Gemcitabine in the treatment of advanced head and neck cancer.

AIMS: Several new chemotherapy agents show varying degrees of activity in head and neck cancer. One of them is gemcitabine, which is a new nucleoside analogue with an innovative cytostatic mode of action. Gemcitabine has demonstrated a broad spectrum anti-tumoural effect and a favourable toxicity profile. These attributes prompted us to introduce gemcitabine into the treatment of head-and-neck tumours. MATERIALS AND METHODS: Ten heavily pre-treated patients with recurrent and incurable squamous-cell carcinoma of the head and neck (SCCHN) were treated with Gem. The initial cycle consisted of six administrations of the drug (1250 mg/m2 once weekly intravenously over 30 min) followed by a week without cytotoxic treatment. All following cycles were composed of two infusions once weekly (d1, 8), followed by a week of rest. RESULTS: Toxic effects, length of survival and tumour response was assessable in eight patients owing to one suicide and loss of one patient for follow-up. One complete remission, two partial remissions and three 'no change' situations (stable disease) were observed, yielding a response rate of 37.5%. Median survival was 8 months (range 3-12). The incidence of haematological toxicity was low, with grade 3-4 neutropenia in less than 10%. Flu-like symptoms were reported by one-third of patients. CONCLUSIONS: In this small phase-II study, gemcitabine demonstrated a high anti-tumoural activity in SCCHN, with a favourable toxicity profile. Gemcitabine seems to be a promising new drug without severe burden even for patients who are refractory to other cytostatic drugs. Within recent years, the activity and tolerability of gemcitabine was documented in several phase I and phase II trials, especially in combination with cisplatin, and paclitaxel resp, carboplatin/paclitaxel, cisplatin/ifosfamide, and 5-fluorouracil/paclitaxel. The results of these trials will be outlined in the discussion.

A metabolically active dermal replacement (Dermagraft) for vestibuloplasty.

This article describes the use of tissue-engineered dermal replacement in the vestibular extension instead of palatal donor tissue or (split-thickness) skin graft. In three patients the living human-derived fibroblast skin substitute (Dermagraft) was implanted on the wound surface after mucogingival junction and supraperiosteal dissection. Following application of Dermagraft, epithelial closure starting from the resection margins of the defect was observed, obviating further surgical treatment. Vestibular depth was increased and no scarring or frena occurred. Tissue-engineered dermal replacement consisting of living human fibroblasts appears to be a useful substitute for autogenous grafts in pre-prosthetic surgery, offering the advantages of unlimited availability, good colour match and no donor site morbidity.

The buccal fad pad lined with a metabolic active dermal replacement (Dermagraft) for treatment of defects of the buccal plane.

The buccal fad pad flap (BFPF) is an easy to raise pedicled flap for closure of intraoral defects with barely any donor defect. The major disadvantage of the BFPF is the missing epithelial lining, which can induce fibrous tissue formation with resulting functional impairment. To overcome this problem we lined the BFPF with a dermal replacement (Dermagraft) consisting of living metabolic active fibroblasts. In six patients, defects resulting from tumour removal were reconstructed with a combination of the BFPF and Dermagraft and followed up for at least 2 years. In all patients a defect closure was achieved with no functional impairment. The clinical character which was achieved was more a type of defect regeneration than a flap closure. The availability of bioengineered metabolic active tissue can overcome the major problem of the BFPF as an option for defect closure of the buccal side. Furthermore the regeneration of the defects optimises clinical tumour monitoring.

Interferon-induced remission of rapidly growing aggressive fibromatosis in the temporal fossa.

Aggressive fibromatosis is the name for uncommon soft-tissue neoplasms arising within musculoaponeurotic tissue. They show benign histologic features but have an aggressive local behaviour and frequently recur after surgery or radiation. A 48-year-old black woman presented with recurrent aggressive fibromatosis after primary radiotherapy in the left temporal fossa involving the base of the skull. The patient received interferon alpha2a subcutaneously for 6 months. A slow but steady reduction of the tumour was observed, and pre-existing symptoms disappeared.

Recombinant human erythropoietin in the treatment of head and neck tumour anaemia.

At the time of first diagnosis, patients with squamous cell carcinoma in the head and neck are often in the advanced stage of their disease, therefore surgery is not a viable option for treatment. These patients also present frequently a high grade of anaemia as a result of either the malignant process itself or of the following therapy. The incidence of anaemia and the need for transfusion depends on several factors, such as the type and intensity of radiotherapy and radiochemotherapy. Multimode therapeutic concepts such as radio-chemotherapy are being applied with increasing frequency, resulting in an ever increasing need for transfusion with great effects on the patient's quality of life. Even more important to tumour patients is the role of the haemaglobin (Hb) value as a prognostic factor for survival and/or local tumour control. A large number of studies show that recombinant human erythropoietin (r-HuEPO) is effective in the treatment of tumour-induced anaemia and prevention and correction of chemotherapy and radiotherapy-induced anaemia. The simultaneous application of r-HuEPO with chemotherapy can prevent patients with head and neck tumours from developing anaemia or can reduce the extent of the anaemia and the need for transfusion. Comparable effects were observed both in patients undergoing platinum-based and non-platinum-based chemotherapy. The direct correlation between anaemia, tumour hypoxia and poor response to radio and/or chemotherapy has been clinically proven. Recombinant human erythropoietin administration improves the therapeutic outcome and the patients' prognosis.

Minimal residual disease in head and neck cancer.

Squamous cell carcinoma of the head and neck (HNSCC) is a complex disease. Patients with more advanced stages are treated with curative intent by a combination of surgery and radiotherapy, but still about 50% develop a relapse: locally, regionally and at distant sites. This clinical outcome strongly indicates that small histologically undetectable tumor deposits remain at these sites: 'minimal residual disease'. In this article the different aspects related to minimal residual head and neck cancer will be reviewed shortly. The management of patients with head and neck cancer as well as the clinical problems in diagnosis and treatment will be described. The crucial role of minimal residual disease in head and neck cancer will be defined and diagnostic approaches to address the problem will be reviewed. We argue that the infiltration and dissemination of HNSCC takes place beyond the level of histopathological detection, and further that molecular staging will at least in part fill in the gap between anatomical TNM staging and the clinical outcome. However, it is not only the presence of infiltrated or disseminated tumor cells that will determine the prognosis. Also the biological characteristics of the tumor cells at the various sites are important for the clinical follow-up. Promising therapeutic approaches to deal with minimal residual disease will be discussed shortly. Finally the issues 'field cancerization' and second primary tumors in head and neck cancer are addressed as these are closely linked to local recurrence and distant metastases. Moreover, second primary tumors will gain more importance when the primary disease and the frequency of relapses are better controlled.

Vascularization of reactively enlarged lymph nodes analyzed by color duplex sonography.

PURPOSE: This study involved a prospective evaluation of the reliability of sonography, and especially duplex sonography, in confirmation of the benign nature of enlarged cervical lymph nodes. PATIENTS AND METHODS: In 53 untreated patients with enlarged cervical lymph nodes, B-mode, plain, and d-galactose-enhanced color duplex sonography were performed. The B-mode sonomorphology was analyzed for the structure of vascularization. Quantitative parameters such as maximum flow velocity, pulsatility index, and resistive index were also assessed. The benignity of the lymph nodes was confirmed by microscopic analysis. RESULTS: The B-mode showed 20 homogeneous lymph nodes, 23 with a central echogenoic line covering less than one third, and 10 with a distinct hilus sign extending to more than one third of the lymph node diameter. Microscopically, the least fibrotic or chronic inflammatory changes in the parenchyma were observed in the homogeneous lymph nodes, whereas those with central echogeneoity had fibrotic and lipoid hilus changes. Histologically, all lymph nodes had normal afferent and efferent hilus vessels. In 37 lymph nodes, the vessel structure could be reliably visualized by both plain and enhanced color duplex sonography, whereas in 16 it could only be demonstrated after the use of signal enhancement. Nine of 53 lymph nodes had Solbiati-(L/T-) indices below 2, which were suggestive of malignancy. Quantitative flow parameters did not provide useful information. CONCLUSION: Color duplex analysis of enlarged lymph nodes is a useful method for assessment of benignity, especially after application of a signal-enhancing agent.

Camouflage in head and neck region--a non-invasive option for skin lesions.

The technique of camouflage, a non-invasive procedure to correct flaws in the texture and colour of the facial skin, is presented. The acceptance and use of camouflaging by 52 patients with different diagnoses are presented. The advantages of camouflaging are discussed in comparison to medical tattooing.

The infrahyoid flap. A technique for defect closure in the floor of the mouth, the tongue, the buccal mucosa, and the lateral pharyngeal wall.

The surgical technique, indications, and results of the infrahyoid muscle flap are presented. This flap is fed by the superior thyroid vessels and innervated by the ansa cervicalis. The flap is indicated in case of medium-sized defects in the floor of the mouth, the tongue, the buccal mucosa, and the lateral pharyngeal wall. The advantages of the technique presented include the rapid flap elevation close to the original operating field, the ability to use the motor capability of the flap, and the ability to combine it with other local flaps--for example, the platysma flap. This technique appeared to render excellent function for swallowing and speech. Safe flap grafting is possible only if the internal jugular vein is preserved.

Otoplasty: a combined approach to different structures of the auricle.

A technique for otoplasty is presented, which combines the advantages of different methods. The procedure includes a dorsal skin excision, a cartilage incision at the border between the concha and scapha, scoring of the crus superior on the anterior side, and if necessary a reduction of the conchal height and modification of the position of the cauda helicis by cartilage excision. The results of the treatment of 526 ears in 312 patients are retrospectively analysed by a patient questionnaire and a chart review.

Immunocytologic detection of isolated tumor cells in bone marrow of patients with squamous cell carcinomas of the head and neck region.

The well-documented specificity of anticytokeratin monoclonal antibodies for detection of epithelial micrometastatic cancer cells in bone marrow as a prognostic indicator inspired us to apply this approach to patients with squamous cell carcinomas (SSC) of the head and neck region. The sensitivity of the broad-spectrum anticytokeratin monoclonal antibody (mAb) A45-B/B3 used for tumor cell detection was demonstrated by immunostaining of cryostat sections from the respective primary tumors. Analysis of 31 patients with SSC revealed A45-B/B3-positive cells in 10 cases (32.3%) at frequencies of 1-207 per 1 x 10(6) mononuclear cells. Most specimens displayed isolated tumor cells, while cell clusters were found in only two cases (6.5%). The present data suggest that hematogenous dissemination of cancer cells is more frequent than expected from clinicopathologic staging of patients with SSC of the head and neck region.

Silver concentrations in human tissues. their dependence on dental amalgam and other factors.

Human tissue samples (liver, kidney cortex, 5 brain regions: grey matter of cerebrum, white matter of cerebrum, nucleus lentiformis, cerebellum, brain stem) from 173 decreased persons were analysed for silver (Ag) by GF-AAS (Graphite Furnace Atomic Absorption Spectrometry) and the results compared with the number of teeth with amalgam fillings and the concentration of inorganic mercury (Hg), which had been determined in the same tissue samples in a previous study. It was found that the mean Ag concentrations in liver and brain of adult females are approximately twice that of males. Moreover, the Ag concentrations, especially in the brain, depend possibly on age. To exclude these confounding factors as far as possible, the influence of dental amalgam and the correlation of Ag and Hg were evaluated only in a sub-group of 93 males, aged 11-50 years. In this sub-group statistically significant correlations were found between the number of teeth with dental amalgam and the Ag concentrations in the cerebral cortex and the liver. No such correlation was found for the kidney. Ag and inorg. Hg correlate well in this sub-group in the liver, but not in the cerebral cortex or the kidney. Individuals from this sub-group with (i) 0-2 and with (ii) more than 9 teeth with amalgam fillings show mean Ag concentrations (micrograms/kg in tissue wet weight, geom. mean) of 1.59 and 5.41 in the grey matter of cerebrum, 1.42 and 4.25 in the white matter of cerebrum, 1.53 and 4.89 in the nucleus lentiformis, 1.95 and 5.02 in the cerebellum, 1.05 and 3.27 in the brain stem, 3.40 and 8.15 in the liver and 0.42 and 0.44 in the kidney cortex. In contrast, comparing all individuals under investigation with only 0-2 teeth with amalgam no correlation between Ag and inorg. Hg could be found in liver, kidney cortex or cerebral cortex. These results show that amalgam fillings release Ag as well. Considering the different toxicokinetics of Ag and Hg it can be concluded that Ag is a reliable marker for the fact that the elevated concentrations of inorg. Hg found in tissues of individuals with amalgam fillings derive mainly from these fillings and not from other theoretically possible sources.

[Prospective comparative randomized study of tooth apex resection and orthograde root filling with Guttapercha and titanium pins]. / Prospektive randomisierte Studie zur Wurzelspitzenresektion und orthograden Wurzelfüllung mit Guttapercha- und Titanstiften im Vergleich.

The prospective randomised study on the root apex resections with orthograde root filling comparing Guttapercha with Titan pins encompasses 500 patients with 633 operations on all front teeth and premolars. The patients were divided into three preoperative stages so that for this broadly defined diagnoses comparable collectives could be built. After an average postoperative interval of 21 months, 258 patients with 298 resected teeth could be evaluated. From these, 188 root apex resections had been treated with Guttapercha and 110 with Titan pins. 73.5% of the root apex resections were successful, whereby the group treated with Guttapercha was more successful by 7%. The comparatively high failure rate of 26.5% is attributable to the broadly defined diagnosis and the long follow-up period.

Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow.

The emerging clinical relevance of bone marrow micrometastasis has prompted several investigations, using a variety of immunocytochemical approaches. The present study was designed to evaluate some of the variables affecting the immunocytochemical detection of individual epithelial tumor cells in bone marrow. Using an alkaline phosphatase-antialkaline phosphatase staining technique, we evaluated bone marrow aspirates from 358 patients with primary carcinomas of the breast (n = 150), lung (n = 66), prostate (n = 42), or colorectum (n = 100). Individual tumor cells in cytological preparations were detected with monoclonal antibody (MAb) CK2 to the epithelial cytokeratin component 18 (CK18), which has been validated in extensive clinical studies. In addition, the utility of the broad-spectrum MAb A45-B/B3 was explored in this study. The high specificity of MAbs CK2 and A45-B/B3 was supported by analysis of bone marrow from 75 noncarcinoma control patients and by double-marker analysis with MAbs to mesenchymal marker proteins (CD45 and vimentin). In contrast, MAbs E29 and HMFG1, directed to mucin-like epithelial membrane proteins, cross-reacted with hematopoietic cells in 26.7-42.7% of all samples tested. The majority of the 154 positive samples (43.0%) from cancer patients displayed less than 10 CK18-positive cells per 8 x 10(5) marrow cells analyzed. The detection rate, however, was affected by blood contamination of the aspirate, the number of aspirates analyzed, and the number of marrow cells screened per aspiration site. Comparative immunostaining of bone marrow specimens with MAbs CK2 and A45-B/B3 indicated that downregulation of CK18 in micrometastatic carcinoma cells occurs in about 50% of the 172 samples analyzed, regardless of the primary tumor origin.(ABSTRACT TRUNCATED AT 250 WORDS)