Basem Soliman

Comparing Normothermic Machine Perfusion Preservation With Different Perfusates on Porcine Livers From Donors After Circulatory Death.

The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB‐perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.

Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death.

Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group). After the preservation phase all livers were reperfused for 24 h in an isolated perfusion system with whole blood at 38.5°C to simulate transplantation. At the end of transplant simulation, the NMP group showed significantly lower hepatocellular enzyme level (AST: 277 ± 69 U/L; ALT: 22 ± 2 U/L; P < 0.03) compared to both SNMP (AST: 3243 ± 1048 U/L; ALT: 127 ± 70 U/L) and CS (AST: 3150 ± 1546 U/L; ALT: 185 ± 97 U/L). There was no significant difference between SNMP and CS. Bile production was significantly higher in the NMP group (219 ± 43 mL; P < 0.01) compared to both SNMP (49 ± 84 mL) and CS (12 ± 16 mL) with no significant difference between the latter two groups. Histologically, the NMP livers showed preserved cellular architecture compared to the SNMP and CS groups. NMP was able to recover DCD livers showing superior hepatocellular integrity, biliary function, and microcirculation compared to SNMP and CS. SNMP showed some significant benefit over CS, yet has not shown any advantage over NMP.

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4‐6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95‐149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171‐304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4‐8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233–245 2018 AASLD.

Management of Crohn's Disease in the New Era of Gut Rehabilitation and Intestinal Transplantation.

Abstract:Despite recent therapeutic advances, patients with Crohns disease (CD) continue to experience high recurrence with cumulative structural damage and ultimate loss of nutritional autonomy. With short bowel syndrome, strictures, and enteric fistulae being the underlying pathology, CD is the second common indication for home parenteral nutrition (HPN). With development of intestinal failure, nutritional management including HPN is required as a rescue therapy. Unfortunately, some patients do not escape the HPN-associated complications. Therefore, the concept of gut rehabilitation has evolved as part of the algorithmic management of these patients, with transplantation being the ultimate life-saving therapy. With type 2 intestinal failure, comprehensive rehabilitative measures including nutritional care, pharmacologic manipulation, autologous reconstruction, and bowel lengthening is often successful, particularly in patients with quiescent disease. With type 3 intestinal failure, transplantation is the only life-saving treatment for patients with HPN failure and intractable disease. With CD being the second common indication for transplantation in adults, survival outcome continues to improve because of surgical innovation, novel immunosuppression, and better postoperative care. Despite being a rescue therapy, the procedure has achieved survival rates similar to other solid organs, and comparable to those who continue to receive HPN therapy. With similar technical, immunologic, and infectious complications, survival is similar in the CD and non-CD recipients. Full nutritional autonomy is achievable in most survivors with better quality of life and long-term cost-effectiveness. CD recurrence is rare with no impact on graft function. Further progress is anticipated with new insights into the pathogenesis of CD and mechanisms of transplant tolerance.

Developing a protocol for normothermic ex-situ limb perfusion

Ischemia time represents a significant limitation for successful extremity transplantation because of the rapid deterioration of ischemic muscle. Normothermic ex‐situ preservation is an emergent method to prolong the organ viability following procurement, by replicating the physiologic conditions. The aim of this study was to develop an ex‐situ normothermic limb perfusion system to preserve the viability and function of porcine limbs for 12 hours following procurement.

Ex situ 86-hour liver perfusion: Pushing the boundary of organ preservation

For almost 3 decades, cold storage (CS) has been the standard method used to preserve liver grafts prior to transplantation. However, marginal grafts are susceptible to cold ischemia, making CS a suboptimal preservation modality for these organs. The transplant community has recently become increasingly interested in the application of normothermic machine perfusion (NMP), an innovative preservation technique. NMP maintains the liver graft’s metabolism by continuously supplying oxygen and nutrients at physiologic temperature. Studies indicate that NMP can restore energy content, hepatobiliary function, and microcirculation, thus improving liver quality prior to transplantation. More importantly, NMP holds the potential to increase the duration of organ preservation, which can minimize logistical limitations of CS, recondition injured organs, and manipulate the graft to improve transplant outcomes. As of today, the longest recorded maintenance of active liver metabolism of human organs outside of the body is 24 hours and 72 hours in a porcine model. Herein, we report a case describing the metabolic activity of a discarded human liver during 86 hours of ex situ NMP.

Machine Perfusion of Organs

Transplant organ supplies are insufficient to meet the demands, resulting in prolonged patient wait times and waitlist mortality. Offering improved organ preservation, assessment, and resuscitation, machine perfusion of organs can enable the use of marginal organs, thereby expanding the donor pool. The technology is based on the common principle of continuous provision of oxygen and nutrients. Perfusion settings and components vary widely in terms of pump pulsatility, temperature control, oxygen provision, oncotic agents, and pharmacologic supplementation. While this technology was first pioneered in the 1960s, it has seen a recent resurgence. Hypothermic renal perfusion is the most clinically advanced area of perfusion and a source of continued innovation. Liver, heart, and lung perfusion techniques have been introduced into the clinical realm as safe alternatives, and evidence demonstrating clinical efficacy and superiority is accumulating. Machine perfusion of the pancreas and small intestine is being explored predominantly in preclinical models. Machine perfusion of limbs offers improved opportunities for limb transplantation and autologous replantation. Machine perfusion is a promising option to salvage function in marginal organ grafts and may enable prediction of organ function or dysfunction after transplantation.

Surgery in Patients with Hepatic Cirrhosis: Management of Portal Hypertension

The inherent development of portal hypertension (PH) in patients with hepatic cirrhosis and portomesenteric venous thrombosis commonly influences the outcome of any required major surgical intervention. Accordingly, a thorough assessment is often required to define status of hepatic reserve, spectrum of PH, and complexity of the coexisted pathology. This includes comprehensive clinical, biochemical, endoscopic, radiologic, and histopathologic evaluation. In candidates with preserved synthetic liver functions, optimization of nutritional and global health status is imperative to reduce overall morbidity and mortality. With the diagnosis of gut varices and demonstration of portomesenteric abdominal collaterals, directed management strategy is required to avoid the potential risk of provoking life-threatening complications including variceal hemorrhage and surgical bleeding with subsequent development of hepatic failure. With the initial recognition of marginal hepatic reserve or subsequent development of liver failure, organ transplantation should be seriously considered. Accordingly, patients with portal hypertension who are in need for major surgical procedures should be managed at tertiary medical centers. The availability of a multidisciplinary team with expertise in the relevant fields improves the overall outcomes measures including survival and value of health care.

Thoracic and Esophageal Procedures, Lung Transplant in Cirrhotic Patients: Safety and Limiting Factors

Cirrhotic patients may suffer from comorbid thoracic or esophageal conditions, which often necessitate surgical treatment such as cancer resection or lung transplantation. Currently, there are limited data and few protocols to guide surgical decision making for these patients. This chapter discusses the indications and outcomes for the surgical treatment of lung cancer, gastrointestinal reflux disease, esophageal cancer, lung transplantation, and combined liver–lung transplantation in cirrhotic patients. Recognizing when it is safe to operate cirrhotic patients and when it is contraindicated is critical for the safety of these patients.

Abstract: Ex Vivo Normothermic Limb Perfusion and Limb Specific Monitoring Evaluation of Perfusion Quality

PSTM Abstract Supplement practice and associated with angiogenesis and accelerated wound healing. This experimental model evaluated topical negative pressure as a mechanism for non-inva-sive preconditioning for perforator flap microvascularity and perfusion. MethodS: Two gluteal perforator flaps (matched control and intervention) were designed on sixteen 400g Sprague-Dawley male rats. NPWT was applied to the flap area directly continuously at-125mmHg for 7 days, after which the rats were divided into two principal groups. Group A (n=8) underwent 4D computed tomographic and angiography (CTA) with a body volume perfusion protocol after NPWT and euthanized. Group B (n=8), control and intervention flaps were raised, isolated on a single pedicle and laid back down and monitored for a further 7 days. Group B flaps were assessed using laser-assisted indocyanine fluorescence angiography before surgery, following flap harvest and at 7 days prior to euthanasia. Half of all rats in each group were analyzed with Micro-CT to assess the microvasculature. All paired specimens were assessed histologically with H&E and immunohistochem-istry (IHC). ReSultS: There was a 17% increase in CT tissue perfu-sion in skin treated with NPWT versus matched controls (P=0.001). LA-ICGFA demonstrated higher perfusion following NPWT treatment (P=0.006), however no significant difference immediate post flap harvest (P=0.19) but a difference was seen 7 days postoperatively (P=0.03). Micro-CT evaluation showed an increase in average vessel volume (%) from 0.005 in control to 0.009 in the NPWT flaps (P=0.04).H&E analysis showed significant difference in the epidermal thickness (P<0.001), but comparable dermal thickness (P=0.34).Quantitative analysis of CD31 IHC demonstrated a mean area fraction percentage of 4.30 and 2.68 in the NPWT and control flaps respectively (P=0.002).There was partial necrosis in the control (n=3) and NPWT flaps (N=1), however this was <5% in the NPWT flap. ConCluSion: We present novel multimodal approaches using static and dynamic imaging and histological assessment to provide a proof of concept on the use of NPWT for non-invasive conditioning of flaps. The study provides the basis for further investigation and clinical studies with potential for direct translation into clinical practice. Disclosure/Financial support: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. PuRPoSe: Ischemia time represents a significant limitation for successful extremity replantation and transplantation because of the rapid deterioration of ischemic muscle. Static cold storage (SCS) of the limb is the standard clinical practice. Normothermic ex vivo perfusion system has the potential to prolong viability …