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J A Witjes

Publications and source records attributed to J A Witjes.

At least 19 recordsLinked to original sources

Prognostic value of p53 for high risk superficial bladder cancer with long-term followup.

PURPOSE: The risk of muscle invasive disease in a high risk patient with superficial bladder cancer is up to 50%. Identifying patients at risk for progression remains an unsolved problem. A suggested prognosticator is mutations in the p53 tumor suppressor gene. We determined the value of p53 mutation, as demonstrated by mutation analysis, in a clinically selected group of high risk patients with superficial bladder cancer. MATERIALS AND METHODS: p53 Mutation analysis was performed by automated sequencing of bladder wash samples of 105 patients with high risk superficial bladder cancer. The mutation and WT groups were subsequently compared with regard to mortality, progression, disease worsening and the recurrence-free period. RESULTS: A total of 29 patients had a mutation and 76 had WT. Median followup was 58.3 months (range 3 to 161). A total of 13 patients died of bladder cancer, including 6 of 29 with a mutation and 7 of 76 patients in the WT group. p53 Mutation had no significant prognostic value for decreased survival, progression or disease worsening. Recurrence-free survival was significantly lower in the WT group. CONCLUSIONS: We observed a trend toward a worse clinical outcome in high risk patients with a p53 mutation in the bladder wash. However, no significant differences were seen in clinical outcome parameters. Based on these data we conclude that the prognostic value of a p53 mutation is insufficient for individual policy making.

DNA Mutational Analysis↗

[Treatment of testicular cancer clinical stage I: watchful waiting, radiotherapy, chemotherapy or surgical intervention].

Micrometastasis in the retroperitoneal lymph nodes is seen in 20% of patients with a seminoma in clinical stage I and in 30% of patients with a nonseminoma in clinical stage I. It is not possible to detect micrometastases. Nearly all patients recover from the illness irrespective of the treatment choice. This is based on the patient's wish, the doctor's preference, local expertise and risk factors for dissemination. In the case of a seminoma, treatment consists of regular checks ('watchful waiting'), radiotherapy or chemotherapy. In the case of a non-seminoma in clinical stage I without vascular impingement the risk of micrometastases in the retroperitoneal nodes is 15%. Standard treatment consists of watchful waiting. The options 'retroperitoneal lymph node dissection with, in the case of positive nodes, chemotherapy' and 'primary chemotherapy' result in more excessive treatment, but less uncertainty in patients. In the case of a non-seminoma in clinical stage I with vascular impingement, the risk of micrometastases is 50%. Standard treatment in this case consists of watchful waiting or retroperitoneal lymph node dissection with chemotherapy, if necessary, in case of positive lymph nodes. Another option is primary chemotherapy.

Humans↗

False-positive lesions detected by fluorescence cystoscopy: any association with p53 and p16 expression?

To determine p53 and p16 status as molecular markers of bladder cancer, in histologically proven benign bladder biopsies, obtained from lesions suspect for malignancy as judged by fluorescence cystoscopy. Immunohistochemical (IHC) staining was performed for p53 and p16, using the antibodies DO-7 and AB-4, respectively. The tissue sections were scored in percentages of nuclear staining for p53 and p16. Of 247 biopsies, 41/49 lesions appeared suspicious on fluorescence cystoscopy, but were histopathologically benign. 2/40 (5%) were > or =20% p53 positive as compared to 7/128 (5.5%) of all histopathologically benign biopsies. 24/37 (64.9%) were p16 negative (<5% positive cells) as compared to 84/125 (67.2%) of all benign biopsies. Most biopsies had a moderate to high degree of chronic cystitis. False positive lesions of fluorescence cystoscopy did not differ from benign lesions detected by standard white light cystoscopy with regard to p53 and p16 immunoreactivity. Little evidence remains for these lesions to be pre-malignant.

Adult↗

Sperm integrity pre- and post-chemotherapy in men with testicular germ cell cancer.

BACKGROUND: While (partial) recovery of spermatogenesis, observed by means of standard semen analysis, has been seen in testicular cancer patients after chemotherapy with cisplatin, sperm genomic integrity and its implication for the patient's fertility are poorly understood. METHODS: Semen and serum from 22 patients treated for testicular cancer were analysed pre- and post-chemotherapy. Besides routine semen analysis, sperm samples were evaluated by computerized karyometric image analysis (CKIA), chromomycin-A3 assay (CMA3, chromatin condensation) and TdT-mediated dUTP nick-end labelling assay (TUNEL, DNA damage). Serum FSH, LH and testosterone concentrations were measured. RESULTS: Ejaculate volume decreased post-chemotherapy (P<0.05). External sperm characteristics (CKIA morphometry) and sperm counts did not deteriorate after chemotherapy. An improvement in DNA condensation was assessed after chemotherapy (37 versus 50% and 47.5 versus 63.7% for CMA3 and CKIA respectively; both P<0.005); yet a high percentage of TUNEL-positive sperm was found in the samples (21 versus 25% for pre- and post-chemotherapy samples respectively). These values were significantly higher than those of a convenience sample of normozoospermic males attending pre-IVF screening. Serum FSH and LH (IU/l) increased after chemotherapy compared with pretreatment levels (8.1 versus 16.7 and 4.5 vs 6.8; both P<0.05, respectively). CONCLUSIONS: Despite the improvement in sperm chromatin packaging after chemotherapy, an abnormally high percentage of DNA-damaged sperm was found in these samples. As sperm quality does not reach normal levels after treatment, it remains difficult to outline the best strategy and guidance concerning fertility potential of testicular cancer patients.

Adult↗

Review pathology in a diagnostic bladder cancer trial: effect of patient risk category.

OBJECTIVES: Bladder cancer pathologic features are a continuous spectrum from benign to invasive lesions, causing diagnostic difficulties. Review pathology might be an answer, but appears to be of limited value. We studied the effect of patients' risk profile on the value of review pathology. METHODS: We used three Phase III multicenter studies that assessed the value of hexaminolevulinate fluorescence cystoscopy on diagnosis and management. Two studies (Europe and United States) included patients at high risk of carcinoma in situ (CIS), the third study (Europe) included all patients at risk of bladder cancer. Tumors and biopsies were examined by a local and review pathologist. RESULTS: The percentage of patients with CIS was high in the first two studies (20.6% and 15.9%) compared with the epidemiologic data (7.9%) and the third study (7.8%). The numbers of patients (specimens) in the three studies were 209 (927), 277 (986), and 142 (553). Overall conformity for both grade and stage was between 50.5% and 56.6%, comparable to published data. Although conformity was best in the high-risk study, this was predominantly because of the better conformity in low-risk tumors. Conformity in Stage T1, CIS, and invasive tumors was low. The results from Europe and the United States were comparable, although the local pathologist in the United States tended to overstage or overgrade. CONCLUSIONS: Although histologic conformity was greater in the high-risk patient population, this was mainly a result of pTa tumors. The diagnosis of pT1, CIS, and invasiveness appears difficult. Because these tumors significantly influence therapy, review pathology in patients at high risk or suspicious for high risk should be considered.

Carcinoma in Situ↗

Evaluation of chemotherapy with magnetic resonance imaging in patients with regionally metastatic or unresectable bladder cancer.

OBJECTIVES: To determine whether the failure of chemotherapy in patients with regionally metastatic or unresectable transitional cell carcinoma (TCC) of the bladder can be predicted early in the course of chemotherapy with magnetic resonance (MR) imaging. METHODS: In this prospective study, 36 patients with regionally metastatic or unresectable TCC of the urinary bladder underwent MR imaging before and after two, four, and six cycles of chemotherapy with Methotrexate, Vinblastine, Adriamycin (doxorubicin) and Cisplatin (MVAC). The response after two cycles of MVAC was evaluated by using conventional tumour size parameters with unenhanced MR imaging and with changes in the time to the start of tumour or lymph node enhanced at fast dynamic contrast-enhanced MR imaging. The results obtained with these techniques were compared with the findings at histopathology in cystectomy or transurethral resection specimens that were obtained after chemotherapy. Duration of survival was defined as the time from the start of chemotherapy until disease-specific death. Kaplan-Meier curves were drawn to determine the difference in prognosis between responders and nonresponders. RESULTS: After two cycles of chemotherapy, the accuracy, sensitivity, and specificity in distinguishing responders from nonresponders with conventional MR imaging were 69%, 81%, and 50%, respectively. With the fast dynamic contrast-enhanced technique, accuracy, sensitivity, and specificity were 92%, 91%, and 93% respectively. The median bladder cancer specific survival was 28 months for all patients studied. Responders to chemotherapy at fast dynamic contrast-enhanced MR had better median disease-specific survival than nonresponders (42 months vs. 12 months [p<0.0001]). CONCLUSION: We can predict whether a patient will respond to chemotherapy after two cycles of chemotherapy with fast dynamic contrast-enhanced MR imaging.

Adult↗

[In favour of open versus laparoscopic prostatectomy].

Recovery following uncomplicated laparoscopic radical prostatectomy is somewhat faster than that following open prostatectomy. Recovery of erectile function also occurs faster and better. However, these advantages are gained at the cost of more positive resection fields and less favourable oncologic results. Postoperatively, many patients appear to have T3 tumours, which cannot be optimally detected with current imaging techniques. Therefore, an open operation remains preferable.

Humans↗

Current practice in the management of superficial bladder cancer in the Netherlands and Belgian Flanders: a survey.

OBJECTIVE: Because there is no national guideline for the diagnosis, therapy and follow up of (superficial) bladder cancer in the Netherlands and Belgium, the actual patient management may differ between urologists. The purpose of this study is to get insight in the current way urologists diagnose, treat and follow patients with superficial bladder cancer. METHODS: All practising urologists in the Netherlands (n = 293) and Flemish speaking Belgium (Flanders, n = 223) received a questionnaire with regard to the current management of patients with superficial bladder cancer. The results were compared with the guidelines provided by the European Association of Urology (EAU). Also a comparison was made between the two countries and between university and community hospitals. RESULTS: The results show a wide variation in current practice for superficial bladder cancer. Although the majority of urologists do not follow the EAU guidelines, current practice roughly matches these guidelines. There are no major differences between the two countries or between different types of hospitals. Discrepancies between current practice and guidelines are mostly too frequent use of techniques for the diagnosis, treatment and follow-up. CONCLUSION: In all, there is a need for clear guidelines in superficial bladder cancer and an effective implementation of such guidelines into everyday practice.

Belgium↗

Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours.

EORTC protocol 30924 is an international randomized trial reporting a 7.3 year update of a 2 weekly regimen of high-dose intensity chemotherapy with M-VAC plus granulocyte colony stimulating factor (HD-M-VAC) compared to classic M-VAC in advanced transitional cell carcinoma (TCC). Two hundred and sixty three untreated patients with bidimensionally measurable TCC were included. In an intention to treat analysis, there were 28 complete responses (CR) (21%) and 55 partial responses (PR) (41%), for an overall response rate (RR) of 64% on the HD-M-VAC arm. On M-VAC, there were 12 CR (9%) and 53 PR (41%), for an overall RR of 50% . The P-value for the difference in CR was 0.009; and for RR, was 0.06. After a median follow-up of 7.3 years, 24.6% are alive on the HD-M-VAC arm vs. 13.2% on the M-VAC arm. Median progression-free survival was better with HD-MVAC (9.5 months) vs. M-VAC (8.1 months). The mortality hazard ratio (HR) was 0.76. The 2-year survival rate for HD-M-VAC was 36.7% vs. 26.2% for M-VAC. At 5 years, the survival rate was 21.8% in the HD-M-VAC vs. 13.5%. Median survival was 15.1 months on HD-MVAC and 14.9 months on M-VAC. There was one death from toxicity in each arm; and more patients died to malignant disease in the M-VAC arm (76%) than in the HD-M-VAC arm (64.9%). With longer follow-up initial results have been confirmed, and shows that HD-M-VAC produces a borderline statistically significant relative reduction in the risk of progression and death compared to M-VAC.

Adult↗

Evaluation of early pelvic floor physiotherapy on the duration and degree of urinary incontinence after radical retropubic prostatectomy in a non-teaching hospital.

The objective of this study was to study the effect of early pelvic floor re-education on the degree and duration of incontinence and to evaluate the results of radical retropubic prostatectomy (RRP) performed in a non-teaching hospital. This is a non-randomised study. From March 2000 to November 2003, 57 consecutive men, who underwent RRP for localized prostate cancer, participated in a pelvic floor re-educating program. Continence was defined as a loss of no more than 2-g urine on the 24-h pad test and no use of pads. The 24-h pad test was performed once in every 4 weeks until the patient indicated that he was continent. Diurnal and nocturnal continence was achieved after 1, 2, 3, 6 and 12 months post catheter removal in 40, 49, 70, 86 and 88% of all men, respectively. Comparison of our results with current literature suggest that the time period towards continence after a RRP can be shortened relevantly if pelvic floor re-education is started directly after catheter removal.

Adult↗

Urinary NMP22 BladderChek test in the diagnosis of superficial bladder cancer.

OBJECTIVE: To study the diagnostic efficacy of the NMP22 BladderChek test and to compare it to cytology in the detection of bladder cancer. METHODS: We evaluated 106 voided urinary specimens of patients with suspicion of bladder cancer. All voided urine samples were evaluated by the NMP22 BladderChek test, cytology, sediment and culture. The diagnostic value of the NMP22 BladderChek test was evaluated according to correlation with cystoscopic findings and, in case of tumour, histological findings. A negative test result in a pTaG1 tumour was not considered false-negative in this study. The results were compared to the diagnostic value of cytology. Moreover, the value of the combination of cytology and the NMP22 BladderChek test was determined. RESULTS: In total, 29 patients had histologically proven transitional cell carcinoma of the bladder. The NMP22 BladderChek test detected 40% of 15 pTa tumours and 83.3% of the 6 pT1 tumours. Cytology detected pTa in 33.3% and pT1 in 66.6%. The 1 CIS lesion was detected by cytology. In the group of patients in follow-up the sensitivity and specificity were 57.1% (CI 28.8-82.3) and 89.8% (CI 79.2-96.2) for the NMP22 BladderChek test and 42.9% (CI 17.7-71.7) and 93.2% (CI 83.5-98.1) for cytology. CONCLUSION: The NMP22 BladderChek test has a slightly higher sensitivity compared to cytology, without a relevant loss in specificity. Furthermore it is an easy test with instant result. However, no extra tumours were detected by adjunction of the NMP22 BladderChek test.

Adult↗

Prostate cancer: precision of integrating functional MR imaging with radiation therapy treatment by using fiducial gold markers.

The use of intensity-modulated radiation therapy for treatment of dominant intraprostatic lesions may require integration of functional magnetic resonance (MR) imaging with treatment-planning computed tomography (CT). The purpose of this study was to compare prospectively the landmark and iterative closest point methods for registration of CT and MR images of the prostate gland after placement of fiducial markers. The study was approved by the institutional ethics review board, and informed consent was obtained. CT and MR images were registered by using fiducial gold markers that were inserted into the prostate. Two image registration methods--a commonly available landmark method and dedicated iterative closest point method--were compared. Precision was assessed for a data set of 21 patients by using five operators. Precision of the iterative closest point method (1.1 mm) was significantly better (P < .01) than that of the landmark method (2.0 mm). Furthermore, a method is described by which multimodal MR imaging data are reduced into a single interpreted volume that, after registration, can be incorporated into treatment planning.

Adult↗

Does the tertiary Gleason pattern influence the PSA progression-free interval after retropubic radical prostatectomy for organ-confined prostate cancer?

INTRODUCTION: The Gleason sum is an important prognostic parameter for patients treated with radical prostatectomy for localized prostate cancer. However, frequently more than two predominant Gleason patterns are present in one specimen. In this study we investigated the prognostic significance of tertiary Gleason patterns in radical prostatectomy specimens. PATIENTS AND METHODS: Between 1994 and 2001, 277 patients underwent radical retropubic prostatectomy (RRP) for clinically localised prostate cancer in our institute. We collected information on Gleason score and cancer volume (CV) for all tumour localizations, clinical and pathological stage, seminal vesicle invasion (SVI) and extra capsular extension (ECE). In case one pattern was seen in more than 95% of the tumour, this pattern was used both for the primary and secondary Gleason pattern, and any other pattern (actually the secondary pattern) was called tertiary. Charts were examined retrospectively for clinical follow up. PSA progression was defined as two subsequent rising PSA measurements above 0.10 ng/ml. Kaplan-Meier time to PSA progression was compared between patients with and without a tertiary pattern. RESULTS: Overall, of the 223 patients, 106 (48%) were found to have a tertiary pattern, which on average, was 7% of the total tumour volume. Patients with a tertiary pattern had a 5-year risk of PSA progression of 37.3% versus 12.6% in case no tertiary Gleason pattern was present (log rank p=0.0002). There was no prognostic difference between patients with a higher-grade tertiary pattern as compared to those with a lower grade tertiary pattern. CONCLUSIONS: If present, a tertiary Gleason pattern, whether better or worse than the primary or secondary pattern, is an indication for a worse outcome, as indicated by a shorter time to PSA progression. This suggests that tumour multifocality, rather than the presence of a higher-grade tertiary Gleason pattern has prognostic value.

Biomarkers, Tumor↗

High-grade Ta urothelial carcinoma and carcinoma in situ of the bladder.

We sought to review the definition, diagnosis, prognosis, and treatment of high-grade Ta urothelioma carcinoma and carcinomas in situ (CIS) in order to provide evidence-based guidelines for their diagnosis and treatment. The English-language literature on high-grade Ta urothelial carcinoma and CIS was identified and critically reviewed by a panel of 9 international experts. The panel then met at a consensus conference to present their conclusions. Levels of evidence and grades of recommendation were assessed. Findings from approximately 100 publications appearing prior to February 2005 were reviewed and summarized. High-grade Ta urothelial carcinoma and CIS are relatively rare tumors; thus results are often based on small nonrandomized studies. Their assessment is made more difficult owing to inaccuracies in staging and grading. Although there were similar numbers of level 1, level 2, and level 3 evidence citations, guidelines have been developed based only on levels of evidence supporting grade A and grade B recommendations. These evidence-based guidelines have been developed to aid clinicians in the diagnosis and treatment of patients with high-grade Ta urothelial carcinoma and CIS.

Algorithms↗

Comparison of orthotopic sigmoid and ileal neobladders: continence and urodynamic parameters.

OBJECTIVES: The objective this of the study was to compare continence rates and urodynamic parameters among patients who had undergone orthotopic bladder substitution with sigmoid or ileal segments. METHODS: Continent urinary reservoirs were constructed in 112 patients. Fifty patients received a sigmoid neobladder (SN) and 62 patients an ileal neobladder (IN). Thirty-four patients with an SN (mean age 64.4 years), and 20 with an IN (mean age 57.8 years) agreed to postoperative urodynamic evaluation at a median time after surgery of 18 and 37 months, respectively. Continence and urodynamic parameters were compared in both groups. RESULTS: The average reservoir capacity of the SN (296 ml) was lower than the IN (546 ml). The majority of patients voided by the Valsalva maneuver and achieved good peak flow rates [SN group 16.6 (range 7-32) ml/s, IN group 25.5 (range 5-35) ml/s]. Of the patients with an SN 26 (76%) and with an IN 15 (75%) emptied to near completion with a post-void residual (PVR) of less than 100 ml. Daytime continence was achieved in 90% of IN patients and 85% of SN patients. Only 9% of patients with an SN and 60% of patients with an IN were continent at night. CONCLUSION: A neobladder constructed from detubularized ileum or sigmoid achieves adequate capacity with a satisfactory daytime continence rate. Nighttime incontinence in patients with IN can be at least partly explained by periods of high pressure due to neobladder contractions in combination with a relaxed sphincter during sleep. The low nighttime continence rate of the SN is probably related to its small functional capacity.

Adult↗

Efficacy of routine follow-up after first-line treatment for testicular cancer.

To define guidelines for the follow-up management of patients treated for testicular germ cell tumor this study assessed characteristics of patients with recurrent disease. The charts of 505 patients with testicular cancer treated and followed-up at the University Medical Centre Nijmegen between 1982-2000 were reviewed retrospectively. In 42 patients disease recurrence was found during routine follow-up. In a subset of patients no recurrences were seen after first-line treatment: (a) pathological stage IIa nonseminoma patients who were adjuvantly treated with chemotherapy and (b) histologically confirmed complete responders after primary chemotherapy. Furthermore, in low-stage disease no intra-abdominal recurrences were seen in (a) pathological stage I nonseminoma patients and (b) low-stage seminoma patients who received radiotherapy. The risk of recurrent testicular cancer depends on primary therapy and efficacy of it; these results indicate a limited role for follow-up in pathological stage II nonseminoma patients adjuvantly treated with chemotherapy and in histologically confirmed complete responders after chemotherapy. Abdominal computed tomography does not appear necessary in routine follow-up of patients treated for low-stage testicular cancer.

Adolescent↗

Bladder carcinoma in situ in 2003: state of the art.

Carcinoma is situ (CIS) of the bladder is a high-grade non-invasive malignancy with a high tendency of progression and transitional cell carcinoma outside the bladder. The diagnosis is a combination of abnormal cytology and cystoscopy with biopsies. Although cytology has clear limitations in low-grade lesions, such as a low inter- and intra-observer reproducibility, high-grade lesions and CIS should be diagnosed with a high degree of sensitivity and specificity. Currently available urinary markers do not (yet) seem to match cytology. The cystoscopic diagnosis is more difficult, since flat lesions are often difficult to see. The application of fluorescence cystoscopy and resection clearly improves the detection of the number of CIS lesions per patient and also the number of patients with CIS. For treatment of CIS (maintenance) BCG remains the golden standard. BCG appears to be able to prevent or delay progression to muscle invasive disease. BCG refractory patients are at high risk for progression and cancer death, and cystectomy is the treatment of choice. Alternatives for BCG refractory CIS patients, like intravesical chemo-immunotherapy, new chemotherapeutic drugs or photo-dynamic therapy, remain highly experimental. Last but not least, the danger for CIS patients is failure to respond to therapy and a high subsequent chance of progression and cancer-specific death. Unfortunately, despite much research, this prediction is not yet possible with molecular markers in daily practice.

Adjuvants, Immunologic↗

Intravesical gemcitabine: a phase 1 and pharmacokinetic study.

INTRODUCTION: Superficial bladder cancer can be treated by transurethral resection and additional intravesical therapy. Although agents like Mitomycin C, Epirubicin and BCG are routinely used, there is a need for more potent and/or less toxic agents. Gemcitabine is a deoxycytidine analogue, used systemically for several tumours, such as non-localised bladder cancer, where it is effective and well tolerated. We investigated the use of three dose levels of gemcitabine when given intravesically in humans for safety and pharmacokinetic research. MATERIAL AND METHODS: Patients with superficial bladder cancer, except pT1G3 or CIS were included. Six weekly instillations of 1000, 1500 or 2000 mg gemcitabine were given in 50 ml saline for one hour. Dose modifications were defined in case of dose limiting toxicities. Blood samples were taken before, and 5, 30, 60 (= evacuation) and 120 minutes after instillations 1, 3 and 6. Samples were used for blood counts and pharmacokinetics. Side effects were noted. RESULTS: 3, 4 and 3 patients were treated with 1000, 1500, and 2000 mg gemcitabine respectively, of which 2, 3 and 1 patients had highly recurrent tumours before treatment. Seven patients experienced side effects: 2 with dysuria after the first instillation, 2 after instillations 3-6 and 4-6 and in 3 patients headache, fatigue and heavy legs were experienced once. All side effects were reversible, non-limiting and WHO 1. No macroscopic hematuria was seen. Haematology showed only one case of drop in white blood cell count (lowest dose level, after the first instillation). Gemcitabine plasma levels were immeasurable or low, with peak levels between 30 and 60 minutes, decreasing after more instillations. The metabolite difluorodeoxyuridine reached levels of at most 5 microM, indicating a very low passage of the drug to the systemic circulation. CONCLUSION: Intravesical gemcitabine in the dose used has minimal and reversible side effects. Plasma evaluation indicates that its intravesical use is safe.

Administration, Intravesical↗