Publications by authors named "Matteo Cescon"

231 Publications

Liver resection for perihilar cholangiocarcinoma: Impact of biliary drainage failure on postoperative outcome. Results of an Italian multicenter study.

Surgery 2021 Feb 20. Epub 2021 Feb 20.

Department of General Surgery, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy.

Background: Preoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial.

Methods: This is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage.

Results: Of the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P = .003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P = .002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality.

Conclusion: Failure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers' experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality.
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http://dx.doi.org/10.1016/j.surg.2021.01.021DOI Listing
February 2021

How to Preserve Liver Grafts From Circulatory Death With Long Warm Ischemia? A Retrospective Italian Cohort Study With Normothermic Regional Perfusion and Hypothermic Oxygenated Perfusion.

Transplantation 2021 Jan 7. Epub 2021 Jan 7.

1. Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 2. Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK. 3. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 4. Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy. 5. UO Chirurgia Generale e dei Trapianti, AOU Sant'Orsola-Malpighi, Alma Mater Studiorum Università di Bologna, Bologna, Italy. 6. Division of Liver Transplantation, AO Papa Giovanni XXIII, Bergamo, Italy. 7. General Surgery 2U, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. 8. Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplant Unit, Padua University, Padua, Italy. 9. Abdominal Surgery and Organ Transplantation Unit, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS - ISMETT), Palermo, Italy 10. Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy 11. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.

Background: Donation after circulatory death (DCD) in Italy, given its 20-min stand-off period, provides a unique bench-test for normothermic regional perfusion (NRP) and dual hypothermic oxygenated machine perfusion (D-HOPE).

Methods: We coordinated a multicenter retrospective Italian cohort study with 44 controlled DCD donors, who underwent NRP, to present transplant characteristics and results. To rank our results according to the high donor risk, we matched and compared a subgroup of 37 controlled DCD livers, preserved with NRP and D-HOPE, with static-preserved controlled DCD transplants from an established European program.

Results: In the Italian cohort, D-HOPE was used in 84% of cases, and the primary nonfunction rate was 5%. Compared to the matched comparator group, the NRP+D-HOPE-group showed a lower incidence of moderate and severe acute kidney injury (stage 2: 8% vs 27% and stage 3: 3% vs 27%, P=0.001). Ischemic cholangiopathy remained low (2-year proportion free: 97% vs 92%, P=0.317), despite the high-risk profile resulting from the longer donor warm ischemia in Italy (40 vs 18min, P<0.001).

Conclusions: These data suggest that NRP and D-HOPE yield good results in DCD livers with prolonged warm ischemia.
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http://dx.doi.org/10.1097/TP.0000000000003595DOI Listing
January 2021

Development of a Risk Prediction Model for Carbapenem-Resistant Enterobacteriaceae Infection after Liver Transplantation: A Multinational Cohort Study.

Clin Infect Dis 2021 Feb 10. Epub 2021 Feb 10.

Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.

Background: Patients colonized with carbapenem resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT) with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies.

Methods: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray sub-distribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created.

Results: 840 LT recipients found to be colonized with CRE before (n=203) or after (n=637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (IQR 9-42) days after LT. Pre-and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical re-intervention were retained in the prediction model. Median 30 and 60-day predicted risk was 15% (IQR 11-24%) and 21% (IQR 15-33%), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (AUC 74.6, Brier index 16.3) and bootstrapped validation dataset (AUC 73.9, Brier index 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/.

Conclusions: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.
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http://dx.doi.org/10.1093/cid/ciab109DOI Listing
February 2021

Development and validation of an individualized prediction calculator of postoperative mortality within 6 months after surgical resection for hepatocellular carcinoma: an international multicenter study.

Hepatol Int 2021 Feb 3. Epub 2021 Feb 3.

Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, China.

Background: Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection.

Methods: Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves.

Results: Independent factors associated with death within 6 months of surgery included age, Child-Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542-0.748).

Conclusions: An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.
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http://dx.doi.org/10.1007/s12072-021-10140-7DOI Listing
February 2021

Third-party bone marrow-derived mesenchymal stromal cell infusion before liver transplantation: A randomized controlled trial.

Am J Transplant 2020 Dec 28. Epub 2020 Dec 28.

Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open-label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pretransplant intravenous infusion of third-party bone marrow-derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1-year follow-up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion-related complications. The incidence of serious and non-serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56 NK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC-treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance-associated transcripts in 1-year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier: NCT02260375.
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http://dx.doi.org/10.1111/ajt.16468DOI Listing
December 2020

Non-Alcoholic Steatohepatitis as a Risk Factor for Intrahepatic Cholangiocarcinoma and Its Prognostic Role.

Cancers (Basel) 2020 Oct 29;12(11). Epub 2020 Oct 29.

Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, 40138 Bologna, Italy.

Non-alcoholic fatty liver disease (NAFLD) and its most aggressive form, non-alcoholic steatohepatitis (NASH), are causing a rise in the prevalence of hepatocellular carcinoma. Data about NAFLD/NASH and intrahepatic cholangiocarcinoma (iCCA) are few and contradictory, coming from population registries that do not correctly distinguish between NAFLD and NASH. We evaluated the prevalence of NAFLD and NASH in peritumoral tissue of resected iCCA ( = 180) and in needle biopsies of matched liver donors. Data of iCCA patients were subsequently analysed to compare NASH-related iCCA (Group A), iCCA arisen in a healthy liver (Group B) or in patients with classical iCCA risk factors (Group C). NASH was found in 22.5% of 129 iCCA patients without known risk factors and in 6.2% of matched controls (risk ratio 3.625, 95% confidence interval 1.723-7.626, < 0.001), while NAFLD was equally represented in both groups. The overall survival of NASH-related iCCA was inferior to that of patients with healthy liver (38.5 vs. 48.1 months, = 0.003) and similar to that of patients with known risk factors (31.9 months, = 0.948), regardless of liver fibrosis. The multivariable Cox regression confirmed NASH as a prognostic factor (hazard ratio 1.773, 95% confidence interval 1.156-2.718, = 0.009). We concluded that NASH (but not NAFLD) is a risk factor for iCCA and might affect its prognosis. Dissecting NASH from NAFLD by histology is necessary to correctly assess the actual role of these conditions. Prevention protocols for NASH patients should also consider the risk for iCCA and not only HCC. Mechanistic studies aimed to find a direct pathogenic link between NASH and iCCA could add further relevant information.
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http://dx.doi.org/10.3390/cancers12113182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692633PMC
October 2020

The role of hepatobiliary scintigraphy combined with spect/ct in predicting severity of liver failure before major hepatectomy: a single-center pilot study.

Updates Surg 2021 Feb 2;73(1):197-208. Epub 2020 Nov 2.

General Surgery and Transplantation Unit, Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.

Hepatobiliary scintigraphy (HBS) has been demonstrated to predict post-hepatectomy liver failure (PHLF). However, existing cutoff values for future liver remnant function (FLR-F) were previously set according to the "50-50 criteria" PHLF definition. Methods of calculation and fields of application in liver surgery have changed in the meantime. The aim of this study was to demonstrate the role of HBS combined with single photon emission computed tomography (SPECT/CT) in predicting severity of PHLF, according to the International Study Group of Liver Surgery (ISGLS). All patients submitted to major hepatectomy with preoperative HBS-SPECT/CT between November 2016 and December 2019, were analyzed. Patients were resected according to hepatic volumetry. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoffs of FLR function for predicting PHLF according to ISGLS definition and grading. Of the 38 patients enrolled, 26 were submitted to one-stage hepatectomy (living liver donors = 4) and 12 to two-stage procedures (portal vein embolization = 4, ALPPS = 8). Overall, 18 patients developed PHLF according to ISGLS criteria: 12 of grade A (no change in the patient's clinical management) and 6 of grade B (change in clinical management). ROC analysis established increasingly higher cutoffs of FLR-F for predicting PHLF according to the "50-50 criteria", ISGLS grade B and ISGLS grade A/B, respectively. HBS with SPECT/CT may help to assess severity of PHLF following major hepatectomy. Prospective multicenter trials are needed to confirm the effective role of HBS-SPECT/CT in liver surgery.
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http://dx.doi.org/10.1007/s13304-020-00907-2DOI Listing
February 2021

Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure Among Patients Requiring Early Liver Retransplant.

JAMA Surg 2020 12 16;155(12):e204095. Epub 2020 Dec 16.

University Hospital, Pisa, Italy.

Importance: Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015.

Objective: To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant.

Design, Setting, And Participants: This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017.

Main Outcomes And Measures: Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant.

Results: At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk.

Conclusions And Relevance: This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers.
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http://dx.doi.org/10.1001/jamasurg.2020.4095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593884PMC
December 2020

Liver transplantation in Italy in the era of COVID 19: reorganizing critical care of recipients.

Intern Emerg Med 2020 Nov 26;15(8):1507-1515. Epub 2020 Sep 26.

Dipartimento delle insufficienze d'organo e dei trapianti, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, Bologna, Italy.

Transplant programs have been severely disrupted by the COVID-19 pandemic. Italy was one of the first countries with the highest number of deaths in the world due to SARS-CoV-2. Here we propose a management model for the reorganization of liver transplant (LT) activities and policies in a local intensive care unit (ICU) assigned to liver transplantation affected by restrictions on mobility and availability of donors and recipients as well as health personnel and beds. We describe the solutions implemented to continue transplantation activities throughout a given pandemic: management of donors and recipients' LT program, ICU rearrangement, healthcare personnel training and monitoring to minimize mortality rates of patients on the waiting list. Transplantation activities from February 22, 2020, the data of first known COVID-19 case in Italy's Emilia Romagna region to June 30, 2020, were compared with the corresponding period in 2019. During the 2020 study period, 38 LTs were performed, whereas 41 were performed in 2019. Patients transplanted during the COVID-19 pandemic had higher MELD and MELD-Na scores, cold ischaemia times, and hospitalization rates (p < 0.05); accordingly, they spent fewer days on the waitlist and had a lower prevalence of hepatocellular carcinoma (p < 0.05). No differences were found in the provenance area, additional MELD scores, age of donors and recipients, BMI, re-transplant rates, and post-transplant mortality. No transplanted patients contracted COVID-19, although five healthcare workers did. Ultimately, our policy allowed us to continue the ICU's operations by prioritizing patients hospitalized with higher MELD without any case of transplant infection due to COVID-19.
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http://dx.doi.org/10.1007/s11739-020-02511-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519699PMC
November 2020

Direct Antiviral Treatments for Hepatitis C Virus Have Off-Target Effects of Oncologic Relevance in Hepatocellular Carcinoma.

Cancers (Basel) 2020 Sep 19;12(9). Epub 2020 Sep 19.

Center for Applied Biomedical Research (CRBA), Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

Background And Aims: HCV eradication by direct-acting antiviral agents (DAAs) reduces de novo hepatocellular carcinoma (HCC) incidence in cirrhosis; however, contrasting evidence about beneficial or detrimental effects still exists in patients who have already developed HCC.

Methods: we investigated whether sofosbuvir and daclatasvir modulate cell proliferation, invasion capability and gene expression (RNA-seq) in HCC-derived cell lines, hypothesizing possible off-target effects of these drugs. Results observed in HCC cell lines were validated in non-HCC cancer-derived cell lines and a preliminary series of human HCC tissues by qPCR and IHC.

Results: DAAs can affect HCC cell proliferation and migration capability by either increasing or reducing them, showing transcriptomic changes consistent with some unexpected drug-associated effects. Off-target gene modulation, mainly affecting ribosomal genes, mitochondrial functions and histones, points to epigenetics and proliferation as relevant events, consistent with matched phenotypic changes. A preliminary validation of in vitro findings was performed in a restricted cohort of HCC patients previously treated with DAAs, with immunohistochemical correlations suggesting DAA-treated HCCs to be more aggressive in terms of migration and epidermal-to-mesenchymal transition.

Conclusions: Our findings suggested the possible occurrence of off-target effects ultimately modulating cell proliferation and/or migration and potentially justified previous findings showing some instances of particularly aggressive HCC recurrence as well as reduced incidence of recurrence of HCC following treatment with DAAs.
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http://dx.doi.org/10.3390/cancers12092674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565876PMC
September 2020

Stratification of Major Hepatectomies According to Their Outcome: Analysis of 2212 Consecutive Open Resections in Patients Without Cirrhosis.

Ann Surg 2020 11;272(5):827-833

Department of Medical Sciences, Cancer Epidemiology Unit, University of Torino and CPO-Piemonte, Torino, Italy.

Objective: To stratify major hepatectomies (MajHs) according to their outcomes.

Summary Of Background Data: MajHs are associated with non-negligible operative risks, but they include a wide range of procedures. Detailed depiction of the outcomes of different MajHs is the basis for a new classification of liver resections.

Methods: We retrospectively considered patients that underwent hepatectomy in 17 high-volume centers. Patients with an associated digestive/biliary resection were excluded. We analyzed open MajHs in non-cirrhotic patients. MajHs were classified according to the Brisbane nomenclature. Right hepatectomies (RHs) were reference standards. Outcomes were adjusted for potential confounders, including indication, liver function, preoperative portal vein embolization, and enrolling center.

Results: We analyzed a series of 2212 patients. In comparison with RH, left hepatectomy had lower mortality [0.6% vs 2.2%, odds ratio (OR) = 0.25], severe morbidity (11.7% vs 14.4%, OR = 0.62), and liver failure rates (2.1% vs 11.6%, OR = 0.16). Left hepatectomy+Sg1 and mesohepatectomy+/-Sg1 had outcomes similar to RH, except for higher bile leak rate (31.3% and 13.5% vs 6.7%, OR = 4.36 and OR = 2.29). RH + Sg1 had slightly worse outcomes than RH. Right and left trisectionectomies had higher mortality (5.0% and 7.3% vs 2.2%, OR = 2.07 and OR = 2.71) and liver failure rates than RH (19.0% and 22.0% vs 11.6%, OR = 2.03 and OR = 2.21). Left trisectionectomy had even higher severe morbidity (25.6% vs 14.4%, OR = 2.07) and bile leak rates (14.6% vs 6.7%, OR = 2.31).

Conclusions: The term "major hepatectomy" includes resections having heterogeneous outcome. Different MajHs can be stratified according to their mortality, severe morbidity, liver failure, and bile leak rates.
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http://dx.doi.org/10.1097/SLA.0000000000004338DOI Listing
November 2020

Minimally Invasive Stage 1 to Protect Against the Risk of Liver Failure: Results from the Hepatocellular Carcinoma Series of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Italian Registry.

J Laparoendosc Adv Surg Tech A 2020 Oct 9;30(10):1082-1089. Epub 2020 Sep 9.

Department of General Surgery, Azienda Ospedaliero-Universitaria di Bologna, Maggiore Hospital, Bologna, Italy.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been described to treat hepatocellular carcinoma (HCC) but burdened, in its pioneering phase, by high morbidity and mortality. With the advent of minimally invasive (MI) techniques in liver surgery, surgical complications, including posthepatectomy liver failure (PHLF), have been dramatically reduced. The primary endpoint of this study was to compare the short-term outcomes of MI- versus open-ALPPS for HCC, with specific focus on PHLF. Data of patients submitted to ALPPS for HCC between 2012 and 2020 were identified from the ALPPS Italian Registry. Patients receiving an MI Stage 1 (MI-ALPPS) constituted the study group, whereas the patients who received an open Stage 1 (open-ALPPS) constituted the control group. Sixty-six patients were enrolled from 12 Italian centers. Stage 1 of ALPPS was performed in 14 patients using an MI approach (21.2%). MI-ALPPS patients were discharged after Stage 1 at a significantly higher rate compared with open-ALPPS (78.6% versus 9.6%,  < .001). After Stage 2, major morbidity after MI-ALPPS was 8.3% compared with 28.6% reported after open-ALPPS. Mortality was nil after MI-ALPPS. Length of hospital stay was significantly shorter in MI-ALPPS (12 days versus 22 days,  < .001). Univariate logistic regression analysis (Firth method) found that both MI-ALPPS (odds ratio [OR] = 0.05,  = .040) and partial parenchymal transection (OR = 0.04,  = .027) were protective against PHLF. This national multicenter study showed that a less invasive approach to ALPPS first stage was associated with a lower overall risk of PHLF.
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http://dx.doi.org/10.1089/lap.2020.0563DOI Listing
October 2020

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network.

J Inherit Metab Dis 2020 Aug 9. Epub 2020 Aug 9.

Department of Neurosciences, Veneto Institute of Molecular Medicine, University of Padova, Padova, Italy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow-up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence-based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence-based guidance for clinicians incorporating patients' values and preferences.
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http://dx.doi.org/10.1002/jimd.12300DOI Listing
August 2020

Two surgical techniques are better than one: RAVAS and RAPID are answers for the same issue.

Am J Transplant 2021 02 20;21(2):905-906. Epub 2020 Sep 20.

Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Paul Brousse Hospital, Villejuif, France.

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http://dx.doi.org/10.1111/ajt.16301DOI Listing
February 2021

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

Liver Transpl 2021 Feb 7;27(2):231-235. Epub 2020 Oct 7.

Department of General Surgery and Transplantation, Azienda Ospedaliero-Universitaria di Bologna, Alma Mater, Bologna, Italy.

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.
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http://dx.doi.org/10.1002/lt.25878DOI Listing
February 2021

COVID-19 in a young liver transplant recipient: caution for drug-drug interactions.

J Gastrointestin Liver Dis 2020 09 9;29(3):470. Epub 2020 Sep 9.

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.15403/jgld-2672DOI Listing
September 2020

Reply to: "Response to A nomogram based on liver stiffness predicts postoperative complications in patients with hepatocellular carcinoma".

J Hepatol 2020 Nov 21;73(5):1270-1271. Epub 2020 Aug 21.

Department of Medical and Surgical Sciences, General Surgery and Transplantation Unit, University of Bologna, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2020.07.001DOI Listing
November 2020

COVID-19 in solid organ transplant recipients: No difference in survival compared to general population.

Transpl Infect Dis 2021 Feb 2;23(1):e13421. Epub 2020 Aug 2.

Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Bologna, Italy.

Coronavirus disease 2019 (COVID-19) may be associated with worse outcome in solid organ transplant (SOT) recipients. We performed a prospective cohort study of hospitalized patients with confirmed diagnosis of COVID-19, from March 15 to April 30, 2020, at two tertiary hospitals in Emilia-Romagna Region. SOT recipients were compared with non-SOT patients. Primary endpoint was all-cause 30-day mortality. Relationship between SOT status and mortality was investigated by univariable and multivariable Cox regression analysis. Patients were assessed from COVID-19 diagnosis to death or 30-day whichever occurred first. Study cohort consisted of 885 patients, of them 24 SOT recipients (n = 22, kidney, n = 2 liver). SOT recipients were younger, had lower BMI, but higher Charlson Index. At admission they presented less frequently with fever and respiratory failure. No difference in 30-day mortality between the two groups (19% vs 22.1%) was found; however, there was a trend toward higher rate of respiratory failure (50% vs 33.1%, P = .07) in SOT recipients. Superinfections were more represented in SOT recipients, (50% vs 15.5%, P < .001). At multivariate analysis adjusted for main covariates, there was no association between SOT and 30-day mortality HR 1.15 (95% CI 0.39-3.35) P = .79. Our data suggest that mortality among COVID-19 SOT recipients is similar to general population.
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http://dx.doi.org/10.1111/tid.13421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404509PMC
February 2021

Is post-transplant chemotherapy feasible in liver transplantation for colorectal cancer liver metastases?

Cancer Commun (Lond) 2020 09 6;40(9):461-464. Epub 2020 Aug 6.

Department of General Surgery and Transplantation, S. Orsola- Malpighi University Hospital, Bologna, 40138, Italy.

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http://dx.doi.org/10.1002/cac2.12072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494063PMC
September 2020

Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments.

J Gastroenterol 2020 Oct 3;55(10):927-943. Epub 2020 Aug 3.

Gastroenterology Unit, University Hospital Borgo Trento, Verona, Italy.

Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients' survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.
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http://dx.doi.org/10.1007/s00535-020-01711-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519899PMC
October 2020

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

Am J Transplant 2021 02 15;21(2):870-875. Epub 2020 Sep 15.

Department of General Surgery and Transplantation, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1111/ajt.16222DOI Listing
February 2021

Reply to: "Liver stiffness: A novel predictor of postoperative complications in patients with hepatocellular carcinoma".

J Hepatol 2020 Oct 20;73(4):988-989. Epub 2020 Jul 20.

Department of Medical and Surgical Sciences, General Surgery and Transplantation Unit, University of Bologna, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2020.06.017DOI Listing
October 2020

Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications.

J Neurol 2020 Dec 18;267(12):3702-3710. Epub 2020 Jul 18.

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Interaziendale Clinica Neurologica Rete Metropolitana (NeuroMet), Neurologia AOU S. Orsola-Malpighi, Policlinico Sant'Orsola-Malpighi, Building #2, Via Albertoni, 15, 40138, Bologna, Italy.

We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.
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http://dx.doi.org/10.1007/s00415-020-10051-xDOI Listing
December 2020

Living Donor Liver Transplantation for Imatinib-Resistant Gastrointestinal Stromal Tumor Liver Metastases: A New Therapeutic Option in Transplant Oncology.

Liver Transpl 2020 10 13;26(10):1373-1374. Epub 2020 Aug 13.

Medical Oncology Unit, Sant'Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.1002/lt.25844DOI Listing
October 2020

An Uncommon Focal Liver Lesion: Intrahepatic Splenosis.

J Gastrointestin Liver Dis 2020 Jun 3;29(2):257-262. Epub 2020 Jun 3.

Unit of Internal Medicine, University of Bologna, Azienda Ospedaliero Universitaria S.Orsola- Malpighi, Bologna.

Multiple focal liver lesions were incidentally detected in a patient screened by ultrasound for a recent diagnosis of lower limb deep vein thrombosis, for which anticoagulation had been initiated. Past medical history reported a post-traumatic splenectomy 15 years before. Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) showed a subcapsular lesion in liver segment 5 consistent with focal nodular hyperplasia (FNH) and multiple other nodules, with a different pattern from the former, judged as probable hepatic adenomas by MRI but probable hemangiomas by CEUS (hyperenhancement in the late phase). Therefore, another MRI with gadoxetic acid was performed. The diagnosis of FNH was confirmed. The other lesions showed an hyperenhancing pattern in the arterial phase with progressive wash-out in the portal and late phase and marked hypointensity in the hepatobiliary phase. This pattern apparently confirmed the hypothesis of adenomas, with a potential risk of malignancy due to the hepatobiliary phase pattern and the recent occurrence of deep vein thrombosis. Due to the inherent risk of spontaneous bleeding from subcapsular adenomas increased by the ongoing anticoagulant therapy and the recommendation of international guidelines to resect adenomas in male subjects, the patient was directly offered surgery. Pathology of the resected specimens confirmed one FNH but demonstrated intrahepatic splenosis for all other lesions. This case suggests that in the setting of previous splenic trauma any discrepancy between MRI and CEUS findings should lead one to consider also the hypothesis of intrahepatic splenosis.
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http://dx.doi.org/10.15403/jgld-617DOI Listing
June 2020

Gastric Cancer Staging: Is It Time for Magnetic Resonance Imaging?

Cancers (Basel) 2020 May 29;12(6). Epub 2020 May 29.

Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, 40138 Bologna, Italy.

Gastric cancer (GC) is a common cancer worldwide. Its incidence and mortality vary depending on geographic area, with the highest rates in Asian countries, particularly in China, Japan, and South Korea. Accurate imaging staging has become crucial for the application of various treatment strategies, especially for curative treatments in early stages. Unfortunately, most GCs are still diagnosed at an advanced stage, with the peritoneum (61-80%), distant lymph nodes (44-50%), and liver (26-38%) as the most common metastatic locations. Metastatic disease is limited to the peritoneum in 58% of cases; in nonperitoneal distant metastases, the most involved GC metastasization site is the liver (82%). The eighth edition of the tumor-node-metastasis staging system is the most commonly used system for determining GC prognosis. Endoscopic ultrasonography, computed tomography, and 18-fluorideoxyglucose positron emission tomography are historically the most accurate imaging techniques for GC staging. However, studies have recently shown renewed interest in magnetic resonance imaging (MRI) as a useful tool in GC staging, especially for distant metastasis assessment. The technical improvement of diffusion-weighted imaging and the increasing use of hepatobiliary contrast agents have been shown to increase the diagnostic performance of MRI, particularly for detecting peritoneal and liver metastasis. However, no principal oncological guidelines have included the use of MRI as a first-line technique for distant metastasis evaluation during the GC staging process, such as the National Comprehensive Cancer Network Guidelines. This review analyzed the role of the principal imaging techniques in GC diagnosis and staging, focusing on the potential role of MRI, especially for assessing peritoneal and liver metastases.
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http://dx.doi.org/10.3390/cancers12061402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352169PMC
May 2020

Percutaneous radiofrequency ablation in intrahepatic cholangiocarcinoma: a retrospective single-center experience.

Int J Hyperthermia 2020 ;37(1):479-485

Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy.

Very few data are available in literature about the role of radiofrequency ablation (RFA) in intrahepatic cholangiocarcinoma (ICC) and previous studies are mainly case reports and case series on a very small number of patients and nodules. In this study, we aimed to evaluate effectiveness and safety of RFA for the treatment of unresectable ICC. This is a retrospective observational cohort study comprising all consecutive patients treated with RFA for unresectable ICC at Policlinico Sant'Orsola Malpighi Hospital, Bologna, Italy. Primary endpoint was Local Tumor Progression-Free Survival (LTPFS) while Overall Survival (OS) was also assessed as secondary endpoint. From January 2014 to June 2019, 29 patients with 117 nodules underwent RFA. Technique effectiveness 1 month after RFA was 92.3%; median LTPFS was 9.27 months. Univariate analysis and multivariate analysis showed that LTPFS was significantly related to tumor size ≥20 mm. At a median follow up of 39.9 months, median OS from the date of RFA was 27.5 months, with an OS of 89%, 45% and 11% at 1, 2 and 4 years, respectively. Number of overall lesions and the sum of their diameter at the moment of the first RFA significantly affected OS in multivariate analysis. Minor and major complication rates were 14% and 7%, respectively. Tumor size ≥20 mm was associated with lower LTPFS, representing a potential useful threshold value. A careful evaluation of tumor burden appears as a crucial element in choosing the best therapeutic strategy in unresectable ICC.
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http://dx.doi.org/10.1080/02656736.2020.1763484DOI Listing
November 2020

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

J Hepatol 2020 Oct 30;73(4):855-862. Epub 2020 Apr 30.

Department of Medical and Surgical Sciences, General Surgery and Transplantation Unit, University of Bologna, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jhep.2020.04.032DOI Listing
October 2020

A novel online calculator to predict perioperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma: an international multicenter study.

HPB (Oxford) 2020 Dec 25;22(12):1711-1721. Epub 2020 Apr 25.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China. Electronic address:

Background: To develop an easy-to-use model to predict the probability of perioperative blood transfusion (PBT) in patients undergoing liver resection for hepatocellular carcinoma (HCC).

Method: 878 patients from Eastern Hepatobiliary Surgery Hospital of Shanghai were enrolled in the training cohort, while 691 patients from Tongji Hospital of Wuhan and 364 patients from two hospitals from Europe and America served as the Eastern and Western external validation cohorts, respectively. Independent predictors of PBT were identified and used for the nomogram construction. The predictive performance of the model was assessed using the concordance index (C-index) and calibration plot, and externally validated using the two independent cohorts. This model was compared with four currently available prediction risk scores.

Results: Eight preoperative variables were identified as independent predictors of PBT, which were incorporated into the new nomogram model, with a C-index of 0.833 and a well-fitted calibration plot. The nomogram performed well on the externally Eastern and Western validation cohorts (C-indexes: 0.786 and 0.777). The discriminatory ability of the nomogram was superior to the four currently available prediction scores (C-indexes: 0.833 vs. 0.671-0.770). The nomogram was programmed into an online calculator, which is available at http://www.asapcalculate.top/Cal3_en.html.

Conclusion: A nomogram model, using an easy-to-access website, can be used to calculate the PBT risk and identify which patients undergoing HCC resection are at high risks of PBT and can benefit most by using blood conservation techniques.
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http://dx.doi.org/10.1016/j.hpb.2020.03.018DOI Listing
December 2020