Towards reliable diagnostics of prostate cancer via breath.

Early detection of cancer is a key ingredient for saving many lives. Unfortunately, cancers of the urogenital system are difficult to detect at early stage. The existing noninvasive diagnostics of prostate cancer (PCa) suffer from low accuracy (< 70%) even at advanced stages. In an attempt to improve the accuracy, a small breath study of 63 volunteers representing three groups: (1) of 19 healthy, (2) 28 with PCa, (3) with 8 kidney cancer (KC) and 8 bladder cancer (BC) was performed. Ultrabroadband mid-infrared Fourier absorption spectroscopy revealed eight spectral ranges (SRs) that differentiate the groups. The resulting accuracies of supervised analyses exceeded 95% for four SRs in distinguishing (1) vs (2), three for (1) vs (3) and four SRs for (1) vs (2) + (3). The SRs were then attributed to volatile metabolites. Their origin and involvement in urogenital carcinogenesis are discussed.

Efficacy of retrograde ureteropyeloscopic holmium laser lithotripsy for intrarenal calculi >2 cm.

The objectives of this study are to assess the efficacy and safety of retrograde ureteroscopic holmium laser lithotripsy for intrarenal calculi greater than 2 cm in diameter. A total of 24 patients with a stone burden >2 cm were treated with retrograde ureteroscopic laser lithotripsy. Primary study endpoints were number of treatments until the patient was stone free and perioperative complications with a follow-up of at least 3 months after intervention. In 24 patients (11 women and 13 men, 20-78 years of age), a total of 40 intrarenal calculi were treated with retrograde endoscopic procedures. At the time of the initial procedure, calculi had an average total linear diameter of 29.75 ± 1.57 mm and an average stone volume of 739.52 ± 82.12 mm(3). The mean number of procedures per patient was 1.7 ± 0.8 (range 1-3 procedures). The overall stone-free rate was 92%. After 1, 2 and 3 procedures 54, 79 and 92% of patients were stone free, respectively. There were no major complications. Minor postoperative complications included pyelonephritis in three cases (7.5%), of whom all responded immediately to parenteral antibiotics. In one patient the development of steinstrasse in the distal ureter required ureteroscopic fragment disruption and basketing. Ureteroscopy with holmium laser lithotripsy represents an efficient treatment option and allows the treatment of large intrarenal calculi of all compositions and throughout the whole collecting system even for patients with a stone burden of more than 2 cm size.

Explosive gas formation during transurethral resection of the prostate (TURP).

Intravesical explosion during transurethral resection of the prostate (TURP) is an extremely rare event. It might be associated with various degrees of bladder injury ranging from simple mucosal tear to rupture of the bladder. It is believed that intravesical explosion occurs due to formation of explosive gases in the bladder during TURP and its admixture with air. One case of intravesical explosion during TURP resulting in complete intra- and extraperitoneal bladder rupture at our institution is described. The management of this dreaded complication involves open surgery. Although rare, this complication is preventable by taking precautions.

[Low-dose rate brachytherapy with locally integrated beta emitters after internal urethrotomy. A pilot project using an animal model]. / Low-dose-rate-Brachytherapie durch lokal integrierte Betastrahler nach Urethrotomia interna. Ein Pilotprojekt im Tierversuch.

BACKGROUND: The treatment of urethral strictures represents an unsolved urological problem. PATIENTS AND METHODS: The effect of a (32)P-coated urethral catheter in the sense of low-dose rate brachytherapy to modulate wound healing will be analyzed in an animal experiment. RESULTS: Unfortunately it is not possible to present any results because this is being studied for the first time and there are no experiences with low-dose rate brachytherapy and this form of application in the lower urinary tract. Furthermore the animal experiment will only start in the near future. Both decade-long experiences with radiotherapy to treat benign diseases and our own results of previous studies in otolaryngology and ophthalmology let us expect a significantly lower formation of urethral strictures after internal urethrotomy. CONCLUSION: This study will contribute to improving the treatment of urethral strictures as demanded in previous papers.

[Technical aspects of intraoperative assessment of treatment progress in laser lithotripsy]. / Technische Aspekte zur intraoperativen Bewertung des Behandlungsfortschritts bei der Laserlithotripsie.

BACKGROUND: During laser-induced fragmentation, differences in assessing the intraoperative results can depend on the individual characteristics of the laser system used. METHODS: Laser parameters like pulse energy and repetition rate, the penetration depth in silicon tissue, and the laser beam width on photographic paper were determined for three different clinical laser systems. RESULTS: Pulse energy and repetition rate were subject to variations depending on the laser system employed. Significant differences between the three devices were found for penetration depth in silicon and interaction. CONCLUSIONS: Further investigations to ascertain the ablation threshold and fragmentation rate can be based on these findings. Intraoperative assessment of the lithotripsy results should take technical aspects of the laser equipment, stone consistency, and the surgeon's experience into consideration.

[Diode laser. Ex vivo studies on vaporization and coagulation characteristics]. / Der Diodenlaser. Ex-vivo-Untersuchungen zu den Vaporisations- und Koagulationseigenschaften.

INTRODUCTION AND OBJECTIVES: Laser therapy of symptomatic benign prostatic hyperplasia (BPH) remains a challenge for most urologic surgeons. The main goal of laser surgery is to achieve a marked volume reduction and to decrease bladder outlet obstruction and lower urinary tract symptoms with minimal morbidity. Laser therapy encompasses a variety of techniques using different laser wavelengths, application systems, and surgical techniques to achieve contrasting tissue effects. In an in vitro animal model we compared the vaporization and coagulation effects of the potassium-titanyl-phosphate (KTP) laser, holmium:yttrium-aluminum-garnet (Ho:YAG) laser, and diode laser (980 nm). MATERIAL AND METHODS: In an in vitro model using isolated perfused porcine kidneys we investigated the vaporization, the coagulation effect, and the bleeding rate of the KTP, Ho:YAG, and diode lasers on five porcine kidneys each. The application of each laser type was standardized. The area of laser application was 1 cm x 1 cm. The KTP group received an application with 80 W, the Ho:YAG group an application with 10-30 W, and the diode group an application with 30, 60, and 100 W. Hemostasis was measured semiquantitatively. Ablation and coagulation were investigated macro- and microscopically. RESULTS: Concerning the ablation capacity, the diode laser is most effective (more than fivefold) compared to the KTP and Ho:YAG lasers but demonstrated a rather large coagulation zone of up to tenfold in comparison to the KTP and Ho:YAG lasers. Semiquantitatively, in terms of bleeding rate, all lasers were equivalent in this ex vivo model. CONCLUSIONS: Our very early and limited experience indicates that KTP (80 W) and Ho:YAG (30 W) laser application are equivalent in terms of tissue ablation capacity and coagulation in an experimental setting. The diode laser at 980 nm is superior in terms of ablation capacity but has a large coagulation zone. Concerning the bleeding rate all tested lasers are equivalent in this ex vivo model.

Micro-endoscopy of the human vas deferens: a feasibility study of a novel device in several ex vivo models.

The aim of this study was to show limitation as well as potential of micro-endoscopy techniques as an innovative diagnostic and therapeutic approach in andrology. Two kinds of custom-made micro-endoscopes (ME) were tested in ex vivo vas deferens specimen and in post-mortem whole body. The semi-rigid ME included a micro-optic (0.9 mm outer diameter [OD], 10.000 pixels, 120° vision angle [VE], 3-20 mm field depth [FD]) and an integrated fibre-optic light source. The flexible ME was composed of a micro-optic (OD = 0.6 mm, 6.000 pixels, 120° VE, 3-20 mm FD). The ex vivo study included retrograde investigation of the vas deferens (surgical specimen n = 9, radical prostatectomy n = 3). The post-mortem investigation (n = 4) included the inspection of the vas deferens via both approaches. The results showed that antegrade and retrograde rigid endoscopy of the vas deferens were achieved as a diagnostic tool. The working channel enabled therapeutic use including biopsies or baskets. Using the flexible ME, the orifices of the ejaculatory ducts were identified. In vivo cadaveric retrograde cannulation of the orifices was successful. Post-mortem changes of verumontanum hindered the examinations beyond. Orifices were identified shaded behind a thin transparent membrane. Antegrade vasoscopy using flexible ME was possible up to the internal inguinal ring. Further advancement was impossible because of anatomical angle and lack adequate vision guidance. The vas deferens interior was clearly visible and was documented by pictures and movies. Altogether, the described ME techniques were feasible and effective, offering the potential of innovative diagnostic and therapeutic approaches for use in the genital tract. Several innovative indications could be expected.

Local photodynamic therapy reduces tissue hyperplasia in an experimental restenosis model.

Local photodynamic therapy may have potential in preventing myointimal hyperplasia after angioplasty. In this study, the effect of photodynamic therapy was evaluated in an experimental model of restenosis. Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries. Animals were randomly allocated to four groups: group 1, unidirectional injury only; group 2, injury followed by local delivery of photosensitizer; group 3, injury followed by local exposure to monochromatic light; and group 4, where injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (photodynamic therapy). Seven, 14 or 21 days after treatment, all experimental vessels were excised, fixed and processed for histology. An inflammatory and myoproliferative response was observed after injury in vessels from groups 1, 2 and 3. In group 4, after injury followed by photodynamic therapy, the myoproliferative response was significantly reduced. Thus, in this study, tissue hyperplasia after unidirectional injury was effectively suppressed by photodynamic therapy.

Photodegradation of protoporphyrin-dimethylester in solution and in organized environments.

The degradation of sensitizers used in photodynamic therapy (PDT) involves photooxidation either by molecular oxygen or by oxygen intermediates which leads to hydroxyaldehyde and formyl products or to ring opening. Our investigations focused on the spectroscopic changes which protoporphyrin-dimethylester (PP) exhibits upon irradiation. As the microenvironment strongly influences the effects, we used an aprotic organic solvent, L-alpha-phosphatidylcholine dioleoyl (DOPC) liposomes and isogenic fibrosarcoma cells (SSKII) as carriers for PP. Hydroxyaldehyde product isomers develop a new absorption band centred around 670 nm and a new emission band at 676 nm. These characteristics can be used to discriminate them from formyl products and intact PP. In organic solvents, the formation of the hydroxyaldehyde products dominates. In DOPC liposomes and cells, the hydroxyaldehyde yield drops and photooxidation results in attack of the macrocycle. Time-resolved fluorescence spectroscopy of monomeric PP in an organic solvent gives a monoexponential decay time tau of 10.1 +/- 1.3 ns. Upon irradiation a second component with a decay time of 4.9 +/- 0.6 ns, resulting from the hydroxyaldehyde product, was detected. In liposomes and cells the monomeric decay time was significantly longer (15 ns) due to the altered microenvironment. Additionally, we observed in liposomes and in cells a small contribution of a short component (1 ns) which is attributed to an aggregated sensitizer species. In irradiated cells the aggregated fraction doubles, indicating a change in the microenvironment caused by the photodynamic action of the sensitizer.

Ho:YAG laser treatment of hyperplastic inferior nasal turbinates.

OBJECTIVES: Although preliminary studies about the successful use of the Ho:YAG laser in nasal turbinate surgery have been reported, no clinical study has been performed on this procedure. The aim of this prospective clinical study was to assess the long-term effect of Ho:YAG laser in the treatment of hyperplastic inferior nasal turbinates. METHODS: Eighty-five patients with nasal obstruction who did not respond to conservative medical treatment were treated with a pulsed Ho:YAG laser (wavelength of =2080 nm). Fifty-two of these patients were included in this clinical study and were followed for 1 year. RESULTS: Within the first 2 weeks, nasal obstruction was correlated to the extent of nasal crusting. Six months after laser treatment, the mucociliary function test showed no variation compared with the preoperative measurements. One year after laser treatment 77% of the patients demonstrated improved nasal airflow on rhinomanometry and questionnaire. CONCLUSIONS: Ho:YAG-laser treatment of hyperplastic turbinates can be performed as outpatient surgery under local anesthesia and offers controllable ablation of soft tissue in a short operation time with satisfactory results and excellent patient acceptance.

In vivo fluorescence kinetics of porphyrins following intravesical instillation of 5-aminolaevulinic acid in normal and tumour-bearing rat bladders.

The fluorescence kinetics of protoporphyrin IX (PPIX) following intravesical instillation of 5-aminolaevulinic acid (5-ALA) have been studied in vivo in a rat bladder tumour model. 5-ALA dissolved in NaHCO3 was intravesically instilled for 60 min in tumour-bearing and normal bladders of Wistar rats. The fluorescence was excited with the violet lines of a Kr(+)-laser and recorded in vivo by means of a fibre coupled optical multichannel analyser. The fluorescence emission bands of PPIX at lambda = 636 nm and lambda = 708 nm were detected in normal and tumorous urothelium after only 30 min. The maximum fluorescence intensity was obtained in tumorous and normal urothelium 3-4 h after instillation. The ratio of the fluorescence intensity in tumorous to normal urothelium decreased continuously from four to about two during the time range of 6 h. PPIX fluorescence following 5-ALA instillation could also be observed in kidney and liver. Fluorescence from further porphyrin species with emission bands at lambda = 617 nm and lambda = 682 nm was detected in the bladder, indicating an efflux of hydrophilic porphyrins from the hepatic pathway.

Biomodulative effects induced by 805 nm laser light irradiation of normal and tumor cells.

The influence of light emitted from a diode laser centred at lambda = 805 nm was investigated on murine skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK) and urothelial carcinoma cells (J82) in a computer-controlled irradiation chamber. Cells were treated with varying fluences between 0 and 20 J cm-2. The response was tested by analysis of the mitotic index using single cell counting after Orcein staining and proliferation index based on BrdU incorporation during DNA synthesis. While the mitotic index of C2, HCV29 and J82 cells increased at a fluence of 4 J cm-2, irradiation with fluences of 20 J cm-2 resulted in a slight decrease. ZMK tumor cells showed a decrease of the mitotic index with both fluences. No significant differences could be determined when using irradiances between 10 mW cm-2 and 150 mW cm-2. The BrdU test after irradiation showed no significant effects compared to the controls in each cell line.

Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood.

The fluorescence and photosensitivity of endogenously synthesized protoporphyrin IX (PPIX) is increasingly used for the diagnosis and treatment of malignant and certain non-malignant diseases. A selective accumulation of PPIX can be induced by application of 5-aminolevulinic acid (5-ALA), which is a precursor of PPIX in the cellular biosynthetic pathway of heme. The purpose of this study was to monitor the in vivo accumulation of PPIX in different locations of the skin after oral ingestion and to determine the pharmacokinetics of 5-ALA and PPIX in human blood plasma for various routes of application. At the same time we wanted to achieve an optimal treatment scheme but also study possible side-effects of 5-ALA administration. After oral application of 5-ALA in a concentration of 40 mg kg-1 body weight, the fluorescence intensities of PPIX in the skin showed maxima between 6.5 and 9.8 h depending on the location and decreased to values lower than 5% related to the maximum after a mean time of about 40 h. The measured absolute intensities of PPIX fluorescence varied strongly between different patients and different locations on one patient. In the plasma of blood samples, PPIX could be detected via its fluorescence for all studied routes of application with the exception of the ointment, where PPIX levels were below the detection limit of 1 microgram l-1. The highest mean concentration of 742 micrograms l-1 PPIX in the plasma was measured 6.7 h after oral application. For inhalation of 5-ALA, a mean maximum concentration of 12 micrograms l-1 could be detected 4.1 h after application, for intravesical instillation, the mean maximum concentration was found to be 1 microgram l-1 2.9 h after application. The kinetics of 5-ALA in the plasma peaked much earlier with a maximum concentration of 32 mg l-1 about 30 min. after oral administration. The 5-ALA levels did not exceed normal reference values after topical application. The results of our experiments suggest that for a systemic application of 5-ALA side-effects in sensitive patients cannot be excluded.

Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI).

Laser therapy by low light doses shows promising results in the modulation of some cell functions. Various clinical studies indicate that laser therapy is a valuable method for pain treatment and the acceleration of wound healing. However, the mechanism behind it is still not completely understood. To explore the effect of a low-power diode laser (lambda = 780 nm) on normal skin tissue, time-dependent contrast enhancement has been determined by magnetic resonance imaging (MRI). In the examinations, six healthy volunteers (four male and two female) have been irradiated on their right planta pedis (sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic resonance imaging is used to quantify the time-dependent local accumulation of Gadolinium-DPTA, its actual content in the local current blood volume as well as its distribution to the extracellular space. Images are obtained before and after the application of laser light. When laser light is applied the signal to noise ratio increases by more than 0.35 +/- 0.15 (range 0.23-0.63) after irradiation according to contrast-enhanced MRI. It can be observed that, after biomodulation with light of low energy and low power, wound healing improves and pain is reduced. This effect might be explained by an increased blood flow in this area. Therefore, the use of this kind of laser treatment might improve the outcome of other therapeutic modalities such as tumour ionizing radiation therapy and local chemotherapy.

Pharmacokinetics of 5-aminolevulinic-acid-induced porphyrins in tumour-bearing mice.

Photodynamic therapy and photodynamic diagnosis help to support efficient treatment of superficial and early-stage cancer. During the last few years, 5-aminolevulinic acid (5-ALA), a precursor of haemoglobin in the haem biosynthetic pathway, was used to stimulate endogenous porphyrin production. In the following the time dependence of 5-ALA-induced porphyrin concentration will be investigated on several tissues in an in-vivo tumour model. 5-ALA was administered intravenously at a concentration of 50 mg-1 body weight. According to a certain time schedule the animals were sacrificed and 12 different organs as well as the tumour were removed. During excitation with the violet light of a Kr+ laser, porphyrin fluorescence spectra in the range 550-750 nm could be detected on the tissue samples. The intensity of the emission spectra at lambda = 635 +/- 2 nm was taken as a measure of the porphyrin concentration. All tissues showed porphyrin fluorescence. Brightest fluorescence was found on the tumour. A maximum contrast of the fluorescence intensity between the tumour and the non-malignant organs of up to 30 was observed at 4-6 h post-injection. The kinetics of the porphyrin concentration depend on the organ. Simple mathematical models will be derived and discussed.

Magnetic resonance imaging (MRI) controlled outcome of side effects caused by ionizing radiation, treated with 780 nm-diode laser -- preliminary results.

BACKGROUND AND OBJECTIVE: Ionizing radiation therapy by way of various beams such as electron, photon and neutron is an established method in tumor treatment. The side effects caused by this treatment such as ulcer, painful mastitis and delay of wound healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become popular as a therapeutic modality for the acceleration of wound healing and the treatment of inflammation. Evidence for this kind of application, however, is not fully understood yet. This study intends to demonstrate the response of biomodulative laser treatment on the side effects caused by ionizing radiation by means of magnetic resonance imaging (MRI). STUDY DESIGN/PATIENTS AND METHODS: Six female patients suffering from painful mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35). The tissue response was determined by means of MRI after laser treatment in comparison to MRI prior to the beginning of the LLLT. RESULTS: All patients showed complete clinical remission. The time-dependent contrast enhancement curve obtained by the evaluation of MR images demonstrated a significant decrease of enhancement features typical for inflammation in the affected area. CONCLUSION: Biomodulation by LLLT seems to be a promising treatment modality for side effects induced by ionizing radiation.

[Computer-controlled laser irradiation unit for studies of light-induced processes in cell cultures]. / Computergesteuerte Laserbestrahlungseinheit für Untersuchungen lichtinduzierter Prozesse an Zellkulturen.

For the photodynamic treatment of tumours, synergistic effects of photosensitizing substances and light (today usually laser light) are used. With the aim of optimizing photosensitizing drugs and therapy, the effects of light and drug dose were studied in cell experiments. To automate and standardize such in vitro experiments, a laser irradiation chamber was developed. Cells cultured from tumour cell lines are placed on micro-titre plates or in petri dishes, together with the photosensitizer, and subsequently irradiated in the irradiation chamber with a well-defined dose of laser light of a wavelength corresponding to the absorbance of the photosensitizing agent. The plates or dishes are irradiated from below. In this way, light dose errors due to refraction from the meniscus of the cell suspension as occurs with irradiation from above, are avoided. During irradiation, speckle effects on the underside of the plates or petri dishes lead to variation in irradiation. A vibrator keeps the light transmission fibre and thus speckle pattern in motion, guaranteeing a homogeneous irradiation of the cells.

[Brain protective interstitial laser thermotherapy. Therapy of brain tumors without secondary damage]. / Gehirn schonende interstitielle Laserthermotherapie. Therapie von Hirntumoren ohne Umgebungsschäden.

The purpose of interstitial radiosurgery is to deliver a necrotizing dose of heat to an accurately defined focal area without damaging adjacent healthy brain tissue. To achieve this, heat at a temperature of 60-100 degrees C is applied via a laser fiber placed stereotactically in the center of the tumor. With the aid of thermosensitive magnetic resonance imaging (MRI), not only can the heat distribution within and around the tumor be measured during treatment, but also the extent of the lesion produced assessed. Interstitial laser thermotherapy (ILTT) performed under MRI monitoring, could become an important interdisciplinary minimally invasive treatment option for patients with brain tumors. Experimental data on the biological effects of interstitial laser therapy on normal brain tissue are not yet available, and only preliminary clinical studies investigating the effects of laser energy on brain tumors have so far been carried out. This overview presents a description of our own initial results, discusses the present state of our knowledge and current possibilities and limitations of this new treatment modality.