Near-infrared fluorescence-guided metastasectomy for hepatic gastrointestinal stromal tumor metastases using indocyanine green: a case report

INTRODUCTION AND IMPORTANCE: Gastrointestinal stromal tumors are the most prevalent mesenchymal tumors of the gastrointestinal tract. Distant metastases are most often found in the liver or peritoneum with surgery being the preferred treatment option. In our center, fluorescence-guided surgery with indocyanine green is used as standard-of-care for hepatic metastases in colorectal cancer. This case report describes fluorescence-guided metastasectomy for a hepatic gastrointestinal stromal tumor in two patients undergoing open liver resection and radiofrequency ablation.CASE PRESENTATION: A 69-year old women was seen during follow-up after laparoscopic resection of a GIST in the lesser curvature of the stomach. Contrast-enhanced computed tomography imaging showed two suspicious lesions in liver segment VI and VIII. Intraoperative near-infrared fluorescence imaging of the liver clearly revealed the lesion in segment VIII, and an additional lesion in segment V - which was not seen on preoperative CT-imaging, neither on intraoperative ultrasonography. The lesion in segment VI was not seen with NIRF imaging due to its deeper location in the liver parenchyma. The second case is an 82-year old man who was also diagnosed with liver metastases from a GIST in the stomach and was scheduled for near-infrared fluorescence-guided liver resection and radio frequency ablation.CLINICAL DISCUSSION: In this case report we demonstrated the feasibility of fluorescence-guided surgery in detection of liver metastases and treatment planning of two patients with hepatic GIST metastases using indocyanine green.CONCLUSION: NIRF-imaging with ICG is useful for identification of preoperatively discovered lesions, surgical resection planning and margin evaluation, and for detection of additional hepatic GIST metastases. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license (http://creative commons.org/licenses/by-nc-nd/4.0/).Surgical oncolog

Clinical translation and implementation of optical imaging agents for precision image-guided cancer surgery

Introduction The field of tumor-specific fluorescence-guided surgery has seen a significant increase in the development of novel tumor-targeted imaging agents. Studying patient benefit using intraoperative fluorescence-guided imaging for cancer surgery is the final step needed for implementation in standard treatment protocols. Translation into phase III clinical trials can be challenging and time consuming. Recent studies have helped to identify certain waypoints in this transition phase between studying imaging agent efficacy (phase I-II) and proving patient benefit (phase III). Trial initiation Performing these trials outside centers of expertise, thus involving motivated clinicians, training them, and providing feedback on data quality, increases the translatability of imaging agents and the surgical technique. Furthermore, timely formation of a trial team which oversees the translational process is vital. They are responsible for establishing an imaging framework (camera system, imaging protocol, surgical workflow) and clinical framework (disease stage, procedure type, clinical research question) in which the trial is executed. Providing participating clinicians with well-defined protocols with the aim to answer clinically relevant research questions within the context of care is the pinnacle in gathering reliable trial data. Outlook If all these aspects are taken into consideration, tumor-specific fluorescence-guided surgery is expected be of significant value when integrated into the diagnostic work-up, surgical procedure, and follow-up of cancer patients. It is only by involving and collaborating with all stakeholders involved in this process that successful clinical translation can occur. Aim Here, we discuss the challenges faced during this important translational phase and present potential solutions to enable final clinical translation and implementation of imaging agents for image-guided cancer surgery.Surgical oncolog

Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses: a multi-center prospective cross sectional study

BackgroundThe diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions.Methods In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively.Results In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%.Interpretation This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integration of NGS results can prevent repeated EUS/FNA, and can also rigorously change the final diagnosis and treatment plan.Surgical oncolog

Fundamentals and developments in fluorescence-guided cancer surgery

Fluorescence-guided surgery using tumour-targeted imaging agents has emerged over the past decade as a promising and effective method of intraoperative cancer detection. An impressive number of fluorescently labelled antibodies, peptides, particles and other molecules related to cancer hallmarks have been developed for the illumination of target lesions. New approaches are being implemented to translate these imaging agents into the clinic, although only a few have made it past early-phase clinical trials. For this translational process to succeed, target selection, imaging agents and their related detection systems and clinical implementation have to operate in perfect harmony to enable real-time intraoperative visualization that can benefit patients. Herein, we review key aspects of this imaging cascade and focus on imaging approaches and methods that have helped to shed new light onto the field of intraoperative fluorescence-guided cancer surgery with the singular goal of improving patient outcomes.Fluorescence-guided surgery (FGS) using tumour-targeted imaging agents has emerged over the past decade as a method of intraoperative cancer detection; however, the clinical implementation of tumour-targeted FGS remains in the early stages. The authors of this Review discuss how target selection, imaging agents and detection systems could enable real-time intraoperative visualization to benefit patients with cancer.Surgical oncolog

Highlighting the Undetectable - Fluorescence Molecular Imaging in Gastrointestinal Endoscopy

Flexible high-definition white-light endoscopy is the current gold standard in screening for cancer and its precursor lesions in the gastrointestinal tract. However, miss rates are high, especially in populations at high risk for developing gastrointestinal cancer (e.g., inflammatory bowel disease, Lynch syndrome, or Barrett's esophagus) where lesions tend to be flat and subtle. Fluorescence molecular endoscopy (FME) enables intraluminal visualization of (pre)malignant lesions based on specific biomolecular features rather than morphology by using fluorescently labeled molecular probes that bind to specific molecular targets. This strategy has the potential to serve as a valuable tool for the clinician to improve endoscopic lesion detection and real-time clinical decision-making. This narrative review presents an overview of recent advances in FME, focusing on probe development, techniques, and clinical evidence. Future perspectives will also be addressed, such as the use of FME in patient stratification for targeted therapies and potential alliances with artificial intelligence. Key Messages center dot Fluorescence molecular endoscopy is a relatively new technology that enables safe and real-time endoscopic lesion visualization based on specific molecular features rather than on morphology, thereby adding a layer of information to endoscopy, like in PET-CT imaging. center dot Recently the transition from preclinical to clinical studies has been made, with promising results regarding enhancing detection of flat and subtle lesions in the colon and esophagus. However, clinical evidence needs to be strengthened by larger patient studies with stratified study designs. center dot In the future fluorescence molecular endoscopy could serve as a valuable tool in clinical workflows to improve detection in high-risk populations like patients with Barrett's esophagus, Lynch syndrome, and inflammatory bowel syndrome, where flat and subtle lesions tend to be malignant up to five times more often. center dot Fluorescence molecular endoscopy has the potential to assess therapy responsiveness in vivo for targeted therapies, thereby playing a role in personalizing medicine. center dot To further reduce high miss rates due to human and technical factors, joint application of artificial intelligence and fluorescence molecular endoscopy are likely to generate added value

Integration of Three-Dimensional Liver Models in a Multimodal Image-Guided Robotic Liver Surgery Cockpit

Background: Robotic liver surgery represents the most recent evolution in the field of minimally-invasive liver surgery. For planning and guidance of liver resections, surgeons currently rely on preoperative 2-dimensional (2D) CT and/or MR imaging and intraoperative ultrasonography. Translating 2D images into digital 3-dimensional (3D) models may improve both preoperative planning and surgical guidance. The da Vinci (R) robotic surgical system is a platform suitable for the integration of multiple imaging modalities into one single view. In this study, we describe multimodal imaging options and introduce the Robotic Liver Surgery Cockpit; Methods: in-house developed software was used and validated for segmentation and registration to create a virtual reality 3D model of the liver based on preoperative imaging. The accuracy of the 3D models in the clinical setting was objectively assessed in 15 patients by measuring tumor diameters and subjectively with a postoperative conducted questionnaire; Results: Implementation and applicability of the 3D model in the surgical cockpit was feasible in all patients and the quality of the 3D reconstructions was high in 14 (93%) of cases. Tumor diameters measured on CT and/or MR imaging were comparable to automated measurements using the segmentation software and 3D models; Conclusions: the 3D model was successfully incorporated in the robotic surgery console as part of a multimodality imaging platform and aided the surgeon in planning and guidance of the resection. Future studies should focus on further automation of 3D rendering and progress into augmented reality.Surgical oncolog

Integration of Three-Dimensional Liver Models in a Multimodal Image-Guided Robotic Liver Surgery Cockpit

Background: Robotic liver surgery represents the most recent evolution in the field of minimally-invasive liver surgery. For planning and guidance of liver resections, surgeons currently rely on preoperative 2-dimensional (2D) CT and/or MR imaging and intraoperative ultrasonography. Translating 2D images into digital 3-dimensional (3D) models may improve both preoperative planning and surgical guidance. The da Vinci (R) robotic surgical system is a platform suitable for the integration of multiple imaging modalities into one single view. In this study, we describe multimodal imaging options and introduce the Robotic Liver Surgery Cockpit; Methods: in-house developed software was used and validated for segmentation and registration to create a virtual reality 3D model of the liver based on preoperative imaging. The accuracy of the 3D models in the clinical setting was objectively assessed in 15 patients by measuring tumor diameters and subjectively with a postoperative conducted questionnaire; Results: Implementation and applicability of the 3D model in the surgical cockpit was feasible in all patients and the quality of the 3D reconstructions was high in 14 (93%) of cases. Tumor diameters measured on CT and/or MR imaging were comparable to automated measurements using the segmentation software and 3D models; Conclusions: the 3D model was successfully incorporated in the robotic surgery console as part of a multimodality imaging platform and aided the surgeon in planning and guidance of the resection. Future studies should focus on further automation of 3D rendering and progress into augmented reality

Real-time surgical margin assessment using ICG-fluorescence during laparoscopic and robot-assisted resections of colorectal liver metastases

Background: Almost a third of the resections in patients with colorectal liver metastases (CRLM) undergoing curative surgery, end up being tumor-margin positive (1 mm) resections. This pilot study aims to describe the surgical technique for using near-infrared fluorescence imaging to assess tumor-margins in vivo in patients with CRLM undergoing laparoscopic or robot-assisted resections.Methods: Out of our institutional database we selected 16 CRLM based on margin-status (R0; n=8, R1; n=8), which were resected by a minimally-invasive approach using ICG-fluorescence. NIRF images acquired during surgery, from both the resection specimen and the wound bed, were analysed for fluorescent signal. We hypothesized that a protruding fluorescent rim at the parenchymal side of the resection specimen could indicate a too close proximity to the tumor and could be predictive for a tumor-positive surgical margin. NIRF images were correlated to final histopathological assessment of the resection margin.Results: All lesions with a NIRF positive resection plane in vivo were reported as having a tumor-positive margin. Lesions that showcased no protruding rim in the wound bed in vivo were diagnosed as having a tumor-negative margin in 88% of cases. A 5-step surgical workflow is described to document the NIRF signal was used assess the resection margin in vivo for future clinical studies.Conclusions: The pilot study shows that image-guided surgery using real-time ICG-fluorescence has the potential to aid surgeons in achieving a tumor-negative margin in minimally invasive liver metastasectomies. The national multi-centre MIMIC-Trial will prospectively study the effect of this technique on surgical tumor-margins (Dutch Trial Register number NL7674).Surgical oncolog