Corrigendum to 'Transplant oncology - Current indications and strategies to advance the field' [JHEP Reports 6 (2024) 100965].

[This corrects the article DOI: 10.1016/j.jhepr.2023.100965.].

Normothermic Liver Machine Perfusion and Successful Transplantation of Split Liver Grafts: From Proof of Concept to Clinical Implementation.

BACKGROUND: Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day. METHODS: We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity. RESULTS: Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7). CONCLUSIONS: NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.

The BAR Score Predicts and Stratifies Outcomes Following Liver Retransplantation: Insights From a Retrospective Cohort Study.

Liver retransplantation (reLT) yields poorer outcomes than primary liver transplantation, necessitating careful patient selection to avoid futile reLT. We conducted a retrospective analysis to assess reLT outcomes and identify associated risk factors. All adult patients who underwent a first reLT at the Medical University of Innsbruck from 2000 to 2021 (N = 111) were included. Graft- and patient survival were assessed via Kaplan-Meier plots and log-rank tests. Uni- and multivariate analyses were performed to identify independent predictors of graft loss. Five-year graft- and patient survival rates were 64.9% and 67.6%, respectively. The balance of risk (BAR) score was found to correlate with and be predictive of graft loss and patient death. The BAR score also predicted sepsis (AUC 0.676) and major complications (AUC 0.720). Multivariate Cox regression analysis identified sepsis [HR 5.179 (95% CI 2.575-10.417), p < 0.001] as the most significant independent risk factor for graft loss. At a cutoff of 18 points, the 5 year graft survival rate fell below 50%. The BAR score, a simple and easy to use score available at the time of organ acceptance, predicts and stratifies clinically relevant outcomes following reLT and may aid in clinical decision-making.

Transplant oncology - Current indications and strategies to advance the field.

Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.

Diverticulitis with coloenteric fistula mimicking gangrenous appendicitis with perityphlitic abscess. An uncommon presentation of a common disease - A case report.

INTRODUCTION: Diverticulitis is a common gastrointestinal disease usually presenting with a typical clinical picture depending on the stage of the disease. In complicated cases, the clinical presentation may be untypical, thus delaying diagnosis and treatment. PRESENTATION OF CASE: We present a case of a young patient who was initially treated for obscure intraabdominal abscesses presumably due to gangrenous appendicitis; however, intraoperative exploration revealed a normal appendix and a coloenteric fistula resulting from an unknown and untreated perforated diverticulitis. DISCUSSION: A patient with a perityphlitic abscess was initially managed with primary non-operative management (NOM) in accordance with the current Jerusalem guidelines, but surgery was eventually necessary due to failure of NOM. Intraoperative findings revealed a sigmoido-ileal fistula, a rare but potentially detectable complication of diverticulitis through colonoscopy. This case highlights the challenges in diagnosing and treating common surgical diseases with uncommon clinical presentations, emphasizing the importance of a detailed patient history and not relying solely on imaging studies. CONCLUSION: Intraabdominal abscesses require prompt treatment with non-operative management, while intestinal fistulae associated with diverticulitis are a rare consequence of chronic inflammation, often asymptomatic and often detected incidentally during surgery. In most cases simple fistulous tract resection is usually sufficient as first line therapy.

Liver Transplantation in Recipients With a Positive Crossmatch: A Retrospective Single-Center Match-Pair Analysis.

A positive crossmatch (XM+) is considered a contraindication to solid abdominal organ transplantation except liver transplantation (LT). Conflicting reports exist regarding the effects of XM+ on post-transplant outcomes. The goal of this retrospective single-center analysis is to evaluate the influence of XM+ on relevant outcome parameters such as survival, graft rejection, biliary and arterial complications. Forty-nine adult patients undergoing LT with a XM+ between 2002 and 2017 were included. XM+ LT recipients were matched 1:2 with crossmatch negative (XM-) LT recipients based on the balance of risk (BAR) score. Patient and graft survival were compared using Kaplan-Meier survival analysis and the log-rank test. Comparative analysis of clinical outcomes in XM+ and XM- groups were conducted. Patient and graft survival were similar in XM+ and XM- patients. Rejection episodes did not differ either. Recipients with a strong XM+ were more likely to develop a PCR+ CMV infection. A XM+ was not associated with a higher incidence of biliary or arterial complications. Donor age, cold ischemia time, PCR+ CMV infection and a rejection episode were associated with the occurrence of ischemic type biliary lesions. A XM+ has no effects on patient and graft survival or other relevant outcome parameters following LT.

Multidisciplinary Treatment of Liver Metastases from Intracranial SFTs/HPCs: A Report of Three Consecutive Cases.

In the 2016 WHO classification of tumors of the central nervous system, hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) were integrated into a new entity (SFT/HPC). Metastases to bone, liver, lung, and abdominal cavity are of concern. Only 37 cases of patients with liver metastases due to intracranial SFTs/HPCs have been reported. Herein, we present our experience in the management of patients with liver metastases from intracranial SFTs/HCPs. All consecutive patients who were treated for liver metastases from intracranial SFTs/HPCs from January 2014 to December 2020 were enrolled. Overall, three patients were treated for liver metastasis from SFTs/HPCs with curative intent. Two patients with bilobar metastases at presentation required surgical resection, transarterial embolization, stereotactic radiofrequency ablation (SRFA) and systemic therapy. One patient with a singular right liver lobe metastasis was treated with SRFA alone. This patient shows no evidence of liver metastases 39 months following diagnosis. Of the two patients with bilobar disease, one died 89 months following diagnosis, while one is still alive 73 months following diagnosis. Long-term survival can be achieved using a multimodal treatment concept, including surgery, loco-regional and systemic therapies. Referral to a specialized tertiary cancer center and comprehensive long-term follow-up examinations are essential.

Perfusate Enzymes and Platelets Indicate Early Allograft Dysfunction After Transplantation of Normothermically Preserved Livers.

BACKGROUND: Normothermic machine perfusion (NMP) has become a clinically established tool to preserve livers in a near-physiological environment. However, little is known about the predictive value of perfusate parameters toward the outcomes after transplantation. METHODS: Fifty-five consecutive NMP livers between 2018 and 2019 were included. All of the livers were perfused on the OrganOx metra device according to an institutional protocol. Transplant and perfusion data were collected prospectively. RESULTS: Forty-five livers were transplanted after NMP. Five livers stem from donors after circulatory death and 31 (68.9%) from extended criteria donors. Mean (SD) cold ischemia time was 6.4 (2.3) h; mean (SD) total preservation time was 21.4 (7.1) h. Early allograft dysfunction (EAD) occurred in 13 of 45 (28.9%) patients. Perfusate aspartate aminotransferase (P = 0.008), alanine aminotransferase (P = 0.006), lactate dehydrogenase (P = 0.007) and their development over time, alkaline phosphatase (P = 0.013), and sodium (P = 0.016) correlated with EAD. Number of perfusate platelets correlated with cold ischemia time duration and were indicative for the occurrence of EAD. Moreover, von Willebrand Factor antigen was significantly higher in perfusates of EAD livers (P < 0.001), and Δ von Willebrand factor antigen correlated with EAD. Although perfusate lactate and glucose had no predictive value, EAD was more likely to occur in livers with lower perfusate pH (P = 0.008). ΔPerfusate alkaline phosphatase, Δperfusate aspartate aminotransferase, Δperfusate alanine aminotransferase, and Δperfusate lactate dehydrogenase correlated closely with model for early allograft function but not liver graft assessment following transplantation risk score. Bile parameters correlated with extended criteria donor and donor risk index. CONCLUSIONS: Biomarker assessment during NMP may help to predict EAD after liver transplantation. The increase of transaminases and lactate dehydrogenase over time as well as platelets and vWF antigen are important factors indicative for EAD.

Post-Transplant Malignancies following Pancreas Transplantation: Incidence and Implications on Long-Term Outcome from a Single-Center Perspective.

Chronic immunosuppression is associated with an increased risk of malignancy. The main objective of this study is to evaluate the incidence and effect of post-transplant malignancies (PTMs) following pancreas transplantation. The 348 first pancreas transplants performed between 1985 and 2015 were retrospectively analyzed in this study. Incidences of PTMs, as well as patient and graft survival, were evaluated. Out of 348 patients, 71 (20.4%) developed a PTM. Median time to diagnosis was 130 months. Thirty-six patients (50.7%) developed skin cancers (four patients with melanoma, 32 with NMSCs). Solid organ malignancy occurred in 25 (35.2%), hematologic malignancy in ten patients (14.1%). Affected patients were transplanted earlier [2000 (IQR 1993-2004) vs. 2003 (IQR 1999-2008); p < 0.001]. No differences in induction therapy were seen, both groups demonstrated comparable patient and graft survival. Pancreas transplant recipients with solid organ and hematologic malignancies had a three- and six-fold increased hazard of death compared to those with skin cancers [aHR 3.04 (IQR 1.17-7.91); p = 0.023; aHR 6.07 (IQR 1.87-19.71); p = 0.003]. PTMs affect every fifth patient following pancreas transplantation. Skin cancers are the most common malignancies accounting for 50% of all PTMs. These results underscore the importance of close dermatologic follow-up.

The impact of donor pancreas extraction time on graft survival and postoperative complications in pancreas transplant recipients.

BACKGROUND: Simultaneous pancreas kidney transplantation (SPK) is the best therapeutic option for patients with diabetes mellitus type 1 and end-stage renal disease. Recently, donor organ extraction time has been shown to affect kidney and liver graft survival. This study aimed to assess the effect of pancreas donor extraction time on graft survival and postoperative complications. METHODS: We retrospectively analyzed all pancreas transplants performed in two Eurotransplant centers. The association of pancreas extraction time with pancreas graft survival was analyzed by a Cox proportional hazards regression analysis after 3 months, 1 and 5 year. Besides, the effect of pancreas extraction time on the incidence of severe postoperative complications was analyzed. RESULTS: A total of 317 pancreas transplants were included in this study. Death-censored pancreas graft survival was 85.7% after one year and 76.7% after five years. Median pancreas donor extraction time was 64 min [IQR: 52-79 min]. After adjustment for potential confounders, death censored graft survival after 30 days (HR 1.01, 95% CI 0.9-1.03 (p = 0.23), 1 year (HR 1.01, 95% CI 0.99-1.03 (p = 0.22) and 5 years (HR 1.00, 95% CI 0.99-1.02 (p = 0.57) was not associated with pancreas donor extraction time. However, extraction time was significantly associated with a higher incidence of Clavien-Dindo ≥3 complications compared to Clavien-Dindo 1 + 2 complications: OR 1.012, 95% CI 1.00-1.02 (p = 0.039). CONCLUSIONS: Our findings suggest that although no effect on graft survival was found, limiting pancreas extraction time can have a significant impact on lowering postoperative complications.

Recipient age and outcome after pancreas transplantation: a retrospective dual-center analysis.

With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death-censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.

Donor cardiac arrest and cardiopulmonary resuscitation: impact on outcomes after simultaneous pancreas-kidney transplantation - a retrospective study.

Donor cardiac arrest and cardiopulmonary resuscitation (CACPR) has been considered critically because of concerns over hypoperfusion and mechanical trauma to the donor organs. We retrospectively analyzed 371 first simultaneous pancreas-kidney transplants performed at the Medical University of Innsbruck between 1997 and 2017. We evaluated short- and long-term outcomes from recipients of organs from donors with and without a history of CACPR. A total of 63 recipients received a pancreas and kidney graft from a CACPR donor. At 1, and 5-years, patient survival was similar with 98.3%, and 96.5% in the CACPR and 97.0%, and 90.2% in the non-CACPR group (log rank P = 0.652). Death-censored pancreas graft survival was superior in the CACPR group with 98.3%, and 91.4% compared to 86.3%, and 77.4% (log rank P = 0.028) in the non-CACPR group, which remained statistically significant even after adjustment [aHR 0.49 (95% CI 0.24-0.98), P = 0.044]. Similar relative risks for postoperative complications Clavien Dindo > 3a, pancreatitis, abscess, immunologic complications, delayed pancreas graft function, and relative length of stay were observed for both groups. Donors with a history of CACPR are, in the current practice, safe for transplantation. Stringent donor selection and short CPR durations may allow for outcomes surpassing those of donors without CACPR.