Achievement of textbook outcome after hepatectomy combined with thermal ablation for colorectal liver metastases.

BACKGROUND: Hepatic resection combined with intraoperative ablation has been described as a technical solution potentially widening the resectability rate of patients with colorectal liver metastases (CRLM). Nevertheless, the perioperative and oncological benefit provided by this combined approach remains unclear. We hypothesized that textbook outcome (TO), which is a composite measure achieved for patients for whom some desired health indicators are met, may help to refine the indications of this approach. METHODS: Patients submitted to hepatectomy with curative intent in combination with radiofrequency ablation or microwave ablation for CRLM ≤ 3 cm in two tertiary referral centers were included. TO was defined according to a recent definition for liver surgery based on a Delphi process including also the achievement of complete radiological response of the ablated lesion/s at 4 weeks. RESULTS: Between 2015 and 2022, 112 patients were enrolled. Among them, 63 (56.2%) achieved a TO. According to multivariate analysis, minimally invasive (MI) approach (OR 2.72, 95% CI 0.99-7.48, p = 0.050), simultaneous CR resection (OR 0.28, 95% CI 0.11-0.70, p = 0.007), tumor burden score (OR 0.89, 95% CI 0.82-0.96, p = 0.004), and major hepatectomy (OR 0.12, 95% CI 0.03-0.52, p = 0.004) were significantly associated with the achievement of TO. Median overall survival was longer in those patients who were able to achieve a TO compared to those who did not. CONCLUSIONS: The combination of hepatectomy and ablation constitutes a valuable solution in patients affected by multiple CRLM and it may provide, also using a MI approach, adequate perioperative and oncological outcomes, allowing to achieve TO, however, in a selected number of patients and depending on several factors including the burden of disease.

Preoperative MRI radiomic analysis for predicting local tumor progression in colorectal liver metastases before microwave ablation.

PURPOSE: Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA). METHODS: All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7).Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction. RESULTS: Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%).CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p = 0.0003; RAD-T2: AUC = 0.79, p = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p = 0.0001; COMB-T2: AUC = 0.95, p = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10th percentile of signal intensity, while tumor flatness was present in COMB-T2. CONCLUSION: MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.

Multi-institutional analysis of outcomes for thermosphere microwave ablation treatment of colorectal liver metastases: the SMAC study.

OBJECTIVES: Oligometastatic colorectal cancer benefits of locoregional treatments but data concerning microwave ablation (MWA) are limited and interactions with systemic therapy are still debated. The aim of this study is to evaluate safety and effectiveness of Thermosphere™ MWA (T-MWA) of colorectal liver metastases (CLM) and factors affecting local tumor progression-free survival (LTPFS). METHODS: In this multi-institutional retrospective study (January 2015-September 2019), patients who underwent T-MWA for CLM were enrolled. Complications according to SIR classification were collected, primary efficacy and LTP were calculated. Analyzed variables included CLM size at diagnosis and at ablation, CLM number, ablation margins, intra-segment progression, chemotherapy before ablation (CBA), variations in size (ΔSDIA-ABL), and velocity of size variation (VDIA-ABL) between CLM diagnosis and ablation. Uni/multivariate analyses were performed using mixed effects Cox model to account for the hierarchical structure of data, patient/lesions. RESULTS: One hundred thirty-two patients with 213 CLM were evaluated. Complications were reported in 6/150 procedures (4%); no biliary complications occurred. Primary efficacy was achieved in 204/213 CLM (95.7%). LTP occurred in 58/204 CLM (28.4%). Six-, twelve-, and eighteen-month LTPFS were 88.2%, 75.8%, and 69.9%, respectively. At multivariate analysis, CLM size at ablation (p = 0.00045), CLM number (p = 0.046), ablation margin < 5 mm (p = 0.0035), and intra-segment progression (p < 0.0001) were statistically significant for LTPFS. ΔSDIA-ABL (p = 0.63) and VDIA-ABL (p = 0.38) did not affect LTPFS. Ablation margins in the chemo-naïve group were larger than those in the CBA group (p < 0.0001). CONCLUSION: T-MWA is a safe and effective technology with adequate LTPFS rates. Intra-segment progression is significantly linked to LTPFS. CBA does not affect LTPFS. Anticipating ablation before chemotherapy may take the advantages of adequate tumor size with correct ablation margin planning. KEY POINTS: • Thermosphere™-Microwave ablation is a safe and effective treatment for colorectal liver metastases with no registered biliary complications in more than 200 ablations. • Metastases size at time of ablation, intra-segment progression, and minimal ablation margin < 5 mm were found statistically significant for local tumor progression-free survival. • Chemotherapy before ablation modifies kinetics growth of the lesions but deteriorates ablation margins and does not significantly impact local tumor progression-free survival.

Combining Laparoscopic Liver Partitioning and Simultaneous Portohepatic Venous Deprivation for Rapid Liver Hypertrophy.

Future liver remnant (FLR) volume is an important indicator of the risk of posthepatectomy liver failure (PHLF) and limits the feasibility of major hepatectomies. A case series of 5 patients treated with a novel approach is presented. Laparoscopic liver partitioning was combined with subsequent liver venous deprivation (embolization of both the portal and the hepatic veins). Baseline average FLR was 28.8%. All procedures were successfully performed without major complications. Mean 1-, 2- and 4-week hypertrophy of the FLR were 35%, 40.3%, and 46.4%, respectively. Four patients underwent planned surgery after a mean interval of 28 days. Of these, 2 patients achieved sufficient FLR volume and function after 2 weeks and underwent surgery before the 4-week volumetric analysis. One patient did not undergo surgery because of intraoperative diagnosis of peritoneal metastases. No cases of PHLF were observed at 5-day follow-up.

Validation of the easy-to-use lenvatinib prognostic index to predict prognosis in advanced hepatocellular carcinoma patients treated with lenvatinib.

AIM: The identification of new prognostic factors able to stratify hepatocellular carcinoma patients candidate to first-line therapy is urgent. In the present work we validated the prognostic value of the lenvatinib prognostic index. METHODS: Data of Eastern and Western patients treated with lenvatinib as first-line for Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma were recollected. The lenvatinib prognostic index was composed by three classes of risk according with our previous study. The "low risk" group includes patients with prognostic nutritional index (PNI) >43.3 and with previous transarterial chemoembolization. The "medium risk" group includes patients with PNI >43.3, but without previous transarterial chemoembolization and patients with PNI <43.3, albumin-bilirubin grade 1 and Barcelona Clinic Liver Cancer stage B. The "high risk" group includes patients with PNI <43.3, albumin-bilirubin grade 2, and patients with PNI <43.3, albumin-bilirubin grade 1 and Barcelona Clinic Liver Cancer stage C. RESULTS: A total of 717 patients were included. The median overall survival was 20.7 months (95% CI 16.1-51.6) in patients with low risk (n = 223), 16.7 months (95% CI 13.3-47.0) in patients with medium risk (n = 264), and 10.7 months (95% CI 9.3-12.2) in patients with high risk (n = 230; HR 1, 1.29, and 1.92, respectively; p < 0.0001). Median progression-free survival was 7.3 months (95% CI 6.3-46.5) in patients with low risk, 6.4 months (95% CI 5.3-8.0) in patients with medium risk ,and 4.9 months (95% CI 4.3-5.5) in patients with high risk (HR 1, 1.07, 1.47 respectively; p = 0.0009). CONCLUSION: The lenvatinib prognostic index confirms its prognostic value on an external cohort of hepatocellular carcinoma patients treated with Lenvatinib.

Comparison between percutaneous and laparoscopic microwave ablation of hepatocellular carcinoma.

Background: Based on patient and tumor characteristics, some authors favor laparoscopic microwave ablation (LMWA) over the percutaneous approach (PMWA) for treatment of hepatocellular carcinoma (HCC). We compared the two techniques in terms of technique efficacy, local tumor progression (LTP) and complication rates.Study design: A retrospective comparative analysis was performed on 91 consecutive patients (102 HCC tumors) who underwent PMWA or LMWA between October 2014 and May 2019. Technique efficacy at one-month and LTP at follow-up were assessed by contrast-enhanced CT/MRI. Kaplan-Meier estimates and Cox regression were used to compare LTP-free survival (LTPFS).Results: At baseline analysis, LMWA group showed higher frequency of multinodular disease (p < .001) and average higher energy delivered over tumor size (p = .033); PMWA group showed higher rates of non-treatment-naïve patients (p = .001), patients with Hepatitis-C (p = .03) and BCLC-A1 disease (p = .006). Technique efficacy was not significantly different between the two groups (p = .18). Among effectively treated patients, 75 (83 tumors) satisfied ≥6 months follow-up, 54 (57 tumors) undergoing PMWA and 21 (26 tumors) LMWA. LTP occurred in 14/83 cases (16.9%): 12 after PMWA (21.1%) and 2 after LMWA (7.7%). At univariate analysis, technique did not correlate to LTPFS (p = .28). Subgroup analysis showed a trend toward worse LTPFS after PMWA of subcapsular tumors (p = .16). Major complications were observed in six patients (6.6%), 2 after PMWA and 4 after LMWA (3.2% vs 14.3%, p = .049).Conclusions: Technical approach did not affect LTPFS. Complications were reported more frequently after LMWA. Despite higher complication rates, LMWA seems a valid option for treatment of subcapsular tumors.

Germline testing and genetic counseling in biliary tract cancer: an operative proposal to improve the state of art.

INTRODUCTION: A genetic predisposition seems to be involved in biliary tract cancer, but the prevalence of germline mutations in BTC remains unclear, and the therapeutic role of the germline pathologic variants is still unknown. AREA COVERED: The aim of the present work is to systematically review the data available on the hereditary predisposition of biliary tract cancer by a specific research on PubMed, in order to highlight the most important critical points and to define the current possible role of germinal testing and genetic counseling in this setting of patients. EXPERT OPINION: Basing on data already available, we decided to start in our institution a specific genetic protocol focused on biliary tract cancer patients, which includes genetic counseling and, if indicated, germline test. The inclusion criteria are: 1) Patient with personal history of oncologic disease other than BTC, 2) Patient with familiar history of oncologic disease (considering relatives of first and second grade), 3) Patient with ≤ 50 years old, 4) Patient presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair. The aim of the presented protocol is to identify germline pathogenic variants with prophylactic and therapeutic impact, and to collect and integrate a significant amount of clinical, familial, somatic, and genetic data.

Combined Loco-Regional and Systemic Treatment Strategies for Hepatocellular Carcinoma: From Basics to New Developments.

Recent advances in systemic therapeutic options have led to improved survival in patients with advanced hepatocellular carcinoma. In order to optimize patient outcomes across different disease stages, attempts are being made at exploiting combinations of loco-regional treatments and systemic therapeutic regimens. The possibilities of a beneficial synergistic effect are strongly supported by biological evidence of changes in tumor microenvironment and systemic immunity. With the advent of newer interventional technologies and newer biological and immunological drugs, these possibilities keep on gaining interest and expectations, yet many questions remain unanswered as to how to best manipulate and combine the two therapeutic approaches.This review aims at providing a general overview of biological foundations, preliminary clinical applications, critical issues and future directions of this constantly growing field.

Prognostic value of preoperative CT scan derived body composition measures in resected pancreatic cancer.

BACKGROUND: It remains unclear whether preoperative body composition may affect the prognosis of pancreatic cancer patients undergoing surgery. The aim of the present study was to assess the extent to which preoperative body composition impacts on postoperative complication severity and survival in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). METHODS: A retrospective cohort study was performed on consecutive patients who underwent pancreatoduodenectomy with preoperative CT scan imaging available. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), subcutaneous fat area and liver steatosis (LS) were assessed. Sarcopenic obesity was defined as a high VFA/TAMA ratio. Postoperative complication burden was evaluated with the comprehensive complication index (CCI). RESULTS: Overall, 371 patients were included in the study. At 90 days after surgery, 80 patients (22%) experienced severe complications. The median CCI was 20.9 (IQR 0-30). At multivariate linear regression analysis, preoperative biliary drainage, ASA score ≥3, fistula risk score and sarcopenic obesity (37% increase; 95%CI 0.06-0.74; p = 0.046) were associated to an increase in CCI. Patient characteristics associated to sarcopenic obesity were older age, male gender and preoperative LS. At a median follow-up of 25 months (IQR 18-49), median disease-free survival (DFS) was 19 months (IQR 15-22). At cox-regression analysis, only pathological features were associated with DFS, while LS and other body composition measures did not show any prognostic role. CONCLUSION: The combination of sarcopenia and visceral obesity was significantly associated with increased complication severity after pancreatoduodenectomy for cancer. Patients' body composition did not affect disease free survival after pancreatic cancer surgery.

Retrospective Evaluation and Significance of Neutrophil-to-Lymphocyte Ratio Prior to and 1 month Following Microwave Ablation of Hepatocellular Carcinoma.

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) recently demonstrated predictive value for hepatocellular carcinoma (HCC) recurrence after thermal ablation. Microwave ablation (MWA) has been shown to induce changes in the immune landscape after HCC treatment. This study aims at identifying predictors of local tumor progression (LTP) and post-treatment NLR kinetics after MWA. MATERIALS AND METHODS: Data from 108 consecutive patients who underwent percutaneous MWA of 119 HCCs with a 2450 Hz/100 W generator in two institutions from October 2014 to September 2021 were retrospectively reviewed. Forty-five HCCs (42 patients) met inclusion criteria for analysis (technique efficacy, pre- and post-treatment NLR availability, follow-up > 6 months, absence of complications). NLR was analyzed prior to therapy and at 1-month follow-up; difference between the two time points was defined as ΔNLR1stFU. RESULTS: After a median follow-up of 25 months, LTP occurred in 18 HCCs (40%) and 18 patients (42.9%). Multivariate competing risk regression comprising ΔNLR1stFU > 0, cirrhosis etiology and subcapsular location showed that the only independent predictor of LTP was ΔNLR1stFU > 0, on both a per-patient (HR = 2.7, p = 0.049) and per-tumor (HR = 2.8, p = 0.047) analysis. ΔNLR1stFU > 0 occurred in 24/42 patients (57.1%). In this subgroup, higher rates of female patients (p = 0.026), higher mean baseline NLR (p < 0.0001) and lower mean energy/size (p = 0.006) were observed. Upon ROC curve analysis, energy/size < 1414 J/mm predicted ΔNLR1stFU > 0 with 76% sensitivity and 70% specificity (AUC = 0.74). CONCLUSION: NLR increase after ablation was the only independent predictor of LTP, supporting the role of balance between systemic inflammation and immunity in recurrence after MWA. Ablation energy/tumor size predicted NLR increase, reinforcing the concept of immune ablation. LEVEL OF EVIDENCE: III.

Single-Center Retrospective Study Comparing Double Vein Embolization via a Trans-Jugular Approach with Liver Venous Deprivation via a Trans-Hepatic Approach.

PURPOSE: To compare safety, technical and clinical outcomes of double vein embolization (DVE) via a trans-jugular approach with liver venous deprivation (LVD) via a trans-hepatic approach. MATERIALS AND METHODS: A single-center retrospective analysis was conducted on patients undergoing simultaneous portal and hepatic veins embolization in view of a major hepatectomy (June 2019-November 2022). Hepatic vein embolization was performed either by transjugular plug (DVE) or by transhepatic plug followed by glue injection (LVD). Inclusion criteria were availability of pre-procedural CT scan, and availability of CT scans acquired 10 days and 25 days post-procedure. Comparative data included complication rate, fluoroscopy time, dose area product (DAP), Future Liver Remnant volume and function increase (FLR-V and FLR-F increase, respectively) and clinical outcomes. RESULTS: Thirty-six patients (n = 14 DVE; n = 22 LVD) were included. No baseline significant differences were observed among the two groups. One grade-3 complication (2.8%) was observed in the LVD group; one case of technical failure (2.8%) was observed in the DVE group. Fluoroscopy time and DAP were similar between DVE and LVD (29 ± 17.7 vs. 25 ± 8.2 min, p = 0.97; 105.1 ± 63.5 vs. 143.4 ± 79.5 Gy·cm2, p = 0.15). No differences arose at either time-point in FLR-V increase (46.7 ± 23.1% vs. 48.2 ± 28.2%, 52.9 ± 30.9% vs. 53.2 ± 29%, respectively, p = 0.9). FLR-F increase also did not differ significantly (62.8 ± 55.2 vs. 67.4 ± 57.5, p = 0.9). No differences in drop-out rate from surgery were observed. (28.6% vs. 27.3%, p = 0.93). One case of grade-B post-hepatectomy liver failure (2.8%) was observed in the LVD group. CONCLUSION: LVD via transhepatic approach and DVE via transjugular approach seem equally safe and effective. Level of Evidence Level 3, Retrospective Cohort Study.

Radial and longitudinal margins in surgery of perihilar cholangiocarcinoma: When R1 definition is associated with different prognosis.

BACKGROUND: Infiltrated margins of resection (R1) and lymph node invasion are dominant negative predictors of survival in patients with a resectable perihilar cholangiocarcinoma. Less clear is whether survival predictors stratify differently between R0 (tumor-free margins) and R1 patients and whether the prognosis of the latter patients is influenced by the pattern of neoplastic infiltration (ie, radial versus longitudinal infiltration). We retrospectively evaluated a series of reported resected perihilar cholangiocarcinoma to obtain insights on the predictive power of these histologic features. METHODS: The study includes 264 patients with perihilar cholangiocarcinoma treated between 2004 and 2019 in our center and followed up for >18 months. There were 176 patients with R0 (66.6%) and 88 patients with R1 (33.3%), 31 with radial infiltration only, 30 with longitudinal infiltration only, and 27 with both infiltration patterns. In all patients, the criteria for resection was the absence of metastatic involvement (ie, distant organ metastases, liver metastases, and lymph node metastases beyond the hepatoduodenal ligament). Histopathologic specimens of the resected tumors were centrally reviewed by a pathologist unaware of the clinical outcomes. RESULTS: Three- and 5-year long-term survival were significantly better in R0 (respectively) compared to R1 patients (55% and 42% vs 42% and 18%, respectively, P < .05). In R1 patients with radial infiltration only and those with radial + longitudinal infiltration, both disease-free and overall survival were worse than those with longitudinal infiltration only (median disease-free survival of 18 and 23 months, respectively, P < .05, median overall survival of 33 and 39 months, respectively, P < .05). At multivariable analysis, nodal status, side of hepatectomy, grading, and presence of radial margin infiltration were associated with long-term outcome. CONCLUSION: Radial infiltration of resection margins enhances the negative prognostic value of R1 margins in perihilar cholangiocarcinoma patients and should specifically be accounted for in the prediction of the outcome of adjuvant therapy.

Comparing Liver Venous Deprivation and Portal Vein Embolization for Perihilar Cholangiocarcinoma: Is It Time to Shift the Focus to Hepatic Functional Reserve Rather than Hypertrophy?

Purpose: Among liver hypertrophy technics, liver venous deprivation (LVD) has been recently introduced as an effective procedure to combine simultaneous portal inflow and hepatic outflow abrogation, raising growing clinical interest. The aim of this study is to investigate the role of LVD for preoperative optimization of future liver remnant (FLR) in perihilar cholangiocarcinoma (PHC), especially when compared with portal vein embolization (PVE). Methods: Between January 2013 and July 2022, all patients diagnosed with PHC and scheduled for preoperative optimization of FTR, through radiological hypertrophy techniques, prior to liver resection, were included. FTR volumetric assessment was evaluated at two distinct timepoints to track the progression of both early (T1, 10 days post-procedural) and late (T2, 21 days post-procedural) efficacy indicators. Post-procedural outcomes, including functional and volumetric analyses, were compared between the LVD and the PVE cohorts. Results: A total of 12 patients underwent LVD while 19 underwent PVE. No significant differences in either post-procedural or post-operative complications were found. Post-procedural FLR function, calculated with (99m) Tc-Mebrofenin hepatobiliary scintigraphy, and kinetic growth rate, at both timepoints, were greater in the LVD cohort (3.12 ± 0.55%/min/m2 vs. 2.46 ± 0.64%/min/m2, p = 0.041; 27.32 ± 16.86%/week (T1) vs. 15.71 ± 9.82%/week (T1) p < 0.001; 17.19 ± 9.88%/week (T2) vs. 9.89 ± 14.62%/week (T2) p = 0.034) when compared with the PVE cohort. Post-procedural FTR volumes were similar for both hypertrophy techniques. Conclusions: LVD is an effective procedure to effectively optimize FLR before liver resection for PHC. The faster growth rate combined with the improved FLR function, when compared to PVE alone, could maximize surgical outcomes by lowering post-hepatectomy liver failure rates.

Real-World Data on Ivosidenib in Patients with Previously Treated Isocitrate Dehydrogenase 1-Mutated Intrahepatic Cholangiocarcinomas: An Early Exploratory Analysis.

BACKGROUND: The results of the phase III ClarIDHy trial have led to US FDA approval of ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations. OBJECTIVE: In this study, we report the first real-world experience including eight patients with previously treated locally advanced or metastatic IDH1-mutated CCA treated with ivosidenib. PATIENTS AND METHODS: Patients treated with ivosidenib as second and third line for advanced CCA were collected with the aim of evaluating the survival outcomes. A molecular study has been performed by next-generation sequencing assay. RESULTS: After a median follow up of 9.4 months, median progression-free survival (PFS) from the start of treatment with ivosidenib was 4.4 months (95% confidence interval [CI] 3.3-5.8), whereas median overall survival (OS) was not reached. The disease control rate was 62.5%, with two patients achieving a partial response (25%); 12.5% of patients experienced a treatment-related adverse event (AE), but no grade 3 or higher AEs were reported. The observed grade 2 AEs were prolonged QT interval and hypomagnesemia (25% of the sample). Molecular profiling was performed on six of eight patients, highlighting TP53, BAP1, CDKN2A and CDKN2B as the most common co-altered genes in these patients. CONCLUSION: Efficacy outcomes were consistent with those reported in the ClarIDHy trial. Real-world experiences on larger samples are needed in order to confirm our results.

Embolisation of the parenchymal tract after percutaneous portal vein catheterization: a retrospective comparison of outcomes with different techniques in two centres.

BACKGROUND: Embolisation of the parenchymal tract is a key step after any other transhepatic or transplenic percutaneous portal vein catheterization since eventual venous bleeding is difficult to control and may require surgical management. Different techniques have been proposed to perform tract embolisation. The aim of this study is to compare the safety and efficacy of different techniques of haemostasis of the parenchymal tract. MATERIALS AND METHODS: All the interventional procedures with percutaneous transhepatic or transplenic access to the portal vein (excluding ipsilateral portal vein embolisation) from January 2010 to July 2020, in two tertiary hospitals, were retrospectively analyzed. The following data were evaluated: access site, the technique of embolisation, technical success in terms of immediate thrombosis of the tract, safety and clinical efficacy in terms of the absence of hemorrhagic and thrombotic complications. RESULTS: One-hundred-sixty-one patients underwent 220 percutaneous transhepatic or transplenic portal vein catheterization procedures. The main indications were pancreatic islet transplantation, portal anastomotic stenosis after liver transplantation, and portal vein thrombosis recanalization. As embolic materials gelfoam was used in 105 cases, metallic micro-coils in 54 cases, and cyanoacrylic glue in 44 cases; in 17 cases the parenchymal tract was not embolized. Technical success was 98% without significant difference among groups (p-value = 0.22). Eighteen post-procedural abdominal bleedings occurred, all grade 3 and were managed conservatively; difference among groups was not significant (p-value = 0.25). We detected 12 intrahepatic portal branch thromboses not related to the embolisation technique; only one case of non-target embolisation was documented after liver tract embolisation with glue, without clinical consequences. CONCLUSION: Embolisation of the parenchymal tract after percutaneous portal vein catheterization is technically safe and effective. No significant differences were found between coils, glue, and gelfoam in effectiveness and complications rate. LEVEL OF EVIDENCE: Level 3, Cohort study.

Evolution of Surgical Treatment of Colorectal Liver Metastases in the Real World: Single Center Experience in 1212 Cases.

BACKGROUND: In recent years, the treatment of colorectal liver metastases (CRLM) has undergone significant evolution thanks to technical improvements as well as oncological advances, which have been the subject of targeted studies aimed at understanding the details of this heterogeneous disease. The purpose of this study is to put together pieces of this complex scenario by providing an overview of the evolution that has occurred in the context of a single center within a multidisciplinary management approach. METHODS: Between 2005 and 2020, 1212 resections for CRLM were performed at the Hepatobiliary Surgery Division of San Raffaele Hospital, Milan. The series was divided into three historical periods, which were compared in terms of disease characteristics and short- and long-term outcomes: Period 1, 2005-2009 (293 cases); Period 2, 2010-2014 (353 cases); Period 3, 2015-2020 (566 cases). The trends for surgical technical complexity, oncological burden of the disease, use of the laparoscopic approach and use of techniques for hepatic hypertrophy were analyzed year by year. Uni- and multivariate analyses were performed to identify factors associated with inclusion to a laparoscopic approach and with long-term prognosis. RESULTS: The number of resections performed over the years progressively increased, with an increase in the number of cases with a high Clinical Risk Score and a high profile of technical complexity. The proportion of cases performed laparoscopically increased, but less rapidly compared to other malignant tumors. The risk of postoperative morbidity and mortality was similar in the three analyzed periods. Long-term survival, stratified by Clinical Risk Score, improved in Period 3, while overall survival remained unchanged. CONCLUSION: The cultural background, the maturation of technical expertise and the consolidation of the multidisciplinary team have resulted in safe expansion of the possibility to offer a curative opportunity to patients, while continuously implementing into clinical practice evidence provided by the literature.

The Two-Step Treatment for Giant Hepatic Hemangiomas.

The aim of the present study is to analyze the feasibility and the impact of a two-step approach in the treatment of giant hemangiomas (GH) i.e., exceeding 10 cm in maximum diameter, consisting of transarterial embolization (TAE) followed by laparoscopic liver resection (LLR). Ten patients with 11 GH were treated with TAE and subsequent LLR between 2017 and 2020 (Group A). A matched cohort of 10 patients with GH treated with upfront LLR between 2014 and 2017 was identified for comparison (Group B). Data were analyzed regarding intraoperative and postoperative outcomes, including successful completion of LLR, morbidity, and mortality. Successful microparticle embolization of the GH-feeding arteries was performed in all patients in group A. In three cases a liquid embolic agent (Squid-18) was also injected to obtain complete embolization. No complications were observed after TAE. Successful surgery was performed after a mean time interval of 2.2 days from TAE without any case of conversion to laparotomy. Statistically significant differences between group A and group B were found in intraoperative blood loss (250 ± 200 vs. 400 ± 300 mL, p = 0.039), operative time (245 ± 60 vs. 420 ± 60 min, p = 0.027), and length of stay (5 ± 1 vs. 8 ± 2 days, p = 0.046). Our data suggest that two-step TAE + LLR might be a safe and effective option for surgical treatment of GH >10 cm.

Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy.

BACKGROUND: Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib. AIMS AND METHODS: To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival. RESULTS: Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34-0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue. CONCLUSION: Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.