In cancer surgery, intra-operative assessment of the tumor-free margin, which is critical for the prognosis of the patient, relies on the visual appearance and palpation of the tumor. Optical imaging techniques provide real-time visualization of the tumor, warranting intra-operative image-guided surgery. Within this field, imaging in the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-to-background-ratio of contrast agents. In this article, we review the various techniques, contrast agents, and camera systems that are currently used for image-guided surgery. Furthermore, we provide an overview of the wide range of molecular contrast agents targeting specific hallmarks of cancer and we describe perspectives on its future use in cancer surgery.

Optical image-guided cancer surgery is a promising technique to adequately determine tumor margins by tumor-specific targeting, potentially resulting in complete resection of tumor tissue with improved survival. However, identification of the photons coming from the fluorescent contrast agent is complicated by autofluorescence, optical tissue properties, and accurate fluorescent targeting agents and imaging systems. All these factors have an important influence on the image that is presented to the surgeon. Considering the clinical consequences at stake, it is a prerequisite to answer the questions that are essential for the surgeon. What is optical image-guided surgery and how can it improve patient care? What should the oncologic surgeon know about the fundamental principles of optical imaging to understand which conclusions can be drawn from the images? And how do the limitations influence clinical decision making? This article discusses these questions and provides a clear overview of the basic principles and practical applications. Although there are limitations to the intrinsic capacity of the technique, when practical and technical surgical possibilities are considered, optical imaging can be a very powerful intraoperative tool in guiding the future oncologic surgeon toward radical resection and optimal clinical results.

A key aspect for the postoperative prognosis of patients with head and neck cancer is complete tumor resection. In current practice, the intraoperative assessment of the tumor-free margin is dependent on visual appearance and palpation of the tumor. Optical imaging has the potential of traversing the gap between radiology and surgery by providing real-time visualization of the tumor, thereby allowing for image-guided surgery. The use of the near-infrared light spectrum offers 2 essential advantages: increased tissue penetration of light and an increased signal-to-background ratio of contrast agents. In this review, the current practice and limitations of image-guided surgery by optical imaging using intrinsic fluorescence or contrast agents are described. Furthermore, we provide an overview of the various molecular contrast agents targeting specific hallmarks of cancer that have been used in other fields of oncologic surgery, and we describe perspectives on its future use in head and neck cancer surgery.

Objective: In humans, antenatal alcohol exposure elicits various developmental disorders, in particular in the brain. Numerous studies focus on the deleterious effects of alcohol on neural cells. Although recent studies suggest that alcohol can affect angiogenesis in adults, the impact of prenatal alcohol exposure on brain microvasculature remains poorly understood. Methods: We used a mouse model to investigate effects of prenatal alcohol exposure on the cortical microvascular network in vivo and ex vivo and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF) on activity, plasticity, and survival of microvessels. We used quantitative reverse transcriptase polymerase chain reaction, Western blot, immunohistochemistry, calcimetry, and videomicroscopy. We characterized the effect of prenatal alcohol exposure on the cortical microvascular network in human controls and fetal alcohol syndrome (FAS)/partial FAS (pFAS) patients at different developmental stages. Results: In mice, prenatal alcohol exposure induced a reduction of cortical vascular density, loss of the radial orientation of microvessels, and altered expression of VEGF receptors. Time‐lapse experiments performed on brain slices revealed that ethanol inhibited glutamate‐induced calcium mobilization in endothelial cells, affected plasticity, and promoted death of microvessels. These effects were prevented by VEGF. In humans, we evidenced a stage‐dependent alteration of the vascular network in the cortices of fetuses with pFAS/FAS. Whereas no modification was observed from gestational week 20 (WG20) to WG22, the radial organization of cortical microvessels was clearly altered in pFAS/FAS patients from WG30 to WG38. Interpretation: Prenatal alcohol exposure affects cortical angiogenesis both in mice and in pFAS/FAS patients, suggesting that vascular defects contribute to alcohol‐induced brain abnormalities. Ann Neurol ANN NEUROL 2012;72:952–960

To examine the relationship between bronchial hyperresponsiveness (BHR) and respiratory symptoms associated with asthma, we studied a sample of 380 schoolchildren on three occasions at 2-yr intervals. The age of the children at the first study was 8-10 yr. Respiratory symptoms history was assessed by questionnaire, BHR was measured by a histamine inhalation test and atopy was assessed by skin-prick tests to 13 allergens. The cumulative prevalence of BHR in this sample was 27%. The severity of BHR was categorized as severe, moderate, mild or slight. The distribution of severe, moderate and mild BHR was similar at each of the studies. At the third study, when the children were aged 12-14 yr, the prevalence of slight BHR decreased. Children with severe or moderate BHR at age 8-10 yr were atopic, reported current symptoms during the 4 yr of the study and had a high prevalence of severe or moderate BHR in later studies. In this group, 87% of children had current respiratory symptoms and 73% were using asthma medication at age 12-14 yr. In children with mild or slight BHR when first studied, the prevalence of atopy, continuing respiratory symptoms and medication use was much lower. We conclude that severe or moderate BHR is an important risk factor for ongoing morbidity and that comparisons of the prevalence of this severity of BHR in populations may be more informative than comparisons of BHR defined by present criteria.

Objective:  To analyse different treatment strategies and treatment results of hypopharyngeal carcinoma in the Netherlands. Design:  Retrospective study. Setting:  Eight head and neck centres in the Netherlands. Participants:  A total of 893 patients were treated between 1985 and 1994. Patients were mostly treated with radiotherapy alone, combined surgery and radiotherapy and surgery alone. Results:  The 5‐year survival for the whole group was 26%. The 5‐year survival for patients treated with curative intention was 32% and treated with palliative intention was 5%. The 5‐year disease‐free survival after radiotherapy alone was 37%, after surgery alone 41% and after combined therapy 47%. The role of chemotherapy could not be investigated because of a small number of patients treated with chemotherapy in this period. Conclusion:  Combined therapy with surgery and radiotherapy has a better survival for patients with a hypopharyngeal carcinoma in comparison with radiotherapy alone. The N‐stage is more important for the prognosis than the T‐stage.

Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.

No abstract