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Abstract 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

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. [ABSTRACT FROM AUTHOR]

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 posttherapy 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. Posttherapeutic 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. [ABSTRACT FROM AUTHOR]

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), 18F-fluorodeoxyglucose-positron emission tomography combined with noncontrast enhanced CT (18F-FDG-PET/CT), and 18F-FDG-PET combined with ceCT (18F-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 18F-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, 18F-FDG-PET/CT, and 18F-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 18F-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 18F-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 18F-FDG uptake. Conclusion 18F-FDG-PET/ceCT seems to be the most reliable tool for locoregional surveillance of OCSCC patients after resection and reconstruction. Level of Evidence 4. Laryngoscope, 125:1861-1868, 2015 [ABSTRACT FROM AUTHOR]

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. Level of Evidence 2b. Laryngoscope, 123:3043-3048, 2013 [ABSTRACT FROM AUTHOR]

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. Level of Evidence 4. Laryngoscope, 123:2935-2939, 2013 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 18 F-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 18 F-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. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to assess the impact of 18F-fluoro-2-deoxy- D-glucose (18F-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 18F-FDG PET/CT. A case-control analysis was done with 63 patients who disease was staged without 18F-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 18F-FDG PET/CT was found ( p = .05 and p = .027). Conclusions Addition of 18F-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. © 2011 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

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+, contrastenhanced 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-FDGPET/ CT, which is not routine in most centers. [ABSTRACT FROM AUTHOR]

Adequate staging and treatment of the neck in squamous cell carcinoma of the oral cavity and oropharynx (OSCC) is of paramount importance. Elective neck dissection (END) of the clinical N0-neck is widely advocated as neck treatment. With regard to the prevalence of 20-40% of occult neck metastases found in the ND specimens, the majority of patients undergo surgery of the lymphatic drainage basin without therapeutic benefit. Sentinel node biopsy (SNB) has been shown to be a safe, reliable and accurate alternative treatment modality for selected patients. Using this technique, lymphatic mapping is crucial. Previous reports suggested a benefit of single photon emission computed tomography with CT (SPECT/CT) over dynamic planar lymphoscintigraphy (LS) alone. SPECT/CT allows the surgeon for better topographical orientation and delineation of sentinel lymph nodes (SLN's) against surrounding structures. Additionally, SPECT/CT has the potential to detect more SLN's which might harbour occult disease, than LS. SPECT/CT is recommended to be used routinely, although SPECT/CT is not indispensable for successful SNB. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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). A correlation between SUV 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 and T-classification, histological grading, and anatomical subsites of the primary tumor. Nonparametric testing showed a significant correlation between SUV and T-classification ( P < 0.001). On the contrary, no statistically significant correlation was found between SUV and histological tumor grading. Furthermore, no statistical significant correlation between the different anatomical subsites and SUV were found. There was no significant correlation of SUV 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. The role of primary tumor SUV as a predictor of outcome or survival remains unclear. Clinicians should therefore exercise caution in attributing any clinical importance to SUV obtained from a single PET/CT exam. [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]

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 (18F-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 (SUVmax) and whether a positron emission tomography/computed tomography (PET/CT) was performed or not in the follow-up studies. The median SUVmax was chosen as the cutoff value. The patients were then grouped as those with either low or high SUVmax, 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 SUVmax 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 SUVmax 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: 18F-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, 18F-FDG uptake by the primary lesion may be related to better survival. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Background. This study assesses the additional value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/CT (18F-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 18F-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 18F-FDG-PET/CT was 100%, the specificity was 95.7%, the PPV was 59%, and the NPV was 100%. Conclusions. 18F-FDG-PET/CT is superior to panendoscopy. With a negative 18F-FDG-PET/CT, the extent of endoscopy can be reduced to the area of the primary tumor. Due to the costs, 18F-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. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

A correction to the article "Value of Preoperative Mandibular Plating in Reconstruction of the Mandible" by Dr. Eitan Prisman, Dr. Stephan K. Haerle and Dr. Jonathan C. Irish is presented.

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 β1 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-β1 integrin interaction and the downstream signal transduction pathway are critical for postbinding events. An increase of β1 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. [ABSTRACT FROM AUTHOR]

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.

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.

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.)

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 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.)

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: 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.)