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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fallani, Maroni, Bonatti, Comai, Buzzi, Cuna, Vasuri, Caputo, Prosperi, Pisani, Pisillo, Maurino, Odaldi, Bertuzzo, Tondolo, Busutti, Zanfi, Del Gaudio, La Manna and Ravaioli.)

The requirement of blood-circulating sensitive biomarkers for monitoring liver transplant (LT) is currently a necessary step aiming at the reduction of standard invasive protocols, such as liver biopsy. In this respect, the main objective of this study is to assess circulating microRNA (c-miR) changes in recipients' blood before and after LT and to correlate their blood levels with gold standard biomarkers and with outcomes such as rejection or complications after graft. An miR profile was initially performed; then, the most deregulated miRs were validated by RT-qPCR in 14 recipients pre- and post-LT and compared to a control group of 24 nontransplanted healthy subjects. MiR-122-5p, miR-92a-3p, miR-18a-5p, and miR-30c-5p, identified in the validation phase, were also analyzed considering an additional 19 serum samples collected from LT recipients and focusing on different follow-up (FU) times. The results showed significant, FU-related changes in c-miRs. In particular, miR-122-5p, miR-92a-3p, and miR-18a-5p revealed the same trend after transplantation and an increase in their level was found in patients with complications, independently from FU times. Conversely, the variations in the standard haemato-biochemical parameters for liver function assessment were not significant in the same FU period, confirming the importance of c-miRs as potential noninvasive biomarkers for monitoring patients' outcomes.

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., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (© 2021 S. Karger AG, Basel.)

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., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT.

The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6% vs. 9.2%, p < 0.005. After LT, the tumor recurrence rate was significantly different: MC 7.6%, Down-Achieved 20.9%, Down-not Achieved 31.6%, and No-Down 30.4% (p < 0.001). The survival rates at 5 years were: 63% in Down-Achieved, 62% in Down-not Achieved, 63% in No-Down, and 77% in MC (p = n.s.). The only variable related to a better outcome was the effective down-staging to T2 at the histological evaluation of the explanted liver: recurrence rate = 7.8% vs. 26% (p < 0.001) and 5-year patient survival = 76% vs. 67% (p < 0.05). The ATE estimation showed that the mean survival of T3-LT candidates was significantly better than that of T3 patients ineligible for LT [83.3 vs 39.2 months (+44.6 months); p < 0.001]. Long term outcome of T3 down-staged candidates was poorer than that of MC candidates, particularly for cases not achieving down-staging. However, their survival outcome was significantly better than that achieved with non-transplant therapies.

Donation after circulatory death (DCD) is a potential source of reducing organ demand. In Italy, DCD requires a 20-min no-touch period that prolongs warm ischemia and increases delayed graft function (DGF) risk and graft loss. We report here our preliminary experience of sequential use of normothermic regional perfusion (NRP), as standard procedure, and hypothermic oxygenated perfusion (HOPE), as an experimental technique of organ preservation, in 10 kidney transplants (KT) from five DCD Maastricht III with extensive functional warm ischemia time (fWIT) up to 325 min. During NRP, renal function tests were evaluated to accept organs which were retrieved according to standard fashion with biopsy. While waiting for pathology and cross-match results, organs were preserved with HOPE through pressure- and temperature-controlled arterial pulsatile flow. All grafts with Karpinski score ≤4 were used for conventional single KT with mean cold ischemia time of 584 ± 167 min and mean fWIT of 151 ± 132 min. At the end of HOPE, lactate levels increased significantly in all cases with DGF (P = 0.0095), which were 3/10 (30%). No primary nonfunctions were recorded, and all patients had sCr < 1.5 mg/dl at 6-month post-KT. NRP and HOPE for DCD may overcome fWIT limits safely, and lactate during HOPE predicts DGF., (© 2018 Steunstichting ESOT.)

Objective: To evaluate the whole experience of liver transplantation (LT) with donors ≥70 years in a single center not applying specific donor/recipient matching criteria., Background: LT with very old donors has historically been associated with poorer outcomes. With the increasing average donor age and the advent of Model for End-stage Liver Diseases (MELD) score-based allocation criteria, an optimal donor/recipient matching is often unsuitable., Methods: Outcomes of all types of LTs were compared according to 4 study groups: patients transplanted between 1998 and 2003 with donors <70 (group 1, n = 396) or ≥70 years (group 2, n = 88); patients transplanted between 2004 and 2010 with donors <70 (group 3, n = 409), or ≥70 years (group 4, n = 190). From 2003, graft histology was routinely available before cross-clamping, and MELD-driven allocation was adopted., Results: Groups 1 and 2 were similar for main donor and recipient variables, and surgical details. Group 4 had shorter donor ICU stay, lower rate of moderate-to-severe graft macrosteatosis (2.3% vs 8%), and higher recipient MELD score (22 vs 19) versus group 3. After 2003, median donor age, recipient age, and MELD score significantly increased, whereas moderate-to-severe macrosteatosis and ischemia time decreased. Five-year graft survival was 63.6% in group 1 versus 59.1% in group 2 (P = 0.252) and 70.9% in group 3 versus 67.6% in group 4 (P = 0.129). Transplants performed between 1998 and 2003, recipient HCV infection, balance of risk score >18, and pre-LT renal replacement treatments were independently associated with worse graft survival., Conclusions: Even without specific donor/recipient matching criteria, the outcomes of LT with donors ≥70 and <70 years are comparable with appropriate donor management.

Background: Bacterial infection in patients with liver failure can lead to a dramatic clinical deterioration. The indications for liver transplantation and outcome in these patients is still controversial., Methods: All adult patients who underwent liver transplantation between 1 January 2010 and 31 December 2015 were selected from an institutional database. Characteristics of the donors and recipients, and clinical, biochemical and surgical parameters were retrieved from the database. Post-transplant survival rates and complications, including grade III-IV complications according to the Dindo-Clavien classification, were compared between patients with an infection 1 month before transplantation and patients without an infection., Results: Eighty-four patients with an infection had statistically significant higher Model for End-stage Liver Disease (MELD), D-MELD and Balance of Risk (BAR) scores and a higher rate of acute-on-chronic liver failure compared with findings in 343 patients with no infection. The rate of infection after liver transplantation was higher in patients who had an infection before the operation: 48 per cent versus 30·6 per cent in those with no infection before transplantation (P = 0·003). The percentage of patients with a postoperative complication (42 versus 40·5 per cent respectively; P = 0·849) and the 90-day mortality rate (8 versus 6·4 per cent; P = 0·531) was no different between the groups. Multivariable analysis showed that a BAR score greater than 18 and acute-on-chronic liver failure were independent predictors of 90-day mortality., Conclusion: Bacterial infection 1 month before liver transplantation is related to a higher rate of infection after transplantation, but does not lead to a worse outcome., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: An immune function assay shows promise for identifying solid organ recipients at risk for infection or rejection. The following randomized prospective study was designed to assess the clinical benefits of adjusting immunosuppressive therapy in liver recipients based on immune function assay results., Methods: Adult liver recipients were randomized to standard practice (control group; n = 102) or serial immune function testing (interventional group; n = 100) performed with a commercially available in vitro diagnostic assay (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation, immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to 6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed rejection/infection and within 1 week after event resolution., Results: Based on immune function values, tacrolimus doses were reduced 25% when values were less than 130 ng/mL adenosine triphosphate (low immune cell response) and increased 25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune cell response). The 1-year patient survival was significantly higher in the interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer than 14 days after transplantation was significantly lower among patients in the interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs 11%; P < 0.05). Among recipients without adverse events, the study group had lower tacrolimus dosages and blood levels., Conclusions: Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes.

Criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) and post-LT indicators of prognosis are historically based on the measurement of the tumor mass. Recently, high throughput technologies have increased the prediction of recurrence, but these tools are not yet routinely available. The interaction between HCC and the immune system has revealed an imbalance of lymphocyte phenotypes in the peritumoral tissue, and the increase of regulatory T cells with respect to cytotoxic lymphocytes has been linked to a higher rate of post-LT HCC recurrence. Moreover, some inflammatory markers have shown good reliability in predicting cancer reappearance after surgery, as a result of either a systemic inflammatory response or a decreased capacity of the organism to control the tumor growth. Among these markers, the neutrophil-to-lymphocyte ratio appears to be the most promising and easily available serum parameter able to predict HCC recurrence after LT and following other types of treatment, although the exact mechanisms determining its elevation have not been clarified. Post-LT immunosuppression may impact on cancer control, and the exposure to high levels of calcineurin inhibitors or other immunosuppressants has recently emerged as a negative prognostic factor for HCC recurrence and patient survival. Despite the absence of prospective randomized trials, inhibitors of the mammalian target of rapamycin have been shown to be associated with lower rates of tumor recurrence compared to other immunosuppressors, suggesting their use especially in patients with HCC exceeding the conventional indication criteria for LT.

The risk of fascial dehiscence, wound infection and incisional hernias in organ recipients is higher. Retrospective analysis of our departments database, checking the last 12 years (2000-2012), and of the literature (1966-2012) were conducted. In our database we found seven patients: five liver (71.4 %), one kidney (14.3 %), one multivisceral (14.3 %); five males (71.4 %), two females (28.6 %). Five (71.4 %) were operated in urgency setting and two in ordinary setting (28.6 %). The mean/median number of laparotomies before the incisional hernia is of 2.1/1 (range 1-5). In five patients swine intestinal submucosa (71.4 %) have been used and in two porcine dermal collagen (28.6 %). The mean/median age was 48.3/52 years (range 18-61). The mean/median body mass index was 26.7/27 (range 19-34). The mean/median for follow-up after intervention was 40.1/33 months (range 50-21). Recurrence rate was 14.3 %. Complication rate was 28.6 %. Adding the present report, the literature reports 70 cases. 20 % of prosthesis have been implanted inlay, 25.7 % underlay, in 5.7 % intraperitoneal and in 48.6 % were not specified. The mean age ranges from 0.7 to 48.3 years. Kidney, liver, pancreas, bowel and multivisceral transplant are reported. Porcine dermal collagen has been implanted in 24.3 %, human dermal collagen in 51.4 % and swine intestinal submucosa in 24.3 %. The immunosuppression regimens comprehend variable associations of tacrolimus, steroids, mycophenolate mofetil, sirolimus, thymoglobulin, azathioprine/basiliximab and daclizumab. The mean follow-up is 16.2 months. The mean complication rate is 9.4 %. Biological prosthesis seems to be useful and safe in abdominal wall repair surgery in transplanted patients.

Background and Aims: The management of patients treated for hepatitis C recurrence after liver transplantation and not achieving virological response following treatment with interferon plus ribavirin is controversial., Methods: A retrospective analysis of the outcomes of 70 patients non-responders to antiviral treatment after liver transplantation was performed. Twenty-one patients (30.0%; Group A) were treated for ≤ 12 months and 49 (70.0%; Group B) for more than 12 months., Results: The 2 groups were comparable for main demographic, clinical and pathological variables. Median duration of antiviral treatment was 8.2 months in Group A and 33.4 months in Group B. No patient achieved a complete virological response. The 5-year patient hepatitis C-related survival rate was 49.2% in Group A and 88.3% in Group B (P=0.002), while the 5-year graft survival rate was 49.2% in Group A and 85.9% in Group B (P=0.007). The median yearly fibrosis progression rate was 1.21 per year in Group A and 0.40 per year in Group B (P=0.001)., Conclusions: Prolonged antiviral treatment showed an overall beneficial effect in transplanted patients with a recurrent hepatitis C infection and not responding to conventional therapy. The treatment should be continued as long as it is permitted, in order to improve clinical and histological outcomes., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Systemic inflammation markers, such as neutrophil-to-lymphocyte ratio (NLR), have recently emerged as the prognostic factors for recurrence of liver tumors., Methods: We assessed the ability of NLR and of other variables to predict the outcomes of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). A retrospective analysis was performed in 219 patients with HCC who underwent OLT between 1997 and 2009, with a median follow-up of 40 months., Results: Overall 3- and 5-year patient survival rates were 76.6% and 70.7%, respectively. Overall 3- and 5-year recurrence-free survival (RFS) rates were 83.8% and 82.1%, respectively. On univariate analysis, the factors affecting overall survival were α-fetoprotein more than 30 ng/mL (P=0.006), NLR more than or equal to 5 (P<0.0001), hepatitis C infection (P=0.043), and presence of microvascular invasion (MVI; P=0.006). Preoperative treatments (P=0.006), α-fetoprotein more than 30 ng/mL (P=0.003), NLR more than or equal to 5 (P<0.0001), exceeding Milan criteria at final histology (P=0.001), poor tumor differentiation (P=0.02), and presence of MVI (P<0.0001) predicted a lower RFS. Cox's proportional hazard model showed that only increased NLR and presence of MVI independently predicted overall survival and RFS., Conclusions: NLR is an important predictor of outcome after OLT for HCC and should be used to identify OLT candidates at high risk of recurrence.

Non-carcinoid appendiceal malignancies are rare entities, representing less than 0.5% of all gastrointestinal malignancies. Because of their rarity and particular biological behavior, a substantial number of patients affected by these neoplasms do not receive appropriate surgical resection. In this report, we describe a rare case of primary signet-ring cell carcinoma of the appendix with peritoneal seeding which occurred in a 40-year old man admitted at the Emergency Surgery Department with the clinical suspicion of acute appendicitis. After a surgical debulking and right hemicolectomy, the patient had systemic chemotherapy according to FOLFOX protocol. After completion of the latter, the patient underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy. This report offers a brief review of the literature and suggests an algorithm for the management of non-carcinoid appendiceal tumors with peritoneal dissemination.