Incidence and predictors of post-reperfusion syndrome in living donor liver transplantation

A characteristic pattern of hemodynamic changes that may occur in reperfusion phase of liver transplantation (LT) is known as post-reperfusion syndrome (PRS). In this study, we determined the frequency of PRS and evaluated possible predictors of PRS. The medical records of 152 patients who underwent living donor LT were reviewed. PRS was defined as a decrease in mean arterial pressure of more than 30% from the baseline value for more than one min during the first five min after reperfusion. The frequency of PRS was determined, and patients were divided into two groups: PRS group and non-PRS group. Donor factors, preoperative and intraoperative recipient factors, and postoperative outcomes were compared between the two groups. PRS occurred in 58 recipients (34.2%). Preoperative model for end-stage liver disease scores of recipients and percentage of graft steatotic changes were higher in PRS group. PRS group showed higher heart rates and lower hemoglobin values preoperatively. Before reperfusion, PRS group received more transfusion and their urine output was less than that of non-PRS group. Postoperatively, peak bilirubin during the first five d after LT was higher in PRS group. In conclusion, both severity of liver disease and graft steatosis may increase risk for PRS in LT. Further prospective studies of PRS in its relationship to outcome are indicated.     

Clinical characteristics and outcomes of PTLD following intestinal transplantation

Post‐transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single‐center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy‐proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow‐up time of 6.4 (1.6‐14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re‐ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.     

甘氨酸和丙酮酸对于局部缺血再灌注后的全身性保护作用

目的 肠系膜上动脉缺血/再灌注可引起小肠局部损伤,甚至休克和心肺功能障碍。丙酮酸和甘氨酸已被证实对缺血再灌注损伤的局部组织器官有保护作用。本文研究其对小肠缺血再灌注之后全身血流动力学以及心肺功能等的影响。方法 采用雄性SD大鼠,麻醉后建立血流动力学监测,建立肠系膜上动脉缺血90 min、再灌注120 min的模型。24只大鼠随机分为4组：丙酮酸组（再灌注前给予丙酮酸50 mg/kg,n=6）;甘氨酸组（再灌注前给予甘氨酸20 mg/kg,n=6）;林格组（再灌注前给予林格氏液1 mL,n=6）;假手术对照组（n=6）。术中记录平均动脉压、心脏指数、肺动脉压等,并估计循环血管阻力。采集动脉血进行血气分析和心肌标志物检测。观察结束后处死大鼠,取小肠、心脏、肺脏、肝脏进行组织学观察。结果 丙酮酸和甘氨酸均能有效稳定血流动力学参数,维持较好的心功能。其中甘氨酸组复苏所需晶体体积显著少于对照组。丙酮酸、甘氨酸对代谢性酸中毒的抑制作用明显优于林格氏液（P<0.01）。甘氨酸组的小肠、肺、心、肝病理评分和中性粒细胞浸润明显低于林格组（P<0.01）,但仍高于假手术组（P<0.01）。丙酮酸组、甘氨酸组CKMB、肌钙蛋白I水平低于林格组,但仍高于假手术组（P<0.01）。结论 丙酮酸和甘氨酸能在严重的局部缺血再灌注之后稳定全身循环状态,改善休克的复苏效果,既可减轻局部组织器官的缺血再灌注损伤,又可保护心肺等器官的功能。     

Extracorporeal life support as a bridge to high-urgency heart transplantation

Extracorporeal life support (ECLS) represents an effective, emergent therapy for patients with end-stage heart failure or cardiac arrest. However, ECLS is typically not used as a bridge to heart transplantation because of the limited duration of ECLS. In France, high-urgency priority heart transplantation remains a possibility for transplant patients who are on ECLS. In this article, we present our experience with high-urgency priority heart transplantation after ECLS. From July 2004 to December 2009, 242 patients underwent emergent ECLS. Heart transplantation was performed in eight of these patients. Time of ECLS was 6.3 ± 4.6 d. Before heart transplantation, all patients on ECLS had decreased organ dysfunctions and four were conscious. Despite frequent post-operative complications, no death occurred during the first year after transplantation. In our experience, ECLS is a valid method of supporting patients awaiting high-urgency heart transplantation and can be used as a short-term bridge to heart transplantation.     

Immunophenotypic profile and clinical outcome of monoclonal B‐cell lymphocytosis in kidney transplantation

Monoclonal B‐cell lymphocytosis (MBL) is a lymphoproliferative disorder characterized by clonal expansion of a B‐cell population in peripheral blood of otherwise healthy subjects. MBL is divided into CLL (chronic lymphocytic leukemia)‐like, atypical CLL‐like and non‐CLL MBL. The aim of this study was to evaluate immunophenotypic characteristics and clinical outcomes of MBL in kidney transplant (KT) recipients. We retrospectively evaluated 593 kidney transplant (KT) recipients in follow‐up at our center. Among them, 157 patients underwent peripheral blood flow cytometry for different clinical indications. A 6‐color panel flow cytometry was used to diagnose MBL. This condition was detected in 5 of 157 KT recipients. Immunophenotypic characterization of MBL showed four cases of non‐CLL MBL and one case of CLL‐like MBL. At presentation, median age was 65 years (range 61‐73). After a median follow‐up of 3.1 years (95%CI; 1.1‐5) from diagnosis, patients did not progress either to CLL or to lymphoma. The disorder did not increase the risk of malignancy, severe infections, graft loss and mortality among our KT recipients. Surprisingly, all cases were also affected by concomitant monoclonal gammopathy of undetermined significance, which did not progress to multiple myeloma during follow‐up. In conclusion, our data suggest that MBL is an age‐related disorder, with non‐CLL MBL being the most common subtype among KT recipients.     

The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation

Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple logistic regression identified PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06–4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.     

Effects of lazaroids on intestinal ischemia and reperfusion injury in experimental models

Mesenteric ischemia occurs in a number of clinically relevant pathophysiologic processes, including sepsis, hemorrhage, intestinal transplantation, severe burns, and mesenteric thrombosis. The readmission of molecular oxygen into an ischemic tissue promotes the oxidation of resuscitated tissue with certain pathophysiologic mechanisms. Depending on the duration and the intensity of ischemia, reoxygenation of the intestine that has been reperfused may further induce tissue injury. Intestinal ischemia and reperfusion injury can accelerate complex processes between the endothelium and different cell types leading to microvascular injury, cellular necrosis, and apoptosis. The injury due to reperfusion is found predominantly in the intestinal mucosa and submucosa, causing endothelial detachment. The 21-aminosteroids (lazaroids) are a family of compounds that inhibit lipid membrane peroxidation. Many of the performed studies show conflicting results, which reflect differences in experimental design, evolving time that (I/R) is induced, total or partial vascular occlusion, dosage of the lazaroid, and the exact period of time that the lazaroid is administered.     

Cardiac arrest associated with reperfusion of the liver during transplantation: incidence and proposal for a management algorithm

Cardiac arrest associated with reperfusion of the liver allograft in a euvolemic patient is a rare but potentially devastating event. There are few case series describing experience with this complication and no published management protocols guiding treatment. This article is a retrospective case series of patients experiencing post‐reperfusion intraoperative cardiac arrest between 1997 and 2011. Among 1581 liver transplants, 16 (1%) patients experienced post‐reperfusion cardiac arrest. Among patients with intraoperative arrests, 14 (88%) patients required open cardiac massage. Seven (44%) were placed on cardiopulmonary bypass (CPB) when cardiac activity failed to adequately recover. Placement on CPB reversed cardiac pump failure and established a perfusing rhythm in six of seven (86%) recipients, leading to one of seven (14%) intraoperative mortality. Recovery of myocardial function was associated with low early survival with only 3/7 (43%) patients who underwent CPB surviving until discharge. Among all patients who survived the perioperative period, one‐yr survival was 70% (N = 7), and five‐yr survival was 50% (N = 5). Cardiac arrest during liver transplantation is associated with a poor prognosis during the perioperative period. In patients who do not recover cardiac activity after standard resuscitative measures, progression to physiologic support with systemic anticoagulation and CPB may allow correction of electrolyte derangements, maintenance of cerebral perfusion, and myocardial recovery.     

Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation

One of the leading causes of long-term kidney graft loss is chronic allograft injury (CAI), a pathological process triggered by alloantigen-dependent and alloantigen-independent factors. Alloantigen-independent factors, such as cold ischemia (CI) may amplify the recipient immune response against the graft. We investigated the impact of prolonged cold ischemia and the subsequent delayed graft function on CAI in a fully MHC-mismatched rat model of kidney allotransplantation. Prolonged CI was associated with anticipation of proteinuria onset and graft function deterioration (ischemia: 90d; no ischemia: 150d), more severe tubular atrophy, interstitial fibrosis, and glomerulosclerosis, and increased mortality rate (180d survival, ischemia: 0%; no ischemia: 67%). In ischemic allografts, T and B cells were detected very early and were organized in inflammatory clusters. Higher expression of BAFF-R and TACI within the ischemic allografts indicates that B cells are mature and activated. As a consequence of B cell activity, anti-donor antibodies, glomerular C4d and IgG deposition, important features of chronic humoral rejection, appeared earlier in ischemic than in non-ischemic allograft recipients. Thus, prolonged CI time plays a main role in CAI development by triggering acceleration of cellular and humoral reactions of chronic rejection. Limiting CI time should be considered as a main target in kidney transplantation.     

展望受体低氧预适应在原位肝移植中的应用

了解原位肝移植过程中无肝期门静脉淤血引起的肠道淤血性缺氧对肝完全缺血再灌注损伤的影响以及肠道缺氧低氧耐受的内源性保护机制。采用文献回顾的方法加以综述。对肝移植受体肠道黏膜屏障功能的保护可减轻移植肝脏再灌注损伤。受体低氧预适应可能为移植肝脏再灌注损伤的保护提供一条全新的途径。     

Serum albumin level during intestinal exfoliative rejection: a potential predictor of graft recovery and patient outcome

Exfoliative rejection is a severe complication after intestinal transplant. The assessment of mucosa histology is restricted to the area reached by endoscopy. We aim to evaluate the serum albumin (SA) value as a parameter of graft damage and clinical prognosis in intestinal exfoliative rejection (ExR). The present study is a retrospective analysis of 11 episodes of ExR occurred in a cohort of 26 patients. SA levels were measured 24 h after diagnosis and twice a week thereafter and then correlated with parameters of clinical and graft histological recovery (HR). During ExR, all patients had very low SA levels, reaching a minimum average of 1.9 ± 0.3 g/dL. According to the value of albumin levels at ExR diagnosis, the patients were grouped finding a correlation with their clinical evolution. Six ExR episodes presented with severe hipoalbuminemia (<2.2 g/dL; p < 0.05) that correlated with worse patient and graft outcome, ranging from graft loss and need for re‐transplantation to delayed clinical and HR. SA at ExR diagnosis may be an indicator of the severity of the ExR process, and it could also be used as an early predictor of patient and graft outcome.     

Rabbit anti‐rat thymocyte immunoglobulin preserves renal function during ischemia/reperfusion injury in rat kidney transplantation

Ischemia/reperfusion (I/R) injury is an important cause of renal graft dysfunction in humans. Increases in cold and warm ischemia times lead to a higher risk of early post‐transplant complications including delayed graft function and acute rejection. Moreover, prolonged cold ischemia is a predictor of long‐term kidney graft loss. The protective effect of rabbit anti‐rat thymocyte immunoglobulin (rATG) was evaluated in a rat model of I/R injury following syngeneic kidney transplantation. Serum creatinine concentration was evaluated at 16 h and 24 h post‐transplant. Animals were sacrificed 24 h post‐transplant for evaluation of histology, infiltrating leukocytes, nitrotyrosine staining, and apoptosis. rATG was effective in preventing renal function impairment, tissue damage and tubular apoptosis associated with I/R only when was given 2 h before transplantation but not at the time of reperfusion. Pretransplant rATG treatment of recipient animals effectively reduced the amount of macrophages, CD4⁺, CD8⁺ T cells and LFA‐1⁺ cells infiltrating renal graft subjected to cold ischemia as well as granzyme‐B expression within ischemic kidney. On the other hand, granulocyte infiltration and oxidative stress were not modified by rATG. If these results will be translated into the clinical setting, pretransplant administration of Thymoglobuline^® could offer the additional advantage over peri‐transplant administration of limiting I/R‐mediated kidney graft damage.     

A rare complication after allogeneic stem cell transplantation: post‐transplant erythrocytosis

Post‐transplant erythrocytosis is an infrequent complication and has been reported after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in aplastic anemia, acute myeloid leukemia, and chronic myeloid leukemia. The pre‐disposing factors and treatment are not clearly defined. We present 11 post‐transplant erythrocytosis cases. More studies should be conducted to distinguish the pathogenesis and follow‐up for this rare complication.     

Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation – a randomized clinical trial

Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation.     

肠缺血后肺内一氧化氮合酶的表达及其意义

目的　研究不同时相小肠缺血 /再灌注引起的急性肺损伤 (ALI)过程中 ,内皮型一氧化氮合酶 (eNOS)及诱导型一氧化氮合酶 (iNOS)的表达及其在ALI发生中的作用。方法　SD大鼠 ,阻断肠系膜上动脉 (SMA) 60min ,根据不同再灌注时间随机分为A(60min)、B(12 0min)、C(2 40min)组。AC、BC、CC组分别为其对照组。Evans蓝法测定大鼠肺毛细血管通透性、逆转录 聚合酶链式反应 (RT PCR)法测定肺NOSmRNA表达、Western印迹法测定肺组织NOS表达 ,同时进行小肠组织学检查以评价肠损伤程度。结果　肺漏出量随着小肠再灌注时间延长而增加 ,A/AC组 :2 2 9.82± 18.13 /198.0 0± 2 2 .17;B/BC组 :2 74.12± 2 5 .40 /178.48± 2 0 .3 7;C/CC组 :2 69.87±2 0 .93 /195 .68± 10 .99。A与B组间比较差异有显著性。组织学检查 :小肠损伤在A组、B组及C组三组间差异有显著性。肺组织iNOS表达随再灌注时间延长而逐渐增加 ,其中A、C组比较差异有显著性 ,肺组织eNOS表达各组间差异无显著性。结论　肠道缺血 /再灌注损伤 :(1)导致肺毛细血管通透性改变及微血管漏出增加 ;(2 )引起肺内iNOS表达增高 ,且与小肠再灌注时间成正比 ,与肺血管漏出成正比。提示iNOS在肠缺血 /再灌注导致的肺损伤过程中可能起重要作用     

Roux limb volvulus after pancreas transplantation: an unusual cause of pancreatic graft loss

Abstract: Pancreas transplantation with enteric drainage avoids the long‐term urological complications of bladder drainage. Increasing use of this technique raises the possibility of complications from the enteric reconstruction. This report describes a patient five yr after left‐sided pancreas transplant with Roux‐en‐Y enteric drainage, presenting with abdominal pain, leukocytosis and radiological evidence of bowel obstruction. Exploration revealed a volvulus of the Roux limb as it passed through the mesocolon, with necrosis of the allograft duodenum and marked congestion of the pancreas. This is the first report of pancreas graft loss due to this entity, which should be recognized as an unusual cause of abdominal pain after pancreas transplantation. Potential bowel complications related to the sigmoid mesentery in left‐sided pancreas transplantation are additional reasons for right‐sided placement of the pancreas allograft.