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.

Carcinoembryonic antigen-specific, fluorescent image-guided cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer.

This multicentre pilot study investigated the role of peroperative carcinoembryonic antigen (CEA)-specific fluorescence imaging during cytoreductive surgery-hyperthermic intraperitoneal chemotherapy surgery in peritoneal metastasized colorectal cancer. A correct change in peritoneal carcinomatosis index (PCI) owing to fluorescence imaging was seen in four of the 14 included patients. The use of SGM-101 in patients with peritoneally metastasized colorectal carcinoma is feasible, and allows intraoperative detection of tumour deposits and alteration of the PCI. Augmented reality guidance.

Evaluation of the diagnostic work-up in children with myocarditis and idiopathic dilated cardiomyopathy.

The underlying etiology of dilated cardiomyopathy (DCM) in children varies, 14-22% is secondary to myocarditis, and the majority remains idiopathic. Etiology has prognostic value; however, 'a clinical diagnosis of myocarditis' has been frequently used because the gold standard [endomyocardial biopsy (EMB)] is often not performed. Therefore, a consistent diagnostic approach and interpretation is needed. In this multicenter study, we evaluated the diagnostic approach and interpretation of the viral results in children with myocarditis and idiopathic DCM. We included 150 children with DCM, of whom 103 were assigned the diagnosis myocarditis (n = 21) or idiopathic DCM (n = 82) by the attending physician. Viral tests were performed in 97/103 patients, in only 34% (n = 35) some of the tests were positive. Of those patients, we evaluated the probability of the assigned diagnosis using the viral test results. We classified viral test results as reflecting definite or probable myocarditis in 14 children and possible or unlikely myocarditis in 21 children. Based on this classification, 23% of patients were misclassified. We found that in children with DCM, the diagnostic approach varied and the interpretation was mainly based on viral results. Since a 'clinical diagnosis of myocarditis' has been frequently used in daily practice because of the lack of EMB results, a uniform protocol is needed. We propose to use viral test results in several steps (blood PCR, serology, PCR and/or cultures of the gastro-intestinal and respiratory tract, and EMB results) to estimate the probability of myocarditis.

Unstable fragility fractures of the ankle in the elderly: Transarticular Steinmann pin or external fixation.

INTRODUCTION: Because of poor skin conditions and comorbidity, open reduction and internal fixation in ankle fractures is frequently contra-indicated in the elderly. This study reports the results of two temporary fixation types in fragility fractures in the older patient: transarticular Steinmann pin fixation and external fixation. METHODS: Patients aged over 60 treated with a Steinmann pin or external fixation were retrospectively included. Patient, fracture and treatment characteristics were collected. RESULTS: Fifteen patients were included. Nine were managed using a Steinmann pin and six by external fixation. All reached fracture consolidation. Patients treated with a Steinmann pin underwent a median of 2 operations and the pin was left in situ for 80 days. Three patients suffered from superficial wound infection. X-ray showed malreduction in 67% and only two patients returned to pre-injury mobility. A median of 2 operations with 32 fixation days was reported in the external fixation group. This group showed one deep infection. In 50% there was malreduction, one patient experienced disability in ambulation at the end of treatment. CONCLUSION: Both techniques show few complications, but have, as expected, poor results in fracture reduction and functional outcome. External fixation and subsequent internal fixation could result in better functional outcome.