Anatomic Versus Non-anatomic Liver Resection for Intrahepatic Cholangiocarcinoma: A Systematic Review and Patient-Level Meta-Analysis.

BACKGROUND: The current standard treatment for intrahepatic cholangiocarcinoma (ICC) involves complete liver resection with negative surgical margins and lymphadenectomy, followed by adjuvant chemotherapy. Debate is ongoing regarding the necessity of systematic anatomic resection (AR). This study aimed to summarize existing literature to determine whether AR leads to better oncologic outcomes than non-AR for patients with resectable ICC. METHODS: A systematic literature review (PubMed, Embase, and Google Scholar) was performed until December 2023. Only studies comparing the oncologic outcomes of AR and non-AR for ICC using propensity score matching or inverse probability of treatment weighting were considered. A meta-analysis of aggregated data for perioperative variables and a reconstructed patient-level meta-analysis for survival data were performed. RESULTS: Five articles were gathered (n = 930 patients after matching: 465 AR/465 non-AR patients). The overall survival (OS) rates were higher in the AR group than in the non-AR group at 1, 3, and 5 years (71.5%, 46.1% and 34.3% vs. 63.6%, 32.9%, and 24.8%, respectively; hazard ratio [HR] 0.74; 95% CI 0.63-0.87; P < 0.001). The same results were observed for the disease-free survival (DFS) rates (58.3%, 33.4%, and 24.5% for AR vs. 45.6%, 23.1%, and 17.4% for non-AR; HR 0.74; 95% CI 0.63-0.86; P < 0.001). The results were confirmed in the two-stage meta-analysis for OS (HR 0.73; P < 0.001) and DFS (HR 0.73; P < 0.001). No differences were observed between the two approaches in terms of operative time, intraoperative blood loss, overall and major morbidity, and hospital length of stay. CONCLUSIONS: By pooling the available evidence, the current study demonstrated that AR for ICC patients is associated with better OS and DFS without any negative impact on postoperative outcomes.

Radiomics and 256-slice-dual-energy CT in the automated diagnosis of mild acute pancreatitis: the innovation of formal methods and high-resolution CT.

INTRODUCTION: Acute pancreatitis (AP) is a common disease, and several scores aim to assess its prognosis. Our study aims to automatically recognize mild AP from computed tomography (CT) images in patients with acute abdominal pain but uncertain diagnosis from clinical and serological data through Radiomic model based on formal methods (FMs). METHODS: We retrospectively reviewed the CT scans acquired with Dual Source 256-slice CT scanner (Somatom Definition Flash; Siemens Healthineers, Erlangen, Germany) of 80 patients admitted to the radiology unit of Antonio Cardarelli hospital (Naples) with acute abdominal pain. Patients were divided into 2 groups: 40 underwent showed a healthy pancreatic gland, and 40 affected by four different grades (CTSI 0, 1, 2, 3) of mild pancreatitis at CT without clear clinical presentation or biochemical findings. Segmentation was manually performed. Radiologists identified 6 patients with a high expression of diseases (CTSI 3) to formulate a formal property (Rule) to detect AP in the testing set automatically. Once the rule was formulated, and Model Checker classified 70 patients into "healthy" or "unhealthy". RESULTS: The model achieved: accuracy 81%, precision 78% and recall 81%. Combining FMs results with radiologists agreement, and applying the mode in clinical practice, the global accuracy would have been 100%. CONCLUSIONS: Our model was reliable to automatically detect mild AP at primary diagnosis even in uncertain presentation and it will be tested prospectively in clinical practice.

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.

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.

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.