Prevalence and outcomes of patients with sinusoidal obstruction syndrome after liver transplantation: A ten year's experience of a single center in Japan.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) after liver transplantation (LT) is a rare and potentially lethal complication. We retrospectively reviewed the outcomes of patients with post-transplant SOS. METHODS: Between May 2001 and December 2019, of 332 patients who underwent LT, 5 (1.5%) developed SOS. The median age at LT was 1.7 years (range 0.1-66.5). SOS was histopathologically diagnosed and classified as early-onset (<1 month) or late-onset. RESULTS: The median time to diagnosis of SOS was one month after LT. All patients developed acute cellular rejection before SOS, and the cause of SOS was acute cellular rejection in four patients and unknown in one. The treatment of SOS included conversion to tacrolimus from cyclosporine, intrahepatic hepatic vein stent placement, strengthening of immunosuppression, and plasma exchange. The 5-year graft survival rates in patients with and without SOS were 53.0% and 92.5%, respectively (p < 0.001). Of three patients with early-onset SOS, two patients improved and are doing well, and one patient died of graft failure four months after LT. CONCLUSIONS: The cause and treatment of post-transplant SOS are not yet defined. The poor outcomes in patients with early-onset SOS may be improved by strengthening of immunosuppression. Patients with late-onset SOS are ultimately treated by repeat LT.

Hepatocellular adenoma, approximately half and predominantly inflammatory subtype, in 38 Japanese patients with several differences in age, gender, and clinical background factors from Western populations.

AIM: Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries. METHODS: To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations. RESULTS: Thirty-eight cases were found to have HCA without cirrhosis. The male/female ratio was 18/20. Ages ranged from 15 to 79 (average, 43.2) years. Male and elder patients are not rare, furthermore, most of elder patients are male. Glycogen storage disease, past history of medicament use, hepatitis B virus surface antigen-positivity, antihepatitis C virus -positivity, diabetes mellitus, obesity, lipid metabolism disorder and alcoholism were present in of 6, 8, 1, 1, 6, 6, 4, and 6 cases, respectively. As to HCA subtypes, HNF1alpha-inactivated HCA, beta-catenin activated HCA (b-HCA), inflammatory HCA (IHCA) and unclassified HCA (U-HCA) accounted for nine (23.7%), four (10.5%), 17 (44.7%) and eight (21.1%) cases, respectively. Two cases showed coexistence of HCA and hepatocellular carcinoma (HCC) at surgery, and another had HCC which had been detected 23 years after HCA diagnosis. The HCA subtype of one of the former cases was U-HCA, while the remaining two had b-HCA and U-HCA. CONCLUSIONS: In Japanese HCA cases, the proportions of U-HCA, male and elder cases were slightly higher than in Western countries, and most of elder patients were male. IHCA was however common regardless of race, and was assumed to be the predominant subtype of HCA.

Hemochromatosis and Hepatocellular Carcinoma Secondary to Immunoglobulin G4-Related Disease with Hepatopathy: A Case Report.

Immunoglobulin G4-related disease (IgG4-RD) is a recently characterized illness in which lymphocytes and plasma cells infiltrate various anatomical sites. IgG4-hepatopathy, a manifestation of IgG4-RD, is a broader term covering various patterns of liver injury. The clinical course, including the malignant potential of IgG4-RD, remains unclear. Here we report the first case of secondary hemochromatosis and hepatocellular carcinoma (HCC) developing from IgG4-hepatopathy. A 67-year-old man was admitted to our hospital for treatment of deteriorating glucose tolerance. Blood test results showed hypergammaglobulinemia, especially IgG4. He was readmitted 2 months later with dyspnea due to lung disease and pleural effusion, and elevated transaminase levels. He underwent liver and lung biopsies. IgG4-RD was diagnosed and he was treated with steroid therapy, which improved serum IgG4 levels and imaging abnormalities. A follow-up computed tomography (CT) scan conducted 38 months later revealed a tumor (diameter, 50 mm) in liver segments 7 and 8. The resected specimen revealed HCC and abundant siderosis in the background liver, indicating a diagnosis of hemochromatosis. IgG4-positive cells were scarce, probably because of corticosteroid therapy. In the present case, IgG4-RD was well controlled with prednisolone (PSL) and an immunosuppressive agent, and chronic hepatitis was not severe, even though the patient subsequently developed HCC. However, extensive siderosis consistent with hemochromatosis was unexpectedly noted. These findings suggest that secondary hemochromatosis and HCC developed during IgG4-RD with hepatopathy. We believe this case sheds light on IgG4-RD.

Clinicopathological Features of Autoimmune Hepatitis with IgG4-Positive Plasma Cell Infiltration.

BACKGROUND: We aimed to elucidate the characteristics and prognosis of autoimmune hepatitis (AIH) patients with immunoglobulin (Ig) G4-positive plasma cell infiltration. METHODS: We enrolled 84 AIH patients. The number of IgG- and IgG4-positive plasma cells was immunohistochemically counted per high-power field in the portal area. Patients with 3 or more IgG4-positive plasma cells on average and a ratio of IgG4 to IgG-positive plasma cells ≥5% were defined as IgG4-associated AIH (IgG4-AIH), and their clinicopathological characteristics and prognosis were compared to those of the remaining classical-AIH patients. RESULTS: Ten (11.9%) and 74 patients (88.1%) were categorized as IgG4-AIH and classical-AIH patients, respectively. The median age of the IgG4-AIH patients was 67 years, the majority was female (80.0%), and the distribution was similar to that of the classical-AIH patients. The IgG4-AIH patients exhibited significantly more severe phenotypes in portal inflammation, interface hepatitis, fibrosis, and rosette formation. All clinical laboratory data were similar except for serum IgG4 levels, which were higher in IgG4-AIH patients (168.5 vs. 22.9 mg/dL, p = 0.014). During a median follow-up period of 139 months, the relapse rate was significantly lower in the IgG4-AIH group than in the classical-AIH group (11.1 vs. 49.2%; p = 0.048). Twelve (16.2%) and 6 (8.1%) classical-AIH patients underwent liver-related events and liver-related deaths, respectively. In contrast, none of the IgG4-AIH patients progressed to severe liver disease. CONCLUSIONS: The IgG4-AIH patients had more severe inflammation and advanced fibrosis in the liver. However, their prognosis was not poor compared to that of classical-AIH patients. IgG4-AIH may have a phenotype distinct from classical-AIH.

Nineteen-year prognosis in Japanese patients with biopsy-proven nonalcoholic fatty liver disease: Lean versus overweight patients.

BACKGROUND: Many studies have investigated the prognosis of nonalcoholic fatty liver disease (NAFLD); however, most studies had a relatively short follow-up. To elucidate the long-term outcome of NAFLD, we conducted a retrospective cohort study of patients with biopsy-proven NAFLD. METHODS: We re-evaluated 6080 patients who underwent liver biopsy from 1975 to 2012 and identified NAFLD patients without other etiologies. With follow-up these patients, we evaluated the outcome-associated factors. RESULTS: A total of 223 patients were enrolled, 167 (74.9%) was non-alcoholic steatohepatitis (NASH). The median follow-up was 19.5 (0.5-41.0) years and 4248.3 person-years. The risk of type 2 diabetes mellitus (T2DM) and hypertension was 11.7 (95% confidence interval [CI] 8.70-15.6) and 7.99 (95% CI 6.09-10.5) times higher, respectively, in NAFLD patients than in the general population. Twenty-three patients died, 22 of whom had NASH. Major causes of death were extrahepatic malignancy and cardiovascular disease (21.7%) followed by liver-related mortality (13.0%). All-cause mortality was significantly higher in NASH patients than in nonalcoholic fatty liver patients (P = 0.041). In multivariate analysis, older age (hazard ratio [HR] 1.09 [95% CI 1.05-1.14], P<0.001) and T2DM (HR 2.87 [95% CI 1.12-7.04], P = 0.021) were significantly associated with all-cause mortality. The factors significantly associated with liver-related events were older age, T2DM, milder hepatic steatosis, and advanced liver fibrosis. Body mass index wasn't associated with either mortality or liver-related events. CONCLUSIONS: T2DM was highly prevalent in NAFLD patients and was significantly associated with both all-cause mortality and liver-related events. The lean patients' prognosis wasn't necessarily better than that of overweight patients.

[A Case of Intraosseous Meningioma Suspected of Osteosarcoma Based on Preoperative Image Examinations].

Intraosseous meningioma(IM)is one of the less frequent tumors of the skull, which often cannot be distinguished from other common skull tumors based on preoperative radiological findings. Herein, we describe a case of IM suspected to be an osteosarcoma based on preoperative image examinations. A 72-year-old woman experienced an impact to her left parietal area, and a subcutaneous tumor appeared in the same area. It had enlarged gradually over seven months, although she exhibited no obvious symptoms. On preoperative diagnostic imaging, the tumor was mainly found in the skull, extending from the subcutaneous area to the intradural space, and was primarily suspected to be an osteosarcoma. After surgery, the pathological diagnosis was atypical meningioma, and there has been no recurrence for 1 year after the surgery. It is necessary for IM to be considered as a differential diagnosis for skull tumors exhibiting characteristics of osteosarcoma.

Endovascular stent placement for venous complications following pediatric liver transplantation: outcomes and indications.

PURPOSE: Advances in interventional radiology (IVR) treatment have notably improved the prognosis of hepatic vein (HV) and portal vein (PV) complications following pediatric living donor liver transplantation (LDLT); however, graft failure may develop in refractory cases. Although endovascular stent placement is considered for recurrent stenosis, its indications are controversial. METHODS: We enrolled 282 patients who underwent pediatric LDLT in our department from May 2001 to September 2016. RESULTS: 22 (7.8%) HV complications occurred after LDLT. Recurrence was observed in 45.5% of the patients after the initial treatment, and 2 patients (9.1%) underwent endovascular stent placement. The stents were inserted at 8 months and 3.8 years following LDLT, respectively. After stent placement, both patients developed thrombotic obstruction and are currently being considered for re-transplantation. 40 (14.2%) PV complications occurred after LDLT. Recurrence occurred in 27.5% of the patients after the initial treatment, and 4 patients (10.0%) underwent endovascular stent treatment. The stents of all the patients remained patent, with an average patency duration of 41 months. CONCLUSION: Endovascular stent placement is an effective treatment for intractable PV complications following pediatric LDLT. However, endovascular stent placement for HV complications should be carefully performed because of the risk of intrastent thrombotic occlusion and the possibility of immunological venous injury.

Human herpesvirus 8-unrelated primary effusion lymphoma-like lymphoma following tyrosine kinase inhibitor treatment for chronic myelogenous leukemia.

A 69-year-old man was diagnosed with chronic myelogenous leukemia (CML) and treated with dasatinib. After two years on dasatinib, the patient achieved complete molecular response, but dasatinib treatment was discontinued due to exacerbation of pleural effusion. Nilotinib and imatinib were started but stopped due to an increase in pleural effusion. Thoracentesis was performed and he was diagnosed with human herpesvirus 8-unrelated primary effusion lymphoma (PEL)-like lymphoma. Complex chromosomal abnormality, including BCL6 rearrangement, was found on chromosome analysis. To the best of our knowledge, this is the first report of PEL-like lymphoma following tyrosine kinase inhibitor treatment for CML.

Symmetric Lipomatosis Arising in the Tongue Presenting as Macroglossia and Articulatory Disorder.

Symmetric lipomatosis is definitively characterized by symmetric, tumorous lipomatous proliferation of adipose tissue that often develops in the head and neck, shoulders, and upper trunk. However, in the oral region, symmetric lipomatosis of the tongue (SLT) is an extremely rare condition related to generalized lipidosis that is often caused by chronic alcoholism. It is characterized by multiple symmetric lipomatous nodules and diffuse bilateral swelling located within the tongue. We report an extremely rare case of SLT arising in an 80-year-old man with a long history of alcoholic liver cirrhosis. He exhibited multiple soft nodular protrusions on the bilateral margin of the tongue presenting as macroglossia for years. Although MR imaging showed multiple fatty masses on both sides of the tongue, there was no elevated tumor mass on the bilateral margin. The patient underwent bilateral partial glossectomy under general anesthesia. Histopathologically, the resected tumor exhibited diffuse infiltration with mature adipose tissue lacking a fibrous capsule. Due to the lipidosis and the unusual presentation of multiple lesions, the lesion was ultimately diagnosed as SLT. At present, after surgery, the patient wears a full-denture and is in excellent condition, with no sign of recurrence, improved QOL, and recovery of masticatory, articulatory, and speech intelligibility functions.

Massive Neurilemoma of the Hard Plate in Which Preoperative Diagnosis Was Difficult.

The patient was an 84-year-old man who was referred to our hospital in mid-December 2012 for a close examination of a mass arising from the left side of the hard palate that was found by a local dentist. The initial examination revealed the presence of a 3.0-cm elastic soft, dome-shaped mass in the left hard palate. CE-CT showed a lesion of size 1.8 × 1.4 cm in the right hard palate, which extended upward and invaded the nasal cavity. The mass was a solid tumor associated with resorption of surrounding bone and expansion of the greater palatine canal. CE-MRI indicated that the mass extended upward and invaded the nasal cavity, and the mass showed hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and an irregular margin with internal enhancement. Abnormal uptake of FDG on PET-CT (SUVmax = 5.2) was observed in the left hard palate. The biopsy site lesion rapidly increased in size and biopsy was performed again in January 2013 due to suspicion of a malignant tumor. The histopathological diagnosis was a suspected malignant neurogenic tumor. Therefore, the patient underwent partial maxillectomy and a split-thickness skin graft in late February 2013. No recurrence was noted 29 months after the operation.

Protocol liver biopsy is the only examination that can detect mid-term graft fibrosis after pediatric liver transplantation.

AIM: To assessed the clinical significance of protocol liver biopsy (PLB) in pediatric liver transplantation (LT). METHODS: Between July 2008 and August 2012, 89 and 55 PLBs were performed in pediatric patients at two and five years after LT, respectively. We assessed the histopathological findings using the Metavir scoring system, including activity (A) and fibrosis (F), and we identified factors associated with scores of ≥ A1 and ≥ F1. Our results clarified the timing and effectiveness of PLB. RESULTS: The incidences of scores of ≥ A1 and ≥ F1 were 24.7% and 24.7%, respectively, at two years after LT and 42.3% and 34.5%, respectively, at five years. Independent risk factors in a multivariate analysis of a score of ≥ A1 at two years included ≥ 2 h of cold ischemic time, no acute cellular rejection and an alanine amino transaminase (ALT) level of ≥ 20 IU/L (P = 0.028, P = 0.033 and P = 0.012, respectively); however, no risk factors were identified for a score of ≥ F1. Furthermore, no independent risk factors associated with scores of ≥ A1 and ≥ F1 at five years were identified using multivariate analysis. A ROC curve analysis of ALT at two years for a score of ≥ A1 demonstrated the recommended cutoff value for diagnosing ≥ A1 histology to be 20 IU/L. The incidence of scores of ≥ A2 or ≥ F2 at two years after LT was 3.4% (three cases), and all patients had an absolute score of ≥ A2. In contrast to that observed for PLBs at five years after LT, the incidence of scores of ≥ A2 or ≥ F2 was 20.0% (11 cases), and all patients had an absolute score of ≥ F2. In all cases, the dose of immunosuppressants was increased after the PLB, and all ten patients who underwent a follow-up liver biopsy improved to scores of ≤ A1 or F1. CONCLUSION: PLB at two years after LT is an unnecessary examination, because the serum ALT level reflects portal inflammation. In addition, immunosuppressive therapy should be modulated to maintain the ALT concentration at a level less than 20 IU/L. PLB at five years is an excellent examination for the detection of early reversible graft fibrosis because no serum markers reflect this finding.

Spontaneous rupture of aneurysms of the ovarian artery at times remote from pregnancy.

Spontaneous rupture of an aneurysm of the ovarian artery is usually considered a rare complication of pregnancy and the puerperium. However, we observed this emergent condition in a 51-year-old postmenopausal woman. We report here our experiences and consider lessons about diagnosis and management that can be drawn from this case and 5 other published cases in multiparous middle-aged women. These lessons include application of contrast-enhanced computed tomography to focus emergent care, surgical intervention, and association with systemic inflammatory response syndrome. We also consider how the cases might shed new light on the pathogenesis and evolution of this condition.

Methotrexate-associated lymphoproliferative disorder arising in the retromolar triangle and lung of a patient with rheumatoid arthritis.

We report an extremely rare case of massive methotrexate-associated lymphoproliferative disorder (MTX-LPD) arising in the retromolar triangle and lung of a patient with rheumatoid arthritis. The patient was a 75-year-old woman who was referred to our department because of severe pain associated with a unilateral ulcer on the left retromolar triangle. The tumor had an extranodal location in the retromolar triangle and in the right lung. A clinicopathologic examination found a lymphocytic infiltrate with increasingly atypical histopathologic features. Atypical large cells were strongly positive in Epstein-Barr virus-encoded small RNA in situ hybridization and in staining with CD20 antibodies. MTX-LPD was diagnosed based on the medical history and histopathologic results. The lesion responded well to withdrawal of MTX followed by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. There have been no signs of recurrence for 4 years since withdrawal of MTX.

Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

Along with the increasing need for living-donor liver transplantation (LDLT), the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts) of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH). The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038), demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001). Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

An autopsy case of secondary iron-overload cardiomyopathy.

A woman over 70 years of age presented with anemia and appetite loss. She had no history of blood transfusions, although she had been receiving iron infusions for anemia for seven years. She had an elevated serum ferritin level (7,951 ng/mL) one month before admission. Abdominal computed tomography showed increased hepatic density and echocardiography showed normal heart valves and heart-wall motion. The patient eventually experienced atrial tachycardia and atrial fibrillation and died of heart failure. An autopsy revealed iron deposits in the liver, pancreas, adrenal glands, thyroid gland, gastric mucosa and myocardium. Iron-overload cardiomyopathy was diagnosed based on the iron deposits, myocardial disarray and interstitial fibrosis.

Diagnostic challenge: intraductal neoplasms of the pancreatobiliary system.

To help pathologists avoid misdiagnosis of intraductal neoplasms arising from the pancreatobiliary system, we report two cases that illustrate diagnostic pitfalls. The first is of a 66-year-old man who complained of appetite loss. An early examination led to a diagnosis of intraductal papillary mucinous neoplasm. Macroscopically, a multilocular cyst without visible mucin was identified. Histologically, the compartments consisted of complex fusion of tubular glands surrounded by dilated pancreatic duct. The neoplasm resembled an acinar cell cystadenocarcinoma. However, the neoplastic cells were negative for trypsin. Thus, the final histopathologic diagnosis was an unusual cystic variant of intraductal tubulopapillary neoplasm (ITPN) of the pancreas. The second case is of a 71-year-old man who complained of right upper quadrant pain. Although bile duct stone was suspected, a polypoid nodule was extracted. Histologically, the nodule was composed of tubular glands, with some complex fusion and focal dysplasia, consistent with carcinoma. In addition, lack of MUC-5AC expression led to an initial impression of ITPN of the bile duct. However, the neoplasm showed dysplastic cells based on the columnar cells resembling pyloric glands, indicating the sequential progression. Thus, the final histopathological diagnosis was intraductal papillary neoplasm of the bile duct with high-grade intraepithelial neoplasia. Because phenotypic variants of intraductal neoplasms of the pancreatobiliary system exist, ITPN and ITPN-mimicking tumor must be carefully differentiated from other intraductal neoplasms.

The effect of nicorandil on small intestinal ischemia-reperfusion injury in a canine model.

BACKGROUND: It has been shown that nicorandil, which has both ATP-sensitive K+ (KATP) channel opener-like and nitrate-like properties, has an organ-protective effect in ischemia-reperfusion injury in several experimental animal models. AIMS: We evaluate the effectiveness of nicorandil on warm ischemia-reperfusion injury of the small intestine in a canine model. METHODS: Eighteen beagle dogs were divided into three groups: the control group (n=6); the nicorandil group (n=6), to which nicorandil was injected intravenously before the ischemia; and the glibenclamide group (n=6), to which glibenclamide, which closes the KATP channel and does not suppress the nitrate effect of nicorandil, was orally administered, and then nicorandil was injected in the same manner as in the nicorandil group. Both the superior mesenteric artery and vein were clamped for 2 h. Superior mesenteric artery blood flow, small intestinal mucosal tissue blood flow, intramucosal pH, and histopathological analyses were compared among the three groups. RESULTS: Superior mesenteric artery blood flow, mucosal tissue blood flow and pHi after reperfusion were significantly maintained in the nicorandil in comparison with the control and the glibenclamide groups. The histopathological findings showed less severe mucosal damage after reperfusion in the nicorandil group compared with the other two groups. Between the control group and the glibenclamide group, no significant differences were observed in all those parameters. CONCLUSION: This study suggests that nicorandil has a protective effect on small intestinal IR injury, and activation of KATP channels plays an important role in inhibiting small intestinal IR injury.

The effect of nicorandil on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model.

BACKGROUND: We evaluated the effectiveness of nicorandil, which has both K(ATP) channel opener-like and nitrate-like properties, in liver ischemia-reperfusion (IR) injury using a porcine total hepatic vascular exclusion (THVE) model. METHODS: Mexican hairless pigs weighing 25-55 kg were used in this study. The animals were divided into three groups. In the nicorandil group (n = 6), a 100 µg/kg bolus of nicorandil was injected intravenously 30 min before the ischemia, and then a continuous infusion (10 µg/kg/min) was administered intravenously for 30 min until just before the ischemia. In the control group (n = 6), a saline solution was injected in the same manner. In the glibenclamide group (n = 6), glibenclamide (0.1 mg/kg), which closes the K(ATP) channel gate, was orally administered 180 min before the hepatic ischemia, and then nicorandil was injected in the same manner as in the nicorandil group. THVE was performed for 120 min, and animals were observed until 360 min after reperfusion. Serum AST and LDH levels, hepatic tissue blood flow (HTBF), and histologic analyses were compared among the three groups. RESULTS: Serum AST and LDH levels in the nicorandil group were significantly lower than in the other two groups after reperfusion, while no significant difference was observed between the control and the glibenclamide groups. HTBF in the nicorandil group was also significantly higher than in the other two groups after reperfusion, while no significant difference was observed between the control and glibenclamide groups. Additionally, histopathologic analyses revealed that the hepatic tissue was better maintained in the nicorandil group than in the other two groups. CONCLUSION: Our results using a porcine THVE model suggest that nicorandil inhibits hepatic IR injury. The K(ATP) channel-opener aspect of nicorandil might be primarily responsible for the hepatoprotective effect.

The suppression of proinflammatory cytokines improves heart function from non-heart-beating donors following transplantation in a canine model.

We evaluated the effectiveness of a suppressant of the production of proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha on a canine heart transplantation model with non-heart-beating donors (NHBDs).Adult mongrel dogs were divided into 3 groups of 5: a control group; FR-1 in which donors were given FR167653, a potent suppressant of IL-1beta and TNF-alpha production; and FR-2 in which both donors and recipients were given FR167653. After measuring the baseline hemodynamic parameters, including cardiac output (CO), left ventricular pressure (LVP), and maximum and minimum rates of increase in LVP (+/- LVdp/dt), FR167653 was administered continuously for 30 minutes before ischemia in the FR-1 and FR-2 groups. Cardiac arrest was obtained by rapid exsanguination from the abdominal aorta and inferior vena cava. The organ was left in the cadaver for 30 minutes. The coronary vascular beds were washed out with 4 degrees C Celsior solution, and then the donor heart was preserved in 4 degrees C Celsior solution for 4 hours. The donor heart was transplanted orthotopically with cardiopulmonary bypass (CPB). FR167653 was administered intravenously from 15 minutes before aortic-cross clamping until the end of the experiment in the FR-2 group. The recipient was weaned from CPB 1 hour after reperfusion. We compared the hemodynamic parameters at 3 hours after reperfusion with the preoperative values in donor animals with the right atrial pressure at 10 mmHg and a 5 microg/kg/min dopamine infusion. Histopathological analysis was also performed.There were no significant differences in the recovery rates of the hemodynamic parameters between the control and FR-1 groups and between the FR-1 and FR-2 groups. However, the recovery rates of CO and -LVdp/dt in the FR-2 group were significantly (P < 0.05) higher than those in the control group. Histopathological analysis showed that myofilaments were better preserved in the FR-2 group compared with the control group.The administration of a suppressant of proinflammatory cytokines before both ischemia and reperfusion effectively preserves donor heart function after transplantation with NHBDs.

The effect of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on pulmonary ischemia-reperfusion injury in a canine model.

UNLABELLED: This study evaluates the effectiveness of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on warm ischemia-reperfusion injury of the lung using a canine mode. MATERIALS AND METHODS: Ten adult mongrel dogs weighing 13-16 kg were used. After a left thoracotomy, the left pulmonary artery and vein were clamped. The left main bronchus was also clamped and then divided, and complete ischemia of the left lung was maintained for 3 h. The left main bronchus was re-anastomosed before reperfusion of the left lung. The right pulmonary artery was ligated immediately after reperfusion of the left lung. The dogs were divided into two groups: the DHP-PMX group (n = 5, DHP-PMX was performed for 120 min, from 30 min before reperfusion to 90 min after reperfusion) and the control group (n = 5). The body temperature of the animals was maintained at 36 degrees C-37 degrees C during the experiment. The PaO2/FiO2 (P/F ratio), AaDO2, and lt-pulmonary vascular resistance (PVR) were measured at 30, 60, 120, 180, and 240 min after reperfusion in both groups, and the two groups were compared. The water content of the lung tissues and histopathology was also analyzed. RESULTS: The P/F ratio decreased remarkably after reperfusion in the control group, and was significantly (p < .05) lower than that in the PMX-DHF group until 240 min after reperfusion. The AaDO2 was significantly (p < .05) lower in the DHP-PMX group than in the control group at 30, 60, and 120 min after reperfusion. The lt-PVR level differed significantly (p < .05) between the two groups until 240 min after reperfusion. The water content in the control group was significantly (p < .05) higher than that in the DHP-PMX group at 240 min after reperfusion. Lung tissues at 120 and 240 min after reperfusion were better preserved pathologically in the DHP-PMX group. CONCLUSION: DHP-PMX therapy reduced warm ischemia-reperfusion injury in the lung using a canine model.