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Background: To determine whether 18F‐PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18F‐PET/CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy. Methods: A total of 54 patients with head and neck cancer were prospectively enrolled in this single‐center, randomized study from 03/2012‐04/2015. Patients underwent FDG‐PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow‐up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS). Results: Thirty‐two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P >.05) during clinical follow‐up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P >.05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P <.01). Conclusions: Early response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no prognostic value concerning PFS and cannot identify high risk patients for consolidation therapy. Imaging responders showed a significantly longer PFS compared to nonresponders and therefore PET/CT might serve as a prognostic biomarker. Trial registration: Clinical Trials.gov identifier: NCT01435252. [ABSTRACT FROM AUTHOR]

Background: The Head and Neck Cancer Working Group of Swiss Group for Clinical Cancer Research (SAKK) has investigated the level of consensus (LOC) and discrepancy in everyday practice of diagnosis and treatment in head and neck cancer. Materials and Methods: An online survey was iteratively generated with 10 Swiss university and teaching hospitals. LOC below 50% was defined as no agreement, while higher LOC were arbitrarily categorized as low (51–74%), moderate (75–84%), and high (≥85%). Results: Any LOC was achieved in 62% of topics (n = 60). High, moderate and low LOC were found in 18, 20, and 23%, respectively. Regarding Head and Neck Surgery, Radiation Oncology, Medical Oncology, and biomarkers, LOC was achieved in 50, 57, 83, and 43%, respectively. Conclusions: Consensus on clinical topics is rather low for surgeons and radiation oncologists. The questions discussed might highlight discrepancies, stimulate standardization of practice, and prioritize topics for future clinical research. [ABSTRACT FROM AUTHOR]

Background: The Head and Neck Cancer Working Group of Swiss Group for Clinical Cancer Research (SAKK) has investigated the level of consensus (LOC) and discrepancy in everyday practice of diagnosis and treatment in head and neck cancer. Materials and Methods: An online survey was iteratively generated with 10 Swiss university and teaching hospitals. LOC below 50% was defined as no agreement, while higher LOC were arbitrarily categorized as low (51–74%), moderate (75–84%), and high (≥85%). Results: Any LOC was achieved in 62% of topics (n = 60). High, moderate, and low LOC were found in 18, 20, and 23%, respectively. Regarding Head and Neck Surgery, Radiation Oncology, Medical Oncology, and biomarkers, LOC was achieved in 50, 57, 83, and 43%, respectively. Conclusions: Consensus on clinical topics is rather low for surgeons and radiation oncologists. The questions discussed might highlight discrepancies, stimulate standardization of practice, and prioritize topics for future clinical research. [ABSTRACT FROM AUTHOR]

Background: Between the publication of the Union of International Cancer Control staging system (UICC) 7th and 8th editions, other staging algorithms for oropharyngeal squamous cell carcinoma (OPSCC) were proposed from Radiation Therapy Oncology Group (RTOG), MD Anderson Cancer Center (MDACC), and Yale University. Methods: With C‐statistics, the above‐mentioned five staging algorithms were compared for overall and relapse‐free survival endpoints in a multi‐institutional cohort of OPSCC cases (n = 338) treated with primary surgery. Results: Pathological UICC 8th ed yielded the highest C‐indexes in the entire cohort and in the HPV− subset, whereas MDACC was superior for HPV+ OPSCC. RTOG was the simplest and holistic algorithm with a noninferior discriminatory power. Conclusion: UICC 8th ed, MDACC, and RTOG offer moderate and comparable efficacy for staging in this OPSCC patient cohort undergoing surgical treatment. Notable discrepancy between clinical and pathological UICC 8th ed algorithms poses potential concerns in diagnosis, treatment, research, and data management. [ABSTRACT FROM AUTHOR]

Background: Epithelial–mesenchymal transition and cancer stem‐like cells (CSC) have been linked to increased metastatic potential. We evaluated the prognostic impact of CD44, a CSC biomarker, on depth of invasion (DOI) and outcome in oral squamous cell carcinoma (OSCC). Methods: Using a multivariable logistic regression model, we evaluated in early OSCCs the relationship between CD44 expression at the invasive tumor front, DOI, sentinel lymph node biopsy, extension of nodal involvement, and survival. We also assessed whether CT and/or MRI could predict DOI preoperatively. Results: CD44 expression was associated with increased DOI (P = .018), worse disease‐specific survival (P = .041) but not with positive sentinel lymph node biopsy (P > .05). Each millimeter increase in DOI was associated with a 31.1% higher risk for positive sentinel lymph node biopsy (95% CI: 5.8%‐62.4%, P = .013) and with higher metastatic ratio (P = .015). Preoperative estimation of DOI by CT and/or MRI and histopathological DOI showed a strong correlation (P < .0001). Conclusions: CD44 expression correlates with DOI, which predicts occult lymph node metastasis. Preoperative CT and/or MRI provides an accurate estimation of histopathological DOI. Both pieces of information gained preoperatively can help surgeons tailor their operation in regard to the surgical management of the neck. [ABSTRACT FROM AUTHOR]

Background: Recurrent peripheral facial paresis is a rare symptom that may be caused by multiple pathologic conditions. Methods: We report a case of recurrent peripheral facial palsies caused by an ipsilateral enlarged styloid process. A surgical excision of the process was performed. Results: The treatment was well tolerated. Postoperatively, no further recurrent paresis was observed. Conclusion: To the best of our knowledge, this is the first case study of an enlarged styloid process with facial paresis. A detailed workup, including imaging, should be performed in cases with recurrent facial paresis and/or cases with a history of trauma and facial paresis and, of course, to exclude a neoplastic etiology. [ABSTRACT FROM AUTHOR]

Background: We evaluated the ability of different (18F)fluoro‐deoxy‐d‐glucose (FDG)‐positron emission tomography (PET)‐based and magnetic resonance (MR)‐based parameters to identify prevertebral space (PVS) infiltration by hypopharyngeal carcinoma. Methods: Retrospective study on 59 patients with advanced hypopharyngeal squamous cell carcinoma undergoing cross‐sectional imaging and triple endoscopy for staging. Results: Obliteration of retropharyngeal fat plane on T1‐weighted MR images was found more often (P < .001) in tumors fixated to the PVS. Complete fat plane obliteration best predicted tumor fixation to PVS (accuracy 99%; CI: 97%‐100%; P < .001). With similar accuracy, PET‐based models predicted PVS fixation (combination of standardized uptake value [SUVmax] of the primary tumor and presence of focal FDG‐uptake in prevertebral muscles [accuracy 98%; CI 94%‐100%; P < .001]; metabolic tumor volume [MTV] [accuracy 98%; CI 95%‐100%; P < .001]). Conclusion: Both the MR‐based parameter of complete fat plane obliteration and PET‐based models (increased SUVmax in combination with presence of focal FDG‐uptake of prevertebral muscles; increased MTV) predict PVS involvement independently with high accuracy. [ABSTRACT FROM AUTHOR]

The article discusses contrast‐enhanced 18F‐FDG‐PET/CT for differentiating tumour and radionecrosis in head and neck Cancer. Topics include how radionecrosis is a feared complication after high-dose radiation therapy (RT) of head and neck squamous cell cancer (HNSCC) and how the presence of a permeative growth pattern may identify tumour recurrence/persistence and rule out radionecrosis in patients with HNSCC after RT.

Purpose: The aim of the study was to investigate the relationship between [18F]fluoromethyl-dimethyl-2-hydroxyethylammonium ([18F]FCh) positron emission tomography (PET) parameters, laboratory parameters, and postoperative histopathological results in patients with primary hyperparathyroidism (pHPT) due to parathyroid adenomas.Procedures: This retrospective study was conducted in 52 patients with biochemically proven pHPT. [18F]FCh-PET parameters (maximum standardized uptake value: SUVmax) in early phase (after 2 min) and late phase (after 50 min), metabolic volume, and adenoma-to-background ratio (ABR), preoperative laboratory results (PTH and serum calcium concentration), and postoperative histopathology (location, size, volume, and weight of adenoma) were assessed. Relationship of PET parameters, laboratory parameters, and histopathological parameters was assessed using the Mann-Whitney U test and Spearman correlation coefficient. MRI characteristics of parathyroid adenomas were also analyzed.Results: The majority of patients underwent a PET/MR scan, 42 patients (80.7 %); 10 patients (19.3 %) underwent PET/CT. We found a strong positive correlation between late-phase SUVmax and preoperative PTH level (r = 0.768, p < 0.001) and between late-phase ABR and preoperative PTH level (r = 0.680, p < 0.001). The surgical specimen volume was positively correlated with the PET/MR lesion volume (r = 0.659, p < 0.001). No significant association was observed between other [18F]FCh-PET parameters, laboratory parameters, and histopathological findings. Cystic adenomas were larger than non-cystic adenomas (p = 0.048).Conclusions: [18F]FCh uptake of parathyroid adenomas is strongly correlated with preoperative PTH serum concentration. Therefore, the preoperative PTH level might potentially be able to predict success of [18F]FCh-PET imaging in hyperparathyroidism, with higher lesion-to-background ratios being expected in patients with high PTH. PET/MR is accurate in estimating the volume of parathyroid adenomas. [ABSTRACT FROM AUTHOR]

Background: Aim was to analyze the expression of different cancer testis antigens (CTA) and to assess its prognostic value in salivary gland carcinomas. Methods: Patients with salivary gland carcinomas diagnosed 1994 to 2010 were included. Baseline characteristics, pathohistological, clinical, and outcome data were assessed. Tissue microarrays were constructed and immunohistochemistry for different CTA (NY‐ESO1, NY‐BR1, MAGE A1, MAGE A3, MAGE A4, MAGE C1/CT7, and MAGE C2/CT10) was performed. CTA expression was assessed and statistically correlated with pathological and outcome data. Results: Expression rates of CTA in salivary gland tumors ranged from 0% to 40%. MAGE A4 expression was associated with a lower tumor grade tumor grading (P = .017), and a favorable recurrence‐free (P = .003), disease‐specific (P = .046) and overall survival (P = .028). Conclusions: MAGE A4 is a highly significant prognostic marker in salivary gland carcinoma; its expression is associated with low‐grade histology, a low rate of distant metastasis and a favorable survival. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. B Correction to b B : b B Mol Imaging Biol (2018) 20:857-867 b https://doi.org/10.1007/s11307-018-1179-x This article was updated to correct affiliation 2. [Extracted from the article]

Background Knowledge about prognostic factors in surgically treated patients with oropharyngeal squamous cell carcinoma (SCC) is limited. The purpose of this study was to identify influential factors on survival in a large cohort of patients with surgically treated oropharyngeal SCC. Methods Retrospective analysis of survival estimates in patients with surgically treated oropharyngeal SCC using tumoral positivity for human papillomavirus (HPV) and risk-of-death categories according to a study from 2010 as stratification factors. Results The 5-year overall survival (OS) and disease-specific survival (DSS) rates after surgery alone were higher in HPV-associated oropharyngeal SCC (OS 80% vs 62%; P = .01; DSS 92% vs 76%; P = .03). Patients in the low-risk category had higher survival rates (OS 91%; DSS 99%) than patients in the intermediate-risk group (OS 63%; DSS 83%), and high-risk group (OS 61%; DSS 75%). Conclusion Nonsmokers with HPV-positive oropharyngeal SCC have a better prognosis than smokers with HPV-positive oropharyngeal SCC and also than patients with HPV-negative tumors when treated by surgery alone. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to compare the diagnostic accuracy of positron emission tomography (PET)/MRI with PET/CT for local resectability of head and neck cancer. Methods Sequential contrast-enhanced PET/CT-MRI was performed in 58 patients referred for the staging or restaging of head and neck cancer. Tumors were assessed with PET/CT and PET/MRI for the presence of resectability-defining factors: T4b status (mediastinal invasion, invasion of the prevertebral space, and vascular encasement), and another 8 findings that would imply obstacles for surgical cure (invasion of the laryngeal cartilage, invasion of the preepiglottic fat pad, perineural spread, orbital invasion, bone infiltration, skull base invasion, dural infiltration, and invasion of the brachial plexus). Results The sensitivity/specificity/accuracy of local resectability-defining factors of PET/CT and PET/MRI was 0.92/0.99/0.98 and 0.98/0.99/0.99 ( P = .727), respectively, per lesion, and 0.96/0.87/0.91 and 0.96/0.90/0.93 ( P = .687), respectively, per patient. Conclusion Both contrast-enhanced PET/MRI and contrast-enhanced PET/CT can serve as reliable examinations for defining local resectability of head and neck cancer. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to analyze the role of p16INK4a and the prevalence of human papillomavirus (HPV) in squamous cell carcinoma (SCC) of the nasal vestibule. Methods Patients diagnosed from 1995 to 2014 were included in this study. Assessment of p16INK4a and HPV-DNA polymerase chain reaction (PCR) was performed and analyzed with respect to baseline, clinicopathological, and outcome parameters. The p16INK4a positivity was defined as unequivocal nuclear and cytoplasmic staining of ≥70% of the cells, whereas 50%-69% was considered to be a 'borderline' result. Results There were 46 patients with SCCs of the nasal vestibule, of whom 31 (67.4%) were available for p16INK4a and 30 (65.2%) for analysis of HPV. Expression of p16INK4a was present in 19.4% and showed coincidence with high-risk HPV ( P < .001). Neither p16INK4a nor HPV-DNA had significant impact on outcome. Conclusion Significant immunoreactivity for p16INK4a was present in about one-fifth of the samples and figured as a surrogate marker of high-risk HPV infection. There was no influence on outcome. [ABSTRACT FROM AUTHOR]

Background Applicability of sentinel node biopsy (SNB) for tumors of the floor of mouth (FOM) is controversial. Methods Prospective evaluation of the accuracy of gamma-probe-guided superselective neck dissection of the preglandular triangle of level I for SNB in FOM squamous cell carcinoma (SCC) after preoperative lymphoscintigraphy and single photon emission CT (SPECT)/CT. Results In total, 22 sentinel lymph nodes were harvested in level I. Eight of 22 (36%) were seen on lymphoscintigraphy and 11 (50%) on SPECT/CT. Eleven sentinel lymph nodes (50%) were only detected intraoperatively. In unilateral tumors, 20% were contralateral, and, in midline tumors, 93% showed bilateral level I sentinel lymph nodes. The false-negative rate was 8.3%, the negative predictive value was 96.4%, and the false-omission rate was 3.6%. The ultimate neck control rate, including salvage treatment, was 100%. Conclusion SNB in FOM can be reliably performed using the presented surgical technique. Level I exploration, bilaterally in midline tumors, is mandatory irrespective of the visualization of sentinel lymph nodes in other levels. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1367-1372, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate prospectively the presence and impact of the gastric carcinogen Helicobacter pylori ( H. pylori) in the upper aerodigestive tract. Previous studies suggested it could represent a risk factor for head and neck squamous cell carcinoma (HNSCC). Methods Serology, rapid urease test, and quantitative polymerase chain reaction (qPCR) for H. pylori were performed in patients with head and neck cancer ( N = 56) and cancer-free controls ( N = 90). Comparison between groups was done using logistic regression analysis. Results Rates of positive serology and rapid urease test did not differ between the 2 groups in logistic regression analysis ( p = .677 and p = .633, respectively). Birth in a developing country and age above 50 years old were predictors of positive serology ( p < .001 and p = .040, respectively). Using qPCR, no biopsy showed the presence of H. pylori. Conclusion This study challenges the concept that H. pylori may be a risk factor for HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: 769-774, 2016 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis To analyze the impact of different types of perineural invasion (PNI) in squamous cell carcinoma (SCC) of the oral cavity on overall survival and recurrence rate, with a special focus on histologic subtypes and tumor stage. Study Design Retrospective case-control study with clinicopathological analysis. Methods Seventeen patients who received primary surgical treatment for SCC of the oral cavity with PNI were matched to a control group. In a histologic review, PNI was classified into subtypes according to an adapted Liebig classification. The term type A was used to describe tumor invasion into the nerve, whereas type B was used to describe circumferential growth around the nerve. Clinical charts were reviewed, and a Kaplan-Meier survival analysis was performed. Results The recurrence-free survival rates were 47.1% versus 80.4% (PNI vs. matched control group, P < 0.05), 60.0% versus 94.1% (PNI in stage I and II disease vs. matched control group, P < 0.05) and 41.7% versus 73.5% (PNI in stage III and IV disease vs. matched control group, P < 0.05). In most cases (n = 9) of PNI, both histologic subtypes (type A and type B) were present. Five cases exclusively showed type A, and three cases exclusively showed type B. Conclusions Perineural invasion in early disease oral carcinoma has a particularly high impact on survival. Both histologic subtypes showed a significantly worse recurrence-free survival rate when compared to the control group. Level of Evidence 3. [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]

A 21-year-old male suffering from severe throat pain after being hit by a bullet in Syria claimed that he was shot through his eye and that the bullet subsequently descended behind his throat. Even though the first medical report stated that this course is implausible, meticulous workup provided evidence that the bullet might have entered the parapharyngeal space in a more cranial position than the one it was found eight months later. Our case highlights that bullets are able to move within the body, rendering ballistic reconstruction difficult. However, after removal of the bullet the patient’s symptoms completely resolved. [ABSTRACT FROM AUTHOR]

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. Head Neck 37: 1477-1482, 2015 [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]

Background The purpose of this study was to analyze the outcome of squamous cell carcinomas (SCCs) of the nasal vestibule and to identify factors predicting recurrence. Methods All patients treated between 1995 and 2012 were included in this study. Outcome was analyzed with respect to modality of therapy, age, sex, tobacco consumption, staging, surgical margins, and histological differentiation pattern. Results Thirty patients were included. Fourteen patients (47%) were found with T4, 1 patient (3%) with T3, 7 patients (23%) with T2, and 8 patients (27%) with T1 disease. Twenty-one patients (70%) were treated surgically. Six patients (29%) needed postoperative radiation because of insufficient surgical margins. Radiation was the first-line treatment in 9 patients (30%). Surgically treated patients with surgical margins <3 mm had significantly more locoregional recurrence compared to those with sufficient resections. Conclusion Advanced T4 carcinomas show a high recurrence rate. Insufficient surgical margins are the main predictor for a locoregional recurrence and should be avoided. © 2014 Wiley Periodicals, Inc. Head Neck 37: 46-51, 2015 [ABSTRACT FROM AUTHOR]

Background Helicobacter pylori is known to cause gastric cancer. Presence and carcinogenicity in the upper aerodigestive system is doubtful. This study examined the prevalence of Helicobacter pylori and related factors in biopsies from the upper aerodigestive tract (UADT) in patients with gastric colonization by Helicobacter pylori. Methods In a case series study, 26 patients with histopathologically confirmed gastric colonization were identified. A polymerase chain reaction (PCR) was performed on matched formalin-fixed and paraffin-embedded tissues of the stomach and the oral cavity, pharynx, or larynx. Results Helicobacter pylori was found in 38% of the samples from the oral cavity, pharynx, and larynx. An association with malignancies in these regions or possible risk factors, such as age, smoking, or alcohol, was not found. Conclusion The upper aerodigestive system seems to be an additional reservoir in a significant percentage of patients presenting with Helicobacter pylori gastritis. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1562-1566, 2014 [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) is highly malignant and refractory to therapy. The majority of existing mouse SCC models involve multiple gene mutations. Very few mouse models of spontaneous SCC have been generated by a single gene deletion. Here we report a haploinsufficient SCC mouse model in which exon 3 of the Tp53BP2 gene (a p53 binding protein) was deleted in one allele in a BALB/c genetic background. Tp53BP2 encodes ASPP2 (ankyrin repeats, SH3 domain and protein rich region containing protein 2). Keratinocyte differentiation induces ASPP2 and its expression is inversely correlated with p63 protein in vitro and in vivo. Up-regulation of p63 expression is required for ASPP2Δexon3/+ BALB/c mice to develop SCC, as heterozygosity of p63 but not p53 prevents them from developing it. Mechanistically, ASPP2 inhibits ΔNp63 expression through its ability to bind IκB and enhance nuclear Rel/A p65, a component of the NF-κB transcription complex, which mediates the repression of p63. Reduced ASPP2 expression associates with tumor metastasis and increased p63 expression in human head and neck SCCs. This study identifies ASPP2 as a tumor suppressor that suppresses SCC via inflammatory signaling through NF-κB–mediated repression of p63. [ABSTRACT FROM AUTHOR]

Aims EGFR-directed therapies are used to treat patients with advanced head and neck squamous cell carcinoma ( SCC). As it is still unclear whether or not EGFR amplification represents an early or late event in head and neck SCC progression, we aimed to determine the frequency of abnormalities of EGFR protein and gene copy numbers in early oral SCC. Methods and results A tissue microarray of cancer tissue from 120 patients with pT1/2 oral SCC was constructed. We investigated EGFR protein expression by immunohistochemistry. EGFR gene copy enumeration was performed using fluorescence in-situ hybridization ( FISH) and the novel automated silver in-situ hybridization ( SISH) technology. Of early oral SCC, 19.3% showed high, 57.1% moderate and 23.6% low EGFR expression. EGFR amplification/polysomy was identified in 8% and 9% of cases by FISH and SISH, respectively. EGFR- SISH had a high concordance with EGFR- FISH (kappa value = 1.0), and both methods showed high conformity with EGFR immunohistochemistry ( P = 0.001 and P = 0.006, respectively). No correlation was found of EGFR protein expression or gene amplification status with pT or pN stage. Conclusions Only a small subgroup of early oral SCC is characterized by EGFR amplification, which can be identified reliably using EGFR- SISH technology. This finding suggests that EGFR gene amplification mostly occurs in advanced stages of oral SCC. [ABSTRACT FROM AUTHOR]

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. © 2012 Wiley Periodicals, Inc. Head Neck, 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. Adult rhabdomyoma is a rare benign tumour with the differentiation of striatedmuscle tissue, whichmainly occurs in the head and neck region. Twenty-six cases of multifocal adult rhabdomyoma are documented in the literature. Method. We report a 55-year-oldmalewith simultaneous diagnosis of 7 adult rhabdomyomas and reviewthe literature of multifocal adult rhabdomyoma. Result. Review of the literature revealed 26 cases of multifocal adult rhabdomyoma, of which only 7 presented with more than 2 lesions. Mean age at diagnosis was 65 years with a male to female ratio of 5.5 : 1. Common localizations were the parapharyngeal space (36%), larynx (15%), submandibular (14%), paratracheal region (12%), tongue (11%), and floor of mouth (9%). Besides the known radiological features of adult rhabdomyoma, our case showed FDG-uptake in (18) F-FDG PET/CT. Conclusion. This is the first case of multifocal adult rhabdomyoma published, with as many as 7 simultaneous adult rhabdomyomas of the head and neck. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To assess the quality of life in long-term survivors with oropharyngeal cancer (OPSCC), compare the results with our historic cohort in relation to the radiation technique, and explore the influence of treatment strategy and p16 expression on quality of life (QoL). Study Design: Retrospective chart analysis and patient response to EORTC QLQ-C30 and EORTC QLQ-H&N35 survey questionnaires. Methods: 98/120 (82%) survivors treated by primary intensity modulated chemoradiation (n = 55), or surgery with (n = 30) or without (n = 13) adjuvant radiotherapy (RT), completed and returned the questionnaires. Results: Surgically treated patients complained about significantly less troubles with dry mouth and teeth compared to the nonsurgically treated group. Comparing patients treated with surgery alone and those receiving any kind of RT (primary or adjuvant) the latter group complained about significantly more problems. Patients with p16-positive tumors demonstrated significantly higher tumor stages, but significantly better scores in physical and role functions. Conclusions: Early disease can be treated with high long-term QoL by surgery alone. Primary surgery with postoperative RT in selected patients with limited primary tumors and advanced neck disease renders excellent QoL. Our results suggest that IMRT is superior to former radiation techniques with regard to QoL, and should be considered as standard of care in patients undergoing RT for OPSCC. Patients with p16 positive tumors appear to show not only a better outcome but also report on a better QoL. Laryngoscope, 2013 [ABSTRACT FROM AUTHOR]

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. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Sentinel node biopsy (SNB) has been proposed for staging of the cN0 neck in early oral/oropharyngeal squamous cell carcinomas (SCC). Because SNB is a minimally invasive procedure, it is thought to be associated with less morbidity than elective neck dissection. Methods Sixty-two consecutive patients were included from 2000 to 2009. Two groups were analyzed consisting of 33 patients after SNB and 29 after elective neck dissection. Subjective impairment and functional shoulder status were assessed with the Neck Dissection Impairment Index (NDII) questionnaire and the modified individual relative Constant Score. Postoperative complications were retrieved from the clinical charts. Results The investigated scores were significantly better in the SNB group. All postoperative complications occurred in the elective neck dissection group. Conclusion SNB is associated with significantly less postoperative morbidity and better shoulder function than elective neck dissection. This supports our opinion that patients with nodal negative early SCC of the oral cavity should be offered SNB. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [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]

Background. Primary sinonasal malignant melanoma (SNMM) is a rare clinical entity. There is neither a classification nor a staging system nor an evidence-based treatment concept established. Our objective was to find potential risk factors predicting the outcome. Methods. Twenty-five patients with histologically confirmed SNMM were consecutively included and retrospectively analyzed. Staging methods were nasal endoscopy, CT, MRI, and positron emission tomography (PET) scan. Patients were selected for a curative or palliative concept. All patients had postoperative follow-up with control-MRI at 3 and 6 months. Restaging was performed when local recurrence occurred. Results. Nineteen patients underwent primary surgery with curative intention; in 16 cases with tumor free margins. Thirteen patients (68%) had transnasal endoscopic surgery, 4 lateral rhinotomy, and 2 transfacial approach with orbital exenteration. Six patients (32%) had palliative therapy and 7 patients (37%) had adjuvant radiotherapy. Despite radical operations, 6 patients (37%) showed local recurrence and 8 patients (50%) developed distant metastasis. In 2 patients with incomplete surgery, regional metastasis was noted. The median disease-free interval was 18 months, and the median overall survival rate was 23 months. Conclusion. SNMMs of the ethmoid and maxillary sinuses have a worse prognosis than other localizations in the nasal cavity; infiltration into the skull base, orbit, or facial soft tissue correlates with a very poor outcome corresponding to the palliative situations. Furthermore, local recurrence insinuates aggressive disease with short survival rate. A main difference from its cutaneous counterpart seems to be a primary tendency to hematogenic spread. Further research is needed to confirm these findings. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [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]

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Objectives: To determine accuracy and intertest agreement of preoperative fine-needle aspiration cytology (FNAC) and intraoperative frozen-section analysis (FS) findings in thyroid surgery, and to assess the influence of intraoperative FS findings on decision making and the utility of FS in thyroid surgery. Design: Retrospective analysis. The results of preoperative FNAC, intraoperative FS, and final histopathological analyses were taken from the histopathology reports. We calculated intertest agreement using the κ statistic. Patients: Two-hundred fifteen patients who underwent primary thyroid surgery. All patients were treated by the same surgeon (S.J.W.). Results: The sensitivity and specificity of FNAC were 57.4% and 91.7%, respectively. The sensitivity and specificity of FS were 32.4% and 96.5%, respectively. The interest agreement was poor (κ = 0.17). In case of malignant FNAC findings, the FS result did not influence treatment decisions; in case of a malignant FS result on the background of a benign, indeterminate, or nondiagnostic FNAC finding, the FS result influenced treatment decisions in 88% of cases. Conclusions: Intraoperative FS did not give additional information in cases where a malignant neoplasm was predicted by the FNAC finding. In this setting, it led to conflicting results and did not contribute to correct decision making. [ABSTRACT FROM AUTHOR]