Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review.

Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.

Infected large pore meshes may be salvaged by topical negative pressure therapy.

PURPOSE: To evaluate the efficacy of negative pressure therapy for superficial and deep mesh infections after ventral and incisional hernia repair by a prospective monocentric observational study. METHODS: During a 6-year period, 724 consecutive open ventral and incisional hernia repairs were performed. Pre- and intraoperative data as well as postoperative complications were prospectively recorded. In case of wound infection, negative pressure therapy (NPT) was our primary treatment. RESULTS: Sixty-three patients (8.7 %) were treated using negative pressure therapy after primary ventral and incisional hernia repair. Infectious complications needing NPT occurred in 54 patients in the retromuscular group (54/523; 10.3 %), none when laparoscopically treated and in 9 patients (9/143; 6.3 %) treated by an open intraperitoneal mesh technique. Considering outcome, all meshes were completely salvaged in the retromuscular mesh group after a median of 5 dressing changes (range, 2-9), while in the intraperitoneal mesh, group 3 meshes needed complete (n = 2) or partial (n = 1) excision. Mean duration to complete wound closure was 44 days (range, 26-63 days). CONCLUSION: NPT is a useful adjunct for salvage of deep infected meshes, particularly when large pore monofilament mesh is used.

Early arterial revascularization after hepatic artery thrombosis may avoid graft loss and improve outcomes in adult liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) represents a devastating complication after liver transplantation (LT), occurring in 1.6%-9.2% of adult recipients. Treatments of HAT include thrombectomy and thrombolysis (with or without redo of the arterial anastomosis), percutaneous thrombolysis through an angiogram, liver retransplantation, and clinical observation. METHODS: We retrospectively analyzed data from 739 adult LTs between January 1992 and September 2009. HAT was classified as early (E-HAT), when occurring within the first 30 days after LT, or late HAT (L-HAT), when diagnosed from the 2nd month onward. HAT suspected clinically was confirmed by Doppler ultrasound and angiography in all cases. Attempted revascularization was defined as early (ER) if performed within the first 2 weeks after LT and late (LR) if performed between 15 and 30 days. RESULTS: After a median follow-up (FU) of 62 months (range, 1-227 months), HAT occurred in 31/739 grafts (4.3%). E-HAT was recorded in 25/31 cases (3.4%) and L-HAT in 11/31 cases (0.8%). ER was performed in 20/31 patients (65%) leading to 62% graft salvage; it was 81% when the revascularization was performed within the first week after LT (P = ns). LR was unsuccessful in all cases (P = .08). The overall incidence of BC among rescued grafts was 54% without graft loss during FU. Graft survival was 79% versus 71%; and 50% versus 50% at 1 and 3 years for E-HAT and L-HAT, respectively (P = ns). CONCLUSIONS: Urgent revascularization in cases of early HAT may decrease graft loss, especially when performed within the first week after LT, with improved overall outcomes.

Prospective evaluation of intraoperative hemodynamics in liver transplantation with whole, partial and DCD grafts.

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.

Improved results for adult split liver transplantation with extended right lobe grafts: could we enhance its application?

OBJECTIVE: Split liver transplantation (SLT) allows grafting of 2 recipients with 1 allograft. Results of adult SLT have improved since its first introduction. Children benefit most from SLT, while among some adult liver transplanters there are concerns about splitting a liver, turning a good quality graft into a marginal one. We performed a single center retrospective review to address this issue. PATIENTS AND METHODS: Between June 2001 and August 2008, we performed 22 extended right liver graft (eRLG) transplantations in 21 adult patients. RESULTS: Eleven donors (50%) did not meet the Eurotransplant criteria for optimal donors. Forty-one percent of eRLG donors showed hemodynamic instability at the time of harvest. Eighteen (82%) splitting procedures were performed ex situ. The main indications for transplantation were alcoholic liver cirrhosis (32%), hepatitis C-related cirrhosis (18%), and acute liver failure (18%). Mean recipient age was 54 years (range, 17-69 years); median Model for End-Stage Liver Disease (MELD) score was 15 (range, 7-40). Patients were followed for a median of 16 months (range, 4-92 months) following transplantation. We observed 5 (23%) vascular and 3 (14%) biliary complications. Overall patient survival was 84% at 3 years; overall graft survival was 79%. For the 11 patients who had undergone transplantation after 2007, we observed a 100% patient and graft survival. CONCLUSION: After an initial learning curve and provided careful selection, exceptions to classical donor criteria for splitting can be accepted with successful outcomes comparable to those after whole liver transplantation.

Improved results for adult split liver transplantation with extended right lobe grafts: could we enhance its application?

OBJECTIVE: Split liver transplantation (SLT) allows grafting of 2 recipients with 1 allograft. Results of adult SLT have improved since its first introduction. Children benefit most from SLT, while among some adult liver transplanters there are concerns about splitting a liver, turning a good quality graft into a marginal one. We performed a single center retrospective review to address this issue. PATIENTS AND METHODS: Between June 2001 and August 2008, we performed 22 extended right liver graft (eRLG) transplantations in 21 adult patients. RESULTS: Eleven donors (50%) did not meet the Eurotransplant criteria for optimal donors. Forty-one percent of eRLG donors showed hemodynamic instability at the time of harvest. Eighteen (82%) splitting procedures were performed ex situ. The main indications for transplantation were alcoholic liver cirrhosis (32%), hepatitis C-related cirrhosis (18%), and acute liver failure (18%). Mean recipient age was 54 years (range, 17-69 years); median Model for End-Stage Liver Disease (MELD) score was 15 (range, 7-40). Patients were followed for a median of 16 months (range, 4-92 months) following transplantation. We observed 5 (23%) vascular and 3 (14%) biliary complications. Overall patient survival was 84% at 3 years; overall graft survival was 79%. For the 11 patients who had undergone transplantation after 2007, we observed a 100% patient and graft survival. CONCLUSION: After an initial learning curve and provided careful selection, exceptions to classical donor criteria for splitting can be accepted with successful outcomes comparable to those after whole liver transplantation.

The choice of recipient does not have a bearing on early outcome in liver transplant patients receiving grafts from non-heart-beating donors: a reappraisal?

INTRODUCTION: Donation after cardiac death has reemerged as a potential way of increasing the supply of organs for transplantation. We retrospectively reviewed the outcomes of non-heart-beating donor (NHBD) liver transplantation (OLT) experience and compared with standard heart-beating donation (HBD) at a single center. METHODS: From October 2003 to November 2006, 13/111 liver transplantations were performed in our institution with NHBD. Living donor liver transplantation, splitting procedures, combined, and pediatric liver transplantations were excluded from this analysis. RESULTS: Donor population was similar in both groups. The median warm ischemia time was 10 minutes (range 6 to 38). The median cold ischemia times 6 hours and 16 minutes (2.4 to 6.30 hours and 9 hours and 14 minutes (2.15 to 15.35 hours) for NHBD and HBD groups, respectively (P = .0002). In the NHBD groups, 4/13 (31%) grafts were retransplanted within 3 months, due to ischemic biliary lesions with severe cholestasis (n = 3) or due to the occurrence of primary nonfunction (n = 1). The retransplantation rate was significantly lower in the HBD group (11/98, 11%; P = .03). One-year patient and graft survivals were 62% and 54% versus 86% and 79%, respectively, for the NHBD and HBD groups (P = .107 and P = .003). CONCLUSION: Liver grafts procured from donors after cardiac death accounted for a significantly greater retransplantation rates, mainly due to nonanastomotic biliary strictures. This risk must be taken into account when transplanting such grafts. Based upon this experience, NHBD cannot rival HBD to be a comparable source of quality organs for liver transplantation.

Comparison of two techniques of arterial anastomosis during adult cadaveric liver transplantation.

Arterial complications are a major source of morbidity and mortality after orthotopic liver transplantation (OLT). The incidence of hepatic artery thrombosis (HAT) ranges from 1.6% to 8%, with a mortality rate that ranges from 11% to 35%. We have described herein a technique of arterial anastomosis aiming to perform the anastomosis as straight as possible to avoid any kinking, redundancy, or malposition of the artery when the liver is released in its final position. We compared this technique with the traditional technique of arterial anastomosis using an aortic Carrel patch, namely, 198 OLT (group A) with the traditional technique and 117 OLT (group B) with the modified technique. An aorto-hepatic bypass was necessary in 25% of the cases in group A and in 21% of the cases in group B (P = .33). Vascular anomalies were present in 20% of cases in group A and in 27.5% in group B (P = .14). Fourteen cases (7%) of HAT developed in group A versus 0 cases in group B (P = .003). In group B, we experienced 2 (1.7%) late arterial stenoses that were successfully treated using percutaneous transluminal angioplasty. The 14 cases of HAT occurring in group A were successfully managed using immediate surgical revascularization with graft salvage in 6 cases (43%), whereas the remaining 8 cases needed urgent retransplantation. We suggest that a technique of arterial anastomosis aimed at avoiding kinking, redundancy, or malposition of the artery may be a viable option to reduce the risk of HAT after OLT.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma.

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (OLT) is usually reserved for Child B and C patients with multiple nodules. The aim of this study was to compare HR and OLT for HCC within the Milan criteria on an intention-to-treat basis. Forty-eight patients were treated by OLT and 38 by HR. Three- and 5-year patient survival rates were significantly higher (P = .0057) in the OLT group (79% and 74%) than after HR (61% and 26%). The 3- and 5-year disease-free survival rate was better (P = .0005) for OLT (74% and 74%) versus HR (41% and 11%). The probability of HCC recurrences after resection was greater (P = .0002) than after transplantation, achieving 31% and 76% for HR and 2% and 2% for OLT at 3 and 5 years after surgery. The median waiting list time was 118 days; two patients dropped out for HCC progression. We concluded that OLT is superior to HR for small HCC in cirrhotic patients assuming that OLT can be performed within 6 to 10 months after listing to reduce dropouts due to tumor progression.

Selective bilirubin removal by plasma treatment with Plasorba BR-350 for early cholestatic graft dysfunction.

Early cholestatic graft dysfunction is a frequent cause of morbidity after orthotopic liver transplantation (OLT). We analyze the role of selective bilirubin plasma absorption (PAP) using Plasorba BR-350 in 4 OLT patients who had experienced early severe cholestatic graft dysfunction within 15 days after transplantation. Patients were treated with 3 consecutive cycles of PAP with Plasorba BR-350. The median amount of plasma treated was 7500 mL. Median treatment duration was 231 minutes. The average plasma bilirubin level was 37 +/- 1 mg/dL before PAP and decreased to 15 +/- 0.2 mg/dL at the end of the third cycle of PAP; 3 of 4 cases had progressive bilirubin normalization after PAP. The average amount of bilirubin removed from the plasma of the patients during each PAP treatment was 143 +/- 24 mg. At the beginning of each cycle of PAP, the Plasorba BR-350 was able to remove >90% of the total plasma bilirubin, a percentage that decreased to 60%, 50%, and 40% after 2 L, 4 L, and 7 L of plasma were treated, respectively. Liver biopsies performed after the third treatment showed reduced cholestasis when compared with the pretreatment biopsy specimen. The preliminary data suggested that PAP selective for bilirubin removal may not only reduce the bilirubin level, but may also improve the histological pattern of the graft in terms of reduced cholestatic signs.

The role of hepatic biopsy to detect macrovacuolar steatosis during liver procurement.

The ability to predict graft function before transplantation has proven to be a difficult task, especially for macrovacuolar steatosis that is considered a major cause of posttransplant dysfunction. It is well known that macrovacuolar steatosis greater than 25% influences the short- and long-term outcomes of liver transplantation. We retrospectively analyzed frozen sections from 43 donor livers comparing preoperative laboratory/clinical values, and liver ultrasound of a cohort of donors without (group A, n=21) versus with steatosis of 25% to 35% (group B, n=22) upon liver biopsy performed during harvesting. We analyzed the possible correlations between preoperative donor data and the degree of macrovacuolar steatosis. None of the biochemical and clinical parameters were related to the degree of hepatic steatosis. The only difference between the two groups was the echographic pattern, with evidence of 27% fatty liver by ultrasound in group B and 5% in group A (p=.04). The specificity of hepatic ultrasound for macrovacuolar steatosis was 95% and the sensitivity was only 27%, while the positive and negative predictive value were 86% and 55%, respectively. In conclusion, liver biopsy during donor harvesting remains the gold standard to identify macrovacuolar steatosis greater than 25%. Hepatic ultrasound has a role to exclude the presence of steatosis in normal livers due to its high specificity, but it is not useful to make the diagnosis of a fatty liver since it has a low sensitivity and negative predictive value. Thereafter a liver ultrasound positive for hepatic steatosis alone should not be considered a valuable tool to discard an organ from transplantation.

Long-term results of in situ split-liver transplantation.

BACKGROUND: Split-liver transplantation (SLT) offers immediate expansion of the cadaver donor pool. The principal beneficiaries have been adult and pediatric recipients with excellent outcomes. This study analyzed a single-center experience of adult to adult in situ SLT in adult recipients. PATIENTS AND METHODS: Fourteen consecutive adult-to-adult in situ SLT have been performed at our institution since 1998. The extended right lobe comprising segment 1 was transplanted in to adult patients, the left lateral segment, for pediatric transplants. RESULTS: Donors of SLT were significantly younger (P = .03) than those of whole liver transplants. Survival rates of patients receiving a split liver were 83%, 73%, and 73% at 1, 3, and 5 years after the transplant respectively and grafts of 73%, 73%, and 73% for SLT and 76%, 70%, and 66% for whole liver transplants (P = .44). The rate of biliary complication after SLT was 21%, which was comparable to that after whole organ transplantation (17%). The incidence of hepatic artery thrombosis and primary nonfunction was not significantly different between split liver and whole organ transplantation performed during the same time period (7% versus 4.6% P = .67 and 7% versus 2.6% P = .32, respectively). CONCLUSION: This limited single-center experience confirmed that both early and long-term results of SLT are comparable to those of traditional whole liver organ transplantation.

A single-center experience of late retransplantation of the liver.

Liver retransplantation is considered to carry a higher risk than primary transplantation. However, there are an increasing number of retransplant candidates, especially owing to late graft failure. The aim of this study was to analyze a single-center experience in late liver retransplantation. The overall rate of primary retransplantation was 11.4% (28 re-OLT out of 245 primary OLT); the 14 (52%) who underwent retransplantation at more than 3 months after the first transplant were analyzed by a medical record review. Causes of primary graft failure leading to retransplantation were chronic hepatic artery thombosis in five cases (36%); recurrent HCV cirrhosis in four cases (29%); chronic rejection in two cases (14%); veno-occlusive disease; hepatic vein thrombosis or idiopathic graft failure in one case each (7%). UNOS status at re-OLT was always 2A, all patients were hospitalized; three were intensive care unit bound. ICU and total hospital stay had been 7 +/- 5 and 28 +/- 16 days, respectively. One- and 2-year patient and graft survivals were 84% and 62% and 67% and 67%, respectively. Death occurred in four patients. Two out of the three recovered in ICU at the time of retransplantation, at a median interval of 15 +/- 9 days after retransplantation. The survival rate after late retransplantation is improving, and this option should be considered to be a efficient way to save lives, especially by defining the optimal timing for retransplantation.

Quality-of-life assessment before and after liver transplantation.

BACKGROUND: Quality-of-life (QoL) assessment includes health status, disability, psychological wellness, and social performance. We sought to evaluate the effect of liver transplantation (OLT) on the QoL of patients awaiting the procedure and its variations up to 8 years afterwards. METHODS: LEIPAD-perceived QoL and BSI-psychological distress tests were used. Patients were divided in four groups (waiting list patients, 1 to 2 years after LT, 3 to 4 years after LT, 5 to 8 years after LT). Patients were also evaluated for type and severity of liver disease. RESULTS: We evaluated 126 patients, 71% male, 29% female, median age 60.7 years (range 40 to 76 years), median follow-up 4 years (range 1 to 8). The patients on the waiting list scored worse both in global stress index (GSI) and total LEIPAD scores than transplanted patients. Upon univariate linear regression analysis, the only dimension associated with time groups was LEIPAD--physical functioning, showing a progressive improvement of perceived physical status with time from transplant. Severity of liver disease showed a protective effect, probably reflecting a better control of stressful events from patients transplanted at advanced stages of liver disease. Protective effects were found for male sex, retired, cohabitant patients, and the degree of education. Housewife and widow patients showed negative associations with BSI and LEIPAD dimensions. No independent predictors of QoL were found in this study. CONCLUSIONS: OLT improves most, but not all, QoL and psychological distress domains.

Right lobe living related graft loss due to intrahepatic multiple arterio-portal fistulas.

We report a case of a 38-year-old Caucasian female with ileal carcinoid and bilobar hepatic metastases. After resection of the primary tumor, octreotide therapy was prescribed. Carcinoid histology was positive for chromogranin A and sinaptophsine and negative for MIB1. At 1-year, a follow-up computed tomography scan, Octreoscan, and PET scan were negative for extrahepatic involvement. The patient underwent right lobe living related liver transplantation donated by her sister. Acute hepatic artery thrombosis was successfully revascularized 24 hours after transplantation. Extrahepatic biliary ischemia was treated by a bilio-digestive anastomosis. Eight months later, ascites and clinical and serologic signs of liver failure developed; a liver biopsy revealed fibrosis. Spiral computed tomography scan and hepatic angiography showed multiple intrahepatic arterio-portal fistulas resulting in arterialization and inversion of the portal flow in the absence of graft outflow obstruction.

Successful minimally invasive management of late portal vein thrombosis after splenectomy due to splenic artery steal syndrome following liver transplantation: a case report.

Portal vein thrombosis (PVT) after liver transplantation (OLT), which occurs in 1% to 2.7% of cases, can compromise patient and graft survival. Percutaneous transhepatic portal vein angioplasty offers an option to treat PVT, diminishing surgically related morbidity and the need for retransplantation. We describe a case of late PVT after OLT, which was successfully treated by a minimally invasive percutaneous transhepatic approach using both mechanical fragmentation and pharmacologic lysis of the thrombus followed by anticoagulation. The patient has had a good clinical course with normal graft function and patent portal blood flow at 6-month follow-up. This case report confirms the possibility of successful recanalization of the portal vein in a patient with late PVT after liver transplantation. Sustained anticoagulation/antiaggregation therapy for at least 6 months after the procedure is advisable.

[Surgical complications after kidney transplantation]. / Le complicanze chirurgiche ed urologiche del trapianto di rene.

Chronic renal failure needs substitutive treatment such as haemodialysis and peritoneal dialysis for the patient to survive. Kidney transplantation (KTx) improves survival of the patient with chronic renal failure. Since the first KTx, performed by Merrill in Boston in 1959, advances in medical therapy, immunosuppressive therapy and refinements in surgical technique have improved the quality of life of the transplant patient. We present a review of the incidence, diagnosis and therapy of surgical complications after KTx reported in the literature and a retrospective analysis of 297 consecutive cadaveric donor kidney transplants done in our institution from September 1993 to September 2002. Vascular complications represent 5-10% of postoperative complications. Our experience showed an incidence of 1.7% renal artery thrombosis, 1.4% renal vein thrombosis, 1.7% renal artery stenosis, 1.4% arterial rupture due to fungal arteritis, 0.7% spontaneous graft ruptures and 12% lymphoceles. Urological complications account for 10-15% of postoperative complications. In our series we found an incidence of 7.4% urinary leakage, 2.7% urinary obstruction and 3% urinary reflux. Gastrointestinal complications represent 16% of postoperative complications. Our series showed 1% pancreatitis with an overall mortality of 33% and an incidence of 1.7% intestinal perforations. Surgical complications still represent a challenge that increments morbidity and mortality among kidney transplant recipients. Data shown may offer some guidance on how to deal with early and late post-transplant surgical complications.