Intraoperative molecular imaging of colorectal lung metastases with SGM-101: a feasibility study.

PURPOSE: Metastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during minimally invasive surgery. Intraoperative fluorescence imaging has the potential to overcome these challenges. The aim of this study was to assess feasibility of targeting CLM with the carcinoembryonic antigen (CEA) specific fluorescent tracer SGM-101. METHODS: This was a prospective, open-label feasibility study. The primary outcome was the number of CLM that showed a true positive fluorescence signal with SGM-101. Fluorescence positive signal was defined as a signal-to-background ratio (SBR) ≥ 1.5. A secondary endpoint was the CEA expression in the colorectal lung metastases, assessed with the immunohistochemistry, and scored by the total immunostaining score. RESULTS: Thirteen patients were included in this study. Positive fluorescence signal with in vivo, back table, and closed-field bread loaf imaging was observed in 31%, 45%, and 94% of the tumors respectively. Median SBRs for the three imaging modalities were 1.00 (IQR: 1.00-1.53), 1.45 (IQR: 1.00-1.89), and 4.81 (IQR: 2.70-7.41). All tumor lesions had a maximum total immunostaining score for CEA expression of 12/12. CONCLUSION: This study demonstrated the potential of fluorescence imaging of CLM with SGM-101. CEA expression was observed in all tumors, and closed-field imaging showed excellent CEA specific targeting of the tracer to the tumor nodules. The full potential of SGM-101 for in vivo detection of the tracer can be achieved with improved minimal invasive imaging systems and optimal patient selection. TRIAL REGISTRATION: The study was registered in ClinicalTrial.gov under identifier NCT04737213 at February 2021.

Video-assisted thoracic surgery S7 segmentectomy: use of virtual reality surgical planning and simulated reality intraoperative modelling.

Preoperative planning and perioperative guidance are crucial in anatomical sublobar pulmonary resections. Preoperative virtual reality visualization of the computed tomography scan and intraoperative guidance through a soft-tissue dynamic lung model (simulated reality) can provide better insights into patient-specific anatomy for the surgical team. Using these imaging techniques, we present a right-sided video-assisted thoracoscopic surgery segment 7 resection.

Essential Surgical Plan Modifications After Virtual Reality Planning in 50 Consecutive Segmentectomies.

BACKGROUND: Lately, increased interest in pulmonary segmentectomy has been observed. Segmental border identification is extremely difficult on 2-dimensional computed tomography (CT). Preoperative application of virtual reality (VR) can provide better insight into patient-specific anatomy. The aim of this study was to investigate the added clinical value of 3-dimensional (3D) VR using PulmoVR for preoperative planning. METHODS: Patients with an indication for pulmonary segmentectomy were included between June 2020 and September 2021 at the Erasmus Medical Center, Rotterdam, The Netherlands. CT scans were (semi)automatically segmented to visualize lung segments, segmental arteries, veins, and bronchi. Three surgeons made a surgical plan on the basis of the conventional CT scan and subsequently analyzed the VR visualization. The primary outcome was the incidence of critical (ensuring radical resection) preoperative plan modifications. Secondarily, data on observed anatomic variation and perioperative (oncologic) outcomes were collected. RESULTS: A total of 50 patients (median age at surgery, 65 years [interquartile range, 17.25 years]) with an indication for pulmonary segmentectomy were included. After supplemental VR visualization, the surgical plan was adjusted in 52%; the tumor was localized in a different segment in 14%, more lung-sparing resection was planned in 10%, and extended segmentectomy, including 1 lobectomy, was planned in 28%. Pathologic examination confirmed radical resection in 49 patients (98%). CONCLUSIONS: This 3D VR technology showed added clinical value in the first 50 VR-guided segmentectomies because a 52% change of plan with 98% radical resection was observed. Furthermore, 3D VR visualization of the bronchovasculature, including various anatomic variations, provided better insight into patient-specific anatomy and offered lung-sparing possibilities with more certainty.

Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study.

INTRODUCTION: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993. MATERIALS AND METHODS: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed. RESULTS: In total, 12 168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001). CONCLUSION: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.

Robotic Thymectomy for Thymomas: A Retrospective Follow-up Study in the Netherlands.

BACKGROUND: The Maastricht University Medical Center+ is a Dutch center of expertise appointed by the Netherlands Federation of University Medical Centers for the treatment of thymomas. The aim of this study was to investigate the long-term oncologic, surgical, and neurologic outcomes of all patients who underwent a robotic thymectomy for a thymoma at Maastricht University Medical Center+. METHODS: We retrospectively analyzed the clinical-pathologic data of all consecutive patients with a thymoma who underwent robotic thymectomy using the DaVinci robotic system at Maastricht University Medical Center+ between April 2004 and December 2018. Follow-up data were collected from 60 referring Dutch hospitals. RESULTS: In total, 398 robotic thymectomies were performed, and 130 thymomas (32.7%) were found. Median follow-up time was 46 months; median procedure time, 116 minutes; and median hospitalization time, 3 days. In 8.4% of patients, a conversion was performed, and in 20.8%, a complication was registered. The majority of myasthenic patients with a thymoma went into remission, mostly within 12 to 24 months after thymectomy (81%). No statistical difference was found in the number of complications, conversions, incomplete resections, or deaths between patients with myasthenia gravis and nonmyasthenic patients. Thirty-six patients (27.7%) underwent postoperative radiotherapy. The recurrence rate was 9.1%, and the 5-year thymoma-related survival rate was 96.6%. CONCLUSIONS: Robotic thymectomy was found to be safe and feasible for early stage thymomas, most advanced-stage thymomas, and thymomatous myasthenia gravis. A national guideline could contribute to the improvement of the oncologic follow-up of thymic epithelial tumors in the Netherlands.

Multidisciplinary Virtual Three-Dimensional Planning of a Forequarter Amputation With Chest Wall Resection.

We present the case of a 74-year-old man with a history of a squamous cell carcinoma in the left axilla. The patient underwent a multidisciplinary surgical resection through an extended forequarter amputation with thoracic wall resection and reconstruction. With regard to the complexity of the case, three-dimensional virtual reality-based patient-specific reconstructions were used as a supplemental tool to conventional computed tomography imaging to plan the procedure. With this report, we aim to stimulate further research to improve and automate the workflow and to bring virtual and augmented reality reconstructions into the surgical theater of the future.

Current and Future Applications of Virtual, Augmented, and Mixed Reality in Cardiothoracic Surgery.

BACKGROUND: This review aims to examine the existing literature to address currently used virtual, augmented, and mixed reality modalities in the areas of preoperative surgical planning, intraoperative guidance, and postoperative management in the field of cardiothoracic surgery. In addition this innovative technology provides future perspectives and potential benefits for cardiothoracic surgeons, trainees, and patients. METHODS: A targeted, nonsystematic literature assessment was performed within the Medline and Google Scholar databases to help identify current trends and to provide better understanding of the current state-of-the-art extended reality (XR) modalities in cardiothoracic surgery. Related articles published up to July 2020 were included in the review. RESULTS: XR is a novel technique gaining increasing application in cardiothoracic surgery. It provides a 3-dimensional and realistic view of structures and environments and offers the user the ability to interact with digital projections of surgical targets. Recent studies showed the validity and benefits of XR applications in cardiothoracic surgery. Examples include XR-guided preoperative planning, intraoperative guidance and navigation, postoperative pain and rehabilitation management, surgical simulation, and patient education. CONCLUSIONS: XR is gaining interest in the field of cardiothoracic surgery. In particular there are promising roles for XR applications in televirtuality, surgical planning, surgical simulation, and perioperative management. However future refinement and research are needed to further implement XR in the aforementioned settings within cardiothoracic surgery.

Optimal delineation of the clinical target volume for thymomas in the post-resection setting: A multi-center study.

BACKGROUND: The definition of the clinical target volume (CTV) for post-operative radiotherapy (PORT) for thymoma is largely unexplored. The aim of this study was to analyze the difference in CTV delineation between radiation oncologists (RTO) and surgeons. METHODS: This retrospective multi-center study enrolled 31 patients who underwent PORT for a thymoma from five hospitals. Three CTVs were delineated per patient: one CTV by the RTO, one CTV by the surgeon (blinded to the results of the RTO) and a joint CTV after collaboration. Volumes (cm3), Hausdorff distances (HD) and Dice similarity coefficients (DSC) were analyzed. RESULTS: RTO delineated significantly bigger CTVs than surgeons (mean: 93.9 ± 63.1, versus 57.9 ± 61.3 cm3, p = 0.003). Agreement was poor between RO and surgeons, with a low mean DSC (0.34 ± 0.21) and high mean HD of 4.5 (±2.2) cm. Collaborative delineation resulted in significantly smaller volumes compared to RTO (mean 57.1 ± 58.6 cm3, p < 0.001). A mean volume of 18.9 (±38.1) cm3 was included in joint contours, but missed by RTO. Conversely, a mean volume of 55.7 (±39.9) cm3 was included in RTO's delineations, but not in the joint delineations. CONCLUSIONS: To the best of our knowledge, this is the first study investigating CTV definition in thymoma. We demonstrated a significant variability between RTO and surgeons. Joint delineation prompted revisions in smaller CTV as well as favoring the surgeons' judgement, suggesting that surgeons provided relevant insight into other risk areas than RTO. We recommend a multidisciplinary approach to PORT for thymomas in clinical practice.

Ki67 (MIB-1) as a Prognostic Marker for Clinical Decision Making Before Extended Pleurectomy Decortication in Malignant Pleural Mesothelioma.

INTRODUCTION: The role of surgery for early stage malignant pleural mesothelioma (MPM) remains controversial. Current expert opinion is only to treat patients surgically as part of multimodality therapy. It is still challenging to identify patients who will not benefit from surgery. We specifically evaluated tumor-related parameters in combination with clinical parameters to identify prognostic markers for survival. METHODS: Clinical data of 27 consecutive patients with MPM treated with extended pleurectomy and decortication within a multimodality approach were collected and analyzed. Several tumor (immuno-)histopathologic characteristics were determined on resected tumor material, among which MTAP and Ki67 (MIB-1). Univariable and multivariable analyses served to correlate clinical and tumor-related parameters to overall survival (OS) and progression-free survival (PFS). RESULTS: The median PFS (mPFS) was 15.3, and the median OS (mOS) was 26.5 months. Patients with a Ki67 score greater than 10% had a significantly shorter PFS (mPFS = 8.81 versus 25.35 mo, p = 0.001) and OS (mOS 19.7 versus 44.5 mo, p = 0.002) than those with a Ki67 score less than or equal to 10. Receiver operating characteristic curve analysis for Ki67 revealed an area under the curve of 0.756 with a sensitivity of 90% and specificity of 71% for a cutoff of 10% for Ki67. Patients with loss of MTAP had a significantly shorter mPFS (9 versus 21.1 mo, p = 0.014) and mOS (19.7 versus 42.6 mo, p = 0.047) than those without MTAP loss. CONCLUSIONS: In our study, Ki67 was prognostic for OS and PFS in patients with MPM treated with extended pleurectomy/decortication in a multimodality approach. Determination of Ki67 before surgery combined with specific clinical parameters could assist in clinical decision making by identifying patients, with high Ki67, who are unlikely to benefit from surgery.

Defining oligometastatic non-small cell lung cancer: concept versus biology, a literature review.

OBJECTIVE: In this review, the concept of (synchronous) oligometastatic disease in patients with non-oncogene-driven non-small cell lung cancer (NSCLC) will be placed in the context of tumor biology and metastatic growth patterns. We will also provide considerations for clinical practice and future perspectives, which will ultimately lead to better patient selection and oligometastatic disease outcome. BACKGROUND: The treatment landscape of metastasized NSCLC has moved from "one-size fits all" to a personalized approach. Prognosis has traditionally been poor but new treatment options, such as immunotherapy and targeted therapy, brighten future perspectives. Another emerging development is the recognition of patients with so-called "oligometastatic" state of disease. Oligometastatic disease has been recognized as a distinct clinical presentation in which the tumor is stated to be early in its evolution of metastatic potential. It is suggested that this stage of disease has an indolent course, comes with a better prognosis and therefore could be considered for radical multimodality treatment. METHODS: Narrative overview of the literature synthesizing the findings of literature retrieved from searches of computerized databases, hand searches, and authoritative texts. CONCLUSIONS: Oligometastatic NSCLC is a broad spectrum disease, with a variable prognosis. Although the biology and behavior of "intermediate state" of metastatic disease are not fully understood, there is evidence that a subgroup of patients can benefit from local radical treatment when integrated into a multimodality regime. The consensus definition of oligometastatic NSCLC, including accurate staging, may help to uniform future trials. The preferable treatment strategy seems to sequential systemic treatment with subsequent local radical treatment in patients with a partial response or stable disease. Prognostic factors such as N-stage, number and site of distant metastases, tumor volume, performance status, age, and tumor type should be considered. The local radical treatment strategy has to be discussed in a multidisciplinary team meeting, taking into account patient characteristics and invasiveness of the procedure. However, many aspects remain to be explored and learned about the cancer biology and characteristics of intermediate state tumors.

Virtual reality and artificial intelligence for 3-dimensional planning of lung segmentectomies.

BACKGROUND: There has been an increasing trend toward pulmonary segmentectomies to treat early-stage lung cancer, small intrapulmonary metastases, and localized benign pathology. A complete preoperative understanding of pulmonary anatomy is essential for accurate surgical planning and case selection. Identifying intersegmental divisions is extremely difficult when performed on computed tomography. For the preoperative planning of segmentectomies, virtual reality (VR) and artificial intelligence could allow 3-dimensional visualization of the complex anatomy of pulmonary segmental divisions, vascular arborization, and bronchial anatomy. This technology can be applied by surgeons preoperatively to gain better insight into a patient's anatomy for planning segmentectomy. METHODS: In this prospective observational pilot study, we aim to assess and demonstrate the technical feasibility and clinical applicability of the first dedicated artificial intelligence-based and immersive 3-dimensional-VR platform (PulmoVR; jointly developed and manufactured by Department of Cardiothoracic Surgery [Erasmus Medical Center, Rotterdam, The Netherlands], MedicalVR [Amsterdam, The Netherlands], EVOCS Medical Image Communication [Fysicon BV, Oss, The Netherlands], and Thirona [Nijmegen, The Netherlands]) for preoperative planning of video-assisted thoracoscopic segmentectomies. RESULTS: A total of 10 eligible patients for segmentectomy were included in this study after referral through the institutional thoracic oncology multidisciplinary team. PulmoVR was successfully applied as a supplementary imaging tool to perform video-assisted thoracoscopic segmentectomies. In 40% of the cases, the surgical strategy was adjusted due to the 3-dimensional-VR-based evaluation of anatomy. This underlines the potential benefit of additional VR-guided planning of segmentectomy for both surgeon and patient. CONCLUSIONS: Our study demonstrates the successful development and clinical application of the first dedicated artificial intelligence and VR platform for the planning of pulmonary segmentectomy. This is the first study that shows an immersive virtual reality-based application for preoperative planning of segmentectomy to the best of our knowledge.

Epipleural surgical block and ultrasound-guided erector spinae plane block for analgesia in VATS

Thoracic surgery is still associated with severe postoperative pain. In this video tutorial, we present 2 techniques that could be used as an additional method in a multimodal postoperative analgesia strategy for video-assisted thoracic surgery. We present the combination of an epipleural surgical infiltration of a local anesthetic with an ultrasound-guided erector spinae plane block.

Incidence of end-stage renal disease after heart transplantation and effect of its treatment on survival.

AIMS: Many heart transplant recipients will develop end-stage renal disease in the post-operative course. The aim of this study was to identify the long-term incidence of end-stage renal disease, determine its risk factors, and investigate what subsequent therapy was associated with the best survival. METHODS AND RESULTS: A retrospective, single-centre study was performed in all adult heart transplant patients from 1984 to 2016. Risk factors for end-stage renal disease were analysed by means of multivariable regression analysis and survival by means of Kaplan-Meier. Of 685 heart transplant recipients, 71 were excluded: 64 were under 18 years of age and seven were re-transplantations. During a median follow-up of 8.6 years, 121 (19.7%) patients developed end-stage renal disease: 22 received conservative therapy, 80 were treated with dialysis (46 haemodialysis and 34 peritoneal dialysis), and 19 received a kidney transplant. Development of end-stage renal disease (examined as a time-dependent variable) inferred a hazard ratio of 6.45 (95% confidence interval 4.87-8.54, P < 0.001) for mortality. Tacrolimus-based therapy decreased, and acute kidney injury requiring renal replacement therapy increased the risk for end-stage renal disease development (hazard ratio 0.40, 95% confidence interval 0.26-0.62, P < 0.001, and hazard ratio 4.18, 95% confidence interval 2.30-7.59, P < 0.001, respectively). Kidney transplantation was associated with the best median survival compared with dialysis or conservative therapy: 6.4 vs. 2.2 vs. 0.3 years (P < 0.0001), respectively, after end-stage renal disease development. CONCLUSIONS: End-stage renal disease is a frequent complication after heart transplant and is associated with poor survival. Kidney transplantation resulted in the longest survival of patients with end-stage renal disease.

Immersive 3D virtual reality imaging in planning minimally invasive and complex adult cardiac surgery.

Aims: Increased complexity in cardiac surgery over the last decades necessitates more precise preoperative planning to minimize operating time, to limit the risk of complications during surgery and to aim for the best possible patient outcome. Novel, more realistic, and more immersive techniques, such as three-dimensional (3D) virtual reality (VR) could potentially contribute to the preoperative planning phase. This study shows our initial experience on the implementation of immersive VR technology as a complementary research-based imaging tool for preoperative planning in cardiothoracic surgery. In addition, essentials to set up and implement a VR platform are described. Methods: Six patients who underwent cardiac surgery at the Erasmus Medical Center, Rotterdam, The Netherlands, between March 2020 and August 2020, were included, based on request by the surgeon and availability of computed tomography images. After 3D VR rendering and 3D segmentation of specific structures, the reconstruction was analysed via a head mount display. All participating surgeons (n = 5) filled out a questionnaire to evaluate the use of VR as preoperative planning tool for surgery. Conclusion: Our study demonstrates that immersive 3D VR visualization of anatomy might be beneficial as a supplementary preoperative planning tool for cardiothoracic surgery, and further research on this topic may be considered to implement this innovative tool in daily clinical practice. Lay summary: Over the past decades, surgery on the heart and vessels is becoming more and more complex, necessitating more precise and accurate preoperative planning. Nowadays, operative planning is feasible on flat, two-dimensional computer screens, however, requiring a lot of spatial and three-dimensional (3D) thinking of the surgeon. Since immersive 3D virtual reality (VR) is an upcoming imaging technique with promising results in other fields of surgery, we aimed in this study to explore the additional value of this technique in heart surgery. Our surgeons planned six different heart operations by visualizing computed tomography scans with a dedicated VR headset, enabling them to visualize the patient's anatomy in an immersive and 3D environment. The outcomes of this preliminary study are positive, with a much more reality-like simulation for the surgeon. In such, VR could potentially be beneficial as a preoperative planning tool for complex heart surgery.

Multicenter Phase II Clinical Trial of Isolated Lung Perfusion in Patients With Lung Metastases.

BACKGROUND: Up to 66% of patients show local pulmonary disease progression after pulmonary metastasectomy. Regional treatment with isolated lung perfusion (ILuP) may improve local control with minimal systemic adverse effects. The aims of this study were to evaluate local and distant control after ILuP, determine the effect on overall survival compared with historical controls, and confirm the safety and feasibility of ILuP. METHODS: A total of 107 patients with resectable pulmonary metastases of colorectal carcinoma, osteosarcoma, and soft-tissue sarcoma were included in a prospective phase II study of pulmonary metastasectomy combined with ILuP with 45 mg melphalan at 37°C. Local and distant control, overall survival, lung function, and 90-day mortality and morbidity were monitored. RESULTS: We report 0% mortality, low morbidity, and no long-term pulmonary toxicity. For colorectal carcinoma, median time to local pulmonary progression, median time to progression, and median survival time were 31, 14, and 78 months, respectively. Median time to local progression was not reached for sarcoma, whereas median time to progression and median survival time were 13 and 39 months, respectively. The 5-year disease-free rate and pulmonary progression-free rate were 26% and 44% for colorectal carcinoma and 29% and 63% for sarcoma, respectively. CONCLUSIONS: ILuP with melphalan combined with metastasectomy is feasible and safe. Compared with historical controls, favorable results were obtained in this phase II study for local control. Further evaluation of locoregional lung perfusion techniques with other chemotherapeutic drugs is warranted.

Acute Pump Thrombosis in the Early Postoperative Period After HeartMate 3 Implantation.

There are no reports of acute pump thrombosis in the latest, continuous flow left ventricular assist devices type HeartMate 3, other than thrombus ingestion. We present a case of early thrombosis of the pump and outflow graft, necessitating acute pump and outflow graft replacement. A combination of low-flow episodes and subtherapeutic levels of anticoagulation was the most likely cause.

18F-FDG PET/CT in the Diagnosis and Management of Continuous Flow Left Ventricular Assist Device Infections: A Case Series and Review of the Literature.

Implantable continuous flow left ventricular assist devices (LVADs) are increasingly used in end-stage heart failure treatment as a bridge-to-transplant and destination therapy (DT). However, LVADs still have major drawbacks, such as infections that can cause morbidity and mortality. Unfortunately, appropriate diagnosis of LVAD-related and LVAD-specific infections can be very cumbersome. The differentiation between deep and superficial infections is crucial in clinical decision-making. Despite a decade of experience in using fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) to diagnose various infections, its use in LVAD patients remains scarce. In this case series, we review the current evidence in literature and describe our single center experience using F-FDG PET/CT for the diagnosis and management of LVAD infections.