Correlation Between Splenectomy and Portal Vein Complications in Living Donor Liver Transplantation.

OBJECTIVES: In adults undergoing living donor liver transplantation (LDLT), the transplanted livers are partial grafts, and the portal venous pressure is higher than that observed with whole liver grafts. In patients undergoing LDLT concomitant with splenomegaly, portal venous flow is often diverted to collateral vessels, leading to a high risk of portal vein thrombosis. In such cases, occlusion of the collateral veins is important; however, complete occlusion of all collaterals without blocking the blood flow through the splenic artery causes portal hypertension and liver failure. We aimed to examine the effect of performing a splenectomy concomitant with LDLT to reduce portal vein complications. METHODS: Between 1991 and 2017, we performed 170 LDLT operations, including 83 in adults. For this cohort study, adult cases were divided into 2 groups. Group I was those who underwent LDLT without splenectomy (n = 60); Group II was those who underwent LDLT with splenectomy for the reduction of portal hypertension (n = 23). We investigated the incident rates of complications, including blood loss, lethal portal vein thrombosis (intrahepatic thrombosis), acute rejection, and so on. We also investigated the survival rates in both groups. RESULTS: The incident rate of lethal portal vein thrombosis in Group II was significantly lower than that observed in Group I (4.4% vs 21.7%, respectively, P = .0363). There were no statistically significant differences observed between the groups with respect to blood loss, survival rates, and other such parameters. CONCLUSION: LDLT concomitant with splenectomy might effectively reduce the occurrence of portal vein complications in adults.

Effect of Middle Hepatic Vein Tributaries Preserving Technique Until Just Before Graft Retrieval on Donors' Surgical Outcomes in Living Donor Liver Transplantation.

BACKGROUND: The technique of preserving the major tributaries of the middle hepatic vein (MHV) (V5 and V8) until just before graft retrieval is beneficial to minimize congestion time of the graft. However, it remains unclear whether this technique exerts a burden on donors in terms of operative time, blood loss, and postoperative hepatic dysfunction. In this study we investigated adverse effects of the MHV tributaries preserving technique until immediately before graft retrieval on donors' surgical outcomes. METHODS: Data from 71 donors who underwent right hepatectomy without MHV for a liver transplantation at our hospital from January 2002 to August 2016 were retrospectively reviewed. Donors were divided into 3 groups as follows: group 1 (n = 12), no MHV tributary reconstruction; group 2 (n = 33), single MHV tributary reconstruction; group 3 (n = 26), 2 or 3 MHV tributaries reconstruction. Donor operation time, blood loss, proportion of the remnant liver, maximum postoperative total bilirubin, aspartate aminotransferase, alanine transaminase, minimum platelets, prothrombin time, albumin level, number of days in hospital from surgery to discharge, and surgical complications were compared. RESULTS: Compared with groups 2 and 3, group 1 exhibited shorter average operational time and less average blood loss, but the difference was not significant. Comparisons of all other factors indicated no significant differences. CONCLUSION: The technique of preserving the major tributaries of the MHV until just immediately before graft retrieval does not appear to impose an apparent burden on donors.

Arterial Complication After Simultaneous Pancreas-Kidney Transplantation From an Abdominal Aortic Aneurysm Donor: A Case Report.

BACKGROUND: With the current disparity between the donor organ availability and recipient needs, various marginal organs with anatomical variations or concomitant diseases have begun to be used. We present a case of simultaneous pancreas-kidney transplantation (SPKTx) from a marginal donor with a giant abdominal aortic aneurysm who was incidentally found to be an organ donor after brain death. CASE PRESENTATION: The donor was a 66-year-old man who died of brain hemorrhage. We performed cannulation of the aorta from the distal part of left common iliac artery because the aneurysm extended from pararenal aorta to the bilateral common iliac artery. Furthermore, we prepared the left common carotid artery as the backup root of cannulation. Fortunately, we could perfuse the organs from the left common iliac artery. Subsequently, we retrieved the heart, liver, pancreas, and kidney grafts and performed SPKTx. The recipient received anatomically and functionally normal organs. At 19 days after transplantation, a rupture of the renal artery occurred on the graft side. We detected the bleeding point and it was managed quickly. CONCLUSIONS: We safely retrieved the organs from a marginal donor and performed the cooperative donation using a creative approach. We dealt with the complications through cautious postoperative management.

Effects of Subnormothermic Perfusion Before Transplantation for Liver Grafts from Donation After Cardiac Death: A Simplified Dripping Perfusion Method in Pigs.

BACKGROUND: Liver transplantation from donors after cardiac death (DCD) provides a solution to the donor shortage. However, DCD liver grafts are associated with a high incidence of primary graft nonfunction. We investigated the effectiveness of subnormothermic porcine liver perfusion, before transplantation from DCD, on graft viability. METHODS: Landrace pigs (25-30 kg) were randomly allocated to 3 groups (5 per group): heart-beating (HB) graft, transplanted after a 4-hour period of cold storage (CS); DCD graft, retrieved 20 minutes after apnea-induced cardiac arrest (respiratory withdrawal) and transplanted after a 4-hour period of CS; and subnormothermic ex vivo liver perfusion (SELP) graft, retrieved in the same manner as the DCD graft but perfused with a subnormothermic oxygenated Krebs-Henseleit buffer (21-25°C, 10-15 cm H2O) for 30 minutes in a simplified dripping manner, without a machine perfusion system, after the 4-hour period of CS, and subsequently transplanted. RESULTS: Although all animals in the HB group survived for >7 days, all animals in the DCD group died within 12 hours after transplantation. In the SELP group, 2 recipients survived for >7 days and another 2 recipients were killed on day 5. The survival rate was significantly better for SELP than for DCD grafts (P = .0016). The values of tumor necrosis factor α were not significantly different between the SELP and HB groups. Preserved structure of the parenchyma was observed in the SELP group on histologic examination. CONCLUSIONS: A simplified subnormothermic perfusion before liver transplantation is expected to improve graft viability and survival.

A Case of Successful Simultaneous Pancreas-Kidney Transplantation Using the Injured Pancreas Graft.

OBJECTIVE: Graft injuries sometimes occur and may cause complications such as the leakage of pancreatic secretions, which is often lethal. We report our experience of a case of successful simultaneous pancreas-kidney transplantation using injured pancreas graft. PATIENTS AND METHODS: The recipient was a 57-year-old woman with type 1 diabetes mellitus, and the donor was a 30-year-old man with a brain injury. In the donation, the pancreas parenchyma, splenic artery, and gastroduodenal artery were injured iatrogenically. We therefore reconstructed these arteries using vessel grafts and then performed simultaneous pancreas-kidney transplantation. RESULTS: Five days after transplantation, we noted a high titer of amylase in the ascites; therefore, we performed an urgent laparotomy. The origin of the amylase was the injured pancreatic parenchyma, and continued washing and drainage were carried out. We reconstructed the duodenojejunostomy using the Roux-en-Y technique to separate the passage of food from the pancreas graft to prevent injury to other organs due to exposure to pancreatic secretions. Thereafter, we inserted a decompression tube into the anastomosis thorough the blind end of the jejunum. Finally, we inserted 3 drainage tubes for lavage. Following this procedure, the patient recovered gradually and no longer required hemodialysis and insulin therapy. She was discharged from our hospital 56 days after transplantation. CONCLUSION: The restoration of the injured graft was possible by management of pancreatic secretions and use of the donor's vessel grafts. Shortage of donors is a problem throughout the world; thus, it is important to use injured grafts for transplantation if possible.

Splenectomy for Severe Intestinal Bleeding Caused by Portal Hypertensive Enteropathy After Pediatric Living-Donor Liver Transplantation: A Report of Three Cases.

BACKGROUND: The incidence of portal vein thrombosis after pediatric living-donor liver transplantation (LDLT) is reported to be higher than that after deceased-donor or adult liver transplantation. Portal vein thrombosis can cause portal hypertension and related complications, including portal hypertensive gastropathy or portal hypertensive enteropathy (PHE). PHE, in particular, can lead to severe intestinal bleeding, which is extremely difficult to treat. However, the pathogenesis of and appropriate treatment for PHE are not clearly defined, especially after pediatric LDLT. METHODS: Herein, we report three cases of refractory intestinal bleeding caused by PHE after pediatric LDLT, which were treated with splenectomy. RESULTS: The time between LDLT and splenectomy was 43, 92, and 161 months, respectively. All 3 patients were discharged from the hospital without any peri-operative complications and were doing well, with no adverse effects at 174, 81, and 12 months after splenectomy, respectively. Although shunt surgeries, including the use of a meso-Rex shunt, are reported to be a useful option when the portal vein is completely occluded, adhesiotomy around the liver graft would be required, which could damage the hepatopetal collateral vessels that maintain portal vein flow to the graft. Therefore, shunt surgeries, which can lead to re-transplantation, are considered to be highly risky as a first-line treatment option, particularly considering the limited accessibility to deceased donor organs in our country. CONCLUSIONS: Our data demonstrate that simple splenectomy, although considered a palliative treatment, can be a safe and effective method to control severe intestinal bleeding caused by PHE after pediatric LDLT.

Poor Long-Term Outcomes of Adult Liver Transplantation Involving Elderly Living Donors.

BACKGROUND: Donor hepatectomy requires particular care to ensure the safety of the donor and the success of the liver transplantation. The aim of this study was to evaluate the effect of donor age on the postoperative outcomes of liver transplant donors and the long-term graft survival rates. METHODS: We retrospectively reviewed 56 consecutive adult patients who underwent living donor liver transplantation at our institution between April 2001 and August 2010. Donors and recipients were divided into 2 groups, based on the age of the donor: the elderly donor group (donor age ≥50 years) and the younger donor group (donor age <50 years). Perioperative variables, postoperative complication rates, and long-term graft survival rates were compared between the 2 groups. RESULTS: The average ages in the elderly donor group and younger donor group were 58 years and 32 years, respectively. Baseline data excluding the age of the donor did not differ between the groups, nor did the overall complication rates of the donors. Hospital stays were longer in the elderly donor group than in the younger donor group (25 vs 18 days, P < .05). The 1-, 3-, and 5-year graft survival rates were 80%, 60%, and 50% in the elderly donor group, and 89%, 87%, and 82% in the younger donor group, respectively (P = .0002). CONCLUSIONS: Donor hepatectomy can be performed safely in elderly patients. However, compared with younger donors, their hospital stays were longer and the graft survival rates were shorter.

The Significance of Screening for HLA Antibodies in the Long-Term Follow-up of Pediatric Liver Transplant Recipients.

BACKGROUND: Post-transplant donor-specific anti-HLA antibodies (DSA) reportedly have detrimental effects on the outcomes of organ transplantation. However, the prevalence of post-transplant DSA in the long term after pediatric liver transplantation remains unclear, and the significance of post-transplant DSA is unknown. The aim of this cross-sectional study was to determine the prevalence of and characteristics of patients with post-transplant DSA. MATERIALS AND METHODS: Of the 84 pediatric liver transplant recipients who were followed up in the outpatient department of our institution, 34 patients with available HLA typing data were included after they or their parent(s) provided informed consent for DSA evaluations. Luminex single-antigen bead assays were performed, and a mean fluorescence intensity of ≥1000 was used as the cut-off for a positive reaction. RESULTS: No class I DSA were detected, whereas class II DSA were detected in 11 patients (32%). There were no differences in age at transplantation, immunosuppressive drugs, or follow-up period between the DSA-positive and DSA-negative patients. The rate of positive pre-transplant complement-dependent cytotoxicity crossmatch was higher with class II DSA than without, although the difference was not statistically significant. CONCLUSIONS: The utility of screening for class I DSA was insignificant in the long-term follow-up of pediatric liver transplant recipients. The prevalence of class II DSA was relatively high; therefore, screening for class II DSA might be justified, although a follow-up survey of the association between post-transplant class II DSA and the long-term clinical course needs to be conducted.

Relationship Between Bile Duct Reconstruction and Complications in Living Donor Liver Transplantation.

OBJECTIVES: In living donor liver transplantation (LDLT), the recipient bile duct is thin and short. Bile duct complications often occur in LDLT, with persistent long-term adverse effects. Recently, we began to perform microsurgical reconstruction of the bile duct. The purpose of this study was to investigate the relationship between bile duct reconstruction methods and complications in LDLT. METHODS: From 1991 to 2014, we performed 161 LDLTs (pediatric:adult = 90:71; left lobe:right lobe = 95:66). In this study, we retrospectively investigated the initial bile duct complications in LDLT and performed univariate and multivariate analyses to identify the independent risk factors for complications. RESULTS: The most frequent complication was biliary stricture (9.9%), followed by biliary leakage (6.8%). On univariate and multiple logistic regression analysis, the independent risk factors for biliary stricture were bile leakage (P = .0103) and recurrent cholangitis (P = .0077). However, there were no risk factors for biliary leakage on univariate analysis in our study. The reconstruction methods (hepaticojejunostomy or duct-to-duct anastomosis) and reconstruction technique (with or without microsurgery) were not risk factors for biliary stricture and leakage. CONCLUSION: In this study, the most frequent complication of LDLT was biliary stricture. The independent risk factors for biliary stricture were biliary leakage and recurrent cholangitis. Duct-to-duct anastomosis and microsurgical reconstruction of the bile duct were not risk factors for biliary stricture and leakage.

Successful Case of Somatostatin Analog Stopping Gastrointestinal Bleeding, One of the Most Frequent Complications After Simultaneous Pancreas-kidney Transplantation: A Case Report.

OBJECT: Pancreas transplantation has the highest surgical complication rate of all routinely performed organ transplantation procedures. The complications are not only caused by the pancreas itself but also occur due to issues with the transplant recipient. We report the case of a patient who experienced massive gastrointestinal bleeding after simultaneous pancreas-kidney transplantation (SPK), which was stopped successfully using somatostatin analog. PATIENTS AND METHODS: The patient was a 45-year-old woman with diabetes mellitus type 1 who underwent SPK with enteric drainage. She had melena 5 days after SPK. RESULTS: At first, we suspected that the melena was caused by the transplanted duodenum because of rejection and ischemic changes. The patient experienced severe bleeding 9 days after SPK. We quickly performed open surgery and inserted an endoscope from the recipient's ileum to investigate the transplanted duodenum. However, no bleeding source was found, including in the transplanted duodenum and the recipient's ileum end. We determined that the bleeding source was the recipient's ascending colon. We attempted to perform endovascular treatment but could not detect the source of the bleeding; therefore, we used somatostatin analog to let the blood vessels shrink and reduce pancreatic output. Thereafter, the function of the transplanted pancreas and kidney gradually recovered, and the recipient was discharged 154 days after SPK. CONCLUSION: Gastrointestinal bleeding is a lethal complication and has several different causes, such as mucosal rejection, ischemic changes, and exocrine output of the pancreas graft. Somatostatin analog is one of the most acceptable treatments for patients who have gastrointestinal bleeding after SPK.

Edaravone, a free radical scavenger, improves the graft viability on liver transplantation from non-heart-beating donors in pigs.

BACKGROUND: Although liver transplantation from non-heart-beating donors (NHBDs) is an effective way to overcome shortage of donors, primary graft nonfunction is often noted in these grafts. We have previously reported that edaravone, a free radical scavenger, has a cytoprotective effect on warm ischemia-reperfusion injury and improves the function of liver grafts from NHBDs in a rat model of ischemia-reperfusion. The purpose of this study was to investigate the effects of edaravone on liver transplantations from NHBDs. METHODS: Pigs were divided into three groups: (1) a heart-beating (HB) group (n = 5), in which liver grafts were retrieved from HB donors; (2) a non-heart-beating (NHB) group (n = 4), in which liver grafts were retrieved under apnea-induced NHB conditions; and (3) an edaravone-treated (ED) group (n = 5), in which liver grafts were retrieved in the same manner as the NHB group and treated with edaravone at the time of perfusion (3 mg/L in University of Wisconsin [UW] solution), cold preservation (1 mg/L in UW solution), and after surgery (1 mg/kg/d). The grafts from all groups were transplanted after 4 hours of cold preservation. RESULTS: In the ED group, the 7-day survival rate was significantly higher than that in the NHB group (80% versus 0%, P = .0042, Kaplan-Meier log-rank test). Furthermore, on histologic examination, the structure of sinusoids in the ED group was well preserved and similar to that in the HB group. CONCLUSIONS: Edaravone may improve the viability of liver grafts from NHBDs.

Risk factors for portal vein stenosis in living-donor liver transplantation.

BACKGROUND: In living-donor liver transplantation (LDLT), the recipient's portal vein is short. Furthermore, portal vein thrombosis and stenosis can be lethal complications. We had begun the systemic administration of gabexate mesilate, a strong serine protease inhibitor, which has cytoprotective effects of endothelial cells. It is often effective on disseminated intravascular coagulation. The purpose of this study was to examine the effects of gabexate mesilate and to reveal risk factors for portal vein stenosis in LDLT. METHODS: From 1991 to 2012, we performed 153 LDLTs. For the present cohort study, patients were divided into 2 groups. In group I, we treated with gabexate mesilate mildly (0-20 mg/kg/d; n = 29). In group II, we treated with gabexate mesilate at full dose (40 mg/kg/d; n = 124). We investigated the survival rates of both groups and performed univariate and multivariate analyses to identify the independent risk factors for portal vein stenosis. RESULTS: The survival rate of group II was significantly better than that of group I (P < .05). On univariate analysis, the risk factors identified to be associated with a P value of <.20 were old age (P = .0385), heavy body weight (P = .1840), tall height (P = .1122), small lumen diameter of portal vein (P = .1379), high volume of blood loss (P = .0589), small amount of gabexate mesilate infusion (P = .0103), and large graft weight (P = .1326). On multiple logistic regression analysis we identified old age (P = .0073) and small amount of gabexate mesilate infusion (P = .0339) to be the independent risk factors for portal vein stenosis. CONCLUSIONS: On multivariate analysis, we found that gabexate mesilate infusion contributed to the reduction of portal vein stenosis.

Impact of the 2011 Great East Japan Earthquake on the resumption of alcohol consumption after living-donor liver transplantation for alcoholic cirrhosis: a report of two cases.

Alcoholic liver disease (ALD) is a leading indication for liver transplantation (LT) in Western countries. The rate of resumption of alcohol abuse is 7% to 95% after LT for ALD. A high prevalence of alcohol abuse has been observed in disaster-exposed populations; however, little is known about the association between resumption of alcohol abuse after LT and disasters. Between June 2007 and March 2011, 3 patients with alcoholic cirrhosis (2 men and 1 woman) underwent living-donor LT (LDLT) at Tohoku University Hospital, Sendai, Japan. The female patient died of graft failure 6 months after LDLT. The other patients (ages 55 and 56 years), who survived to discharge, resumed alcohol abuse after the 2011 Great East Japan Earthquake. Before transplantation, both patients had been abusing alcohol for >35 years, with a daily ethanol intake of 110 g and 140 g, respectively. The period of abstinence from alcohol consumption ranged from 4 to 6 months. After transplantation, patients showed good compliance with treatment and seemed at low risk of relapse until the earthquake. One patient was living in the nuclear evacuation zone at Fukushima, and resumed alcohol consumption after the evacuation. Another patient resumed alcohol consumption while temporarily living apart from his family during restoration work after the disaster. Extreme stress and changes in living arrangements after the Great East Japan Earthquake seemed to trigger the desire to drink. This is the first report on patients who underwent LT for ALD and who resumed alcohol consumption after a disaster.

[Home parenteral nutrition in the elderly].

The number of elderly patients receiving home parenteral nutrition (HPN) has been increasing. This could result from several factors such as advances in HPN therapy and the natural aging of long-term older patients on HPN. Our experience shows that elderly patients receiving HPN are likely to be highly dependent on family members to supervise their HPN therapy. Therefore, indepth education of family members is essential before HPN is initiated. The important points to manage the elderly HPN patients are as follows: 1) It takes a long time for the elderly to learn the technique. 2) They often make technical mistakes. 3) In many cases, patients are not living with their children. Therefore, it is often difficult for them to support the patient's HPN therapy. 4) Nurses play an important role in giving instructions on catheter care and HPN techniques to the patient or family members.

Biphasic effect of hydrogen peroxide on field potentials in rat hippocampal slices.

In the CA1 region of rat hippocampal slices, H2O2 (0.294-2.94 mM) caused initial augmentation, and subsequent long-lasting depression, of population spikes and excitatory postsynaptic potentials. The effect of H2O2 may not be mediated by its degradation product, hydroxyl radicals, because an iron chelator deferoxamine did not block the effect. A catalase inhibitor 3-amino-1,2,4-triazole only modestly attenuated the initial augmentation, suggesting that the effect of H2O2 is not attributable to catalase-dependent O2 generation, either. An N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid had no influence on the effect of H2O2, whereas a gamma-aminobutyric acid type A receptor channel blocker picrotoxin attenuated long-lasting depression, indicating that gamma-aminobutyric acid-mediated inhibition is altered during the depression phase. The initial augmentation but not subsequent depression was attenuated by a phospholipase A2/C inhibitor 4-bromophenacyl bromide, suggesting the involvement of lipid signaling molecule(s) in the enhancement of excitatory synaptic transmission. These results suggest that H2O2 regulates hippocampal synaptic transmission via multiple mechanisms.

[Variant angina due to deficiency of intracellular magnesium by anorexia nervosa].

A 51-year-old man who had a past history of gastric resection for medically uncontrollable gastric ulcer has loss of appetite that recurs periodically. And he has frequently presented spontaneous angina early in the morning since 1984. He was diagnosed as having variant angina by the documentation of typical ST elevation during anginal attack and also by showing coronary artery spasm (#2 and #12) during hyperventilation on coronary arteriography. A large quantity of calcium blocking agents and nitrates could not improve his symptoms. Lack of intracellular magnesium by loss of appetite was suspected from a daily excretion of urine magnesium (5.3 mEq) and magnesium tolerance test (56.7%). To confirm the effect of magnesium administration, the second coronary arteriography was performed. After magnesium sulphate (80 mEq, hourly) was injected, coronary artery spasm could not be induced by ergonovine. And orally magnesium oxide, calcium blocking agents and nitrates were started. Anginal attack disappeared with increasing urine magnesium.

Proteinuria induced by transplantable rat pituitary tumor MtT SA5. Model for homologous protein-overload proteinuria.

Intensive proteinuria accompanied by marked renal enlargement occurs in rats bearing functioning pituitary tumor MtT SA5. Urinalysis showed that protein excretion was up to 700 mg/day, and that the excreted protein consisted mostly of albumin. However, serum total protein and albumin levels remained almost unchanged. Histological examination revealed glomerular lesions, hyaline casts in the tubules, and proliferation of the tubular epithelium. The glomerular lesions consisted of accumulation of proteinaceous material in the subcapsular space; its organization and formation of fibrous crescents was with or without epithelial crescents. Electron microscopy revealed loss of foot processes and accumulation of absorption droplets in glomerular epithelial cells. Removal of the tumor resulted in a rapid reduction in urinary protein excretion. However, proteinuria persisted for at least 4 weeks after tumor removal with levels of approximately one-fourth of those before tumor removal. Histological changes of the kidneys resolved to some extent but damage still remained in the glomerular epithelial cells 4 weeks after tumor removal. Although proteinuria in animals bearing functioning pituitary tumors has long been implicated in hyperprolactinemia, the present study suggests that proteinuria in tumor-bearing rats is a control mechanism for overproduction of albumin in the liver stimulated by elevated serum growth hormone since hyperalbuminemia and possibly the hyperfibrinogenemia would cause the elevation of blood viscosity, resulting in thrombosis, unless control mechanisms were present. This proteinuria may serve for studies of glomerular permeability disorders as a model for homologous protein-overload proteinuria.