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P Jichlinski

Publications and source records attributed to P Jichlinski.

At least 19 recordsLinked to original sources
PubMed2006

An open pharmacokinetic study of hexylaminolevulinate-induced photodiagnosis after intravesical administration.

BACKGROUND AND OBJECTIVES: Hexylaminolevulinate-mediated photodiagnosis of superficial bladder cancer recently gained marketing authorisation in Europe and is therefore being used increasingly, especially to visualise flat tumours such as carcinoma in situ. Although no significant adverse effects related to the drug have been reported to date, precise information with respect to the safety of this procedure in clinical practice has not yet been published. In the present study, we investigated the possible systemic absorption of different hexylaminolevulinate concentrations and characterised the adverse effects after bladder instillation. METHODS: Twelve patients with known bladder cancer received a 2-hour administration of 50 mL of phosphate-buffered saline containing 4 mmol/L, 8 mmol/L or 16 mmol/L of hexylaminolevulinate. Safety was primarily evaluated by monitoring adverse effects. Standard haematology and clinical biochemistry were assessed by the local hospital laboratory. Measurements of hexylaminolevulinate, 5-aminolevulinate and protoporphyrin IX in plasma and solution collected after instillation were performed, as were fluorescence measurements in the urothelium and the skin by using an optical fibre-based spectrofluorometer. RESULTS: No hexylaminolevulinate was found in the plasma. Furthermore, 5-aminolevulinate and protoporphyrin IX showed no significant increases in plasma after intravesical instillation of hexylaminolevulinate 4 mmol/L, 8 mmol/L or 16 mmol/L for 2 hours. This implies a very low systemic absorption at the administered doses with a hexylaminolevulinate uptake from the bladder of about 5%. Neither skin sensitivity nor adverse reactions that could be attributed to the drug were reported. Renal and liver function were not affected by the hexylaminolevulinate doses used in this study. CONCLUSION: We demonstrated for the first time that hexylaminolevulinate-mediated photodiagnosis is a safe procedure for a patient undergoing this examination, the drug being only minimally systemically absorbed after intravesical instillation. Therefore, no or only minimal adverse effects compared with those seen with conventional photosensitising agents can be expected.

Administration, Intravesical↗
PubMed2005

Urological complications in renal transplantation from cadaveric donor grafts: a retrospective analysis of 20 years.

INTRODUCTION: This study is a retrospective analysis of ureteral complications and their management from a monocenter series of 277 consecutive renal transplantations. MATERIALS AND METHODS: From September 1979 to June 1999, 277 renal transplantations (cadaveric origin) were performed in 241 patients. The ureter from the kidney graft was inserted into the bladder according to the technique of extravesical implantation described by Lich-Gregoir and Campos-Freire. The study analyzed the time of occurrence and the type of complications observed. The different procedures to restore the transplanted urinary tract are presented. RESULTS: Complications occurred in 43/277 renal transplantations (15.5%). Anastomotic urine leakage or ureteral stricture were the most frequent. The time to appearance of these complications was either short (<1 month) or late (>1 month) in a similar number of cases. Most cases were managed surgically: 33/43 cases (76.7%). The most frequent surgical repair was ureterovesical reimplantation (n=13), followed by: ureteroureteral end-to-end anastomosis (native ureter-ureter transplant, n=5); pyeloureteral anastomosis (native ureter-renal pelvis transplant, n=5); simple revision of ureterovesical implantation (n=4); resection and end-to-end anastomosis of the transplant ureter (n=2); calico-vesicostomy (graft-bladder, n=1); implantation according to Boari (n=1); pyelovesicostomy with bipartition of bladder (n=1), and pyeloileocystoplasty with detubularized ileal graft (n=1). No deaths related to any of the urological complications were reported. However, 2 consecutive vesico-renal refluxes led to the loss of the kidney graft in the long-term. CONCLUSION: The rate of complications observed in this retrospective analysis is similar to the experience of other studies, ranging from 2 to 20%. If the classical extravesical ureteral bladder implantation is to remain an attractive technique due to its simplicity, the surgical team at the training center should be aware of all the means to prevent any ureteral complications, such as the choice of another implantation technique and/or insertion of a transient ureteral stent.

Adolescent↗
PubMed2003

Comparison of aminolevulinic acid and hexylester aminolevulinate induced protoporphyrin IX distribution in human bladder cancer.

PURPOSE: Successful photodynamic therapy of epithelial cancer requires a specific photosensitization of malignant tissue. We evaluate the intensity and localization of protoporphyrin IX (PpIX) in superficial transitional cell carcinoma and nonmalignant cells of the human bladder following topical administration of its precursor, either aminolevulinic acid (ALA) or hexylester aminolevulinate (HAL). MATERIALS AND METHODS: Solutions of ALA or HAL were instilled into the bladder of 18 patients presenting with recurrent transitional cell carcinoma. The distribution of PpIX through the bladder wall was studied on frozen biopsies using fluorescence microscopy and correlated with pathological findings. RESULTS: Topical bladder instillation with 180 mmol (3%) ALA administered for 6 hours or 8 mmol (0.2%) HAL administered for 4 hours gave similar results regarding intensity and tissue distribution of PpIX fluorescence, whereas 8 mmol HAL administered for 2 hours followed by 2 hours of resting time (2+2 hours concept) induced a PpIX fluorescence twice as high. The fluorescence remained limited to cancer cells. Only a trace of PpIX fluorescence was observed in suburothelial connective tissue, that is chorion, but none in the bladder smooth muscle regardless of experiment conditions. CONCLUSIONS: HAL is an excellent precursor for PpIX synthesis in bladder cancer. With the 2+2 hour topical administration condition it yielded the highest PpIX fluorescence intensity and fluorescence contrast between normal and malignant urothelial cells. This approach allows us to optimize PpIX tissue distribution for photodynamic therapy in superficial bladder cancer.

Administration, Intravesical↗
PubMed2002

[Ureteral lithiasis, what treatment?].

Extracorporeal shock wave lithotripsy and ureteroscopy are minimal invasive techniques, both of which have definitively become essential for the treatment of ureteral stones resistant to conservative treatment. At the time of evidence-based medicine, no study makes it possible to recommend one of these methods rather than the other. For stones of identical size and location, this review of the literature shows that extracorporeal shock wave lithotripsy and ureteroscopy prove of comparable effectiveness and innocuousness. The urologist thus has two alternatives of which the technical control, the availability of the endoscopes or lithotriptors as well as the desire and comfort of the patients are the factors which condition his choice of the method for the treatment of ureteral stones.

Decision Making↗
PubMed2002

[Fluorescence cystoscopy in bladder cancer: what future?].

Bladder transitional cell carcinoma, limited to the lamina propria, or superficial in 80% of the cases, is characterized by a high recurrence rate up to 70% in the three years following the first treatment. However, the constant evolution of the endoscopic techniques, useful to its diagnosis and treatment, contributed to reduce about by half this recurrence rate at three months. The actual development concerns new fluorescence detection methods, adapted to the standard endoscopic equipment. This new technique or fluorescence cystoscopy aims at improving the visual contrast between tumor and normal tissue in order to obtain a precise mapping of the diseased bladder. Thus, it allows to detect a carcinoma in situ (CIS) with a sensitivity around 80 to 90%. Its impact on the progression of the disease remains however to be demonstrated.

Aminolevulinic Acid↗
PubMed2001

Invasive bladder carcinoma: a pilot study of conservative treatment with accelerated radiotherapy and concomitant cisplatin.

From November 1992 to December 1997, 25 patients (inoperable or refusing cystectomy) were included in a prospective study to assess the feasibility, tolerance, and curative potential of accelerated radiotherapy (RT) and concomitant cisplatin. Median age was 74 years (range 49-86). Stage distribution was as follows: 1 T1, 10 T2, 8 T3, and 6 T4. Two patients had clinically positive pelvic nodes. The goal was to deliver a total dose of 40 Gy to the whole pelvis and bladder in 4 weeks using a concomitant boost of 20 Gy to the tumor or to the whole bladder during the third and fourth weeks (total dose 60 Gy), with daily cisplatin (6 mg/m(2)) before RT for patients with creatinine clearance > 50 ml/min. All but one patient completed the RT protocol. Daily cisplatin was successfully delivered in 18 patients. One patient presented with grade III ototoxicity. Diarrhea was scored grade III in two and grade IV in two patients. Acute urinary toxicity was scored grade III in one patient. Posttreatment late effects included bladder grade II and grade III in two patients and one patient, respectively; large bowel grade III in one; urethral grade III in one; and femoral head radionecrosis in one. Four-year overall and disease-specific survival rates were 23% and 35%, respectively. The latter was 60% for patients with T2 tumors. The 4-year actuarial locoregional control rate for all patients was 61%. In summary, accelerated RT and concomitant cisplatin is feasible with acceptable tolerance even in relatively old patients. Although outcome was better for patients with low-stage tumors, local control and survival rates appeared similar to those of standard RT schedules for a similar patient population.

Aged↗
PubMed2001

Photodynamic therapy in superficial bladder cancer: past, present and future.

For many reasons, such as toxicity and lack of selectivity of photosensitisers, as well as complexity of technical procedures and inconstant therapeutic results, photodynamic therapy of highly recurrent superficial bladder cancer never gained wide acceptance in the urological community. However, the 25 years of experience combined with the recent discovery of new photosensitisers, such as protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) or ALA-derivatives or hypericin open new, very interesting perspectives in this therapeutic field.

Humans↗
PubMed2001

Radiation therapy alone or combined surgery and radiation therapy in squamous-cell carcinoma of the penis?

To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the penis, treated between 1962 and 1994, was performed. The median age was 59 years (range: 35-76 years). According to the International Union Against Cancer (UICC) 1997 classification, there were 12 (29%) T1, 24 (59%) T2, 4 (10%) T3 and 1 TX (2%) tumours. The N-classification was distributed as follows: 29 (71%) patients with N0, 8 (20%) with N1, 3 (7%) with N2 and 1 (2%) with N3. Forty-four per cent (n=18) of the patients underwent surgery: partial penectomy with (n=4) or without (n=12) lymph node dissection, or total penectomy with (n=1) or without (n=1) lymph node dissection. 23 patients were treated with radiation therapy alone, and all but 4 of the patients who were operated upon received postoperative radiation therapy (n=14). The median follow-up period was 70 months (range 20-331 months). In a median period of 12 months (range 5-139 months), 63% (n=26) of the patients relapsed (local in 18, locoregional in 2, regional in 3 and distant in 3). Local failure (stump in the operated patients, and the tumour bed in those treated with primary radiation therapy) was observed in 4 out of 16 (25%) patients treated with partial penectomy +/-postoperative radiotherapy versus 14 out of 23 (61%) treated with primary radiotherapy (P=0.06). 15 (83%) out of 18 local failures were successfully salvaged with surgery. In all patients, 5- and 10-year survival rates were 57% (95% confidence interval (CI), 41-73%) and 38% (95% CI, 21-55%), respectively. The 5-year local and locoregional rates were 57% (95% CI, 41-73%) and 48% (95% CI, 32-64%), respectively. In patients treated with primary radiotherapy, 5- and 10-year probabilities of surviving with penis preservation were 36% (95% CI, 22-50%) and 18% (95% CI, 2-34%), respectively. In multivariate analyses, survival was significantly influenced by the N-classification, and surgery was the only independent factor predicting the locoregional control. We conclude that, in patients with squamous-cell carcinoma of the penis, local control is better in patients treated with surgery. However, there seems to be no difference in terms of survival between patients treated by surgery and those treated by primary radiotherapy +/-salvage surgery, with 39% having organ preservation.

Adult↗
PubMed2001

Routine experimental system for defining conditions used in photodynamic therapy and fluorescence photodetection of (non-) neoplastic epithelia.

A common method to induce enhanced short-term endogenous porphyrin synthesis and accumulation in cell is the topical, systemic application of 5-aminolevulinic acid or one of its derivatives. This circumvents the intravenous administration of photosensitizers normally used for photodynamic therapy (PDT) of fluorescence photodetection. However, in the majority of potential medical indications, optimal conditions with respect to the porphyrin precursor or its pharmaceutical formulation have not yet been found. Due to ethical restrictions and animal right directives, the number of available test objects is limited. Hence, definition and use of nonanimal test methods are needed. Tissue and organ cultures are a promising approach in replacing cost intensive animal models in early stages of drug development. In this paper, we present a tissue culture, which can among others be used routinely to answer specific questions emerging in the field of photodynamic therapy and fluorescence photodetection. This technique uses mucosae excised from sheep paranasal sinuses or pig bladder, which is cultured under controlled conditions. It allows quasiquantitative testing of different protoporphyrin IX precursors with respect to dose-response curves and pharmacokinetics, as well as the evaluation of different incubation conditions and/or different drug formulations. Furthermore, this approach, when combined with the use of electron microscopy and fluorescence-based methods, can be used to quantitatively determine the therapeutic outcome following protoporphyrin IX-mediated PDT.

Aminolevulinic Acid↗
PubMed2000

[Percutaneous nephrostomy in treatment of urinary tract obstructions and malformations in the child].

Percutaneous nephrostomy (NP) is a routinely applied procedure in adults, but sparsely reported in the pediatric population. We report the treatment of acute obstructive renal diseases in 15 children aged one day to 6 years. The causes of obstruction included pelvi-ureteral junction stenosis (10 cases) by calculus or complicated by pyonephrosis, vesico-ureteral junction stenosis (2 cases), urethral valves and stenosis (2 cases) and one complex urogenital malformation. Catheter placement was performed under ultrasonographic guidance without immediate complication. NP should be considered as a primary preoperative modality for urinary tract obstruction in the pediatric population.

Adult↗
PubMed1999

Chromosomal abnormalities in renal cell neoplasms associated with acquired renal cystic disease. A series studied by comparative genomic hybridization and fluorescence in situ hybridization.

Sporadic renal cell carcinomas (RCCs) display different chromosomal abnormalities according to their morphology; gains of chromosomes 7 and 17 and loss of Y are commonly observed in papillary lesions, whereas loss of 3p sequences and multiple losses of specific chromosomes are found in non-papillary and chromophobe cell carcinomas, respectively. Acquired renal cystic disease (ARCD) is associated with an increased incidence of renal cell tumours, especially papillary lesions. The aim of this study was to examine a series of ARCD-related tumours for chromosomal abnormalities and to compare the findings with those abnormalities commonly observed in sporadic RCCs. Nine tumours from four patients with ARCD were examined using comparative genomic hybridization (CGH) and interphase cytogenetics. Gain of chromosomes 7 and 17 was observed in all four papillary lesions and loss of Y in three. In addition, gain of chromosome 16 was observed in three papillary tumours. Three chromophobe RCCs originating from the same kidney showed different genomic profiles; two had no abnormalities, whereas one showed loss of chromosome 17p. Two non-papillary RCCs failed to show chromosome 3p alterations. In conclusion, renal cell tumours developing in ARCD may show chromosomal abnormalities both similar to and different from those seen in sporadic tumours.

Adult↗
PubMed1999

Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study.

Exogenous administration of 5-aminolaevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of protoporphyrin IX (PpIX) in photodynamic therapy (PDT) and fluorescence photodetection (PD). Recently, results have shown that the chemical modification of ALA into its more lipophilic esters circumvents limitations of ALA-induced PpIX like shallow penetration depth into deep tissue layers and inhomogeneous biodistribution and enhances the total PpIX formation. The present clinical pilot study assesses the feasibility and the advantages of a topical ALA ester-based fluorescence photodetection in the human bladder. In this preliminary study 5-aminolaevulinic acid hexylester (h-ALA) solutions, containing concentrations ranging from 4 to 16 mM, were applied intravesically to 25 patients. Effects of time and drug dose on the resulting PpIX fluorescence level were determined in vivo with an optical fibre-based spectrofluorometer. Neither local nor systemic side-effects were observed for the applied conditions. All conditions used yielded a preferential PpIX accumulation in the neoplastic tissue. Our clinical investigations indicate that with h-ALA a twofold increase of PpIX fluorescence intensity can be observed using 20-fold lower concentrations as compared to ALA.

Aged↗
PubMed1999

Optimisation of the formation and distribution of protoporphyrin IX in the urothelium: an in vitro approach.

PURPOSE: To optimize conditions for photodynamic detection (PDD) and photodynamic therapy (PDT) of bladder carcinoma, urothelial accumulation of protoporphyrin IX (PpIX) and conditions leading to cell photodestruction were studied. MATERIALS AND METHODS: Porcine and human bladder mucosae were superfused with derivatives of 5-aminolevulinic acid (ALA). PpIX accumulation and distribution across the mucosa was studied by microspectrofluorometry. Cell viability and structural integrity were assessed by using vital dyes and microscopy. RESULTS: ALA esters, especially hexyl-ALA, accelerated and regularized urothelial PpIX accumulation and allowed for necrosis upon illumination. CONCLUSIONS: hexyl-ALA used at micromolar concentrations is the most efficient PpIX precursor for PDD and PDT.

Aminolevulinic Acid↗
PubMed1998

Persistence of parvovirus B19 DNA in testis of patients with testicular germ cell tumours.

Germ cell tumours (GCT) of the testis are the most common malignant tumours occurring in young adults. In view of the young age of patients, the increasing incidence of GCT and the overexpression of wild-type p53 observed in a majority of tumours, the possibility of the involvement of a virus in the development of this cancer was considered. Testicular GCT were analysed for the presence of cytomegalovirus and Epstein-Barr virus (EBV), which are known to cause overexpression of wild-type p53 protein, and parvovirus B19. The testicular tissue of 39 patients with testicular GCT and 12 patients with healthy testicular tissues was tested for presence of viral DNA by PCR. Neither cytomegalovirus nor EBV DNAs were detected in the 39 tumours analysed, but parvovirus B19 DNA sequences were demonstrated in the testicular tissue of 85% (33/39 cases) of patients with GCT. The sera of 16 of the 39 patients with GCT were tested for the presence of parvovirus B19 IgM and IgG. B19-specific IgG was detected in the sera of 11 patients (69%). Only one case was positive for parvovirus B19 IgM, which was also shown to have B19 genome sequences in the serum by PCR, indicating that in a majority of cases an acute B19 infection can be excluded as being the source of the B19 DNA sequences in the testis. B19 DNA could not be detected in normal testicular tissue and thus parvovirus B19 could play a role, direct or indirect, in the development of testicular GCT or have tropism for the tumour cells.

Adolescent↗
PubMed1997

[Endoscopic treatment of pyelo-ureteral junction disease].

The advent of "minimal invasive surgery" with the development of new endoscopic techniques modified many therapeutical concepts in urology as in other fields. The treatment of the ureteropelvic junction obstruction reserved in the past to open surgery can nowadays be successfully realized with endopelvic or endoureteral techniques under visual or fluoroscopic guidance. The authors present their experience with two new techniques: antegrade endopyelotomy under visual control or retrograde fluoroscopic endopyelotomy. Based on experimental and clinical studies which demonstrated the extraordinary capacity of the incised ureter to regenerate and regain a peristaltic activity, these treatments offer a cure rate nearly as high as open pyeloplasty.

Adolescent↗
PubMed1997

[The status of urodynamic examination in urologic evaluation].

Urodynamics encompass a number of functional tests of the lower and occasionally the upper urinary tract. These tests comprise uroflowmetry, cystometry or measurement of bladder pression during bladder filling and voiding, urethral pressure profile, electromyography (EMG) of the external urethral sphincter, pressure-flow studies and video-urodynamics. Alone or in combination these examinations have become essential elements of urological clinical work-up, since they do not only allow to precisely classify a functional disorder but also to establish an adequate therapy. Urodynamics are nowadays standard in any urological department.

Diagnosis, Differential↗