The Importance of Multiorgan Procurement in the Improvement of Residents' Open Surgical Skills.

INTRODUCTION: The multiorgan procurement (MOP) represents a chance for the general surgery resident to learn the fundamental steps of open abdominal surgery. The objective of this study was to evaluate the impact of MOP on the residents' open surgical skills. METHODS: Residents' surgical skills were assessed during a 6-month transplant rotation (October 2020-March 2021) using a modified Objective Structured Assessment of Technical Skills with the global rating scale. The surgeries were self-assessed by residents and tutors based on 9 specific steps (SS) and 4 general skills (GS). Each item was rated from 1 (poor) to 5 (excellent) with a maximum score of 45 points for SS and 20 for GS. A crossed-effects linear regression analysis was performed both to evaluate any associations between GS/SS scores and some prespecified covariates, and to study differences in the assessments performed by residents and tutors. RESULTS: Residents actively participated in a total of 59 procurements. In general, there were no significant differences in SS/GS mean scorings between residents (n = 15) and tutors (n = 5). There was a significantly positive association between mean GS/SS scorings and the number of donor surgeries performed (at least 5). Comparing the evaluations of the tutors with the residents, this significance was retained only when scorings were assigned by the tutors. CONCLUSIONS: MOP was shown to improve basic open surgical skills among residents. Awareness of the utility of a clinical rotation in transplant surgery should be raised also on an institutional level.

The role of cold ischemia time and hypothermic perfusion in predicting early hepatocellular carcinoma recurrences after liver transplantation.

AIM: The aim of the study was to identify predictors of early tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: Retrospective cohort study in 237 consecutive liver recipients with HCC between 2016 and 2021. Multivariate logistic analysis was performed to identify predictors of early HCC recurrences. The impact of hypothermic-oxygenated perfusion (HOPE) on outcome was analyzed after propensity score weighting. RESULTS: Early recurrences were observed in 15 cases. Microvascular invasion (OR 3.737, 95% CI 1.246-11.206, p = 0.019) and cold ischemia time (OR 1.155, 95% CI 1.001-1.333, p = 0.049) were independently associated with a lower risk of HCC recurrences. After balancing for relevant variables, patients in the HOPE group had lower rates of tumor recurrence (weighted OR 0.126, 95% CI 0.016-0.989, p = 0.049) and higher recurrence free survival (weighted HR 0.132, 95% CI 0.017-0.999, p = 0.050). CONCLUSION: Reducing cold ischemia time and graft perfusion with HOPE can lead to lower rates of early HCC recurrences and higher recurrence-free survival.

Surgical Treatment of Hepatocellular Carcinoma: Multicenter Competing-risk Analysis of Tumor-related Death Following Liver Resection and Transplantation Under an Intention-to-treat Perspective.

BACKGROUND: Early-stage hepatocellular carcinoma could benefit from upfront liver resection (LR) or liver transplantation (LT), but the optimal strategy in terms of tumor-related outcomes is still debated. We compared the oncological outcomes of LR and LT for hepatocellular carcinoma, stratifying the study population into a low-, intermediate-, and high-risk class according to the risk of death at 5-y predicted by a previously developed prognostic model. The impact of tumor pathology on oncological outcomes of low- and intermediate-risk patients undergoing LR was investigated as a secondary outcome. METHODS: We performed a retrospective multicentric cohort study involving 2640 patients consecutively treated by LR or LT from 4 tertiary hepatobiliary and transplant centers between 2005 and 2015, focusing on patients amenable to both treatments upfront. Tumor-related survival and overall survival were compared under an intention-to-treat perspective. RESULTS: We identified 468 LR and 579 LT candidates: 512 LT candidates underwent LT, whereas 68 (11.7%) dropped-out for tumor progression. Ninety-nine high-risk patients were selected from each treatment cohort after propensity score matching. Three and 5-y cumulative incidence of tumor-related death were 29.7% and 39.5% versus 17.2% and 18.3% for LR and LT group ( P = 0.039), respectively. Low-risk and intermediate-risk patients treated by LR and presenting satellite nodules and microvascular invasion had a significantly higher 5-y incidence of tumor-related death (29.2% versus 12.5%; P < 0.001). CONCLUSIONS: High-risk patients showed significantly better intention-to-treat tumor-related survival after upfront LT rather than LR. Cancer-specific survival of low- and intermediate-risk LR patients was significantly impaired by unfavorable pathology, suggesting the application of ab-initio salvage LT in such scenarios.

Renal Vessel Extension With Cryopreserved Vascular Grafts: Overcoming Surgical Pitfalls in Living Donor Kidney Transplant.

In LDKT, right kidneys and kidneys with anomalous vascularization are often deferred because of concerns on complications and vascular reconstructions. To date, only few reports have examined renal vessel extension with cryopreserved vascular grafts in LDKT. The aim of this study is to investigate the effect of renal vessel extension on short-term outcomes and ischemia times in LDKT. From 2012 to 2020, recipients of LDKT with renal vessels extension were compared with standard LDKT recipients. Subset analysis of rights grafts and grafts with anomalous vascularization, with or without renal vessel extension, was performed. Recipients of LDKT with (n = 54) and without (n = 91) vascular extension experienced similar hospital stays, surgical complications and DGF rates. For grafts with multiple vessels, renal vessel extension granted a faster implantation time (44±5 vs. 72±14 min), which resulted comparable to that of standard anatomy grafts. Right kidney grafts with vascular extension had a faster implantation time compared to right kidney grafts without vascular lengthening (43±5 vs. 58±9 min), and a comparable implantation time to left kidney grafts. Renal vessel extension with cryopreserved vascular grafts allows faster implantation time in right kidney grafts or grafts with anomalous vascularization, maintaining similar surgical and functional outcomes.

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Extracellular Vesicles Derived from Mesenchymal Stromal Cells Delivered during Hypothermic Oxygenated Machine Perfusion Repair Ischemic/Reperfusion Damage of Kidneys from Extended Criteria Donors.

The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome.

Assessment and Management of Transplant Renal Artery Stenosis. A Literature Review.

BACKGROUND: Transplant renal artery stenosis (TRAS) following kidney transplantation is a possible cause of graft failure. This review aimed to summarize the evidence about physiopathology, diagnosis and early and late effectiveness of the endovascular treatment (EVT), including angioplasty and stenting procedures. METHODS: A literature research was performed using Pubmed, Scopus and the Cochrane Library databases (January 2000-September 2020) according to PRISMA guidelines. Studies were included if they describe EVT, percutaneous transluminal angioplasty or stent placement of TRAS, published in English and with a minimum of ten patients. RESULTS: Fifty-six studies were included. TRAS incidence ranges from 1% up to 12% in transplanted kidneys. The TRAS risk factors were: elderly donor and recipient, cytomegalovirus match status, Class II Donor Specific Antibodies (DSA), expanded donor criteria, delayed graft functioning and other anatomical and technical factors. The highest frequency of TRAS presentation is after 3-6 months after kidney transplantation. The most frequent localization of stenosis was para-anastomotic (ranging from 25% to 78%). In 9 studies, all patients were treated by percutaneous transluminal angioplasty (PTA), in 16 studies all patients received percutaneous transluminal stenting (PTS) and in 21 series patients received either PTA or PTS. The twelve months patency rates after EVT ranged from 72% to 94%. The overall complication rate was 9%, with pseudoaneurysms and hematomas as most frequent complications. CONCLUSIONS: TRAS can be successfully and safely treated through an endovascular approach. Stent delivery seems to guarantee a higher patency rate compared to simple angioplasty, however further studies are needed to confirm these results.

Multiple organ retrieval in a brain dead left ventricular assist device donor.

Left ventricular assist device (LVAD) support in donors may contribute in preserving proper haemodynamics and systemic perfusion during organ retrieval thus decreasing the risk of multiple organ injury. This is an option to expand the current organ supply. We report on intra-abdominal organs procurement strategy in a selected LVAD recipient who suffered a fatal cerebrovascular accident at the time of COVID-19 pandemic outbreak. The liver and kidneys grafts have been successfully transplanted.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

The Relationship between Timing of Pretransplant Kidney Biopsy, Graft Loss, and Survival in Kidney Transplantation: An Italian Cohort Study.

INTRODUCTION: Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. METHODS: Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. RESULTS: CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, p value = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12-0.60; p value = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14-0.94; p value = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. DISCUSSION/CONCLUSION: Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

A Successful Urgent Liver Retransplant From a Donor With a Left Ventricular Assist Device.

Organ shortage is one of the major limitations in the field of liver transplantation, which has led to the consideration of extended criteria donors as a way to expand the donor pool. The use of extended criteria donors in cases of high Model for End-Stage Liver Disease scores or urgent recipients could be complicated by increased postoperative mortality. Donors on left ventricular assist devices could be considered extended criteria donors because of the mechanical circulatory support itself and the potential of chronic liver damage due to right ventricular failure, but experiences in the literature are limited. Here, we report the first case of an urgent liver retransplant procured from a left ventricular assist device donor.

Restoration of portal flow with varix in liver transplantation for patients with total portal vein thrombosis: An effective strategy in the largest center experience.

INTRODUCTION: Postoperative complications and worse prognosis still burden liver transplantations (LT) with complex portal vein thrombosis (CPVT). When an engorged left gastric vein (LGV) is present, the portal inflow is restorable with an anastomosis between the graft portal vein and the LGV of the recipient. We analyzed short- and long-term results of this procedure in 12 LT with CPVT. METHODS: Between 2005 and 2019, 55 patients with CPVT underwent LT. We applied this technique in 12 patients. In six cases, we placed a vascular graft to obtain a tension-free structure. We evaluated patency, short- and long-term results. RESULTS: No intraoperative complication was observed. The median duration of LT, blood transfusion, deceased donor age, and MELD score of the recipients were 7 h, 1250 mL, 72 years, and 19. Seven patients were affected by hepatocellular carcinoma. No major complications or PVT recurrence were observed. One patient required a liver re-transplantation for primary non-functioning syndrome. The mean hospital stay was 20 days. The actuarial patient survival was 85% with a mean FU of 4 years. The two late deaths were due to hepatocellular carcinoma recurrence and sepsis for cholangitis. CONCLUSIONS: This technique in presence of both CPVT and engorged LGV is feasible and safe for patients, with good short- and long-term results.

The Role of Ex Situ Hypothermic Oxygenated Machine Perfusion and Cold Preservation Time in Extended Criteria Donation After Circulatory Death and Donation After Brain Death.

Hypothermic oxygenated machine perfusion (HOPE) has the potential to counterbalance the detrimental consequences of cold and warm ischemia time (WIT) in both donation after brain death (DBD) and donation after circulatory death (DCD). Herein we investigated the protective effects of HOPE in extended criteria donor (ECD) DBD and overextended WIT DCD grafts. The present retrospective case series included 50 livers subjected to end-ischemic HOPE or dual DHOPE in 2 liver transplantation (LT) centers from January 2018 to December 2019. All DCD donors were subjected to normothermic regional perfusion before organ procurement. Results are expressed as median (interquartile range [IQR]). In the study period, 21 grafts were derived from overextended WIT DCD donors (total WIT 54 [IQR, 40-60] minutes and 75% classified as futile), whereas 29 were from ECD DBD. A total of 3 biliary complications and 1 case of ischemia-type biliary lesion were diagnosed. The rate of early allograft dysfunction (EAD) was 20%, and those patients had higher Comprehensive Complication Index scores. Through a changing point analysis, cold preservation time >9 hours was associated with prolonged hospital stays (P = 0.02), higher rates of EAD (P = 0.009), and worst post-LT complications (P = 0.02). Logistic regression analyses indicated a significant relationship between cold preservation time and EAD. No differences were shown in terms of the early post-LT results between LTs performed with DCD and DBD. Overall, our data are fully comparable with benchmark criteria in LT. In conclusion, the application of DHOPE obtained satisfactory and promising results using ECD-DBD and overextended DCD grafts. Our findings indicate the need to reduce cold preservation time also in the setting of DHOPE, particularly for grafts showing poor quality.

Complex Liver Transplantation Using Venovenous Bypass With an Atypical Placement of the Portal Vein Cannula.

In liver transplantation (LT) medical literature, venovenous bypass (VVB) with the interposition of a venous graft attached to the inferior mesenteric vein (IMV) or to the splenic vein (SV) has not been reported previously. Here, we report the decompression of the portomesenteric compartment in 2 patients with complex cases of orthotopic LT. A femoroaxillary percutaneous VVB was installed prior to abdominal opening to decompress massive collateral veins in the abdominal wall. In the first patient, the IMV was connected to a donor vein graft with a lateroterminal anastomosis, and the distal part of the vein graft was cannulated and connected to the VVB. In the second patient, because of the excessive size of the spleen, it was necessary to perform a splenectomy to gain sufficient space in the abdomen to implant the new liver. The SV was connected to a donor vein graft with a terminoterminal anastomosis, and the distal part of the vein graft was cannulated and connected to the VVB. In both patients, the decompression of the portomesenteric compartment was crucial to reduce portal hypertension and to access the hepatic hilum, where the dissection was very complex due to previous major surgeries. In conclusion, VVB with the interposition of a venous graft attached to the IMV or to the SV during LT is a safe and simple technique, and it may be useful for patients needing VVB with no standard access to the portal compartment, particularly in the case of severe portal hypertension and re-LTs.

Heterotopic segmental liver transplantation on splenic vessels after splenectomy with delayed native hepatectomy after graft regeneration: A new technique to enhance liver transplantation.

We describe a patient with liver metastases from colorectal cancer treated with chemotherapy and hepatic resection, who developed unresectable multifocal liver recurrence and who received liver transplantation using a novel planned technique: heterotopic transplantation of segment 2-3 in the splenic fossa with splenectomy and delayed hepatectomy after regeneration of the transplanted graft. We transplanted a segmental liver graft after in-situ splitting without any impact on the waiting list, as it was previously rejected for pediatric and adult transplantation. The volume of the graft was insufficient to provide liver function to the recipient, so we performed this novel operation. The graft was anastomosed to the splenic vessels after splenectomy, and the native liver portal flow was modulated to enhance graft regeneration, leaving the native recipient liver intact. The volume of the graft doubled during the next 2 weeks and the native liver was removed. After 8 months, the patient lives with a functioning liver in the splenic fossa and without abdominal tumor recurrence. This is the first case reported of a segmental graft transplanted replacing the spleen and modulating the portal flow to favor graft growth, with delayed native hepatectomy.

Author Correction: Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors: First Italian Clinical Trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Double Single-Side Kidney Transplants With Bench Vascular Reconstruction: A Further Challenge Beyond the Marginality Without Future Preclusions.

BACKGROUND: Double kidney transplantation allows the use of marginal kidneys with a significant improvement in the recovery of renal function expected after transplantation, although with a greater anesthesiologic and surgical risk. One-sided positioning, more cautious in the event of functional exhaustion, can be complex due to vascular anomalies. MATERIALS AND METHODS: We report the case of 2 double unilateral kidney transplants with vascular reconstructions. The first is a double kidney transplant from a 83-year-old donor. Both kidneys (score 5) had 2 arteries and the arterial patch was not usable. A cryopreserved arterial graft was used for the packaging of an arterial axis with which a single T-L anastomosis was performed; the 2 veins were also joined with the packaging of a single anastomosis. The second case is a double kidney transplant from a cadaveric donor performed on a recipient suffering from severe diffuse atheromasia. The right kidney had 2 arteries and the left kidney had 3 arteries (both score 5). The aortic patches and veins of the 2 kidneys were joined together and a single arterial and venous anastomosis was performed. RESULTS: The course has been uneventful. In both cases there were no perioperative vascular complications. CONCLUSIONS: The use of marginal organs is an increasingly common reality. Bench vascular reconstructions can further increase donation resources, safely enhancing the transplantation of already marginal organs that would otherwise not be usable and allowing the contralateral vascular axis to be kept intact.

A nomogram based on liver stiffness predicts postoperative complications in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Liver stiffness measurement (LSM), assessed by transient elastography (Fibroscan), has been demonstrated to predict post-hepatectomy liver failure in patients who undergo hepatic resection for hepatocellular carcinoma (HCC). However, other complications are also likely to be related to the underlying grade of liver fibrosis. Herein, we aimed to identify predictors of postoperative complications and to build and develop a novel nomogram able to identify patients at risk of developing severe complications. METHODS: Data from patients who underwent hepatectomy for HCC between 2006 and 2016 at 2 referral centres were retrospectively reviewed. All surgical complications were recorded and scored using the comprehensive complication index (CCI), ranging from 0 (uneventful course) to 100 (death). A CCI ≥26.2 was used as a threshold to define severe complications. RESULTS: During the study period, 471 patients underwent hepatic resection for HCC. Among them, 50 patients (10.6%) had a CCI ≥26.2. Age, model for end-stage liver disease (MELD) score and LSM values, together with serum albumin, were independent predictors of high CCI. The nomogram built on these variables was internally validated and showed good performance (optimism-corrected c-statistic = 0.751). A regression equation to predict the CCI was also established by multiple linear regression analysis: [LSM (kPa) × 0.254] + [age (years) × 0.118] + [MELD score (pt.) × 1.050] - [albumin (g/dl) × 2.395] - 3.639. CONCLUSION: A novel nomogram, combining LSM values, age and liver function tests provided an excellent preoperative prediction of high CCI in patients with resectable HCC. This predictive model could be used as a reference for clinicians and surgeons to help them in clinical decision-making. LAY SUMMARY: Liver stiffness measurement is increasingly being used to assess the degree of liver fibrosis in patients with cirrhosis and/or chronic hepatitis. Using Fibroscan, we developed a novel nomogram to predict severe complications following liver resection for hepatocellular carcinoma, according to the new comprehensive complication index. This tool could be used as a reference for clinicians and surgeons to help them in clinical decision-making.