http://repub.eur.nl/res/aut/24828/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37401/ 2012-10-01T00:00:00Z Clinically relevant cartilaginous subglottic stenosis was found in 2 patients with Shwachman-Diamond syndrome (SDS) for which tracheotomy was required in one case. Considering the pathogenesis of SDS, including deficient chondrogenesis, we hypothesise that subglottic stenosis may be a rare symptom of SDS. Otorhinolaryngologist and paediatricians should be aware of the risk of airway pathology in patients with SDS. http://repub.eur.nl/res/pub/31294/ 2012-03-01T00:00:00Z Chemoradiation (CRT) is a valuable treatment option for advanced hypopharyngeal squamous cell cancer (HSCC). However, long-term toxicity and quality of life (QOL) is scarcely reported. Therefore, efficacy, acute and long-term toxic effects, and long-term QOL of CRT for advanced HSCC were evaluated,using retrospective study and post-treatment quality of life questionnaires. in a tertiary hospital setting. Analysis was performed of 73 patients that had been treated with CRT. Toxicity was rated using the CTCAE score list. QOL questionnaires EORTC QLQ-C30, QLQ-H&N35, and VHI were analyzed. The most common acute toxic effects were dysphagia and mucositis. Dysphagia and xerostomia remained problematic during long-term follow-up. After 3 years, the disease-specific survival was 41%, local disease control was 71%, and regional disease control was 97%. The results indicated that CRT for advanced HSCC is associated with high locoregional control and disease-specific survival. However, significant acute and long-term toxic effects occur, and organ preservation appears not necessarily equivalent to preservation of function and better QOL. http://repub.eur.nl/res/pub/37978/ 2012-02-13T00:00:00Z Bioluminescence imaging (BLI) has shown its appeal as a sensitive technique for in vivo whole body optical imaging. However, the development of injectable tumor-specific near-infrared fluorescent (NIRF) probes makes fluorescence imaging (FLI) a promising alternative to BLI in situations where BLI cannot be used or is unwanted (e.g., spontaneous transgenic tumor models, or syngeneic mice to study immune effects). In this study, we addressed the questions whether it is possible to detect tumor progression using FLI with appropriate sensitivity and how FLI correlates with BLI measurements. In addition, we explored the possibility to simultaneously detect multiple tumor characteristics by dual-wavelength FLI (~700 and ~800 nm) in combination with spectral unmixing. Using a luciferase-expressing 4T1-luc2 mouse breast cancer model and combinations of activatable and targeting NIRF probes, we showed that the activatable NIRF probes (ProSense680 and MMPSense680) and the targeting NIRF probes (IRDye 800CW 2-DG and IRDye 800CW EGF) were either activated by or bound to 4T1-luc2 cells. In vivo, we implanted 4T1-luc2 cells orthotopically in nude mice and were able to follow tumor progression longitudinally both by BLI and dual-wavelength FLI. We were able to reveal different probe signals within the tumor, which co-localized with immuno-staining. Moreover, we observed a linear correlation between the internal BLI signals and the FLI signals obtained from the NIRF probes. Finally, we could detect pulmonary metastases both by BLI and FLI and confirmed their presence histologically. Taken together, these data suggest that dual-wavelength FLI is a feasible approach to simultaneously detect different features of one tumor and to follow tumor progression with appropriate specificity and sensitivity. This study may open up new perspectives for the detection of tumors and metastases in various experimental models and could also have clinical applications, such as image-guided surgery. http://repub.eur.nl/res/pub/34155/ 2011-10-11T00:00:00Z Background: In oral cancer surgery, intraoperative optical imaging could help the surgeon to determine adequate tumor-free margins. Methods: Tumor-specific near-infrared fluorescence agents targeting epidermal growth factor receptor (CW800 EGF) or glucose transporter system (CW800 2-DG) were administered to mice with tongue carcinoma and cervical lymph node metastases. Tumor growth was followed by bioluminescence imaging. Fluorescence signals were compared with a control group of healthy animals. Results: Significantly higher fluorescence was found in tongue tumors and cervical lymph node metastases compared with that in control animals. Fluorescence correlated with histopathology. Tumor-to-background ratio of CW800 EGF in the tongue was 13.8 (SD = 6.1) and in the lymph nodes 15.7 (SD = 8.8). For CW800 2-DG, the tumor-to-background ratio in the tongue was 4.6 (SD = 2.1) and in the lymph nodes 33.9 (SD = 18.4). Conclusions: Optical imaging can be used to detect oral cancer and cervical lymph node metastases and could potentially improve complete surgical resection by real-time image-guided surgery. http://repub.eur.nl/res/pub/33832/ 2011-09-01T00:00:00Z Chronic serous otitis media is a common problem in the daily routine of the otorhinolaryngologist. In the majority of cases, the cause is related to dysfunction of the eustachian tube due to viral or bacterial rhinitis and occasionally to nasopharyngeal tumors. We report a case of a patient presenting with chronic serous otitis media that was resistant to conventional therapy. MRI with gadolinium finally revealed that the middle ear fluid was caused by leakage of cerebrospinal fluid (CSF) due to bone destruction by a temporal meningioma. The CSF leakage was closed by surgery. Histopathology confirmed meningioma in the temporal bone. Copyright http://repub.eur.nl/res/pub/33959/ 2011-06-01T00:00:00Z Objective: To assess the feasibility of optical imaging using activatable near-infrared fluorescence (NIRF) agents to detect oral cancer and cervical lymph node metastasis in vivo. Design: In vivo study. Setting: University medical center. Subjects: Female nude mice aged 4 to 6 weeks. Intervention: Luciferase-expressing OSC-19-luc cells were injected into the tongues of nude mice. A control group of nude mice was injected in the tongue with a physiologic saline solution. Tumor growth was followed by bioluminescence imaging. After 3 weeks, animals were randomly allocated to intravenous administration of 1 of 2 activatable NIRF agents: ProSense680 or MMPSense680. Fluorescence imaging of the mice was performed, and the tumor to background ratio (TBR) was determined on histologic sections of the tongue and cervical lymph nodes after resection at necropsy. Main Outcome Measure: Fluorescence signals. Results: The fluorescence signals in tongue tumor and cervical lymph node metastases were significantly higher than those in control animals. The mean (SD) TBR of ProSense680 in the tongue was 15.8 (8.1) and in the lymph nodes was 11.8 (3.6). For MMPSense680, the mean (SD) TBR in the tongue was 18.6(9.4) and in the lymph nodes was 10.5(4.0). Conclusions: Oral cancer and cervical lymph node metastases can be detected by targeting increased proteolytic activity at the tumor borders using NIRF optical imaging. These NIRF agents could be used for real-time image-guided surgery, which has the potential to improve the complete surgical resection of oral cancer. http://repub.eur.nl/res/pub/25536/ 2011-04-06T00:00:00Z 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. http://repub.eur.nl/res/pub/22181/ 2010-11-01T00:00:00Z Background: The free jejunum graft is a well-established reconstruction technique after total laryngopharyngectomy. However, besides necrosis of the jejunum graft, the two most important complications are pharyngocutaneous fistula formation and dysphagia due to stricture formation. Objectives: This study aims to develop an L-shaped reconstruction technique of the free jejunum graft to decrease pharyngocutaneous fistula formation and long-term stricture formation after total laryngopharyngectomy. Methods: An L-shaped side-to-end anastomosis was performed at the proximal end of the jejunum graft in six patients treated for piriform sinus carcinoma. Patient and operation characteristics and follow-up were recorded. Results: A successful jejunum transfer was performed in all six patients. No pharyngocutaneous fistula or stricture formation occurred during a median follow-up of 23 months (range: 18-30 months). Swallowing rehabilitation started at the median 12th postoperative day (range: 5-150 days). Four patients developed dysphagia at a median of 2 months (range: 1-6 months) after oral intake was started. X-barium swallow revealed a redundant pouch of the transferred jejunum graft, which resulted in compression on the jejunum interposition during swallowing. In three patients, an operation was required to resolve these problems. After the revision operation, no dysphagia occurred during a median follow-up of 12 months (range: 7-13 months). Conclusions: Because of dysphagia complaints in the majority of our patients, we cannot recommend the described technique and should find other means to improve direct postoperative results and long-term quality of life in this difficult-to-treat group of patients. http://repub.eur.nl/res/pub/20858/ 2010-09-01T00:00:00Z To determine the early and long-term morbidity of patients treated with a total laryngopharyngectomy and reconstruction using a jejunum interposition or gastric pull-up procedure. It is a retrospective study; and it is conducted in tertiairy referral center. Sixty-three patients were included in whom 70 reconstructions were performed (51 jejunum interpositions and 19 gastric pull-up procedures) between 1990 and 2007. The studied parameters were success rate of the reconstruction, early and long-term complication rate, and functional outcome including quality of life. Subjective quality of life analysis was determined by two questionnaires: the EORTC Quality of Life Questionnaire (QLQ)-C30 Dutch version 3.0, and the EORTC-Head and Neck (H & N 35). The success rates were 84 and 74%, respectively. The procedures were associated with a high complication rate (63% after jejunum interposition and 89% after gastric pull-up), and a lengthy rehabilitation. Surviving patients were found to have a good long-term quality of life. Complete oral intake was achieved in 97%, and speech rehabilitation in 95%. These procedures are associated with significant morbidity, high complication rates, lengthy rehabilitation, but a good long-term quality of life. http://repub.eur.nl/res/pub/28665/ 2010-06-01T00:00:00Z Aim: To analyse the cases of failure of free jejunum transfer with subsequent secondary reconstruction methods after ablative surgery for malignant tumours of the laryngopharyngeal region and the cervical oesophagus with reconstruction using a jejunum interposition. Materials and methods: Four cases in which failure of the jejunum interposition was managed with a second free or pedicle transfer were identified. The electronic files of patients were studied and analysed for patient characteristics and failure of reconstruction; type of salvage surgery and outcome; swallowing function and rehabilitation; postoperative complications; recurrence of tumour; patient survival and cause of death. Results: Failure of the interposition occurred within 11 days in all patients, with oral bleeding being the most prominent sign. To replace the failed jejunum transfer, two new free jejunum transfers, two gastric pull-ups and one colon interposition after the second failure of a jejunum transfer were used. Three patients started swallowing rehabilitation, of which two achieved complete oral intake, defined as the redundancy of a feeding tube. The median disease-free period and overall survival was 28 and 42 months, respectively. Conclusion: Failure of a free jejunum transfer is a rare but inevitable complication when performed in a high-risk patient population, with oral bleeding being the most important sign of necrosis. Salvage of the buried jejunum interposition is hardly ever possible and secondary reconstruction can be performed using a new jejunum interposition or gastric pull-up procedure with considerable early postoperative complications, but relatively good results regarding swallowing rehabilitation and patient survival. http://repub.eur.nl/res/pub/20625/ 2010-01-01T00:00:00Z 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.