Early Timing of Thyroidectomy for Hyperthyroidism in Graves' Disease Improves Biochemical Recovery.

BACKGROUND: The role of thyroidectomy as an early treatment for hyperthyroidism has been poorly investigated. Our aim was to examine its success rates, particularly focusing on thyroidectomy as an early treatment. METHODS: Patients with thyroidectomy for hyperthyroidism between February 2008 and October 2014 were included. They were divided into two groups (early and delayed thyroidectomy), and patient characteristics, treatment indications, complications and time to biochemical recovery were analyzed. RESULTS: Ninety-nine patients met the inclusion criteria, of whom 65 (66%) suffered from Graves' disease, 25 (25%) from toxic goiters and 9 (9%) from amiodarone-induced hyperthyroidism. Structural abnormalities of the thyroid (39 patients, 39%) represented the most frequent indications for thyroidectomy. Forty-six patients (46%) underwent an early and 53 (54%) a delayed surgical approach. Patients with Graves' disease undergoing early thyroidectomy did not suffer more often from complications but had a significantly faster biochemical recovery after surgery than those with a delayed thyroidectomy, as judged by a shorter time to reach TSH (121 ± 24 vs. 240 ± 31 days, p = 0.007) and fT4 (91 ± 29 vs. 183 ± 31 days p = 0.015) levels in the normal range. As expected, there were no recurrences of hyperthyroidism. CONCLUSIONS: Early thyroidectomy was neither associated with permanent complications nor thyroid storm, but with a significantly improved biochemical recovery and therefore has to be recommended early in patients with Graves' disease.

The presence of aberrant p53 pattern is a negative prognostic predictor in squamous cell carcinoma of the nasal vestibule.

The aim of this study was to analyze the role of Ki-67, p53, and the "aberrant p53 pattern" in squamous cell carcinomas of the nasal vestibule. Patients between 1995 and 2014 were included. Baseline characteristics and outcome were analyzed with respect to immunohistochemical staining of Ki-67 and p53. "Aberrant p53 pattern" was represented by a moderate or strong staining of at least 60% of the tumor cells or a complete absence of immunoreactivity. Forty-six patients were included of whom 31 (67.4%) were available for Ki-67 and 32 (69.9%) for p53 immunohistochemistry. The "aberrant pattern" of p53 was present in 50% of the patients. While immunoreactivity for both Ki-67 and p53 was not related to each other or outcome, the "aberrant p53 pattern" was associated with a worse disease-free survival (p = 0.014). The "aberrant p53 pattern" is a negative prognostic factor in squamous cell carcinoma of the nasal vestibule and might enable a patient-tailored treatment.

Delayed diagnosis of sinonasal lymphoma due to bilateral manifestation.

The objective of this study is to analyze the presenting symptoms, the time to correct diagnosis and outcome of a European patient cohort with sinonasal lymphoma focusing on unilateral vs. bilateral sinonasal involvement. In a retrospective setting in a European tertiary referral center, eleven patients (9 males, 2 females) with sinonasal lymphoma diagnosed between 2002 and 2015 were identified and divided into a unilateral and bilateral group according to their CT finding. Clinical findings on first presentation, the presence of B symptoms, the radiologic findings, overall survival and disease-specific survival were assessed. 55 % of the patients suffered from bilateral manifestation, which was associated with a delayed diagnosis (10 vs. 1.5 months, p < 0.05). B symptoms (67 vs. 0 %) and death of disease (50 vs. 0 %) were observed only in the bilateral group. Nasal NK/T-cell lymphoma was the most frequent diagnosis, followed by diffuse large B-cell lymphoma. Bilateral mucosal manifestation with B symptoms was shown to be common within the rare entity of sinonasal lymphomas and patients with bilateral sinonasal manifestation are at risk for a delayed diagnosis with worse outcome.

ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63.

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 ASPP2(Δexon3/+) 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.

Less may be more: nodal treatment in neck positive head neck cancer patients.

Ongoing debates about the need and extent of planned neck dissection (PND), and required nodal radiation doses volumes lead to this evaluation. Aim was to assess nodal control after definitive intensity modulated radiation therapy (IMRT ± systemic therapy) followed by PND in our head neck cancer cohort with advanced nodal disease. Between 01/2005 and 12/2013, 99 squamous cell cancer HNC patients with pre-therapeutic nodal metastasis ≥3 cm were treated with definitive IMRT followed by PND. In addition, outcome in 103 patients with nodal relapse after IMRT and observation only (no-PND cohort) were analyzed. Prior to PND, PET-CT, fine needle aspirations, ultrasound and palpation were assessed regarding its predictive value. Patterns of nodal relapse were assessed in patients with isolated neck failure after definitive IMRT alone. 70/99 (70 %) PND specimens showed histopathological complete response (hCR), which translated into statistically significantly superior survival compared with partial response (hPR) with 4-year overall survival, disease specific survival and nodal control rates of 90/83/96 vs 67/60/78 % (p = 0.002/0.001/0.003). 1/99 patient developed isolated subsequent nodal disease. 64/2147 removed nodes contained viable tumor (3 %). Predictive information of the performed diagnostic investigations was not reliable. 17/70 hCR patients showed true negative findings in available three to four investigations (0/29 hPR). 27/103 no-PND patients developed isolated neck disease (26 %) with successful salvage in 21/24 [88 %, or 21/27 (78 %)]. Nearly all failures occurred in the prior nodal gross tumor volume area. A more restrictive approach regarding PND and/or nodal IMRT dose-volumes may be justified.

Combined PET/CT-perfusion in patients with head and neck cancers might predict failure after radio-chemotherapy: a proof of concept study.

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.

Zenker's diverticulum: outcome of endoscopic surgery is dependent on the intraoperative exposure.

The purpose of the present study is to evaluate long-term outcome and patients' satisfaction after endoscopic therapy of Zenker's diverticulum (ZD) and to analyze the results of the stapler technique in comparison with the application of the carbon dioxide (CO2) laser. A retrospective cohort study with outcome analysis of patients undergoing endoscopic cricopharyngeal myotomy with either stapler or CO2 laser between October 2000 and December 2010 by a single surgeon was performed. Patient's medical charts were reviewed with respect to symptoms before intervention, intra and post operative complications, reasons for the choice of endoscopic technique, and postoperative relief of symptoms. Long-term follow-up was acquired by a standardized self-assessment questionnaire. Seventy-four patients (51 men, 23 women) with a median age at operation of 74 years (range 45-93 years) were enrolled in this study. Forty-five patients underwent endoscopic repair of a ZD with stapler, 29 patients with CO2 laser. The mean follow-up was 4.7 years. We did not observe significant differences for intra and post operative complications, hospital stay, time until normal oral food intake, need for revision, and long-term subjective symptom relief between the two groups. Overall complication (12 %) and recurrence rate (11 %) for the endoscopic techniques were low. Endoscopic surgery had also a high success rate in recurrence cases (87.5 %). According to our study, the most important factor for the success rate of endoscopic treatment was the intraoperative exposure of the ZD. The endoscopic minimally invasive approach is a safe and effective treatment modality and can be considered as the treatment of choice for primary and recurrent ZD. The intraoperative exposure is decisive for the technique applied and the long-term success.

Human papilloma virus and survival of oropharyngeal cancer patients treated with surgery and adjuvant radiotherapy.

Impact of p16 protein, a surrogate marker for human papilloma virus induced cancer, p53 and EGFR as well as clinical factors on survival in a patient cohort with oropharyngeal squamous cell carcinoma (OPSCC) treated by surgical resection and adjuvant radiotherapy (RT) ± concomitant chemotherapy (CT). This is a retrospective analysis of patient's charts and tumor tissue. 57 patients were consecutively included and their tumor tissue assembled on a tissue microarray following immunohistochemical analysis. Survival times were estimated by means of Kaplan-Meier analysis. The importance of clinical and immunohistochemical factors for outcome was estimated by cox proportional hazard models. With 88% 5-year overall survival, 91% 5-year disease-specific survival and 91% 5-year disease-free survival, respectively, we found excellent survival rates in this surgically treated patient cohort of mainly advanced OPSCC (93% AJCC stage III or IV). The only factors positively influencing survival were p16 overexpression as well as p53 negativity and even more pronounced the combination of those biomarkers. Survival analysis of patients classified into three risk categories according to an algorithm based on p16, smoking, T- and N-category revealed a low, intermediate and high-risk group with significant survival differences between the low and the high-risk group. Patients with OPSCC can be successfully treated by surgery and adjuvant RT ± CT with a clear survival benefit of p16 positive, p53 negative patients. We recommend considering a combination of immunohistochemical (p16, p53) and clinical factors (smoking, T- and N-category) for risk stratification.

EGFR expression and copy number changes in low T-stage oral squamous cell carcinomas.

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.

Validity of frozen section in sentinel lymph node biopsy for the staging in oral and oropharyngeal squamous cell carcinoma.

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.

Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma.

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.

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx.

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.

Impact of the new TNM Staging System (8th edition) on oral tongue cancers.

AIM OF THE STUDY: For tumours of the oral tongue, the most recent 8th edition of the AJCC/UICC staging system has introduced depth of infiltration (DOI) as a novel parameter. With this study we wanted to investigate its impact regarding this risk stratification compared with the preceding 7th edition. METHODS: Between 2008 and 2017, 161 patients of two tertiary referral centres in Switzerland (Kantonsspital St. Gallen and University Hospital Zurich) with T1 N0 or T2 N0 tongue cancers were enrolled in this study. The primary tumours were restaged according to the 8th edition of the TNM classification. Kaplan-Meier curves for overall and disease-specific survival were calculated. RESULTS: According to the 7th edition, of the 161 patients, 102 were staged after surgery as pT1 (stage I) and 59 as pT2 (stage II). According to the 8th edition, 36 patients (22.4%) were re-staged to a higher stage. Of these 36 patients, 8 (22.2%) experienced a recurrence, and 9 (25%) died. In the remaining, not re-staged group, 20 patients (16.0%) experienced a recurrence (p = 0.55) and 14 (11.2%) died (p = 0.025*). The 7th edition showed a statistically significant difference between pT1 and pT2 tumours for overall survival (p = 0.025), but not for disease-specific survival (p = 0.091), whereas the 8th edition was able to well discriminate between pT1, pT2 and pT3 for both overall (pT1 vs pT2, p = 0.016*; pT2 vs pT3, p = 0.031*) and disease-specific survival (pT1 vs pT2, p = 0.037*; pT2 vs pT3, p = 0.023*). CONCLUSION: The recent TNM 8th edition provides a more accurate prediction of overall and disease-specific survival for this subgroup of patients. Hence, a more aggressive treatment should be considered for patients re-staged to pT3 due to depth of infiltration.

Evaluation of 18F-FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma.

BACKGROUND: To determine whether 18 F-PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18 F-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.

The expression of PD-L1 in salivary gland carcinomas.

Objective was to analyze the role of PD-L1 and its relation to demographic, patho-clinical and outcome parameters in salivary gland carcinoma (SGC) patients. Patients treated for salivary gland carcinomas between 1994 and 2010 were included. A retrospective chart review for baseline characteristics, pathohistological, clinical and outcome data was performed. Immunohistochemistry for PD-L1 was performed using tissue microarrays. PD-L1 expression was assessed in tumor cells and tumor-infiltrating immune cells (TIIC) and statistical analysis with regard to baseline and outcome data was performed. Expression of PD-L1 (by means ≥1% of the cells with PD-L1 positivity) was present in the salivary gland carcinoma cells of 17%, in the TIIC of 20% and in both tumor cells and TIIC of 10% the patients. PD-L1 expression in tumor cells and both tumor cells and TIIC was related to tumor grading (p = 0.035 and p = 0.031, respectively). A trend towards higher grading was also seen for PD-L1 expression in TIICs (p = 0.058). Patients with salivary duct carcinomas and PD-L1 expressing TIICs showed a significantly worse DFS and OS (p = 0.022 and p = 0.003, respectively), those with both tumor cells and TIIC expressing PD-L1 a significantly worse DFS (p = 0.030). PD-L1 expression is present in 17% and 20% of salivary gland carcinoma cells and TIIC. Ten percent of the patient showed a PD-L1 positivity in both tumor cells and TIIC. This is related to high tumor grading and therefore might be a negative prognostic factor.

Recurrent unilateral peripheral facial palsy in a patient with an enlarged styloid process.

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.

Use of MRI and FDG-PET/CT to predict fixation of advanced hypopharyngeal squamous cell carcinoma to prevertebral space.

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.

Preoperative assessment of CD44-mediated depth of invasion as predictor of occult metastases in early oral squamous cell carcinoma.

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.

Predictive Value of Pretherapeutic Maximum Standardized Uptake Value (Suvmax) In Laryngeal and Hypopharyngeal Cancer.

The aim of the study was to evaluate whether pretherapeutic metabolic tumor parameters from 18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging could predict larynx preservation in laryngeal and hypopharyngeal cancer patients prior to primary chemoradiation. Tumor metabolic parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were retrospectively assessed in a consecutive cohort of laryngeal and hypopharyngeal cancer patients undergoing primary (chemo-)radiation. Main outcome measures were larynx preservation and survival. The study included 97 patients with a median follow-up of 32 months (IQR 20-54.5). For hypopharyngeal cancer, multivariable analysis showed that patients with a primary tumor's SUVmax > 9.5 entailed a higher risk of undergoing salvage pharyngolaryngectomy after chemoradiation (HR = 8.64, 95% CI = 1.1-67.3, P = 0.040). In laryngeal cancer, SUVmax did not predict the need for salvage laryngectomy. The only predictor for larynx preservation in laryngeal cancer patients was T-classification at initial diagnosis (HR = 6.67, 95% CI = 0.82-53.9, P = 0.039). In conclusion, SUVmax of primary tumor could be used as a predictor of larynx preservation prior to primary chemoradiation in hypopharyngeal cancer patients. This information may be important for patient counseling, as high SUVmax was correlated with reduced probability of larynx preservation. However, in laryngeal cancer patients, SUVmax does not seem to be predictive of outcome.