Marius Bredell

Sentinel lymph node mapping by indocyanin green fluorescence imaging in oropharyngeal cancer - preliminary experience

BackgroundSentinel lymph node (SLN) detection and biopsy is gaining popularity in the treatment of Head and Neck cancer. Various methods in this regard have been described, each with their respective advantages and disadvantages. The aim of this paper was to evaluate the potential application of Indocyanin Green (ICG) in the mapping and detection of sentinel lymph nodes (SLN) in cancers of the head and neck.MethodsPatients with oropharyngeal cancer and N0 neck who were scheduled for primary tumor ablation as well as a neck dissection were selected. One milliliter of Indocyanin green was injected around the tumor and the sentinel node detection was performed by aiming the infra red video camera on the cervical area. When no detection was possible transcutaneously, a cervical incision was made, a sub-platysmal flap raised and further detection was done to visualize the fluorescing lymph nodes.ResultsDetection of cervical SLN was only possible when 5 mm or less tissue covered the sentinel lymph node. Accurate and clear detection of the lymph drainage pattern and SLN was possible. There is some uptake in other tissues such as the submandibular gland which is easily distinguishable from lymphatic tissue.ConclusionIndocyanin green fluorescence is a potential valuable potential tool in the detection of SLN in patients with oropharyngeal cancer which warrants further investigation.

Uptake and fate of surface modified silica nanoparticles in head and neck squamous cell carcinoma.

BackgroundHead and neck squamous cell carcinoma (HNSCC) is currently the eighth leading cause of cancer death worldwide. The often severe side effects, functional impairments and unfavorable cosmetic outcome of conventional therapies for HNSCC have prompted the quest for novel treatment strategies, including the evaluation of nanotechnology to improve e.g. drug delivery and cancer imaging. Although silica nanoparticles hold great promise for biomedical applications, they have not yet been investigated in the context of HNSCC. In the present in-vitro study we thus analyzed the cytotoxicity, uptake and intracellular fate of 200-300 nm core-shell silica nanoparticles encapsulating fluorescent dye tris(bipyridine)ruthenium(II) dichloride with hydroxyl-, aminopropyl- or PEGylated surface modifications (Ru@SiO2-OH, Ru@SiO2-NH2, Ru@SiO2-PEG) in the human HNSCC cell line UMB-SCC 745.ResultsWe found that at concentrations of 0.125 mg/ml, none of the nanoparticles used had a statistically significant effect on proliferation rates of UMB-SCC 745. Confocal and transmission electron microscopy showed an intracellular appearance of Ru@SiO2-OH and Ru@SiO2-NH2 within 30 min. They were internalized both as single nanoparticles (presumably via clathrin-coated pits) or in clusters and always localized to cytoplasmic membrane-bounded vesicles. Immunocytochemical co-localization studies indicated that only a fraction of these nanoparticles were transferred to early endosomes, while the majority accumulated in large organelles. Ru@SiO2-OH and Ru@SiO2-NH2 nanoparticles had never been observed to traffic to the lysosomal compartment and were rather propagated at cell division. Intracellular persistence of Ru@SiO2-OH and Ru@SiO2-NH2 was thus traceable over 5 cell passages, but did not result in apparent changes in cell morphology and vitality. In contrast to Ru@SiO2-OH and Ru@SiO2-NH2 uptake of Ru@SiO2-PEG was minimal even after 24 h.ConclusionsOur study is the first to provide evidence that silica-based nanoparticles may serve as useful tools for the development of novel treatment options in HNSCC. Their long intracellular persistence could be of advantage for e.g. chronic therapeutic modalities. However, their complex endocytotic pathways require further investigations.

Splintless orthognathic surgery: A novel technique using patient- specific implants (PSI)

In the past few years, advances in three-dimensional imaging have conducted to breakthrough in the diagnosis, treatment planning and result assessment in orthognathic surgery. Hereby error-prone and time-consuming planning steps, like model surgery and transfer of the face bow, can be eluded. Numerous positioning devices, in order to transfer the three-dimensional treatment plan to the intraoperative site, have been described. Nevertheless the use of positioning devices and intraoperative splints are failure-prone and time-consuming steps, which have to be performed during the operation and during general anesthesia of the patient. We describe a novel time-sparing and failsafe technique using patient-specific implants (PSI) as positioning guides and concurrently as rigid fixation of the maxilla in the planned position. This technique avoids elaborate positioning and removal of manufactured positioning devices and allows maxillary positioning without the use of occlusal splints.

Head and Neck Cancer in the Elderly: A Retrospective Study over 10 Years (1999 - 2008)

IntroductionTreatment of elderly patients is in many ways different from that for younger ones. The aim of the present study was to identify the particular characteristics and needs of elderly patients suffering from head and neck cancer. From these patterns, considerations for this special group can be deduced.Patients and MaterialThe subjects for this study consisted of 376 patients suffering from head and neck cancer that were treated between 1999 and 2008, 99 (26.3.%) of whom were older than 70 years and were evaluated retrospectively concerning smoking/alcohol abuse, ASA status, kind of malignant neoplasm, localization and treatment.ResultsThe male-female ratio was 53:46, and mean age, 79 years (71 - 98). Out of 95 patients with a squamous cell carcinoma, 4 patients had a verrucous form. Out of 99 patients, 26 had a maxillary carcinoma and 12 patients had experienced previous non-head-and-neck cancer. An ASA score of 2 or 3 was found in 86 of the patients.ConclusionThe group of patients with head and neck cancer who were older than 70 years was characterized by a higher portion of female patients, a higher number of maxillary carcinomas, and a higher prevalence of previous second cancer.Making decisions in cancer therapy for elderly patients is challenging. Patients suffering from operable head and neck cancer should be treated with curative intent and with regard to quality of life if a careful assessment of comorbidities is performed preoperatively.

Oral squamous cell carcinoma in non-smoking and non-drinking patients.

IntroductionOf the many different factors associated with an increased risk for oral squamous cell carcinoma (SCC), tobacco and alcohol seem to be the most studied. The aim of the current study was to evaluate the clinicopathologic characteristics of patients without the mentioned risk factors.Patients and MethodsOut of 278 patients (159 male and 119 female patients) with oral SCC, 67 patients had no history of tobacco or alcohol use. The minimum follow-up time was 12 months.ResultsOf the 67 patients, 45 (67.2%) were women, and the mean age was 70 years. The most common tumor sites were mandibular alveolar ridge (22) and maxilla (18). Fifteen patients experienced a recurrence, and 10 developed lymph node metastases during the follow-up period.ConclusionThe group of patients with no tobacco and alcohol use tends toward a higher proportion of females, a higher proportion of patients over 70 years, and a higher number of oral maxillary SCC.

Evaluation of the pectoralis major flap for reconstructive head and neck surgery

PurposeThe pectoralis major myocutaneous flap (PMMF) is a commonly used flap in reconstructive head and neck surgery, but in literature, the flap is also associated with a high incidence of complications in addition to its large bulk. The purpose of the study is the evaluation of the reliability and indication of this flap in reconstructive head and neck surgery.Patients and methodsThe records of all patients treated with a PMMF between 1998 and 2009 were systematically reviewed. Data of recipient localization, main indication, and postoperative complications were analyzed.ResultsThe male to female ratio was 17:3, with a mean age of 60 years (45-85). Indications in 7 patients were recurrence of a squamous cell carcinoma, in one case an osteoradionecrosis and in 12 cases an untreated squamous cell carcinoma. In 6 male patients (30%), a complication appeared leading to another surgery.ConclusionThe PMMF is a flap for huge defects in head and neck reconstructive surgery, in particular when a bulky flap is needed in order to cover the carotid artery or reconstructive surgery, but the complication rate should not be underestimated in particular after radiotherapy.

Clinical reliability of radial forearm free-flap procedure in reconstructive head and neck surgery.

Objective: The purpose of the study was to evaluate the indications, reliability, and complications of the radial forearm fasciocutaneous flap (RFFF) procedure in reconstructive head and neck surgery. Methods: The records of 81 patients who were treated with an RFFF between 1998 and 2009 were systematically reviewed. Data of recipient localization, previous T status, and postoperative complications were analyzed. Results: From the 50 male and 31 female patients, 4 patients (3 men and 1 woman) experienced flap failure during the first 36 hours: in 1 patient because of arterial and in 3 patients because of venous complications. None of the 4 patients had preoperative radiotherapy. A dehiscence was observed in 2 patients without a need for further surgery. Conclusions: With a success rate of more than 95%, the RFFF is a reliable flap and a workhorse, particularly in defects where thinness is needed to substitute for the oral mucosa, such as on the floor of the mouth or the tongue.

Follow up after IMRT in oral cavity cancer: update.

PurposeExcept for early stages (T1/2 N0), the prognosis for patients with oral cavity cancer (OCC) is known to be worse than for those with pharyngeal carcinoma. While definitive intensity modulated radiation therapy (IMRT)-chemotherapy affords loco-regional control rates (LRC) of approximately 80% in advanced pharyngeal cancer, corresponding rates are reported to be much lower for OCC. The aim of this work was to evaluate loco-regional disease control and overall survival (OAS) in a relatively large OCC patient cohort treated in the IMRT era.Methods and materialsBetween October 2002 and June 2011, 160 OCC patients were treated with curative intention IMRT at our department. 122 patients (76%) were referred with primary disease and 38 patients (24%) with a recurrent OCC at least 3 months after surgery alone. Definitive IMRT was performed in 44/160 patients (28%), whilst 116 patients underwent previous surgery. Simultaneous systemic therapy was administered in 72%.ResultsPatients with postoperative IMRT (+/−systemic therapy) with R0-1 status (n = 99) reached significantly higher LRC/OAS rates than patients following IMRT for macroscopic disease (n = 61), with 84%/80% versus 38%/33% at 3 years, respectively (p < 0.0001). This was found in patients treated for initial, as well as recurrent, disease. Less than 2% persisting grade 3/4 late effects were observed.ConclusionsIMRT for R0-1 situations translated into a highly significant superior LRC and OAS compared to the IMRT cohort treated for macroscopic disease. Treatment was well tolerated.

Registration for computer-navigated surgery in edentulous patients: A problem-based decision concept

BACKGROUND Surgical navigation is a commonly used tool in cranio-maxillofacial surgery. Registration is the key element for precision, and a number of studies have shown different techniques to be accurate. Nonetheless, uncertainty surrounds the special situation in edentulous patients and a practical approach to what can be a challenging problem. MATERIALS AND METHODS Four registration strategies for the Brainlab VectorVision(2) system are presented for surgical navigation of edentulous patients: three landmark-based, point-to-point techniques and one surface-based matching strategy are evaluated. RESULTS The methods described differ in overall accuracy as well as in the region covered. In general, the more time-consuming and invasive the technique, the more precise it is. The non-invasive techniques are less precise, and they cover only small regions with sufficient accuracy. CONCLUSIONS Taking into account which type of accuracy is clinically relevant and that the whole skull does not always need to be covered with the greatest possible accuracy, all the described techniques have their indications. The simpler and less invasive techniques can spare time, decrease costs, and harm patient. A decision tree is presented to the reader.

Current relevance of hypoxia in head and neck cancer

Head and Neck cancer (HNC) is a complex mix of cancers and one of the more common cancers with a relatively poor prognosis. One of the factors that may assist us in predicting survival and allow us to adjust our treatment strategies is the presence of tumor hypoxia. In this overview we aim to evaluate the current evidence and potential clinical relevance of tumor hypoxia in head and neck cancer according to an extensive search of current literature. An abundance of evidence and often contradictory evidence is found in the literature. Even the contradictory evidence and comparisons are difficult to judge as criteria and methodologies differ greatly, furthermore few prospective observational studies exist for verification of the pre-clinical studies. Despite these discrepancies there is clear evidence of associations between prognosis and poor tumor oxygenation biomarkers such as HIF-1α, GLUT-1 and lactate, though these associations are not exclusive. The use of genetic markers is expanding and will probably lead to significantly more and complex evidence. The lack of oxygenation in head and neck tumors is of paramount importance for the prediction of treatment outcomes and prognosis. Despite the wide array of conflicting evidence, the drive towards non-invasive prediction of tumor hypoxia should continue.