Subnormothermic and Normothermic Ex Vivo Liver Perfusion as a Novel Preservation Technique

Due to the worldwide organ shortage, interest in the use of marginal liver allografts has increased. More widespread use of marginal grafts is limited by graft injury from cold storage and the risk of poor outcomes after transplantation. Warm (subnormothermic and normothermic) ex vivo liver perfusion has emerged as a novel preservation strategy to recover marginal organs and potentially increase the organ pool. Over the last decade, advances in the field have taken warm ex vivo liver perfusion from the laboratory to clinical trials. While most investigation thus far has focused on the rescue of marginal grafts for expansion of the donor pool, warm perfusion (WP) preservation also has great potential to facilitate novel graft interventions prior to transplantation

Donor outcomes in anonymous live liver donation

BackgroundDeath rates on liver transplant waiting lists range from 5%-25%. Herein, we report a unique experience with 50 anonymous persons who volunteered to address this gap by offering to donate part of their liver to a recipient with whom they had no biological connection or prior relationship (A-LLD).MethodsCandidates were screened to confirm excellent physical, mental, social, and financial health. Demographics and surgical outcomes were analyzed. Qualitative interviews after donation examined motivation and experiences. Validated self-reported questionnaires assessed personality traits and psychological impact.Results50 A-LLD liver transplants (LT) were performed between 2005 and 2017. Most donors had a university education, a middle-class income, and a history of prior altruism. Half were women. Median age was 38.5 years (range 20-59 yrs.). Thirty-three (70%) learned about this opportunity through public or social media. Saving a life, helping others, generativity, and reciprocity for past generosity were motivators. Social, financial, healthcare, and legal supports in Canada were identified as facilitators. A-LLD identified most with the personality traits of agreeableness and conscientiousness. The median hospital stay was six days. There was one Dindo-Clavien Grade 3 complication that completely resolved. One-year recipient survival was 91% in 22 adults and 97% in 28 children. No A-LLD reported regretting their decision.ConclusionsThis is the first and only report of the motivations and facilitators of A-LLD in a large cohort. With rigorous protocols, outcomes are excellent. A-LLD has significant potential to reduce the gap between transplant organ demand and availability

Liver transplantation is a preferable alternative to palliative therapy for selected patients with advanced hepatocellular carcinoma

Background: Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT). Materials & Methods: All patients listed in the Toronto liver transplant program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiological images were reviewed by two independent radiologists. The primary endpoint was patient survival. Results: Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p=0.02) and tumor burden (p <0.001). The majority of those listed underwent LT (n=69, 72%). Both tumor progression on waiting list (HR 4.973 [1.599 – 15.464], p=0.006) and peak AFP ≥400ng/ml (HR 4.604 [1.660 – 12.768], p=0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% (n=24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p=0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93%, 71%, and 66%. Conclusion: LT provides significantly better survival rates than palliation for patients with selected advanced HCC

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Living donor liver transplantation for patients with advanced hepatocellular carcinoma

Liver transplantation (LT) is the treatment of choice for patients with hepatocellular carcinoma (HCC) and underlying liver disease. Given the organ scarcity, LT for patients with HCC have been restricted to those patients associated with the highest survivals. However, many patients with extended criteria HCC can still benefit from LT, but due to deceased organ shortage, they are not offered that opportunity. Living donor liver transplantation (LDLT) emerged as a successful strategy to overcome organ shortage around the world and as LDLT experience grows, this technique might offer the opportunity to expand the indications of LT to patients with advanced HCC. Therefore, since LDLT is not competing for deceased donor organs, many patients with extended criteria HCC who could still benefit from transplantation may have access to this treatment option. In this review, we will discuss the role of LDLT for patients with advanced-stage HCC and how LDLT allows for safe expansion of HCC transplant criteria

Comprehensive review of the application of MP and the potential for graft modification

IntroductionFollowing procurement, the liver graft is exposed to an ischemic period that triggers several pathophysiologic changes in response to oxygen deprivation. Therefore, the goal during organ preservation is to attenuate such response and provide an adequate environment that prepares the graft for its metabolic reactivation following implantation. This has been widely achieved via static cold storage preservation, where the maintenance of the graft using cold preservation solutions reduce its metabolic activity and confer cytoprotection until transplantation. However, despite being the gold standard for organ preservation, static cold storage holds several disadvantages. In addition, the ongoing organ shortage has led to the use of unconventional grafts that could benefit from therapies pre-transplant. Organ preservation via machine perfusion systems appears as a promising solution to address both.MethodsHere, we aim to present a state-of-the-art narrative review regarding liver graft modification options using machine perfusion systems in combination with adjuvant strategies including immunomodulation, gene therapy and pharmacotherapy.ResultsAvailable reports are scarce and mostly on experimental animal models. Most of the literature reflects the use of normothermic or subnormothermic machine perfusion devices given that these particular type of machine allows for a metabolically active organ, and therefore facilitates its modification. Although limited, promising findings in available reports suggest that organ preservation using machine perfusion system when combined with alternative therapies can be feasible and safe strategies for graft modification.DiscussionFurther research on clinical settings are needed to better elucidate the true effect of graft modification pre-transplant on short- and long-term graft and patient survival. There is a long way ahead to develop guidelines and approve these novel therapies for clinical practice. However, the path looks promising