Coagulation effects of a recently developed hydroxyethyl starch (HES 130/0.4) compared to hydroxyethyl starches with higher molecular weight.

BACKGROUND: Hydroxyethyl starches (HES) are known to interfere with blood coagulation according to molecular weight, the degree of substitution and the C2/C6 ratio. A recently developed low molecular hydroxyethyl starch (HES 130/0.4) was designed to reduce the blood compromising potency. METHODS: In this study, effects of a 30% in vitro haemodilution with the new HES preparation (HES 130/0.4) in comparison to HES 200/0.5, HES 450/0.7 and sodium chloride solution were investigated using intrinsic and extrinsic activated thrombelastography (TEG) and plasmatic coagulation tests. RESULTS: Whereas plasmatic tests revealed no prolongation of coagulation by HES in comparison to sodium chloride, the TEG variables clotting time, clot formation time and maximal clot firmness showed a significant (P<0.05) inhibition by all the HES preparations. The inhibition was most pronounced in HES 450 (P<0.05 vs HES 130) while HES 130 did not show a statistically significant difference in extrinsic activated maximal clot firmness when compared to sodium chloride. CONCLUSION: These in vitro results demonstrate that hydroxythyl starches especially compromise clot polymerisation. The new preparation HES 130/0.4 seems to inhibit platelet function to a lesser extent than hydroxyethyl starch preparations with a higher molecular weight and degree of substitution.

Cisplatinum and interstitial laser therapy for advanced head and neck cancer: a preclinical study.

BACKGROUND AND OBJECTIVE: Direct intratumor injection of cisplatinum (CDDP) and laser therapy were tested for improved treatment of squamous cell carcinoma (SCCA). STUDY DESIGN/MATERIALS AND METHODS: Human SCCA tumors were grown as s.c. transplants in nude mice and injected with CDDP (0.4-1.2 mg/gm) in water or in collagen-based gel carrier with epinephrine (epi-gel), followed by interstitial laser therapy (ILT) via 0.6 mm fiberoptics (532 nm/300 J). RESULTS: Tumors injected with CDDP epi-gel exhibited a partial response with 2-4-fold tumor growth delay, compared to aqueous drug or untreated SCCA transplants during 10-week follow-up. Combined drug and laser therapy significantly decreased tumor volume with recurrence in only 25% (2/8) of animals tested, compared to 66% tumor regrowth (10/15) after ILT alone. CONCLUSION: These initial results suggest laser chemotherapy may become an effective treatment for advanced head and neck cancer.

MRI-guided laser interstitial thermal therapy (LITT) of head and neck tumors: progress with a new method.

A less invasive method for treatment of tumors is being tested based on interstitial photothermal ablation via infrared Nd:YAG laser fiber optics. The technique can be applied safely and effectively for therapy of common tumors in humans. In the current study five patients were treated by interstitial laser palliation with the Nd:YAG laser using special fiberoptic applicator tips, which distribute laser energy efficiently throughout the tumor volume. Magnetic resonance imaging (MRI) scanning was employed to locate the tumor, position the fibers correctly, and monitor the development of thermal necrosis in the tumors. Two patients were diagnosed with adenoid cystic carcinoma of the paranasal sinuses, one with a recurrent carcinoma of the tongue and oropharynx, one with a recurrent carcinoma limited to the oropharynx, and one patient with a carcinoma of the epi- and oropharynx. The maximum follow-up without recurrence was 2 years in a patient with an adenoid cystic carcinoma tumor of the paranasal sinuses. There were no immediate or delayed complications. Anatomical structures including eyes, brain, and important vessels were recognized by MRI during laser therapy. MRI-guided interstitial laser photothermal ablation appears to be a safe and effective method for treatment of selected tumors of the head and neck region with particular applications in palliation of inoperable tumor recurrences.

Fluorescence imaging and spectroscopy of 5-aminolevulinic acid induced protoporphyrin IX for the detection of neoplastic lesions in the oral cavity.

BACKGROUND: Semiquantitative fluorescence measurements following topical application of 5-aminolevulinic acid (5-ALA) in 16 patients with neoplastic lesions of the oral cavity were performed. METHODS: Time course and type of porphyrin accumulation were analyzed in neoplastic and surrounding healthy tissue by measuring emission spectra of 5-ALA-induced protoporphyrin IX fluorescence. Fluorescence images in the red and green spectral range from the tumor tissue were recorded with a charge-coupled device camera. RESULTS: Protoporphyrin IX fluorescence was detected in the oral mucosa of all patients after local application of 5-ALA. Protoporphyrin IX in neoplastic tissue accumulated earlier in comparison with the surrounding normal tissue. The maximum fluorescence contrast of 10:1 between tumor and host tissue was generally seen 1-2 hours after application, allowing a demarcation of tumor tissue even with the naked eye. CONCLUSION: Labeling of mucosal lesions of the oral cavity with Protoporphyrin IX fluorescence induced by the local application of 5-ALA seems to be a promising diagnostic procedure for neoplastic lesions that are difficult to visualize under white light examination. It is the aim of further investigations to evaluate the relevance of this new diagnostic procedure as a noninvasive and sensitive method for patients with oral cancer.

Photodynamic treatment for cancers of the head and neck.

A clinical study using photodynamic therapy (PDT) for the treatment of head and neck cancer was conducted between 1988 and 1994. 83 patients with Tis-2 tumors of the face, oropharynx and larynx were included into the study protocol. The study was designed in accordance with the GCP-guidelines as a prospective controlled protocol. At 48 h after an intravenous injection of 2 mg kgbw-1 Photosan-3 the laser illumination (630 nm) of the tumor and tumor-surrounding tissue was performed at 100 mW cm-2 and 100 J cm-2. A control biopsy from the former tumor area was taken 2 months after PDT to evaluate the histological response of the treated tumors. 51 out of 57 patients with basal cell carcinoma, 6 out of 7 patients with squamaous cell carcinoma of the skin, 6 out of 7 patients with oropharynx carcinoma and 11 out of 12 patients with larynx carcinoma showed a complete histologically confirmed response to the tumor following a single course of PDT over a follow up time of 13-71 months.

[Photodynamic diagnosis of neoplasms of the mouth cavity after local administration of 5-aminolevulinic acid]. / Photodynamische Diagnostik von Neoplasien der Mundhöhle nach lokaler Applikation von 5-Aminolävulinsäure.

BACKGROUND: The aim of photodynamic diagnosis (PDD) is the complete visualization of all neoplastic lesions in a tumorous organ after topical or systemic application of a tumor selective photosensitizer. In this investigation we performed semiquantitative fluorescence measurements following topical application of 5-aminolevulinic acid (5-ALA) in 11 patients with neoplastic lesions of the oral cavity. METHODS: Time course and type of porphyrin accumulation were analyzed in neoplastic and surrounding normal tissue by measuring emission spectra of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence at regular intervals for up to three hours following 15 min continuous rinsing of a 0.4% 5-ALA solution. After excitation with violet light of a high pressure xenon arc lamp (375-440 nm), fluorescence images in the red spectral range from the tumor tissue and the corresponding macroscopic visible tumor were recorded with a CCD camera. A quantitative analysis of the fluorescence contrast in neoplastic and surrounding tissue was performed using an optical multichannel analyzer. RESULTS: PpIX fluorescence was detected in the oral mucosa of all patients after local application of 5-ALA. PpIX in neoplastic tissue accumulated earlier in comparison to the surrounding normal tissue. The fluorescence contrast between tumor and host tissue was 10:1 and the maximum fluorescence was measured 1-2 hours following 5-ALA application. CONCLUSION: Labeling of mucosal lesions of the oral cavity with PpIX fluorescence induced by the local application of 5-ALA seems to be a promising diagnostic procedure for neoplastic lesions. Further investigations are required to assess the value of this new diagnostic procedure as a non-invasive and sensitive method for patients with head and neck cancer not only in pre- and postoperative diagnostic studies but also for a fluorescence-guided resection of tumors.

[Initial results with MRI-controlled laser-induced interstitial thermotherapy of head and neck tumors]. / Erste Ergebnisse der MRT-gesteuerten laserinduzierten interstitiellen Thermotherapie von Kopf- und Halstumoren.

Laser-induced interstitial thermo-therapy (LITT) was introduced as a minimally invasive form of therapy for tumors in different anatomic regions. However, in the orofacial region, it has not been used so far for inoperable T4 carcinomas. Since vascular and neural structures are often close to the tumor or are even involved, online monitoring of LITT is necessary. The aim of our study was to establish a method of monitoring LITT with MRI (magnetic resonance imaging) in the orofacial region. Five patients with T4 carcinomas of the orofacial region underwent LITT under anesthesia. A 1.5 T whole-body imager with a circular polarized head coil was used. Before and after the intervention, the region of interest was studied using T1- and T2-weighted sequences in axial and coronal planes, with and without contrast enhancement (intravenous Gd-DTPA). Temperature distribution was monitored with a T1-weighted 2D-FLASH (fast low angle shot) sequence. The positioning of the optical fibers was monitored with MRI. Nd:YAG laser equipment was used for laser application. The necrosis was best seen on contrast-enhanced MRI. Immediately after LITT, the outcome could be determined by MRI. We proposed that MRI-guided LITT be used for neoplasms in the orofacial region at advanced stages.

Effect of photodynamic treatment of human endothelial cells on cell volume and cell viability.

Photodynamic therapy (PDT) has yielded promising results in the treatment of malignant tumors. However, the mechanisms leading to tumor destruction during PDT are still not completely understood. In addition to effects on the microcirculation, damage to cellular structures has been observed following exposure of cells to PDT. A phenomenon preceding these events might possibly be cell swelling. We therefore studied the influence of treatment with Photofrin(R) (PF) and laser light on volume changes and cell viability of endothelial cells. Endothelial cells were obtained from human umbilical cord veins (HUVEC) by an adaption of the method of Maruyama. After subcultivation the cells were harvested and transferred as a cell suspension into a specially designed incubation chamber. Cells received either PF in concentrations of 1.5 or 3.0 mu g/ml and laser illumination 60 min post incubation (630 nm; 40 mW/cm(2), 4 Joule), PF alone, or laser treatment only. Following start of PF incubation and after phototreatment cell samples were taken for volume measurements using flow cytometry, and for studies of cellular morphology using scanning electron microscopy. Simultaneously, cell viability was monitored by the trypan blue exclusion test and the colorimetric MTT assay. Both control groups, HUVEC receiving PF or laser treatment alone, revealed constant cell volumes and cell viability during the entire course of the experiment. After PDT (60 min post-incubation) with 1.5 and 3.0 mu g PF/ml cell volume of HUVEC was increased at 15 min to 122%+/-6% and 140%+/-10% of baseline (100%), at 60 min to 152%+/-9% and 134%+/-18%, respectively (p<0.01). The number of viable cells was significantly reduced of samples treated with 1.5 and 3.0 mu g PF/ml at 15 min after PDT to 81%+/-3% and 76%+/-10% of baseline (100%), at 60 min after PDT to 32%+/-14% and 20%+/-15%, respectively (p<0.01). Scanning electron microscopy of cells exposed to PDT following 60 min incubation with Photofrin (3.0 mu g/ml) revealed significant cell damage. At the highest PF concentration HUVEC showed loss of microvilli and formation of blebs on the cellular surface. Our study demonstrates that PDT induces a significant increase in endothelial cell volume and a loss of cell viability. We suggest that swelling and damage of endothelial cells following PDT is a primary event finally contributing to cessation of blood flow and subsequent necrosis of tumors.

[Endoscopic and extracorporeal shock wave lithotripsy of salivary calculi]. / Die endoskopische und extrakorporale Stosswellen-Lithotripsie von Speichelsteinen.

Shock wave lithotripsy of salivary gland stones has become more and more efficient in the treatment of sialolithiasis during the last years. We use two different methods in our hospital: Extracorporeal shock wave lithotripsy (ESWL) and endoscopically intracorporeal lithotripsy (EISL). The results of both therapies are compatible; 60-70% could be successfully treated. The indication is different due to the localisation of the salivary gland stone. Stones that are located in the glandula or very proximal in the duct should be fragmented by extracorporeal lithotripsy. Stones located in the duct and multiple intraductal stones should be treated by the intracorporeal method. Clinical experiments showed that some salivary stones do not fragment easily. The reason is still unknown. We examined the ability of fragmentation in relation to the physicochemical analysis of the stone. The stones were examined by infrared spectroscopy. This study revealed that pure carbonate apatite stones are more difficult to destroy than stones containing some protein.

[Clinical and electron microscopy study of sudden deafness treatment with the 10% HES 200/0.5 and pentoxifylline combination]. / Klinische und elektronenmikroskopische Untersuchung zur Hörsturztherapie mit der Kombination 10% HES 200/0.5 und Pentoxifyllin.

The incidence of sudden hearing loss has increased. The pathogenetic mechanisms are still unknown, but viral infections and vascular phenomena with acute impairment of microvascular perfusion are thought to play a major role. Infusion of hydroxyethyl starch (HES) is used as a regimen to treat sudden hearing loss. In our clinic, anaphylactic reactions due to HES have not been observed so far. However, the use of HES is still discussed controversially due to long-term storage of HES molecules in tissue and due to high incidence of long-lasting pruritus. In a retrospective analysis of 118 patients treated with HES for sudden hearing loss, we observed pruritus starting in 64% of patients one to three weeks after therapy. This symptom with a duration between two weeks and four months was refractory to medical interventions. During therapy with HES improvement of hearing was observed in 75% of patients, in 62% improvement of hearing persisted still at the end of the observation period (7 months post infusionem). Light and electron microscopic assessment of human skin biopsies of one patient after treatment with HES showed storage of HES especially within dermal macrophages. Pathogenetically a pathway independent of histamin seems responsible for the induction of pruritus. Accordingly, classic antihistaminic drugs had no therapeutic effect in our patients. Dextran is used as an alternative to hydroxyethyl starch. In contrast to HES, the often mentioned higher incidence of severe anaphylactic reactions due to dextran has dramatically decreased with hapten inhibition (after preinjection of monovalent haptendextran Promit).(ABSTRACT TRUNCATED AT 250 WORDS)

[Photodynamic diagnosis and therapy of neoplasms of the facial skin after topical administration of 5-aminolevulinic acid]. / Photodynamische Diagnostik und Therapie von Neoplasien der Gesichtshaut nach topischer Applikation von 5-Aminolävulinsäure.

Topical application of 5-aminolevulinic acid (5-ALA) is a useful instrument for photodynamic diagnosis and therapy of skin tumours. Diagnostic fluorescence imaging after laser light irradiation (410 nm) revealed a high, tumour-specific fluorescence even in tumour areas not apparent prior to this examination technique. This demonstrates the possibility of photodynamic diagnosis to detect skin tumours. In the therapeutic group 8 patients with 6 solar keratoses and 12 basal cell carcinomas underwent laser light irradiation using a wavelength of 635 nm (dosage 100 J/cm2) 6 hours after topical application of 5-ALA in W/O emulsion. 2-12 hours after laser application we observed reddened tumour tissue with mild oedema, subsequently followed by a crust and epithelised within 4-6 weeks. 2 months after PDT a complete response was observed for all solar keratoses and for 10 of 12 basal cell carcinomas. Photodynamic therapy following topical application of 5-ALA may be an alternative treatment modality for skin tumours.

Use of the Draw-A-Person with conduct-disordered children.

The Draw-A-Person test was administered to 40 conduct-disordered and 40 nonconduct-disordered children and adolescents. There were 20 boys and 20 girls, ages 10 to 16 years, in each group. Two independent judges rated the drawings for presence or absence of indicators of aggressiveness that should accompany a conduct disorder, but no significant differences were found between groups or sexes.

[Damage to tumor cells by photodynamic therapy]. / Die Schädigung von Tumorzellen durch die photodynamische Therapie.

Photodynamic therapy (PDT) is a new, promising method in the treatment of cancer. To gain insights into PDT-mediated tumour destruction we studied the influence of treatment with Photofrin and laser light on changes in cell volume and cell viability. A-Mel-3 tumour cells were subjected to Photofrin or illumination with laser light, or a combination of both (PDT). Cell volume was measured by flow cytometry and cell viability by the trypan blue exclusion test for up to 60 min after PDT and the respective controls. In addition, scanning and transmission electron microscopy were performed. Tumour cells incubated in concentrations of 0.75, 1.5 and 3.0 micrograms Photofrin/ml revealed a rapid increase in cell volume to 117%, 207% and 235% 30 min after PDT and to 147%, 210% and 199% 60 min after PDT. Cell viability with 1.5 and 3.0 micrograms Photofrin/ml and laser light was reduced to 83% and 44% at 30 min after PDT and to 38% and 17% 60 min after PDT. At Photofrin concentrations of 1.5 micrograms/ml and exposure to laser light scanning electron microscopy revealed extreme loss of microvilli and formation of blebs on the cellular surface. Transmission electron microscopy showed swollen mitochondria and ruptures of the cell membrane. This study demonstrates that PDT induces a significant time-dependent and dose-related increase in tumour cell volume. We suggest that the PDT-induced swelling of tumour cells contributes to the increase of interstitial fluid pressure and to impairment of microvascular perfusion of tumours.

Photodynamic laser therapy of basal-cell carcinoma of the lid.

Photodynamic therapy (PDT) remains an experimental approach for the treatment of small, mainly superficial malignant tumors. When given intravenously, hematoporphyrin derivative (HpD) selectively photosensitizes tumor tissue. Activated by light of 630 nm wave-length, HpD leads to tumor necrosis. This paper presents the results of PDT to eyelid basal-cell carcinomas in 21 patients. All lesions primarily responded to the treatment and became necrotic. A generalized photosensitization lasting for more than 4 weeks was seen in all patients. In five patients, lid malformations due to scar formation were noted, being marked in three cases. Ten patients showed a recurrence of tumor after 3-12 months. At present, PDT has no advantage over well-established therapies for basal-cell carcinomas of the eyelid.

[Importance of increased interstitial fluid pressure in therapy of malignant tumors of the head-neck area]. / Die Bedeutung des erhöhten interstitiellen Flüssigkeitsdrucks bei der Therapie von Malignomen der Kopf-Hals-Region.

Animal experiments showed that elevated interstitial fluid pressure (IFP) is associated with poor blood supply and inadequate supply of drugs to solid tumours. IFP is approximately 0 mmHg in most normal tissues. Up to now there have been only few studies showing elevated interstitial pressure in human tumours in situ: Mammary carcinomas, cervical carcinomas and colorectal cancers have an elevated IFP. We measured IFP in squamous cell carcinomas of the head and neck region in humans using the "wick-in-needle" technique. In all lesions (n = 25), the IFP was elevated (4-39 mmHg). The IFP increased with tumour size. The highest IFP was 39 mmHg in a 26 ml tumour. These results show that squamous cell carcinomas of the head and neck region in humans have an elevated interstitial fluid pressure. The elevation of IFP associated with inadequate delivery of drugs to the interstitium of malign tumours may reduce the response to therapy.

[Photodynamic laser therapy in the field of otorhinolaryngology]. / Die photodynamische Lasertherapie im Bereich der Hals-, Nasen-, Ohrenheilkunde.

A clinical study was conducted on the application of photodynamic therapy on tumours in the head and neck region to assess the value of this new modality for superficial cancer (Tis-T2). Patients with recurrent laryngeal papillomatosis were included in a photodynamic treatment pilot study. 2 mg/kg body weight of haematoporphyrin-derivative (Photosan-3) was administered 48 hours prior to laser irradiation intravenously. The patients rooms were advised to avoid daylight for two to three weeks. Tumours of the facial skin were irradiated homogeneously by means of an optical bench. Directly after laser application we observed an extensive extravasation of the tumour tissue, whereas the surrounding normal tissue showed mild erythema. A dry crust formed subsequently, which disappeared within two weeks associated with re-epithelisation. Mucous membrane tumours showed fibrin layers in the tumour area 24 hours after laser application with selective tumour necrosis. These lesions also epithelised completely within three weeks. Scarring never occurred. Laryngeal tumours as well as laryngeal papillomas were treated by a cylindrical light applicator system and the patients admitted to intensive care unit for 24 hours after laryngoscopy because of risk of laryngeal oedema. 94 patients with tumours of the head and neck with different histological origins were treated photodynamically, as well as 21 patients with laryngeal papillomatosis. Two months after photodynamic laser treatment, controlled biopsies of the former tumour area were performed. 5 patients had a relapse during a maximum follow-up of 4.5 years. This signified a histologically confirmed full response rate of 95%, accompanied by good plastic and functional results.(ABSTRACT TRUNCATED AT 250 WORDS)

[Photodynamic therapy with hematoporphyrin derivatives in cervico-facial basaliomas and epidermoid carcinoma in stage I and II]. / Terapia fotodinámica con derivados hematoporfirínicos en los estadios I y II de basaliomas y carcinomas epidermoides de localización cervicofacial.

Cancer of the cervico-facial region often requires destructive procedures followed by complicated reconstructive surgical techniques. We have studied 77 patients with T1 and T2 head and neck cancers, who get photodynamic therapy using hematoporphyrin derivates. Biopsies taken two months after therapy revealed histologic complete responses in 95% of the cases. Additionally the cosmetic results of the photodynamic therapy were superior to conventional surgery.