Percutaneous embolization of carotid paragangliomas using solely Onyx.

BACKGROUND AND PURPOSE: Paragangliomas are highly vascularized usually benign neoplasms arising from nerve tissue. Endovascular preoperative embolization is used to facilitate surgery but is often not complete, due to tiny feeding arteries not feasible for selective catheterization. Our purpose was to evaluate angiographic and clinical outcome using Onyx for percutaneous glomus tumor embolization. MATERIALS AND METHODS: A consecutive series of 4 patients with 6 paragangliomas located at the bifurcation of the common carotid artery were treated with percutaneous embolization using Onyx as the sole embolic material. RESULTS: Complete devascularization of the 6 paragangliomas was achieved using a percutaneous embolization technique with Onyx as a sole agent, combined with an endovascular microballoon that offered protection of the internal carotid artery. CONCLUSIONS: Further documentation is necessary to prove the higher grade of devascularization of paragangliomas with Onyx compared with other embolic material and the associated potential to facilitate surgery. Nevertheless, Onyx seems to be safe when used percutaneously due to its lavalike pattern flow and its controllable properties, allowing slow tumor bed penetration.

[Incidence, latency, and prognosis of local and regional recurrences in patients with upper aerodigestive tract cancer treated by laser microsurgery: influence of initial tumor parameters]. / Lokale und regionäre Rezidive von laserchirurgisch behandelten Plattenepithelkarzinomen des oberen Aerodigestivtrakts: Häufigkeit, Latenz und Prognose sowie Einfluss der initialen Tumorparameter.

INTRODUCTION: The aim of the present study is to identify clinical factors that influence the incidence and the prognosis of local and regional recurrences. PATIENTS AND METHODS: The data of 1,426 patients with newly diagnosed squamous cell carcinoma of the upper aerodigestive tract who were treated by curative laser microsurgery between August 1986 and December 2002 were reviewed. RESULTS: In 381 patients (27%), tumor recurrences were detected during follow-up. The frequency of local as well as regional recurrences significantly correlated with the initial stage of tumors. Recurrences of advanced carcinomas occurred considerably sooner than those of stage II and I cancer. During the 4th year of follow-up, patients with early stage disease had a recurrence rate twice as high as those with advanced carcinomas. Survival with recurrence was adversely affected by adjuvant radiotherapy as part of initial treatment, simultaneous local and regional manifestation of recurrence, male sex, advanced stage of initial disease, and by oral or hypopharyngeal site of the primary tumor. CONCLUSION: Early carcinomas of the upper aerodigestive tract recur at a lower rate than advanced stage diseases, but after a longer mean latency period. As a consequence, these patients should receive close follow-up also during the 3rd and 4th years after treatment, particularly as the prognosis of their recurrences is most often favorable.

Platysma myofascial flap for reconstruction of oropharyngeal defects after transoral laser microsurgery of locally advanced carcinomas.

INTRODUCTION: Transoral laser microsurgery of locally advanced carcinomas of the lateral oropharynx often results in exposure of major vessels of the neck and may be accompanied by a substantial risk of intra- and post-operative bleeding. PROCEDURE: Six patients with tonsillar cancers radiologically infiltrating the parapharyngeal space underwent ipsilateral neck dissection with temporary protection of neck vessels. While the neck remained open, transoral laser resection of the primary tumour was performed. Pharyngeal defects were subsequently closed by a superiorly based platysma myofascial flap. RESULTS: All tumours were completely resected. Intra- and post-operative bleeding complications requiring blood transfusion or surgical revision did not occur. None of the patients developed a cervical fistula. During a mean follow-up time of 24.8 months, no local and/or regional recurrence was observed. CONCLUSION: The described approach is oncologically safe and seems to ensure reliable protection of neck vessels during and after transoral laser resection of locally advanced oropharyngeal carcinomas, as well as to prevent fistula formation.

[Transoral resection of locally advanced squamous cell carcinoma of the lateral oropharynx: combination of CO2 laser microsurgery with flap reconstruction]. / Transorale Resektion lokal fortgeschrittener Plattenepithelkarzinome der Oropharynxseitenwand: Kombination der CO2-Lasermikrochirurgie mit einer primären Defektdeckung.

INTRODUCTION: Transoral laser microsurgery of locally advanced carcinomas of the lateral pharynx often results in exposure of major vessels of the neck and is accompanied by a substantial risk of intra- and postoperative bleeding. We therefore only perform these operations after external protection of neck vessels, if necessary combined with flap reconstruction. PATIENTS AND METHODS: Between October 2001 and December 2004, 11 locally advanced squamous cell carcinomas of the lateral oropharynx that reached the major vessels of the neck were treated as follows: after ipsilateral neck dissection with temporary protection of the jugular vein and carotid arteries, the neck remained open while transoral laser surgery of the primary tumor was performed. Pharyngeal defects were subsequently closed by either primary suture or a platysma myofascial flap. All patients underwent adjuvant radiotherapy. RESULTS: All primary tumors were completely resected. None of the patients required tracheotomy or placement of a percutaneous endoscopic gastrostomy tube. The mean duration of nasogastric feeding tubes was 12.7 days. In one case, the routine radiological contrast study revealed a blind cervical fistula 10 days after surgery. This healed spontaneously within 7 days. One mild postoperative hemorrhage had to be stopped by endoscopic coagulation under general anesthesia. During a mean follow-up of 19.4 months, none of the patients developed a local and/or regional recurrence. CONCLUSION: The surgical procedure described ensures sufficient protection of neck vessels during and after the transoral resection of advanced carcinomas of the pharynx. It successfully combines the advantages of minimally invasive laser microsurgery with those of flap reconstruction known from traditional surgery.

[Parinaud's oculoglandular syndrome. A rare differential diagnosis of "red eye"]. / Okuloglanduläres Syndrom nach Parinaud. Seltene Differenzialdiagnose des "roten Auges".

Two cases of Parinaud's oculoglandular syndrome, which represents an ocular manifestation of cat-scratch disease, are reported. The symptoms are subacute and include unilateral conjunctivitis and pre-auricular lymphadenopathy. Diagnosis primarily relies on the recognition of suggestive clinical signs in conjunction with positive serologic testing. In most cases, therapy is not necessary.

[Solitary neurofibroma of the parapharyngeal space]. / Solitäres Neurofibrom im Parapharyngealraum.

A 21 year old male patient presented with dysphagia. Clinical examination as well as CT and MRT showed a tumor in the right parapharyngeal space. The tumor was resected completely using a transcervical approach. The pathological examination showed a neurofibroma. In this case report, preoperative diagnosis, therapy and follow-up of this rare tumor are discussed.

[Tonsillectomy by CO@ laser microsurgery--an analysis of clinical and morphological data]. / Die mikrochirurgische Tonsillektomie mit dem CO2-Laser. Eine Analyse klinischer und morphologischer Daten.

BACKGROUND: Tonsillectomy by CO(2) laser microsurgery is an almost bloodless procedure that has developed to an alternative to traditional dissection tonsillectomy during recent years. It has been suggested that the laser technique more precise than the conventional one, however, attempts to investigate this morphologically have not yet been undertaken. In addition, there is a need for large clinical studies to compare the postoperative bleeding risk of both procedures. METHODS: The charts of 617 patients who underwent routine tonsillectomy between 1995 and 1998 at the ENT department of Darmstadt Hospital, were retrospectively investigated with regard to postoperative bleeding events. A total of 467 patients were treated by the conventional technique and 150 by CO(2) laser microsurgery (continuous mode, 5 W). Moreover, 2 mm serial sections of tonsils of 56 consecutive patients treated in 1999 (31 conventional and 25 laser tonsillectomies) were used to determine peritonsillar (Vp) and tonsillar tissue volumes (Vt). RESULTS: The postoperative bleeding risk following laser tonsillectomy differed slightly from that following the conventional technique (12.0% vs 14.6%; P=0.499; Fisher's exact test). However, the incidence of severe bleeding events requiring revision in general anesthesia was significantly reduced (0.7% vs 4.9%; P=0.015; Fisher's exact test). Tonsillar specimens that were removed by laser surgery contained significantly less peritonsillar tissue than those from conventional procedures (Vp/Vt 5.1%+/-0.6% vs 10.8%+/-1.1%; P below 0.001; Mann-Whitney U-test). CONCLUSION: CO(2) laser microsurgery improves the precision of tonsillectomy and provides a maximum protection for the peritonsillar tissue. The incidence of severe bleeding events is markedly reduced. Laser tonsillectomy is therefore recommended for patients with clotting disorders or those requiring a particularly exact preparation technique.

Effect of keratinocyte growth factor on the proliferation, clonogenic capacity and colony size of human epithelial tumour cells in vitro.

PURPOSE: The effect of recombinant human keratinocyte growth factor (rHuKGF) on the proliferation, clonogenic capacity and colony size of low-passage human epithelial tumour cells was tested in vitro. MATERIALS AND METHODS: Five tumour cell cultures derived from head and neck squamous cell carcinomas, three cultures derived from pleural effusions of carcinomas of different origin and normal human nasal epithelial cells were analysed in passages 2-4. Expression of FGF7 and its receptor (FGFR2) were determined by the RNase protection assay. Cells were incubated with rHuKGF (10-200 ng ml(-1)) 3 days before or immediately after plating for clonal growth in serum-depleted media. To determine cellular radiosensitivity, single doses of 1-8 Gy X-rays were applied. Colony formation as well as colony size, reflecting the number of cell divisions, was determined after 10-15 days of growth in rHuKGF-treated and control cells. RESULTS: Normal nasal epithelial cells showed a two- to threefold increase in the number of cell divisions due to rHuKGF-treatment. In tumour cell cultures, significant stimulation of proliferation occurred in only one of eight samples. Tumour cells expressed FGF7 mRNA and protein, and low levels of FGFR2 mRNA. The addition of rHuKGF to the medium of the tumour cell cultures influenced neither radiation-induced impairment of proliferation nor clonogenic cell survival. CONCLUSION: rHuKGF has been shown to ameliorate the radiation tolerance of normal epithelia. The minimum in vitro tumour cell response to rHuKGF compared with normal epithelial cells suggests a potential for selective protection of normal epithelia during radiotherapy. The low FGFR2 expression as well as the FGF7 expression in the tumour cells may contribute to their resistance to rHuKGF treatment.

Clinical relevance of Fas (APO-1/CD95) expression in laryngeal squamous cell carcinoma.

BACKGROUND: Expression of Fas receptors renders tumor cells potentially susceptible to the host immune system. In squamous cell carcinomas of the head and neck, Fas has recently been found to be down-regulated in some cases; its prognostic value and correlation with clinicopathologic parameters, however, is yet to be delineated. METHODS: Paraffin-embedded specimens of 88 primary laryngeal squamous cell carcinomas were investigated for Fas protein expression by immunohistochemistry. Apoptotic tumor cells were visualized using the nick end labeling method. To assess the immunologic reaction to the neoplasm, the intensity of lymphoplasmocytic stroma reaction was determined. The mean follow-up time amounted to 45.9 months (range, 1-144 months). RESULTS: In tumor-adjacent normal mucosa and in most well-differentiated tumors, Fas expression was restricted to basal and parabasal cell layers. A diffuse pattern of staining reactions predominated in high-grade lesions (p <.001). The degree of Fas expression revealed a positive relationship with the intensity of lymphoplasmocytic stroma reaction (p =.002) but was unrelated to clinicopathologic parameters and to apoptotic rates of tumors. Neither Fas nor the lymphoplasmocytic stroma reaction had any impact on patient survival. CONCLUSIONS: Up-regulation of cell surface Fas expression in laryngeal carcinoma seems to have a stimulatory effect on the immune cell infiltration of the stromal tissue. Its lack of clinical relevance might be due to an inhibition of intracellular Fas signal transduction, which represents a frequent strategy of tumor cells to escape Fas-mediated apoptosis.

Radiotherapy combined with simultaneous chemotherapy with mitomycin-C and 5-fluorouracil for inoperable head and neck cancer.

The feasibility and effectiveness of a combined chemoradiotherapy treatment modality for locally advanced head and neck cancer was tested in a phase II trial. From March 1995 to June 1998, 35 patients with advanced squamous cell carcinoma of the head and neck were treated with a continuous intravenous infusion of 5-fluorouracil (600 mg m-2 24 h-1 for Days 1 to 5 (120 h)) and mitomycin-C (10 mg m-2 intravenously) on Day 5 during the first week of radiotherapy and on Day 36. 31 patients had stage IV disease; 4 patients had stage III; and 1 patient had stage II. Patient ages ranged from 42-69 years (median 56.7 years). The tumours involved were as follows: oral cavity (n = 11); oropharynx (n = 14); hypopharynx/larynx (n = 10). Radiotherapy was delivered to a total dose of 70 Gy with conventional fractionation (2 Gy per fraction, five times a week). Chemotherapy was well tolerated and all patients received the intended dose. Mild nausea occurred in five patients. After a mean follow-up of 21 months (range 10-44 months), 8 (23%) patients remain alive. A complete response was seen in 28 (80%) patients. When a recurrence appeared, it was within the first year after treatment. 1- and 2-year overall survival rates were 46% and 23%, respectively. Grade 3 mucositis occurred in 17% of patients. Grade 1-2 thrombopaenia occurred in 3 (9%) patients, grade > 2 leukopaenia in 4 (11%) patients, and grade > or = 2 anaemia in 3 (9%) patients. We observed a treatment interruption of maximum 1 week for six patients owing to mucositis. Febrile neutropaenia or aplasia were not observed. The concomitant use of 5-fluorouracil, mitomycin-C and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. This protocol showed good locoregional response with a very low toxicity profile.

[Prognostic significance of expression of p53, bcl-2 and bax in squamous epithelial carcinoma of the larynx--a multivariate analysis]. / Prognostische Bedeutung der Expression von p53, bcl-2 und bax im Plattenepithelkarzinom des Larynx--Eine multivariate Analyse.

BACKGROUND AND OBJECTIVE: Conventional clinicopathologic parameters do not accurately reflect the clinical outcome of patients with head and neck carcinoma. The establishment of additional prognostic factors that may give insight into the biologic features of a tumor is therefore an essential goal. The present study analyses the expression patterns of p53, bcl-2, and bax with regard to their relationships with conventional tumor parameters and to their prognostic significance in patients with laryngeal squamous cell carcinoma. PATIENTS/METHODS: Paraffin-embedded tissue sections of 88 primary laryngeal squamous cell carcinomas diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. The mean follow-up time was 45.9 months. RESULTS: Bcl-2 immunoreactivity was positively correlated with an advanced clinical stage, a high T category, regional lymph node metastasis, and a high histological grading. Significant relationship between clinicopathologic parameters and p53 or bax expression were not detectable. The age of the patients, advanced disease, positive bcl-2 expression, and a high level of p53 expression were significantly associated with shortened disease-specific survival in univariate analysis. In multivariate analysis, age, clinical stage, and p53 expression had independent prognostic value. CONCLUSIONS: Although expression of p53 and bcl-2 was found to be clinically relevant in univariate analysis, only p53 but not bcl-2 was an independent predictor of patient outcome. This superiority of p53 in multivariate analysis points to its central role within cell cycle and death regulation, with which it influences two important parameters of tumor progression.

Prognostic significance of p53/bcl-2 co-expression in patients with laryngeal squamous cell carcinoma.

OBJECTIVE: The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. DESIGN: Retrospective study. METHODS: Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. RESULTS: Age of patients, advanced disease (stages HI and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. CONCLUSIONS: The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax.

Value of 31P NMR spectroscopy in predicting the response of a xenografted human hypopharynx carcinoma to irradiation.

PURPOSE: An early indicator of tumor sensitivity to irradiation could provide useful information on the effectiveness of therapy and may facilitate more individual designs of treatment protocols. The aim of the present study was to evaluate the potential of in vivo 31P nuclear magnetic resonance spectroscopy in predicting the response of a xenografted human hypopharynx carcinoma to radiotherapy. METHODS: The tumor had been serially heterotransplanted to athymic mice. 31P NMR spectra were collected before and at four intervals (24, 48, 72, and 120 h) after irradiation with 15 Gy or 30 Gy. Alterations of phosphorus metabolism were compared with the growth delays, the histological appearance, and the mitotic activity of the treated tumors. RESULTS: Radiation with 30 Gy induced increases of the phosphodiester level (P < 0.001) as well as of the tumor pH (P < 0.05) and decreases of the phosphomonoester level (P < 0.001) within 48 h. The changes clearly preceded measurable tumor responses and were accompanied by severe histological destruction and marked depression of mitotic indices. However, none of these spectral alterations was significantly correlated with individual delays of tumor growth. The only parameters allowing a prediction of radiation-induced tumor responses were the pre-treatment levels of phosphomonoesters and -diesters. The 31P NMR spectroscopic changes observed after therapy with 15 Gy were either unsystematic or insignificant. CONCLUSIONS: Pretreatment levels of tumor phospholipids were indicative of radiosensitivity in the xenografted human hypopharynx carcinoma investigated here. However, since phosphorus metabolism varies considerably among different tumor lines, it seems unlikely that there exists a uniform 31P NMR spectroscopic parameter predicting tumor response to radiation therapy.

[Postoperative antibiotic therapy of cervical lymphadenitis caused by nontuberculous, atypical mycobacteria]. / Die postoperative antibiotische Therapie von zervikalen Lymphadenitiden durch nichttuberkulöse, atypische Mykobakterien.

BACKGROUND: Cervical lymphadenitis caused by atypical mycobacteria is increasingly observed in immunocompetent children between 1 and 5 years of age. Surgical excision of all affected lymph nodes represents the treatment of choice. However, due to the infiltrative nature of the disease, surgery is occasionally unable to provide a complete cure and is associated with a high risk of recurrence. Such cases might derive benefit from an additional antibiotic therapy. METHODS: The study includes 4 children with demonstrated or clinically suspected nontuberculous mycobacterial lymphadenitis, in whom partial surgery had been performed. Postoperatively, two patients were treated with clarithromycin, rifabutin, and protionamide, the others with clarithromycin alone. Antibiotics were administered orally for 6-12 weeks and were continued four weeks after local signs of inflammation were no longer detectable. RESULTS: In all cases, symptoms of lymphadenitis resolved within 1-2 months and did not recur. One patient was affected by WHO grade I leukopenia after 6 weeks, which soon disappeared after administration of rifabutin and protionamid had been discontinued. CONCLUSIONS: Postoperative antibiotic therapy seems to be an effective approach to treat residual disease following incomplete surgery. It remains to be clarified, however, if such a therapy should comprise combinations of agents or if administration of clarithromycin alone might be sufficient.

Spontaneous apoptosis in laryngeal squamous cell carcinoma is independent of bcl-2 and bax protein expression.

BACKGROUND: bcl-2 and bax genes are known to be involved in the control of apoptotic cell death, an important mechanism of growth regulation that influences the biologic behavior of tumors. The aim of the current study was to investigate the relationship of bcl-2 and bax expression to the rate of spontaneous apoptosis in laryngeal carcinomas, and to assess its relations to clinicopathologic features of tumors. METHODS: Immunohistochemical analyses for bcl-2 and bax were performed on paraffin embedded tissue sections from 134 primary laryngeal squamous cell carcinomas. To visualize apoptotic cells, the nick end labeling method was used. The proliferative activity of tumors was analyzed by determination of mitotic indices. RESULTS: bcl-2 immunoreactivity was positively correlated with tumor grade (P < 0.00001), high T category (P < 0.02), metastatic involvement of cervical lymph nodes (P < 0.003), and supraglottic or subglottic location of primary tumors (P < 0.00005). An inverse relation was found between bcl-2 and bax expression (P < 0.004). The frequency of spontaneous apoptosis was closely associated with mitotic activity (P < 0.0004) but appeared to be unrelated to protein levels of bcl-2 or bax as well as to bcl-2:bax ratios. CONCLUSIONS: The results of this study point to the significance of cell proliferation as a major determinant of the rate of spontaneous apoptosis in laryngeal carcinomas. The bcl-2:bax expression ratio obviously does not affect the incidence of apoptosis, but it may be considered as a marker of disease progression and poor prognosis.