Hans-Juerg Leisinger

Fluorescence excitation and emission spectra of ALA-induced protoporphyrin IX in normal and tumoral tissue of the human bladder

In vivo spectrofluorometric analysis represents a tool to obtain information about fluorophore distribution in tissue. Based on a Peltier-cooled CCD we designed a fluorescence excitation and emission spectrograph which allows to obtain tissue spectra endoscopically and in a clinical environment. Clinical studies were performed on patients with positive cytology or tumor recurrence in the urinary bladder. Patients received a 50 ml instillation of 3% ALA solution at pH 5.5 during 3 to 4 hours and underwent a normal white light cystoscopic examination together with light induced fluorescence photodetection at 5 to 8 hours after the beginning of the instillation. Local fluorescence measurements with a single fiber were performed before photodetection. These showed fluorescence ratios between tumor and normal tissue of 1.5 to 20 with the strongest ratios for exophytic papillary tumors. Fluorescence excitation between 380 nm and 450 nm revealed that the higher Protoporphyrin IX (PPIX) signal on tumor tissue is accompanied by a decrease of the autofluorescence at the emission wavelength of 500 nm.

Laser lithotripsy with the Ho :YAG laser : fragmentation process revealed by time-resolved imaging

Improvements of endoscopic techniques have renewed the interest of urologists in laser lithotripsy in recent years. Laser energy can be easily transmitted through flexible fibers thereby enabling different surgical procedures such as cutting, coagulating and lithotripsy. The Ho:YAG laser offers multiple medical applications in Urology, among them stone fragmentation. However, the present knowledge of its fragmentation mechanism is incomplete. The objective was therefore to analyze the fragmentation process and to discuss the clinical implications related to the underlying fragmentation mechanism. The stone fragmentation process during Ho:YAG laser lithotripsy was observed by time resolved flash video imaging. Possible acoustic transient occurrence was simultaneously monitored with a PVDF-needle hydrophone. Fragmentation was performed on artificial and cystine kidney stones in water. We observed that though the fragmentation process is accompanied with the formation of a cavitation bubble, cavitation has only a minimal effect on stone fragmentation. Fragment ejection is mainly due to direct laser stone heating leading to vaporization of organic stone constituents and interstitial water. The minimal effect of the cavitation bubble is confirmed by acoustic transients measurements, which reveal weak pressure transients. Stone fragmentation with the Holmium laser is the result of vaporization of interstitial (stone) water and organic stone constituents. It is not due to the acoustic effects of a cavitation bubble or plasma formation. The fragmentation process is strongly related with heat production thereby harboring the risk of undesired thermal damage. Therefore, a solid comprehension of the fragmentation process is needed when using the different clinically available laser types of lithotripsy.

Usefulness of fluorescence photodetection of neoplastic urothelial foci in bladder cancer following intravesical instillation of delta-aminolevulinic acid (5-ALA)

An excellent knowledge of histopathological risk factors of superficial bladder transitional cell carcinoma is mandatory to establish the prognosis of the disease. Presence or absence of carcinoma in situ (CIS) in superficial bladder cancer is one of the most powerful risk indicators. This study examines the usefulness of fluorescence photodetection of neoplastic urothelial foci in bladder cancer following intravesical instillation of delta-aminolevulinic acid (5-ALA). Following bladder instillation of an aqueous solution of 5-ALA in 43 cases, a Krypton ion laser and a Xenon arc-lamp were successively used as excitation source of the PPIX fluorescence. Tissular samples were respectively taken during bladder wall photodetection, either by the means of a video camera, or under direct endoscopic observation. A good correlation was observed between the fluorescence findings and the histopathological diagnosis. On a total of 298 biopsies, 49/110 carcinomatous lesions were detected by the fluorescence, whose more than 36% were CIS. PPIX induced fluorescence with topical bladder instillation of 5-ALA is an efficient and useful method of mapping the mucosa in bladder carcinoma. Moreover, in case of a multifocal disease, this method seems very helpful in finding and treating any residual malignant spots at the end of a transurethral bladder resection.

Fluorescence imaging photodetection of early cancer in the bronchi with mTHPC and in the bladder with ALA-induced protoporphyrin IX: preliminary clinical results

Clinical results obtained endoscopically with an imaging fluorescence photodetection apparatus based on the use of one excitation wavelength and detection of the fluorescence emission performed in two separate spectral windows are presented. Early cancer photodetection of micro-invasive and in situ carcinoma of the bronchial mucosa after intravenous injection of meso-tetrahydroxyphenylchlorin (m-THPC) was performed during sessions involving photodynamic therapy. Preliminary results are also presented in the context of detecting transitional cell carcinoma of the bladder performed by fluorescence imaging photodetection of protoporphyrin IX (PPIX) following topical application of 5-delta aminolevulinic acid (ALA).

Urethral stricture vaporization with the KTP laser provides evidence for a favorable impact of laser surgery on wound healing

The objective of this study was to evaluate and compare the safety and efficacy of the KTP 532 laser to direct vision internal urethrotomy (DVIU) in the management of urethral strictures. A total of 32 patients were randomized prospectively in this study, 14 DVIU and 18 KTP 532 laser. Patients were evaluated postoperatively with flowmetry and in the case of recurrence with cystourethrography at 3, 12, 24 weeks. With the KTP 532 laser complete symptomatic and uredynamic success was achieved in 15 (83%) patients at 12 and 24 weeks. Success rate was lower in the DVIU group with 9 (64%) patients at 12 weeks and 8 (57%) patients at 24 weeks. Mean preoperative peak-flow was improved from 6 cc/s to 20 cc/s at 3, 12 and 24 weeks with the KTP laser. With DVIU mean preoperative peak-flow was improved from 5.5 cc/s to 20 cc/s at 3 weeks followed by a steady decrease to 13 cc/s at 12 weeks and to 12 cc/s 24 weeks. No complication was observed in either group of patients. Our results confirm that stricture vaporization with the KTP 532 laser is a safe and efficient procedure. The better results after laser surgery make it also a valuable alternative in the endoscopic treatment of urethral strictures. These findings suggest a favorable influence of laser surgery on wound healing with less wound contraction and scarring. The lack of contraction of laser wounds might be related to the absence and the lack of organization of myofibroblasts in laser induced lesions.

Wound repair in rat urinary bladder following electrocautery or holmium laser incision

Woundhealing is a complex phenomenon which varies according the type of tissue but is also depending from the type of tissue injury. Electrocautery mainly induces coagulation necrosis while thermal damages induced by the Holmium laser primarily lead to tissue vaporization which may induce less tissue injury. The aim of this study was to evaluate the healing process of the Holmium laser induced lesions compared to electrocautery induced lesions in urothelial tissue by assessing the inflammatory response and myofibroblast behavior in sequential healing phases. A surgical wound was created in the urinary rat bladder of 32 rats either by electrocautery or by laser (N=16). The inflammatory response, the total lesion depth and the myofibroblast activity during woundhealing was then analyzed on a qualitative basis on days 0/2/4/8. The overall inflammatory response was comparable in both groups up to days two and four. However, at day eight less cellular inflammatory reaction and less myofibroblast activity was found in the specimen of lesions created by the Holmium laser. These results suggest that wound repair may be a less invasive process after Holmium laser than electrocautery.

Combination of thermocoagulation and vaporization using an Nd:YAG/KTP laser versus TURP in BPH treatment: results of a multicenter prospective study

Laser treatment of BPH as minimally invasive therapy has found wide employment in the last few years. The objective here was to study the effects of combined technique of coagulation and vaporization with an Nd:YAG/KTP laser on BPH compared to TURP. Thirty-eight patients presenting symptomatic BPH were randomized and treated either by a laser coagulation/vaporization using an ADD fiber at settings of 40 - 60 W for the Nd:YAG and of 36 W for the KTP alike in 21 cases or by TURP in 17 cases. Symptom score, uroflow and residual urine were assessed preoperatively at 1, 3, 6 and 12 months. No transfusion in any group. Similar postoperative catheterization time. Treatment failure in 2 TURP patients and in 2 laser patients. Comparing AUA score, Qmax and residual urine, both forms of treatment were similar at 1 year. Nd:YAG/KTP laser is equivalent to TURP at 1 year for around 40 g prostates.

Treatment of urethral strictures with the KTP 532 laser

The objective of this study was to evaluate and compare the safety and efficacy of the KTP 532 laser to direct vision internal urethrotomy (DVIU) in the management of urethral strictures. A total of 32 patients were randomized prospectively in this study, 14 DVIU and 18 KTP 532 laser. Patients were evaluated postoperatively with flowmetry and in the case of recurrence with cystourethrography at 3, 12, 24 weeks. With the KTP 532 laser complete symptomatic and urodynamic success was achieved in 15 (83%) patients at 12 and 24 weeks. Success rate was lower in the DVIU group with 9 (64%) patients at 12 weeks and 8 (57%) patients at 24 weeks. With the KTP mean preoperative peak-flow was improved from 6 cc/s to 20 cc/s at 3, 12 and 24 weeks. With DVIU mean preoperative peak-flow was improved from 5.5 cc/s to 20 cc/s at 3 weeks followed by a steady decrease to 13 cc/s at 12 weeks and to 12 cc/s 24 weeks. No complications were observed in either group of patients. Our results confirm that stricture vaporization with the KTP 532 laser is a safe and efficient procedure. It thus represents a valuable alternative in the endoscopic treatment of urethral strictures.