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BACKGROUND: The extent of surgical management of regional lymph nodes in the treatment of cutaneous head and neck melanoma on and anterior to O'Brien's watershed line is controversial. By comparing patients' cohorts of two separate melanoma expert centers we investigate the effectiveness of comprehensive versus (super-) selective neck dissection approach.METHODS: Sixty patients with macroscopic (palpable) neck node metastases (N2b) from anterior scalp and face melanoma were retrospectively studied. Forty therapeutic modified radical neck dissections (MRND; levels I-V) combined with elective parotidectomy from The Netherlands Cancer Institute (NCI) were compared with 16 (super-) selective neck dissections [(S)SND; 3-4 levels] and 4 solely MRNDs from Erasmus Medical Center (EMC). Cohorts were analyzed for site of recurrence, overall survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS).RESULTS: Clinical characteristics of patients were equal in both groups. In the NCI cohort 62.5% (n = 25) of patients recurred versus 65% (n = 13) in the EMC cohort. None of the NCI recurrences affected the parotid gland in contrast to 3 patients in the EMC group. Survival characteristics were not different between the two groups: OS (p = 0.56), MSS (p = 0.98), DFS (p = 0.92).CONCLUSION: This study does not support to continue the practice of routine elective parotidectomy and MRND in melanoma patients undergoing a lymph node dissection for macroscopic (palpable) nodal disease and justifies (S)SND.

Objectives: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL). DESIGN Randomized controlled trial. SETTING Tertiary cancer hospital. PATIENTS Adults to be treated with high-dose cisplatin (>= 75 mg/m(2)). INTERVENTION Selected by randomization, 0.1 M STS gel on one side and placebo gel on the other side was transtympanically applied to the middle ear 3 hours before cisplatin administration. After amendment, the placebo ear was left untreated. Main Outcome Measure: Primary outcome was safety and feasibility. Secondary outcomes included pharmacokinetic analysis of systemic cisplatin and preliminary activity of STS. Clinically relevant CIHL was defined as a >= 10 dB threshold shift at pure-tone average 8-10-12.5 kHz (PTA(8-12.5)). Response to STS was defined as a threshold shift at PTA(8-12.5) in the STS-treated ear of >= 10 dB smaller than the untreated ear. Results: Twelve patients were treated. Average CIHL at PTA(8-12.5) was 12.7 dB in untreated ears and 8.8 dB SPL in STS-treated ears (p = 0.403). Four patients did not develop CIHL. Four out of eight patients with CIHL responded to STS: CIHL at PTA(8-12.5) in STS-treated ears was 18.4 dB less compared to untreated ears (p = 0.068). Grade 1 adverse events were reported. Pharmacokinetic results were available for 11 patients. Conclusion: Transtympanic application of STS was safe and feasible. Based on our pharmacokinetic analysis, we postulate that transtympanic STS does not interfere with the systemically available cisplatin. Our results provide a preliminary proof of concept for transtympanic application of STS in preventing CIHL and warrants further evaluation on a larger scale.

Nowadays, a substantial number of head and neck cancer patients are treated by organ-preserving chemoradiation (CRT), with a possible increased risk of complications after planned or salvage neck dissections. We try to determine the risk pattern of surgical site complications (SSC) post-CRT.(c) 2020 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background: Surgical resection is the standard of care for parotid gland tumors. Comprehensive reports on the surgical complications of parotidectomy are lacking. This study focuses on surgical wound complications of parotid gland surgery.Patients and methods: In the period 2002-2012, 390 consecutive patients (395 procedures) who underwent parotid gland surgery were selected for retrospective analysis. Based on subsequent management, the impact of surgical site complications was graded by the Clavien-Dindo Classification (CDC).Results: In 83 (21.0%) of the procedures, at least one complication was registered. In total, 118 complications were described. Rated to CDC, 61 patients (15.4%) were graded as class 2 or higher. This implies therapy was dictated. Fortyfive (11.4%) of the complications were surgical site infections (551). In 9 patients (2.3%) surgical complications required a surgical intervention under general anesthesia (CDC class 3b), and in 19 patients (4.8%) other invasive treatment (CDC class 3a) was needed.Conclusions: The Clavien-Dindo Classification proved to be very useful for retrospective registration of surgical complications. Of the 61 patients, 33 were managed by conservative therapy. No risk profile was found for patients at risk for direct surgical complications. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background: Sentinel lymph node (SN) biopsy (SLNB) has proven to be a valuable tool for staging melanoma patients. Since its introduction in the early 1990s, this procedure has undergone several technological refinements, including the introduction of single photon emission computed tomography combined with computed tomography (SPECT/CT) as well as radio- and fluorescence-guidance. The purpose of the current study was to evaluate the effect of this technological evolution on SLNB in the head and neck region. Primary endpoint was the false-negative (FN) rate. Secondary endpoints were number of harvested SNs, overall operation time, operation time per harvested SN and postoperative complications. Patients and Methods: A retrospective database was queried for cutaneous head and neck melanoma patients who underwent SLNB at The Netherlands Cancer Institute between 1993 and 2016. The implementation of new detection techniques was divided in 4 groups: (1) 1993-2005, with preoperative lymphoscintigraphy and intraoperative use of both a gamma ray detection probe and patent blue (n = 30); (2) 2006-2007, with addition of preoperative roadmaps based on SPECT/CT (n = 15); (3) 2008-2009, with intraoperative use of a portable gamma camera (n = 40); and (4) 2010-2016, with the addition of near-infrared fluorescence guidance (n = 192). Results: A total of 277 patients were included. At least one SN was identified in all patients. A tumor-positive SN was found in 59 patients (21.3%), 10 in group 1 (33.3%), 3 in group 2 (20.0%), 6 in group 3 (15.0%) and 40 in group 4 (20.8%). Regional recurrences of patients with tumor-negative SNs resulted in an overall FN rate of 11.9% (FN groups 1: 16.7%; 2: 0%; 3: 14.3%; 4: 11.1%). The number of harvested nodes increased with advancing technologies (P = 0.003) whereas Breslow thickness and operation time per harvested SN decreased (P = 0.003 and P = 0.017, respectively). There was no significant difference in percentage of tumor-positive SNs, overall operation time and complication rate between the different groups. Conclusion: The use of advanced detection technologies led to a higher number of identified SNs without increase in overall operation time, which may indicate an improved surgical efficiency. Operation time per harvested SN decreased, the average FN rate remained 11.9% and unchanged over 23 years. There was no significant change in postoperative complication rate.

Background: Surgical resection of tongue cancer may impair swallowing and speech. Knowledge of tongue muscle architecture affected by the resection could aid in patient counseling. Diffusion tensor imaging (DTI) enables reconstructions of muscle architecture in vivo. Reconstructing crossing fibers in the tongue requires a higher‐order diffusion model.Purpose: To develop a clinically feasible diffusion imaging protocol, which facilitates both DTI and constrained spherical deconvolution (CSD) reconstructions of tongue muscle architecture in vivo.Study Type: Cross‐sectional study.Subjects/Specimen: One ex vivo bovine tongue resected en bloc from mandible to hyoid bone. Ten healthy volunteers (mean age 25.5 years; range 21–34 years; four female).Field Strength/Sequence: Diffusion‐weighted echo planar imaging at 3 T using a high‐angular resolution diffusion imaging scheme acquired twice with opposing phase‐encoding for B0‐field inhomogeneity correction. The scan of the healthy volunteers was divided into four parts, in between which the volunteers were allowed to swallow, resulting in a total acquisition time of 10 minutes.Assessment: The ability of resolving crossing muscle fibers using CSD was determined on the bovine tongue specimen. A reproducible response function was estimated and the optimal peak threshold was determined for the in vivo tongue. The quality of tractography of the in vivo tongue was graded by three experts.Statistical Tests: The within‐subject coefficient of variance was calculated for the response function. The qualitative results of the grading of DTI and CSD tractography were analyzed using a multilevel proportional odds model.Results: Fiber orientation distributions in the bovine tongue specimen showed that CSD was able to resolve crossing muscle fibers. The response function could be determined reproducibly in vivo. CSD tractography displayed significantly improved tractography compared with DTI tractography (P = 0.015).Data Conclusion: The 10‐minute diffusion imaging protocol facilitates CSD fiber tracking with improved reconstructions of crossing tongue muscle fibers compared with DTI.Level of Evidence: 2Technical Efficacy: Stage 1

Background Parotidectomy in melanoma of the coronal scalp and face with clinically involved cervical lymph node metastasis is based on predicted cervical lymphatic drainage described by O'Brien. Methods In total, 40 parotidectomies with en bloc therapeutic neck dissection were retrospectively analyzed. Results Lymphatic spread of melanoma to the parotid lymph nodes was observed in 10 of 40 specimens (25%). Eight of the 10 parotid-positive patients developed a recurrence vs 17 of the 30 parotid-negative patients (P = 0.28). There were no differences in overall survival, melanoma-specific survival, and disease-free survival between the parotid-positive and parotid-negative patients. Conclusion Although in this series no survival differences were found, parotidectomy still merits a sustained role in therapeutic neck dissection procedures to improve regional control and to prevent facial nerve damage after surgery for a second relapse from occult metastases in the parotid.

Background TNM staging of melanoma has recently been altered by the introduction of the 8th edition of the AJCC Cancer Staging manual. The purpose of this study is to analyze the inter-observer variation of histopathology reports and its effect on recommended treatment policy. Methods We retrospectively analyzed 296 cases, diagnosed as primary cutaneous head and neck melanoma (2005–2016), referred to the Netherlands Cancer Institute (NCI) for treatment after prior diagnosis in another hospital (non-NCI). All reports were analyzed for patients demographics, tumor characteristics and histopathologic features. Results In 53% and 40% of the cases, the histopathologic parameters were discordant, according to AJCC 7th and 8th edition, respectively. This indicated a perfect inter-observer agreement for the measurement of Breslow thickness (Intraclass correlation coefficient (ICC) = 0.981) and a substantial agreement for subtype (kappa statistic (κ) = 0.648) and ulceration (κ = 0.802), while only moderate for dermal mitotic activity (κ = 0.472). After NCI review, recommended treatment policies were changed in 13% and 11% of the patients when applying TNM 7 and TNM 8, respectively. Scheduling sentinel lymph node biopsy (SLNB) changed in 14 (5%) and 10 (3%) cases when using TNM 7 and TNM 8, respectively. Conclusion Review by a NCI pathologist of histopathologic parameters of primary cutaneous head and neck melanoma led to significant changes in treatment decision. Introduction of the AJCC 8th edition led to slightly less discordances between NCI and non-NCI reports and consequently smaller impact on treatment planning. Expert review remains indicated when a SLNB is considered for additional staging in selected cases.

Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for aggressive retreatment in recurrent pleomorphic adenoma (RPA). However, although the diagnostic category ‘carcinoma ex‐pleomorphic adenoma’ suggests that malignant transformation of a pleomorphic adenoma is a regular event, this has to date not been shown to occur in sequential lesions of one patient. Here, we show the molecular events in transformation to malignancy of a pleomorphic adenoma of the parotid gland. Detailed molecular analysis revealed an LIFR/PLAG1 translocation characteristic for pleomorphic adenoma and, next to this, a PIK3R1 frameshift mutation and several allelic imbalances. In subsequent malignant recurrences, the same LIFR/PLAG1 translocation, PIK3R1 frameshift mutation, and allelic imbalances were present in addition to TP53 mutations. Thus, this case not only shows malignant transformation of SGPA, but also demonstrates that molecular analysis can be of help in recognising malignancy in the rare instance of RPA.

Background We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. Methods Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan–Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. Results All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. Conclusions The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.

Objective Dysphagia or difficulty in swallowing is a potentially hazardous clinical problem that needs regular monitoring. Real-time 2D MRI of swallowing is a promising radiation-free alternative to the current clinical standard: videofluoroscopy. However, aspiration may be missed if it occurs outside this single imaged slice. We therefore aimed to image swallowing in 3D real time at 12 frames per second (fps). Materials and methods At 3 T, three 3D real-time MRI acquisition approaches were compared to the 2D acquisition: an aligned stack-of-stars (SOS), and a rotated SOS with a golden-angle increment and with a tiny golden-angle increment. The optimal 3D acquisition was determined by computer simulations and phantom scans. Subsequently, five healthy volunteers were scanned and swallowing parameters were measured. Results Although the rotated SOS approaches resulted in better image quality in simulations, in practice, the aligned SOS performed best due to the limited number of slices. The four swallowing phases could be distinguished in 3D real-time MRI, even though the spatial blurring was stronger than in 2D. The swallowing parameters were similar between 2 and 3D. Conclusion At a spatial resolution of 2-by-2-by-6 mm with seven slices, swallowing can be imaged in 3D real time at a frame rate of 12 fps.

Introduction: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy.Materials and methods: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated.Results: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated posttreatment xerostomia and dysphagia >= grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p =.007; 0.016/gy, 95%CI 0.001-0.031, p =.036). Follow-up at 24 months had similar results.Conclusion: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life. (C) 2020 The Authors. Published by Elsevier B.V.

Objective MRI of the tongue requires acceleration to minimise motion artefacts and to facilitate real-time imaging of swallowing. To accelerate tongue MRI, we designed a dedicated flexible receiver coil. Materials and methods We designed a flexible 12-channel receiver coil for tongue MRI at 3T and compared it to a conventional head-and-neck coil regarding SNR and g-factor. Furthermore, two accelerated imaging techniques were evaluated using both coils: multiband (MB) diffusion-tensor imaging (DTI) and real-time MRI of swallowing. Results The flexible coil had significantly higher SNR in the anterior (2.1 times higher, P = 0.002) and posterior (2.0 times higher, P < 0.001) parts of the tongue, while the g-factor was lower at higher acceleration. Unlike for the flexible coil, the apparent diffusion coefficient (P = 0.001) and fractional anisotropy (P = 0.008) deteriorated significantly while using the conventional coil after accelerating DTI with MB. The image quality of real-time MRI of swallowing was significantly better for hyoid elevation (P = 0.029) using the flexible coil. Conclusion Facilitated by higher SNR and lower g-factor values, our flexible tongue coil allows faster imaging, which was successfully demonstrated in MB DTI and real-time MRI of swallowing.

Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow‐up time and (for SGC patients) histological subtype. The mean follow‐up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow‐up, 52 patients with SGC and 74 patients with SGPA developed BC. The median time to BC was 6 years after SGC and 7 after SGPA. The cumulative risk at 10 years of follow‐up was 3.1% after SGC and 3.5% after SGPA (95% Confidence Interval (95%CI) 2.1%–4.7% and 2.6%–4.6%, respectively). BC incidence was 1.59 times (95%CI 1.19–2.09) higher in the SGC‐cohort than expected based on incidence rates in the general population. SGPA‐patients showed a 1.48 times (95%CI 1.16–1.86) higher incidence. Women with SGC or SGPA have a slightly increased risk of BC. The magnitude of risk justifies raising awareness, but is no reason for BC screening., Salivary and mammary gland tumors share biological and epidemiological characteristics, suggesting common risk factors. Investigation of nationwide cohorts of patients with salivary gland cancer or pleomorphic adenoma with long‐term follow‐up data and complete cancer incidence information, highlights an increased risk of breast cancer in these patients.

For radical resection of squamous cell carcinoma of the oral cavity, a tumor-free margin of at least 5 mm is required. Unfortunately, establishing in-depth margins is a surgical conundrum. Knowing that the hybrid sentinel node (SN) tracer indocyanine green (ICG)-Tc-99m-nanocolloid generates temporary tattoolike markings at the site of administration, we studied the ability to apply this tracer for tumor margin demarcation combined with SN biopsy. Methods: Nineteen patients with clinical T1-T2 oral tongue tumors received the traditional superficial 3 or 4 deposits of ICG-Tc-99m-nanocolloid (0.1 mL each), and in 12 patients additional deposits were placed deeply using ultrasound guidance (total of 6; 0.07 mL each). SN mapping was performed using lymphoscintigraphy and SPECT/CT. Before and directly after tumor excision, fluorescence imaging was performed to monitor the tracer deposits in the patient (fluorescent deposits were not used to guide the surgical excision). At pathologic examination, primary tumor samples were studied in detail. Results: The number of tracer depositions did not induce a significant difference in the number of SNs visualized (P = 0.836). Reproducible and deep tracer deposition proved to be challenging. The fluorescent nature of ICG-Tc-99m-nanocolloid supported in vivo and ex vivo identification of the tracer deposits surrounding the tumor. Pathologic examination indicated that in 66.7% (8/12), all fluorescence was observed within the resection margins. Conclusion: This study indicates that tumor margin demarcation combined with SN identification has potential but that some practical challenges need to be overcome if this technique is to mature as a surgical guidance concept. Future studies need to define whether the technology can improve the radical nature of the resections.

Background: To explore variation in numbers and treatment between hospitals that treat head and neck cancer (HNC) in the Netherlands. Material and methods: Patient, tumor and treatment characteristics were collected from the Netherlands Cancer Registry, while histopathological features were obtained by linkage to the national pathology record register PALGA. Inter-hospital variation in volume, stage, treatment, pathologically confirmed loco-regional recurrence and overall survival rate was evaluated by tumor site. Results: In total, 2094 newly diagnosed patients were included, ranging from 65 to 417 patients in participating hospitals treating HNC in 2008. Oral cavity cancer was mainly treated by surgery only, ranging from 46 to 82% per hospital, while the proportion of surgery with (chemo)radiotherapy ranged from 18 to 40%. Increasing age, male sex, and high stage were associated with a higher hazard of dying. In oropharynx cancer, the use of (chemo)radiotherapy varied from 31 to 82% between hospitals. We found an indication that higher volume was associated with a lower overall hazard of dying for the total group, but not by subsite. Low numbers, e.g. for salivary gland, nasopharynx, nasal cavity and paranasal sinus, did not permit all desired analyses. Conclusion: This study revealed significant interhospital variation in numbers and treatment of especially oropharyngeal and oral cavity cancer. This study is limited because we had to rely on data recorded in the past for a different purpose. To understand whether this variation is unwanted, future research should be based on prospectively collected data, including detailed information on recurrences, additional case-mix information and cause of death.

In head and neck squamous cell carcinoma (HNSCC), the search for better prognostic factors beyond TNM-stage is ongoing. Lymph node ratio (LNR) (positive lymph nodes/total lymph nodes) is gaining interest in view of its potential prognostic significance. All HNSCC patients at the Netherlands Cancer Institute undergoing neck dissection for lymph node metastases in the neck region between 2002 and 2012 (n = 176) were included. Based on a protocol change in specimen processing, the cohort was subdivided in two distinct consecutive periods (pre and post 2007). The prognostic value of LNR, N-stage, and number of positive lymph nodes for overall survival was assessed. The mean number of examined lymph nodes after 2007 was significantly higher (42.3) than before (35.8) (p = 0.024). The higher number concerned mostly lymph nodes in level V. The mean number of positive lymph nodes before 2007 was 3.3 vs. 3.6 after 2007 (p = 0.745). By multivariate analysis of both pre- and post-2007 cohort data, two factors remained associated with an increased hazard of dying: N2 [HR 2.1 (1.1–4.1) and 2.4 (1.0–5.8)] and >3 positive lymph nodes [HR 2.0 (1.1–3.5) and 3.1 (1.4–6.9)]. Hazard ratio for LNR >7 % was not significantly different: pre 2007 at 2.2 (1.3–3.8) and post 2007 at 2.1 (1.0–4.8, p = 0.053). In this study, changes in specimen processing influenced LNR values, but not the total number of tumor positive nodes found. Therefore, in HNSCC, the number of positive nodes seems a more reliable parameter than LNR, provided a minimum number of lymph nodes are examined.

Background: Head and neck rhabdomyosarcoma (HNRMS) survivors are at risk to develop adverse events (AEs). The impact of these AEs on psychosocial well‐being is unclear. We aimed to assess psychosocial well‐being of HNRMS survivors and examine whether psychosocial outcomes were associated with burden of therapy.Procedure: Sixty‐five HNRMS survivors (median follow‐up: 11.5 years), treated in the Netherlands and the United Kingdom between 1990 and 2010 and alive ≥2 years after treatment visited the outpatient multidisciplinary follow‐up clinic once, in which AEs were scored based on a predefined list according to the Common Terminology Criteria for Adverse Events. Survivors were asked to complete questionnaires on health‐related quality of life (HRQoL; PedsQL and YQOL‐FD), self‐perception (KIDSCREEN), and satisfaction with appearances (SWA). HRQoL and self‐perception scores were compared with reference values, and the correlation between physician‐assessed AEs and psychosocial well‐being was assessed.Results: HNRMS survivors showed significantly lower scores on PedsQL school/work domain (P ≤ 0.01, P = 0.02, respectively), YQOL‐FD domains negative self‐image and positive consequences (P ≤ 0.01, P = 0.04, respectively) compared with norm data; scores on negative consequences domain were significantly higher (P = 0.03). Over 50% of survivors negatively rated their appearances on three or more items. Burden of AEs was not associated with generic HRQoL and self‐perception scores, but was associated with disease‐specific QoL (YQOL‐FD).Conclusion: In general, HRQoL in HNRMS survivors was comparable to reference groups; however, survivors did report disease‐specific consequences. We therefore recommend including specific questionnaires related to difficulties with facial appearance in a systematic monitoring program to determine the necessity for tailored care.

Objective: To illustrate a case of sensorineural hearing loss (SNHL) after immunotherapy based on T cell receptor (TCR) gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma.Patient: We present a 59-year-old woman with profound subacute bilateral SNHL including unilateral deafness after immunotherapy based on TCR gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma. Ten days after treatment, the patient developed hearing loss of 57 dB hearing loss air conduction at pure-tone average 0.5-1-2-4 kHz in the right ear, and >100 dB hearing loss air conduction at pure-tone average 0.5-1-2-4 in the left ear. The right ear recovered partially, while the left ear remained deaf, despite oral prednisolone (1.0 mg/kg) and salvage treatment with three transtympanic injections of 0.5 ml dexamethasone (4.0 mg/ml).Conclusion: Based on our presented case and a vast amount of literature there is circumstantial evidence that TCR gene therapy for melanoma targets the perivascular macrophage-like melanocytes in the stria vascularis, resulting in SNHL. We suggest that SNHL after TCR gene therapy may be caused by a disruption of the blood-labyrinth-barrier and the endolymphatic potential and/or a sterile inflammation of the stria vascularis. In severe cases like our subject, we posit that endolymphatic hydrops or hair cell loss may cause irreversible and asymmetrical deafness. Steroid prophylaxis via transtympanic application is debatable.

Purpose Even when guided by SPECT/CT planning of nodal resection in the head-and-neck area is challenging due to the many critical anatomical structures present within the surgical field. In this study the potential of a (SPECT/)MRI-based surgical planning method was explored. Hereby MRI increases the identification of SNs within clustered lymph nodes (LNs) and vital structures located adjacent to the SN (such as cranial nerve branches). Method and patients SPECT/CT and pathology reports from 100 head-and-neck melanoma and 40 oral cavity cancer patients were retrospectively assessed for SN locations in levels I–V and degree of nodal clustering. A diffusion-weighted-preparation magnetic resonance neurography (MRN) sequence was used in eight healthy volunteers to detect LNs and peripheral nerves. Results In 15% of patients clustered nodes were retrospectively shown to be present at the location where the SN was identified on SPECT/CT (level IIA: 37.2%, level IIB: 21.6% and level III: 15.5%). With MRN, improved LN delineation enabled discrimination of individual LNs within a cluster. Uniquely, this MRI technology also provided insight in LN distribution (23.2 ± 4 LNs per subject) and size (range 21–372 mm3), and enabled non-invasive assessment of anatomical variances in the location of the LNs and facial nerves. Conclusion Diffusion-weighted-preparation MRN enabled improved delineation of LNs and their surrounding delicate anatomical structures in the areas that most often harbor SNs in the head-and-neck. Based on our findings a combined SPECT/MRI approach is envisioned for future surgical planning of complex SN resections in this region.

With exponentially increasing numbers of basal cell carcinoma (BCC) of the head and neck region, also the locally advanced BCCs are increasing in number. These tumours are associated with aggressive biological behaviour with invasion of soft tissues, organs or bone and present with wide variation in management strategies. The objectives of the study was to describe the biological behaviour of aggressive BCCs and their clinical presentation in the head and neck region with a series of cases treated in our tertiary hospital, discuss management plans of such complex cases in terms of surgical planning and reconstruction. A series of five cases of aggressive BCC in the head and neck region with involvement of organs such as nose, orbit, temporal bone, facial nerve, paranasal sinuses and mandible was studied. Locally advanced, aggressive BCC should be evaluated and treated as head and neck tumours. Multidisciplinary team (MDT) discussion is advisable wherein the strategies on surgical excision, reconstruction options, facial nerve rehabilitation, indications for prosthesis and further adjuvant treatment such as radiotherapy and chemotherapy are carefully planned.

Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. It occurs predominantly in the head and neck area and often behaves aggressively. In this single-institution retrospective observational cohort study, we describe the results of a treatment strategy that we developed over the past decades. Endpoints of this study were local, regional and distant control, disease-specific survival and overall survival. In total 47 patients with head and neck MCC, diagnosed in the Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI-AvL) between 1984 and 2012, were included in this study. Local tumor control was 82 % (95 % CI 71-95 %) at 5 years. Regional lymph node metastases were found at the moment of diagnosis in 13 cases (28 %). In the group of patients who were initially cN0, the 5-year regional control was 80 % (68-95 %). The 5-year metastasis-free interval probability was 80 % (68-94 %). The disease-specific survival (DSS) at 5 years was 70 % (56-86 %). An overall survival of 54 % (40-72 %) was found at 5-year follow-up and of 37 % (23-59 %) at 10-year follow-up. Univariable Cox regression analysis of many clinical and pathological variables did not identify any predictors for DSS. The MCC has a high propensity for locoregional and distant spread in the head and neck region. Undertreatment, especially of the lymph nodes in the neck, is a serious problem as regional (micro)metastasis are common even in T1 tumors. Future research will have to elucidate the role of the sentinel lymph node procedure versus the elective selective node dissection and standardized elective local and regional radiotherapy in the head and neck area.

For radical resection of squamous cell carcinoma of the oral cavity, a tumor-free margin of at least 5 mm is required. Unfortunately, establishing in-depth margins is a surgical conundrum. Knowing that the hybrid sentinel node (SN) tracer indocyanine green (ICG)

In oral cancer treatment, function loss such as speech and swallowing deterioration can be severe, mostly due to reduced lingual mobility. Until now, there is no standardized measurement tool for tongue mobility and pre-operative prediction of function loss is based on expert opinion instead of evidence based insight. The purpose of this study was to assess the reliability of a triple-camera setup for the measurement of tongue range of motion (ROM) in healthy adults and its feasibility in patients with partial glossectomy. A triple-camera setup was used, and 3D coordinates of the tongue in five standardized tongue positions were achieved in 15 healthy volunteers. Maximum distances between the tip of the tongue and the maxillary midline were calculated. Each participant was recorded twice, and each movie was analysed three times by two separate raters. Intrarater, interrater and test–retest reliability were the main outcome measures. Secondly, feasibility of the method was tested in ten patients treated for oral tongue carcinoma. Intrarater, interrater and test–retest reliability all showed high correlation coefficients of >0.9 in both study groups. All healthy subjects showed perfect symmetrical tongue ROM. In patients, significant differences in lateral tongue movements were found, due to restricted tongue mobility after surgery. This triple-camera setup is a reliable measurement tool to assess three-dimensional information of tongue ROM. It constitutes an accurate tool for objective grading of reduced tongue mobility after partial glossectomy.

Background The radiation and concomitant high-dose intra-arterial or intravenous cisplatin (RADPLAT) phase III trial compared intra-arterial (IA) to intravenous (IV) cisplatin-based chemoradiation for head and neck cancer. Long-term efficacy and toxicity are reported after a median follow-up of 7.5 years. Methods Patients with inoperable squamous cell carcinoma (SCC) of the oropharynx, oral cavity, or hypopharynx, were randomized between radiotherapy (RT) + IA cisplatin 150 mg/m2, followed by systemic rescue or RT + I.V. cisplatin 100 mg/m2. RT consisted of 46 Gy to the affected and elective areas, followed by a boost of 24 Gy. Results Among 237 patients, 57 recurred locally, 35 regionally, and 80 locoregionally. There were 32 second primary tumors, 65 distant metastases, and 154 deaths. Locoregional control and overall survival were not different between the treatment arms. Late dysphagia was worse in the I.V. arm (log-rank p = .014). Conclusion IA cisplatin did not improve tumor control compared to I.V. administered cisplatin, despite the higher dose in IA delivery of the drug. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

ImportancePatients with head and neck cancer may experience chemoradiotherapy-induced hearing loss, but the weighing of involved variables has been subjective. Identification of patient and treatment characteristics to predict the absolute posttreatment hearing level is important for effective counseling of patients undergoing chemoradiotherapy.ObjectiveTo predict treatment-induced hearing loss among patients with head and neck cancer.Design, Setting, and ParticipantsA retrospective cohort study was performed at The Netherlands Cancer Institute. One hundred and fifty-six patients with head and neck cancer treated with concomitant chemoradiotherapy as the primary treatment modality from January 1, 1997, through December 31, 2011, were enrolled. Follow-up was complete on March 1, 2012, and data were analyzed from April 1, 2011, through November 5, 2013.InterventionsHigh-dose intravenously administered cisplatin-based concomitant chemoradiotherapy. Cisplatin, 100 mg/m2, was administered in 3 courses on days 1, 22, and 43 during 7 weeks of radiotherapy (total radiation dose, 70 Gy in 35 fractions).Main Outcomes and MeasuresPosttreatment bone conduction hearing threshold at pure-tone average frequencies of 1, 2, and 4 kHz, based on pure-tone audiometry after completion of treatment. Predictors included baseline hearing levels, radiation dose to the cochlea, and cisplatin dose. A multilevel mixed-effects linear regression model for predicting whether or not posttreatment hearing was at least 35 dB was established, and cross-validated sensitivity and specificity were obtained.ResultsOf 156 patients who received high-dose concomitant chemoradiotherapy, 15 were missing the exact radiation dose to the cochlea and 41 had no data on posttreatment pure-tone audiometry. Nineteen patients had a hearing level of at least 35 dB for at least 1 ear before the treatment. The remaining 81 patients (162 ears) had a total cumulative cisplatin dose ranging from 315 to 600 (median, 546) mg. The radiation dose to the cochlea ranged from 1.1 to 70.9 (median, 13.6) Gy. Based on data from the 81 patients (162 ears), the area under the receiver operating characteristic curve was 0.68, with a sensitivity of 29% (95% CI, 13%-51%) and a specificity of 97% (95% CI, 88%-100%), resulting in a positive predictive value of 78%.Conclusions and RelevancePatient and treatment characteristics can be used to predict hearing level after concomitant chemoradiotherapy for head and neck cancer. This step may constitute the first in evidence-based individual counseling for treatment-induced hearing loss.

Purpose To evaluate the hybrid approach in a large population of patients with melanoma in the head and neck, on the trunk, or on an extremity who were scheduled for sentinel node (SN) biopsy. Materials and Methods This prospective study was approved by the institutional review board. Between March 2010 and March 2013, 104 patients with a melanoma, including 48 women (average age, 54.3 years; range, 18.5-87.4 years) and 56 men (average age, 55.2 years; range, 22.4-77.4 years) (P = .76) were enrolled after obtaining written informed consent. Following intradermal hybrid tracer administration, lymphoscintigraphy and single photon emission computed tomography/computed tomography were performed. Blue dye was intradermally injected prior to the start of the surgical operation (excluding patients with a facial melanoma). Intraoperatively, SN sentinel node s were initially pursued by using gamma tracing followed by fluorescence imaging ( FI fluorescence imaging ) and, when applicable, blue-dye detection. A portable gamma camera was used to confirm SN sentinel node removal. Collected data included number and location of the preoperatively and intraoperatively identified SN sentinel node s and the intraoperative number of SN sentinel node s that were radioactive, fluorescent, and blue. A two-sample test for equality of proportions was performed to evaluate differences in intraoperative SN sentinel node visualization through FI fluorescence imaging and blue-dye detection. Results Preoperative imaging revealed 2.4 SN sentinel node s (range, 1-6) per patient. Intraoperatively, 93.8% (286 of 305) of the SN sentinel node s were radioactive, 96.7% (295 of 305) of the SN sentinel node s were fluorescent, while only 61.7% (116 of 188) of the SN sentinel node s stained blue (P < .0001). FI fluorescence imaging was of value for identification of near-injection-site SN sentinel node s (two patients), SN sentinel node s located in complex anatomic areas (head and neck [28 patients]), and SN sentinel node s that failed to accumulate blue dye (19 patients). Conclusion The hybrid tracer enables both preoperative SN sentinel node mapping and intraoperative SN sentinel node identification in melanoma patients. In the setup of this study, optical identification of the SN sentinel node s through the fluorescent signature of the hybrid tracer was superior compared with blue dye-based SN sentinel node visualization.

Aim The aim of this study is to prove that facial surface electromyography (sEMG) conveys sufficient information to predict 3D lip shapes. High sEMG predictive accuracy implies we could train a neural control model for activation of biomechanical models by simultaneously recording sEMG signals and their associated motions. Materials and methods With a stereo camera set-up, we recorded 3D lip shapes and simultaneously performed sEMG measurements of the facial muscles, applying principal component analysis (PCA) and a modified general regression neural network (GRNN) to link the sEMG measurements to 3D lip shapes. To test reproducibility, we conducted our experiment on five volunteers, evaluating several sEMG features and window lengths in unipolar and bipolar configurations in search of the optimal settings for facial sEMG. Conclusions The errors of the two methods were comparable. We managed to predict 3D lip shapes with a mean accuracy of 2.76 mm when using the PCA method and 2.78 mm when using modified GRNN. Whereas performance improved with shorter window lengths, feature type and configuration had little influence.

In oral cancer, loss of function due to surgery can be unacceptable, designating the tumour as functionally inoperable. Other curative treatments can then be considered. Currently, predictions of these functional consequences are subjective and unreliable. We want to create patient-specific models to improve and objectify these predictions. A first step was taken by controlling a 3D lip model with volunteer-specific sEMG activities. We focus on the lips first, because they are essential for speech, oral food transport, and facial mimicry. Besides, they are more accessible to measurements than intraoral organs. 3D lip movement and corresponding sEMG activities are measured in five healthy volunteers, who performed 19 instructions repeatedly, to create a quantitative lip model by establishing the relationship between sEMG activities of eight facial muscles bilaterally on the input side and the corresponding 3D lip displacements on the output side. The relationship between 3D lip movement and sEMG activities was accommodated in a state-space model. A good relationship between sEMG activities and 3D lip movement was established with an average root mean square error of 2.43 mm for the first-order system and 2.46 mm for the second-order system. This information can be incorporated into biomechanical models to further personalise functional outcome assessment after treatment.

Objectives/Hypothesis The purpose of this study was to determine whether concomitant chemoradiation (CCRT)-induced hearing loss is progressive over time or not. Study Design Long-term (LT) follow-up study. Methods Between 1999 and 2004, 158 patients with head and neck cancer were treated with intravenous (IV) CCRT (n = 80) or intraarterial CCRT (n = 78). Audiometry was performed before, short-term (ST), and LT posttreatment. Differences in hearing were assessed with a multivariable linear regression analysis, incorporating the effect of aging. Results Long-term audiometry (median 4.5 years) was available in 67 patients (42%). At ST follow-up, a deterioration of 21.6 decibel was seen compared to baseline at pure-tone averages (PTA) 8-10-12.5 kHz. At LT follow-up, this deterioration further increased with 5 decibel (P = 0.005). Only in CCRT-IV patients was a significant progressive treatment-induced hearing loss seen, at PTA 8-10-12.5 kHz (P = 0.005), PTA 1-2-4 kHz air conduction (P = 0.014), and PTA 0.5-1-2 kHz bone conduction (P = 0.045). Conclusion CCRT-induced hearing impairment was progressive over time, especially in higher frequencies and only in CCRT-IV patients, with a modest deterioration of 5 decibel 4.5 years post-treatment.

Background Both radiotherapy (RT) and cisplatin-based chemoradiotherapy (CRT) in patients with head and neck cancer may cause sensorineural hearing loss (SNHL). The purpose of this review was to provide more insight into SNHL because of CRT compared to RT. Methods Comprehensive search of Medline and Embase with the terms “radiotherapy” combined with “ototoxicity,” “head and neck squamous cell carcinoma,” and synonyms. Results Of the 2507 studies found, 21 were included in this study. Pooled analysis could not be committed because of heterogeneity. Incidence rates of SNHL after RT and CRT varied considerably, with percentages ranging from 0% to 43% and 17% to 88%, respectively. Factors that influenced the risk of SNHL were radiation dose to the cochlea, follow-up time, age, baseline hearing level, and cisplatin dose. Conclusion The wide range of SNHL incidence rates makes it impossible to draw any conclusions on the severity of RT- and CRT-induced ototoxicity. To allow for future comparison of study outcomes, development of uniform criteria is of utmost importance. © 2014 Wiley Periodicals, Inc. Head Neck 37: 281-292, 2015

ObjectiveThe increasing volume of head and neck squamous cell carcinoma (HNSCC) patients can lead to longer intervals between histopathological diagnosis and primary treatment. This could cause psychological distress to the patient, but more importantly could possibly lead to tumor progression and decreased survival. Accordingly, this study investigates these relationships.MethodsThe correlation of professional delay and clinical characteristics of 2493 patients, treated between 1990 and 2011 with oral, oropharyngeal, hypopharyngeal and laryngeal SCC, was investigated. Patients were divided in two groups based on treatment delay, defined as the interval between histopathological diagnosis and initial treatment. Univariate and multivariate proportional hazards models were used to assess disease specific survival (DSS) and disease free survival (DFS).ResultsYear of diagnosis, tumor site and therapy were significantly related to treatment delay. Tumor stage was not related to treatment delay. Multivariate regression models revealed that the group with a delay of more than 30 days had a better DSS (HR .838, CI .697-.922, p = .041) and DFS (HR .816, CI .702-.947), p = .007) than the group treated within 30 days.ConclusionIn our study, treatment delay up to 90 days is not related to impaired survival. This argument can be used extremely cautiously to comfort patients who have to wait several weeks for treatment. Although, possible tumor progression during treatment delay could have led to increased morbidity subsequent to more extensive treatment. Also, possible negative psychological impact of delay in treatment should not be underestimated.

Background The purpose of this study was to provide anatomic guidance for the extent (technique) of suboccipital node dissection. Methods Five human cadaver necks (9 sides) were studied. Boundaries were the superior nuchal line and external occipital protuberance (cranial), the nuchal ligament (medial), an imaginary line through C7 (caudal), and the posterior wall of the auditory channel (anterior). The overlying skin and complete thickness of the cranial part of the trapezius muscle and fascia sheath was included (deep). Results An average number of 4 lymph nodes per suboccipital side were found. Diameters ranged from 1 to 6 mm. Twenty nodes (63%) were located in the subcutaneous tissue, 12 (37%) were found just underneath the superficial fascia of the trapezius muscle. Conclusion Suboccipital nodes are small and mainly located in the subcutaneous layer, with a minority just underneath the superficial fascia of the trapezius muscle. This anatomic knowledge was used to refine the suboccipital dissection. © 2013 Wiley Periodicals, Inc. Head Neck 36: 682–686, 2014

Objectives: The aim of this study is to determine a set of MRI lymph node characteristics predictive for extranodal tumor spread (ENS) in head and neck cancer patients.Methods: In 39 patients, 60 lymph nodes with on MRI a minimal axial diameter of more than 1 cm or an inhomogeneous enhancement were studied. Two radiologists evaluated all MR-images for findings potentially indicative of the presence of ENS. Sensitivity, specificity and odds ratios based on logistic regression were calculated.Results: On MR-imaging, 20 lymph nodes were staged positive for ENS. On histopathology, 30 nodes were positive for ENS. In total, 14 nodes (23%) were scored differently on MR-imaging and histopathology. The MR-finding "infiltration of adjacent planes" established a specificity of 100% (lower 90% confidence bound: 91%) and sensitivity of 50% (95% confidence interval [CI]: 28-72%).Conclusion: The MRI finding "infiltration of adjacent planes" may be high enough (100% in our study) to be used for treatment planning. (C) 2013 Elsevier Ltd. All rights reserved.

Objective. This study was conducted to assess the value of CT and MR imaging in the preoperative evaluation of ICA encasement.Methods. Based upon three patient groups this study was performed. Retrospective analysis of 260 neck dissection reports from 2001 to 2010 was performed to determine unexpected peroperative-diagnosed encasement. Two experienced head and neck radiologists reviewed 12 scans for encasement.Results. In four out of 260 (1.5%) patients undergoing neck dissection, preoperative imaging was false negative as there was peroperative encasement of the ICA. Of 380 patients undergoing preoperative imaging, the radiologist reported encasement of the ICA in 25 cases. In 342 cases no encasement was described, 125 of these underwent neck dissection, and 2 had encasement peroperatively. The interobserver variation kappa varied from 0.273 to 1 for the different characteristics studied.Conclusion. These retrospectively studied cohorts demonstrate that preoperative assessment of encasement of the ICA using MRI and/or CT was of value in evaluation of ICA encasement and therefore contributively in selecting operable patients (without ICA encasement), since in only 1.5% encasement was missed. However, observer variation affects the reliability of this feature.

To describe the outcome of patients with poorly differentiated thyroid cancer (PDTC) presenting with gross extrathyroidal extension (ETE). After obtaining Institutional Review Board approval, we performed a retrospective review of a consecutive series of thyroid cancer patients treated by primary surgical resection with or without adjuvant therapy at Memorial Sloan-Kettering Cancer Center from 1986 to 2009. Out of 91 PDTC patients, 27 (30%) had gross ETE (T4a), and they formed the basis of our study. Of 27 patients, 52% were women. The median age was 70 years (range 27-87 years). Ten patients (37%) presented with distant metastases; four to bone, three to lung, and three to both bone and lung. All patients had extended total thyroidectomy, except two who had subtotal thyroidectomy. Twenty patients (74%) had central compartment neck dissection and 11 also had lateral neck dissection. Four patients had pN0, six (30%) pN1a, and 10 (50%) pN1b neck disease. Twenty-one patients (77%) had adjuvant therapy: 15 (55%) radioactive iodine (RAI) only, three (11%) postoperative external beam radiation (EBRT) only, and three (11%) had both RAI and EBRT. Overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and regional recurrence-free survival (RRFS) were calculated by the Kaplan Meier method. The median follow-up time was 57 months (range 1-197 months). The 5 year OS and DSS were 47% and 49%, respectively. This poor outcome was due to distant metastatic disease; 10 patients had distant metastases at presentation and a further six developed distant metastases during follow-up. Locoregional control was good with 5-year LRFS and RRFS of 70% and 62%, respectively. Overall, eight patients (30%) had recurrences: two had distant alone, two regional, two regional and distant, one local and distant, and one had local, regional, and distant recurrence. Aggressive surgery in patients with PDTC showing gross ETE resulted in satisfactory locoregional control. Due to the small proportion of patients who received EBRT (22%), it is not possible to analyze its benefit on locoregional control. Of significance is the observation that the majority of patients (60%) who presented with or subsequently developed distant metastases eventually died of distant disease. New systemic therapies to target distant metastatic disease are required for improvements in outcome

Background. Tumor volume is a significant prognostic factor in the treatment of malignant head and neck tumors. Unfortunately, it is not routinely measured because of the workload involved. Methods. Twenty-one patients, between 2009 and 2010, were studied. Dynamic contrast-enhanced MRI (DCE-MRI) at 3.0T was performed. A workstation previously developed for semi-automated segmentation of breast cancers on DCE-MRI was used to segment the head and neck cancers. The Pearson correlation analysis was used to assess the agreement between volumetric measurements and the manually derived gross tumor volume (GTV). Results. In 90.5% of the patients (19 of 21) correlation could be made between DCE-MRI and the manually derived GTV. The Pearson correlation coefficient between the automatically derived tumor volume at DCE-MRI and the manually derived GTVs was R 2 ¼ 0.95 (p < .001). Conclusion. Semi-automated tumor volumes on DCE-MRI were representative of those derived from the manually derived GTV (R 2 ¼ 0.95; p < .001). V C 2012 Wiley Periodicals, Inc. Head Neck 35: 521-526, 2013

Purpose This study was designed to examine the feasibility of combining lymphoscintigraphy and intraoperative sentinel node identification in patients with head and neck melanoma by using a hybrid protein colloid that is both radioactive and fluorescent. Methods Eleven patients scheduled for sentinel node biopsy in the head and neck region were studied. Approximately 5 h before surgery, the hybrid nanocolloid labeled with indocyanine green (ICG) and technetium-99m (99mTc) was injected intradermally in four deposits around the scar of the primary melanoma excision. Subsequent lymphoscintigraphy and single photon emission computed tomography with computed tomography (SPECT/CT) were performed to identify the sentinel nodes preoperatively. In the operating room, patent blue dye was injected in 7 of the 11 patients. Intraoperatively, sentinel nodes were acoustically localized with a gamma ray detection probe and visualized by using patent blue dye and/or fluorescence-based tracing with a dedicated near-infrared light camera. A portable gamma camera was used before and after sentinel node excision to confirm excision of all sentinel nodes. Results A total of 27 sentinel nodes were preoperatively identified on the lymphoscintigraphy and SPECT/CT images. All sentinel nodes could be localized intraoperatively. In the seven patients in whom blue dye was used, 43% of the sentinel nodes stained blue, whereas all were fluorescent. The portable gamma camera identified additional sentinel nodes in two patients. Ex vivo, all radioactive lymph nodes were fluorescent and vice versa, indicating the stability of the hybrid tracer. Conclusions ICG–99mTc-nanocolloid allows for preoperative sentinel node visualization and concomitant intraoperative radio- and fluorescence guidance to the same sentinel nodes in head and neck melanoma patients. Electronic supplementary material The online version of this article (doi:10.1245/s10434-011-2180-7) contains supplementary material, which is available to authorized users.

Purpose To determine the incidence and pattern of cervical lymphatic drainage in patients with melanomas located on the upper limb or trunk, and to evaluate our current neck dissection protocol for those patients with a N+ neck. Methods Of 1192 melanoma patients who underwent sentinel node biopsy, 631 were selected with a primary tumor on the upper limb or trunk. All lymphoscintigrams, SPECT/CT images and operative reports were reviewed to determine the exact locations of sentinel nodes visualized preoperatively and dissected during operation. Results Thirty-nine (6.2 %) of 631 patients with a melanoma on the upper limb or trunk showing cervical lymph node drainage were identified. In 34 (87 %) of 39 patients, sentinel nodes were excised from level IV or Vb, and in 30 of those 39 patients simultaneous from the axilla. In the remaining five patients (13 %), sentinel nodes were collected from level IIb, level III or the suboccipital region. All collected sentinel nodes were located in the intended dissection area for N+ patients. Thirteen patients (33 %) had a total of 22 tumor-positive sentinel nodes in either the axilla (n = 10), level IV (n = 2), Vb (n = 9) or suboccipital (n = 1). Conclusions Only a minority of the patients with upper limb or trunk melanomas demonstrated lymphatic drainage to cervical lymph node basins, with preferential drainage to levels IV and Vb. Our current dissection protocol of levels II–V, with or without extension to the suboccipital region, in those patients with involved cervical sentinel nodes seems sufficient.

Background. High rates of positive surgical margins are reported after a maxillectomy. A large part of tumors that are preoperatively considered ''operable'' can thus not be resected with tumor-free margins. Methods. This was a retrospective study on medical files of 69 patients that underwent maxillectomy as primary treatment for a squamous cell carcinoma. Results. More than one third (39%) of all resections performed is incomplete, with dorsal or dorsocranial-positive surgical margins in two thirds. Correlation of tumor extension on preoperative imaging to surgical margins status revealed that dorsal and cranial tumor extension were significant prognostic factors for tumor positive surgical margins (p ¼ .006 and p ¼ .031, respectively). Positive margins were associated with a 2-fold increased risk of death (hazard ratio, 2.4; 95% confidence interval, 1.2-4.9). Conclusion. Cranial or dorsal tumor extension on preoperative imaging was a significant risk factor for positive surgical margins after maxillectomy with significant negative influence on overall survival. V C 2012 Wiley Periodicals, Inc. Head Neck 34: 1652-1656, 2012

The purpose of this study was to compare the lymphoscintigraphic drainage patterns of a hybrid sentinel node tracer consisting of the fluorescent dye indocyanine green (ICG) and 99mTc-nanocolloid with the drainage pattern of 99mTc-nanocolloid alone, the current standard tracer in many European countries. Methods: Twenty-five patients with a melanoma in the head and neck region (n = 10), a melanoma on the trunk (n = 6), or penile carcinoma (n = 9) who were scheduled for sentinel node biopsy were prospectively included. First, the standard 99mTc-nanocolloid procedure was performed. After injection at the lesion site, lymphoscintigraphy was performed with a 10-min dynamic study and static planar images at 10 min and 2 h after injection, followed by SPECT/CT. The same scintigraphic procedure was repeated after injection of hybrid ICG–99mTc-nanocolloid the same afternoon in 10 patients or the next morning in 15 patients. The paired images of both injections were evaluated, and count rates in the sentinel nodes were calculated and compared. Sentinel nodes were surgically localized using blue dye, a γ-ray detection probe, a portable γ-camera, and a fluorescence camera. Results: Lymphatic drainage was visualized in all 25 patients using 99mTc-nanocolloid, leading to the identification of 66 sentinel nodes in total. These same sentinel nodes were also identified during the second scintigraphic procedure with ICG–99mTc-nanocolloid. Moreover, a high correlation between the radioactive counting rates in the sentinel nodes of both scintigraphic studies was observed (mean R2 = 0.83). Intraoperatively (4–23 h after the second injection), all preoperatively identified sentinel nodes could be localized using radio- and fluorescence guidance combined. In total, 95% of the sentinel nodes could be intraoperatively visualized by means of fluorescence imaging, whereas merely 54% stained blue. Ex vivo, all radioactive sentinel nodes were fluorescent and vice versa. No adverse reactions were observed. Conclusion: The lymphatic drainage pattern of ICG–99mTc-nanocolloid is identical to that of 99mTc-nanocolloid. This observation, together with the added value of intraoperative fluorescence guidance, warrants wider evaluation of hybrid ICG–99mTc-nanocolloid as a tracer for sentinel node procedures.

A carotid body paraganglioma is a rare tumour of the neck, which occurs at the level of the carotid bifurcation.A 52-year-old man was referred with a 10-year history of a swelling on the right side of his neck. Imaging revealed that this was a carotid body paraganglioma. The tumour showed no hormonal activity and there were no other paraganglioma localisations. We removed the tumour surgically, and histological examination confirmed the diagnosis of paraganglioma. Genetic investigation revealed that the patient was a carrier of a mutation in the succinate dehydrogenase complex, subunit D (SDHD) gene.A paraganglioma of the carotid body is usually benign and slow-growing. It is familial in about 50% of cases, with a characteristic mutation in the SDHD-gene. Surgical removal is often the treatment of choice. If there is too high a risk of injury due to surgery, or in cases of inoperability, a "wait and see" policy with radiological follow-up is implemented. Diagnostics, treatment and follow-up demand a multidisciplinary approach.

Background and Objectives The aim of this study is to evaluate lymphatic drainage with sentinel node location data in patients with head and neck cutaneous melanoma, and to determine the implications for the extent of therapeutic neck dissections. Methods Sixty-five patients with head and neck cutaneous melanoma without evidence of regional metastases at ultrasound guided fine needle aspiration cytology examination were included. Lymphatic drainage patterns were investigated using planar and dynamic lymphoscintigraphy, and SPECT/CT. Biopsy of sentinel nodes was guided by images and gamma probe. The incidence of discordant sentinel nodes was determined by comparing actual drainage patterns to “O'Briens map” and to the treatment guidelines of The Netherlands Cancer Institute. Results Sentinel node identification was successful in 98% of the patients. Fifteen patients (23%) were diagnosed with a tumor-positive sentinel node. Two sentinel node-negative patients (3%) developed a regional lymph node metastasis (false-negative ratio: 12%). Twenty-three percent of the harvested sentinel nodes were discordant according to “O'Brien's map,” while 14% were discordant according to the treatment guidelines of The Netherlands Cancer Institute (P

Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam, Amsterdam, The Netherlands, Department of Surgical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam, Amsterdam, The Netherlands, Department of Oral and Maxillofacial Surgery, Academic Medical Hospital, Amsterdam, The Netherlands, Department of Phonetic Sciences, University of Amsterdam, Amsterdam, The Netherlands.

Objectives/Hypothesis: To assess device life of the new Provox Vega 22.5 and 20 Fr prostheses, to establish whether the optimized airflow characteristics of these devices materialize in better voice characteristics in comparison to Provox2, and to assess the feasibility of voice prosthesis replacement with the new Smart Inserter. Study Design: Prospective clinical phase II study. Methods: Prospective clinical phase II study including two patient cohorts (Provox Vega 22.5 Fr: N = 33; Provox Vega 20 Fr: N = 26). Device-life assessment, subjective data collection with study-specific structured questionnaires, perceptual analysis (Comparative Mean Opinion Score), and objective voice analysis (standard Dutch text, maximum phonation time, and dynamic range). Results: Device life of both prostheses appears comparable to Provox2. Several voice characteristics were better in Vega 22.5, which coincides well with patients' preference. Voicing with Vega 20 appears comparable to Provox2. Use of Smart Inserter showed a short learning curve, and was considered an improvement by the clinicians. Conclusions: The new Provox Vega 22.5 and 20 Fr prostheses have a device life comparable to Provox2, whereas voicing is better than (with the 22.5Fr version) or comparable (with the 20 Fr version) to Provox2. The Smart Inserter, after a short learning curve, turns out to be a further improvement of the anterograde replacement of these indwelling devices.

We introduced and evaluated a portable gamma-camera for intraoperative visualization of sentinel nodes in the head and neck region. METHODS: Planar lymphoscintigraphy and SPECT/CT were performed after peritumoral injection of (99m)Tc-nanocolloid in 25 patients (head and neck melanoma or oral cavity carcinoma). Sentinel nodes were localized intraoperatively with a portable gamma-camera and a hand-held gamma-probe. The portable gamma-camera was used to determine the distribution of remaining radioactivity after excision of the sentinel nodes. RESULTS: The portable gamma-camera visualized all 70 preoperatively identified sentinel nodes. Sentinel nodes at difficult sites could be localized more efficiently, and in 6 patients, 9 additional nodes (1 tumor-positive) were identified with the portable gamma-camera after excision. CONCLUSION: Intraoperative identification of sentinel nodes in the head and neck region with a portable gamma-camera is feasible and might lead to detection of more sentinel nodes

Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3–5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed.

Despite successful efforts to control tobacco and alcohol consumption in the western world, several developed countries report rising oropharyngeal squamous cell carcinoma (OPSCC) incidence figures, specifically in young individuals. Similar to anogenital cancers, a significant proportion of OPSCC (up to 60%) is caused by sexually acquired HPV infection and the rise in OPSCC has been attributed to changing sexual behaviours in the Western World. Accordingly, patients with HPV-positive OPSCC report divergent sexual histories and absence of classical risk factors as tobacco and alcohol exposure compared to patients with HPV-negative OPSCC. The profile of HPV-positive OPSCC differs from HPV-negative OPSCC in several other significant aspects, including a unique molecular biologic tumor characteristics and improved clinical behaviour. Thus, a further increase in HPV-positive OPSCC will impact significantly upon clinical management of OPSCC, unless it is halted by adequate preventive measures aimed at reduction of HPV-associated disease. HPV vaccination has been recently offered to young females in an attempt to reduce HPV-induced cervical cancer and may ultimately result in a decline of OPSCC incidence as well. Until then, close collaboration between otolaryngologists/head and neck surgeons and anogenital/genitourinary specialists is warranted to optimize clinical management of HPV-induced malignancy and improve detection of second primary tumor development.