Intraoperative Assessment of Tumor Resection Margins in Breast-Conserving Surgery Using 18F-FDG Cerenkov Luminescence Imaging: A First-in-Human Feasibility Study.

In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by 18F-FDG. Its high-resolution and small size imaging equipment make CLI a promising technology for intraoperative margin assessment. A first-in-human study was conducted to evaluate the feasibility of 18F-FDG CLI for intraoperative assessment of tumor margins in BCS. Methods: Twenty-two patients with invasive breast cancer received 18F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased 99mTc-nanocolloid activity of 150 MBq to facilitate nodal detection against the γ-probe background signal (cross-talk) from 18F-FDG. The cross-talk and 99mTc dose required was evaluated in 2 lead-in studies. Immediately after excision, specimens were imaged intraoperatively in an investigational CLI system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 patients were included in the analysis dataset. Cerenkov luminescence images from incised BCS specimens were analyzed postoperatively by 2 surgeons blinded to the histopathology results, and mean radiance and margin distance were measured. The agreement between margin distance on CLI and histopathology was assessed. Radiation doses to staff were measured. Results: Ten of the 12 patients had an elevated tumor radiance on CLI. Mean radiance and tumor-to-background ratio were 560 ± 160 photons/s/cm2/sr and 2.41 ± 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (κ = 0.81 and 0.912, respectively). Sentinel lymph nodes were successfully detected in all patients. The radiation dose to staff was low; surgeons received a mean dose of 34 ± 15 µSv per procedure. Conclusion: Intraoperative 18F-FDG CLI is a promising, low-risk technique for intraoperative assessment of tumor margins in BCS. A randomized controlled trial will evaluate the impact of this technique on reexcision rates.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.

A computerized gamma probe simulator to train surgeons in the localization of sentinel nodes.

BACKGROUND: The technique of sentinel node biopsy (SNB) may be used as a staging technique for cancer patients. SNB involves the localization of lymph nodes that have accumulated a radioactive tracer, and this requires surgeons to gain and demonstrate skills in the use of hand-held radiation detectors (gamma probes). METHODS: A computerized gamma probe simulator (GAPS) has been developed as a training tool to provide realistic simulations of the clinical distribution of radioactivity, without the use of radioactive materials, and a realistic simulation of the count rate response from a gamma probe. Electromagnetic spatial tracking of the surgeon's movement of the probe allows objective assessment of the user's accuracy in localizing a virtual sentinel node. The physical accuracy of the simulation has been validated, with a spatial accuracy of (0.06 mm), and a count rate error of 0.28%. RESULTS: The GAPS has been used in the training of 94 breast surgeons, with a mean error node localization of 3.8 mm (range, 0.1-16 mm) and a mean search time of 131 s (range 36-314 s), showing that objective feedback on performance can be given by the system. Modification to train for other sentinel node applications is simple, and the system has been used for training in the application of penile sentinel node surgery. CONCLUSION: A computerized gamma probe simulator has been developed which provides realistic training tasks for surgeons in sentinel node biopsy, with a wide range of simulated clinical cases, allowing the objective assessment of a trainee's performance in the use of a hand-held gamma probe without the use of radioactive sources.

Repeat planar white cell scanning to monitor short-term therapy of active inflammatory bowel disease: a methodological study and comparison with clinical scores and novel inflammatory markers.

OBJECTIVES: Radiolabelled white cell scans provide non-invasive quantification of inflammatory activity. Clinical activity scores measure severity of disease but are partly subjective. White cell scans may provide a suitable method of monitoring the treatment response of active inflammatory bowel disease. METHODS: Ten subjects with active ulcerative colitis and 13 subjects with active Crohn's disease were recruited. White cell scans were carried out before and 2 weeks after treatment. Prior to each scan, activity scores for ulcerative colitis or Crohn's disease were calculated and serum and faecal tumour necrosis factor-alpha and calprotectin measured. White cell scan activity at 1 h was calculated by using a validated visual grading system. RESULTS: Following anti-inflammatory treatment, 70% of white cell scans improved, 17% remained unchanged and 13% deteriorated. In the ulcerative colitis subgroup subjects there was modest agreement for change in scan score and activity scores. In the Crohn's disease subjects there was better agreement between change of white cell scan score and clinical scores. Planar white cell scans correlated with the van Hees activity index (r=0.68, P=0.002) and faecal calprotectin (r=0.58, P=0.0003). Changes in planar white cell scans correlated with changes in serum calprotectin (r=0.45, P=0.05). CONCLUSION: Non-invasive white cell scanning is a feasible and objective method to monitor the anti-inflammatory efficacy of treatments for active inflammatory bowel disease.