Assessment of cervical volume and spectral Doppler parameters in tumour dominant vessel of patients with locally advanced squamous cell cervical carcinoma.

We evaluated cervical volume and spectral Doppler parameters: peak systolic velocity (PSV), resistance index (RI) and pulsatility index (PI) in the tumour dominant vessel of 50 patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB and their changes during treatment. The patients underwent transvaginal Doppler ultrasonography prior to treatment, after external beam radiation therapy (EBRT) and 6 weeks after brachytherapy. Radiotherapy decreased cervical volume and PSV values of the tumour dominant vessel. The PSV values before EBRT in G1 + G2 tumours were higher than in G3 tumours. No correlations between cervical volume, PSV, RI and PI values with disease-free survival (DFS) and overall survival (OS) were found. We concluded, that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results. Spectral Doppler parameters PSV, RI and PI of tumour dominant vessel did not predict prognosis for these patients.Impact StatementWhat is already known on this subject? Transvaginal Doppler sonography is considered as a useful diagnostic method in patients with cervical carcinoma. However, despite numerous studies, the value of spectral Doppler parameters in tumour dominant vessel and cervical volume of patients with locally advanced cervical SCC is still not well defined.What the results of this study add? In our prospective study, we found that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results and spectral Doppler parameters of tumour dominant vessel did not predict prognosis for these patients.What the implications are of these findings for clinical practice and/or further research? Our study underlines the limited value of spectral Doppler technique in patients with cervical carcinoma. Further research should be focussed on identifying and validating novel prognostic and predictive factors.

The assessment of spectral Doppler parameters in uterine arteries of patients with locally advanced squamous cell cervical cancer.

OBJECTIVES: Evaluate spectral Doppler parameters peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index(RI) and pulsatility index (PI) in infiltrated and non-infiltrated uterine arteries of patients with locally advanced (stages II B,III B) squamous cell cervical cancer and their changes during treatment. MATERIAL AND METHODS: the study group included 36 patients aged 35-78 years old. At diagnosis, PSV, EDV, RI and PI inuterine arteries were examined and compared with MRI findings. All patients underwent transvaginal doppler ultrasonographyprior to the treatment, after external beam radiation therapy and six weeks after the last application of brachytherapy. RESULTS: The median PSV value in the first examination was higher in infiltrated uterine arteries than compared to non-infiltratedones (p = 0.001). The PSV values for all vessels decreased between the first and the third observation (p < 0.001).There was a significant difference in PI values between infiltrated and non-infiltrated uterine arteries between the first andthe third examination (p = 0.027). CONCLUSIONS: In patients with locally advanced cervical cancer of uterine arteries, assessment of PSV but not EDV, RI or PIcan be helpful in differentiating infiltrated from non-infiltrated vessels. In this group of patients, radiotherapy decreasesPSV, but not EDV, RI or PI values in uterine arteries. An observation conducted from the onset of radiotherapy to end ofthe follow-up in uterine arteries reveals that PI, but not RI, PSV or EDV, is different in infiltrated and non-infiltrated vessels.

Assessment of VEGF and EGFR in the study of angiogenesis of eyelid carcinomas.

A tumor represents an abnormal tissue growth that can arise from any ocular structure, such as eyelids, muscles or the optic nerve. At the eyelids, there are two main tumor types: basal cell carcinoma and squamous cell carcinoma. Angiogenesis plays a crucial role in growth, invasion and metastasis processes of any tumor. It is well known the fact that without new vessels formation tumors cannot exceed 1-2 mm diameter. Immunohistochemical analysis has been performed on 43 cases of primary carcinomas of the eyelid, diagnosed between 2010 and 2014 in the Laboratory of Pathological Anatomy of the University Emergency County Hospital of Craiova, Romania. Biological material was represented by surgical resection samples, coming from the Clinic of Ophthalmology the anteriorly named Hospital. Within the immunohistochemical study, we have evaluated epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression in a group of 43 cutaneous carcinomas of the eyelid, depending on the type and differentiation grade of the tumor. Of the 43 samples, 23 came from patients with eyelid basal cell carcinoma and 20 came from patients with eyelid squamous cell carcinoma. In our study, EGFR and VEGF immunoexpression was superior for squamous cell carcinomas, compared to basal cell carcinomas, fact that was statistically significant. Regarding squamous cell carcinomas, the immunoexpression of these two markers was superior in moderate÷poor differentiated forms, compared to well differentiated forms, fact that was statistically significant. The markers used in this study were found to be associated with the acquisition of aggression and angiogenic phenotypes by analyzed carcinomas.

Usefulness of Pseudocontinuous Arterial Spin-Labeling for the Assessment of Patients with Head and Neck Squamous Cell Carcinoma by Measuring Tumor Blood Flow in the Pretreatment and Early Treatment Period.

BACKGROUND AND PURPOSE: For the assessment of the treatment response in non-surgical treatment, tumor blood flow provides the functional information of the tumor which is different from the morphological information such as tumor volume. The purpose of this study was to evaluate the diagnostic value of tumor blood flow values obtained by pseudocontinuous arterial spin-labeling in patients with head and neck squamous cell carcinoma. MATERIALS AND METHODS: Forty-one patients with head and neck squamous cell carcinoma were evaluated by using pseudocontinuous arterial spin-labeling. Quantitative tumor blood flow was calculated at the pretreatment and the early treatment periods in all the patients, and the percentage change of tumor blood flow between the two was calculated. At the early treatment period, based on their tumor volume reduction rate, we divided the patients into stable disease and partial response groups for a subgroup analysis. The local control or failure was confirmed either by histopathology or by radiologic evaluation within the follow-up. RESULTS: Pretreatment tumor blood flow in patients in the failure group was significantly lower than that in patients in the local control group. In the subgroup analysis of patients with stable disease, the percentage change of tumor blood flow was significantly larger (due to the tumor blood flow increase from pretreatment value) in the local control group than in the failure group. In addition, in patients with a partial response, the percentage change of tumor blood flow was significantly smaller (due to the tumor blood flow decrease from the pretreatment value) in the local control group than in the failure group. The accuracy for determination of the local control group or the failure group in pretreatment tumor blood flow was 0.83 and that in the combination use of the percentage change of tumor blood flow and tumor volume in the early treatment period was 0.93. CONCLUSIONS: Tumor blood flow obtained by pseudocontinuous arterial spin-labeling can be useful for the determination of local control. The combined use of the percentage change of tumor blood flow and tumor volume had particularly high diagnostic accuracy.

Angiogenesis in superficial esophageal squamous cell carcinoma: assessment of microvessel density based on immunostaining for CD34 and CD105.

OBJECTIVE: The esophagus is the only organ where changes in the superficial microvasculature from normal squamous epithelium to invasive cancer are evident by magnifying endoscopy. We investigated in detail the features of angiogenesis in early-stage esophageal cancer using CD34 and CD105 immunostaining, and also the correlation between angiogenesis and mononuclear cell infiltration. MATERIALS AND METHODS: Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia, and 45 samples of superficial esophageal cancer, we determined the microvessel density at hot spots showing positive staining for CD34 and CD105. We observed the histological features of CD34- and CD105-positive microvessels that corresponded to observations made by magnifying endoscopy. We then investigated the correlation between microvessel density and each histological situation or the grade of mononuclear cell infiltration. RESULTS: The histological features of CD34- and CD105-positive microvessels were able to explain the morphological changes in the microvasculature during cancer progression observed by magnifying endoscopy. The microvessel density for CD34 or CD105 was significantly correlated with each of the histological types (P < 0.001, rS = 0.51 and 0.76, respectively). Mononuclear cell infiltration at CD105 hot spots was most frequent in M1 and M2 cancer (94.7%). The correlation between the degree of mononuclear cell infiltration and microvessel density for CD105 staining was also significant (P < 0.001, rS = 0.49). CONCLUSIONS: The microvessel density based on CD34 and CD105 immunostaining can be used to corroborate observations of superficial esophageal squamous cell carcinoma made by magnifying endoscopy. Mononuclear cell infiltration may play an important role in angiogenesis at the early stage of cancer progression.

Comparison of consecutive bolus tracking and flash replenishment measurements for the assessment of tissue hemodynamics using contrast-enhanced ultrasound (CEUS) in an experimental human squamous cell carcinoma model.

PURPOSE: To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model. Since the underlying tissue is the same, strong correlations between parameter outcomes of both techniques are expected. METHODS AND MATERIALS: Human hypopharynx-carcinoma-cells were subcutaneously injected into the left flank of 18 female athymic-nude-rats. After 10 days of subcutaneous tumour growth, bolus tracking and flash-replenishment measurements were performed consecutively in the same imaging plane in each rat after bolus-injection of SonoVue via the lateral tail vein using a high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed with dedicated software (VueBox®, Bracco-Suisse®). From BT measurements, the parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. RESULTS: In all rats, BT and FR measurements could be completed successfully. Highly significant correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT, rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and WiRBT and WiRFR and WiPIBT. CONCLUSION: Whereas bolus tracking can be used in a wide range of modalities including CEUS, CT and MR, FR as a technique for the assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield different parameters, the underlying tissue hemodynamics are equal. In this work, we were able to demonstrate strong correlations between different parameters of both modalities in a small-animal-tumor-model, indicating that flash-replenishment is a valid alternative to the more established bolus-tracking technique. Although the lack of absolute, quantitative parameters hinders a direct comparison of both modalities, FR and BT should both be suitable for a relative comparison, e.g. between baseline and follow-up examinations.

Quantitative assessment of first-pass perfusion using a low-dose method at multidetector CT in oesophageal squamous cell carcinoma: correlation with VEGF expression.

AIM: To investigate the correlation between vascular endothelial cell growth factor (VEGF) expression and first-pass perfusion parameters at multidetector computed tomography (MDCT) using a low-dose technique, and to determine how to discriminate VEGF positivity from VEGF negativity by perfusion CT in oesophageal squamous cell carcinomas. MATERIALS AND METHODS: Thirty-two patients with oesophageal squamous cell carcinomas underwent first-pass perfusion with 64-section MDCT at 50 mAs. Perfusion parameters, including perfusion, peak enhanced density (PED), time to peak (TTP), and blood volume (BV), were measured. Postoperative specimens were assessed for VEGF expression. Correlation tests were performed to determine the associations between each CT perfusion parameter and VEGF expression. The cut-off values of perfusion parameters were obtained statistically to discriminate VEGF positivity from VEGF negativity. RESULTS: Mean perfusion, PED, TTP, and BV were 38.47 ± 30.26 ml/min/ml, 24.68 ± 9.65 HU, 28.35 ± 9.03 s, and 11.82 ± 6.06 ml/100 g, respectively. PED or BV were significantly higher in the VEGF-positive group than in the VEGF-negative group (all p < 0.05), but no significant difference in perfusion or TTP was found between the VEGF-positive and VEGF-negative groups (all p > 0.05). In VEGF positivity, PED and BV were correlated with VEGF expression (r = 0.576 and 0.765, respectively; all p < 0.05), whereas perfusion and TTP were not (r = 0.361 and 0.239, respectively; all p > 0.05). A threshold of BV (10.23 ml/100 g) achieved a sensitivity of 94.4%, and a specificity of 92.9% for discriminating VEGF positivity from VEGF negativity. CONCLUSION: BV could reflect tumour VEGF expression, and could be an indicator for evaluating angiogenesis in oesophageal tumours.

Preliminary assessment of dynamic contrast-enhanced CT implementation in pretreatment FDG-PET/CT for outcome prediction in head and neck tumors.

BACKGROUND: Recently published data show some controversy concerning the impact of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in predicting head and neck tumors (HNT) outcome. Assessment of tumor blood supply parameters using dynamic contrast-enhanced CT (DCE-CT) may deliver additional information concerning this important question. PURPOSE: To evaluate the contribution of DCE-CT implemented in pretherapeutic FDG-PET/CT protocol for prognosis prediction in patients with HNT. MATERIAL AND METHODS: Ten consecutive patients (median age 50 years, range 47-74 years) with histologically proven HNT underwent FDG-PET/CT with DCE-CT before treatment. FDG uptake was measured by maximum standardized uptake value (SUV(max)). Relative tumor blood volume (rTBV) was determined from DCE-CT using Patlak analysis. Intratumoral heterogeneity was assessed by means of lacunarity analysis. Obtained values were compared with time-to-progression and overall survival. PET and DCE-CT images were compared on a pixel-by-pixel basis using Pearson coefficient of correlation. RESULTS: Three patients with lower FDG uptake (SUV(max): 8+/-1) and five patients with higher FDG uptake (SUV(max): 15+/-4, P=0.004) were free of local recurrence for 24 months. Two groups of patients with significantly differing lower (group A: 0.37+/-0.02, n=6) and higher (group B: 0.52+/-0.01, n=4; P<0.01), tumor heterogeneity (lacunarity) were identified. Corresponding mean rTBV was higher in group A (9.6+/-1.8 ml/100 ml) than in group B (6.2+/-0.6 ml/100 ml). All six patients with homogeneous tumor blood supply (lower lacunarity) and higher rTBV were free of local recurrence during 24 months, while two of four patients with heterogeneous tumor blood supply (higher lacunarity) and lower rTBV died during follow-up due to tumor relapse. A weak correlation between FDG-PET and DCE-CT rTBV was observed (R(2)=0.1). CONCLUSION: FDG-PET/CT and DCT-CT are complementary methods for surveillance assessment in patients with HNT. Implementation of DCE-CT in the pretreatment FDG-PET/CT protocol may improve tumor outcome prediction.

Narrow band imaging and high definition television in the assessment of laryngeal cancer: a prospective study on 279 patients.

Narrow band imaging (NBI) is an optical technique in which a filtered light reveals superficial carcinomas in view of their neoangiogenic pattern. The accuracy of NBI is implemented by combining it with a high definition television (HDTV) camera. The aim of this study was to prospectively evaluate the diagnostic gain of NBI and HDTV in the assessment of laryngeal squamous cell carcinoma (LSCC). Between April 2007 and December 2008, we analyzed by NBI with or without HDTV 279 patients divided in two groups: Group A included 96 patients affected by LSCC and Group B included 183 subjects under follow-up after treatment for the same disease. Overall, 50 of 279 patients (18%) showed "suspicious" NBI findings histologically confirmed as neoplastic. The sensitivity, specificity, accuracy, positive and negative predictive rates of flexible NBI, HDTV with white light, and HDTV with NBI in both groups confirmed the value of these two technologies. In the pre- and intraoperative settings, NBI with or without HDTV provided better definition of tumor staging and surgical margins. NBI has also a role in the postoperative setting, due to its ability in early detection of persistences, recurrences, and metachronous tumors.

Assessment of changes in vascularity and blood volume in canine sarcomas and squamous cell carcinomas during fractionated radiation therapy using quantified contrast-enhanced power Doppler ultrasonography: a preliminary study.

Radiation therapy does not only target tumour cells but also affects tumour vascularity. In the present study, changes in tumour vascularity and blood volume were investigated in five grade 1 oral fibrosarcomas, eight other sarcomas (non-oral soft tissue and bone sarcomas) and 12 squamous cell carcinomas in dogs during fractionated radiation therapy (total dose, 45-56 Gy). Contrast-enhanced power Doppler ultrasound was performed before fraction 1, 3, 6, 8, 10, 12, 14 and 15 or 16 (sarcomas) or 17 (squamous cell carcinomas). Prior to treatment, median vascularity and blood volume were significantly higher in squamous cell carcinomas (P=0.0005 and 0.001), whereas measurements did not differ between oral fibrosarcomas and other sarcomas (P=0.88 and 0.999). During the course of radiation therapy, only small, non-significant changes in vascularity and blood volume were observed in all three tumour histology groups (P=0.08 and P=0.213), whereas median tumour volume significantly decreased until the end of treatment (P=0.04 for fibrosarcomas and other sarcomas, P=0.008 for squamous cell carcinomas). It appeared that there was a proportional decrease in tumour volume, vascularity and blood volume. Doppler measurements did not predict progression free interval or survival in any of the three tumour groups (P=0.06-0.86). However, the number of tumours investigated was small and therefore, the results can only be considered preliminary.

Vascularity index of laryngeal cancer derived from 3-D ultrasound: a predicting factor for the in vivo assessment of cervical lymph node status.

To demonstrate whether a calculated vascularity index (VI) can predict metastases of cervical lymph nodes, the VI values of the primary tumors were obtained by using 3-D sonography in 87 subjects with laryngeal cancer confirmed by laryngoscope and biopsy. N-staging of the subjects was determined by pathological nodal harvesting. The relationship between the VI and pathological N-staging was evaluated by correlation coefficient. To test the accuracy of the VI for predicting cervical lymph node involvement, a receiver operating characteristic (ROC) curve was constructed, and the best operating point was determined by Youden's index. For comparison, 2-D sonography was applied to detect metastatic cervical lymph nodes. The accuracy, sensitivity and specificity of the VI, 2-D sonography and a combination of the two methods for diagnosis of metastatic cervical lymph nodes were compared. There was a positive linear correlation between the VI and pN-staging (r=0.740, p<0.001). The area under the ROC curve for the VI was 0.919. The best operating point of the VI was 4.4565, which derived higher sensitivity than that of 2-D sonography (95% vs. 81%, p=0.031), but lower specificity (75% vs. 95%, p=0.012). The combination of the two methods yielded a higher accuracy (97% vs. 85% and 89%, p=0.002 and 0.016), a higher sensitivity to 2-D sonography (95% vs. 81%, p=0.031) and a higher specificity to VI (98% vs. 75%, p=0.002). The VI of laryngeal cancer can be a useful factor for predicting metastases of cervical lymph nodes.

Assessment of vascular remodeling under antiangiogenic therapy using DCE-MRI and vessel size imaging.

PURPOSE: To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index (VSI) as a novel biomarker of therapy response. MATERIALS AND METHODS: In two independent experiments, nude mice bearing human skin squamous cell carcinoma xenografts were treated with a vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or a multitargeted tyrosine kinase inhibitor (SU11248). Changes in tumor vascularity were assessed by DCE-MRI and vessel size imaging. DCE-MRI data were analyzed applying a two-compartment model (Brix), calculating the parameters Amplitude and k(ep). RESULTS: For both experiments Amplitude decreased significantly in treated tumors while k(ep) did not change significantly. VSI showed controversial results. VSI was significantly increased in SU11248-treated A431 tumors, whereas no changes were found in bevacizumab-treated HaCaT-ras-A-5RT3 tumors. Immunohistology confirmed these results and suggest differences in the maturation of tumor vascularization as a possible explanation. CONCLUSION: DCE-MRI and vessel size imaging provide reliable and supplementing biomarkers of antiangiogenic therapy response. The results of both methods are in excellent agreement with histology. Nevertheless, our results also indicate that vascular remodeling is complex and that a uniform response cannot be expected for different tumors and therapies.

Quantitative assessment of first-pass perfusion of oesophageal squamous cell carcinoma using 64-section MDCT: initial observation.

AIM: To clarify the feasibility of first-pass perfusion computed tomography (CT) using 64-section multidetector CT (MDCT) for tumour microcirculation of oesophageal squamous cell carcinoma, and to determine the threshold value of first-pass perfusion values for the discrimination between the microcirculation of the tumour and normal oesophagus. MATERIALS AND METHODS: Forty-one patients with pathologically confirmed oesophageal squamous cell carcinomas served as the test group, which was subdivided into subgroups according to the pathological grades or the status of lymph node metastasis. Forty patients with a normal oesophagus served as controls. All patients underwent volume-based perfusion imaging using 64-section MDCT. Perfusion parameters including perfusion (PF), peak enhancement (PE), blood volume (BV), and time to peak (TTP) were measured. The differences in perfusion parameters between the test and control groups, and between the subgroups were compared statistically. The cut-off values were obtained statistically to discriminate microcirculation between the tumour and normal oesophagus. RESULTS: Mean values for the BV and TTP of the tumour were 12.57+/-5.15 ml/100g (range 2.9-25.6) and 33.71+/-14.12 s (range 6-65), respectively. Mean values for the BV and TTP of the normal oesophagus were 4.33+/-3.6 ml/100 g (range 0.3-11.7) and 24.15+/-11.67 s (range 6-48), respectively. The BV and TTP were statistically higher in the test group than in the control group (p<0.05), but no statistical differences in the PF and PE were found between the test and control groups (p>0.05). There were no statistical differences in all parameters between the subgroups of pathological grades, and between subgroups with and without lymph-node metastases (p>0.05). For the discrimination of microcirculation of the tumour from that of the normal oesophagus, a threshold BV value of 6.65 ml/100g was determined and achieved a sensitivity of 95.1%, and specificity of 90%. CONCLUSION: The first-pass perfusion technique using 64-section MDCT could be valuable to assess the microcirculation of oesophageal squamous cell carcinomas.

[Preliminary study of tumor perfusion assessment with multidetector CT in carcinoma of esophagus and cardia].

OBJECTIVE: To investigate the clinical application of first-pass perfusion MDCT in the assessment of tumor angiogenesis in carcinoma of esophagus and cardia. METHODS: CT perfusion was performed with multi-detector row CT (MDCT) in 44 patients with carcinoma of esophagus and esophagogastric junction, who was diagnosed with pathological results and did not received any anti-tumor therapy. Twenty-one patients with peripheral lung cancer but normal esophagus were served as controls. Perfusion parameters were compared between normal and malignant esophagus, between adenocarcinoma and squamous cell carcinoma, as well as between tumors with metastases and those without metastases. RESULTS: Carcinoma of esophagus and esophagogastric junction showed higher blood flow, peak enhancement index, blood volume, and shorter time to peak compared with normal esophagus (P < 0.05). There were no statistically significant differences in perfusion parameters between adenocarcinoma and squamous cell carcinoma (P > 0.05), whereas tumors with metastases showed higher blood flow and shorter time to peak compared with those without metastases (P < 0.05). CONCLUSION: MDCT perfusion could assess tumor vascularity in carcinoma of esophagus and esophagogastric junction, and tumor vascularity or angiogenesis was not influenced by its histological type. However, high blood flow and short time-to-peak may be helpful to predict tumor metastases.

Assessment of tumor microcirculation with dynamic contrast-enhanced MRI in patients with esophageal cancer: initial experience.

PURPOSE: To investigate the feasibility and impact of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on tumor characterization and response to radiochemotherapy (RCT) in patients with esophageal cancer. MATERIALS AND METHODS: A total of 48 patients underwent DCE-MRI to assess tumor microcirculation based on a two-compartment model function. Effects of RCT on kinetic parameters were studied in 12 patients with squamous cell carcinoma. RESULTS: Tumor microcirculation differs with respect to histological subtype: squamous cell carcinomas showed lower values of amplitude A (leakage space, P = 0.015) and higher contrast agent exchange rates (k(21), P = 0.225) compared with adenocarcinomas. RCT led to a significant decrease of the contrast agent exchange rate (P = 0.005), while amplitude A increased moderately after therapy (P = 0.136). CONCLUSION: DCE-MRI is feasible in patients with esophageal cancer, reveals therapeutic effects, and may thus be useful in therapy management and monitoring.

Assessment of vascularity as an index of angiogenesis in periradicular granulomas. Comparison with oral carcinomas and normal tissue counterparts.

AIM: To quantify vascularity in periradicular granulomas using different endothelial markers, and assess its value as an index of angiogenesis by comparing granulomas with healthy periodontal ligament (PDL). To use oral tumours, compared with adjacent normal mucosa, as positive controls. METHODOLOGY: Paraffin-embedded sections were stained with antibodies to von Willebrand factor (vWF), a pan-endothelial marker, and CD105, a putative marker for angiogenic vessels. Vascularity was quantified by different methods reflecting vessel volume and density. RESULTS: Irrespective of the marker or method used, vascularity values were similar in periradicular granuloma and PDL. Both tissues were highly vascularized, with levels similar to those found in oral squamous cell carcinoma. Vascularity was significantly higher in the latter than in normal mucosa. Fewer vessels were positive for CD105 than for vWF in the normal mucosa, whereas similar numbers were found in the other tissues examined. CONCLUSIONS: A comparison of vascularity in oral tumours and normal oral mucosa provided evidence of angiogenesis in the former. Staining with CD105 added limited value to staining with vWF in these tissues. In contrast, a comparison of periradicular granuloma and PDL failed to demonstrate evidence of angiogenesis in the granuloma. As all vessels were similarly stained with vWF and CD105 in granuloma and PDL, a possible hypothesis is that all vessels are newly formed in these tissues. A more plausible alternative is that CD105 expression may reflect the metabolic activity or intrinsic characteristics of the tissues, rather than the presence of angiogenic vessels.

[Impact of multi-layer spiral CT angiography of bronchial artery and pulmonary artery in assessment of the main blood supply to the primary lung cancer].

OBJECTIVE: To investigate the blood supply of primary lung cancer (PLC) using CT angiography for bronchial artery (BA) and pulmonary artery (PA). METHODS: Thin-section enhanced multi-layer spiral CT (MSCT) were carried out in 147 primary lung cancer patients and 46 healthy subjects as control. Three-dimensional images of bronchial artery and pulmonary artery were obtained using volume render (VR) and multi-planar reconstruction (MPR) or maximum intensity projection (MIP) at the workstation, and their morphological findings and relationship with the mass were assessed. RESULTS: 136 primary lung cancer patients and 32 healthy controls were evaluated for at least one bronchial artery displayed clearly in VR. The detective rate of the bronchial artery was 92.5% and 69.6%, respectively. The bronchial artery caliber and the total section area of lesion side in lung cancer patients were significantly larger than that on the contralateral side and that of the control (P < 0.05). Bronchial artery on the lesion side in lung cancer was dilated and tortuous, directly penetrating into the mass with reticularly anastomosed branches. In the PLC patients, all PA were shown clearly with normal morphological image though crossing over the masses in 54 patients; In 25 PLC patients, the PA being essentially intact, was pushed around and surrounded the mass, giving the "hold ball" sign; In 40 other PLC patients, PA being also intact, the mass surrounded and buried the PA from the outside, crushing the PA flat resulting in an eccentric or centrifugal shrinkage, forming the "dead branch" sign; In the rest 28 patients, the PA was surrounded and even compressed, forming the "residual root" sign. CONCLUSION: Primary lung cancer patient shows dilated bronchial arteries and increased bronchial artery blood flow, whereas pulmonary arteries just pass through the mass or are compressed by the mass. It is further demonstrated that the bronchial artery, instead of the pulmonary artery, is the main vessel of blood supply to the primary lung cancer as shown by MSCT angiography of bronchial artery and pulmonary artery.

Assessment of tumor oxygenation in human cervical carcinoma by use of dynamic Gd-DTPA-enhanced MR imaging.

Increased knowledge of the physiological basis behind the signal enhancement in tumors during dynamic contrast-enhanced magnetic resonance (MR) imaging may be useful in development of predictive assays based on this technique. In the present work, the relative signal intensity (RSI) increase in gadopentetate dimeglumine (Gd-DTPA)-enhanced MR images of patients with cervical carcinoma was related to tumor perfusion, vascular density, cell density, and oxygen tension (pO(2)). The patients were subjected to MR imaging before the start of treatment (N = 12) and after two weeks of radiotherapy (N = 8). Perfusion was determined from the kinetics of contrast agent in tumors and arteries, vascular density and cell density were determined from tumor biopsies, and pO(2) was determined by polarographic needle electrodes. The maximal RSI was correlated to perfusion (P = 0.002) and cell density (P = 0.004), but was not related to vascular density. There was also a correlation between pO(2) and perfusion (P < 0.001). Moreover, pO(2) tended to be correlated to cell density (P = 0.1), but was not related to vascular density. There was a significant correlation between RSI and pO(2), regardless of whether the median pO(2) (P < 0.001) or the fraction of pO(2) readings below 2.5 mmHg (P < 0.001), 5 mmHg (P < 0.0001), or 10 mmHg (P < 0.001) was considered. Our results suggest that the Gd-DTPA-induced signal enhancement in MR images of cervical tumors is influenced by both perfusion and cell density. These parameters are also of major importance for tumor oxygenation, leading to a correlation between signal enhancement and oxygenation. Dynamic contrast-enhanced MR imaging may therefore possibly be useful in prediction of treatment outcome.

Contribution of doppler sonography blood flow information to the diagnosis of metastatic cervical nodes in patients with head and neck cancer: assessment in relation to anatomic levels of the neck.

BACKGROUND AND PURPOSE: Although sonographic evaluation of cervical adenopathy by use of size criteria is effective, the sensitivity and specificity fall short of that required to make adequate judgments regarding neck dissection. Therefore, we tested whether the combined use of size criteria and Doppler sonographic findings would improve the predictive ability for metastatic cervical nodes. METHODS: We analyzed 338 histologically proved cervical lymph nodes (108 metastatic and 230 nonmetastatic) in 73 patients with head and neck cancer. The sonographic topography of the nodes was compared with dissected specimens, and their position in the neck was categorized into three levels (I, II, and III+IV). The diagnostic accuracy of sonography was evaluated by using the single criterion of short-axis diameter of the node or by the combined criteria of short-axis diameter and Doppler blood flow features (the absence or presence of normal hilar flow). RESULTS: As compared with the single criterion of short-axis nodal diameter, the combined criteria of nodal size and Doppler blood flow patterns increased the diagnostic accuracy of sonography at all levels in the neck. Accordingly, the best cut-off values were improved to 6, 7, and 5 mm for nodes at levels I, II, and III+IV, respectively. In addition, the combined criteria yielded high sensitivites (> or = 89%) and specificities (> or = 94%). CONCLUSION: Hilar blood flow information obtained by Doppler sonography significantly improves diagnostic accuracy for the detection of nodes metastatic from head and neck squamous cell carcinoma.

Prognostic assessment of sonography and tumor volumetry in advanced cancer of the head and neck by use of doppler ultrasonography.

OBJECTIVE: The objective of this trial was to examine the degree of tumor vascularity in lymph node metastases as depicted by computer-assisted color Doppler sonography and the tumor volumes associated with prognosis in carcinomas of the oropharynx and hypopharynx after primary radiochemotherapy. PATIENTS AND METHODS: In a prospective trial, 25 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx (stage IV UICC 1997) were treated with radiochemotherapy. The color Doppler findings were quantified with a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD). As important prognostic cofactor, total tumor volume (TTV) was calculated from CT sections and related to the degree of vascularity. RESULTS: Low CPD in neck metastases showed a correlation with better overall survival. A high-CPD group and a high-TTV group (median survival 10.1 months) were determined and were compared with all other CPD/TTV combinations (median survival 28.4 months); the difference in survival was significant (P = 0.002). CONCLUSION: The results indicate that high tumor vascularity in combination with high TTV indicates a particularly bad prognosis in patients treated with primary radiochemotherapy for head and neck cancer.