Radiomic Gradient in Peritumoural Tissue of Liver Metastases: A Biomarker for Clinical Practice? Analysing Density, Entropy, and Uniformity Variations with Distance from the Tumour.

The radiomic analysis of the tissue surrounding colorectal liver metastases (CRLM) enhances the prediction accuracy of pathology data and survival. We explored the variation of the textural features in the peritumoural tissue as the distance from CRLM increases. We considered patients with hypodense CRLMs >10 mm and high-quality computed tomography (CT). In the portal phase, we segmented (1) the tumour, (2) a series of concentric rims at a progressively increasing distance from CRLM (from one to ten millimetres), and (3) a cylinder of normal parenchyma (Liver-VOI). Sixty-three CRLMs in 51 patients were analysed. Median peritumoural HU values were similar to Liver-VOI, except for the first millimetre around the CRLM. Entropy progressively decreased (from 3.11 of CRLM to 2.54 of Liver-VOI), while uniformity increased (from 0.135 to 0.199, p < 0.001). At 10 mm from CRLM, entropy was similar to the Liver-VOI in 62% of cases and uniformity in 46%. In small CRLMs (≤30 mm) and responders to chemotherapy, normalisation of entropy and uniformity values occurred in a higher proportion of cases and at a shorter distance. The radiomic analysis of the parenchyma surrounding CRLMs unveiled a wide halo of progressively decreasing entropy and increasing uniformity despite a normal radiological aspect. Underlying pathology data should be investigated.

CT-based radiogenomics of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive disease with increasing incidence and its genetic alterations could be the target of systemic therapies. AIMS: To elucidate if radiomics extracted from computed tomography (CT) may non-invasively predict ICC genetic alterations. METHODS: All consecutive patients with a diagnosis of a mass-forming ICC (01/2016-06/2022) were considered. Inclusion criteria were availability of a high-quality contrast-enhanced CT and molecular profiling by NGS or FISH for FGFR2 fusion/rearrangement. The CT scan at diagnosis was considered. Genetic analyses were performed on surgical specimens (resectable patients) or biopsies (unresectable ones). The radiomic features were extracted using the LifeX software. Multivariate predictive models of the commonest genetic alterations were built. RESULTS: In the 90 enrolled patients (58 NGS/32 FISH, median age 65 years), the most common genetic alterations were FGFR2 (20/90), IDH1 (10/58), and KRAS (9/58). At internal validation, the combined clinical-radiomic models achieved the best performance for the prediction of FGFR2 (AUC = 0.892) and IDH1 status (AUC = 0.819), outperforming the pure clinical and radiomic models. The radiomic model for predicting KRAS mutations achieved an AUC = 0.767 (vs. 0.660 of the clinical model) without further improvements with the addition of clinical features. CONCLUSIONS: CT-based radiomics provides a reliable non-invasive prediction of ICC genetic status with a major impact on therapeutic strategies.

Cornerstones and divergencies in the implementation and use of liver hypertrophy techniques: results from a nationwide survey for the set-up of the prospective registry.

BACKGROUND: The aim of this national survey on liver hypertrophy techniques was to track the trends of their use and implementation in Italy and to detect analogies and heterogeneities among centers. METHODS: In December 2022, Italian centers with liver resection activity were specifically contacted and asked to fill an online questionnaire composed of 6 sections including a total of 51 questions. RESULTS: 46 Italian centers filled the questionnaire. The proportion of major/total number of liver resections was 27% and the use of hypertrophy techniques was required in 6,2% of cases. The most frequent reason of drop out was disease progression in 58.5% of cases. Most frequently used techniques were PVE and ALPPS with an increasing use of hepatic venous deprivation (HVD). Heterogeneous answers were provided regarding the cutoff values to indicate the need for hypertrophy techniques. Criteria to allocate a patient to different hypertrophy techniques are not standardized. CONCLUSIONS: The use of hypertrophy techniques is deep-rooted in Italy, documenting the established value of their role in improving resectability rate. While an evolution of techniques is detectable, still significant heterogeneity is perceived in terms of cutoff values, indications and managing protocols.

Towards a Standardization of Learning Curve Assessment in Minimally Invasive Liver Surgery.

OBJECTIVE: The aim was to analyze the learning curves of minimal invasive liver surgery(MILS) and propose a standardized reporting. SUMMARY BACKGROUND DATA: MILS offers benefits compared to open resections. For a safe introduction along the learning curve, formal training is recommended. However, definitions of learning curves and methods to assess it lack standardization. METHODS: A systematic review of PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in MILS. The primary outcome was the number needed to overcome the learning curve. Secondary outcomes included endpoints defining learning curves, and characterization of different learning phases(competency, proficiency and mastery). RESULTS: 60 articles with 12'241 patients and 102 learning curve analyses were included. The laparoscopic and robotic approach was evaluated in 71 and 18 analyses and both approaches combined in 13 analyses. Sixty-one analyses (60%) based the learning curve on statistical calculations. The most often used parameters to define learning curves were operative time (n=64), blood loss (n=54), conversion (n=42) and postoperative complications (n=38). Overall competency, proficiency and mastery were reached after 34 (IQR 19-56), 50 (IQR 24-74), 58 (IQR 24-100) procedures respectively. Intraoperative parameters improved earlier (operative time: competency to proficiency to mastery: -13%, 2%; blood loss: competency to proficiency to mastery: -33%, 0%; conversion rate (competency to proficiency to mastery; -21%, -29%), whereas postoperative complications improved later (competency to proficiency to mastery: -25%, -41%). CONCLUSIONS: This review summarizes the highest evidence on learning curves in MILS taking into account different definitions and confounding factors. A standardized three-phase reporting of learning phases (competency, proficiency, mastery) is proposed and should be followed.

The tumor microenvironment of VETC+ hepatocellular carcinoma is enriched of immunosuppressive TAMs spatially close to endothelial cells.

BACKGROUND AND AIM: VETC (vessel that encapsulate tumor cluster) is a peculiar vascular phenotype observed in hepatocellular carcinoma (HCC), associated with distant metastases and poor outcome. VETC has been linked to the Tie2/Ang2 axis and is characterized by lymphocytes poor (cold) tumor microenvironment (TME). In this setting the role of Tumor Associated Macrophages (TAMs) has never been explored. Aim of the study is to investigate the presence and features of TAMs in VETC+ HCC and the possible interplay between TAMs and endothelial cells (ECs). METHODS: The series under study included 42 HCC. Once separated according to the VETC phenotype (21 VETC+; 21 VETC-) we stained consecutive slides with immunohistochemistry for CD68, CD163 and Tie2. Slides were then scanned and QuPath used to quantify morphological features. RESULTS: VETC+ cases were significantly (p < 0.001) enriched with large, lipid rich CD163+ TAMs (M2 oriented) that were spatially close to ECs; HCC cells significantly (p: 0.002) overexpressed Tie2 with a polarization toward ECs. CONCLUSIONS: The pro-metastatic attitude of VETC is sustained by a strict morphological relationship between immunosuppressive M2-TAMs, ECs and Tie2-expressing HCC cells.

Peaglet: A user-friendly probabilistic Kernel density estimation of intracranial cortical and subcortical stimulation sites.

BACKGROUND: Data on human brain function obtained with direct electrical stimulation (DES) in neurosurgical patients have been recently integrated and combined with modern neuroimaging techniques, allowing a connectome-based approach fed by intraoperative DES data. Within this framework is crucial to develop reliable methods for spatial localization of DES-derived information to be integrated within the neuroimaging workflow. NEW METHOD: To this aim, we applied the Kernel Density Estimation for modelling the distribution of DES sites from different patients into the MNI space. The algorithm has been embedded in a MATLAB-based User Interface, Peaglet. It allows an accurate probabilistic weighted and unweighted estimation of DES sites location both at cortical level, by using shortest path calculation along the brain 3D geometric topology, and subcortical level, by using a volume-based approach. RESULTS: We applied Peaglet to investigate spatial estimation of cortical and subcortical stimulation sites provided by recent brain tumour studies. The resulting NIfTI maps have been anatomically investigated with neuroimaging open-source tools. COMPARISON WITH EXISTING METHODS: Peaglet processes differently cortical and subcortical data following their distinguishing geometrical features, increasing anatomical specificity of DES-related results and their reliability within neuroimaging environments. CONCLUSIONS: Peaglet provides a robust probabilistic estimation of the cortical and subcortical distribution of DES sites going beyond a region of interest approach, respecting cortical and subcortical intrinsic geometrical features. Results can be easily integrated within the neuroimaging workflow to drive connectomic analysis.

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.

Object-oriented hand dexterity and grasping abilities, from the animal quarters to the neurosurgical OR: a systematic review of the underlying neural correlates in non-human, human primate and recent findings in awake brain surgery.

Introduction: The sensorimotor integrations subserving object-oriented manipulative actions have been extensively investigated in non-human primates via direct approaches, as intracortical micro-stimulation (ICMS), cytoarchitectonic analysis and anatomical tracers. However, the understanding of the mechanisms underlying complex motor behaviors is yet to be fully integrated in brain mapping paradigms and the consistency of these findings with intraoperative data obtained during awake neurosurgical procedures for brain tumor removal is still largely unexplored. Accordingly, there is a paucity of systematic studies reviewing the cross-species analogies in neural activities during object-oriented hand motor tasks in primates and investigating the concordance with intraoperative findings during brain mapping. The current systematic review was designed to summarize the cortical and subcortical neural correlates of object-oriented fine hand actions, as revealed by fMRI and PET studies, in non-human and human primates and how those were translated into neurosurgical studies testing dexterous hand-movements during intraoperative brain mapping. Methods: A systematic literature review was conducted following the PRISMA guidelines. PubMed, EMBASE and Web of Science databases were searched. Original articles were included if they: (1) investigated cortical activation sites on fMRI and/or PET during grasping task; (2) included humans or non-human primates. A second query was designed on the databases above to collect studies reporting motor, hand manipulation and dexterity tasks for intraoperative brain mapping in patients undergoing awake brain surgery for any condition. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed more appropriate. Results: We provided an updated overview of the current state of the art in translational neuroscience about the extended frontoparietal grasping-praxis network with a specific focus on the comparative functioning in non-human primates, healthy humans and how the latter knowledge has been implemented in the neurosurgical operating room during brain tumor resection. Discussion: The anatomical and functional correlates we reviewed confirmed the evolutionary continuum from monkeys to humans, allowing a cautious but practical adoption of such evidence in intraoperative brain mapping protocols. Integrating the previous results in the surgical practice helps preserve complex motor abilities, prevent long-term disability and poor quality of life and allow the maximal safe resection of intrinsic brain tumors.