[The subclavicular route for the pectoralis major myocutaneous flap]. / Der infraklavikuläre Durchzug des M.-pectoralis-major-Lappens.

BACKGROUND: The pectoralis major myocutaneous flap (PMMF) is an important reconstructive tool for lesions in the head and neck region. Using the supraclavicular route, the PMMF reliably transfers large amounts of well-vascularized skin and muscle into defects of the upper aerodigestive tract. However, limited length and arc of rotation as well as excessive bulk can be problematic. PATIENTS AND METHODS: In the current study, these problems have been addressed by passing the pedicle deeply to the clavicle. Following flap harvest, the pedicle was passed in the subclavicular plane in 15 head and neck cancer patients for primary and secondary reconstruction. RESULTS: Using this route it was possible to increase the medium length of PMMF to 3 cm compared to the supraclavicular route. No total flap necrosis occurred, however, temporary complications were observed in three of 15 cases (20%)--partial flap necrosis occurred in two cases and fistula formation was observed in one case. This rate is in accordance with complication rates described for the supraclavicular route. However, in long-term follow-ups we observed a fracture of the clavicle in two patients in whom, in contrast to the others, the periostium was not only prepared posteriorly but over the whole circumference. CONCLUSIONS: The subclavicular route for PMMF increases the length and arc of rotation available for reconstruction without compromising vascular supply to a higher degree than with the conventional supraclavicular route. Furthermore, this concept decreases the bulk of the PMMF pedicle which is functionally and cosmetically favourable. Thus, the subclavicular route of PMMF is safe and allows an extension of the reconstructive possibilities.

[Argon plasma coagulation (APC) for palliative treatment of tracheostomal recurrences]. / Die palliativ-chirurgische Behandlung von Tracheostomarezidiven mit der Argon-Plasma-Koagulation (APC).

INTRODUCTION: To reduce tumor recurrences in the tracheostomal region mostly surgical measures come to the fore. PATIENTS AND METHODS: In six incurable patients with peristomal tumor recurrence, we performed nine palliative tumor reductions using argon plasma coagulation (APC). This electrosurgical non-contact technique has been described to produce effective hemostasis and favorable wound surfaces. RESULTS: In all nine procedures APC led to rapid and reliable hemostasis. Postoperative bleedings did not occur, and dry wound surfaces adjusted to the level of surrounding body contours considerably facilitated the wound aftercare. After eight of nine APC operations the immediate insertion of conventional cannulas was feasible instead of the tracheostomy tubes needed in the interim, and the patients were again able to change the cannula themselves. Two laryngectomized individuals could resume use of their voice prosthesis. CONCLUSION: APC is particularly suitable for the palliative surgical treatment of tumor recurrences in the tracheostomal region, because it helps to circumvent typical problems of conventional surgery.

Serum level and tissue expression of c-erbB-1 and c-erbB-2 proto-oncogene products in patients with squamous cell carcinoma of the head and neck.

The proto-oncogene products erbB-l (EGF-Receptor) and erbB-2 (HER-2/neu), distinct members of the epidermal growth factor receptor family, are frequently overexpressed in squamous cell carcinoma of the head and neck (SCCHN). The accumulation of these transmembrane proteins may lead to significant amounts of the respective extracellular receptor domains (ECD) that are shed from the tumour cell surface and enter blood circulation, thus representing potential serum tumour markers. For erbB-l and erbB-2, we determined the ECD serum levels with enzyme-linked immunosorbent assays and evaluated the protein expression in tumour tissue by immunohistochemistry. The present study included 49 patients (37 untreated, 12 recurrences) and the same number of age- and sex-matched healthy controls. In 24 patients ECD serum levels were determined before and 6 weeks after surgery. Mean ECD serum levels for erbB-1 and erbB-2 were 54.8+/-1.6 and 153.7+/-6.1 fmol/ml in cancer patients, and 54+/-1.5 and 147.9+/-4.5 fmol/ml in healthy controls, respectively. There was no significant difference between untreated and recurrent disease. Serum ECD follow-ups 6 weeks after surgery revealed a significant 12.3% decline of erbB-1 but no change of erbB-2 values. Immunohistochemistry showed strong staining for erbB-1 in 78% and erbB-2 in 47% of the SCCHN specimens. No correlation was detectable between receptor ECD serum levels and receptor tissue expression, tumour stage, and tumour differentiation. Hence, ECD serum levels of erbB-1 and erbB-2 are not considered to be valuable tumour markers in SCCHN.

Establishment and characterization of four cell lines derived from human head and neck squamous cell carcinomas for an autologous tumor-fibroblast in vitro model.

To study interactions between tumor cells and stromal elements, we established carcinoma cell lines as well as tumor-derived and skin fibroblast cultures from four patients with squamous cell carcinoma of the head and neck. For the characterization of the tumor cell lines we a) determined population doubling times, b) assessed morphological features by light and electron microscopy, c) investigated the expression of typical markers by immunohistochemistry, including various intermediate filaments and surface antigens, d) compared these findings with expression patterns in the respective original tumor specimens, e) evaluated p53 mutations in tumor specimens and cell lines, f) performed chromosome analysis, g) investigated the tumorigenicity in athymic mice, and h) tested the formation of both tumor and mixed tumor-fibroblast multicellular spheroids. Tumor cell cultures were considered established cell lines when maintained and passaged over a period of two years after primary explantation. The in vitro morphology of the cell lines showed well preserved characteristics of squamous cell carcinoma, and electron microscopy as well as immunohistochemistry revealed their squamous type of differentiation. All cell lines presented the same p53 genotype as the respective original tumors. Furthermore, they were successfully xenotransplanted into nude mice and formed both pure and mixed three dimensional spheroids. This experimental model allows the in vitro and in vivo investigation of various tumor-fibroblast interactions.

Immune complexes are potent inhibitors of interleukin-12 secretion by human monocytes.

We have studied the effect of immune complexes (IC) on interleukin (IL)-12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum IgG almost completely inhibited IL-12 (p70 and p40) secretion induced by interferon-gamma and lipopolysaccharide in human blood-derived monocytes. Neutralizing anti-IL-10 antibodies plus indomethacin restored IL-12 secretion in the presence of IC to a high extent, indicating that IL-10 and prostaglandin (PG) partially mediate the IC-induced inhibition of IL-12 secretion. However, neutralization of tumor necrosis factor (TNF)-alpha by specific antibodies also incompletely restored IL-12 secretion. Indeed, monocytes secrete high levels of TNF-alpha upon stimulation by IC. We found that exogenously added TNF-alpha caused a profound inhibition of monocytic IL-12 secretion in the absence of IC, again mediated via the induction of IL-10 and PG. In summary, IC inhibit IL-12 secretion via TNF-alpha-induced IL-10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell-mediated immune responses.

Antitumor activity of anti-epidermal growth factor receptor monoclonal antibodies and cisplatin in ten human head and neck squamous cell carcinoma lines.

Head and neck squamous cell carcinomas (HNSCC) frequently display increased levels of epidermal growth factor receptor (EGFR) and since the receptor is located on the cell surface, anti-EGFR antibodies appear to be suitable agents for antitumor therapy. We investigated the effect of murine EMD 55900 and rat ICR 62 monoclonal antibodies (MAb) directed against EGFR both as single agents and in combination with cisplatin. ELISA detection showed the amount of EGFR protein in HNSCC lines UM-SCC-10A, -10B, -11B, -14A, -14B, 14C, -22B and HLac 79, 8029NA, 8029DDP to range between 20 and 8100 fmol/mg protein. Compared to A431 cells, seven HNSCC lines were high and three low receptor expressors. Only low levels of TGF alpha were found in the supernatants of some untreated HNSCC lines, probably due to the consumption of TGF alpha by EGFR. Consequently, occupation of EGFR by MAb led to marked accumulation of TGF alpha in cell supernatants. Colorimetric MTT assay showed both MAbs (0.3-30nM) to have comparable dose-dependent growth inhibition which correlated with the EGFR content of the respective cell lines (p < 0.05). Using 30nM MAb, seven high receptor expressing HNSCC lines were growth inhibited by at least 20% to a maximum of 61% (mean = 38%). Combined treatment with MAb and cisplatin led to a significant decrease in cisplatin IC50 values in 5 cell lines expressing more than 1200 fmol EGFR/mg (dose modification by factor 2.1-4.1). In conclusion, anti-EGFR MAb exert direct antiproliferative activity in HNSCC lines and show additive effects in combination with cisplatin.

Immune complex-induced interleukin-6, interleukin-10 and prostaglandin secretion by human monocytes: a network of pro- and anti-inflammatory cytokines dependent on the antigen:antibody ratio.

We have used two experimental models of immune complexes to study the secretion of interleukin (IL)-10, IL-6 and their connection with the immune complex-induced synthesis of prostaglandin (PG) E2 by human monocytes in vitro. Immune complexes formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum immunoglobulins induced the release of IL-6 and IL-10 in a dose- and antigen: antibody ratio-dependent manner. Antigen-antibody complexes formed near equivalence were most effective in induction of a cytokine response. PGE2 could augment the immune complex-induced IL-6 and IL-10 secretion, but alone, did not induce cytokine secretion. IL-10 was capable of down-regulating the release of IL-6 and PGE2. Additionally, we demonstrated that endogenously synthesized IL-10 limited the immune complex-induced secretion of proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta. All three regulatory factors examined here share anti-inflammatory properties and are closely associated with the T helper type 2 (Th2) immune response. We conclude that immune complexes, besides their well-known ability no cause acute and chronic inflammation, can mediate immunosuppressive effects and influence the balance of Th1/Th2 responses.

Distinct antigen-induced cytokine pattern upon stimulation with antibody-complexed antigen consistent with a Th1-->Th2-shift.

The consequences of complexing an antigen with specific antibodies upon the antigen-induced immune response were studied with respect to secretion of interleukin-2 (IL2), interleukin-6 (IL6), interleukin-10 (IL10) and interferon-gamma (IFN gamma). We found that the tetanus toxoid antigen-induced cytokine pattern was mainly dependent on the antigen/antibody ratio. While tetanus toxoid antigen alone induced a typical Th1-like cytokine pattern with high levels of IL2 and IFN gamma, equivalent or antibody-excess immune complexes induced a marked secretion of IL6 and IL10 while failing to induce IL2 and IFN gamma secretion. As the cytokine pattern plays a crucial role in the development of specific immune responses towards infectious agents, our results indicate that immune complexes--typically occurring during the course of chronic infectious diseases--may play an important role in the modulation of immune responses. Since a shift from Th1 to Th2 immune responses has been discussed as a pathogenetic factor in HIV-induced immunodeficiency, the role of circulating immune complexes as a possible cause for this shift should be considered.

[Immune complexes induce the secretion of Th2 cytokines in human monocytes]. / Immunkomplexe induzieren die Sekretion von Th2-Zytokinen in humanen Monozyten.

Two experimental models of immune complexes were used to study the secretion of interleukin (IL)-10, IL-6, IL-1 beta and TNF-alpha by human monocytes in vitro. Immune complexes formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum immunoglobulins induced the release of IL-6 and IL-10 in a dose- and antigen: antibody ratio-dependent manner. Antigen-antibody complexes formed near equivalence were most effective in induction of a cytokine response. Additionally, we demonstrated that endogenously synthesized IL-10 limited the immune complex-induced secretion of proinflammatory cytokines tumor necrosis factor-alpha, IL-6 and IL-1 beta. IL-10 is an anti-inflammatory cytokine and closely associated with the T helper type 2 (Th2) immune response. We conclude that immune complexes, besides their well known ability to cause acute and chronic inflammation, can mediate immunosuppressive effects and influence the balance of Th1/ Th2 responses.

[Roentgenologic and nuclear medicine findings in alkaptonuric ochronosis]. / Röntgenologische und nuklearmedizinische Befunde bei der alkaptonurischen Ochronose.

In alkaptonuria, a recessively inherited disturbance of amino acid metabolism, deposits of oxydation products of homogentisinic acid result in the disease pattern of ochronosis. Due to the enhanced brittleness of the supporting and gliding tissue, ochronotic arthropathy develops at the vertebral column and later at the major joints with typical roentgenological changes especially in the intervertebral space and the intervertebral disk, as well as the adjacent vertebral bodies. The bone scintigram shows enhanced accumulation in the base and tectorial plates as well as in the adjacent sclerosing zones in the spongiosa of the affected vertebral bodies.