Non-linear image blending improves visualization of head and neck primary squamous cell carcinoma compared to linear blending in dual-energy CT.

AIM: To compare non-linear and linear image-blending post-processing techniques in dual-energy CT (DECT) of primary head and neck squamous cell carcinoma (SCC) regarding subjective and objective image quality. MATERIALS AND METHODS: Head and neck DECT studies from 69 patients (48 male, 21 female; mean age 62.3 years) were retrospectively evaluated. All tumour lesions were histologically confirmed SCC. Linearly blended 80/140 kVp images series with varying weighting factors of 0.3 (M_0.3), 0.6 and 0.8 were compared with non-linearly blended images. Attenuation of tumour lesion, various soft-tissue structures, the internal jugular vein, and image noise were measured, tumour signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Overall image quality, delineation of tumour lesion, image sharpness, and noise level were rated individually by three radiologists using five-point Likert scales. Interobserver agreement was calculated using intraclass correlation coefficient (ICC). RESULTS: Enhancement of tumour lesions (non-linear, 137.5 ± 20.1 HU; M_0.3, 92.7 ± 14.4 HU; M_0.6, 110 ± 15.4 HU; M_0.8, 123 ± 18.2 HU), CNR (non-linear, 12 ± 8; M_0.3, 4 ± 4.7; M_0.6, 7.5 ± 5.5; M_0.8, 8 ± 5.5), subjective overall image quality and tumour delineation were significantly increased (all p < 0.001) with the non-linear blending technique compared to all investigated linear blending weighting factors. Overall interobserver agreement was substantial (ICC 0.70; 95% CI: 0.66-0.73). CONCLUSION: Post-processing of DECT using a non-linear blending technique provides improved objective and subjective image quality of head and neck SCC compared to linearly blended images series.

Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer.

BACKGROUND: We aimed to investigate the prognostic value of tumour-infiltrating lymphocytes' (TILs) expression in pretreatment specimens from patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT). METHODS: The prevalence of CD3+, CD8+, CD4+ and FOXP3+ TILs was assessed using immunohistochemistry in tumour tissue obtained from 101 patients before CRT and was correlated with clinicopathological characteristics as well as local failure-free- (LFFS), distant metastases free- (DMFS), progression-free (PFS) and overall survival (OS). Survival curves were measured using the Kaplan-Meier method, and differences in survival between the groups were estimated using the log-rank test. Prognostic effects of TIL subset density were determined using the Cox regression analysis. RESULTS: With a mean follow-up of 25 months (range, 2.3-63 months), OS at 2 years was 57.4% for the entire cohort. Patients with high immunohistochemical CD3 and CD8 expression had significantly increased OS (P=0.024 and P=0.028), PFS (P=0.044 and P=0.047) and DMFS (P=0.021 and P=0.026) but not LFFS (P=0.90 and P=0.104) in multivariate analysis that included predictive clinicopathologic factors, such as age, sex, T-stage, N-stage, tumour grading and localisation. Neither CD4 nor FOXP3 expression showed significance for the clinical outcome. The lower N-stage was associated with improved OS in the multivariate analysis (P=0.049). CONCLUSION: The positive correlation between a high number of infiltrating CD3+ and CD8+ cells and clinical outcome indicates that TILs may have a beneficial role in HNSCC patients and may serve as a biomarker to identify patients likely to benefit from definitive CRT.

Head and neck cancer relapse after chemoradiotherapy correlates with CD163+ macrophages in primary tumour and CD11b+ myeloid cells in recurrences.

BACKGROUND: We investigated the prognostic role of tumour-associated macrophages (TAMs) in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT). METHODS: The expression of CD68+, CD163+ and CD11b+ cells was assessed using immunohistochemistry in n=106 pre-treatment tumour biopsy samples and was correlated with clinicopathological characteristics, including T-stage, N-stage, grading, tumour localisation, age and sex as well as local failure-free survival (LFFS), distant metastases-free survival (DMFS), progression-free (PFS), and overall survival (OS). Finally, TAMs expression and vessel density (CD31) were examined in n=12 available early local recurrence samples and compared with their matched primary tumours . The diagnostic images and radiotherapy plans of these 12 patients were also analysed. All local recurrences occurred in the high radiation dose region (⩾70 Gy). RESULTS: With a median follow-up of 40 months, OS at 2 years was 60.5%. High CD163 expression in primary tumours was associated with decreased OS (P=0.010), PFS (P=0.033), LFFS (P=0.036) and DMFS (P=0.038) in multivariate analysis. CD163 demonstrated a strong prognostic value only in human papillomavirus (p16(INK4))-negative patients. Early local recurrence specimens demonstrated a significantly increased infiltration of CD11b+ myeloid cells (P=0.0097) but decreased CD31-positive vessel density (P=0.0004) compared with their matched primary samples. CONCLUSIONS: Altogether, baseline CD163 expression predicts for an unfavourable clinical outcome in HNSCC after definitive CRT. Early local recurrences showed increased infiltration by CD11b+ cells. These data provide important insight on the role of TAMs in mediating response to CRT in patients with HNSCC.

Concomitant chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy as definitive, first line treatment of squamous cell carcinoma of the head and neck. A retrospective single center analysis.

PURPOSE: Despite the lack of evidence to support its implementation in the clinical practice, induction chemotherapy (IC) before chemoradiotherapy (CRT) is often used in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). We retrospectively examined the tolerability, feasibility, and clinical outcome of both concepts in a single center analysis. PATIENTS AND METHODS: In all, 83 patients were treated between 2007 and 2010 with IC + CRT (n = 42) or CRT alone (n = 41). IC consisted of docetaxel, cisplatin and 5-fluorouracil (TPF), or cisplatin and 5-fluorouracil (PF). All patients were scheduled to receive 2 cycles of PF during concurrent CRT. Adverse events were assessed according to the common toxicity criteria of adverse events (CTCAE v. 3.0). Associations were tested using the χ² test, and survival estimates were calculated according to Kaplan-Meier. RESULTS: The median follow-up was 30.35 months (range 2.66-61.25 months). At 2 years, the overall survival rate was significantly higher for primary CRT compared to IC + CRT group (74.8 % vs. 54 %, respectively; p = 0.041). Significantly more treatment-related overall grade 4 toxicities were documented in the IC + CRT group compared to the CRT group (42.9% vs. 9.8%; p = 0.001). Renal toxicity ≥ grade 2 occurred in 52.4 % vs. 7.3 % (p < 0.001), respectively. In all, 93 % of the patients with primary CRT compared to 71 % with IC + CRT received the planned full radiotherapy dose (p = 0.012). CONCLUSION: This is, to our knowledge, the largest retrospective study to compare IC + CRT with primary CRT. IC showed high acute toxicity, compromised the feasibility of concurrent CRT, and was associated with reduced overall survival rates compared to primary CRT. The lack of clinical benefit in conjunction with the increased toxicity does not support implementation of IC.

[Secretion scale by Murray et al. for FEES®: comparison of reliability and validity of the German long and short version]. / Sekretbeurteilungsskala nach Murray et al. für FEES(®) : Reliabilitäts- und Validitätsvergleich der deutschen Lang- und Kurzversion.

BACKGROUND: Accumulation of secretions in the hypopharynx, aditus laryngis and trachea constitute a cardinal trait of oropharyngeal dysphagia. For the evaluation of the degree of severity a 4-point secretion scale by Murray et al. is used internationally in a long and a short version. However, a validated German translation of the long version of this scale does not yet exist. Also, it has not yet been scientifically proven that both versions of the scale are equally valid. OBJECTIVES: This study aimed at the validation of the German translation of the long version of the secretion scale by Murray et al. and at a comparison of reliability and validity of the short and long versions. MATERIAL AND METHODS: A total of 40 videos of fiberoptic endoscopic evaluation of swallowing (FEES(®)), 10 for each severity level, were rated by 4 otorhinolaryngologists (ENT specialists) independently and with different randomizations for examination of the reliability and validity. Two rating sessions for each of the scale versions were conducted. Intrarater and interrater reliability as well as the agreement of the ratings with a reference standard were analyzed. RESULTS: Both the intrarater reliability (Spearman correlations: ρs > 0.840***) and the interrater reliability (Krippendorff's alpha: α > 0.850) yielded very good results and the concurrent validity was highly significant (ρs > 0.981***). DISCUSSION: The German translation of the secretion scale by Murray et al. can be considered reliable and valid, with comparable test accuracy of the short and long versions. Hence, the scale can be recommend for the graduation of pharyngolaryngotracheal secretions and should be integrated into the standardized evaluation of FEES(®) diagnostics for clinical and scientific purposes.

[Penetration-Aspiration Scale according to Rosenbek. Validation of the German version for endoscopic dysphagia diagnostics]. / Penetrations-Aspirations-Skala nach Rosenbek. Validierung der deutschen Version für die endoskopische Dysphagiediagnostik.

BACKGROUND: The Penetration-Aspiration Scale was developed by Rosenbek et al. to enable standardized documentation of this cardinal symptom of a swallowing disorder. OBJECTIVES: The objective was to create and validate a German version of the Penetration-Aspiration Scale according to the guidelines governing the translation of foreign language measurement tools. MATERIALS AND METHODS: Both reliability and validity were examined based on the ratings of 80 randomized endoscopically evaluated swallows, 10 for each severity level. Ratings were carried out by four independent raters: two with more than 3 years' experience with dysphagia and a further two with less than 3 years' experience. The swallows were rerated after 4 weeks. RESULTS: Both intrarater (Kendall's Tau: τs > 0.643; median 0.773; ps < 0.001) and interrater reliability were highly significant (two-way mixed single ICC coefficient of 0.799 for the first rating session and 0.728 for the second session; ps < 0.001). Results from the raters with less than 3 years' experience were significantly different from the reference standard in three out of four cases, whereas this was not the case for the more experienced raters. However, for each film, the median of the individual ratings from all four raters correlated almost perfectly with the reference standard (first rating session: τ = 0.894; second rating session: τ = 0.843; ps < 0.001). CONCLUSION: The German version of the Penetration-Aspiration Scale according to Rosenbek presented here was demonstrated to be both reliable and valid. Despite its dependency on the raters' experience, it can therefore be used as a graduation instrument for swallowing disorders in German-speaking countries and make an important contribution to evidence-based medicine in dysphagiology for both clinical and scientific use.

[Epithesial craniofacial reconstructions after mutilating surgery in head and neck cancer patients]. / Epithetische Wiederherstellungsmöglich-keiten nach mutilierenden onkologi-schen Eingriffen in der Kopf-Hals-Region.

The construction of facial prostheses is frequently used as a remedial treatment method in otorhinolaryngology. Modern prostheses are often attached to the face via bone anchored titanium implants and magnetic attachments. The use of specialised silicones and colouring techniques produces prostheses which realistically mimic lost facial tissues and significantly enhance patient quality of life. The article provides an overview of the possibilities of modern epithetics in the treatment of facial defects resulting from head and neck tumors.

Pre-treatment haemoglobin level predicts response and survival after TPF induction polychemotherapy in advanced head and neck cancer patients.

OBJECTIVE: To investigate the prognostic value of the pre-treatment haemoglobin level in patients with advanced squamous cell head and neck cancer treated with induction polychemotherapy. DESIGN: Seventy-two patients with advanced squamous cell head and neck cancer received primary combination chemotherapy consisting of docetaxel 75 mg/m(2) on day 1, cisplatin 100 mg/m(2) on day 1, and 5-fluorouracil (5-FU) 1000 mg/m(2)/day on days 1-4 (total dose 4000 mg/m(2)), repeated on days 1, 22 and 43 followed by chemoradiation. The data collected included pre-treatment haemoglobin, response to treatment, disease-free and overall survival. RESULTS: The pre-treatment haemoglobin level was found to be a significant predictor of response to induction chemotherapy (P = 0.01) and an independent predictor of overall survival [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.58-1.03, P = 0.0001] and disease free survival (HR 2.09, 95% CI 1.41-3.09, P = 0.0001). Furthermore N-stage was found to be a significant prognostic factor of overall survival (HR 9.24, 95% CI 6.90-21.34, P = 0.005). The Eastern Cooperative Oncology Group performance status scale was also found to be significant for disease free survival (HR 7.66, 95% CI 2.61-22.46, P = 0.003). CONCLUSION: In patients with advanced squamous cell head and neck cancer, the haemoglobin level prior to induction chemotherapy is significantly related to outcome including response and survival.

Differentiation of benign and malignant parotid tumors using deconvolution-based perfusion CT imaging: feasibility of the method and initial results.

AIM: We evaluated the feasibility of perfusion CT (CTP) of the parotid gland and attempted to differentiate benign from malignant tumors. MATERIALS AND METHODS: CTP was performed in 17 patients with benign tumors and 10 patients with malignant parotid tumors. Data were postprocessed by using deconvolution-based perfusion analysis. Postprocessing-generated maps showed blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability surface product (PS). Regions of interest were placed through the tumor site and the contralateral healthy parotid tissue. Ratios of the perfusion values between the tumors and the contralateral healthy structures were also calculated. Pearson correlation coefficients were determined to compare the agreement between the two readers. RESULTS: Perfusion maps of all tumors were successfully obtained. High Pearson correlation coefficients comparing the two readers' visually measured abnormalities were observed (r=0.79-0.86, P=0.001) for all perfusion maps, The MTT and PS values between malignant and benign tumors were not significantly different. The BF and BV values were statistically significant different between the benign and malignant tumors (0.00

Low-tube-voltage 80-kVp neck CT: evaluation of diagnostic accuracy and interobserver agreement.

BACKGROUND AND PURPOSE: Low-tube-voltage acquisition has been shown to facilitate substantial dose savings for neck CT with similar image contrast compared with standard 120-kVp acquisition. However, its potential for the detection of neck pathologies is uncertain. Our aim was to evaluate the effects of low-tube-voltage 80-kV(peak) acquisitions for neck CT on diagnostic accuracy and interobserver agreement. MATERIALS AND METHODS: Three radiologists individually analyzed 80-kVp and linearly blended 120-kVp image series of 170 patients with a variety of pathologies who underwent dual-energy neck CT. Reviewers were unblinded to the clinical indication for CT but were otherwise blinded to any other data or images and were asked to state a final main diagnosis. Findings were compared with medical record charts, CT reports, and pathology results. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each observer. Interobserver agreement was evaluated by using intraclass correlation coefficients. RESULTS: Diagnoses were grouped as squamous cell carcinoma-related (n = 107, presence/absence of primary/recurrent squamous cell carcinoma), lymphoma-related (n = 40, presence/absence of primary/recurrent lymphoma), and benign (n = 23, eg, abscess). Cumulative sensitivity, specificity, positive predictive value, and negative predictive value for 80-kVp and blended 120-kVp images were 94.8%, 93.0%, 95.9%, and 91.1%, respectively. Results were also consistently high for squamous cell carcinoma-related (94.8%/95.3%, 89.1%/89.1%, 94.3%/94.4%, 90.1%/91.0%) and lymphoma-related (95.0%, 100.0%, 100.0%, 95.2%) 80-kVp/120-kVp image series. Global interobserver agreement was almost perfect (intraclass correlation coefficient, 0.82, 0.80; 95% CI, 0.76-0.74, 0.86-0.85). Calculated dose-length product was reduced by 48% with 80-kVp acquisitions compared with the standard 120-kVp scans (135.5 versus 282.2 mGy × cm). CONCLUSIONS: Low-tube-voltage 80-kVp CT of the neck provides sufficient image quality with high diagnostic accuracy in routine clinical practice and has the potential to substantially decrease radiation exposure.

Response and progression-free survival in oropharynx squamous cell carcinoma assessed by pretreatment perfusion CT: comparison with tumor volume measurements.

BACKGROUND AND PURPOSE: Perfusion CT (PCT) provides a rapid, reliable, and non-invasive technique for assessing tumor vascularity. The purpose of this study was to assess whether pretreatment dynamic perfusion CT (PCT) may predict response to induction chemotherapy and midterm progression-free survival (PFS) in advanced oropharynx squamous cell carcinoma (SCCA) and to compare the results with those derived by tumor volume measurements. MATERIALS AND METHODS: Nineteen patients underwent routine contrast-enhanced CT (CECT), pretreatment PCT, and conventional endoscopy. Tumor response was determined according to radiologic (RECIST) criteria. The PCT parameters, tumor volume, radiologic response, and PFS were analyzed with use of Cox-proportional hazards model, receiver operating characteristic (ROC), and Kaplan-Meier analysis. RESULTS: The baseline blood flow (BF), blood volume (BV), and permeability surface area product (PS) were significantly higher, whereas mean transit time (MTT) was significantly lower in the responders than in the nonresponders (P < or = .002). BV showed 100% sensitivity, MTT and PS had the highest specificity (100%), and BF showed 84.2% sensitivity and 66.7% specificity for prediction of tumor response after induction chemotherapy. The pretreatment tumor volume correlated with PFS in the pooled patients group (r = 0.4; P < .0001), whereas postinduction tumor volume correlated significantly with PFS in the responders and nonresponders (r = 0.22-0.64; P < or = .006). Pretreatment tumor volume (P = .0001) and BF (P = .001) were significant predictors for PFS. CONCLUSIONS: Pretreatment PCT parameters may predict response after induction chemotherapy. Tumor volume and BF values may predict PFS in patients with advanced oropharyngeal SCCA.

Prognostic relevance of volumetric analysis in tumour specimens of hypopharyngeal cancer.

OBJECTIVE: The purpose of this study was to investigate the prognostic relevance of the tumour specimen's volume in patients with squamous cell cancers of the hypopharynx. DESIGN: Tumour specimens of 67 patients treated primarily with surgery were evaluated, prospectively. Pathologic tumour volume was described as the product of the three longest diameters of the tumour in cubic millimeters (mm(3)). Statistical analysis was performed to determine the relation of pathologic tumour volume to pTNM stages as well as to patients' survival. This study has been approved by our institutional review board. RESULTS: Pathologic tumour volume was significantly associated with pT (P = 0.006) and pN (P = 0.01). The univariate evaluation of tumour variables showed pathologic tumour volume (P = 0.01) and pN (P = 0.04) as the only parameters which were significantly associated with overall survival. Entering these variables in a Cox regression model, pathologic tumour volume had the most impact on overall survival (P = 0.03). Most important thereby is the fact that we could distinguish within the pN0 group between the more and the less favourable cases. CONCLUSION: Pathologic tumour volume could be an essential prognostic indicator and the inclusion of this parameter in future clinical trials is recommended.

Phosphatidylcholine and lysophosphatidylcholine in intestinal mucus of ulcerative colitis patients. A quantitative approach by nanoElectrospray-tandem mass spectrometry.

BACKGROUND: A defective mucus composition represents a key pathogenetic factor for intestinal injury. Phosphatidylcholine (PC) is an essential component contributing to formation of a hydrophobic mucus layer. For evaluation of PC in the pathogenesis of inflammatory bowel disease, the concentration and composition of PC in the rectal mucus of patients with ulcerative colitis was determined. Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) allows quantification of PC species and enables analysis of crude extracts. METHODS: Lipid extracts of material obtained by light scrapings of the intestinal lumen were analysed quantitatively by nanoESI MS/MS with synthetic internal PC and lysophosphatidylcholine (LPC) standards. PC and LPC species from rectoscopically acquired mucus aliquots of patients with ulcerative colitis were compared to Crohn disease and control subjects. RESULTS: Patients with inactive ulcerative colitis showed significantly less PC and LPC (median 346 [IQR: 230-405] pmol total PC/mg dry weight) in rectal mucus compared to Crohn disease (median 126 [IQR: 465-1941] pmol total PC/mg dry weight) and control subjects (median 1285 [IQR: 850-1639] pmol total PC/mg dry weight) (P < 0.05). The molecular species of PC and LPC were not significantly different between the groups. The most abundant species were PC 16:0/18:1; PC 16:0/18:2; PC 18:0/18:1; PC 18:0/18:2; LPC 16:0; and LPC 18:0. CONCLUSION: NanoESI MS/MS is a suitable tool for analysing and quantifying small amounts of PC in human mucus. Patients with ulcerative colitis have significant less PC in their intestinal mucus despite a comparable PC molecular species composition pattern. This suggests that a low amount of protective mucus PC is a characteristic feature in ulcerative colitis and explains an increased susceptibility to luminal contents.