympus SonoSurg (ultrasonic surgical system); and CUSA (ultrasonic aspirator). Furthermore, we have reported the short-term outcomes of laparoscopic liver transection with the SPST method. Methods: The study included 14 consecutive patients who underwent laparoscopic partial liver resection with the SPST method at a single institution between August 2008 and June 2010. Results: The median operative time was 201 minutes (range, 97 to 332 min) and the median blood loss was 5 mL (range, 5 to 250 mL). There was no requirement for blood transfusion, no intraoperative complications, and no cases of conversion to open laparotomy. There were no liver transection-related complications such as postoperative bile leakage, bleeding, or infection. All surgical margins were negative, with a mean margin of 4.6 mm, and no local recurrence was observed at an average follow-up of 37.6 months. Conclusions: The SPST method is a simple, efficient, and cost-effective surgical technique for laparoscopic liver resection. It is associated with low intraoperative blood loss and good short-term outcomes. We recommend that the SPST method should be used as a standard technique for laparoscopic liver transection (Supplemental Digital Content 1, http://links.lww.com/SLE/A103).

Laparoscopic Liver Mobilization: Tricks of the Trade to Avoid Complications

Laparoscopic liver resection is gaining popularity because of the availability of new laparoscopic instruments and advanced techniques. Laparoscopic liver mobilization is not only necessary for pure laparoscopic liver resection but also for laparoscopy-assisted hepatectomy. Laparoscopy-assisted hepatectomy significantly reduces the length of the laparotomy incision, and it is a good educational transition to the more advanced laparoscopic liver resection. Laparoscopic liver mobilization is a simple and easy procedure if surgeons know what challenges to expect. Here, the technique of liver mobilization is summarized, along with those challenges.

Hemoadsorption of High-Mobility Group Box Chromosomal Protein 1 Using a Column for Large Animals

Background: High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. Materials and Methods: In this study, we produced a new adsorbent material by chemically treating polystyrene fiber. We first determined whether the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1 solution and a plasma sample from a swine model of acute liver failure. We then constructed a column by embedding fabric sheets of the newly developed fibers into a cartridge and tested the ability of the column to reduce plasma HMGB1 levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute liver failure. Results: The in vitro adsorption test of the new fiber showed high performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and 94% in the acute liver failure swine plasma, 2 h incubation at 37°C; p < 0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the HMGB1 concentration at the outlet versus the inlet of the column was significantly lower in swine hemoperfused with the newly developed column (53 and 61% at the beginning and end of perfusion, respectively) than in those animals hemoperfused with the control column (94 and 93% at the beginning and end of perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of HMGB1 was significantly lower during perfusion with the new column than with the control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion). Conclusion: These data suggest that the newly developed column has the potential to effectively adsorb HMGB1 during hemoperfusion in swine.

Harness Traction Technique (HARNESS): Novel Method for Controlling the Transection Plane During Laparoscopic Hepatectomy.

We present our experience using a novel method for controlling the transection plane, which we termed as the Harness Traction Technique (HARNESS) and evaluate its usefulness. From May 2009 to March 2012, laparoscopic hepatectomies using HARNESS were performed on 35 patients. After the superficial hepatic parenchyma on the line was transected at 1 to 2 cm depth, 5 mm tape was placed along the groove of the line and tied to prevent it from slipping off. Tape was tied and pulled using a forceps toward the best direction for minimizing the bleeding, moving the transection point to the appropriate position and creating good tension for parenchymal transection at the transection point. There were no conversions to laparotomy or intraoperative complications. HARNESS is useful for controlling the dissection line during laparoscopic hepatectomy, leading to precise and safe laparoscopic liver parenchymal dissection.

Outcomes of ABO Compatible and DSA Positive Living Donor Liver Transplantation

Background We analyzed the outcomes of ABO compatible and DSA positive living donor liver transplantation (LDLT) focusing on preformed or de novo donor specific anti-HLA antibody (DSA). Patients and Methods We have decided immunosuppression protocol including portal infusion (PI) therapy depending on the results of lymphocyte cytotoxicity test (LCT) and ABO incompatibility. In all cases, we employed 3 drugs (CNI, antimetabolite, and steroid) for systemic immunosuppression. In ABO compatible and LCT negative cases, we used PGE1 for PI therapy. In ABO compatible and LCT positive cases, we used PGE1 and gabexate mesylate for PI therapy. In ABO incompatible (ABOI) cases, we used 3 drugs (PGE1, gabexate mesylate, and steroid) for PI therapy in addition to plasma exchange and rituximab. We investigated following 2 issues. I) Preformed DSA: Twenty-five recipients whose anti-HLA antibody test (screening test, PRA) was examined were divided into 4 groups depending on the result of (PRA and ABO incompatible (ABOI))=(-, -), (+, -), (-, +), (+, +), and 6-month survival was assessed in each group. In the group of (+, -), anti-HLA antibody test (single antigen test, Luminex) was performed and preformed DSA positive recipients were identified. II) De novo DSA: In the 273 LDLTs, recipients who developed antibody mediated rejection (AMR) were retrospectively identified and the outcomes were assessed. Results I) Six-month survivals were 62, 81, 100, 100% in (-, -), (+, -), (-, +), and (+, +), respectively. Out of the 9 patients in (+, -), 4 recipients were strongly positive for preformed DSA (>10,000MFI). All 4 recipients were adult female. There were 3 cases of PBC and 1 case of hepatitis C. All of them postoperatively received immunosuppression including PI therapy and their postoperative courses were uneventful. None of them developed AMR. II) Four recipients were identified to have developed AMR postoperatively. Two of them (cases 1 and 2) developed AMR in 2008 and 2010 and DSA was not determined in these years, but their pre and postoperative results of LCT suggested that de novo DSA appeared. Two of them (cases 3 and 4) developed AMR in 2015 and 2016 and DSA was negetive preoperatively but became strongly positive postoperatively. Three (cases 1 to 3) died of AMR and 1 (case 4) survived after re-transplantation. Three (cases 1, 3, and 4) did not receive PI therapy because of individual reasons. Conclusion Outcomes of recipients who had preformed DSA was satisfactory but those of recipients who developed do novo DSA was poor. Our immunosuppression protocol including PI therapy may be associated with the outcomes.