David R. Colnot

Clinical Significance of Micrometastatic Cells Detected by E48 (Ly-6D) Reverse Transcription-Polymerase Chain Reaction in Bone Marrow of Head and Neck Cancer Patients

Purpose: Despite improvements in locoregional treatment of head and neck squamous cell carcinoma (HNSCC), local and distant failure rates remain high. The strongest prognostic indicator of HNSCC is the presence of lymph node metastases in the neck, but the value of this indicator has limitations when using for the individual patient. The presence of micrometastatic cells in bone marrow has been shown to be a putative prognostic indicator in HNSCC and other epithelial malignancies, which might allow more accurate staging and selection of patients for whom adjuvant or experimental therapy is recommended. The gene encoding the E48 antigen is selectively expressed by HNSCC, and the detection of E48 transcripts in bone marrow by reverse transcription-polymerase chain reaction (RT-PCR) presumably represents the presence of micrometastatic cells. The purpose of this study was to determine the association between the presence of micrometastatic cells in bone marrow of HNSCC patients and clinical outcome. Experimental Design: A total of 162 patients treated surgically for primary HNSCC underwent a single bone marrow aspiration from the upper iliac crest for detection of micrometastatic cells using E48 RT-PCR. In total, 139 patients were evaluable. The primary statistical endpoints were disease-free survival and distant metastasis-free survival. In addition, bone marrow samples of 30 noncancer controls were evaluated. Results: E48 RT-PCR indicated the presence of micrometastatic cells in the bone marrow in 56 of 139 (40%) of the HNSCC patients and 0 of 30 of the noncancer controls (P < 0.0001). The presence of micrometastatic cells had no significant influence on disease-free survival or distant metastasis-free survival for the whole group of HNSCC patients (P = 0.1460 and P = 0.2912, respectively). For patients with ≥2 lymph node metastases, however, the presence of micrometastatic cells was associated with a poor distant metastasis-free survival (P = 0.0210). Conclusions: The presence of micrometastatic cells in bone marrow of HNSCC patients with ≥2 lymph node metastases is correlated with a poor distant metastasis-free survival. In this subgroup of HNSCC patients, E48 RT-PCR seems to be a valuable tool to identify patients who are at increased risk for development of distant metastases and therefore might benefit from experimental adjuvant systemic therapy.

Lymphoscintigraphy and Ultrasound Guided Fine Needle Aspiration Cytology of Sentinel Lymph Nodes in Head and Neck Cancer Patients

Accurate staging of the regional lymph nodes is crucial for the appropriate management of patients with squamous cell carcinoma of the head and neck (HNSCC). However, the current diagnostic modalities have low accuracy for N0 neck, and even the most optimal procedure, ultrasound-guided fine needle aspiration cytology (USgFNAC), still has a sensitivity of only 42%-73%. In this study we evaluated whether the identification of the sentinel node might improve the selection of lymph nodes for USgFNAC. Twelve HNSCC patients received 3-4 peritumoral injections of 10-30 MBq 99mTc-labeled colloidal albumin, and the sentinel node was identified by dynamic scintigraphy and marked on the skin using a handheld probe, and/or by scintillation counting of the aspirates. After sentinel node identification USgFNAC was performed. Correct aspiration of the identified sentinel node(s) was confirmed by scintillation counting. In 11 out of 12 cases the sentinel node(s) could be visualized by dynamic planar imaging. In one case the sentinel node(s) were identified by scintillation counting only. In a number of patients different or supplementary lymph nodes were aspirated on the basis of sentinel node identification. These initial data strongly suggest that sentinel node identification might improve the staging of the neck by USgFNAC.

Mastoid obliteration with S53P4 bioactive glass in cholesteatoma surgery

Abstract Conclusion: Evaluation of the follow-up of 67 patients shows that S53P4 bioactive glass (BAG) granules are safe and effective as obliteration material in cholesteatoma surgery. Objectives: To investigate the safety and efficacy of mastoid obliteration using S53P4 BAG in cholesteatoma surgery. Clinical outcomes were infection control (Merchant’s grading), cholesteatoma recidivism, and audiometric performance. Methods: Retrospective follow-up study at the Diakonessenhuis, Utrecht, the Netherlands. Eighteen young (age <17 years) and 49 adult (age ≥17 years) patients treated for cholesteatoma underwent tympanomastoidectomy with mastoid obliteration using S53P4 BAG in the period 2012–2015. Outcome was monitored with clinical otoscopy, otorrhea incidence measurement (Merchant’s grading), DW-MRI, and audiographic performance analyses (pure tone average and air bone gap). Results: During the follow-up period (mean = 22 months; range = 12–54 months) cholesteatoma recidivism was observed in 6% of the patients (four ears), mostly in young patients (three ears). An acceptably dry ear (Merchant grade 0–1) was achieved in 96% of all cases. The remaining 4% of cases scored a Merchant grade 2. Overall, both air conduction thresholds and air bone gap were slightly lowered when comparing post-operative values to pre-operative values and significantly in the case of ossicular reconstruction. In none of the patients (0%) did post-operative wound infections occur.

Chapter 14:Bioactive Glasses in Infection Treatment

Bone infection, whether acute or chronic, is a difficult-to-treat condition that may result from a large number of pathogens, often including multi-resistant strains. Bioactive glass S53P4 (BAG-S53P4) has been shown to inhibit bacterial growth and bacterial biofilm formation in vitro. The bacterial growth-inhibiting properties of BAG-S53P4 stem partly from the release of ions (sodium, calcium, phosphate, and silicate) in aqueous conditions and the elevation of pH and osmotic pressure in the environment. The use of BAG-S53P4 in head and neck surgery to treat chronically infected sinus and mastoid cavities has shown excellent results. More recently, investigations of the use of BAG-S53P4 in treating chronic bone infections in orthopaedics and trauma have also yielded promising results. To date, bioactive glass is the only medical device specifically approved for the treatment of bone defects in osteomyelitis without requiring the application of local antibiotics.

Bradycardia in Children During General Anaesthesia

Bradycardia in association with anaesthesia may lead to insufficient cardiac output and decreased delivery of oxygen to vital organs. In children the heart rate is the dominant factor for cardiac output, since the developing heart is less compliant and contractile and stroke volume cannot increase much. Thus, when bradycardia occurs in children during anaesthesia, cardiac output falls and may lead to serious cardiac arrhythmias and even cardiac arrest. In this chapter, the incidence, causes and risk factors, as well as the consequences and possible treatment of bradycardia in children during general anaesthesia are described and discussed. A focus is made on the incidence and causes of bradycardia in children undergoing adenotonsillectomy under general anaesthesia.