Cristiano Quintini

Three‐dimensional print of a liver for preoperative planning in living donor liver transplantation

The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3‐dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D‐printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D‐printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D‐printed models and native livers. Liver Transpl 19:1304–1310, 2013.

Use of tissue plasminogen activator in liver transplantation from donation after cardiac death donors.

Ischemic‐type biliary stricture (ITBS) occurs in up to 50% after liver transplantation (LT) from donation after cardiac death (DCD) donors. Thrombus formation in the peribiliary microcirculation is a postulated mechanism. The aim was to describe our experience of tissue plasminogen activator (TPA) administration in DCD‐LT. TPA was injected into the donor hepatic artery on the backtable (n = 22). Two recipients developed ITBS including one graft failure. Although excessive postreperfusion bleeding was seen in 14 recipients, the amount of TPA was comparable between those with and without excessive bleeding (6.4 ± 2.8 vs. 6.6 ± 2.8 mg, p = 0.78). However, donor age (41 ± 12 vs. 29 ± 9 years, p = 0.02), donor BMI (26.3 ± 5.5 vs. 21.7 ± 3.6 kg/m2, p = 0.03), previous laparotomy (50% vs. 0%, p = 0.02) and lactate after portal reperfusion (6.3 ± 4.6 vs. 2.8 ± 0.9 mmol/L, p = 0.005) were significantly greater in recipients with excessive bleeding. In conclusion, the use of TPA may lower the risk of ITBS‐related graft failure in DCD‐LT. Excessive bleeding may be related to poor graft quality and previous laparotomy rather than the amount of TPA. Further studies are needed in larger population.

“Splenic artery steal syndrome” is a misnomer: The cause is portal hyperperfusion, not arterial siphon

Splenic artery embolization (SAE) improves hepatic artery (HA) flow in liver transplant (OLT) recipients with so‐called splenic artery steal syndrome. We propose that SAE actually improves HA flow by reducing the HA buffer response (HABR). Patient 1: On postoperative day (POD) 1, Doppler ultrasonography (US) showed patent vasculature with HA resistive index (RI) of 0.8. On POD 4, aminotransferases rose dramatically; his RI was 1.0 with no diastolic flow. Octreotide was begun, but on POD 5 US showed reverse diastolic HA flow with no signal in distal HA branches. After SAE, US showed markedly improved flow, RI was 0.6, diastolic flow in the main artery, and complete visualization of all distal branches. By POD 6, liver function had normalized. RI in the main HA is 0.76 at 2 months postsurgery. Patient 2: On POD 1, RI was 1.0. US showed worsening intrahepatic signal, with no signal in the intrahepatic branches and reversed diastolic flow despite good graft function. On POD 7, SAE improved the intrahepatic waveform and RI (from 1.0 to 0.72). Patient 3: Intraoperative reverse diastolic arterial flow persisted on PODs 1, 2, and 3, with progressive loss of US signal in peripheral HA branches. SAE on POD 4 improved the RI (0.86) and peripheral arterial branch signals. Patient 4: US on POD 1 showed good HA flow with a normal RI (0.7). A sudden waveform change on POD 2 with increasing RI (0.83) prompted SAE, after which the wave form normalized, with reconstitution of a normal diastolic flow (RI 0.68). In conclusion, these reports confirm the usefulness of SAE for poor HA flow but suggest that inflow steal was not the problem. Rather than producing an increase in arterial inflow, SAE worked by reducing portal flow and HABR, thereby reducing end‐organ outflow resistance. Evidence of this effect is the marked reduction of the RI after the SAE to 0.6, 0.72, 0.86, and 0.68, in patients 1‐4, respectively. SAE reduces excessive portal vein flow and thereby ameliorates an overactive HABR that can cause graft dysfunction and ultimately HA thrombosis. Liver Transpl 14:374–379, 2008.

Fluid and electrolyte management: putting a plan in motion.

Fluid and electrolyte management is challenging for clinicians, as electrolytes shift in a variety of settings and disease states and are dependent on osmotic changes and fluid balance. The development of a plan for managing fluid and electrolyte abnormalities should start with correcting the underlying condition. In most cases, this is followed by an assessment of fluid balance with the goal of achieving euvolemia. After fluid status is understood and/or corrected, electrolyte imbalances are simplified. Many equations are available to aid clinicians in providing safe recommendations or at least to give a starting point for correcting the abnormalities. However, these equations do not take into consideration the vast differences between clinical scenarios, thus making electrolyte management more challenging. The supplementation plan, whether delivered intravenously or orally, must include an assessment of renal and gastrointestinal function, as most guidelines are established under the assumption of normal digestion, absorption and excretion. After the plan is developed, frequent monitoring is vital to regain homeostasis. A fluid and electrolyte management plan developed by a multidisciplinary team is advantageous in promoting continuity of care and producing safe outcomes.

Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in donation after cardiac death porcine livers

The effects of normothermic machine perfusion (NMP) on the postreperfusion hemodynamics and extrahepatic biliary duct histology of donation after cardiac death (DCD) livers after transplantation have not been addressed thoroughly and represent the objective of this study. Ten livers (5 per group) with 60 minutes of warm ischemia were preserved via cold storage (CS) or sanguineous NMP for 10 hours, and then they were reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, the arterial and portal vein flows were stable in the NMP group during the entire reperfusion simulation, whereas they decreased dramatically in the CS group after 16 hours of reperfusion (P < 0.05); these findings were consistent with severe parenchymal injury. Similarly, significant differences existed between the CS and NMP groups with respect to the release of hepatocellular enzymes, the volume of bile produced, and the levels of enzymes released into bile (P < 0.05). According to histology, CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhaging, denudated biliary epithelium, and submucosal bile duct necrosis, whereas NMP livers showed very mild injury to the liver parenchyma and biliary architecture. Most importantly, Ki‐67 staining in extrahepatic bile ducts showed biliary epithelial regeneration. In conclusion, our findings advance the knowledge of the postreperfusion events that characterize DCD livers and suggest NMP as a beneficial preservation modality that is able to improve biliary regeneration after a major ischemic event and may prevent the development of ischemic cholangiopathy in the setting of clinical transplantation. Liver Transpl 20:987–999, 2014.

Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small‐for‐size syndrome

The aim of the study is to define the role of the HABR in the pathophysiology of the SFS liver graft and to demonstrate that restoration of hepatic artery flow (HAF) has a significant impact on outcome and improves survival. Nine pigs received partial liver allografts of 60% liver volume, Group 1; 8 animals received 20% LV grafts, Group 2; 9 animals received 20% LV grafts with adenosine infusion, Group 3. HAF and portal vein flow (PVF) were recorded at 10 min, 60 min and 90 min post reperfusion, on POD 3 and POD 7 in Group 1, and daily in Group 2 and 3 up to POD 14. Baseline HAF and PVF (ml/100g/min) were 29 ± 12 (mean ± SD) and 74 ± 8 respectively, with 28% of total liver blood flow (TLBF) from the HA and 72% from the PV. PVF peaked at 10 mins in all groups, increasing by a factor of 3.8 in the 20% group compared to an increase of 1.9 in the 60% group. By POD 7‐14 PVF rates approached baseline values in all groups. The HABR was intact immediately following reperfusion in all groups with a reciprocal decrease in HAF corresponding to the peak PVF at 10 min. However in the 20% group HAF decreased to 12 ± 8 ml/100 g/min at 90 min and remained low out to POD 7‐14 despite restoration of normal PVF rates. Histopathology confirmed evidence of HA vasospasm and its consequences, cholestasis, centrilobular necrosis and biliary ischemia in Group 2. HA infusion of adenosine significantly improved HAF (p < .0001), reversed pathological changes and significantly improved survival (p = .05). An impaired HABR is important in the pathophysiology of the SFSS. Reversal of the vasospasm significantly improves outcome. Liver Transpl 15:1448–1457, 2009.

Comparable graft and patient survival in lean and obese liver transplant recipients

Obesity is among the great health problems facing Americans today. More than 32% of the US population is considered obese on the basis of a body mass index (BMI) exceeding 30 kg/m2. Obesity increases the risk for numerous perioperative complications, but how obesity affects the outcome of liver transplantation remains unclear. We compared graft/patient survival after orthotopic liver transplantation performed at the Cleveland Clinic between April 2005 and June 2011 in 2 groups: obese patients with a BMI ≥ 38 kg/m2 and lean patients with a BMI between 20 and 26 kg/m2. We included 47 obese patients and 183 lean patients, whose demographics and baseline characteristics were well balanced after weighting with the inverse propensity score. After we controlled for observed confounding, no significant differences were observed in graft/patient survival between obese and lean patients (P = 0.30). The estimated hazard ratio for obese patients to experience graft failure or death was 1.19 [95% confidence interval (CI) = 0.85‐1.67]. There were 134 patients who had follow‐up for more than 3 years, and they included 27 obese patients and 107 lean patients. Within this subset, the odds of having metabolic syndrome were significantly greater for obese patients (46%) versus lean patients (21%; odds ratio = 4.76, 99.5% CI = 1.66‐13.7, P < 0.001). However, no significant association between obesity and any other long‐term adverse outcomes was found. In conclusion, this study shows that transplant outcomes were comparable for lean and obese recipients. We thus recommend that even morbid obesity per se should not exclude patients from consideration for transplantation. Liver Transpl 19:907‐915, 2013.

Mortality of Intra-Abdominal Desmoid Tumors in Patients With Familial Adenomatous Polyposis A Single Center Review of 154 Patients

Introduction:Intra-abdominal desmoid tumors are one of the leading causes of death in patients with familial adenomatous polyposis. Their behavior is unpredictable and their biology is poorly understood, accounting for the lack of a standardized medical and surgical approach. The aim of this study was to evaluate the mortality rate of patients with intra-abdominal desmoid tumors and to identify prognostic factors for the evolution of the disease. Materials and Methods:A total of 154 patients with intra-abdominal desmoid tumors were included in the study. Each tumor was staged and each patient was categorized according to the stage of their most advanced tumor. Mortality was analyzed and the univariate risk factors associated with survival were included in a multivariable Cox regression model. A scoring system was derived from the multivariate analysis to refine outcomes within stages. Results:Five-year survival of patients with stage I, II, III, and IV intra-abdominal desmoid tumor were 95%, 100%, 89%, and 76% respectively (P < 0.001). Severe pain/narcotic dependency, tumor size larger than 10 cm, and need for total parenteral nutrition were shown to further define survival within stages. Five-year survival rate of stage IV patient with all of the above-mentioned risk factors was only 53%. Conclusions:Our study confirmed the validity of the staging system to predict mortality in patients with intra-abdominal desmoid tumors and identified additional risk factors able to better define the risk of death within each stage. Risk stratification is crucial in directing patients with advanced disease and poor prognosis to the most appropriate medical and surgical options.

Measurement of CD4+ T-cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation.

Hashimoto K, Miller C, Hirose K, Diago T, Aucejo F, Quintini C, Eghtesad B, Corey R, Yerian L, Lopez R, Zein N, Fung J. Measurement of CD4+ T‐cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01169.x
© 2009 John Wiley & Sons A/S.

Ex Vivo Normothermic Machine Perfusion Is Safe, Simple, and Reliable: Results From a Large Animal Model

Introduction. Normothermic machine perfusion (NMP) is an emerging preservation modality that holds the potential to prevent the injury associated with low temperature and to promote organ repair that follows ischemic cell damage. While several animal studies have showed its superiority over cold storage (CS), minimal studies in the literature have focused on safety, feasibility, and reliability of this technology, which represent key factors in its implementation into clinical practice. The aim of the present study is to report safety and performance data on NMP of DCD porcine livers. Materials and Methods. After 60 minutes of warm ischemia time, 20 pig livers were preserved using either NMP (n = 15; physiologic perfusion temperature) or CS group (n = 5) for a preservation time of 10 hours. Livers were then tested on a transplant simulation model for 24 hours. Machine safety was assessed by measuring system failure events, the ability to monitor perfusion parameters, sterility, and vessel integrity. The ability of the machine to preserve injured organs was assessed by liver function tests, hemodynamic parameters, and histology. Results. No system failures were recorded. Target hemodynamic parameters were easily achieved and vascular complications were not encountered. Liver function parameters as well as histology showed significant differences between the 2 groups, with NMP livers showing preserved liver function and histological architecture, while CS livers presenting postreperfusion parameters consistent with unrecoverable cell injury. Conclusion. Our study shows that NMP is safe, reliable, and provides superior graft preservation compared to CS in our DCD porcine model.