REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

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.

Fully covered versus partially covered self-expandable metal stents for palliation of distal malignant biliary obstruction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Self-expandable metal stents (SEMSs) are standardly used for distal malignant biliary obstruction (dMBO). Although data suggest that covered versus uncovered SEMSs increase the time to recurrent biliary obstruction (TRBO), no data are available for fully covered (FC) versus partially covered (PC) designs. METHODS: PubMed, Scopus, and Cochrane databases were screened up to January 2023 for studies concerning dMBO treated by an FC- or PC-SEMS and describing adverse events (AEs), recurrences, or TRBO for specific design subpopulations. Pooled proportions or means were calculated using a random-effects model. Several subanalyses were preplanned, including a subanalysis restricted to prospective studies and unresectable diseases. Heterogeneity and publication bias were explored. Standardized differences (d-values) were calculated between groups. RESULTS: From 1290 records, 62 studies (3327 using FC-SEMSs and 2322 using PC-SEMSs) were included. FC- versus PC-SEMSs showed negligible differences in the rate of total AEs (12% vs 9.9%) and all specific AEs, including cholecystitis (2.5% vs 2.6%). In a subanalysis restricted to prospective studies and unresectable diseases, the rate of RBO was comparable between FC-SEMSs (27.3% [95% confidence interval {CI}, 23.7-31.2], I2 = 35.34%) and PC-SEMSs (25.3% [95% CI, 20.2-30.7], I2 = 85.09%), despite small differences (d-values between .186 and .216) in the rate of ingrowth (.5% vs 2.9%) favoring FC-SEMSs and migration (9.8% vs 4.3%) favoring PC-SEMSs. TRBO was shorter for FC-SEMSs (238 days [95% CI, 191-286], I2 = 63.1%) versus PC-SEMSs (369 days [95% CI, 290-449], I2 = 71.9%; d-value = .116). CONCLUSIONS: Despite considerable heterogeneity and small standardized differences, PC-SEMSs consistently exhibited longer TRBO than FC-SEMSs across analyses, without any other differences in AE rates, potentially proposing PC-SEMSs as the standard comparator and TRBO as the primary outcome for future randomized studies on dMBO. (Clinical trial registration number: CRD42023393965.).

Efficacy and safety of endoscopic ultrasound-guided hepaticogastrostomy: a meta-regression analysis.

BACKGROUND: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a valid option for EUS-guided biliary drainage that has been increasingly used in the last decade. The aims of this study were to provide a systematic review with meta-analysis and meta-regression of the features and outcomes of this procedure. METHODS: The MEDLINE, Scopus, Web of Science, and Cochrane databases were searched for literature pertinent to EUS-HGS. Meta-analysis of the proportions and meta-regression of potential modifiers of the main outcome measures were applied. The main outcome was technical success; secondary outcomes were clinical success and procedure-related adverse events (AEs). RESULTS: 33 studies, including 1644 patients, were included in the meta-analysis. Malignant biliary obstruction (MBO) was the underlying cause in almost all cases (99.6%); the main indications for EUS-HGS were duodenal/papillary invasion (34.8%), surgically altered anatomy (18.4%), and hilar stenosis (16.0%). The pooled technical success of EUS-HGS was 97.7% (95%CI 96.1%-99.0%; I 2 = 0%), the intention-to-treat clinical success rate was 88.1% (95%CI 84.7%-91.2%; I 2 = 33.9%), and procedure-related AEs occurred in 12.0% (95%CI 9.8%-14.5%; I 2 = 20.4%), with cholangitis/sepsis (2.8%) and bleeding (2.3%) the most frequent. The rate of procedure-related AEs was lower with the use of dedicated stents on univariable meta-regression analysis. Meta-regression showed that technical success and clinical success rates were modified by the centers' experience (>4/year). CONCLUSIONS: EUS-HGS represents an effective and safe procedure for EUS-guided biliary drainage in patients with MBO. Future studies should address the impact of center experience, patient selection, and the use of dedicated stents to improve performance of this technique.

Technical failure during colorectal endoscopic full-thickness resection: the "through thick and thin" study.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is an effective and safe technique for nonlifting colorectal lesions. Technical issues or failures with the full-thickness resection device (FTRD) system are reported, but there are no detailed data. The aim of our study was to quantify and classify FTRD technical failures. METHODS: We performed a retrospective study involving 17 Italian centers with experience in advanced resection techniques and the required devices. Each center shared and classified all prospectively collected consecutive failures during colorectal EFTR using the FTRD from 2018 to 2022. The primary outcome was the technical failure rate and their classification; secondary outcomes included subsequent management, clinical success, and complications. RESULTS: Included lesions were mainly recurrent (52 %), with a mean (SD) dimension of 18.4 (7.5) mm. Among 750 EFTRs, failures occurred in 77 patients (35 women; mean [SD] age 69.4 [8.9] years). A classification was proposed: type I, snare noncutting (53 %); type II, clip misdeployment (31 %); and type III, cap misplacement (16 %). Among endoscopic treatments completed, rescue endoscopic mucosal resection was performed in 57 patients (74 %), allowing en bloc and R0 resection in 71 % and 64 %, respectively. The overall adverse event rate was 27.3 %. Pooled estimates for the rates of failure, complications, and rescue endoscopic therapy were similar for low and high volume centers (P = 0.08, P = 0.70, and P = 0.71, respectively). CONCLUSIONS: Colorectal EFTR with the FTRD is a challenging technique with a non-negligible rate of technical failure and complications. Experience in rescue resection techniques and multidisciplinary management are mandatory in this setting.

'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.

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.

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.

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.

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.

Deceased Donor Liver Transplantation After Radioembolization for Hepatocellular Carcinoma and Portal Vein Tumoral Thrombosis: A Pilot Study.

Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT). However, when receiving transarterial radioembolization (TARE), a considerable percentage of such patients are able to achieve a radiologic complete response with adequate survival rates. In this pilot prospective study, we evaluated the effect of TARE in downstaging HCC patients with PVTT to meet criteria for DDLT. Between May 2013 and November 2016, patients were evaluated to be enrolled into our "Superdownstaging" protocol. Patients received yttrium-90 TARE and were enlisted for DDLT in case of complete and sustained (6 months) radiological response. Patients with tumor thrombus in the main trunk and/or in the contralateral portal vein branch were excluded. TARE was effective in downstaging and receiving DDLT in 5/17 patients (29.4%). The 5-year overall survival was significantly higher in patients who underwent DDLT compared with those who were not transplanted (60.0% versus 0.0%, P = 0.03). Three out of 5 patients developed recurrence within 1 year after LT. The current series showed a clear survival gain in those patients who were able to receive DDLT after TARE but careful selection for DDLT is however advised.

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

BACKGROUND AND AIMS: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. APPROACH AND RESULTS: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. CONCLUSIONS: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.

Pattern of macrovascular invasion in hepatocellular carcinoma.

BACKGROUND AND AIMS: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. METHODS: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. RESULTS: MaVI prevalence was 11.1%, and median survival of these patients was 6.0 months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4 months in those with PS > 1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1 months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). CONCLUSIONS: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.

Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: An inverse probability of treatment weighting analysis.

PURPOSE: Data from common clinical practice were used to generate balanced cohorts of patients receiving either sorafenib or lenvatinib, for unresectable hepatocellular carcinoma, with the final aim to investigate their declared equivalence. METHODS: Clinical features of lenvatinib and sorafenib patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival was the primary endpoint and occurrence of adverse events was the secondary. RESULTS: The analysis included 385 patients who received lenvatinib, and 555 patients who received sorafenib. In the unadjusted cohort, lenvatinib did not show a survival advantage over sorafenib (HR: 0.85, 95% CI 0.70-1.02). After IPTW adjustment, lenvatinib still not returned a survival advantage over sorafenib (HR: 0.82, 95% CI: 0.62-1.07) even in presence of balanced baseline characteristics. Lenvatinib provided longer survival than sorafenib in patients previously submitted to TACE (HR: 0.69), with PS of 0 (HR: 0.73) or without extrahepatic disease (HR: 0.69). CONCLUSION: Present results confirmed randomized controlled trial in the real-life setting, but also suggests that in earlier stages some benefit can be expected.