Endoscopic CO2 Laser Resection Using the Inversion Technique in 22 Combined Laryngoceles.

OBJECTIVE: To demonstrate the feasibility of transoral resection of, even large, combined laryngoceles by endoscopic CO2 laser resection using the inversion technique. METHODS: A retrospective study over a 25-year period of 20 patients with 22 combined laryngoceles. All patients were operated on using the CO2 laser inversion technique. Pre- and postoperative computed tomography (CT)-scans or magnetic resonance (MR) imaging were available in all patients. RESULTS: There were no surgical problems during all procedures. One patient required a tracheotomy pre-operatively due to a compromised airway. All procedures were without intraoperative complications. Postoperatively, there were two complications: one hemorrhage, and one patient developed a granuloma with airway compromise. In two patients, residual disease was detected on postoperative imaging. One of them was re-operated several years later due to the progression of this residual external component of the laryngocele. One patient had a non-significant small internal laryngocele recurrence. The recurrence rate in this series was 2/22 (9.1%). The majority of patients (15/20) could be discharged from the hospital the day after surgery. CONCLUSION: The results of this study show excellent control of combined laryngoceles using the CO2 laser inversion technique, with a short hospital stay and a low rate of complications and recurrence. Even in large combined laryngoceles, CO2 laser excision using the inversion technique should be considered. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2742-2746, 2023.

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.

Transtracheal Use of the CriCath Cannula in Combination With the Ventrain Device for Prevention of Hypoxic Arrest due to Severe Upper Airway Obstruction: A Case Report.

A patient recently treated with surgery and radiation for oropharyngeal cancer presented with impending hypoxic respiratory and cardiac arrest in a difficult airway scenario. A CriCath cannula in combination with the Ventrain device and its active expiratory ventilation technology enabled oxygenation and ventilation for 60 minutes until a surgical airway was established. This case report is the first to describe the intended use of Ventrain technology in an emergent "can't ventilate-can't intubate" scenario.

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.

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. Laryngoscope, 128:697-700, 2018.

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 < 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 < 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.

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.

Evaluation of the use of freehand SPECT for sentinel node biopsy in early stage oral carcinoma.

RATIONALE: Inadequate intraoperative visualization of the sentinel node can hamper its harvest. Freehand SPECT is a 3D tomographic imaging modality based on the concepts of SPECT, which can be used for intraoperative visualization and navigation towards the sentinel node in order to improve its localization and removal during surgery. PATIENTS AND METHODS: The use of freehand SPECT was evaluated during 66 sentinel node biopsy procedures in early stage oral cancer patients. Intraoperative detection of sentinel nodes was compared with preoperative identified sentinel nodes on lymphoscinitigraphic examination. Additional value of freehand SPECT was subjectively scored by the surgeon directly following the biopsy procedure. RESULTS: Freehand SPECT was able to detect 94% of sentinel nodes intraoperatively. Most sentinel nodes not detected (7 out of 9) were located in level I of the neck. Freehand SPECT appeared to be of additional value for facilitating the intraoperative detection of the sentinel node in 24% of procedures. CONCLUSION: The use of the freehand SPECT system is feasible in the intraoperative detection of sentinel nodes in early stage oral cancer. Freehand SPECT provides helpful information facilitating the SN biopsy procedure in a quarter of cases. However, freehand SPECT cannot detect all SNs which are located in the vicinity of the injection site.

Sentinel node biopsy for early-stage oral cavity cancer: the VU University Medical Center experience.

BACKGROUND: Sentinel node biopsy (SNB) in head and neck cancer is recently introduced as the staging technique of oral squamous cell carcinoma. We report the results of SNB in patients diagnosed with a T1-T2 oral squamous cell carcinoma and clinically negative (N0) neck in a single center. METHODS: A retrospective analysis of 90 previously untreated patients who underwent SNB between 2007 and 2012 was performed. The SNB procedure consisted of preoperatively performed lymphoscintigraphy, intraoperative detection using blue dye, and gamma probe guidance and histopathologic examination including step-serial sectioning (SSS) and immunohistochemical (IHC) staining. A positive SNB was followed by neck dissection, whereas regular follow-up with ultrasound-guided fine-needle aspiration cytology (FNAC) was done in case of a negative SNB. RESULTS: The lymphoscintigraphic identification rate was 98% (88 of 90 patients) and the surgical detection rate was 99% (87 of 88 patients). The upstaging rate was 30%. Sensitivity of SNB was 93% and the negative predictive value was 97%. The median follow-up was 18 months (range, 2-62 months). Overall survival (OS) and disease-free survival (DFS) for SNB negative were 100% and 84% and for SNB positive patients 73% and 88%, respectively. CONCLUSION: SNB is a reliable diagnostic staging technique for the clinically negative neck in patients with early-stage (T1-T2, cN0) oral squamous cell carcinoma.

Preclinical evaluation of 89Zr-labeled anti-CD44 monoclonal antibody RG7356 in mice and cynomolgus monkeys: Prelude to Phase 1 clinical studies.

RG7356 is a humanized antibody targeting the constant region of CD44. RG7356 was radiolabeled with (89)Zr for preclinical evaluations in tumor xenograft-bearing mice and normal cynomolgus monkeys to enable study of its biodistribution and the role of CD44 expression on RG7356 uptake.   Studies with (89)Zr-RG7356 were performed in mice bearing tumor xenografts that differ in the level of CD44 expression (CD44(+) or CD44(-)) and RG7356 responsiveness (resp or non-resp): MDA-MB-231 (CD44(+), resp), PL45 (CD44(+), non-resp) and HepG2 (CD44(-), non-resp). Immuno-PET whole body biodistribution studies were performed in normal cynomolgus monkeys to determine normal organ uptake after administration of a single dose. At 1, 2, 3, and 6 days after injection, (89)Zr-RG7356 uptake in MDA-MB-231 (CD44(+), resp) xenografts was nearly constant and about 9 times higher than in HepG2 (CD44(-), non-resp) xenografts (range 27.44 ± 12.93 to 33.13 ± 7.42% ID/g vs. 3.25 ± 0.38 to 3.90 ± 0.58% ID/g). Uptake of (89)Zr-RG7356 was similar in MDA-MB-231 (CD44(+), resp) and PL45 (CD44(+), non-resp) xenografts. Studies in monkeys revealed antibody uptake in spleen, salivary glands and bone marrow, which might be related to the level of CD44 expression. (89)Zr-RG7356 uptake in these normal organs decreased with increasing dose levels of unlabeled RG7356. (89)Zr-RG7356 selectively targets CD44(+) responsive and non-responsive tumors in mice and CD44(+) tissues in monkeys. These studies indicate the importance of accurate antibody dosing in humans to obtain optimal tumor targeting. Moreover, efficient binding of RG7356 to CD44(+) tumors may not be sufficient in itself to drive an anti-tumor response.

Pilot study on the feasibility of PET/CT lymphoscintigraphy with 89Zr-nanocolloidal albumin for sentinel node identification in oral cancer patients.

UNLABELLED: With conventional imaging techniques such as planar lymphoscintigraphy and SPECT/CT, preoperative sentinel node (SN) identification can be difficult when the SN is near the primary tumor, as is the case in floor-of-mouth carcinomas. PET/CT lymphoscintigraphy may improve the detection and localization of such SNs. METHODS: In this study, the clinical feasibility of PET/CT lymphoscintigraphy using (89)Zr-nanocolloidal albumin was evaluated in 5 oral cancer patients. PET/CT lymphoscintigraphy was performed after peritumoral injection of (89)Zr-nanocolloidal albumin. The routine SN procedure, including SPECT/CT using (99m)Tc-nanocolloidal albumin, was performed on the same patients 7-9 d after the injection of (89)Zr-nanocolloidal albumin. RESULTS: Comparison of radiocolloid distribution on PET/CT and SPECT/CT showed identical drainage patterns. Moreover, PET/CT was able to identify additional foci near the primary tumor. CONCLUSION: This pilot PET/CT study on SN detection indicated that lymphoscintigraphy using (89)Zr-nanocolloidal albumin is feasible.

Phase 0 microdosing PET study using the human mini antibody F16SIP in head and neck cancer patients.

UNLABELLED: The aim of this microdosing phase 0 clinical study was to obtain initial information about pharmacokinetics, biodistribution, and specific tumor targeting of the antitenascin-C mini antibody F16SIP. METHODS: Two milligrams of F16SIP, labeled with 74 MBq of (124)I, were intravenously administered to patients with head and neck cancer (n = 4) scheduled for surgery 5-7 d later. Immuno-PET scans were acquired at 30 min and 24 h after injection. For pharmacokinetic analysis, blood samples were taken at different time points after infusion. Tissue uptake was extracted from whole-body PET scans. In addition, ex vivo radioactivity measurements of blood and of biopsies from the surgical specimens were performed. RESULTS: (124)I-F16SIP was well tolerated. Uptake was visible mainly in the liver, spleen, kidneys, and bone marrow and diminished over time. Tumor uptake increased over time, with all 4 tumors visible on 24-h PET images. The tumor-to-blood ratio was 7.7 ± 1.7 at the time of surgery. Pharmacokinetic analysis revealed good bioavailability of (124)I-F16SIP. CONCLUSION: Performing a microdosing immuno-PET study appeared feasible and demonstrated adequate bioavailability and selective tumor targeting of (124)I-F16SIP.The results of this study justify further clinical exploration of (124)I-F16SIP-based therapies.

Visualization of the sentinel node in early-stage oral cancer: limited value of late static lymphoscintigraphy.

OBJECTIVE: Various lymphoscintigraphic imaging protocols exist for sentinel node (SN) identification in early-stage oral cancer. This study aimed to evaluate the clinical value of performing additional late lymphoscintigraphic imaging. METHODS: We retrospectively analysed early (directly following injection of 99mTc-Nanocoll) and late (2-4 h after injection) imaging results of 60 early-stage (T1-T2, cN0) oral cancer patients scheduled for SN procedure. Lymphoscintigraphic results of late imaging were categorized into: (a) no visualization of additional hotspots considered to be SNs; (b) additional hotspots visualized that are considered to be SNs and (c) hotspots visualized only during late imaging. Histopathological results of the harvested SNs were related to the corresponding hotspot. RESULTS: In all patients (n=60) lymphoscintigraphy was able to visualize a hotspot that was identified as an SN. In 51/60 (85%) patients, early imaging was able to visualize at least one hotspot, whereas in 9/60 (15%) patients, mostly with oral cavity tumours other than mobile tongue and floor-of-mouth tumours, only late imaging was able to visualize hotspots. In 14/51 (27%) patients, late imaging resulted in additionally visualized hotspots marked as SNs, resulting in a more extensive surgical procedure. These additionally removed SNs appeared to be of no clinical relevance, as all SNs identified during early imaging correctly predicted whether the neck was positive or negative for cancer. CONCLUSION: Results of this study indicate that additional late lymphoscintigraphic imaging should be performed only in selected cases.

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.

89Zr-nanocolloidal albumin-based PET/CT lymphoscintigraphy for sentinel node detection in head and neck cancer: preclinical results.

UNLABELLED: Identifying sentinel nodes near the primary tumor remains a problem in, for example, head and neck cancer because of the limited resolution of current lymphoscintigraphic imaging when using (99m)Tc-nanocolloidal albumin. This study describes the development and evaluation of a nanocolloidal albumin-based tracer specifically dedicated for high-resolution PET detection. METHODS: (89)Zr was coupled to nanocolloidal albumin via the bifunctional chelate p-isothiocyanatobenzyldesferrioxamine B. Quality control tests, including particle size measurements, and in vivo biodistribution and imaging experiments in a rabbit lymphogenic metastasis model were performed. RESULTS: Coupling of (89)Zr to nanocolloidal albumin appeared to be efficient, resulting in a stable product with a radiochemical purity greater than 95%, without affecting the particle size. PET showed distinguished uptake of (89)Zr-nanocolloidal albumin in the sentinel nodes, with visualization of lymphatic vessels, and with a biodistribution comparable to (99m)Tc-nanocolloidal albumin. CONCLUSION: (89)Zr-nanocolloidal albumin is a promising tracer for sentinel node detection by PET.

The potential role of non-FDG-PET in the management of head and neck cancer.

Positron emission tomography (PET) is a functional imaging modality that is widely used in oncology. The integration of PET with CT (PET-CT) provides at the same time also detailed morphological information, which is especially attractive for the anatomically complex head and neck region. The most widely used PET-tracer for imaging the enhanced metabolism of tumours is ¹8F-fluorodeoxyglucose (¹8FDG), but several new tracers for imaging of metabolic features other than glucose consumption (non-FDG tracers) have been developed with the aim to perform better than ¹8FDG in specific indications. For initial staging of head and neck squamous cell carcinoma (HNSCC) these tracers until now did not show a better performance than ¹8FDG. Most data suggest a potential role for non-FDG metabolic tracers for treatment response prediction and surveillance of HNSCC. This information may provide a guide for further individualized treatment decisions. The possibility of PET to image biologic features and molecular targets as key drivers of malignant growth and survival provides another important tool for treatment guidance. The presence of the biologic feature hypoxia, a common phenomenon in head and neck cancer, is associated with a poor response to (chemo) radiotherapy. Therefore, knowledge of hypoxia may influence treatment decisions. Several candidate hypoxia PET tracers are discussed. With the increasing knowledge of critical molecular targets in head and neck cancer (e.g. the epidermal growth factor receptor), many novel targeted anticancer therapeutics become available among which monoclonal antibodies and small molecular tyrosin kinase inhibitors. Upon labelling of these drugs with a positron emitter, their distribution within the human body can be quantitatively imaged by PET. In this way, PET can be used for better understanding of in vivo tumour biology, guidance of drug development, and appropriate treatment selection for the individual patient (personalized medicine). Altogether, the potential role of non-FDG-PET in the management of HNSCC seems to be guidance and surveillance of treatment of the individual patient.