Surgical resection is the gold standard for treating synchronous colorectal liver metastases (CRLM). The resection of the primary tumor and metastatic lesions can follow different sequences: “simultaneous”, “bowel-first”, and “liver-first”. Conservative approaches, such as parenchymal-sparing surgery and segmentectomy, may serve as alternatives to major hepatectomy. A comprehensive search of Medline, Epistemonikos, Scopus, and the Cochrane Library was conducted. Studies evaluating patients who underwent surgery for CRLM and reported survival results were included. Other secondary outcomes were analyzed, including disease-free survival, perioperative complications and mortality, and recurrence rates. Quality assessment was performed using the AMSTAR-2 method. No significant differences in overall survival, disease-free survival, and secondary outcomes were observed when comparing simultaneous to “bowel-first” resections, despite a higher rate of perioperative mortality in the former group. The 5-year OS was significantly higher for simultaneous resection compared to “liver-first” resection. No significant differences in OS and DFS were noted when comparing “liver-first” to “bowel-first” resection, or anatomic to non-anatomic resection. Our umbrella review validates simultaneous surgery as an effective oncological approach for treating SCRLM, though the increased risk of perioperative morbidity highlights the importance of selecting suitable patients. Non-anatomic resections might be favored to preserve liver function and enable future surgical interventions.

Background: Liver transplantation (LT) is the gold standard for end-stage liver disease, yet postoperative complications challenge patients and physicians. Indocyanine green (ICG) clearance, a quantitative dynamic test of liver function, is a rapid, reproducible, and reliable test of liver function. This study aimed to systematically review and summarize current literature analyzing the association between ICG tests and post-LT outcomes. Methods: This systematic review was conducted according to PRISMA guidelines. MEDLINE and Cochrane Library, as main databases, and other sources were searched until August 2022 to identify articles reporting the prognostic value of postoperative ICG tests associated with outcomes of adult LT recipients. Risk of bias of included articles was assessed using Quality In Prognosis Studies tool. Methodological quality varied from low to high across risk of bias domains. Results: Six studies conducted between 1994 and 2018 in Europe, America, and Asia were included. The study population ranged from 50 to 332 participants. ICG clearance on the first postoperative day was associated with early allograft dysfunction, graft loss, 1-month and 3-month patient survival probability, prolonged ICU, and hospital stay. The dichotomized ICG plasma disappearance rate (PDR) provided a strong association with medium-term and long-term outcomes: PDR less than 10%/min with 1-month mortality or re-transplantation (odds ratio: 7.89, 95% CI 3.59–17.34, P<0.001) and PDR less than 16.0%/min with 3-month patient survival probability (hazard ratio: 13.90, 95% CI 4.67–41.35, P<0.01). The preoperative model for end-stage liver disease and body mass index were independent prognostic factors for early allograft dysfunction, early complications, and prolonged ICU stay; post-LT prothrombin time and INR were independently associated with graft loss and bilirubin with a prolonged hospital stay. Conclusion: This review shows that ICG clearance tests are associated with graft function recovery, suggesting that a potential prognostic role of ICG test, as an aid in predicting the post-LT course, could be considered.

Background: Lymphadenectomy in the operative management of hepatocellular carcinoma (HCC) remains controversial, with no recommendation for routine practice. Our study aimed to assess the effects of lymphadenectomy in addition to hepatic resection (HR) compared to HR alone for adults with HCC. Methods: This systematic review was conducted according to PRISMA guidelines until March 2023, searching and selecting the relevant literature comparing lymph node dissection or sampling, combined with HR, and with no lymph node removal. Critical appraisal of the included studies was performed using the ROBINS-I tool. Fixed- or random-effect meta-analysis models were carried out, and inter-studies were assessed for heterogeneity. Results: Fourteen studies were selected during the screening process. Data from eight studies containing 32,041 HCC patients were included in the quantitative synthesis. In total, 12,694 patients underwent lymph node dissection (LND), either selectively for preoperatively diagnosed or intraoperatively suspected lymph node metastasis (LNM) or unselectively (i.e., regardless of suspected LNM). According to LN status, 1-, 3- and 5-year mortality rates were higher in the LNM group with respect to both clinically negative LN (OR 3.25, 95% CI 2.52–4.21; p < 0.001; OR 3.79, 95% CI 2.74–5.24; p < 0.001; OR 3.92, 95% CI 2.61–5.88; p < 0.001) and proven LN0 (OR 1.75, 95% CI 1.0–3.04; p = 0.05; OR 2.88, 95% CI 1.79–4.63; p < 0.001; OR 2.54, 95% CI 1.33–4.84; p < 0.001). Moreover, the summary estimates of two controlled trials showed no significant difference in overall survival between LND groups and those without LND for negative LN patients. Conclusions: Lymph node dissection does not appear to improve overall survival, according to the available literature; thus, this does not support its routine adoption as part of standard liver resection for HCC. A case-by-case decision remains advisable.

The epidemiological surge of early-onset colorectal cancer (EOCRC) is characterized by accelerated biological kinetics and disproportionately high rates of systemic relapse following curative-intent surgery. Because standard anatomical staging (TNM) lacks the resolution to accurately capture the intrinsic regenerative capacity of microscopic residual disease, we investigated the transcriptomic architecture of post-surgical failure in a strictly defined, curative-intent clinical pan-cohort. Unbiased transcriptomic profiling of the localized (M0) discovery sub-cohort identified IGF2 as the most significantly upregulated correlate of metachronous relapse. High-resolution isoform analysis revealed that this transcriptional output is predominantly driven by the embryonic (P4) and placental (P5) promoters. Systematic allele-specific expression (ASE) analysis supported widespread biallelic IGF2 expression consistent with relaxation of imprinting-domain control. This signal was not restricted to relapsing tumors, suggesting a recurrence-independent oncofetal baseline across the EOCRC spectrum. Because this foundational epigenetic unlocking is functionally insufficient on its own to execute systemic metastasis, we distilled the additional transcriptional plasticity required for dissemination into an internally derived and bootstrap-stabilized 5-gene recurrence-risk module Multivariable analysis across the combined pan-cohort supported an independent association between the high-risk module and systemic relapse (p < 0.001), capturing prognostic dimensions completely unresolved by classical pathological covariates and baseline staging. Ultimately, our findings reframe EOCRC aggressiveness as the product of a dual-hit architecture. This framework resolves the clinical paradox of widespread IGF2 LOI co-existing with heterogeneous outcomes, offering a biologically grounded basis for molecular risk stratification beyond anatomical boundaries.