Osteoporosis therapy in patients with inflammatory rheumatic diseases and osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVES: The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. MATERIALS AND METHODS: A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. RESULTS: Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. CONCLUSION: Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.

Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC).

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common malignancy worldwide. The past decades have not led to substantial improvement in diagnosis and therapy. Analysis of miRNA-expression may help to determine the progression profiles and outcomes of many different diseases, including HNSCC. Therefore, in this investigation, 43 formalin-fixed, paraffin-embedded (FFPE) samples of oral squamous cell carcinoma were micro-dissected, analysed for expression of 30 miRNAs and were compared with non-tumorous tissue. Furthermore, correlation analysis was performed, investigating possible correlations of miRNA-expression and patient or tumour-linked data, such as age, sex, tumour stage and size. miRNA extraction from FFPE samples functioned well for OSCC, and several miRNAs were differently expressed in tumours compared with non-tumorous tissue (i.e., miR-99*; miR-224; miR-205*), indicating their possible utility as biomarkers. Moreover, some miRNAs showed significant correlations with clinical and pathological data (e.g. tumour size: miR-3156, P = 0.033; T-stage: miR-212, P = 0.0009).

Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma.

MAGE-A proteins are highly expressed in oral squamous cell carcinoma (OSCC) and are promising targets for cancer immunotherapy. This study examined the presence of MAGE-A expression within the tumor center (TC) and tumor invasive front (TIF) and evaluated its relationship to poor prognosis. The expression rate of each MAGE-A subtype, A1-A12, was examined in 68 OSCCs at the TIF and TC. Slides (1-µm) of tissue microarrays (diameter =0.6 mm) were immunohistochemically stained, and the findings were correlated to clinical data. Approximately 95% of the tumors had MAGE-A expression. Higher expression in the TC was shown significantly for MAGE-A1, -A5, -A6, -A9 and -A12 (P<0.05). MAGE-A2 and -A3 exhibited the opposite behavior (not significant, P>0.05). Age, tumor size, grade and survival time were not associated with the expression of certain MAGE-A subgroups. When expression in the whole tumor tissue was considered, only MAGE-A1 was expressed at a significantly higher rate in male patients (P=0.034). At the TIF, MAGE-A9 and the UICC disease stage were significantly correlated (P=0.0263), and MAGE-A6 and the UICC disease stage exhibited a strong trend (P=0.0596). The expression of MAGE-A3, -A4, -A5, -A9 and -A11 was significantly associated with lymph node metastasis, while MAGE-A4 was expressed in all regions of the tumors (TIF and TC). This study showed that higher expression of most MAGE-A antigens occurred at the TC rather than at the TIF. MAGE­A1, -A3, -A4, -A5, -A9 and -A11 were significantly associated with clinically advanced stages of disease and seem to be of particular interest.

Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas.

OBJECTIVES: Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors. MATERIALS AND METHODS: This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS. RESULTS: In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient's age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13. CONCLUSION: Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs. CLINICAL RELEVANCE: The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.

Performance of cone beam computed tomography in comparison to conventional imaging techniques for the detection of bone invasion in oral cancer.

Detecting bone invasion in oral cancer is crucial for therapy planning and the prognosis. The present study evaluated cone beam computed tomography (CBCT) for detecting bone invasion in comparison to standard imaging techniques. A total of 197 patients with diagnoses of oral cancer underwent CBCT as part of preoperative staging between January 2007 and April 2013. The sensitivity, specificity, and accuracy of CBCT were compared with panoramic radiography (PR), multi-slice computed tomography (CT) or magnetic resonance imaging (MRI), and bone scintigraphy (BS) using McNemar's test. Histopathology and clinical follow-up served as references for the presence of bone invasion. CBCT and BS (84.8% and 89.3%, respectively), as well as CBCT and CT/MRI (83.2%), showed comparable accuracy (P = 0.188 and P = 0.771). CBCT was significantly superior to PR, which was reconstructed based on a CBCT dataset (74.1%, P = 0.002). In detecting bone invasion, CBCT was significantly more accurate than PR and was comparable to BS and CT/MRI. However, each method has certain advantages, and the best combination of imaging methods must be evaluated in prospective clinic trials.

Correlation of MAGE-A tumor antigens and the efficacy of various chemotherapeutic agents in head and neck carcinoma cells.

OBJECTIVES: The present study examined the relationship between MAGE-A tumor antigens and the efficacy of diamindichloridoplatin (DDP), 5-fluorouracil (5-FU), docetaxel, and paclitaxel for in vitro treatment of head and neck cancer. METHODS: In the present study, five cell lines of human squamous cell carcinomas were treated with DDP (25-400 µM), 5-FU (0.75-12 mM), docetaxel (1.56-25 nM), and paclitaxel (1.56-25 nM) for a period of 24 or 48 h. The efficacy of the agents was observed dynamically using real-time cell analysis. Subsequently, the expression levels of MAGE-A1, MAGE-A5, MAGE-A8, MAGE-A9, MAGE-A11, and MAGE-A12 were determined by quantitative real-time polymerase chain reaction. Chemosensitivity and MAGE-A-expression were correlated by linear regression. RESULTS: The tumor cell lines showed a highly differentiated response to the chemotherapeutic agents. Expression of MAGE-A11 was significantly associated with a poorer response to treatment with DDP, 5-FU, docetaxel, and paclitaxel. Two cell lines, one of which was MAGE-A11-positive, showed a significant and concentration-dependent cisplatin-induced growth spurt during the first 24 h after treatment. MAGE-A5 was connected to a positive effect on treatment with paclitaxel within the first 24 h after application. In association with docetaxel treatment, MAGE-A8 was connected to a poorer susceptibility. CONCLUSIONS: The results describe, for the first time, a correlation between these MAGE-A tumor antigens and the susceptibility of head and neck cancer cells to DDP, 5-FU, docetaxel, and paclitaxel. CLINICAL RELEVANCE: These findings could affect the antineoplastic treatment of patients with MAGE-A11-positive tumors.

Oxidative and nitrosative stress and apoptosis in oral mucosa cells after ex vivo exposure to lead and benzo[a]pyrene.

Exposure of human oral mucosa to lead (Pb) and benzo[a]pyrene (BaP) by inhalation and ingestion can lead to pathological conditions via apoptosis and oxidative and nitrosative stress. However, few studies have investigated the effects of Pb and BaP on oral mucosa cells. Furthermore, previous studies focused on chronic Pb and BaP exposure. Therefore, we evaluated important markers of apoptosis and oxidative and nitrosative stress in oral mucosa cells by incubating the cells with Pb and BaP for 5-360 min. Ex vivo samples of human oral mucosa were exposed to Pb or BaP, and immunohistochemical staining was performed to evaluate active caspase-3, 8-epi-prostaglandin F2 alpha (8-epi-PGF2a), and 3-nitrotyrosine (3-NT). Pb and BaP treatments significantly increased active caspase-3 levels in a time-dependent manner. Furthermore, the treatments induced an early increase in 3-NT level, which ceased with longer incubation times. 8-Epi-PGF2a level increased only after prolonged incubation with Pb, and this elevation was irrespective of BaP incubation duration. Smokers' samples had significantly lower levels of markers of oxidative and nitrosative stress than did nonsmokers' samples. Thus, single, short-term exposure to Pb or BaP increases the levels of apoptosis markers and markers of oxidative and nitrosative stress.

Cytocompatibility of brushite and monetite cell culture scaffolds made by three-dimensional powder printing.

This study investigated the cytocompatibility of low-temperature direct 3-D printed calcium phosphate scaffolds in vitro. The fabrication of the scaffolds was performed with a commercial 3-D powder printing system. Diluted phosphoric acid was printed into tricalcium phosphate powder, leading to the formation of dicalcium phosphate dihydrate (brushite). Hydrothermal conversion of the brushite matrices led to the formation of dicalcium phosphate anhydrous (monetite). The biocompatibility was investigated using the osteoblastic cell line MC3T3-E1. Cell viability and the expression of alkaline phosphatase served as parameters. The culture medium was analyzed for pH value, concentration of free calcium and phosphate ions and osteocalcin. Both types of scaffolds showed a considerable increase of cell proliferation and viability; the monetite matrices were a little inferior compared with the brushite ones. The activity of alkaline phosphatase showed a similar pattern. Optical and electron microscopy revealed an obvious cell growth on the surface of both materials. Analysis of the culture medium showed minor alterations of pH value within the physiological range. The concentrations of free calcium and phosphate ions were obviously different among brushite and monetite cultures, due to their different solubility. The content of osteocalcin of the culture medium was reduced by the printed scaffolds due to adsorption. We conclude that the powder printed brushite and monetite matrices have a suitable biocompatibility for their use as cell culture scaffolds. Both materials enable osteoblastic cells in vitro to proliferate and differentiate due to the expression of typical osteoblastic markers.

[Pimecrolimus (Elidel) for therapy of lichen ruber mucosae]. / Pimecrolimus (ELIDEL) zur Behandlung des Lichen planus mucosae.

Oral lichen planus (OLP) is a common chronic inflammatory disorder with criteria of auto-reactive disease. Treatment consists on topical application of corticosteroids, vitamin A derivates or cyclosporin. Calcineurin inhibitors as tacrolimus and pimecrolimus decrease the production of cytokines and inhibit T-cell proliferation. These substances have recently been introduced for local therapy of chronic inflammatory skin disorders. The aim of our study was to evaluate the effectiveness and side effects of local pimecrolimus in OLP. A group of five patients with histological proven OLP were treated with topical pimecrolimus 1% ointment twice daily to the affected area. Prior to treatment and after 7, 14, 28 and 42 days the lesions were assessed clinically and by photographs. The discomfort scores were evaluated by visual analogue scale (VAS) weekly. All five patients (median age 65.6 years) were female and showed involvement of the buccal mucosa. All lesions showed a reduction of inflammation activity during the treating period. The VAS scores decreased significantly under treatment (p=0,0014). Pimecrolimus ointment was tolerated well with no signs of itching or burning. However, 4 out of 5 patients complained about the reduced adherence properties of the cream. Although no complete remission of OLP has been observed in our series, signs of inflammatory activity of OLP as redness and burning sensations were reduced by topical pimecrolimus. Further controlled randomized studies have to be conducted to compare topical pimecrolimus with topical corticosteroid as standard therapy. The adherence properties of pimecrolimus 1% cream should be improved for intra-oral application.

Comparison of static and dynamic computer-assisted guidance methods in implantology.

The planning of dental implant position and its transfer to the operation site can be considered as one of the most important factors for the long-term success of implant-supported prosthetic and epithetic restorations. This study compares computer-assisted fabricated surgical templates as the static method with intro-operative image guided navigation as the dynamic method for transfer of three-dimensional pre-operative planning. For the static method, the systems Med3D, coDiagnostix/ gonyX, and SimPlant were used. For the dynamic method, the systems RoboDent und VectorVision2 were applied. A total of 746 implants were inserted between August 1999 and December 2005 in 206 patients. The static approach was used most frequently, accounting for 611 fixtures in 168 patients. The failure ratios within the first 6 months were 1.31% in the statically controlled insertion group compared to 2.96% in the dynamically controlled insertion group. Complications related to an incorrect position of the implants have not been observed so far in either group. All computer-assisted methods included in this study were successfully applied in a clinical setting after a certain start-up period. The indications for application of computer-assisted methods in implantology are currently given in difficult anatomical situations. Due to uncomplicated handling and low resource demands, the static template technique can be recommended as the method of choice for the majority of all cases falling into this category.

[Oral squamous cell carcinoma Retrospective analysis of therapy results and prognosis by neoadjuvant, preoperative radio-chemotherapy]. / Plattenepithelkarzinom der Mundhöhle Retrospektive Analyse der Therapieergebnisse und Uberlebensraten bei neoadjuvanter, präoperativer Radiochemotherapie.

We investigated the charts of 129 patients treated for oral squamous cell carcinoma (SCC) in the Department of Oral and Maxillofacial Surgery, University of Cologne, between 1995 and 2004. Only patients treated preoperatively with combined radio-chemotherapy (carboplatin/39.6 Gy) were included. The purpose of the present study was to show the therapeutic outcome and the survival rates for this regimen. The mean age of the patients was 56.6 years. Male patients outnumbered female patients by 3:1. The floor of the mouth was the most common location (48.1%), and three out of four tumours (76.7%) had a G2 grading, while 82.9% were keratinized. Grade T4 was most the common (53.4%), and all patients were operated after preoperative treatment. In 82.2% of the cases, there were no tumour cells detectable microscopically (R0). In 34.1% there were viable tumour cells in the cervical lymph nodes, whereas in 66.7% these cells were found in the primary tumour despite preoperative treatment. A total of 38.8% of patients showed a recurrence of SCC. Mean survival was 4.8 years and 5 year survival 46.6%. The overall survival time of the disease was significantly influenced by pT (P=0.004), pN (P>0.001), R0 resections (P=0.0002), viable tumour cells in lymph node metastasis (P=0.0001), viable tumour cells in the primary (P=0.0004) and recurrence of the disease (P>0.001). In comparison to the current literature, no improvements in prognosis and survival of oral squamous cell carcinoma could be observed.

[Neurinoma of the hard palate in an 11-year-old girl. Case report]. / Neurinom des harten Gaumens bei einem elfjährigen Mädchen. Ein Fallbericht.

BACKGROUND: Neurinomas or schwannomas are benign, encapsulated growing tumors of the Schwann cells of the nerve sheets; 25-45% are located in the head and neck region. They are found rarely in the oral cavity. Most of the intraoral schwannomas are located on the tongue. Other less common locations are the buccal mucosa, palate, floor of the mouth, gingiva and lips. The therapy of choice is complete surgical excision. CASE REPORT: An 11-year-old girl presented with a 3-month history of painless swelling of the hard palate. CT scan showed a right palatinal mass of 2 cm, reaching into the right maxillary sinus. After complete surgical excision the histological findings showed a neurinoma (Antoni type A). During a 2-year follow-up, there were no signs of recurrence. Because of the benign tumor type we considered the young patient to be healed.

[Endosonographic imaging of tumor thickness in oral squamous cell cancer and its effect on the incidence of lymph node metastases]. / Endosonographische Darstellung der Tumordicke von oralen Plattenepithelkarzinomen und deren Einfluss auf die Inzidenz von Lymphknotenmetastasen.

BACKGROUND: The correlation between increasing tumor thickness and lymph node metastases as well as reduced survival in oral cancer has been proven by several studies. In most investigations the tumor thickness was assessed in histological sections. The aim of our prospective study was to assess tumor thickness in oral squamous cell carcinoma (OSCC) by intraoral ultrasonography and to evaluate the predictive value of tumor thickness for incidence of cervical lymph node involvement and survival. PATIENTS AND METHODS: A total of 64 patients with primary carcinomas of the oral cavity (stage I-IV) were included. Endosonographic assessment of patients was carried out using a 7.5-mHz probe (Hitachi EUP F334). The primary tumor could be visualized in all cases as a hypoechoic, sometimes irregular mass. RESULTS: The average tumor thickness in all tumors was 14+/-7 mm. The N+ patients showed a greater tumor thickness (15+/-7 mm) than N0 OSCCs with 12+/-6 mm (p =0.032, t -test). Less advanced T1/T2 carcinomas revealed a tumor thickness of 10+/-5 mm in contrast to T3/T4 carcinomas with 16+/-7 mm (p <0.001, t-test). The overall survival was reduced in patients with tumors thicker than 14 mm (48.9 versus 28.3 months, p =0,0102 log rank test). CONCLUSION: Although this technique facilitates the accurate assessment of tumor thickness in OSCC, only in less advanced tumors could endosonography provide additional information, since these tumors were not visible on CT or MRT scans. Nonetheless endosonography is a fast, cost-effective, and reliable technique for assessment of tumor extent in oral cancer.

[Quality of life of patients with squamous cell carcinoma of the oral cavity]. / Die Veränderung der Lebensqualität während und nach der Behandlung von Mundhöhlenkarzinomen.

OBJECTIVE: The aim of this study was to assess the changes in quality of life during and after treatment in patients with cancer of the oral cavity. PATIENTS AND METHODS: In the period between October 1999 and September 2000, 57 patients of the Department of Craniomaxillofacial Surgery, University of Cologne, underwent surgery, radiation therapy or the combination of both for the treatment of cancer of the oral cavity. Before, during and after the therapy their quality of life was measured with two psychometric scales. RESULTS: The average loss of quality of life in the female group was less than in the male group. Younger patients suffered more than older ones did. All patients had a loss of quality of life 3 months after the beginning of the therapy. The biggest decrease was in the group of patients treated with combined therapy, and the lowest loss in the radiated group. During the assessment period of 9 months, there were significant differences between all three groups. The size of the tumor did not show any influence on the reduction of quality of life. Patients with cancer of the tongue or maxilla showed more loss of quality of life than patients with tumors located in other regions of the oral cavity. CONCLUSION: Location of the tumor, age, gender of the patient, and type of therapy influenced the quality of life, while the size of the tumor did not.

[Ampicillin and sulbactam concentrations in the irradiated mandible after oral squamous cell cancer]. / Untersuchungen zum Ampicillin/Sulbactam-Spiegel im bestrahlten Unterkieferknochen bei Patienten mit oralen Plattenepithelkarzinomen.

INTRODUCTION: Radiation therapy of the oral and maxillo-facial region increases the risk of an infected osteoradionecrosis (IORN) which is a severe complication. Therefore, perioperative antibiotics for the prophylaxis of ORN is a standard in clinical oncology. The combination therapy of ampicillin and sulbactam (Unacid) promises a good therapeutic and prophylactic outcome. PATIENTS: We compared the concentration of Unacid in bone and blood specimens of 22 irradiated patients. All patients were irradiated with 39.6 Gy prior to surgery. The specimens were obtained during the operation 3 weeks after the end of the radiation therapy. RESULTS: The concentration of ampicillin/sulbactam in the blood was 124.9/64.5 microg/ml. The bone specimens showed a concentration of ampicillin/sulbactam of 5.54/1.21 microg/g. The concentration of the antibiotic in the bone was three to four times lower than in non-irradiated patients. Nevertheless, this concentration exceeds the minimum inhibitory concentration for bacteria in the oral cavity such as streptcoccae (MHK90<0.25 microg/ml) or staphylococcae (MHK90=0.12-2.0 microg/ml). CONCLUSIONS: The results of this study suggest, that Unacid is an effective antibiotic in the prophylaxis of ORN in irradiated patients with head and neck tumors.

Primary intraosseous carcinoma of the jaws arising from an odontogenic cyst--a case report.

BACKGROUND: Squamous cell carcinoma of the jaw located purely in the bone is extremely rare. Most of these intraosseous carcinomas, also called odontogenic carcinomas are thought to arise from the epithelial lining of an odontogenic cyst. CASE REPORT: A primary intraosseous carcinoma arising from an odontogenic cyst in a 64-year-old woman is reported. No subjective symptoms were noted by the patient. Multiple retained teeth with associated presumed cystic lesions were evident in the lower jaw on a routine radiograph. Histology revealed an intraosseous carcinoma after removal of the teeth and "cystectomy". No metastasis was detected. Segmental resection of the mandible, selective neck dissection and reconstruction with an iliac bone graft was performed. The patient is free of disease after 3 years. CONCLUSION: Although primary intraosseous carcinoma is rare, this case emphasizes the importance of careful histological examination of apparently innocuous odontogenic cysts. In addition, as malignant changes in their epithelial lining are always possible, "cystic" lesions should not only be removed but as completely as possible.

[Evaluation of her-2/neu amplification/overexpression in OSCC with fluorescence in situ hybridization (FISH) and immunohistochemistry]. / Uberexpression/Amplifikation des her-2/neu-Protoonkogens in oralen Plattenepithelkarzinomen.

INTRODUCTION: The human epidermal growth factor receptor ( her-2/ neu) protooncogene encodes a membrane tyrosine kinase with homology to the epidermal growth factor receptor (EGFR). Amplification and protein overexpression have been identified in various solid tumors and a significant association with poor clinical outcome was reported. This investigation was performed to assess the frequency of her-2/ neu overexpression and to compare these results with clinical outcome in OSCC. MATERIAL AND METHODS: Archival biopsy specimens from 97 untreated OSCCs were evaluated using a polyclonal antibody A0485 (Dako). Only membrane staining intensity and pattern were evaluated according to the guidelines of the clinical trial assay recommendations (0-3+) for breast carcinoma. Score 0 and 1+ were interpreted as negative for HER-2/NEU protein overexpression and 2+ and 3+ as positive. FISH analysis with directly labeled probes for her-2/ neu and chromosome 17 was performed on the same specimens. The ratio between her-2/ neu and chromosome 17 signals was calculated after selection of 20-40 non-overlapping tumor cells. The tumor was considered amplified if the ratio was above 2. RESULTS: In 11 out of 97 biopsies (11.3%) membranous overexpression (score 2+ and 3+) of her-2/ neu was shown by immunohistochemistry. FISH analysis in 42 cases revealed amplification in 14 cases. Concordance between immunohistochemistry and FISH was found in 86%. Clinical-pathological data as well as survival revealed no correlation with her-2/ neu status. DISCUSSION: In spite of missing correlation between survival and her-2/ neu overexpression in our study, the predictive value of the her-2/ neu protooncogene in adjuvant therapy in OSCC needs further investigation.

Comparison of the in vivo efficiency of photofrin II-, mTHPC-, mTHPC-PEG- and mTHPCnPEG-mediated PDT in a human xenografted head and neck carcinoma.

BACKGROUND AND OBJECTIVE: One of the approaches to enhance the selectivity and efficiency of photodynamic therapy (PDT) was the conjugation of the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) to the water-soluble polymer polyethylene glycol (PEG). Several studies have demonstrated that mTHPC-PEG has a higher selectivity and a longer circulating half-life than free mTHPC, whereas no in vivo effect of this benefit could be seen. STUDY DESIGN/MATERIALS AND METHODS: In a model of RAG-2-mice bearing a human oral squamous cell carcinoma xenograft (XF 354), the in vivo efficiency assessed as growth retardation or remission caused by Photofrin II and free mTHPC was compared with mTHPC coupled in two different ways to polyethylene glycol (PEG). One hundred and fourty-nine female RAG-2-mice were randomised into one control group and 13 therapy groups. Treatment parameters were adapted from those routinely applied in animal studies. RESULTS: Photofrin II-mediated PDT and mTHPC-mediated PDT were both in vivo highly effective, whereas mTHPC induced less scars. The in vivo results after mTHPC-PEG-mediated PDT were disappointing, whereas the effectiveness of mTHPCnPEG-mediated PDT, a newly coupled macromolecular photosensitizer, were promising. CONCLUSIONS: These results demonstrated the impact of the method of linkage between the photoactive agent mTHPC and polyethylene glycol (PEG) upon the in vivo effectiveness. mTHPC and mTHPCnPEG are promising photosensitizers for the future, especially for the cosmetic treatment needs of head and neck surgery.

[Clinical pilot study of interstitial photodynamic therapy for treatment of advanced head and neck tumors]. / Klinische Pilotstudie zur interstitiellen photodynamischen Therapie für die Behandlung von fortgeschrittenen Kopf-Hals-Tumoren.

BACKGROUND: Photodynamic therapy is a new treatment modality which uses a photochemical reaction to destroy tumour tissue. To date this treatment has only been applied effectively to the surface of small, superficial tumours due to the limitations imposed by light penetration. With the use of fibres introduced into the substance of the tumour, more bulky lesions can be treated successfully. STUDY: We describe the first clinical use of such a treatment in the management and, specifically, the amelioration of advanced head and neck cancer. We describe our results in 12 patients, in 11 of whom we were able to improve quality of life. In one patient there was no observable effect. The side-effects were minimal. DISCUSSION: We suggest that interstitial photodynamic therapy may be of use in the palliative care of patients with advanced disease and bulky tumours. It may also be of use in benign, bulky tumors, but this point requires further study.

Photodynamic therapy of head and neck cancer.

Photodynamic therapy (PDT) is an alternative treatment option for tumours of the head and neck. The principle of PDT is based on a photochemical reaction which is initiated by light activation of a photosensitizing drug causing tumour cell death. PDT damage heals mainly by regeneration rather than scarring. Due to this organpreserving principle of PDT, important structures are maintained with very good functional and cosmetic outcome. This article will review the principle of PDT and the different indications for PDT of tumours of the head and neck, focusing on small and advanced tumours of the oral cavity and the larynx as well as papillomatosis of the larynx. A critical review on the literature will be accomplished.