Readout-Segmented Echo-Planar DWI for the Detection of Cholesteatomas: Correlation with Surgical Validation.

BACKGROUND AND PURPOSE: MR imaging has become an important tool for the detection of cholesteatomas of the middle ear. Various diffusion-weighted imaging sequences are available and have shown promising results. This study aimed to evaluate readout-segmented echo-planar DWI for the detection of cholesteatoma and compare the results with surgical validation. MATERIALS AND METHODS: Fifty patients with chronic otitis media (24 females and 26 males; range, 12-76 years of age; mean age, 41 years) who underwent MR imaging before an operation of the middle ear (1-169 days) were included. The MR imaging protocol consisted of axial and coronal readout-segmented echo-planar DWI with b-values of 0 and 1000 s/mm2 and 3-mm slice thickness. The readout-segmented echo-planar diffusion-weighted images were fused with standard T2-weighted sequences for better anatomic assignment. The results of the MR imaging evaluation were correlated with the results from the operation. RESULTS: Readout-segmented echo-planar DWI detected 22 of the 25 cases of surgically proved cholesteatoma. It has an accuracy of 92% (95% confidence interval, 80.8%-97.8%), a sensitivity of 88%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 89%. In 1 case, a positive finding for cholesteatoma with readout-segmented echo-planar DWI could not be proved by histology, and in 3 cases, histology yielded a cholesteatoma that was not detected with MR imaging. CONCLUSIONS: Readout-segmented echo-planar DWI is a promising and reliable MR imaging sequence for the detection and exclusion of cholesteatoma.

Approximation of head and neck cancer volumes in contrast enhanced CT.

BACKGROUND: Tumor volume may serve as a predictor of response to radiochemotherapy (RCT) in head and neck squamous cell carcinoma (HNSCC). Computer assisted tumor volumetry requires time-consuming slice-by-slice manual or semi-automated segmentation. We questioned how accurately primary tumor and suspect cervical lymph node (LN) volumes can be approximated by the maximum tumor diameters in three dimensions. METHODS: In contrast-enhanced diagnostic CT scans of 74 patients with incident advanced HNSCC, manual slice-by-slice segmentation volumetry of primary tumor, total- and largest suspect cervical LN served as the reference method. In the same scans, maximum orthogonal diameters were measured using the distance measurement tool in standard visualization software in axial and coronal sections. From these diameters, approximate volumes were calculated using the cubic and ellipsoid formula. A second segmentation volumetry was performed in contrast enhanced radiotherapy-planning CT scans obtained prior to primary concurrent RCT 24 days (+/- 13 days) following the initial diagnostic CT scans. Intraclass correlation coefficients and Bland-Altman analyses were used to compare results. RESULTS: Slice-by-slice manual segmentation volumetry of primary and LN volumes revealed a lognormal distribution and ranged from 0 to 86 ml and 0 to 129 ml, respectively. Volume approximations in diagnostic CT scans with the ellipsoid formula resulted in an -8 % underestimation of tumor volumes (95 % CI -14 % to -1 %; p = 0.022) and an -18 % underestimation of suspect cervical LN volumes (95 % CI -25 % to -12 %; p = 0.001). Inter rater intraclass correlation for primaries was 0.95 (95 % CI +0.92 to +0.97; p = 0.001), and intra rater intraclass correlation was 0.99 (95 % CI +0.98 to +0.99; p = 0.001). The cubic formula resulted in pronounced overestimation of primary and LN volumes. Primary tumor volumes obtained by the second segmentation volumetry in radiotherapy-planning CT scans obtained on average 24 days following the initial volumetry resulted in larger primary tumor volumes (mean bias +28 %, 95 % CI +14 % to +41 %; p = 0.001). Tumor volume increase correlated with time between the diagnostic and planning CTs (r = 0.24, p = 0.05) and was approximately 1 % per day. DISCUSSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC using maximum orthogonal diameters underestimates volumes based on segmentation in multiple slices. Due to time difference and safety margins, segmented volumes in radiotherapy-planning CT scans tend to be larger than in diagnostic CT scans. CONCLUSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC are easily available from diagnostic CT scans. Volume estimates are applicable over a wide range of tumor and LN sizes and may be useful in clinical decision-making and oncologic research.

Rac1 as a potential therapeutic target for chemo-radioresistant head and neck squamous cell carcinomas (HNSCC).

BACKGROUND: In order to improve therapy for HNSCC patients, novel methods to predict and combat local and/or distant tumour relapses are urgently needed. This study has been dedicated to the hypothesis that Rac1, a Rho GTPase, is implicated in HNSCC insensitivity to chemo-radiotherapy resulting in tumour recurrence development. METHODS: Parental and radiation-resistant (IRR) HNSCC cells were used to support this hypothesis. All cells were investigated for their sensitivity to ionising radiation and cisplatin, Rac1 activity, its intracellular expression and subcellular localisation. Additionally, tumour tissues obtained from 60 HNSCC patients showing different therapy response were evaluated for intratumoral Rac1 expression. RESULTS: Radiation-resistant IRR cells also revealed resistance to cisplatin accompanied by increased expression, activity and trend towards nuclear translocation of Rac1 protein. Chemical inhibition of Rac1 expression and activity resulted in significant improvement of HNSCC sensitivity to ionising radiation and cisplatin. Preclinical results were confirmed in clinical samples. Although Rac1 was poorly presented in normal mucosa, tumour tissues revealed increased Rac1 expression. The most pronounced Rac1 presence was observed in HNSCC patients with poor early or late responses to chemo-radiotherapy. Tissues taken at recurrence were characterised not only by enhanced Rac1 expression but also increased nuclear Rac1 content. CONCLUSIONS: Increased expression, activity and subcellular localisation of Rac1 could be associated with lower early response rate and higher risk of tumour recurrences in HNSCC patients and warrants further validation in larger independent studies. Inhibition of Rac1 activity can be useful in overcoming treatment resistance and could be proposed for HNSCC patients with primary or secondary chemo-radioresistance.

Radiological detection of extracapsular spread in head and neck squamous cell carcinoma (HNSCC) cervical metastases.

BACKGROUND: Extracapsular spread of cervical lymph nodes deteriorates the prognosis of patients with head and neck squamous cell carcinoma. Postoperative radiochemotherapy is superior to postoperative radiotherapy alone in patients with histologically proven extracapsular spread. If extracapsular spread can be detected preoperatively, patients may favor primary radiochemotherapy instead of primary surgery plus postoperative radiochemotherapy. METHODS: Computed tomography (CT) scans of nodal positive head and neck squamous cell carcinoma patients treated between 2008 and 2010 with comprehensive neck dissection as part of first line surgical treatment were retrospectively scanned for extracapsular spread by two blinded radiologists. If a positive lymph node was identified by the pathologist, CT scans were assessed for extracapsular spread retrospectively. CT criteria for Extracapsular spread were apparent fat and soft tissue infiltration or infiltration of sternocleidomastoid muscle, internal jugular vein or carotid artery. Radiologic judgment was compared with histological evidence of extracapsular spread and specificity and sensitivity of CT detection was calculated. RESULTS: Forty-nine patients with histologically proven positive lymph nodes (pN+) were included. Extracapsular spread was histologically proven in 17 cases; the number of all affected lymph nodes was not listed. Radiologist 1 found extracapsular spread in CT scans of 15/49 patients and radiologist 2 in 16/49 patients (Cohen's kappa=0.86; p<0.01). Sensitivity of radiologic extracapsular spread detection was 73% (95% confidential index (CI): 44.0-89.7%) and specificity 91% (75.0-98.0%). CONCLUSION: Extracapsular spread depicted on computed tomography using strict criteria has high specificity.

Neuroendocrine differentiation in head and neck squamous cell carcinoma.

OBJECTIVE: Tumours with neuroendocrine differentiation frequently express chromogranin A, synaptophysin and somatostatin receptors. The role of neuroendocrine differentiation in head and neck squamous cell carcinoma is not yet clear. METHOD: The presence of chromogranin A, synaptophysin and somatostatin receptors was studied immunohistochemically in 78 head and neck squamous cell carcinoma specimens. RESULTS: Sparse chromogranin A expression was found in 41 per cent, associated with high chromogranin A messenger RNA expression and the presence of dense core granules. Low synaptophysin expression was found in 18 per cent. The highest staining scores were found for somatostatin receptor 5 (82 per cent), followed by somatostatin receptor 1 (69 per cent) and somatostatin receptor 2 (54 per cent), whereas somatostatin receptors 3 and 4 expression was low. Expression was not correlated with tumour stage or survival. CONCLUSION: Cells with neuroendocrine differentiation are sparsely scattered in some head and neck squamous cell carcinomas. Their pathophysiological role is elusive. In contrast, somatostatin receptor and particularly somatostatin receptor 5 expression is frequent in head and neck squamous cell carcinoma. Somatostatin receptor expression is not considered to indicate neuroendocrine differentiation in head and neck squamous cell carcinoma.

Initial staging examinations for head and neck squamous cell carcinoma: are they appropriate?

OBJECTIVES: The presence of distant metastases affects the therapeutic regime in patients with head and neck squamous cell carcinoma. This study evaluated the necessity to undertake bone scanning, chest computed tomography and abdominal ultrasonography in patients presenting with primary advanced head and neck squamous cell carcinoma. STUDY DESIGN: Retrospective analysis, university setting. METHODS: One hundred and sixty-three patients with head and neck squamous cell carcinoma who were scheduled for major surgery underwent screening for distant metastases. Chest, head and neck computed tomography, abdominal ultrasonography and bone scanning were performed in all patients. RESULTS: Distant metastases were detected in 5.52 per cent of the 163 patients. All of these patients had locoregional advanced (stage IV) tumours. Computed tomography scanning of the lungs revealed metastases in six patients. Bone metastases were found in three patients. Only one patient with primary liver metastases was detected by abdominal ultrasonography; this patient also had pulmonary metastases. CONCLUSIONS: Computed tomography of the thorax is the most important technique for screening patients with head and neck squamous cell carcinoma.