Prediction of lymph-node metastasis and lymphatic invasion of superficial pharyngeal cancer on narrow band imaging with magnifying endoscopy.

OBJECTIVE: We studied factors related to lymphatic invasion and lymph-node metastasis in patients with superficial pharyngeal cancer who underwent transoral surgery. METHODS: The study group comprised 67 patients with superficial pharyngeal cancer (92 lesions) in whom squamous cell carcinoma was histopathologically diagnosed. The primary endpoint was clinicopathological findings according to the presence or absence of lymph-node metastasis, lymphatic invasion, or both. The secondary endpoints were (1) endoscopic findings according to the presence or absence of subepithelial invasion and (2) tumor thickness according to the endoscopic findings. RESULTS: Lymph-node metastasis, lymphatic invasion, or both were related to the white light findings of the main macroscopic type (p = 0.006), the NBI magnifying endoscopy findings of the classification of type B vessels (p = 0.005) and avascular area (AVA) (p = 0.003), and the histopathological findings of subepithelial invasion (p = 0.027), solitary nests (p = 0.013), venous invasion (p = 0.003), and tumor thickness (p = 0.028). The white light findings of white coat (p = 0.027), main macroscopic type (p = 0.005), and protruding type (p = 0.027) and the NBI magnifying endoscopy findings of the classification of type B vessels (p = 0.0002) were significantly related to subepithelial invasion. Tumor thickness was significantly related to the white light findings of white coat (p = 0.0002), main macroscopic type (p < 0.0001), protruding type (p < 0.0001), and mixed type (p = 0.017) and the NBI magnifying endoscopy findings of the classification of type B vessels (p < 0.0001) and AVA (p = 0.005). CONCLUSION: Detailed assessment by means of NBI magnifying endoscopy at the time of transoral surgery may contribute to the prediction of lymphatic invasion and lymph-node metastasis in patients with superficial pharyngeal cancer.

Extrusion of embolization coils through the carotid artery in a radiated neck.

Extrusion of embolization coils is an exceedingly rare event. We present and discuss a unique case of coil extrusion through the carotid artery into the pharyngeal soft tissue in the setting of soft tissue radionecrosis (STRN). A 55-year-old man with previous chemoradiation therapy presented with massive transoral hemorrhage. Control of the bleeding was accomplished by coil embolization of the right carotid artery system. The patient subsequently developed spiking fevers, and an exploration of the neck revealed coil extrusion through the common carotid artery and into the neck and pharynx. Although the incidence of coil extrusion in the head and neck is remarkably low, this complication must be considered in the heavily radiated neck and a high index of suspicion should be maintained in the setting of radionecrosis and signs and symptoms of systemic infection. Appropriate management requires early recognition and removal of foreign material with wound stabilization.

[Angiogenesis: a new therapeutic target of thoracic and laryngopharyngeal carcinoma]. / L'angiogenèse: une nouvelle cible thérapeutique des cancers thoraciques et ORL.

Angiogenesis or new blood vessel formation is a complex and fundamental event in the process of tumor growth and metastatic dissemination. Actually, most of antiangiogenic agents target the VEGF considered like the most potent proangiogenic factor. These molecules directly inhibit VEGF or the kinase activity of its receptor (VEGFR) and represent a significant therapeutic progress in several solid tumors types. First clinical studies of antiangiogenic agents in thoracic and laryngopharyngeal carcinomas have shown promise mainly in combination with other therapies (chemotherapy, other targeted therapies or radiotherapy). Besides common antiangiogenic therapies-induced adverse events, risks of bleeding caused by tumor necrosis mainly in squamous cell lung carcinomas have been observed during early clinical trials. Assessment of surrogate markers of target inhibition could allow a better selection of patients able to benefit from antiangiogenic treatments eventually combined with chemotherapy or molecules targeting others metabolic pathways.

MR perfusion measurements on pharyngeal tumors: comparison of quantification strategies.

For the case of pharyngeal carcinomas, the clinical value as well as the stability of several evaluation methods of MR tomographic perfusion measurement are compared. Eighteen patients suffering from histologically proven squamous cell carcinomas were investigated by MR tomography (1.5 T, 0.2 mmol/kg Gd-DTPA) prior to and during radiation therapy. Perfusion measurements were performed using a double-echo FLASH sequence. Parameters describing regional blood flow, blood volume, mean transit time, and interstitial concentration of contrast medium (CM) were calculated, applying seven different combinations of correction approaches (separating the shortening of T1 and T2*, arterial input function (AIF), and tumor shunts). Their correlations to MR independent tumor physiological parameters were analyzed (metabolic activity measurements using 18F-FDG-PET, polarographical pO2 measurement, tumor volume). Significant improvements of the correlation between perfusion-dependent and other tumor physiological parameters could be achieved by decoupling the shortening of T1 and T2* and by applying of the tumor shunt model. Deconvolution from the AIF deteriorated the correlation. Therefore, the elimination of the T1 shortening due to interstitial CM proves to be essential for MR perfusion measurements on contrast medium uptaking lesions. Depending on the measurement conditions (temporal resolution, signal-to-noise ratio), the consideration of the AIF can even make the results significantly worse by introducing additional measuring errors.

CT angiography before embolization for hemorrhage in head and neck cancer.

We present a patient with advanced head and neck carcinoma and a bleeding pseudoaneurysm diagnosed by means of CT angiography; this was not apparent on conventional digital subtraction angiograms. The information provided by CT angiography facilitated rapid identification of the pseudoaneurysm and treatment with embolization. CT angiography may be helpful before embolization in cases of hemorrhage in head and neck cancer.

ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature.

Physiological differences between tumor and normal vasculature provide a target for drug discovery. In particular, the immature nature of tumor vasculature may render it intrinsically sensitive to disruption by agents affecting the endothelial cell cytoskeleton, including tubulin-binding agents. In this article, we report the synthesis of a water-soluble phosphate prodrug, ZD6126, of the tubulin-binding agent N-acetylcolchinol. In vitro studies demonstrate the comparative tubulin-binding properties of the prodrug and active drug, and show the induction of pronounced, reversible changes in endothelial cell morphology at subcytotoxic doses. Neither ZD6126 nor N-acetylcolchinol showed effects on the growth of human umbilical vein endothelial cells at concentrations below 100 micro M. In contrast, changes in endothelial cell morphology were seen at much lower, noncytotoxic concentrations (0.1 micro M) of ZD6126 and more pronounced effects were seen in proliferating versus confluent endothelial cell cultures. In vivo studies were carried out using a murine tumor model (CaNT) with single administration of a dose well below the maximum tolerated dose. These studies showed a large reduction in vascular volume, induction of extensive necrosis in tumors, and a reduced tumor cell yield in a clonal excision assay, consistent with vascular rather than cytotoxic effects. A viable rim of tumor remained after single-dose administration and minimal growth delay was observed. However, well-tolerated, multiple administration regimens led to pronounced tumor-growth delay. In the human xenograft FaDu, the growth delay given by a single dose of paclitaxel was enhanced by combination with a single dose of ZD6126, and the growth delay given by the combination was greater than the sum of the growth delays from the individual treatments. These findings show that ZD6126 is a promising antivascular agent for the treatment of solid tumors.

MR perfusion measurement of contrast uptaking lesions: consideration of T2* shortening due to interstitial contrast agent.

AIM: In MR perfusion measurements of contrast uptaking lesions, time intensity curves are hampered by T 1 shortening as well as by the change of T 2 * due to interstitial contrast material (CM). Using double echo sequences, the influence of T 1 can be mathematically eliminated. For correction of the T 2 * influence an empirical algorithm using time-intensity-curves exclusively measured in the suspected lesion is proposed. METHODS: The interstitial CM concentration is assumed to be proportional to the change of the intensity for T E = 0 or to the change of the relaxation rate DeltaR 1 respectively. The intravascular CM concentration is estimated from DeltaR 2 *. It is adjusted to zero for a time point sufficiently late after the bolus injection by subtraction of the interstitial concentration. This method was applied to double echo FLASH measurements on 15 pharyngeal tumors. RESULTS: The proposed correction transforms the time dependence of the estimated intravascular CM concentration into a plausible course. CONCLUSION: Double echo perfusion measurements can be corrected for the interstitial CM induced T 2 * shortening without additional measurements with proneness to errors. This does not necessarily improve the diagnostic value, since possibly "implied multivariate aspects" of uncorrected parameters (here: contrast uptake of the lesion is related to tumor neoangiogenesis as well) are eliminated.

Hypervascular parapharyngeal schwannoma: an unusual case.

This report describes a 13-year-old girl who had a right pulsatile neck mass of the parapharyngeal space. We examined the patient with computerized tomography and angiography preoperatively and a heterogeneous, hypervascular mass was detected on her right neck. Intraoperative findings and the postoperative histopathologic diagnosis showed that this mass was a schwannoma that originates from cervical sympathetic chain and the superior thyroid artery supplied the mass. After careful scrutiny of English literature, this clinical manifestation is an unusual event.

Expression of granulocyte colony-stimulating factor receptor and platelet-derived endothelial cell growth factor in oral and oropharyngeal precancerous lesions.

Epithelial hyperplasia and dysplasia have been diagnosed as precancerous lesions and have been discussed in relationship to carcinogenesis. We analyzed the immunohistochemical expression of granulocyte colony-stimulating factor receptor (G-CSFR) and platelet-derived endothelial cell growth factor (PD-ECGF) in oral and oropharynx; 33 samples of normal epithelium, 28 samples of hyperplasia, 16 samples of dysplasia and 58 samples of squamous cell carcinoma. Also, we examined mean vessel density (MVD) by using CD34 staining and proliferating cell nuclear antigen (PCNA) staining. Dysplasia and head and neck Squamous Cell Carcinoma (SCC) exhibited higher G-CSFR expression and MVD than normal or hyperplastic epithelium (p <0.01). In the PD-ECGF staining, significant differences were found between SCC and normal epithelium, hyperplasia and dysplasia (p<0.001). In dysplasia and hyperplasia, PD-ECGF expression was significantly correlated with PCNA expression (r=0.345, p=0.025), however it was not correlated with the MVD. G-CSFR expression was not correlated with either PCNA or MVD. These results suggest that G-CSFR and PD-ECGF might be concerned with different carcinogenesis pathways of the squamous cells in the oral region and that PD-ECGF may be concerned with epithelial proliferation rather than angiogenesis.

Fibrin induces IL-8 expression from human oral squamous cell carcinoma cells.

In recent studies, we have demonstrated that fibrin is present in association with tumor cells in oral squamous cell carcinoma (OSCC) in vivo. We hypothesized that this fibrin can directly induce the expression of known angiogenic factors from oral tumor cells. Since IL-8 is known to be the major inducer of angiogenesis caused by these cells, we examined the ability of fibrin to stimulate IL-8 expression from OSCC cells in vitro. A physiologically relevant concentration of fibrin was found to cause a dose and time-dependent stimulation of IL-8 expression from oral and pharyngeal tumor cells but not from a non-tumorigenic oral cell line. Fibrinogen, thrombin and collagen were all unable to induce significant IL-8 expression, establishing the specificity of fibrin in causing this response. Gel filtration chromatography confirmed the molecular identity of the IL-8 antigen detected in the ELISA system used. These results suggest that fibrin may promote angiogenesis in oral tumors in vivo by directly upregulating the expression of IL-8 from tumor cells.

[Correlation of tumor microvessel density with prognosis in laryngopharyngeal malignant melanoma].

OBJECTIVE: To investigate the relationship between microvessel density and clinicopathology, as well as the prognosis in pharyngo-laryngeal malignant melanoma. METHODS: Specific endothelial cell markers with immunohistochemistry and microvessel density with morphometry in 28 cases of laryngopharyngeal malignant melanoma. RESULTS: There was no correlation between the microvessel density (MVD) and the tumor size, Clark grade, as well as Breslow grade; however, significant correlation was found between the MVD and the AJC's grade, as well as the proliferating cell nuclear antigen (PCNA) labelling index. Microvessel counts were associated with overall survival by Kaplan-Meier analysis. An average vessel count of less than 36.5 (x 200) suggested a better survival, but a higher vessel count of more than 36.5 (x 200) showed a trend to worse the overall survival. CONCLUSION: The results suggest a significant relationship between MVD and prognosis; moreover, MVD may be a useful prognostic indicator in laryngopharyngeal malignant melanoma.

[Single fibrous tumor of the parapharyngeal space]. / Tumor fibroso solitario del espacio parafaríngeo.

A solitary fibrous tumor (SFT) of the parapharyngeal space presented with local symptoms (hearing loss, nasal obstruction, and paralysis of the soft palate and tongue). SFT, originally described as a mesothelial tumor of the pleura, now is recognized as a mesenchymal tumor that occurs in different locations. In the head and neck region, about 50 cases have been reported. This is the fifth published report of an SFT of the parapharyngeal space. The diagnosis was confirmed by immunohistochemical (positivity for vimentin, CD34, and CD99) and ultrastructural markers (fibroblastic characteristics).

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.

Evolving experience with direct puncture therapeutic embolization for adjunctive and palliative management of head and neck hypervascular neoplasms.

OBJECTIVES: The use of percutaneous, direct puncture therapeutic embolization (DPTE) of hypervascular head and neck neoplasms is a relatively new modality that may be used to supplement or supplant conventional endovascular transarterial embolization. Although the preliminary clinical experience reported by a single group has been favorable, extensive case series experience is lacking. This prompted us to review our recent clinical experience with these techniques to determine safety, efficacy, and emerging role in the overall neurointerventional therapeutic armamentarium. STUDY DESIGN: A retrospective analysis of the previous 34 consecutive cases of hypervascular tumors undergoing DPTE referred to our service for therapeutic devascularization was performed. METHODS: Complete case record review was undertaken. Twenty-six of 34 cases involved DPTE of head and neck neoplasms. Conventional diagnostic angiography was performed for therapeutic planning and to assist in precise localization. When performed, standard microcatheter transarterial embolization techniques were used either before or after attempted DPTE. Cyanoacrylate embolic mixtures (n-butyl cyanoacrylate [NBCA], lipiodol, powdered tungsten) were used in 21 of 24 cases, and absolute ethanol in 3 of 24. Direct puncture angiography of the targeted tumor neovasculature was always performed before DPTE. RESULTS: Twenty-four of 26 cases had technically successful DPTE. Combined transarterial embolization with DPTE was used in 16 of 24 cases, although for the last 12 cases, 9 were treated predominantly or exclusively by DPTE. There were no major or minor clinical complications, and there was one asymptomatic technical complication. Total or near-total devascularization was achieved in all cases. All preoperative cases had excellent hemostasis within the resected tumor bed. CONCLUSIONS: Our results lend further support to the safety and efficacy of DPTE in the management of hypervascular neoplasms of the head and neck. With our increasing experience, this technique is evolving into a primary therapeutic modality for optimal tumor devascularization.

Regional blood flow, capillary permeability, and compartmental volumes: measurement with dynamic CT--initial experience.

Sequential computed tomographic scanning was performed in patients with neck tumors after contrast material administration. For data analysis, a pharmacokinetic two-compartment model was employed that takes into account both capillary blood supply and bidirectional diffusion of the contrast agent across the capillary wall. This approach offers the possibility to quantitatively characterize tissue microcirculation with regional blood flow, capillary permeability, and relative compartmental volumes.

The value of magnetic resonance imaging in the differential diagnosis of parapharyngeal space tumours.

Between 1987 and 1993 14 patients with a parapharyngeal space tumour were imaged by magnetic resonance imaging (MRI). The vagal body tumours, presenting in the poststyloid compartment, all showed flow voids with anterior and medial displacement of the internal carotid artery. None of the salivary gland tumours, all presenting in the prestyloid compartment with posterior displacement of the internal carotid artery, showed flow voids. MRI is superior compared with other modalities in evaluating the differential diagnosis, especially regarding vascular vs non-vascular tumours. It should encompass T1 SE images to assess the presence or absence of flow voids. In vascular tumours angiography must be used to assess feeding vessels, multiplicity, and sides involved. T1 GE images are useful as they allow superior identification of the internal carotid artery and its relation with the tumour accordingly. In addition to T1 SE images, T2 SE images may help in the evaluation of the differential diagnosis. In all non-vascular tumours aspiration cytology is required to differentiate between benign and malignant disease.