Radiomics of Intrahepatic Cholangiocarcinoma and Peritumoral Tissue Predicts Postoperative Survival: Development of a CT-Based Clinical-Radiomic Model.

BACKGROUND: For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. METHODS: All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009-2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60 days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). RESULTS: The study enrolled 215 patients. After a median follow-up period of 28 months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3 years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. CONCLUSIONS: The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.

Genomic events stratifying prognosis of early gastric cancer.

BACKGROUND: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. METHODS: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. RESULTS: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). CONCLUSIONS: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.

'Potentially curative therapies' for hepatocellular carcinoma: how many patients can actually be cured?

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) is predicated on early diagnosis such that 'curative therapies' can be successfully applied. The term 'curative' is, however, poorly quantitated. We aimed to complement our previous work by developing a statistical model to predict cure after ablation and to use this analysis to compare the true curative potential of the various 'curative' therapies. METHODS: We accessed data from 1571 HCC patients treated in 5 centres receiving radiofrequency (RFA) or microwave (MWA) ablation and used flexible parametric modelling to determine the curative fraction. The results of this analysis were then combined with our previous estimations to provide a simple calculator applicable to all patients undergoing potentially curative therapies. RESULTS: The cure fraction was 18.3% rising to about 40% in patients with good liver function and very small tumours. CONCLUSION: Cure for HCC treated with ablation occurs in the order of 20% to 30%, similar to that achievable by resection but much inferior to transplantation where the analogous figure is >70%. We provide a 'calculator' that permits clinicians to estimate the chance of cure for any individual patient, based on readily available clinical features.

Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node-negative intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Lymph-nodal status is an important predictor of survival in intrahepatic cholangiocarcinoma (iCCA), but the need to perform lymphadenectomy in patients with clinically node-negative (cN0) iCCA is still under debate. The aim of this study was to determine whether adequate lymphadenectomy improves long-term outcomes in patients undergoing liver resection for cN0 iCCA. METHODS: We performed a retrospective cohort study on consecutive patients who underwent radical liver resection for cN0 iCCA at five tertiary referral centers. A propensity score based on preoperative data was calculated and used to generate stabilized inverse probability of treatment weight (IPTW). Overall and recurrence-free survival of patients undergoing adequate (≥6 retrieved lymph nodes) vs. inadequate lymphadenectomy were compared. Interactions between adequacy of lymphadenectomy and clinical variables of interest were explored through Cox IPTW regression. RESULTS: The study includes 706 patients who underwent curative surgery for cN0 iCCA. Four-hundred and seventeen (59.1%) received adequate lymphadenectomy. After a median follow-up of 33 months (IQR 18-77), median overall survival was 39 months (IQR 23-109) and median recurrence-free survival was 23 months (IQR 8-74). After stratification according to nodal status at final pathology, node-positive patients had longer overall survival (28 vs. 23 months; hazard ratio 1.82; 95% CI 1.14-2.90; p = 0.023) and disease-free survival (13 vs. 9 months; hazard ratio 1.35; 95% CI 1.14-1.59; p = 0.008) after adequate lymphadenectomy. Adequate lymphadenectomy significantly improved survival outcomes in patients without chronic liver disease, and in patients with less-advanced tumors (solitary tumors, tumor size <5 cm, carbohydrate antigen 19-9 <200 U/ml). CONCLUSIONS: Adequate lymphadenectomy provided better survival outcomes for patients with cN0 iCCA who were found to be node-positive at pathology, supporting the routine use of adequate lymphadenectomy for cN0 iCCA. IMPACT AND IMPLICATIONS: Lymphadenectomy is essential for the surgical staging of intrahepatic cholangiocarcinoma (iCCA). While its role in patients with preoperative suspicion of nodal metastases is implicit, the impact of lymphadenectomy on survival of patients with clinically node-negative (cN0) disease is still under debate. In this large retrospective study on patients who underwent surgical resection for cN0 iCCA, we show that adequate lymphadenectomy (i.e. retrieving ≥6 lymph nodes) significantly improves survival and lowers the risk of tumor recurrence. Lymphadenectomy during surgical resection of iCCA is actually underperformed by the surgical community, resulting in inadequate staging and possibly worse long-term outcomes. The results of this study should empower surgeons and clinicians to push for adequate lymphadenectomy even for cN0 iCCA. Since patients with no chronic liver disease and with less-advanced tumors receive a significant benefit from lymphadenectomy, our results might guide decision making in patients at high-risk of postoperative complications.

Cure Probabilities After Resection Of Pancreatic Ductal Adenocarcinoma: A Multi-Institutional Analysis Of 2554 Patients.

OBJECTIVE: To assess the probability of being cured from pancreatic ductal adenocarcinoma (PDAC) by pancreatic surgery. SUMMARY BACKGROUND DATA: Statistical cure implies that a patient treated for a specific disease will have the same life expectancy as if he/she never had that disease. METHODS: Patients who underwent pancreatic resection for PDAC between 2010 and 2021 were retrospectively identified using a multi-institutional database. A non-mixture statistical cure model was applied to compare disease-free survival to the survival expected for matched general population. RESULTS: Among 2554 patients, either in the setting of upfront (n=1691) or neoadjuvant strategy (n=863), the cure model showed that the probability that surgery would offer the same life-expectancy (and tumor-free) as the matched general population was 20.4% (95%CI: 18.3, 22.5). Cure likelihood reached the 95% of certainty (time-to-cure) after 5.3 years (95%CI: 4.7, 6.0). A preoperative model was developed based on tumor stage at diagnosis (P=0.001), radiological size (P=0.001), response to chemotherapy (P=0.007), American Society of Anesthesiology class (P=0.001) and pre-operative Ca19-9 (P=0.001). A post-operative model with the addition of surgery type (P=0.015), pathological size (P=0.001), tumour grading (P=0.001), resection margin (P=0.001), positive lymphnode ratio (P=0.001) and the receipt of adjuvant therapy (P=0.001) was also developed. CONCLUSIONS: Patients operated for PDAC can achieve a life-expectancy similar to that of general population and the likelihood of cure increases with the passage of recurrence-free time. An online calculator was developed and available at https://aicep.website/?cff-form=15.

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.

European' health care indicators and pancreatic cancer incidence and mortality: A mediation analysis of Eurostat data and Global Burden of Disease Study 2019.

AIM: To highlight correlations existing between incidence and mortality of pancreatic cancer, and health care indicators in 36 European countries. METHODS: The Global Burden of Disease (GBD) and Eurostat databases were queried between 2004 and 2019. Incidence and mortality were age-standardized. From Eurostat, indicators regarding expenditure, hospital beds, medical technology, health personnel, physicians by medical specialty and unmet needs for medical examination were extracted. Correlations between GBD and Eurostat data were analysed through mediation analysis applying clustering for countries. RESULTS: Incidence increased by +0.6% per year (p = 0.001) and mortality by +0.3% (p = 0.001), being increasing for most of the European countries considered. Incidence and mortality were strongly positively correlated (p = 0.001). Higher current health expenditure, expenditure in inpatient curative care, the number of available beds, the number of computed tomography scan, magnetic resonance units, practising medical doctors were all related to higher incidence (p < 0.05), whereas the unmet need for medical examinations was related to lower incidence. When the mediator' effect of incidence was handled, these indicators, together with expenditure on outpatient curative cares, the number of pet scanners and of radiation therapy equipment, were related to lower mortality (p < 0.05). CONCLUSIONS: Health care environment correlates with reported incidence and mortality of pancreatic cancer. This highlights both that ameliorated socio-economic societies suffer from higher incidence but lower mortality, as well as the epidemiological bias originating from countries' diagnostic ability.

Fluorescence Cholangiography Using Indocyanine Green Improves the Identification of Biliary Structures During Laparoscopic Cholecystectomy.

BACKGROUND: This cross-sectional survey aimed to determine whether fluorescence cholangiography using indocyanine green (ICG-FC) can improve the detection of the cystic duct and the main bile duct during laparoscopic cholecystectomy (LC). METHODS: The survey was distributed to 214 surgeons (residents/faculties) in 2021. The confidence in the identification of the cystic duct and of the main bile duct was elicited on a 10-point Likert scale before/after the use of ICG-FC. This was repeated for three LCs ranging from a procedure deemed easy to a LC for acute cholecystitis. RESULTS: There were 149 responses. ICG-FC increased the responders' confidence in identifying the cystic duct, raising the median value from 6 (IQR, 5-8) with white light up to 9 (IQR, 9-10) with ICG-FC (paired p < 0.001). This increase was even more evident when identifying the main bile duct, where the median confidence value increased from 5 (IQR, 4-7) with white light to 9 (IQR, 8-10) with the use of ICG-FC (p < 0.001). ICG-FC significantly increased the detection of residents of the main bile duct in case of intermediate difficulty LCs and in LCs for acute cholecystitis. CONCLUSIONS: The results support that the use of near-infrared imaging can ameliorate detection of biliary structures, especially of the main bile duct and this was particularly true for young surgeons and in more complex situations.

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.

Trial sequential analysis of EUS-guided gallbladder drainage versus percutaneous cholecystostomy in patients with acute cholecystitis.

BACKGROUND AND AIMS: Meta-analytic comparison of EUS-guided gallbladder drainage (EUS-GBD) versus percutaneous gallbladder drainage (PT-GBD) for acute cholecystitis (AC) brings the risk of spurious results if too few studies are included. Trial sequential analysis (TSA) can overcome this, providing information about its credibility. METHODS: Comparative studies between EUS-GBD, using lumen-apposing metal stents, and PT-GBD for AC until July 2021 were used for conventional meta-analysis and TSA, which allowed the use of monitoring boundaries and the estimation of the required information size (RIS) needed to prove credibility. RESULTS: Four studies accrued 535 patients. Technical success was in favor of PT-GBD (relative risk [RR], .967; P = .036), but TSA estimated that 1663 participants would be needed to avoid a Type I error (false positive). Clinical success was similar (RR, .965; P = .146), and TSA supported the absence of any demonstrable superiority of one therapy rather than a Type II error (false negative). EUS-GBD reduced overall adverse events (RR, .424; P < .001) and unplanned readmissions (RR, .215; P < .001), and TSA confirmed the avoidance of a Type I error, with early RIS achievement, providing necessary credibility. EUS-GBD had fewer reinterventions (RR, .244; P < .001), but a Type I error was not avoided, needing additional 97 patients to the accrued 535 to prove credibility. CONCLUSIONS: PT-GBD can provide superior technical success than EUS-GBD if a very large sample size is accrued, thus limiting the single-patient benefit. Clinical success is probably equivalent. EUS-GBD convincingly decreased overall adverse events and unplanned readmissions, whereas the need for reinterventions requires additional studies.

Robotic versus laparoscopic left colectomy: a systematic review and meta-analysis.

BACKGROUND: This study aimed to review the new evidence to understand whether the robotic approach could find some clear indication also in left colectomy. METHODS: A systematic review of studies published from 2004 to 2022 in the Web of Science, PubMed, and Scopus databases and comparing laparoscopic (LLC) and robotic left colectomy (RLC) was performed. All comparative studies evaluating robotic left colectomy (RLC) versus laparoscopic (LLC) left colectomy with at least 20 patients in the robotic arm were included. Abstract, editorials, and reviews were excluded. The Newcastle-Ottawa Scale for cohort studies was used to assess the methodological quality. The random-effect model was used to calculate pooled effect estimates. RESULTS: Among the 139 articles identified, 11 were eligible, with a total of 52,589 patients (RLC, n = 13,506 versus LLC, n = 39,083). The rate of conversion to open surgery was lower for robotic procedures (RR 0.5, 0.5-0.6; p < 0.001). Operative time was longer for the robotic procedures in the pooled analysis (WMD 39.1, 17.3-60.9, p = 0.002). Overall complications (RR 0.9, 0.8-0.9, p < 0.001), anastomotic leaks (RR 0.7, 0.7-0.8; p < 0.001), and superficial wound infection (RR 3.1, 2.8-3.4; p < 0.001) were less common after RLC. There were no significant differences in mortality (RR 1.1; 0.8-1.6, p = 0.124). There were no differences between RLC and LLC with regards to postoperative variables in the subgroup analysis on malignancies. CONCLUSIONS: Robotic left colectomy requires less conversion to open surgery than the standard laparoscopic approach. Postoperative morbidity rates seemed to be lower during RLC, but this was not confirmed in the procedures performed for malignancies.

Emilia-Romagna Surgical Colorectal Cancer Audit (ESCA): a value-based healthcare retro-prospective study to measure and improve the quality of surgical care in colorectal cancer.

PURPOSE: Surgery is the main treatment for non-metastatic colorectal cancer. Despite huge improvements in perioperative care, colorectal surgery is still associated with a significant burden of postoperative complications and ultimately costs for healthcare organizations. Systematic clinical auditing activity has already proven to be effective in measuring and improving clinical outcomes, and for this reason, we decided to evaluate its impact in a large area of northern Italy. METHODS: The Emilia-Romagna Surgical Colorectal Audit (ESCA) is an observational, multicentric, retro-prospective study, carried out by 7 hospitals located in the Emilia-Romagna region. All consecutive patients undergoing surgery for colorectal cancer during a 54-month study period will be enrolled. Data regarding baseline conditions, preoperative diagnostic work-up, surgery and postoperative course will be collected in a dedicated case report form. Primary outcomes regard postoperative complications and mortality. Secondary outcomes include each center's adherence to the auditing (enrolment rate) and evaluation of the systematic feedback activity on key performance indicators for the entire perioperative process. CONCLUSION: This protocol describes the methodology of the Emilia-Romagna Surgical Colorectal Audit. The study will provide real-world clinical data essential for benchmarking and feedback activity, to positively impact outcomes and ultimately to improve the entire healthcare process of patients undergoing colorectal cancer surgery. CLINICAL TRIAL REGISTRATION: The study ESCA is registered on the clinicaltrials.gov platform (Identifier: NCT03982641).

Determinants of outcomes of transmural EUS-guided gallbladder drainage: systematic review with proportion meta-analysis and meta-regression.

BACKGROUND AND AIMS: Transmural EUS-guided gallbladder drainage (EUS-GBD) has been increasingly used in the treatment of gallbladder diseases. Aims of the study were to provide a comprehensive meta-analysis and meta-regression of features and outcomes of this procedure. METHODS: MEDLINE, Scopus, Web of science, and Cochrane databases were searched for literature pertinent to transmural EUS-GBD up to May 2021. Random-effect meta-analysis of proportions and meta-regression of potential modifiers of outcome measures considered were applied. Outcome measures were technical success rate, overall clinical success, and procedure-related adverse events (AEs). RESULTS: Twenty-seven articles were identified including 1004 patients enrolled between February 2009 and February 2020. Acute cholecystitis was present in 98.7% of cases. Pooled technical success was 98.0% (95% CI 96.3, 99.3; heterogeneity: 23.6%), the overall clinical success was 95.4% (95% CI 92.8, 97.5; heterogeneity: 35.3%), and procedure-related AEs occurred in 14.8% (95% CI 8.8, 21.8; heterogeneity: 82.4%), being stent malfunction/dislodgement the most frequent (3.5%). Procedural-related mortality was 1‰. Meta-regression showed that center experience proxied to > 10 cases/year increased the technical success rate (odds ratio [OR]: 2.84; 95% CI 1.06, 7.59) and the overall clinical success (OR: 3.52; 95% CI 1.33, 9.33). The use of anti-migrating devices also increased the overall clinical success (OR: 2.16; 95% CI 1.07, 4.36) while reducing procedure-related AEs (OR: 0.36; 95% CI 0.14, 0.98). CONCLUSION: Physicians' experience and anti-migrating devices are the main determinants of main clinical outcomes after EUS-GBD, suggesting that treatment in expert centers would optimize results.

Forecasting outcomes after cholecystectomy in octogenarian patients.

BACKGROUND: Although gallstone disease increases with aging, elderly patients are less likely to undergo cholecystectomy. This is because age itself is a negative predictor after cholecystectomy. The ACS-NSQIP risk calculator can therefore help surgeons decide whether to operate or not. However, little is known about the accuracy of this model outside the ACS National Surgical Quality Improvement Program. The aim of the present study is to evaluate the ability of the ACS-NSQIP model to predict the clinical outcomes of patients aged 80 years or older undergoing elective or emergency cholecystectomy. STUDY DESIGN: The study focused on 263 patients over 80 years of age operated on between 2010 and 2019: 174 were treated as emergencies because of acute cholecystitis (66.2%). Outcomes evaluated are those predicted by the ACS-NSQIP calculator within 30 days of surgery. The ACS-NSQIP model was tested for both discrimination and calibration. Differences among observed and expected outcomes were evaluated. RESULTS: When considering all patients, the discrimination of mortality was very high, as it was that of severe complications. Considering only the elective cholecystectomies, the discrimination capacity of ACS-NSQIP risk calculator has consistently worsened in each outcome while it remains high considering the emergency cholecystectomies. In the evaluation of the emergency cholecystectomy, the model showed a very high discriminatory ability and, more importantly, it showed an excellent calibration. Comparisons between main outcomes showed small or even negligible differences between observed and expected values. CONCLUSION: The results of the present study suggest that clinical decisions on cholecystectomy in a patient aged 80 years or older should be assisted through the ACS-NSQIP model.

EISOR Delivery: Regional experience with sharing equipe, equipment & expertise to increase cDCD donor pool in time of pandemic.

Donation after circulatory death (DCD) programs are expanding in Europe, in the attempt to expand donors pool. Even in controlled DCD donors, however, a protracted warm ischemia time occurring in the perimortem period might damage organs, making these unsuitable for transplantation. Implementing a strategy of extracorporeal interval support for organ retrieval (EISOR), a regional reperfusion with normothermic, oxygenated blood provides a physiologic environment allowing extensive assessment of potential grafts, and potentially promotes recovery of native function. Here we report the results of a multi-center retrospective cohort study including 29 Maastricht Category III controlled DCD donors undergoing extracorporeal support in a regional DCD/EISOR Training Center, and in the network of referring In-Training Centers, under the liaison of the regional Transplant Coordination Center during COVID-19 pandemic, between March 2020 and November 2021. The study aims to understand whether a mobile, experienced EISOR team implementing a consistent technique and sharing its equipe, expertise and equipment in a regional network of hospitals, might be effective and efficient in implementing the regional DCD program activity even in a highly stressed healthcare system.

Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma: a textbook outcome analysis.

BACKGROUND: The Textbook Outcome (TO) is a quality indicator accounting for both efficacy and safety. Herein, we aimed to assess TO in patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). METHODS: All consecutive patients undergoing RFA for HCC between 2014 and 2020, were included. TO was defined as 1) no post-RFA complications or mortality within 30 days after RFA, 2) no prolonged hospital stay 3) no 30-day readmission and 4) the achievement of a complete response (CR) of the target lesion/s at 1-month. RESULTS: Overall, 50.3% of 376 patients fulfilled all the quality indicators to achieve TO. Probabilities of TO achievement decreased in presence of moderate comorbidities (odds ratio[OR]:0.43; 95%C.I.:0.22-0.80;p=0.008), a performance status of 1 (OR: 0.58;95%C.I.:0.37-0.89; p=0.013), the treatment of 2 nodules (OR: 0.71; 95%C.I.:0.41-0.98; p=0.048) or ≥3 nodules (OR: 0.41; 95%C.I.: 0.22 - 0.78; p = 0.007); the treatment of 2-3cm nodules (OR:0.49;95%C.I.:0.31-0.79;p=0.003) or >3cm nodules (OR: 0.36;95%C.I.:0.18-0.73;p=0.004). Risk-stratification provided TO achievement ranging between 77.9% and 14.3%. Patients with TO also had improved survival (p = 0.028). CONCLUSION: About half of patients get TO from RFA. Stratification by clinical and tumoral characteristic should aid provision of RFA in clinical practice, facilitating patient information and providing reference values for future comparative studies.

Role of circulating microRNAs to predict hepatocellular carcinoma recurrence in patients treated with radiofrequency ablation or surgery.

BACKGROUND: Loco-regional treatments have improved the survival of patients with early hepatocellular carcinoma (HCC), but tumor relapse is a frequent event and survival rates remain low. Moreover, conflicting evidences address early HCC patients to surgery or radiofrequency ablation (RFA), with the clinical need to find predictive non-invasive biomarkers able to guide treatment choice and define patients survival. METHODS: Two independent case series of treatment-naïve HCC patients treated with local RFA, and a cohort of 30 HCC patients treated with liver surgery were enrolled. On the basis of literature evidence, we customized a panel of 21 miRNAs correlated with relapse and prognosis after local curative treatment of HCC. RESULTS: Expression levels of let-7c predict tumor relapse after RFA; we also investigated the same panel in a small cohort of HCC patients undergoing surgery, finding no statistically significance in predicting tumor relapse or survival. Moreover, interaction test indicated that let-7c expression levels are predictive for identifying a subset of patients that should be addressed to surgery. CONCLUSION: Results from this study could predict prognosis of early HCC patients, helping to address early HCC patients to surgery or RFA treatment.

The largest western experience on salvage hepatectomy for recurrent hepatocellular carcinoma: propensity score-matched analysis on behalf of He.RC.O.Le.Study Group.

BACKGROUND: We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments. METHODS: Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments). RESULTS: 2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS. CONCLUSION: SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.

Benchmarking postoperative outcomes after open liver surgery for cirrhotic patients with hepatocellular carcinoma in a national cohort.

BACKGROUND: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined. METHODS: Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3). RESULTS: A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups). CONCLUSION: We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons.

First 100 minimally invasive liver resections in a new tertiary referral centre for liver surgery.

BACKGROUND: In the last decades, there has been an exponential diffusion of minimally invasive liver surgery (MILS) worldwide. The aim of this study was to evaluate our initial experience of 100 patients undergoing MILS resection comparing their outcomes with the standard open procedures. MATERIALS AND METHODS: One hundred consecutive MILS from 2016 to 2019 were included. Clinicopathological data were reviewed to evaluate outcomes. Standard open resections were used as the control group and compared exploiting propensity score matching. RESULTS: In total, 290 patients were included. The rate of MILS has been constantly increasing throughout years, representing the 48% in 2019. Of 100 (34.5%) MILS patients, 85 could be matched. After matching, the MILS conversion rate was 5.8% (n = 5). The post-operative complication rates were higher in the open group (45.9% vs. 31.8%, P = 0.004). Post-operative blood transfusions were less common in the MILS group (4.7% vs. 16.5%, P = 0.021). Biliary leak occurred in 2 (2.4) MILS versus 13 (15.3) open. The median comprehensive complication index was higher in the open group (8.7 [0-28.6] vs. 0 [0-10.4], P = 0.0009). The post-operative length of hospital stay was shorter after MILS (median 6 [5-8] vs 8 [7-13] days, P < 0.0001). CONCLUSIONS: The rate of MILS has been significantly increasing throughout the years. The benefits of MILS over the traditional open approach were confirmed. The main advantages include lower rates of post-operative complications, blood transfusions, bile leaks and a significantly decreased hospital stay.