Role of protein induced by vitamin-K absence-II in transplanted patients with HCC not producing alpha-fetoprotein.

Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52-2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48-2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26-3.35; p =0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.

Microwave ablation followed by cTACE in 5-cm HCC lesions: does a single-session approach affect liver function?

PURPOSE: Microwave ablation (MWA) and conventional transarterial chemoembolization (cTACE) are locoregional treatments commonly performed in very early, early and intermediate stages of hepatocellular carcinoma (HCC). Despite combined locoregional approaches have shown encouraging results in obtaining complete tumor necrosis, their application in a single session is poorly described. Our aim was to evaluate the safety and efficacy of single-session MWA and cTACE treatment in 5-cm HCCs and its influence on liver function. MATERIALS AND METHODS: All 5-cm HCCs treated by MWA and cTACE performed in a single-session in our Interventional Radiology unit between January 2020 and December 2022 were retrospectively recorded and analyzed. Patients with poor or missing pre- and post-treatment imaging were excluded. Technical success, clinical success, and complications rate were examined as primary endpoints. Pre- and post-treatment liver function laboratory parameters were also evaluated. RESULTS: A total of 15 lesions (mean lesion diameter, 5.0 ± 1.4 cm) in 15 patients (11 men; mean age, 67.1 ± 8.9 years) were retrospectively evaluated. Technical and clinical success were 100% and 73%, respectively. Four (27%) cases of partial response and no cases of progressive or stable disease were recorded. AST and ALT values have found to be significantly higher in post-treatment laboratory tests. No other significant differences between pre- and post-treatment laboratory values were registered. AST and ALT pre- and post-treatment higher differences (ΔAST and ΔALT) were significantly associated with a lower clinical success rate. CONCLUSION: MWA and cTACE single-session approach is safe and effective for 5-cm HCCs, without significant liver function impairment. A post-treatment increase in AST and ALT values may be a predictor for clinical failure.

The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis.

OBJECTIVE: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). BACKGROUND: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. METHODS: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. RESULTS: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. CONCLUSIONS: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma.

AIM: To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment. METHODS: A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT. RESULTS: A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51-0.79; p < 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35-0.83; p = 0.006). CONCLUSIONS: Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.

Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario.

BACKGROUND: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.

Indocyanine Green Fluorescence Navigation in Liver Surgery: A Systematic Review on Dose and Timing of Administration.

BACKGROUND: Indocyanine green (ICG) fluorescence has proven to be a high potential navigation tool during liver surgery; however, its optimal usage is still far from being standardized. METHODS: A systematic review was conducted on MEDLINE/PubMed for English articles that contained the information of dose and timing of ICG administration until February 2021. Successful rates of tumor detection and liver segmentation, as well as tumor/patient background and imaging settings were also reviewed. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Out of initial 311 articles, a total of 72 manuscripts were obtained. The quality assessment of the included studies revealed usually low; only 9 articles got qualified as high quality. Forty articles (55%) focused on open resections, whereas 32 articles (45%) on laparoscopic and robotic liver resections. Thirty-four articles (47%) described tumor detection ability, and 25 articles (35%) did liver segmentation ability, and the others (18%) did both abilities. Negative staining was reported (42%) more than positive staining (32%). For tumor detection, majority used the dose of 0.5 mg/kg within 14 days before the operation day, and an additional administration (0.02-0.5 mg/kg) in case of longer preoperative interval. Tumor detection rate was reported to be 87.4% (range, 43%-100%) with false positive rate reported to be 10.5% (range, 0%-31.3%). For negative staining method, the majority used 2.5 mg/body, ranging from 0.025 to 25 mg/body. For positive staining method, the majority used 0.25 mg/body, ranging from 0.025 to 12.5 mg/body. Successful segmentation rate was 88.0% (range, 53%-100%). CONCLUSION: The time point and dose of ICG administration strongly needs to be tailored case by case in daily practice, due to various tumor/patient backgrounds and imaging settings.

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients.

Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.

Liver transplantation for metastatic wild-type gastrointestinal stromal tumor in the era of molecular targeted therapies: Report of a first case.

The gastrointestinal stromal tumor (GIST) is a digestive neoplasm of mesenchymal lineage. The treatment strategy for receptor tyrosine kinase-mutated GISTs is well defined. Wild-type GISTs (WT-GISTs) respond unsatisfactorily to specific kinase inhibitors. Moreover, evidence shows that repeat surgery has limited benefit. We report the case of a young female patient who was diagnosed with liver metastatic WT-GIST, after initial radical resection and adjuvant therapy with molecular targeted drugs. Due to the disease progression, a two-stage surgery was performed, with the removal of extrahepatic lesions followed by a total hepatectomy. The patient is disease-free after 4 years from liver transplantation (LT), performed under everolimus-based immunosuppression. The treatment of WT-GISTs remains a significant challenge due to the frequent resistance to tyrosine kinase inhibitors (TKIs). Liver transplantation might represent an effective treatment option for such disease.

The Intention-to-Treat Effect of Bridging Treatments in the Setting of Milan Criteria-In Patients Waiting for Liver Transplantation.

In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC-dependent LT failure, defined as pretransplant tumor-related delisting or posttransplant recurrence. The study was registered at www.clinicaltrials.gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1083 MC-in patients (no LRT = 182; LRT = 901) were balanced using 8 variables: age, sex, Model for End-Stage Liver Disease (MELD) value, hepatitis C virus status, hepatitis B virus status, largest lesion diameter, number of nodules, and alpha-fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo-population of 2019 patients listed for LT was analyzed, comparing 2 homogeneous groups of untreated (n = 1077) and LRT-treated (n = 942) patients. Tumor progression after LRT was the most important independent risk factor for HCC-dependent failure (subhazard ratio [SHR], 5.62; P < 0.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male sex, and period of wait-list registration. One single LRT was protective compared with no treatment (SHR, 0.51; P < 0.001). The positive effect was still observed when 2-3 treatments were performed (SHR, 0.66; P = 0.02), but it was lost in the case of ≥4 LRTs (SHR, 0.80; P = 0.27). In conclusion, for MC-in patients, up to 3 LRTs are beneficial for success in intention-to-treat LT patients, with a 49% to 34% reduction in failure risk compared with untreated patients. This benefit is lost if more LRTs are required. A poor response to LRT is associated with a higher risk for HCC-dependent transplant failure.

Impact of aberrant left hepatic artery ligation on the outcome of liver transplantation.

The preservation of a graft's aberrant left hepatic artery (LHA) during liver transplantation (LT) ensures optimal vascularization of the left liver but can also be considered a risk factor for hepatic artery thrombosis (HAT). In contrast, ligation of an aberrant LHA may lead to hepatic ischemia with the potential risk of graft dysfunction and biliary complications. The aim of this study was to prospectively analyze the impact on the surgical strategy for LT of 5 tests performed to establish whether an aberrant LHA was an accessory or a replaced artery, thus leading to the design of a decisional algorithm. From August 2005 to December 2016, 395 whole LTs were performed in 376 patients. Five parameters were evaluated to determine whether an aberrant LHA was an accessory or a replaced artery. On the basis of our decision algorithm, an aberrant LHA was ligated during surgery when assessed as accessory and preserved when assessed as replaced. A total of 138 anatomical variants of hepatic arterial vascularization occurred in 120/395 (30.4%) grafts. Overall, the incidence of an aberrant LHA was 63/395 (15.9%). The LHA was ligated in 33 (52.4%) patients and preserved in 30 (47.6%) patients. After a mean follow-up period of 50.9 ± 39.7 months, the incidence of HAT, primary nonfunction, early allograft dysfunction, biliary stricture or leaks, and overall survival was similar in the 2 groups. In conclusion, once shown to be an accessory, an LHA can be safely ligated without clinical consequences on the outcome of LT. Liver Transplantation 24 204-213 2018 AASLD.

Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer.

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between "high-" and "low-benefit" patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors ("no-benefit group"; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor ("large-benefit group"; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910-1919).

Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients, a multicentre cohort study.

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients.

A Novel Prognostic Index in Patients With Hepatocellular Cancer Waiting for Liver Transplantation: Time-Radiological-response-Alpha-fetoprotein-INflammation (TRAIN) Score.

OBJECTIVE: A novel and easy prognostic score based on the combination of pre-operatively available variables in patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) has been developed from a long waiting time (WT) training set and then validated in a short-WT set. SUMMARY OF BACKGROUND DATA: The role of radiological response to loco-regional therapies, alpha-fetoprotein modification, inflammatory markers, and length of WT has been recently shown to be important selection criteria for the risk of intention-to-treat (ITT)-death and recurrence. METHODS: The training set consisted of 179 HCC patients listed for LT during the period January 2000 to December 2012 from the UCL Brussels Transplant Centre; the validation set consisted of 110 patients listed during the period January 2005 to December 2014 from the Ancona Liver Centre. RESULTS: The proposed Time-Radiological-response-Alpha-fetoprotein-INflammation (TRAIN) score was the best predictor of microvascular invasion. A TRAIN score ≥1.0 excellently stratified both the investigated populations in terms of ITT and recurrence survivals. When compared with Milan criteria, the proposed score allowed obtaining an increase of potentially transplantable patients (+8.9% in training set and 24.6% in validation set) without additive recurrence risks. CONCLUSIONS: The proposed TRAIN score is an easy selection tool based on variables available before LT. This score enables the selection process to be refined in the 2 different scenarios of long and short WT. In case of longer WT, the score is better at predicting risk of death during the WT; in case of short WT, the score is better at identifying risk of post-LT recurrence.

Carbapenem-Resistant Klebsiella pneumoniae influences the outcome of early infections in liver transplant recipients.

BACKGROUND: Infections remain a leading cause of morbidity and mortality among liver transplant (LT) recipients. The aim of our study was to define the factors associated with outcome of early bacterial and fungal infections in a cohort of patients who underwent LT at the University Hospital of Ancona over a nine year period. METHODS: All consecutive patients who underwent LT in our center were considered. An early infection was defined as occurring in the first month post-transplantation. RESULTS: Among 330 patients who underwent LT from August 2005 to October 2014, 88 (27 %) had at least one infection documented within 30 days after transplantation. In 54 cases only one site was involved, in 34 cases ≥2 sites. There were 43 (30 %) pneumonia, 40 (27 %) surgical site infections, 31 (22 %) blood stream infections, and 30 (21 %) urinary tract infections. Gram-negative bacteria accounted for 64 % of the culture-positive cases, followed by Gram-positive bacteria (30 %) and fungi (6 %). A high proportion of drug-resistant strains was found within either Gram-negative (79 %) or Gram-positive (81 %) bacteria. There were 27 out 88 patients (31 %) who died within 180 days from the transplant. Factors independently associated with a higher risk of mortality were: renal replacement therapy (HR 11.797 [CI95 % 3.082-45.152], p < 0.0001), multisite infections (HR 4.865 [CI95 % 1.417-16.700], p = 0.012) and being infected with carbapenem-resistant Klebsiella pneumoniae (CRKP; HR 5.562 [CI95 % 1.186-26.088], p = 0.030). CONCLUSIONS: Overall, these data indicate that early infections in LT patients are characterized by significant mortality. In particular, an early infection caused by CRKP has an adverse impact on survival in these patients suggesting an urgent need for adopting preventive measures to avoiding this complication.

Importance of radiological detection of early pulmonary acute complications of liver transplantation: analysis of 259 cases.

PURPOSE: Pulmonary complications are common causes of morbidity and mortality after orthotopic liver transplantation (OLT) and consist of atelectasis, pleural effusion, pulmonary oedema, adult respiratory distress syndrome (ARDS) and pneumonia. The aim of this paper is to describe the incidence of pulmonary complications after OLT during the first postoperative week and to evaluate the informative value of the chest X-ray (CXR) in clinical practice. MATERIALS AND METHODS: Patients who underwent OLT at the Ancona Transplant Centre between August 2005 and August 2012 were included in this retrospective study. The CXR and, if performed, the thoracic computed tomography (TCT) scans performed during the first 7 postoperative days were reviewed, and the radiological findings for atelectasis, pleural effusion, pulmonary oedema, ARDS and pneumonia were independently assessed and quantified by two radiologists according to the Fleischner Society criteria. Cases of pneumothorax after thoracentesis were assessed. Development of pneumonia was defined as the simultaneous presence of positive CXR or TCT and positive serological or fluid samples and clinical symptoms; the prevalence of infectious agents was assessed. The radiological reports produced in the clinical setting were compared with the findings. RESULTS: Among 259 patients included, atelectasis was observed in 227 patients (87.6 %); pleural effusion in 250 (96.5 %); pulmonary oedema in 204 (78 %); ARDS in seven patients (2.6 %); and pneumothorax in 37 patients (14 %). Pneumonia occurred in 32 cases (12.3 %). Pulmonary oedema was underestimated in the radiological reports in 104 cases (40 %). CONCLUSIONS: Knowledge about postoperative pulmonary complications and collaboration between the radiologist and clinician are essential for improving the management of OLT recipients.

Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT).

Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result. However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients. The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed. The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.

A Novel Use of Autologous Fibrin by Intracatheter Injection in Persistent Postoperative Biliary Defects: Technical Note on a Preliminary Experience.

PURPOSE: To introduce percutaneous selective injection of autologous platelet-rich fibrin as a novel technique for persistent bile leakage repair and sharing the results of our preliminary experience. MATERIALS AND METHODS: Seven patients (57.1% females; mean age 69.6 ± 8 years) with the evidence of persistent bile leak secondary to hepatobiliary surgery and ineffective treatment with percutaneous transhepatic biliary drainage were submitted to fibrin injection. Platelet-rich fibrin, a dense fibrin clot promoting tissue regeneration, was obtained from centrifuged patient's venous blood. Repeated percutaneous injections through a catheter tip placed in close proximity to the biliary defect were performed until complete obliteration at fistulography. Technical and clinical success were evaluated. RESULTS: Bile leaks followed pancreaticoduodenectomy in five and major hepatectomy in two patients. Technical success defined as fibrin injection at BD site was achieved in all seven patients, and clinical success defined as a complete healing of the BD at fistulography was achieved in six patients. The median time to BD closure was 76.7 ± 40.5 days and the average procedure number was 3 ± 1 per patient. In one patient, defect persistance after four treatments required gelatin sponge injection. No major complications occurred. One case of post-procedural transitory hyperpirexia was registered. CONCLUSION: In persistent biliary defects, despite prolonged biliary drainage stay, percutaneous injection of autologous platelet-rich fibrin appears as a readily available and feasible emergent technique in promoting fistulous tracts obliteration still mantaining main ducts patency.

Prevention of Post-Hepatectomy Liver Failure in Cirrhotic Patients Undergoing Minimally Invasive Liver Surgery for HCC: Has the Round Ligament to Be Preserved?

Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The aim of this study was to assess whether the preservation of the round ligament (RL) may mitigate portal hypertension, thus decreasing the risk of PHLF and ascites in cirrhotic patients while undergoing minimally invasive liver surgery (MILS). All the cirrhotic patients who underwent MILS for HCC from 2016 to 2021 in two international tertiary referral centers were retrospectively analyzed, comparing cases with the RL preserved vs. those with the RL divided. Only patients with cirrhosis ≥ Child A6, portal hypertension, and ICG-R15 > 10% were included. Main postoperative outcomes were compared, and the risk factors for postoperative ascites (severe PHLF, grade B/C) were investigated through a logistic regression. After the application of the selection criteria, a total of 130 MILS patients were identified, with 86 patients with the RL preserved and 44 with the RL divided. The RL-preserved group showed lower incidences of severe PHLF (7.0% vs. 20.5%, p = 0.023) and ascites (5.8% vs. 18.2%, p = 0.026) in comparison with the RL-divided group. After uni/multivariate analysis, the risk factors related to postoperative ascites were RL division and platelets < 92 × 103/µL, calculated with ROC analysis. The preservation of the round ligament during MILS may mitigate portal hypertension, preventing PHLF and ascites in cirrhotic patients with borderline liver function.

Portal vein thrombosis and liver transplantation: management, matching, and outcomes. A retrospective multicenter cohort study.

BACKGROUND AND AIMS: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients. METHODS: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant. RESULTS: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis.Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT ( P <0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present. CONCLUSIONS: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of specific risk factors may improve the outcomes even in patients with PVT grades 3-4.

Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma.

Importance: The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. Objective: To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. Design, Setting, and Participants: This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. Interventions: LR, PRFA, or TACE. Main Outcomes and Measures: Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. Results: A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. Conclusions and Relevance: For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.