Laparoscopic versus open parenchymal sparing liver resections for high tumour burden colorectal liver metastases: a propensity score matched analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has proved effective in the treatment of oligometastatic disease (1 or 2 colorectal liver metastases CRLM) with similar long-term outcomes and improved short-term results compared to open liver resection (OLR). Feasibility of parenchymal sparing LLR for high tumour burden diseases is largely unknown. Aim of the study was to compare short and long-term results of LLR and OLR in patients with ≥ 3 CRLM. METHODS: Patients who underwent first LR of at least two different segments for ≥ 3 CRLM between 01/2012 and 12/2021 were analysed. Propensity score nearest-neighbour 1:1 matching was based on relevant prognostic factors. RESULTS: 277 out of 673 patients fulfilled inclusion criteria (47 LLR and 230 OLR). After match two balanced groups of 47 patients with a similar mean number of CRLM (5 in LLR vs 6.5 in OLR, p = 0.170) were analysed. The rate of major hepatectomy was similar between the two group (10.6% OLR vs. 12.8% LLR). Mortality (2.1% OLR vs 0 LLR) and overall morbidity rates (34% OLR vs 23.4% LLR) were comparable. Length of stay (LOS) was shorter in the LLR group (5 vs 9 days, p = 0.001). No differences were observed in median overall (41.1 months OLR vs median not reached LLR) and disease-free survival (18.3 OLR vs 27.9 months LLR). CONCLUSION: Laparoscopic approach should be considered in selected patients scheduled to parenchymal sparing LR for high tumour burden disease as associated to shorter LOS and similar postoperative and long-term outcomes compared to the open approach.

Non-anatomical liver resection for hepatocellular carcinoma: the SegSubTe classification to overcome the problem of heterogeneity.

BACKGROUND: The superiority of anatomical resection (AR) vs. non-anatomical resection (NAR) in the surgical management of hepatocellular carcinoma (HCC) is debated. ARs are well-defined procedures, whereas the lack of NAR standardization results in heterogeneous outcomes. This study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the tumor. METHODS: A single-center retrospective analysis of pre- and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was conducted. The quality of surgery was assessed classifying the type of vascular supply and the level of surgical section (segmental, subsegmental or terminal next to the tumor) of vascular pedicles feeding the HCCs; then, the population was divided in "SegSubTe-IN" or "SegSubTe-OUT" groups, and the tumor recurrence and survival were analyzed. RESULTS: Ninety-seven patients who underwent NAR were included; 76% were SegSubTe-IN and 24% were SegSubTe-OUT. Total disease recurrence, local recurrence and cut-edge recurrence in the SegSubTe-IN vs. SegSubTe-OUT groups were 50% vs. 83% (P = 0.006), 20% vs. 52% (P = 0.003) and 16% vs. 39% (P = 0.020), respectively. SegSubTe-OUT odds ratio for local recurrence was 4.1 at univariate regression analysis. One-, three-, and five-year disease-free survival rates in the SegSubTe-IN vs. SegSubTe-OUT groups were 81%, 58% and 35% vs. 46%, 21% and 11%, respectively (P < 0.001). CONCLUSIONS: The SegSubTe classification is a useful tool to stratify and standardize NAR for HCC, aiming at improving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC.

A retrospective single-centre analysis of the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in liver transplantation: every nodule matters.

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64-0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48-0.72] when LI-RADS-5 and LI-RADS-TR-V (P = 0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P = 0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54-0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P = 0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to LI-RADS protocol seems to contribute to tumour burden and should be entered in the Metroticket 2.0 calculator in order to grant appropriate performance.

Treatment of hepatocellular carcinoma beyond the Milan criteria. A weighted comparative study of surgical resection versus chemoembolization.

BACKGROUND: Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) is debated. The aim of the study was to assess overall-survival (OS) and disease-free-survival (DFS) for HCC beyond MC when treated by trans-arterial-chemoembolization (TACE) or surgical resection (SR). METHOD: between 2005 and 2015, all patients with a first diagnosis of HCC beyond MC(1 nodule>5 cm, or 3 nodules>3 cm without macrovascular invasion) were evaluated. Analyses were carried out through Kaplan-Meier, Cox models and the inverse probability weighting (IPW) method to reduce allocation bias. Sub-analyses have been performed for multinodular and single large tumors compared with a MC-IN cohort. RESULTS: 226 consecutive patients were evaluated: 118 in SR group and 108 in TACE group. After IPW, the two pseudo-populations were comparable for tumor burden and liver function. In the SR group, 1-5 years OS rates were 72.3% and 35% respectively and 92.7% and 39.3% for TACE (p = 0.500). The median DFS was 8 months (95%CI:8-9) for TACE, and 11 months (95%CI:9-12) for SR (p < 0.001). TACE was an independent predictor for recurrence (HR 1.5; 95%CI: 1.1-2.1; p = 0.015). Solitary tumors > 5 cm and multinodular disease had comparable OS and DFS as Milan-IN group (p > 0.05). CONCLUSION: Surgery allowed a better control than TACE in patient bearing HCC beyond MC. This translated into a significant benefit in terms of DFS but not OS.

Functional liver imaging score (FLIS) can predict adverse events in HCC patients.

PURPOSE: To assess the performance of FLIS in predicting adverse outcomes, namely post-hepatectomy liver failure (PHLF) and death, in patients who underwent liver surgery for malignancies. METHODS: All consecutive patients who underwent liver resection and 1.5 T gadoxetic acid MR were enrolled. PHLF and overall survival (OS) were collected. Two radiologists with 18 and 8 years of experience in abdominal imaging, blinded to clinical data, evaluated all images. Radiologists evaluated liver parenchymal enhancement (EnQS), biliary contrast excretion (ExQS), and signal intensity of the portal vein relative to the liver parenchyma (PVsQs). Reliability analysis was computed with Cohen's Kappa. Cox regression analysis was calculated to determine which factors are associated with PHLF and OS. Area Under the Receiver Operating Characteristic curve (AUROC) was computed. RESULTS: 150 patients were enrolled, 58 (38.7 %) in the HCC group and 92 (61.3 %) in the non-HCC group. The reliability analysis between the two readers was almost perfect (κ = 0.998). The multivariate Cox analysis showed that only post-surgical blood transfusions and major resection were associated with adverse events [HR=8.96 (7.98-9.88), p = 0.034, and HR=0.99 (0.781-1.121), p = 0.032, respectively] in the whole population. In the HCC group, the multivariable Cox analysis showed that blood transfusions, major resection and FLIS were associated with adverse outcomes [HR=13.133 (2.988-55.142), p = 0.009, HR=0.987 (0.244-1.987), p = 0.021, and HR=1.891 (1.772-3.471), p = 0.039]. The FLIS AUROC to predict adverse outcomes was 0.660 (95 %CIs = 0.484-0.836), with 87 % sensitivity and 33.3 % specificity (81.1-94.4 and 22.1-42.1). CONCLUSIONS: FLIS can be considered a promising tool to preoperative depict patients at risk of PHLF and death.

COVID-19 and Liver Surgery: How the Pandemic Affected an Italian Medium-Volume HBP Center.

Introduction: While the COVID-19 pandemic is still ongoing, it is even more evident that victims of the pandemic are not only those who contract the virus, but also the countless patients suffering from other serious diseases (i.e., tumor) who have undergone delayed potentially life-saving surgery due to a lack of beds. Like many hospitals, ours also initially blocked all elective oncologic surgery, but these operations were "recovered" and reintegrated in a relatively short time, thanks to the establishment of COVID-free wards and operating rooms with staff dedicated to oncological surgery. In tis context, our aim is to assess whether and how the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) pandemic has impacted our hepatobiliary surgery unit. Methods: From our prospective database, we retrospectively took data from patients undergoing liver surgery in 2018-2019 (pre-COVID) and 2020-2021 (COVID period). Patients admitted to COVID-free wards must necessarily have a negative nasal swab from the previous 24 h. Results: Between January 1, 2018, and December 31, 2019 (Group 1), 101 patients were treated; during the pandemic [January 1, 2020, and December 31, 2021 (Group 2)], 126 patients were treated. There was no statistical difference between the groups. The median postoperative hospital stay was 7 days for both groups; 7 patients had major complications (Clavien-Dindo > 3) in Group 1 and 11 in Group 2 (p = 0.795). A total of 4 patients died in Group 1 and 6 during the pandemic (p = 0.754). Tumor burden was significantly greater in Group 2 where nodule size, lymphadenectomy, and extrahepatic disease were significantly greater (p = 0.011, p = 0.004, and p = 0.026, respectively). Conclusion: During the COVID pandemic, our HPB unit managed to offer a volume of tertiary-center hepatobiliary surgery without a significant impact in terms of length of stay, morbidity, or mortality despite the increase in tumor burden during the pandemic years.

Left Anterior Sectorectomy: An Alternative to Left Hepatectomy for Tumors Invading the Distal Part of the Left Portal Vein.

BACKGROUND: Liver tumors invading the distal part of the umbilical portion of the left portal vein usually require left hepatectomy. The recent introduction of the concept of left anterior sector, an independent anatomo-functional unit including the anterior portion of the left liver and supplied by the distal part of the umbilical portion of the left portal vein, could represent the rational for an alternative surgical approach. The aim of this study was to introduce the novel surgical procedure of ultrasound-guided left anterior sectorectomy. METHODS: Among 92 consecutive patients who underwent hepatectomy, 3 patients with tumor invading the distal part of the umbilical portion of the left portal (two with colorectal liver metastases and one with neuroendocrine tumor liver metastases) underwent left anterior sectorectomy alone or in association with liver multiple metastasectomies. RESULTS: Mean operation time was 393 min; post-operative morbidity and mortality were not observed. After a mean FU of 23 months (range 19-28), no local recurrence occurred. CONCLUSIONS: In presence of tumors invading the distal part of the umbilical portion of the left portal, left anterior sectorectomy could be considered as an anatomic radical surgical option that is safe but more conservative than a left hepatectomy.

Is It Just a Matter of Surgical Extension to Achieve the Cure of Hepatocarcinoma? A Meta-Analysis of Propensity-Matched and Randomized Studies for Anatomic Versus Parenchyma-Sparing Liver Resection.

BACKGROUND: The benefit of anatomic (AR) versus parenchyma-sparing resection (PSR) in hepatocarcinoma (HCC) is still debated. The aim of the study was to compare AR vs. PSR in terms of overall survival (OS) and disease-free survival (DFS). METHODS: A systematic review was conducted using Medline and Google Scholar. To reduce intra- and inter-study heterogeneity, only propensity-matched studies and randomized clinical trials (RCT) were evaluated and a generic inverse variance meta-analysis was run. A sub-analysis was performed in case of tumor microvascular invasion (MVI). RESULTS: Eleven propensity-matched and one RCT were evaluated, with a total of 3445 patients (AR = 1776 and PSR = 1669). Tumor burden and liver function were comparable among studies (I2 < 50%, p > 0.5). OS was similar between AR and PSR (HR 0.93; 95%CI, 0.75-1.15; p = 0.50, I2 = 41%). DFS was improved in AR at 1 year (RR 0.84; 95%CI, 0.72-0.97; p = 0.02; I2 = 36%) and 3 years (RR 0.90; 95%CI, 0.83-0.98; p = 0.02; I2 = 40%) but not at 5 years (RR 0.94; 95%CI, 0.87-1.01; p = 0.07; I2 = 41%). Furthermore, in the presence of MVI, no difference in OS and DFS was observed between AR and PSR. CONCLUSION: When liver function and tumor burden are comparable, AR and PSR achieved similar overall survival. AR improved local control in the early period after surgery. Furthermore, in the presence of MVI, the extension of surgery was not associated with better OS and DFS.

Finding the seed of recurrence: Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment.

The treatment for hepatocellular carcinoma (HCC) relies on liver resection, which is, however, burdened by a high rate of recurrence after surgery, up to 60% at 5 years. No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient. Recently liquid biopsy has shown interesting results in diagnosis, prognosis and treatment allocation strategies in other types of cancers, since its ability to identify circulating tumor cells (CTCs) derived from the primary tumor. Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC. In fact, after being modified by the epithelial-mesenchymal transition, CTCs circulate as "seeds" in peripheral blood, then reach the target organ as dormant cells which could be subsequently "awakened" and activated, and then initiate metastasis. Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections, particularly in the case of microvascular invasion, which has been recently pointed as a histological sign of the spread of those cells. Thus, their presence, also in the early stages, may justify the recurrence event also in the contest of liver transplant. Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics. Moreover, it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies, and in perspective, it could also become a new method to allocate organs for transplantation, according to the risk of relapse after liver transplant. The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC, highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.