Clinical Research Directory

Construction and Clinical Validation of a Predictive Model for Postoperative Adjuvant Therapy in Hepatocellular Carcinoma Based on Whole-Slide Digital Pathological Images and Deep Learning

Hepatocellular Carcinoma (HCC) is a common global malignancy, ranking 6th in incidence and 3rd in mortality, causing \~480,000 annual deaths. China accounts for over 45% of global cases, bearing a heavy disease burden. Radical resection is key for long-term survival in early-stage patients, but the 5-year postoperative recurrence rate reaches 50%-70%, limiting prognosis . Postoperative adjuvant therapies like Transarterial Chemoembolization (TACE) and Tyrosine Kinase Inhibitors (TKIs, e.g., sorafenib, lenvatinib) are widely used for high-risk recurrence patients TACE is suitable for intermediate-stage HCC by embolizing tumor vessels and perfusing chemo drugs ; multitarget TKIs inhibit pathways like VEGFR/PDGFR for anti-angiogenesis and anti-proliferation, serving as standard advanced HCC treatment . However, TACE has only 50%-60% objective response rate, with some patients suffering liver damage ; TKIs extend Recurrence-Free Survival (RFS) by 3-5 months in high-risk patients but have \<20% response rate in unselected populations, and \>50% incidence of grade 3-4 adverse events (hypertension, hand-foot skin reaction, proteinuria), leading to 20% treatment discontinuation. Currently, no efficient biomarkers exist for identifying beneficiaries, so treatment decisions rely on clinical experience (tumor size, vascular invasion), resulting in poor individualization, medical resource waste, and extra patient burden. Recent studies show the Tumor Immune Microenvironment (TIME) affects TACE/TKI sensitivity . TIME features (immune cell infiltration like CD8⁺ T cells, PD-L1 expression, spatial structure) correlate with treatment response. For example, immune-inflammatory TIME (high CD8⁺ T cell density) may improve response, while immune-exempt/desert phenotypes indicate resistance . However, TIME assessment relies on high-cost, complex technologies (mIHC, spatial transcriptomics) with poor standardization, limiting clinical use. AI (especially deep learning) enables mining deep pathological info from routine HE-stained Whole Slide Imaging (WSI, generated postoperatively for all HCC patients without extra sampling). WSI's cellular/tissue details map TIME features-models like CNN/ViT can predict "HE morphology → immune status" . HE-WSI deep learning models have high accuracy in predicting MSI (AUC 0.88) in colorectal cancer 18, PD-L1 (AUC 0.80) and TMB (AUC 0.91) in non-small cell lung cancer , and HCC recurrence risk (AUC 0.82)/immune infiltration (AUC 0.78) . Yet no studies focus on "postoperative adjuvant therapy efficacy prediction" with multicenter validation. Thus, building an HCC postoperative adjuvant therapy prediction model via HE-WSI and deep learning can clarify TIME's role and overcome tech limitations. This project integrates multicenter clinicopathological data and AI to establish/validate TACE/TKI efficacy prediction models, providing a reliable tool for HCC postoperative treatment decisions.

3D Liver Volumetry

The study aims to improve preoperative evaluation of liver resection volume in patients undergoing major hepatectomies. Accurate prediction of the planned resection and the future liver remnant (FLR) is critical to minimize the risk of postoperative liver failure, which is associated with increased morbidity and mortality. Conventional imaging-based volumetry may have limited accuracy. This study investigates the use of individualized 3D liver models combined to enhance visualization and volumetric analysis of liver anatomy and resection boundaries. Patients are recruited in the liver outpatient clinic and, upon consent, preoperative 3D models are created using Medics 3D. During surgery, the planned resection is guided by the individualized 3D models. Postoperatively, the resected specimen undergoes CT-based volumetry to compare the predicted resection volume from the 3D model with the actual volume. Routine postoperative follow-up is conducted. The study aims to optimize surgical planning, enhance the accuracy of future liver remnant prediction.

Prevention of Pulmonary Complications After Laparoscopic Liver Surgery

* Background: Postoperative pulmonary complications (PPCs) are the most common complications after major upper abdominal surgery. PPCs include respiratory infections, severe atelectasis, pleural effusion, bronchospasm, aspiration pneumonitis, pneumothorax, exacerbation of chronic pulmonary condition, and respiratory failure. Although PPC rates are higher after open liver surgery, PPCs still occur in approximately 12-13% of patients undergoing laparoscopic liver surgery. Preoperative respiratory physiotherapy education reduces PPCs after open major abdominal surgery and after laparoscopic colorectal surgery. The aim of this study is to investigate the impact of enhanced perioperative pulmonary physiotherapy on the incidence of PPCs after laparoscopic liver surgery. * Methods: A prospective, multicentre, single-blinded, randomized controlled trial will be conducted according to the study protocol at participating centers. A total of 326 patients scheduled for laparoscopic liver surgery will be randomized at a 1:1 ratio into intervention group or standard Enhanced Recovery After Surgery (ERAS) -based perioperative education group. Surgeons/ researchers are blinded to the patient allocation. Patients in the intervention group receive preoperative breathing education in a single session and an educational video to guide pulmonary training at home. Pulmonary training lasts for 7 days prior to surgery and for 7 days postoperatively. The training includes deep breathing, and coughing, pursed lip breathing and positive expiratory pressure (PEP) therapy. Patients receive instructions for conducting exercises along with an individual risk assessment at a preoperative ambulatory visit. The exercise session (10min) is to be performed two times daily for total of 14 days. The control group receives standard perioperative breathing education. Primary outcome is the rate of postoperative pulmonary complications within 14 days of operation. Secondary outcomes include 90-day mortality, Clavien-Dindo classified complications, length of hospital stay, intensive care unit (ICU) stay, and hospital costs. * Discussion: Little effort is currently put into preventing pulmonary complications after surgery, although PPCs aggravate considerable morbidity and costs to health care system. ERAS Society protocols concentrate mainly on optimizing postoperative recovery. Laparoscopic techniques as such and frequent manipulation of the diaphragm during liver surgery provoke PPCs at a considerable rate. Aim of the study is to present a short-and-easy perioperative pulmonary physiotherapy initiative and evaluate its impact on PPC rate and PPCs ramifications, including direct costs, after laparoscopic liver surgery.

ORANGE SEGMENTS: Open Versus Laparoscopic Parenchymal Preserving Postero-Superior Liver Segment Resection

The international and multicentre ORANGE SEGMENTS - Trial is a prospective, double blinded, randomized controlled study comparing patients undergoing parenchymal preserving resection of postero-superior liver segments (involving one or two of segments 4a, 7, 8). All patients will be participating in an enhanced recovery programme. Primary outcome is time to functional recovery. Secondary study parameters include hospital length of stay, intraoperative blood loss, operation time, liver specific morbidity, readmission percentage, resection margin, quality of life, body image and cosmesis , reasons for delay of discharge after functional recovery, long term incidence of incisional hernias, hospital and societal costs during one year, time to adjuvant chemotherapy initiation, overall five-year survival.

High Versus Low Pneumoperitoneum PressUre for Parenchymal Transection in Minimally Invasive Major Liver Surgery

Minimally invasive techniques in liver surgery gain popularity as they facilitate postoperative recovery while achieving comparable oncologic outcomes to the open approach. No consensus on the application of pneumoperitoneum pressure in minimal invasive liver resections (MILR) has been reached yet, as prospective clinical studies are scarce. The positive pressure of the CO2 pneumoperitoneum reduces intraoperative blood loss during MILR alongside the development of new transection devices and advancements in inflow control. Low-pressure pneumoperitoneum on the other hand has been shown to decrease postoperative pain scores and analgesic consumption in comparison to standard pneumoperitoneum, and international guidelines recommend the application of "the lowest intra-abdominal pressure allowing adequate exposure of the operative field rather than a routine pressure". Nevertheless, evidence for the application of low-pressure pneumoperitoneum is only moderate to low, requiring additional studies to better define its safety. To address this oxymoron, the investigators conduct a randomized non-inferiority trial to investigate the effect of low in comparison to high-pressure pneumoperitoneum during the transection phase of major MILR on intraoperative blood loss while also evaluating the risk of embolic complications.

Institut Paoli Calmettes Hepatic Surgery Database

Database of patients who undergo hepatic surgery for: benign diseases, primary or secondary liver cancer at Institut Paoli-Calmettes