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Objectives: Computed tomography perfusion (CTP) can provide information about angiogenesis and blood-flow characteristics in tumours. [18F]Fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) is one of the major oncological imaging techniques which provides information about viability of the tumour cell and partly also about its aggressiveness. The aim of the study was to investigate the relationship between FDG and CTP data in patients with head and neck cancers.Materials and Methods: Forty-one patients with a clinically suspected head and neck cancer were prospectively included. All patients underwent a combined PET/CT with an integrated CTP examination in the area of the head and neck tumour. CTP data (BF, BV and MTT) and PET data (SUVmax, SUVmean, TLG, PETvol) were compared between tumours and (1) healthy contralateral tissue, (2) inflammatory lesions, (3) metastatic lymph nodes, and CTP data and PET data were correlated in tumours.Results: Thirty-five patients had a head and neck cancer. All CTP data were statistically different between tumours, inflammatory lesions, healthy tissue and metastatic lymph nodes; PET/CT data were in part significantly different. CTP and PET parameters were not significantly correlated.Conclusion: CTP and PET parameters were not significantly correlated; thus, the additional CTP values provide additional insights into tumour behaviour and their glycolytic status. [ABSTRACT FROM AUTHOR]

The aims of this study were to assess a cohort of patients with head and neck squamous cell carcinoma (HNSCC) for: (1) the prevalence of synchronous distant metastases (DM) as detected by the initial staging by using (18)F-FDG PET/CT, (2) the prevalence of metachronous DM, and (3) the validity of published risk factors with special emphasis on the maximum standardized uptake value (SUV max) for the prediction of DM. Two hundred and ninety nine patients with advanced HNSCC were included. Following risk factors at the time of diagnosis and during follow-up were analyzed: advanced T/N stage, poor histological differentiation, level IV/Vb lymph nodes, primary site in the larynx/hypopharynx, and SUV max. The prevalence of DM at initial staging and during follow-up was 10% and 11%, respectively. At initial staging, primary site in the larynx/hypopharynx and neck nodes in level IV/Vb, and during follow-up only level IV/Vb nodes achieved statistical significance. The sensitivity for (18)F-FDG PET/CT with regard to the detection of DM was 96.8%, the specificity 95.4%, the positive predictive value (PV) 69.8%, and the negative PV 99.6%. Patients without DM showed a significantly better overall survival (OS) than patients developing DM (p<0.001). There was no significant difference in OS with regard to the time of diagnosis of DM. The prevalence for synchronous and metachronous DM in advanced HNSCC is considerable. (18)F-FDG PET/CT is highly accurate for initial staging and follow-up. DM carries a bad prognosis regardless of the time of diagnosis. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Using a retrospective approach, the aim of this study was to confirm the previously described value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in patients with primary extranodal lymphoma of the head and neck region. Additionally, the clinical significance of the semiquantitative analysis of the standardized uptake value (SUV), its predictive role in the follow-up setting, and its value in detection of synchronous primaries were studied. Study Design: Retrospective chart review. Methods: Twenty-six patients with a primary extranodal head and neck lymphoma (22 diffuse large B-cell lymphoma, one Hodgkin's lymphoma, three malignant T-cell lymphomas) were included. We retrospectively evaluated the clinical outcomes according to the maximum standardized uptake values of the primary lesion (SUV(max)) and whether a positron emission tomography/computed tomography (PET/CT) was performed or not in the follow-up studies. The median SUV(max) was chosen as the cutoff value. The patients were then grouped as those with either low or high SUV(max), respective to the cutoff value. Event-free survival and cumulative survival were endpoints of interest. Results: Nineteen patients (73%) were above the age of 60 years; the median age was 70 years (range, 28-87 years). Most primary sites were in the Waldeyer's ring (15 patients, 60%), whereas in four patients (27%) only the palatine tonsil was affected. The SUV(max) ranged from 5.8 to 33.9. In one patient, relevant fluorodeoxyglucose (FDG) uptake within the intestine revealed a cecal adenocarcinoma as a secondary primary. Twenty of the 25 clinically followed patients (80%) achieved complete remission after treatment. Patients with high SUV(max) showed favorable survival (log-rank test, P = .044). A tendency for longer survival within the group with follow-up PET/CT studies could be noted but with no significant statistical difference (P = .349). Conclusions: (18)F-FDG-PET/CT imaging is a potent primary staging tool. It also has application as an instrument for evaluation of follow-up and response to therapy in patients suffering from primary extranodal lymphoma and for detection of secondary malignancies. Furthermore, (18)F-FDG uptake by the primary lesion may be related to better survival. [ABSTRACT FROM AUTHOR]

Introduction: Sentinel lymph node biopsy for oral and oropharyngeal squamous cell carcinoma is a well-established staging method. One variation is to inject a radioactive tracer near the primary tumor of the patient. After a few minutes, audio feedback from an external hand-held [Formula: see text]-detection probe can monitor the uptake into the lymphatic system. Such probes place a high cognitive load on the surgeon during the biopsy, as they require the simultaneous use of both hands and the skills necessary to correlate the audio signal with the location of tracer accumulation in the lymph nodes. Therefore, an augmented reality (AR) approach to directly visualize and thus discriminate nearby lymph nodes would greatly reduce the surgeons' cognitive load., Materials and Methods: We present a proof of concept of an AR approach for sentinel lymph node biopsy by ex vivo experiments. The 3D position of the radioactive [Formula: see text]-sources is reconstructed from a single [Formula: see text]-image, acquired by a stationary table-attached multi-pinhole [Formula: see text]-detector. The position of the sources is then visualized using Microsoft's HoloLens. We further investigate the performance of our SLNF algorithm for a single source, two sources, and two sources with a hot background., Results: In our ex vivo experiments, a single [Formula: see text]-source and its AR representation show good correlation with known locations, with a maximum error of 4.47 mm. The SLNF algorithm performs well when only one source is reconstructed, with a maximum error of 7.77 mm. For the more challenging case to reconstruct two sources, the errors vary between 2.23 mm and 75.92 mm., Conclusion: This proof of concept shows promising results in reconstructing and displaying one [Formula: see text]-source. Two simultaneously recorded sources are more challenging and require further algorithmic optimization., (© 2023. The Author(s).)

An integrated augmented reality (AR) surgical navigation system that potentially improves intra-operative visualization of concealed anatomical structures. Integration of real-time tracking technology with a laser pico-projector allows the surgical surface to be augmented by projecting virtual images of lesions and critical structures created by multimodality imaging. We aim to quantitatively and qualitatively evaluate the performance of a prototype interactive AR surgical navigation system through a series of pre-clinical studies. Four pre-clinical animal studies using xenograft mouse models were conducted to investigate system performance. A combination of CT, PET, SPECT, and MRI images were used to augment the mouse body during image-guided procedures to assess feasibility. A phantom with machined features was employed to quantitatively estimate the system accuracy. All the image-guided procedures were successfully performed. The tracked pico-projector correctly and reliably depicted virtual images on the animal body, highlighting the location of tumour and anatomical structures. The phantom study demonstrates the system was accurate to 0.55 ± 0.33mm. This paper presents a prototype real-time tracking AR surgical navigation system that improves visualization of underlying critical structures by overlaying virtual images onto the surgical site. This proof-of-concept pre-clinical study demonstrated both the clinical applicability and high precision of the system which was noted to be accurate to <1mm., Competing Interests: The authors have declared that no competing interests exist.

Background: Squamous cell carcinoma in the head and neck region is one of the most widespread cancers with high morbidity. Classic treatment comprises the complete removal of the lymphatics together with the cancerous tissue. Recent studies have shown that such interventions are only required in 30% of the patients. Sentinel lymph node biopsy is an alternative method to stage the malignancy in a less invasive manner and to avoid overtreatment. In this paper, we present a novel approach that enables a future augmented reality device which improves the biopsy procedure by visual means., Methods: We propose a co-calibration scheme for axis-aligned miniature cameras with pinholes of a gamma ray collimating and sensing device and show results gained by experiments, based on a calibration target visible for both modalities., Results: Visual inspection and quantitative evaluation of the augmentation of optical camera images with gamma information are congruent with known gamma source landmarks., Conclusions: Combining a multi-pinhole collimator with axis-aligned miniature cameras to augment optical images using gamma detector data is promising. As such, our approach might be applicable for breast cancer and melanoma staging as well, which are also based on sentinel lymph node biopsy.

Background: When locating the sentinel lymph node (SLN), surgeons use state-of-the-art imaging devices, such as a 1D gamma probe or less widely spread a 2D gamma camera. These devices project the 3D subspace onto a 1D respectively 2D space, hence loosing accuracy and the depth of the SLN which is very important, especially in the head and neck area with many critical structures in close vicinity. Recent methods which use a multi-pinhole collimator and a single gamma detector image try to gain a depth estimation of the SLN. The low intensity of the sources together with the computational cost of the optimization process make the reconstruction in real-time, however, very challenging., Results: In this paper, we use an optimal design approach to improve the classical pinhole design, resulting in a non-symmetric distribution of the pinholes of the collimator. This new design shows a great improvement of the accuracy when reconstructing the position and depth of the radioactive tracer. Then, we introduce our Sentinel lymph node fingerprinting (SLNF) algorithm, inspired by MR-fingerprinting, for fast and accurate reconstruction of the tracer distribution in 3D space using a single gamma detector image. As a further advantage, the method requires no pre-processing, i.e. filtering of the detector image. The method is very stable in its performance even for low exposure times. In our ex vivo experiments, we successfully located multiple Technetium 99m (Tc-99m) sources with an exposure time of only one second and still, with a very small L 2 -error., Conclusion: These promising results under short exposure time are very encouraging for SLN biopsy. Although, this device has not been tested on patients yet, we believe: that this approach will give the surgeon accurate 3D positions of the SLN and hence, can potentially reduce the trauma for the patient.

The aim of the study was to assess regional control and survival in primary irradiated oropharyngeal cancer patients with advanced neck disease (≥cN2a) receiving planned neck dissection (PND) irrespective of the nodal response compared to salvage neck dissection (SND) in case of regional persistence or reccurence in relation to tumoral p16 overexpression. 96 consecutive patients treated at the University Hospital of Zurich, Switzerland were included. Tissue microarray-based scoring of p16 expression was obtained. 5 years overall (OS) and disease-specific survival (DSS) in the PND and SND cohort were 70 vs. 57 % (p = 0.20) and 80 vs. 65 % (p = 0.14), respectively. Regional control in PND and SND achieved 95 vs. 87 % (p = 0.29), respectively. There was no statistically significant impact of neck treatment (PND vs. SND) on regional control or survival among patients with p16-negative tumors (5 years OS 59 vs. 50 %, p = 0.66; 5 years DSS 59 vs. 57 %, p = 0.89) nor among patients with p16-positive tumors (5 years OS 84 vs. 67 %, p = 0.21; 5 years DSS 95 vs. 81 %, p = 0.24). The type of neck dissection after primary intensity-modulated radiotherapy (IMRT) had no impact on regional control and survival even in human papillomavirus (HPV)-associated disease. Therefore we are convinced that based on the accuracy of newer diagnostic modalities the surveillance of a radiologically negative neck after primary chemoradiation (CRT) is oncologically safe irrespective of p16 expression of the tumor.

Purpose: Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed., Methods: Three to 24 hours before surgery, all patients received a dose of Tc-nanocolloid (10-175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT., Results: Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1-10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients., Conclusions: Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.

Background: Adult laryngotracheal reconstruction for airway stenosis and after oncologic ablation can be extremely challenging., Methods: Patients with the above conditions not amenable to or refractory to conventional treatments were offered specialized reconstruction by wrapping a contoured costal cartilage graft with a vascularized microvascular carrier. All constructs were lined with buccal mucosa grafts. Decannulation rates, quality of life questionnaires, and pulmonary function tests were performed and analyzed., Results: Eleven patients underwent this procedure, 6 for stenosis and 5 for laryngotracheal oncologic defects. Ten patients were successfully decannulated after the procedure (91%). Median time to decannulation was 4 months. At mean follow-up of 76 months, all evaluated patients had a serviceable voice, tolerated a normal diet, and had minimal subjective shortness of breath., Conclusion: Vascularized composite autograft can be successfully used to treat severe subglottic stenosis or reconstruct large laryngotracheal defects not amenable to or refractory to conventional treatments., (© 2014 Wiley Periodicals, Inc.)

Background: [18F]FDG-PET/CT imaging is broadly used in head and neck cancer (HNSCC) patients. CT perfusion (CTP) is known to provide information about angiogenesis and blood-flow characteristics in tumors. The aim of this study was to evaluate the potential relationship of FDG-parameters and CTP-parameters in HNSCC preand post-therapy and the potential prognostic value of a combined PET/CT with CTP., Methods: Thirteen patients with histologic proven HNSCC were prospectively included. All patients underwent a combined PET/CT with integrated CTP before and after therapy. Pre- and post-therapeutic data of CTP and PET of the tumors were compared. Differences were tested using Spearman's rho test and Pearson's correlation. A p-value of p <0.05 was considered statistically significant. Correlations were calculated using Pearson's correlation. Bootstrap confidence intervals were calculated to test for additive confidence intervals., Results: Three patients died due to malignancy recurrence, ten patients were free of recurrence until the end of the follow-up period. Patients with recurrent disease had significantly higher initial CTP-values compared to the recurrence-free patients: BFpre 267.4 (171.2)ml/100 mg/min, BVpre 40.9 (8.4)ml/100 mg and MTTpre 8.2 (6.1)sec. No higher SUVs initially but significantly higher TLG compared to patients without recurrence were found. Post-therapeutic PET-values differed significantly between the two groups: SUVmaxpost 6.0 (3.2), SUVmeanpost 3.6 (2.0) and TLG 21751.7 (29794.0)., Conclusion: In our proof of concept study, combined PET/CT with integrated CTP might show complementary prognostic data pre- and post chemo-radiotherapy. CTP may be used to predict local tumor recurrence, while FDGPET/CT is still needed for whole-body staging.

Purpose: Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma., Methods: An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up., Results: An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%., Conclusion: These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Sentinel lymph node biopsy is a reliable technique for accurate determination of the cervical lymph node status in patients with early oral and oropharyngeal cancer but analyses on the distribution pattern of metastatic spread within sentinel lymph nodes are lacking., Methods: The localizations of carcinoma deposits were analyzed with a virtual microscope by creating digital images from the microscopic glass slides., Results: Metastatic deposits were not randomly distributed within sentinel lymph nodes but were predominant in the central planes closer to the lymphatic inlet. Initial evaluation of the 4 most central slices achieved a high rate of 90% for the detection of micrometastases and of 80% for the detection of isolated tumor cells (ITCs)., Conclusion: Based on the distribution we recommend an initial cut through the hilus and to proceed with the 4 most central 150-µm slices. Complete step sectioning is only required in case of a so far negative result., (© 2014 Wiley Periodicals, Inc.)

Objective: Follow-up of patients with oral cavity squamous cell carcinoma (OCSCC) after tumor resection and reconstruction with tissue transfer is challenging. We compared contrast-enhanced computed tomography (ceCT), (18) F-fluorodeoxyglucose-positron emission tomography combined with noncontrast enhanced CT ((18) F-FDG-PET/CT), and (18) F-FDG-PET combined with ceCT ((18) F-FDG-PET/ceCT) to determine the accuracy for detection of residual/recurrent disease after flap reconstruction for OCSCC., Study Design and Methods: Two readers (R1, R2) retrospectively reviewed a total of 27 (18) F-FDG-PET/ceCT scans in patients after resection of stage II to IV OCSCC. They recorded the presence of local persistence/recurrence (LR), lymph node metastasis, or distant metastasis independently for ceCT, (18) F-FDG-PET/CT, and (18) F-FDG-PET/ceCT. Histological workup, imaging follow-up, or clinical follow-up served as the standard of reference. Maximum standardized uptake value (SUVmax) was evaluated to discriminate between physiological uptake and LR., Results: The highest accuracy to detect LR was achieved with (18) F-FDG-PET/ceCT, with a sensitivity/specificity of 88%/89% and 88%/79% for R1 and R2, respectively, as compared to ceCT with 75%/79% for R1 and 88%/68% for R2 and (18) F-FDG-PET/CT with 88%/58% for both R1 and R2. Receiver-operating-characteristic analysis determined a cutoff value for SUVmax of 7.2, yielding a sensitivity and specificity of 75% and 94%, respectively, to distinguish LR from physiological (18) F-FDG uptake., Conclusion: (18) F-FDG-PET/ceCT seems to be the most reliable tool for locoregional surveillance of OCSCC patients after resection and reconstruction., Level of Evidence: 4., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Previous preclinical studies of localized intraoperative virtual endoscopy-image-guided surgery (LIVE-IGS) for skull base surgery suggest a potential clinical benefit., Objective: The first aim was to evaluate the registration accuracy of virtual endoscopy based on high-resolution magnetic resonance imaging under clinical conditions. The second aim was to implement and assess real-time proximity alerts for critical structures during skull base drilling., Design and Setting: Patients consecutively referred for sinus and skull base surgery were enrolled in this prospective case series., Participants: Five patients were used to check registration accuracy and feasibility with the subsequent 11 patients being treated under LIVE-IGS conditions with presentation to the operating surgeon (phase 2)., Intervention: Sixteen skull base patients were endoscopically operated on by using image-based navigation while LIVE-IGS was tested in a clinical setting., Main Outcome and Measures: Workload was quantitatively assessed using the validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire., Results: Real-time localization of the surgical drill was accurate to ~1 to 2 mm in all cases. The use of 3-mm proximity alert zones around the carotid arteries and optic nerve found regular clinical use, as the median minimum distance between the tracked drill and these structures was 1 mm (0.2-3.1 mm) and 0.6 mm (0.2-2.5 mm), respectively. No statistical differences were found in the NASA-TLX indicators for this experienced surgical cohort., Conclusions and Relevance: Real-time proximity alerts with virtual endoscopic guidance was sufficiently accurate under clinical conditions. Further clinical evaluation is required to evaluate the potential surgical benefits, particularly for less experienced surgeons or for teaching purposes., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

Unlabelled: (D)-(18)F-fluoromethyltyrosine (d-(18)F-FMT), or BAY 86-9596, is a novel (18)F-labeled tyrosine derivative rapidly transported by the l-amino acid transporter (LAT-1), with a faster blood pool clearance than the corresponding l-isomer. The aim of this study was to demonstrate the feasibility of tumor detection in patients with non-small cell lung cancer (NSCLC) or head and neck squamous cell cancer (HNSCC) compared with inflammatory and physiologic tissues in direct comparison to (18)F-FDG., Methods: 18 patients with biopsy-proven NSCLC (n = 10) or HNSCC (n = 8) were included in this Institutional Review Board-approved, prospective multicenter study. All patients underwent (18)F-FDG PET/CT scans within 21 d before d-(18)F-FMT PET/CT. For all patients, safety and outcome data were assessed., Results: No adverse reactions were observed related to d-(18)F-FMT. Fifty-two lesions were (18)F-FDG-positive, and 42 of those were malignant (34 histologically proven and 8 with clinical reference). Thirty-two of the 42 malignant lesions were also d-(18)F-FMT-positive, and 10 lesions had no tracer uptake above the level of the blood pool. Overall there were 34 true-positive, 8 true-negative, 10 false-negative, and only 2 false-positive lesions for d-(18)F-FMT, whereas (18)F-FDG was true-positive in 42 lesions, with 10 false-positive and only 2 false-negative, resulting in a lesion-based detection rate for d-(18)F-FMT and (18)F-FDG of 77% and 95%, respectively, with an accuracy of 78% for both tracers. A high d-(18)F-FMT tumor-to-blood pool ratio had a negative correlation with overall survival (P = 0.050), whereas the (18)F-FDG tumor-to-blood pool ratio did not correlate with overall survival., Conclusion: d-(18)F-FMT imaging in patients with NSCLC and HNSCC is safe and feasible. The presented preliminary results suggest a lower sensitivity but higher specificity for d-(18)F-FMT over (18)F-FDG, since there is no d-(18)F-FMT uptake in inflammation. This increased specificity may be particularly beneficial in areas with endemic granulomatous disease and may improve clinical management. Further clinical investigations are needed to determine its clinical value and relevance for the prediction of survival prognosis., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: The purpose of this study was to evaluate the efficacy of preoperative versus intraoperative mandibular contouring using rapid prototyping technology., Methods: Ten patients requiring mandibular reconstruction had a preoperative mandibular plate contoured to a fabricated 3D mandibular model based on preoperative imaging. A traditional intraoperative plate was also contoured. Two surgeons blinded to the study compared the plates with respect to conformance, surface-area contact, and best overall match. A cost-benefit analysis was then performed., Results: The average time to contour was 867 ± 243 seconds and 833 ± 289 seconds for the preoperative and intraoperative plates, respectively (p = .83). Interobserver analysis revealed no statistically significant differences in conformance (p = .38) or surface area contact (p = .14). In 7 of 9 cases, the preoperative plate was selected for the final reconstruction. In 1 case, an intraoperative plate was not contoured because of the lateral extent of the tumor., Conclusion: In cases of mandibular distortion secondary to disease, pathologic fracture or defects involving multiple mandibular subsites this method is particularly advantageous., (© 2013 Wiley Periodicals, Inc.)

Unlabelled: Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of (99m)Tc-PAMA-cobalamin in 10 patients with various metastatic tumors., Methods: Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300-500 MBq of (99m)Tc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor activity using SPECT/CT over the tumor region after 4 h was measured in comparison to disease-free lung parenchyma. Patients 3-10 received between 20 and 1,000 μg of cobalamin intravenously before injection of (99m)Tc-PAMA-cobalamin. The study population comprised 4 patients with adenocarcinomas of the lung, 3 with squamous cell carcinomas of the hypopharyngeal region, 1 with prostate adenocarcinoma, 1 with breast, and 1 with colon adenocarcinoma., Results: The median age of the study group was 61 ± 11 y. Six of 10 patients showed positive tumor uptake on (99m)Tc-PAMA-cobalamin whole-body scintigraphy. The scan was positive in 1 patient with colon adenocarcinoma, in 3 of 4 lung adenocarcinomas, in 1 of 3 hypopharyngeal squamous cell carcinomas, and in 1 breast adenocarcinoma. Renal uptake was between 1% and 3% for the left kidney. Predosing with cobalamin increased the tumor uptake and improved blood-pool clearance. The best image quality was achieved with a predose of 20-100 ug of cold cobalamin. The mean patient dose was 2.7 ± 0.9 mSv/patient., Conclusion: To our knowledge, we report for the first time on (99m)Tc-PAMA-cobalamin imaging in patients with metastatic cancer disease and show that tumor targeting is feasible.

Objectives/hypothesis: To identify or confirm any new or suggested independent histopathological predictors in Merkel cell carcinoma (MCC) of the head and neck (HN) correlated with outcome., Study Design: Retrospective chart and pathology review., Methods: Between 1990 and 2010, 58 patients with Merkel cell carcinoma of the head and neck HNMCC were identified for study. Pathologic specimens were reviewed and evaluated for independent prognostic factors and correlated with locoregional recurrence and disease-specific survival., Results: The 2- and 5-year disease-specific survival (DSS) rates were 72.7% and 63.6%, respectively. The local and regional recurrence rates were 12.0% and 24.1%, respectively. A total of 25.9% of the patients developed distant metastases during follow-up. Tumor size (< 1 cm vs. > 1 cm) and the presence of a positive deep resection margin were independently found to be significantly associated with regional recurrence (P = 0.01 and P = 0.04, respectively). No other prognostic factors could be identified., Conclusion: Adjuvant radiotherapy cannot remediate a positive resection margin. Given these results, consideration for revision surgery should be considered for a positive deep margin. Frozen section analysis may help to define the margins in this invasive and aggressive disease., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Skull base surgery (SBS) involves operative tasks in close proximity to critical structures in a complex three-dimensional (3D) anatomy. The aim was to investigate the value of virtual planning (VP) based on preoperative magnetic resonance imaging (MRI) for surgical planning in SBS and to compare the effects of virtual planning with 3D contours between the expert and the surgeon in training., Study Design: Retrospective analysis., Methods: Twelve patients with manually segmented anatomical structures based on preoperative MRI were evaluated by eight surgeons in a randomized order using a validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire., Results: Multivariate analysis revealed significant reduction of workload when using VP (P<.0001) compared to standard planning. Further, it showed that the experience level of the surgeon had a significant effect on the NASA-TLX differences (P<.05). Additional subanalysis did not reveal any significant findings regarding which type of surgeon benefits the most (P>.05)., Conclusions: Preoperative anatomical segmentation with virtual surgical planning using contours in endoscopic SBS significantly reduces the workload for the expert and the surgeon in training., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The transcription factor sex determining region Y (SRY)-box 2 (SOX2) (3q26.3-q27) has been recently identified as a recurrently activated major oncogene in squamous cell carcinoma of various sites. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is currently unclear., Aim: To correlate SOX2 protein expression with the occurrence of occult lymph node metastasis and relapse free survival in early oral SCC., Methods: SOX2 expression in 120 T1/T2 oral SCC patients was evaluated using a tissue microarray technique. Intensity of SOX2 expression was quantified by assessing the Intensity/Reactivity Scores (IRSs). These scores were correlated with the lymph node status of biopsied sentinel lymph nodes and recurrence. Log rank univariate and Cox regression multivariate analysis was used to determine statistical significance., Results: Twenty-six of 120 primary tumours (21.7%) showed high SOX2 expression. High expression levels of SOX2 significantly correlated with negative lymph node status in univariate (p=0.001) and multivariate analysis (p=0.003). Sensitivity was found to be 95.6% with a negative predictive value of 92.3%. Specificity was 32% with a positive predictive value of 45.7%., Conclusion: SOX2 up-regulation is frequent in early SCC of the oral cavity and associated with decreased risk of lymphatic metastasis. SOX2 immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Analysis of the lymphatic drainage pattern, the reliability of a negative sentinel lymph node biopsy (SLNB), as well as the impact of sentinel lymph node (SLN) metastases on regional control and survival in patients with early stage oral and oropharyngeal squamous cell carcinoma (SCC)., Methods: A prospective consecutive cohort analysis was conducted which included 111 patients diagnosed between 2003 and 2010. Endpoints of the study were neck control rate, overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS), depending on the size of occult metastases., Results: Forty-nine of 111 patients (38%) had positive SLNs, 10 had isolated tumor cells (ITCs), 19 had micrometastases, and 13 had macrometastases. OS, DSS, and DFS at 3 years for SLN-negative and SLN-positive patients was 98% and 71%, 95% and 76%, and 98% and 73%, respectively. Furthermore, there was a statistically significant difference between the SLN-negative group and ITCs in DSS as well as between the SLN-negative group and patients with micrometastases in OS and DSS and between the SLN-negative group and patients with macrometastases in all 3 survival estimates., Conclusion: Our study is the first to demonstrate that even small tumor deposits only detectable by the extensive histopathologic workup of the SLNB protocol have a significant impact on tumor control and survival in early Oropharyngeal SCC. Whether these findings will translate into different treatment strategies based on the upstaged neck has to be further investigated., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives/hypothesis: The aim was to compare the value of 18-Fluoro-Deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) regarding contralateral lymph node (LN) metastasis in the neck., Study Design: Retrospective analysis of 61 patients staged by 18F-FDG-PET/CT., Methods: Cytology/histology served as a reference standard. Further, metabolic midline invasion (MI) of the primary tumor and the presence of bilateral LN metastases were assessed., Results: A true positive rate in the ipsilateral neck of 80% versus 65% in the contralateral neck was found (P = 0.067). Median-standardized uptake value (SUV)-max for suspicious LN ipsilaterally was 7.6 versus 5.8 contralaterally (P = 0.038). There was no positive correlation between metabolic MI and bilateral metastasis (P = 0.82)., Conclusions: The rate of true positive detected LN by 18F-FDG-PET/CT is less on the contralateral neck side; therefore, all suspicious LNs should be verified by cytology. A high SUV in the contralateral neck suggests metastatic disease regardless of nodal size. Metabolic MI needs to be addressed carefully as it was not predictive for bilateral LN involvement., Level of Evidence: 4., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Assess the influence of 2 different patient positions during [18F]fluorodeoxyglucose (FDG) uptake phase on physiologic FDG accumulation of the floor of mouth (FOM) muscles., Study Design: A prospective study design was used., Methods: Two hundred prospectively enrolled patients were included in the study: (a) head and neck cancer (HNC) patients in supine or (b) sitting position, (c) patients with other malignant tumours in supine or (d) sitting position. An intra-individual analysis was done on patients (b) and (d) when such scans were available. Maximum standardized uptake values without correction and corrected for blood pool activity were assessed., Results: The inter-individual analysis (sitting vs supine) revealed no significant differences (P = 0.17 and P = 0.56). The subgroup analysis on the patients with HNC (P = 0.56 and P = 0.15) and in patients with other malignancies (P = 0.14 and P = 0.08) revealed no significant difference; neither did the intra-individual analysis., Conclusions: The supine or sitting position during the uptake phase for FDG-positron emission tomography/computed tomography has no effect on the amount and distribution of physiologic FDG activity in the muscles of the FOM.

Sinonasal carcinomas are uncommon neoplasms accounting for approximately 3% to 5% of all upper respiratory tract malignancies. Sinonasal malignancies in most cases do not cause early symptoms and present in an advanced stage of disease. Exact staging necessitates a clinical and endoscopic examination with biopsy and imaging. Tumor resection using an open or endoscopic approach is usually considered the first treatment option. In general, sinonasal carcinomas are radiosensitive, so adjuvant or neoadjuvant radiation treatment may be indicated in advanced disease. Multidisciplinary surgical and medical oncologic approaches, including ablation and reconstruction, have enhanced the survival outcome over the past few decades., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Objectives: The potential of avoiding a secondary surgery for therapeutic neck dissection (TND) by sentinel node (SN) positivity makes the intraoperative evaluation of SNs an attractive option. The aim of this study was to analyze accuracy of intraoperative frozen section (FS) for detection of occult metastases in a large single institutional patient cohort undergoing SN-biopsy., Methods: Between 2000 and 2010, 92 consecutive patients with early stage oropharyngeal squamous cell carcinoma (OSCC) (cT1/cT2/cN0) were prospectively enrolled. Detection rate of occult metastases by monoslice FS was compared with the definitive histopathologic work up by step serial sectioning (SSS) and immunohistochemistry (IHC). In case of SN-positivity on FS TND was performed in the same narcosis., Results: 15/92 patients revealed positive SNs by FS compared to 34/92 after SSS and IHC. Sensitivity, NPV and FNR for the detection of all sizes of metastases by FS was 47, 77, and 52%, for isolated tumor cells (ITC) 8, 86, 92%, for micrometastases 43, 90, 57%, and for macrometastases 93, 98, 7%., Conclusion: Sensitivity of FS by the monoslice depends on the metastases size and allows a single-stage procedure in half of the SN-positive patients. To improve sensitivity for small tumor deposits either a multislice-technique or molecular methods are needed., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The aim of this study was to assess the impact of (18) F-fluoro-2-deoxy-D-glucose ((18) F-FDG) PET/CT on survival for patients with head and neck squamous cell carcinoma correlated with a matched patient cohort., Methods: In all, disease in 58 patients was initially staged using (18) F-FDG PET/CT. A case-control analysis was done with 63 patients who disease was staged without (18) F-FDG-PET/CT., Results: Disease-specific survival (DSS) and overall survival (OS) did not show significant differences between both groups. Statistical analysis revealed no difference in DSS and OS between the 2 groups for patients treated by radiochemotherapy (p = .975 and p = .671). In the analysis of survival in patients treated by a combined approach (surgery + radiochemotherapy), a significant difference in favor of patients evaluated by (18) F-FDG PET/CT was found (p = .05 and p = .027)., Conclusions: Addition of (18) F-FDG PET/CT in patients treated by surgery and conformal radiochemotherapy improves outcome. This may be due to the more comprehensive topographic orientation of the primary tumor for the surgeon., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: The aim of this study was to compare imaging modalities for staging the neck in a prospective cohort of patients evaluated by CT, ultrasound with fine-needle aspiration cytology (FNAC), and [(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT with the histologic evaluation of the neck dissection as the standard of reference., Methods: In all, 76 consecutive patients were prospectively enrolled., Results: Ultrasound-guided FNAC showed the highest level of agreement with histology for exact N classification. Ultrasound-guided FNAC showed the smallest percentage of overstaged patients, 7%, versus 16% with PET/CT, 13% with CT, and 13% with ultrasound. The rate of understaged patients was comparable between the imaging modalities. With regard to the endpoint N0 versus N+ there were no statistically significant differences to be found., Conclusions: Ultrasound-guided FNAC seems to correlate best with histologic staging compared with PET/CT and CT. None of the modality is reliable enough to replace elective neck treatment in cN0 necks., (Copyright © 2011 Wiley Periodicals, Inc.)

The aim this study was to evaluate imaging findings using position emission tomography (PET) in combination with computed tomography (CT) and 18F-fluorodeoxyglucose ((18)F-FDG) in sinonasal malignant melanoma (SNMM) of the head and neck in a retrospective analysis of a consecutive cohort of patients. (18)F-FDG-PET/CT examinations were performed for initial staging and compared with CT or magnetic resonance tomography (MRI), and (18)F-FDG-PET alone. Medical records were reviewed retrospectively with regard to the location and the size of the tumor. Furthermore, locoregional and distant metastases with a consecutive change in therapy detected by (18)F-FDG-PET/CT were assessed. Ten patients suffering from sinonasal malignant melanoma were staged and followed by (18)F-FDG-PET/CT imaging. A total of 34 examinations were obtained. (18)F-FDG-PET/CT depicted all primary tumors adequately. Aside from one cerebral metastasis all regional and distant metastases were truly identified by using this method. In summary, if available, (18)F-FDG-PET/CT is a valuable imaging modality for staging and re-staging sinonasal malignant melanoma to evaluate expansion of the primary tumor, locoregional disease, and distant metastases.

Background: The objective of this study was to link expression patterns of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC)., Methods: Expression levels of Bmi-1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease-specific, and recurrence-free survival., Results: The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi-1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi-1 expression (P = .008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167-2.838); this correlation was also observed for atypical cytoplasmic Bmi-1 expression (P = .001; HR, 2.164; 95% CI, 1.389-3.371) and for negative p16 expression (P < .001; HR, 0.292; 95% CI, 0.178-0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P < .001; HR, 8.485; 95% CI, 4.237-16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P = .011; HR, 1.838; 95%CI, 1.146-2.947) and the combined marker expression patterns (P < .001; HR, 6.254; 95% CI, 2.869-13.635) were correlated with overall survival, disease-specific survival (tumor classification: P = .002; HR, 2.807; 95% CI, 1.477-5.334; combined markers: P = .002; HR, 5.386; 95% CI, 1.850-15.679), and the combined markers also were correlated with recurrence-free survival (P = .001; HR, 8.943; 95% CI, 2.562-31.220)., Conclusions: Cytoplasmic Bmi-1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease-specific and recurrence-free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up., (Copyright © 2011 American Cancer Society.)

Purpose: To assess the diagnostic value of O-2-fluoro-18(F)-ethyl-L-tyrosine ((18)F-FET) positron emission tomography/computed tomography (PET/CT) for patients with advanced head and neck squamous cell carcinoma compared with 18F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT at initial staging and following radiochemotherapy., Procedures: Thirteen patients were prospectively enrolled; each of them underwent an (18)F-FDG PET/CT and (18)F-FET PET/CT before treatment. Ten of those were scanned 10 weeks after treatment., Results: Sensitivity, specificity, and accuracy for (18)F-FDG PET/CT (primary and lymph node metastases) at initial staging were 89%, 50%, and 81%. For (18)F-FET PET/CT the numbers were 70%, 90%, and 74%. Sensitivity, specificity, and accuracy for (18)F-FDG PET/CT at follow-up were 71%, 65%, and 67%. For (18)F-FET PET/CT the numbers were 29%, 100%, and 83%. Additionally, (18)F-FDG PET/CT detected a higher number of second malignancies or distant metastases., Conclusions: (18)F-FET is no substitute for (18)F-FDG. Although it is more specific, too many malignant lesions are missed due to its lower sensitivity.

In patients with early head and neck squamous cell carcinoma (HNSCC), occult lymph node metastasis is difficult to predict by clinical or pathological parameters. However, such parameters are necessary to select patients either for elective neck dissection or the sentinel lymph node (SLN) procedure. The membrane glycoprotein podoplanin is normally expressed in lymphatic endothelial cells. Recently, expression of podoplanin by cancer cells was demonstrated to promote tumor cell motility and tumor lymphangiogenesis in vitro. The value of cancer cell-expressed podoplanin was to be determined as a predictive marker for SLN metastasis in early HNSCC of the oral cavity and oropharynx. One hundred twenty patients with HNSCC of the oral cavity and oropharynx undergoing a SLN biopsy were enrolled in this prospective clinical trial of SLN biopsy. Cancer cell-expressed podoplanin was determined by immunohistochemistry using tissue microarrays. Podoplanin expression was quantified by the intensity reactivity score and categorized into expression and nonexpression. SLN examination revealed occult metastasis in 45 patients (37.5%). Twenty-nine of 120 (24.2%) primary HNSCC showed podoplanin expression. Podoplanin expression correlated significantly with SLN metastasis (p = 0.029) and remained a significant predictor for lymph node status even after controlling for tumor stage (p = 0.028). As a predictive marker for SLN metastasis, however, podoplanin expression reached a sensitivity of a mere 36% and a specificity of 83%. Podoplanin expression is associated with metastasis to lymph nodes in vivo. Podoplanin immunohistochemistry in early HNSCC of the oral cavity and oropharynx may help to select patients for the SLN procedure and to identify patients with increased risk for presence of occult lymph node metastasis in the neck., (Copyright © 2011 UICC.)

Background: Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections., Objectives: To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease., Methods: E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance., Results: pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005) in univariate and multivariate analysis., Conclusion: These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx., Level of Evidence: 2b.

Background: Cystic lymph node metastasis (CLNM) is commonly found in human papillomavirus (HPV)-associated tonsillar squamous cell carcinoma (SCC). The aim of this study was to compare the accuracy in detecting cystic lymph node metastasis from tonsillar SCC between contrast-enhanced CT, ¹⁸F- fluorodeoxyglucose-positron emission tomography (FDG-PET), non-enhanced ¹⁸F-FDG-PET/CT, and contrast-enhanced ¹⁸F-FDG-PET/CT., Methods: Thirty-four patients with a tonsillar SCC undergoing a pretreatment contrast-enhanced ¹⁸F-FDG-PET/CT followed by a neck dissection as a standard of reference were included. The contrast-enhanced CT part, the ¹⁸F-FDG-PET part, the non-enhanced ¹⁸F-FDG-PET/CT part, and the contrast-enhanced ¹⁸F-FDG-PET/CT were assessed separately for correct N classification and the differentiation of N0 versus N+. RESULTS.: Contrast-enhanced ¹⁸F-FDG-PET/CT, non-enhanced ¹⁸F-FDG-PET/CT, and contrast-enhanced CT are equally accurate for correct neck staging. Regarding pN0 versus pN+, contrast-enhanced CT and contrast-enhanced ¹⁸F-FDG-PET/CT are superior to non-enhanced ¹⁸F-FDG-PET/CT (p = .017)., Conclusion: Contrast-enhanced CT and contrast-enhanced ¹⁸F-FDG-PET/CT perform equally and better than non-enhanced ¹⁸F-FDG-PET/CT in detecting CLNM in tonsillar SCC. Therefore, in patients scheduled for ¹⁸F-FDG-PET/CT, we strongly suggest performing a contrast-enhanced ¹⁸F-FDG-PET/CT, which is not routine in most centers., (Copyright © 2010 Wiley Periodicals, Inc.)

Unlabelled: (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET)/CT imaging of squamous cell carcinoma of the head and neck (HNSCC) renders the possibility to study metabolic tumor activity by measuring FDG-uptake expressed as maximum standardized uptake value (SUV(max)). A correlation between SUV(max) and several factors including T-classification, histological tumor differentiation or different anatomic subsites is of potential interest in HNSCC. The aim of this study was to evaluate how metabolic tumor activity derived from FDG-PET correlates with prognostic clinical and pathological parameters including these factors. 262 patients with HNSCC undergoing PET/CT for initial staging were assessed separately for a potential correlation between SUV(max) and T-classification, histological grading, and anatomical subsites of the primary tumor. Nonparametric testing showed a significant correlation between SUV(max) and T-classification (P < 0.001). On the contrary, no statistically significant correlation was found between SUV(max) and histological tumor grading. Furthermore, no statistical significant correlation between the different anatomical subsites and SUV(max) were found. There was no significant correlation of SUV(max) and tumor grading after adjustment for T-stage and anatomical localization of the tumor, neither., Conclusion: Metabolic tumor activity correlates with T-stage of HNSCC. However, histological tumor grading does not correlate with SUV(max). The role of primary tumor SUV(max) as a predictor of outcome or survival remains unclear. Clinicians should therefore exercise caution in attributing any clinical importance to SUV(max) obtained from a single PET/CT exam.

Epstein-Barr virus (EBV) uses nasal mucosa-associated lymphoid tissue (NALT) as a portal of entry to establish life-long persistence in memory B cells. We previously showed that naïve and memory B cells from NALT are equally susceptible to EBV infection. Here we show that memory B cells from NALT are significantly more susceptible to EBV infection than those from remote lymphatic organs. We identify beta(1) integrin, which is expressed the most by naïve B cells of distinct lymphoid origin and by memory B cells from NALT, as a mediator of increased susceptibility to infection by EBV. Furthermore, we show that BMRF-2-beta(1) integrin interaction and the downstream signal transduction pathway are critical for postbinding events. An increase of beta(1) integrin expression in peripheral blood memory B cells provoked by CD40 stimulation plus B-cell receptor cross-linking increased the susceptibility of non-NALT memory B cells to EBV infection. Thus, EBV seems to utilize the increased activation status of memory B cells residing in the NALT to establish and ensure persistence.

Background: This study assesses the additional value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/CT ((18)F-FDG-PET/CT) with respect to synchronous primaries in patients undergoing panendoscopy for staging of head and neck squamous cell carcinoma., Methods: In all, 311 patients underwent both modalities. Cytology, histology, and/or clinical/imaging follow-up served as reference standard., Results: The prevalence of second primary tumors detected by panendoscopy was 4.5%, compared with 6.1% detected by (18)F-FDG-PET/CT. The sensitivity for panendoscopy was 74%, the specificity was 99.7%, the positive predictive value (PPV) was 93%, and the negative predictive value (NPV) was 98%. The sensitivity for (18)F-FDG-PET/CT was 100%, the specificity was 95.7%, the PPV was 59%, and the NPV was 100%., Conclusions: (18)F-FDG-PET/CT is superior to panendoscopy. With a negative (18)F-FDG-PET/CT, the extent of endoscopy can be reduced to the area of the primary tumor. Due to the costs, (18)F-FDG-PET/CT is recommended only in advanced disease to assess potential distant disease. In early-stage cancer, panendoscopy is accurate enough to rule out secondary tumors.

Background: Lymphatic mapping for sentinel node biopsy (SNB) has been shown to be crucial for detection of sentinel lymph nodes (SLN). Previous reports suggested a benefit of single photon emission computed tomography with CT (SPECT/CT) over dynamic planar lymphoscintigraphy (LS) alone. The aim was to assess whether there is an additional value of SPECT/CT over LS alone for lymphatic mapping of SLNs in oral/oropharyngeal SCC., Methods: A consecutive cohort of 58 patients was evaluated using SNB with additional SPECT/CT to preoperative LS., Results: In the entire cohort of 58 patients undergoing LS and SPECT/CT, hot spots could be revealed in all but 4 cases. The guidance of the handheld gamma probe was able to reveal 9 additional SLNs within 3 patients not detected by either modality. Lymphoscintigraphy showed full concordance with SPECT/CT in 81% of the cases. SPECT/CT was able to detect additional HS in 11 patients, in 1 case even with additional metastatic disease. The false negative rate for SNB was 6%, and the negative predictive value 98%., Conclusions: SPECT/CT has the potential to detect more SLNs, which might harbor occult disease, than LS alone. With regard to the excellent results achieved with LS and the intraoperative use of the gamma probe, SPECT/CT is not indispensable for successful SNB. Both imaging modalities have difficulties in detecting level I sentinel nodes close to the injection site.

Purpose: The aim of the study was to evaluate (18)F-FDG-PET/CT for the detection of synchronous primaries at initial staging of patients with head and neck squamous cell carcinoma (HNSCC)., Methods: FDG-PET/CT images acquired between March 2001 and October 2007 in 589 consecutive patients (147 women, 442 men; mean age 61.5 years, age range 32-97 years) with proven HNSCC were reviewed for the presence of synchronous primaries. Cytology, histology and/or clinical and imaging follow-up served as reference standard., Results: FDG-PET/CT showed 69 suspected synchronous primaries in 62 patients of which 56 were finally confirmed in 44 patients. Of the 56 second cancers, 46 (82%) were found in the aerodigestive tract in the following locations: lung (26, 46%), head and neck (15, 17%), oesophagus (5, 9%). Ten second cancers (18%) were located outside the aerodigestive tract (colon, five; stomach, lymphoma, breast, thymus and kidney, one each). Six patients had three synchronous primaries and three patients had four synchronous cancers. Nine synchronous cancers were not detected by PET/CT (four head and neck, two lung, two oesophageal, one gastric). False-positive PET/CT findings were mainly related to benign FDG uptake in the intestine due to benign or precancerous polyps or physiological FDG uptake in other head and neck regions. Overall the prevalence of synchronous second primaries according to the reference standard was 9.5%, of which 84% were detected with FDG-PET/CT. In 80% of the patients, therapy was changed because of the detection of a synchronous primary., Conclusion: FDG-PET/CT detects a considerable number of synchronous primaries (8.0% prevalence) at initial staging of patients with HNSCC. Synchronous cancers were predominantly located in the aerodigestive tract, primarily in the lung, head and neck and oesophagus. Detection of second primaries has an important impact on therapy. PET/CT should be performed before panendoscopy.