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Background: Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. Patients and Methods: The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). Results: Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). Conclusion: LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

Background: We investigated the effects of single (SL-ET) and double leg (DL-ET) high-intensity interval training on O2 deficit (O2Def) and mean response time (MRT) during square-wave moderate-intensity exercise (DL-MOD), and on the amplitude of V˙O2p slow component (SCamp), during heavy intensity exercise (DL-HVY), on 33 patients (heart transplant = 13, kidney transplanted = 11 and liver transplanted = 9). Methods: Patients performed DL incremental step exercise to exhaustion, two DL-MOD tests, and a DL-HVY trial before and after 24 sessions of SL-ET (n = 17) or DL-ET (n = 16). Results: After SL-ET, O2Def, MRT and SCamp decreased by 16.4% ± 13.7 (p = 0.008), by 15.6% ± 13.7 (p = 0.004) and by 35% ± 31 (p = 0.002), respectively. After DL-ET, they dropped by 24.9% ± 16.2 (p < 0.0001), by 25.9% ± 13.6 (p < 0.0001) and by 38% ± 52 (p = 0.0003), respectively. The magnitude of improvement of O2Def, MRT, and SCamp was not significantly different between SL-ET and DL-ET after training. Conclusions: We conclude that SL-ET is as effective as DL-ET if we aim to improve V˙O2p kinetics in transplanted patients and suggest that the slower, V˙O2p kinetics is mainly caused by the impairment of peripherals exchanges likely due to the immunosuppressive medications and disuse.

We investigated the effects of single (SL-ET) and double leg (DL-ET) high-intensity interval training on OPatients performed DL incremental step exercise to exhaustion, two DL-MOD tests, and a DL-HVY trial before and after 24 sessions of SL-ET (After SL-ET, OWe conclude that SL-ET is as effective as DL-ET if we aim to improve V˙O

The shortage of organs and the growing need for them over recent years have led to the adoption of less stringent donor acceptance criteria, resulting in the approval of marginal organs for transplant, especially from elderly donors. This implies a higher risk of graft dysfunction, a higher frequency of immunological and vascular complications, and shorter graft survival. Several strategies have been implemented in clinical practice to assess graft quality and suitability for transplantation. We have started to test the prospective intraoperative use of thermo-vision cameras during graft reperfusion. Images were acquired using the FLIR One Pro thermo-vision camera for android devices. We hypothesized that thermal images would give a better perspective about the quality of arterial perfusion and graft revascularization of the renal cortex. Thermo-vision cameras provide an easy-to-use, noninvasive, cost-effective tool for the global assessment of kidney graft cortical microcirculation in the immediate post-reperfusion period, providing additional data on the immediate viability and function of a graft.

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

The aim of the present study was to investigate whether LT candidates with sarcopenia are at an increased risk of receiving an inappropriate standard liver volume (SLV) estimation by standard body weight (BW)-derived SLV formula. Non-BW-SLV estimation formulas were tested in 262 LDLT donors and compared to a standard BW-SLV formula. The anthropometric parameters used were the thoracic width (TW-SLV) and thoracoabdominal circumference (TAC-SLV). Subsequently, sarcopenic and non-sarcopenic LDLT candidates (total, 217 patients) were compared in terms of estimated BW-SLV (routine method) and non-BW-SLV. In donors, TW-SLV showed comparable concordance with CT scan measured total liver volume as BW-SLV. The performance of TAC-SLV was low. In recipients, the prevalence of pre-LT sarcopenia was 30.4%. Sarcopenic patients were attributed a significantly lower BW-SLV than non-sarcopenic (sarcopenia vs no-sarcopenia, 1063.8 ml [1004.1-1118.4] vs. 1220.7 ml [1115.0-1306.6], P < 0.001), despite comparable TW-SLV, age, body height, and gender prevalence. As a result, sarcopenic patients received a graft with a statistically lower weight at organ procurement and developed more frequently a small-for-size syndrome (SFSS) according to the Dahm et al. (27.7% vs. 6.8%, P < 0.01) and Kyushu (28.7% vs. 9.2%, P < 0.01) definition. Therefore, In sarcopenic patients, BW-SLV formulas are affected by an high risk of SLV underestimation, thus exposing them to an increased risk of post-LT SFSS.

BACKGROUND: The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass (SMM). In living-donor liver transplantation (LDLT), liver graft regeneration (GR) represents a crucial process to normalize the portal hypertension and to meet the metabolic demand of the recipient. Limited data are available on the correlation between pre-LDLT low SMM and GR. METHODS: Retrospective study on a cohort of 106 LDLT patients receiving an extended left liver lobe graft. The skeletal muscle index (SMI) at L3 level was used for muscle mass measurement, and the recommended cut-off values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity. GR was evaluated as rate of volume increase at 1 month post-LT [graft regeneration rate (GRR)]. RESULTS: The median GRR at 1 month post-LT was 91% (IQR, 65–128%) and a significant correlation with graft volume-to-recipient standard liver volume ratio (GV/SLV) (rho −0.467, P

The liver–gut axis has been identified as crucial mediator of liver regeneration. Thus, the use of a T-tube in liver transplantation (LT), which interrupts the enterohepatic bile circulation, may potentially have a detrimental effect on the early allograft functional recovery. We retrospectively analyzed a cohort of 261 patients transplanted with a whole liver graft, with a duct-to-duct biliary anastomosis, who did not develop any surgical complication within postoperative day 14. Early allograft dysfunction (EAD) was defined according to the criteria of Olthoff et al. (EAD-O), and graded according to the Model for Early Allograft Function (MEAF) score. EAD-O developed in 24.7% of recipients and the median MEAF score was 4.0 [interquartile range 2.9–5.5]. Both MEAF and EAD predicted 90-day post-LT mortality. A T-tube was used in 49.4% of cases (n = 129). After a propensity score matching for donor age, cold and warm ischemia time, donor risk index, balance of risk score, Child–Pugh class C, and MELD score, the T-tube group showed a significantly higher prevalence of EAD-O and value of MEAF than the no-T-tube group (EAD-O: 29 [34.1%] vs 16 [19.0%], p = 0.027; MEAF 4.5 [3.5–5.7] vs 3.7 [2.9–5.0], p = 0.014). In conclusion, T-tube use in LT may be a risk factor for EAD and higher MEAF, irrespective of graft quality and severity of pre-LT liver disease.

To investigate the association between the grade of diastolic dysfunction (DD) and the occurrence of early allograft dysfunction (EAD) in liver transplant patients following the new 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines.From January 2015 to December 2019, we retrospectively analyzed 83 patients who underwent orthotopic liver transplantation (OLTx) and their susceptibility to develop EAD according to the grade of preoperative DD. EAD was defined according to the criteria proposed by Olfhoff et al.; DD was defined with four parameters: E/A, e/e', Left Atrium volume, and Tricuspid Regurgitation velocity.According to the ASE/EACVI guidelines grade II DD was detected in 20 patients (24.1%) undergoing OLTx. A statistically significant association was found between grade II DD and the occurrence of EAD (p-value 0.003). The Kaplan-Meier analysis failed to find any significant difference between the survival probability, nevertheless at the end of a 90-day follow-up period, mortality showed a different trend in classes with more severe diastolic dysfunction.According to the ASE/EACVI guidelines from 2016, patients with grade II DD seem to have a higher propensity to develop early allograft dysfunction EAD after OLTx. Our study advises a need for an urgent prospective multicenter study to elucidate the long-term outcomes of liver transplants patients with diastolic dysfunction.

Background: In deceased donor kidney transplantation (KT), the use of hypothermic machine perfusion (HMP) has been acquiring the status of best practice in the pre-transplant management of kidney grafts. Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP. However, data on the real clinical impact of oxygenation on KT outcome are still heterogeneous. Methods: Retrospective study on a cohort of 103 patients transplanted with a single kidney graft that was managed either with end-ischemic oxygenated (O2 group, Waves Machine, n = 51, 49.5%) or non-oxygenated HMP (no-O2 group, Life Port Kidney Transporter Machine, n = 52, 50.5%), during the period January 2016–December 2020. Oxygenation was performed at pO2 21%. Results: The median cold ischemia time was 29 h:40 min [IQR 26 h:55 min–31 h:10 min] and the prevalence of grafts from extended criteria donors (ECD) was 46.7%, with a median kidney donor profile index (KDPI) of 72 [41–94]. The study groups were homogeneous in terms of recipient characteristics, ischemia times and donor characteristics. O2 and no-O2 groups showed comparable outcomes in terms of delayed graft function (O2 vs no-O2, 21.5% vs 25%, p = 0.58), vascular (0.2% vs 0.2%, p > 0.99) and urologic (13.7% vs 11.5%, p = 0.77) complications, and episodes of graft rejection (11.7% vs 7.7%, p = 0.52). At 1 year follow up, even creatinine serum levels were comparable between the groups (1.27 mg/dL [1.09 and 1.67] vs 1.4 mg/dL [1.9–1.78], p = 0.319), with similar post-transplant trend ( p = 0.870). No significant benefit was either observed in ECD or KDPI > 60 subgroups, respectively. Conclusions: Oxygenation at pO2 21% during HMP seems not to significantly enhance the KT outcomes in terms of postoperative complications or graft function.

Background: Over the last decades relevant epidemiological changes of liver diseases have occurred, together with greatly improved treatment opportunities. Aim: To investigate how the indications for elective adult liver transplantation and the underlying disease etiologies have evolved in Italy. Methods: We recruited from the National Transplant Registry a cohort comprising 17,317 adults patients waitlisted for primary liver transplantation from January-2004 to December-2020. Patients were divided into three Eras:1(2004–2011),2(2012–2014) and 3(2015–2020). Results: Waitlistings for cirrhosis decreased from 65.9% in Era 1 to 46.1% in Era 3, while those for HCC increased from 28.7% to 48.7%. Comparing Eras 1 and 3, waitlistings for HCV-related cirrhosis decreased from 35.9% to 12.1%, yet those for HCV-related HCC increased from 8.5% to 26.7%. Waitlistings for HBV-related cirrhosis remained almost unchanged (13.2% and 12.4%), while those for HBV-related HCC increased from 4.0% to 11.6%. ALD-related cirrhosis decreased from 16.9% to 12.9% while ALD-related HCC increased from 1.9% to 3.9%. Conclusions: A sharp increase in liver transplant waitlisting for HCC and a concomitant decrease of waitlisting for cirrhosis have occurred In Italy. Despite HCV infection has noticeably decreased, still remains the primary etiology of waitlisting for HCC, while ALD and HBV represent the main causes for cirrhosis.

Background: After liver transplantation, HCV/HIV co-infected patients present, compared to the HCV mono-infected ones, increased HCV viral load, rapid progression to liver fibrosis and higher mortality. Liver biopsies (LB), obtained routinely 6 months after transplantation, represent a unique model to assess the early events related to graft re-infection. Here, we used miRNA sequencing of LB obtained from both HCV-and HCV/HIV-infected recipients, to identify transcriptional profiles able to explain the more severe outcome of these latter. Methods: miRNAs of 3 healthy livers, 3 HCV-LB and 3 HCV/HIV-LB were sequenced by Illumina HiSeq2500 platform. The DIANA-miRPath v3.0 webserver and DIANA-microT-CDS algorithm (v5.0) were used to characterize the functions of differentially expressed (DE-) miRNAs, querying the KEGG and Gene Ontology-Biological Process databases. Results: LB obtained from infected patients were characterized, with respect to controls, by a miRNA profile related to viral infection, immune system signaling and DNA damage in HCV-induced carcinogenesis. Instead, HCV-LB and HCV/HIV-LB differed in the expression of miRNAs involved in immunological and apoptotic processes and in extracellular matrix remodeling. Conclusions: liver reinfection processes are associated with early miRNA changes. Further studies are necessary to establish their prognostic role and possible actionability.

Kidneys with multiple renal arteries (MRAs) from different patches, may provide to the surgeon additional technical difficulties that make kidney transplants very challenging. MRAs have been largely debated over the years whether to be anastomosed or not due to the disappointing outcomes when it comes to inappropriate ligation or anastomosis. Some authors empirically reassure that smaller branches can be safely ligated and dissected without intraoperative and postoperative complications or compromising the functional recovery of the graft. Literature is poor about the possible differences in the management of superior and inferior polar arteries. Inferior polar arteries represent a topic of great interest as they may also supply the proximal ureter. The aim of this article is to merge the current knowledge about the management of inferior polar arteries and to highlight if there is any role of the methylene blue dye (MB) in the study of the ureteral vascularization in kidney transplantation. MB can be considered a safe and simple tool of vascular perfusion assessment in kidney transplantation. By injecting the dye-solution into the inferior MRA hidden ureteral branches can be unmasked and guide the surgeon to preserve important vessels. In view of their fundamental role in the vascularization of the ureter, the lower polar arteries of the graft, should be invariably studied by MB. It provides an objective, simple and fast tool for the evaluation of the ureteral vascularization when injected through the inferior MRA of the graft.

BACKGROUND For patients unable to swallow during the immediate post-transplant period, immunosuppressant therapy may be initiated by administering prolonged-release tacrolimus as a suspension via a nasogastric tube. MATERIAL AND METHODS In this sub-study of the DIAMOND randomized controlled trial of prolonged-release tacrolimus in de novo liver transplant recipients, we investigated the pharmacokinetic (PK) profile of prolonged-release tacrolimus when administered via nasogastric tube immediately post-transplant. PK analyses were performed on whole-blood samples collected on Day 1 of tacrolimus administration and on Day 3 post-transplantation. Endpoints included AUC0-24, Cmax, Tmax, and Cmin. RESULTS In total, 10 patients were included in the PK sub-study. The overall mean daily dose of prolonged-release tacrolimus administered via nasogastric tube was higher on Day 1 (0.179 mg/kg) vs. Day 3 (0.140 mg/kg). Mean AUC0-24 was higher and less variable on Day 3 vs. Day 1 (AUC0-24 (coefficient of variation; CV): 301 (50.8) vs. 193 (94.5) ng·h/mL). Mean Cmax was lower and median Tmax was shorter on Day 1 vs. Day 3 (Cmax (CV): 15.1 (73.9) vs. 19.1 (47.9) ng/mL; Tmax (range): 2.0 (2.0-24.0) vs. 4.5 (0.5-24.0) h). A similar pattern was also observed when data were normalized for dose and body weight. CONCLUSIONS In contrast to previously reported findings in healthy volunteers, nasogastric administration of prolonged--release tacrolimus suspension in liver transplant patients did not substantially affect the PK profile of tacrolimus vs. intact capsules. Nasogastric administration is thus a feasible option to ensure appropriate early tacrolimus exposure in de novo liver transplant recipients.

In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co‐infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro‐fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR‐101, miR‐122, miR‐155, miR‐192, miR‐200c, miR‐338, and miR‐532 was determined by quantitative real‐time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV‐infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post‐LT. None of the patients was treated with direct‐acting anti‐HCV drugs. All co‐infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR‐101 (p = .03), miR‐122 (p = .012), and miR‐192 (p = .038) were significantly downregulated in HCV/HIV co‐infected and HCV mono‐infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co‐infected ones. Moreover, in co‐infected recipients but not in mono‐infected ones, miR‐101 inversely correlated with the peripheral HCV‐RNA levels (r = .41, p = .04) and miR‐122 inversely correlated with peripheral HCV‐RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02). In conclusion, as early as 6 months after LT, the presence of HIV‐HCV co‐infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.

Supplemental Digital Content is available in the text., The exact origin of intracardiac thrombi formation during orthotopic liver transplant remains unknown. The altered balance between hypercoagulability, hypocoagulation, and endothelial dysfunction associated with end-stage liver disease is thought to play a pivotal role. Venous stasis, vascular clamping, and reperfusion could also contribute to clot formation. The incidence of intracardiac thrombi formation stands at 4.2%, associated with a mortality rate of 45.5%, and to date, no consensus exists regarding the best way to treat this complication. Intraoperative transesophageal echocardiography is the only effective method for diagnosing intracardiac thrombi formation early, while point-of-care coagulation testing could guide the coagulation management potentially improving patient outcomes.

Assessment of hepatic steatosis (HS) before transplantation requires the pathologist to read a graft biopsy. A simple method based on the evaluation of images from tissue samples with a smartphone could expedite and facilitate the liver selection. This study aims to assess the degree of HS by analysing photographic images from liver needle biopsy samples.Thirty-three biopsy-images were acquired with a smartphone. Image processing was carried out using ImageJ: background subtraction, conversion to HSB colour space, segmentation of the biopsy area, and evaluation of statistical features of Hue, Saturation, Brightness, Red, Green, and Blue channels on the biopsy area. After feature extraction, correlations were made with gold standard HS percentage assessed at two levels (frozen-section vs glass-slide). Sensitivity, specificity, and accuracy were calculated for each feature.Correlations were found for H, S, R. The sensitivity, specificity, and accuracy of the final classifier based on the K* algorithm were 94%, 92%, 94%.Accuracy assessment was performed considering macrovesicular steatosis on specimens with mostly30% HS.The steatosis assessment based on needle biopsy images, proved to be an effective and promising method. Deep learning approaches could also be experimented with a larger set of images.

Nowadays, advanced age does not represent an absolute contraindication to kidney transplantation (KT). However, aging is frequently associated with multiple comorbidities and lower performance status, making KT candidates less surgically fit. Limited data are available on the impact of KT morbidity on elderly recipients’ outcomes. Retrospective study on a single center cohort of 130 KT recipients over 65 years old, representing 16.2% of KT clinical series, during the period 2000–2018. Number and severity of comorbidities were evaluated with the Charlson Comorbidity index (CCI). The median age at transplantation was 67 [IQR66-71] years and median CCI was 5 [IQR4-6]. The prevalence of postoperative complications with a Clavien-Dindo (C-D) severity score > 2 was 29%. Increasing age did not predict KT morbidity in terms of C-D score > 2, infectious, respiratory, cardiologic, urologic or vascular complications, delayed graft function, symptomatic lymphocele, bleeding, acute or chronic rejection. Conversely, CCI score was a predictor of overall complications with C-D score > 2, cardiologic, respiratory and vascular complications, and bleeding. Among others, CCI score, post-KT cardiologic complications, C-D score > 2 were identified as significant predictors of both early mortality and graft loss in univariate analysis. Increasing recipient age did not correlate with graft loss risk and graft loss did not impact patient survival. C-D score > 2 was a predictor of poor survival even in multivariate analysis. Elderly recipients showed a significant vulnerability to KT morbidity which correlates with CCI. While graft loss did not impact recipient survival, severe postoperative complications (C-D > 2) were independently associated increased mortality.

Maximal oxygen consumption (V̇O2max) is impaired in heart (HTx), kidney (KTx), and liver (LTx) transplanted recipients and the contribution of the cardiovascular, central, and peripheral (muscular) factors in affecting V̇O2max improvement after endurance training (ET) has never been quantified in these patients. ET protocols involving single leg cycling (SL) elicit larger improvements of the peripheral factors affecting O2 diffusion and utilization than the double leg (DL) cycling ET. Therefore, this study aimed to compare the effects of SL-ET vs DL-ET on V̇O2max. We determined the DL-V̇O2max and maximal cardiac output before and after 24 SL-ET vs DL-ET sessions on 33 patients (HTx = 13, KTx = 11 and LTx = 9). The DL-V̇O2max increased by 13.8% ± 8.7 (p < 0.001) following the SL-ET, due to a larger maximal O2 systemic extraction; meanwhile, V̇O2max in DL-ET increased by 18.6% ± 12.7 (p < 0.001) because of concomitant central and peripheral adaptations. We speculate that in transplanted recipients, SL-ET is as effective as DL-ET to improve V̇O2max and that the impaired peripheral O2 extraction and/or utilization play an important role in limiting V̇O2max in these types of patients. Novelty: SL-ET increases V̇O2max in transplanted recipients because of improved peripheral O2 extraction and/or utilization. SL-ET is as successful as DL-ET to improve the cardiorespiratory fitness in transplanted recipients. The model of V̇O2max limitation indicates the peripheral factors as a remarkable limitation to the V̇O2max in these patients.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P

Background Despite current advances in liver transplant surgery, post-operative early allograft dysfunction still complicates the patient prognosis and graft survival. The transition from the donor has not been yet fully understood, and no study quantifies if and how the liver function changes through its transfer to the recipient. The indocyanine green dye plasma disappearance rate (ICG-PDR) is a simple validated tool of liver function assessment. The variation rate between the donor and recipient ICG-PDR still needs to be investigated. Materials and methods Single-center retrospective study. ICG-PDR determinations were performed before graft retrieval (T1) and 24 hours after transplant (T2). The ICG-PDR relative variation rate between T1 and T2 was calculated to assess the graft function and suffering/recovering. Matched data were compared with the MEAF model of graft dysfunction. Objective To investigate whether the variation rate between the donor ICG-PDR value and the recipient ICG-PDR measurement on first postoperative day (POD1) can be associated with the MEAF score. Results 36 ICG-PDR measurements between 18 donors and 18 graft recipients were performed. The mean donor ICG-PDR was 22.64 (SD 6.35), and the mean receiver’s ICG-PDR on 1st POD was 17.68 (SD 6.60), with a mean MEAF value of 4.51 (SD 1.23). Pearson’s test stressed a good, linear inverse correlation between the ICG-PDR relative variation and the MEAF values, correlation coefficient -0.580 (p = 0.012). Conclusion The direct correlation between the donor to recipient ICG-PDR variation rate and MEAF was found. Measurements at T1 and T2 showed an up- or downtrend of the graft performance that reflect the MEAF values.

Hemothorax (HT) is a life-threatening condition, mainly iatrogenic and poorly explored in Liver Transplantation (LT) recipients. The aim of this study is to report and analyze for the first time incidence and outcomes of HT in LT recipients, as well as to suggest a management strategy. Data concerning 7130 consecutive adult liver and liver–kidney transplant recipients were retrospectively collected from ten Transplantation Centers’ institutional databases, over a 10-year period. Clinical parameters, management strategies and survival data about post-operative HT were analyzed and reported. Thirty patients developed HT during hospitalization (0.42%). Thoracentesis was found to be the most common cause of HT (16 patients). A non-surgical management was performed in 17 patients, while 13 patients underwent surgery. 19 patients developed thoracic complications after HT treatment, with an overall mortality rate of 50%. The median length of stay in Intensive Care Units was 22 days (IQR25–75 5–66.5). Postoperative hemothorax is mainly due to iatrogenic causes in LT recipients. Despite rare, it represents a serious complication with a high mortality rate and a challenging medical and surgical management. Its occurrence should always be prevented.

Background Liver transplantation (LT) has been used as a last resort in patients with end-stage liver disease due to bile duct injuries (BDI) following cholecystectomy. Our study aimed to identify and evaluate factors that cause or contribute to an extended liver disease that requires LT as ultimate solution, after BDI during cholecystectomy. Methods Data from 8 high-volume LT centers relating to patients who underwent LT after suffering BDI during cholecystectomy were prospectively collected and retrospectively analyzed. Results Thirty-four patients (16 men, 18 women) with a median age of 45 (range 22-69) years were included in this study. Thirty of them (88.2%) underwent LT because of liver failure, most commonly as a result of secondary biliary cirrhosis. The median time interval between BDI and LT was 63 (range 0-336) months. There were 23 cases (67.6%) of postoperative morbidity, 6 cases (17.6%) of post-transplant 30-day mortality, and 10 deaths (29.4%) in total after LT. There was a higher probability that patients with concomitant vascular injury (hazard ratio 10.69, P=0.039) would be referred sooner for LT. Overall survival following LT at 1, 3, 5 and 10 years was 82.4%, 76.5%, 73.5% and 70.6%, respectively. Conclusion LT for selected patients with otherwise unmanageable BDI following cholecystectomy yields acceptable long-term outcomes. CA extern

Preoperative inflammatory biomarkers such as the Platelet-to-Lymphocyte Ratio (PLR) and the Neutrophil-to-Lymphocyte Ratio (NLR) strongly predict the outcome in surgically treated patients with hepatocellular carcinoma (HCC), while nutritional biomarkers such as the Controlling Nutritional Status (CONUT) and the Prognostic Nutritional Index (PNI) show an analogue prognostic value in hepatic resection (HR) but not in liver transplant (LT) cases. Data on the impact of LT on the inflammatory and nutritional/metabolic function are heterogeneous. Therefore, we investigated the post-LT trend of these biomarkers up to postoperative month (POM) 12 in 324 HCC patients treated with LT. Inflammatory biomarkers peaked in the early post-LT period but at POM 3 leveled off at values similar (NLR) or higher (PLR) than pre-LT ones. CONUT and PNI worsened in the early post-LT period, but at POM 3 they stabilized at significantly better values than pre-LT. In LT recipients with an overall survival &gt, 1 year and no evidence of early HCC recurrence, 1 year post-LT NLR and PNI independently predicted patient overall survival, while 1 year post-LT PLR independently predicted late tumor recurrence. In conclusion, at 1 year post-LT, the nutritional status of liver-transplanted HCC patients significantly improved while their inflammatory state tended to persist. Consequently, post-LT PLR and NLR maintained a prognostic value for LT outcome while post-LT CONUT and PNI acquired it.

In deceased donor kidney transplantation (KT), a prolonged cold ischemia time (CIT) is a negative prognostic factor for KT outcome, and the efficacy of hypothermic machine perfusion (HMP) in prolonging CIT without any additional hazard is highly debated. We conducted a retrospective study on a cohort of 154 single graft deceased donor KTs, in which a delayed HMP, after a preliminary period of static cold storage (SCS), was used to prolong CIT for logistic reasons. Primary outcomes were postoperative complications as well as 1 year graft survival and function. 73 cases (47.4%) were managed with HMP and planned KT, while 81 (52.6%) with SCS and urgent KT. The median CIT in HMP group and SCS group was 29 hour:57 minutes [27-31 hour:45 minutes] and 11 hour:25 minutes [9-14 hour:30 minutes], respectively (P < .001). The period of SCS in the HMP group was significantly shorter than in the SCS group (10 vs. 11 hour:25 minutes, P = .02) as well as the prevalence of expanded criteria donors was significantly higher (43.8% vs. 18.5%, P < .01). After propensity score matching for these two baseline characteristics, the HMP and SCS groups showed comparable outcomes in terms of delayed graft function, vascular, and urologic complications, infections, and episodes of graft rejection. At 1 year follow-up, serum creatinine levels were comparable between the groups. Therefore, the use of HMP to prolong the CIT and convert KT into a planned procedure seemed to have an adequate safety profile, with outcomes comparable to KT managed as an urgent procedure and a CIT nearly three time shorter.

Background: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC.Methods: As a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration.Results: APE1’s cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1’s mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix.Conclusions: Our study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA.

BACKGROUND Hypothermic machine perfusion (HMP) appears to exert a reconditioning effect on the ischemic damage of kidney grafts. However, some concerns still remain about its real effectiveness when it is delayed after a preliminary period of static cold storage (SCS) or with prolonged overall cold ischemia time (CIT). MATERIAL AND METHODS The effect of HMP on hemodynamic, metabolic, histological and ultrastructural features of grafts was investigated in 21 single-kidney grafts treated with a delayed HMP after SCS and with a total CIT of over 24 h. RESULTS The mean CIT, SCS, and HMP times were 29 h, 12 h, and 18 h, respectively. Longer SCS was associated with higher vascular resistance and lower arterial flow. In the pre- vs. post-HMP comparison, a significant decrease in arterial resistances and increase of flow were recorded. The hemodynamic improvement was independent of HMP duration. The perfused grafts retained some metabolic activity, with a statistically significant decrease of pH, pO2, and glucose levels, and increase of lactates in the perfusion liquid, by the end of HMP. Longer SCS was associated with higher pH and greater pO2 decrease during HMP. Light microscopy and transmission electronic microscopy revealed no significant variations in nuclear, cytoplasmic, or ultrastructural damage. SCS, HMP, and CIT were not identified as risk factor for delayed graft function or rejection. CONCLUSIONS A delayed and extended HMP can recover the graft hemodynamic function, maintain some metabolic activity, and stabilize the accumulated ischemic damage due to a preliminary SCS.

Background Native hepatectomy represents the most demanding surgical step during orthotopic whole liver transplantation (LT). The surgical risk assessment of LT candidates is currently mainly based on clinical and laboratory data, but even preoperative imaging data may be predictive of a complex native hepatectomy. Methods A retrospective study on a cohort of 110 LT recipients was conducted. The radiologic variables investigated on pre-LT multidetector computed tomography scan were the length of the retrohepatic inferior vena cava (IVC-L), volume of the dorsal liver sector (DLS-V), complete encirclement of the IVC by the DLS (IVC-CE), max diameter of the native liver (L-D), max diameter of the spleen (S-D), and presence of large spontaneous portosystemic shunts (SPSS). The parameters defining complex native hepatectomy were the operative time, number of red blood cell (RBC) units transfused, IVC replacement technique switch, and post-LT relaparotomy for major bleeding. Results In a multivariate analysis, the operative time was predicted by hepatocellular carcinoma (HCC) diagnosis (regression coefficient [RC]: 18.237, P = .009), S-D (RC: 3.733, P = .007), and IVC-CE (RC: 20.174, P = .01); the RBC units transfused by an history of gastroesophageal variceal bleeding (RC: 2.503, P = .039), Model for End-Stage Liver Disease (MELD) score (RC: .259, P = .039), and L-D (RC: –0.519, P = .027); the switch to a IVC replacement technique by L-D (odds ratio [OR]: 0.641, P = .028) and IVC-L (OR: 1.065, P = .023); and the relaparotomy for bleeding by L-D (OR: 0.632, confidence interval [CI]: 0.437 to 0.916, P = .015). Conclusions Pre-LT multidetector computed tomography (MDCT) seems to be a very useful tool in the surgical risk assessment of LT candidates.