Jota Watanabe

Human Leukocyte Antigen Antibodies and Human Complement Activation: Role of Igg Subclass, Specificity, and Cytotoxic Potential

Background. Human leukocyte antigen (HLA) antibodies are defined as complement (C) fixing and clinically relevant based upon the complement-dependent cytotoxicity (CDC) test. However, the sub-lytic activation of individual C components is of critical biologic significance. The requirements of HLA antibodies to activate human C are not known. Methods. IgG, IgM, IgG subclasses, and human C3b deposition upon T cells were evaluated by flow cytometry with sera from HLA-sensitized patients and human monoclonal HLA antibodies. Results. Comparative studies showed that there was poor correlation between the amount of IgG on target cells and their ability to produce CDC. Human C3b deposition was influenced more by the particular serum/cell combination under study than by the amount of IgG, with some combinations showing high IgG and low C3b and others showing low IgG and high C3b. IgG1 was the predominant IgG subclass in all patients. The other subclasses were low or undetectable and did not correlate with C3b deposition. Human monoclonal HLA antibodies, mostly IgG1, did not activate human C efficiently despite high IgG binding. However, combinations of two monoclonal antibodies to different epitopes of the same antigen did produce significant C3b deposition. Conclusions. Contrary to common assumptions, CDC, IgG binding, and IgG subclass are poor predictors of human C activation by HLA antibodies. The mix of specificities in a given serum and the antigens of a particular target cell appear to determine the efficiency of C activation. Measuring both antibody and C3b deposition (or other C component) may improve the assessment of donor-recipient compatibility.

Biological markers of hepatocellular carcinoma for use as selection criteria in liver transplantation

The Milan criteria (MC) have been widely accepted as an effective way of selecting patients with early‐stage hepatocellular carcinoma (HCC) for curative liver transplantation (LT). However, since a substantial subset of HCC patients exists that is beyond the MC but with the potential for good outcomes after LT, several institutions have recently proposed new extended criteria. To explore optimal criteria that can reasonably predict the risk of recurrence, it is considered that new markers of biological behavior are needed in addition to morphological tumor size and number. Several promising candidates for such biological markers have been reported, including serum tumor markers such as alpha‐fetoprotein and des‐gamma‐carboxy prothrombin, inflammatory markers such as C‐reactive protein and neutrophil‐to‐lymphocyte ratio, response to pre‐transplant treatments for bridging therapy or down‐staging, and fluorine‐18‐fluorodeoxyglucose positron emission tomography. However, the role of these biological markers in patient selection criteria for LT has yet to be clarified. This review article aims to summarize the results of recent reported studies and to display perspectives for the establishment of optimal criteria that incorporate such biological markers.

Impact of psoas muscle index on short-term outcome after living donor liver transplantation.

BACKGROUND/AIMS Living donor liver transplantation is an operation with high morbidity and mortality rates. The purpose of this study was to examine factors affecting the short-term outcome after living donor liver transplantation. MATERIALS AND METHODS Forty-seven adult patients who underwent living donor liver transplantation from September 2001 to December 2014 were included. Short-term post-transplant outcomes were evaluated in terms of the onset of postoperative complications of grade 3a and above (Clavien-Dindo classification) and postoperative 120-day mortality. Univariate and multivariate analyses were used to determine possible predictive factors among perioperative variables such as preoperative psoas muscle index (PMI), blood laboratory test results, perioperative nutritional therapy, and operative factors. RESULTS Lower PMI (lower than the first quartile of PMI of donors), higher blood urea nitrogen level (≥14 mg/dL), and blood type incompatibility were independent risk factors for the development of postoperative complications. The 120-day survival rates were significantly lower for the lower PMI group (n=30, 66.7%) than for the higher PMI group (n=17, 94.1%, p=0.034). CONCLUSION A significant correlation was observed between preoperative PMI and short-term postoperative outcomes. Sarcopenia estimated by PMI may serve as a measure of patient frailty and a target for risk stratification.

Downregulation of Cytokine Release by Heat Preconditioning of Livers Used for Transplantation in Rats

We evaluated the changes in the levels of released cytokines following heat preconditioning of the livers used in rat liver transplantation. The donor rats in the heat preconditioning (HP) group were subjected to heat preconditioning 48 h before graft harvesting. The liver isografts were preserved in Euro-Collins solution for 8 h, and then transplanted orthotopically. The one-week survival rate of the HP group was significantly better than that of the control (C) group. The serum levels of interleukin-6 and interleukin-10 were significantly lower in the HP group than in the C group. Histological staining revealed that the stagnation of red blood cells and infiltration of neutrocytes were reduced in the HP group. The expression of intercellular adhesion molecule-1 was decreased around the central vein in the HP group, as revealed by immunohistochemistry. These results indicate that heat preconditioning downregulates cytokine release and reduces the frequency of microcirculation disorders.

An unusual case of subclinical diffuse glucagonoma coexisting with two nodules in the pancreas: characteristic features on computed tomography.

A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT.

Protective Effect of Adeno-Mediated Human Bcl-xL Gene Transfer to the Mouse Liver in a Partial Ischemia/Reperfusion Model

BACKGROUND The protective effect of heat preconditioning has been ascribed to the induction of heat shock proteins (HSP) in the liver. We detected an increase in Bcl-xL expression prior to HSP 70 expression in the rat liver after heat preconditioning. The net effect of overexpression of human Bcl-xL with a recombinant adenovector was estimated in a partial ischemia/reperfusion model of the mouse liver. MATERIALS AND METHODS The time courses of the expression of HSP, Bcl-xL, Bcl-2, Bax, and Bag-1 in the SD rat liver after heat preconditioning were studied by Western blotting. The localizations of Bcl-xL, Bcl-2, and Bax at 6 h after preconditioning were examined by immunostaining. The expression of Bcl-xL in the C57/BL mouse liver after intravenous injection of the recombinant adenovector was assessed by Western blotting and immunostaining. The protective effect of overexpression of Bcl-xL was estimated in a 60-min partial ischemia/reperfusion model of the mouse liver. RESULTS The expression of Bcl-xL peaked 12 h after heat preconditioning. The overexpression of Bcl-xL decreased enzyme release, histological cell injury, and the number of TUNEL-positive cells. CONCLUSION Transfer of the human Bcl-xL gene to the liver had a protective effect against ischemia/reperfusion injury in a mouse model.

Gastric liposarcoma resected by laparoscopic total gastrectomy to achieve a wide surgical margin

Gastric liposarcoma is an extremely rare tumour that usually affects the extremities and retroperitoneum. Preoperative diagnosis is difficult, and operative procedures are not well standardised. A 61-year-old woman presented with melaena, epigastric discomfort and palpitations. Upper endoscopy revealed a submucosal tumour at the posterior gastric fundus with an actively bleeding ulcer on the top. Our preoperative diagnosis was lipoma, and we performed laparoscopic intragastric surgery. However, the histopathological diagnosis was liposarcoma. Laparoscopic total gastrectomy was performed to achieve a wide surgical margin. Several recent series have shown that a positive microscopic margin is associated with a higher rate of local recurrence than a negative margin. We have added a staged operation to obtain a wide margin in cases involving a positive surgical margin. Preoperative diagnosis of liposarcoma is still challenging. Gastric lipoma-like tumours should be resected with a wide margin because of their possibility of malignancy.

Recovery After Critical Illness Polyneuropathy in a Patient With Orthotopic Liver Transplantation: A Case Report

After liver transplantation, some patients show neuromuscular abnormalities. A 43-year-old man with liver cirrhosis due to hepatitis C virus underwent living-donor liver transplantation. He developed severe neuromuscular dysfunction after sepsis, and acute respiratory distress syndrome. After the inflammatory reaction gradually improved, we observed bilateral weakness of the extremities and foot drop. Electrophysiological studies indicated primary axonal degeneration of peripheral motor and sensory fibers without inflammation. Critical illness polyneuropathy was diagnosed. During follow-up, complaints gradually recovered with rehabilitation by approximately 1 year later. Based on this case, we suggest that paralysis should be evaluated for critical illness polyneuropathy in patients with unexplained muscle weakness.

Localized 18F-fluorodeoxyglucose uptake at the pancreatic head during remission phase of autoimmune pancreatitis: A case report

Autoimmune pancreatitis (AIP) is a unique form of pancreatitis, histopathologically characterized by dense lymphoplasmacytic infiltration and fibrosis of the pancreas with obliterative phlebitis. AIP is associated with a good response to steroid therapy. Differentiation between AIP and pancreatic cancer to determine a preoperative diagnosis is often challenging, despite the use of various diagnostic modalities, including computed tomography (CT), magnetic resonance imaging and endoscopic retrograde cholangiopancreatography. It has been reported that 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET)/CT may be a useful tool for distinguishing between the two diseases. In the present case report, a 71-year-old male patient presented with a well-circumscribed, solitary, nodular and homogenous 18F-FDG uptake at the pancreatic head, while receiving maintenance steroid therapy in the remission phase of AIP; preoperatively, the patient had been strongly suspected of having pancreatic cancer. Pathological examination revealed post-treatment relapse of AIP. The present case highlights the diagnostic and management difficulties with AIP in the remission phase. In certain cases, it remains challenging to differentiate the two diseases, even using the latest modalities.

Phenotypic characterization and clinical outcome in ampullary adenocarcinoma

Although various features of ampullary adenocarcinoma have been reported, the impact of genetic alterations and rare subtypes on clinical outcome remains unclear.