Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node

Purpose: At present, the only approved fluorescent tracer for clinical near-infrared fluorescence-guided sentinel node (SN) detection is indocyanine green (ICG), but the use of this tracer is limited due to its poor retention in the SN resulting in the detection of higher tier nodes. We describe the development and characterization of a next-generation fluorescent tracer, nanocolloidal albumin-IRDye 800CW that has optimal properties for clinical SN detection Methods: The fluorescent dye IRDye 800CW was covalently coupled to colloidal human serum albumin (HSA) particles present in the labelling kit Nanocoll in a manner compliant with current Good Manufacturing Practice. Characterization of nanocolloidal albumin-IRDye 800CW included determination of conjugation efficiency, purity, stability and particle size. Quantum yield was determined in serum and compared to that of ICG. For in vivo evaluation a lymphogenic metastatic tumour model in rabbits was used. Fluorescence imaging was performed directly after peritumoral injection of nanocolloidal albumin-IRDye 800CW or the reference ICG/HSA (i.e. ICG mixed with HSA), and was repeated after 24 h, after which fluorescent lymph nodes were excised. Results: Conjugation of IRDye 800CW to nanocolloidal albumin was always about 50% efficient and resulted in a stable and pure product without affecting the particle size of the nanocolloidal albumin. The quantum yield of nanocolloidal albumin-IRDye 800CW was similar to that of ICG. In vivo evaluation revealed noninvasive detection of the SN within 5 min of injection of either nanocolloidal albumin-IRDye 800CW or ICG/HSA. No decrease in the fluorescence signal from SN was observed 24 h after injection of the nanocolloidal albumin-IRDye 800CW, while a strong decrease or complete disappearance of the fluorescence signal was seen 24 h after injection of ICG/HSA. Fluorescence-guided SN biopsy was very easy. Conclusion: Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection. © The Author(s) 2012

A clicking larynx: Diagnostic and therapeutic challenges

A clicking larynx can be described as a clicking sensation in the neck on swallowing or when moving the head, often associated with a tender or painful area in the neck. Diagnosis and therapy are challenging. In this article, we present a case report and overview of the current literature. The clicking larynx most often is reported to be a result of a displaced cornu superior of the thyroid cartilage, an enlarged greater cornu of the hyoid bone, or a short distance between the thyroid cartilage and hyoid bone. If a possible cause is identified, surgery can be offered to the patient, although an explanation of the possible underlying anatomical cause also could be satisfying for the patient and avert surgery

Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium-labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe

Background: PET/CT lymphoscintigraphy using 89Zr-nanocolloidal albumin has the potential to improve the preoperative identification of sentinel lymph nodes (SLNs), especially if located in the near proximity of the primary tumour. This study aims to demonstrate the feasibility of PET/CT lymphoscintigraphy followed by intraoperative detection of 89Zr-nanocolloidal albumin containing SLNs with the use of a handheld high-energy gamma probe. Methods: PET/CT lymphoscintigraphy was performed after peritumoural injection of 89Zr-nanocolloidal albumin in five patients with oral cavity carcinoma planned for surgical resection. SLN biopsy procedure was performed 18 h later. SLNs were detected using detailed information of PET/CT and the high-energy gamma probe. Results: In all patients, SLNs were identified on PET/CT lymphoscintigraphy. Intraoperative detection using the high-energy gamma probe was possible in 10 of 13 SLNs, at a short distance from the SLN. Conclusions: This study demonstrates that intraoperative detection of SLNs containing 89Zr-nanocolloidal albumin using a handheld high-energy gamma probe is feasible, but its clinical use and sensitivity seem to be limited. Trial registration: CCMO NL37222.092.11

Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium-labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe

BACKGROUND: PET/CT lymphoscintigraphy using89Zr-nanocolloidal albumin has the potential to improve the preoperative identification of sentinel lymph nodes (SLNs), especially if located in the near proximity of the primary tumour. This study aims to demonstrate the feasibility of PET/CT lymphoscintigraphy followed by intraoperative detection of89Zr-nanocolloidal albumin containing SLNs with the use of a handheld high-energy gamma probe. METHODS: PET/CT lymphoscintigraphy was performed after peritumoural injection of89Zr-nanocolloidal albumin in five patients with oral cavity carcinoma planned for surgical resection. SLN biopsy procedure was performed 18 h later. SLNs were detected using detailed information of PET/CT and the high-energy gamma probe. RESULTS: In all patients, SLNs were identified on PET/CT lymphoscintigraphy. Intraoperative detection using the high-energy gamma probe was possible in 10 of 13 SLNs, at a short distance from the SLN. CONCLUSIONS: This study demonstrates that intraoperative detection of SLNs containing89Zr-nanocolloidal albumin using a handheld high-energy gamma probe is feasible, but its clinical use and sensitivity seem to be limited. TRIAL REGISTRATION: CCMO NL37222.092.11

Evaluation of vascular features of vocal cords proposed by the European Laryngological Society

A newly proposed classification by the European Laryngological Society (ELS) of glottic lesions by narrow-band imaging (NBI) divides their vascular patterns into longitudinal and perpendicular ones. The latter are further subdivided into the wide and narrow patterns. The longitudinal, wide, and narrow patterns are characteristic of benign disease, papilloma, and malignancy, respectively. The aim of the study was to investigate the diagnostic effectiveness of the classification. Forty patients with glottic lesions underwent microlaryngoscopy. The vascular patterns of all vocal cords were defined with NBI. The affected vocal cords were histologically analysed and comprised the arm (A). Unaffected vocal cords were not histologically analysed but followed-up and comprised the arm (B) and were regarded as true negatives if no suspicious changes appeared during the follow-up. The vocal cords from the arm A were categorised into the benign and malignant group according to the histologic result. The ratio of vascular patterns was determined and the groups were statistically compared using the Chi-square test and Fisher’s exact test. Perpendicular changes were observed in 36.6% (9/26) of benign diseases and in 100% (23/23) of cancer conditions (p OpenSPiltSPi 0.001). Wide perpendicular changes appeared only in papillomas (6/6) while narrow ones mostly in malignancies (23/26) and also in benign conditions (3/26) (p OpenSPiltSPi 0.001). The sensitivity, specificity, positive and negative predictive values, and accuracy were 100, 95, 88, 100 and 96%, respectively. The new ELS classification can be used effectively and safely to differentiate malignant from benign disease

The inability to belch syndrome: A study using concurrent high-resolution manometry and impedance monitoring

Introduction: Although inability to belch has previously been linked to dysfunction of the upper esophageal sphincter (UES), its underlying pathogenesis remains unclear. Our aim was to study mechanisms underlying inability to belch and the effect of UES botulinum toxin (botox) injections in these patients. Methods: We prospectively enrolled consecutive patients with symptoms of inability to belch. Patients underwent stationary high-resolution impedance manometry (HRIM) with belch provocation and ambulatory 24-h pH-impedance monitoring before and 3 months after UES botox injection. Results: Eight patients (four males, age 18–37 years) were included. Complete and normal UES relaxation occurred in response to deglutition in all patients. A median number of 33(15–64) gastroesophageal gas reflux episodes were observed. Despite the subsequent increase in esophageal pressure (from −4.0 [−7.7–4.2] to 8 [3.3–16.1] mmHg; p < 0.012), none of the gastroesophageal gas reflux events resulted in UES relaxation. Periods of continuous high impedance levels, indicating air entrapment (median air presence time 10.5% [0–43]), were observed during 24-h impedance monitoring. UES botox reduced UES basal pressure (from 95.7[41.2–154.0] to 29.2 [16.7–45.6] mmHg; p < 0.02) and restored belching capacity in all patients. As a result, esophageal air presence time decreased from 10.5% (0–43.4) to 0.7% (0.1–18.6; p < 0.02) and esophageal symptoms improved in all patients (VAS 6.0 [1.0–7.9] to 1.0 [0.0–2.5]; p < 0.012). Conclusion: The results of this study underpin the existence of a syndrome characterized by an inability to belch and support the hypothesis that ineffective UES relaxation, with subsequent esophageal air entrapment, may lead to esophageal symptoms

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project : Results from the treatment of mucosal cancers

AIM: Electrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours. PATIENT AND METHODS: Forty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life. RESULTS: Thirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment. CONCLUSION: Electrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results from the treatment of mucosal cancers

Aim Electrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours. Patient and methods Forty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life. Results Thirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment. Conclusion Electrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results of the treatment of skin cancer

AbstractElectrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p < 0.05), as investigated by univariate analysis. Electrochemotherapy was well tolerated and led to a significant improvement of quality of life, estimated by the European Organisation for Research and Treatment of Cancer quality of life questionnaires. At 1-year follow-up, the percentages of overall and disease-free survival were 76% and 89%, respectively. Electrochemotherapy is an effective option for skin cancers of the HN area and can be considered a feasible alternative to standard treatments when such an alternative is appropriate. The precise role for electrochemotherapy in the treatment algorithm for non-melanoma skin cancer of the HN region requires data from future randomised controlled studies.(ISRCTN registry N. 30427