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Brachytherapy-based radiotherapy has been applied for decades in the curative treatment for solitary, ≤ 5 cm bladder tumors. This review provides a historical perspective of this organ sparing approach. A systematic search of the published literature between 1900 and 2019 was performed on the subject of bladder brachytherapy using PubMed, with digitally retrievable articles being supplemented with articles from the personal collection of the authors. The articles were divided into consecutive time periods, each reflecting the impact of authors on the development of brachytherapy treatment: the time of pioneers, early innovators, modifiers, and recent innovators. Three case-controlled studies comparing brachytherapy-based organ-sparing treatment with cystectomy, demonstrated similarity between the two approaches in terms of disease-free and overall survival, whereas brachytherapy-based approach offered the advantage of at least 80% chance of bladder preservation. The overview was organized in a chronological order, starting from the evolution of brachytherapy from radium, followed by remote afterloading and dose-rate adjustments, and closing with modern era of high-dose-rate and image-guided brachytherapy. Importantly, we demonstrated how essential and beneficial for the patients is a close collaboration between radiation oncologists and urologists, and how adopting a modern surgical development, i.e. the laparoscopic implantation technique, which later became robot-assisted, contributed to the success of this multidisciplinary brachytherapy treatment. We concluded that this highly effective brachytherapy method with very limited toxicity deserves more worldwide popularity.

Background: Active surveillance (AS) aims to reduce overtreatment of low-risk prostate cancer (PC). Incorporating multiparametric magnetic resonance imaging (mp-MRI) and MR-guided biopsy (MRGB) in an AS protocol might contribute to more accurate identification of AS candidates. Objective: To evaluate the value of 3. T mp-MRI and MRGB in PC patients on AS at inclusion and after 12-mo follow-up. Design, setting, and participants: Patients with cT1c-cT2 PC, prostate-specific antigen (PSA) ≤10. ng/ml, PSA density 6, >2 positive cores at repeat transrectal ultrasound-guided biopsy (TRUSGB), presence of PC in >3 separate cancer foci upon both MRGB and TRUSGB, or cT3 tumor on mp-MRI. Outcome measurements and statistical analysis: Reclassification rates, treatment after discontinuation, and outcome on radical prostatectomy after discontinuing AS were reported. Uni- and multivariate analyses were performed to identify predictors of reclassification after 1 yr. Results and limitations: From 2009 to 2013, a total of 111 of 158 patients were consecutively and prospectively included. Around initial diagnosis, 36 patients were excluded from the study protocol; mp-MRI + MRGB reclassified 25/111 (23%) patients, and 11 patients were excluded at own request. Reasons for reclassification were as follows: GS upgrade (15/25, 60%); cT3 disease (3/25, 12%); suspicion of bone metastases (1/25, 4%); and multifocal disease upon MRGB (6/25, 24%). Repeat examinations after 1 yr showed reclassification in 33/75 patients (44%). Reasons were the following: GS upgrade upon TRUSGB (9/33, 27%); volume progression upon TRUSGB (9/33, 27%); cT3 disease upon mp-MRI (1/33, 3%); GS upgrade upon MRGB (1/33, 3%); volume progression upon MRGB (1/33, 3%); multifocal disease upon MRGB (2/33, 6%); and upgrade or upstage upon both TRUSGB and MRGB (10/33, 30%). On logistic regression analysis, the presence of cancer at initial mp-MRI and MRGB examinations was the only predictor of reclassification after 1 yr (odds ratio 5.9, 95% confidence interval 2.0-17.6). Conclusions: Although mp-MRI and MRGB are of additional value in the evaluation of PC patients on AS, the value of mp-MRI after 1 yr was limited. As a considerable percentage of GS ≥7 PC after 1 yr was detected only by TRUSGB, TRUSGB cannot be omitted yet. Patient summary: More aggressive tumors are detected if low-risk prostate cancer patients are additionally monitored by magnetic resonance imaging. However, some high-grade tumors are detected only by transrectal ultrasound-guided biopsy. Multiparametric magnetic resonance imaging (MRI) and MR-guided biopsies are of additional value in the initial evaluation of prostate cancer patients on active surveillance. At repeat examinations after 1 yr, transrectal ultrasound-guided biopsies cannot be omitted yet, as MRI could not detect all aggressive tumors.

Het doel van het ERAS-protocol is het postoperatieve herstel te optimaliseren. Om te inventariseren welke invulling landelijk gegeven wordt aan dit protocol, hebben wij een enquete gehouden onder Nederlandse urologen. Hieruit bleek dat er nog veel verschillen bestaan tussen de ziekenhuizen. Om het effect van ERAS te onderzoeken, hebben wij een onderzoek gedaan in onze eigen kliniek. In deze studie hebben wij de resultaten vergeleken van de robotgeassisteerde radicale cystectomie met intracorporele reconstructie (RARC-IC) voor en na de introductie van het ERAS-protocol. 37 patienten zijn geopereerd in de periode voor introductie van het protocol en 71 erna. Preoperatief waren er geen verschillen tussen beide groepen. De OK-tijd verminderde significant en de gemiddelde opnameduur daalde van 14 naar acht dagen. Het aantal complicaties nam niet toe. De afgenomen OK-tijd is te verklaren vanuit het doorlopen van de RARC-leercurve. Verder onderzoek moet aantonen hoe het ideale ERAS-protocol eruit moet zien en wat de meerwaarde is van een dergelijk protocol.

Purpose To report experience and early results of laparoscopic implantation for interstitial brachytherapy (BT) of solitary bladder tumors and the feasibility of a high-dose-rate (HDR) schedule. Methods and Materials From December 2009 to April 2015, 57 patients with a T2 solitary bladder tumor were treated in Arnhem with transurethral bladder resection followed by external beam irradiation, applied to the bladder and regional iliac lymph nodes, 40 Gy in 20 fractions, 5 fractions per week, and within 1 week interstitial HDR BT, in selected cases combined with partial cystectomy and lymph node dissection. The BT catheters were placed via a transabdominal approach with robotic assistance from a Da Vinci robot after a successful initial experience with a nonrobotic laparoscopic approach. The fraction schedule for HDR was 10 fractions of 2.5 Gy, 3 fractions per day. This was calculated to be equivalent to a reference low-dose-rate schedule of 30 Gy in 60 hours. Data for oncologic outcomes and toxicity (Common Toxicity Criteria version 4) were prospectively collected. Results These modifications resulted in an average postoperative hospitalization of 6 days, minimal blood loss, and no wound healing problems. Two patients had severe acute toxicity: 1 pulmonary embolism grade 4 and 1 cardiac death. Late toxicity was mild (n=2 urogenital grade 3 toxicity). The median follow-up was 2 years. Using cumulative incidence competing risk analysis, the 2-year overall, disease-free, and disease-specific survival and local control rates were 59%, 71%, 87%, and 82%, respectively. Conclusions The benefits of minimally invasive surgery for implantation of BT catheters and the feasibility of HDR BT in bladder cancer are documented. The patient outcome and adverse events are comparable to the best results published for a bladder-sparing approach.

De open radicale cystectomie wordt beschouwd als de standaardbehandeling van het spierinvasief blaascarcinoom en bij recidiverend hoogrisico niet-spierinvasief blaascarcinoom. Sinds 2000 wordt de cystectomie steeds meer laparoscopisch en met assistentie van de robot uitgevoerd, al dan niet met een intracorporeel aangelegde urinedeviatie. De resultaten uit de literatuur komen vooral uit retrospectieve studies, waarin de resultaten worden vergeleken met historische open cystectomieseries. In combinatie met de resultaten van enkele kleinere prospectieve series is er aanzienlijk bewijs dat de robotgeassisteerde radicale cystectomie (RARC) een veilige techniek is waarbij minder bloedverlies en bloedtransfusiebehoefte optreedt en patiënten minder lang opgenomen zijn ten opzichte van de open radicale cystectomie (ORC). Ten aanzien van de functionele en oncologische resultaten lijkt de RARC niet onder te doen voor de ORC. Daarbij heeft de RARC een groot ergonomisch voordeel. Een nadeel is dat de aanschaf en het gebruik van een daVinci™-systeem gepaard gaan met hogere kosten.Zowel internationaal als nationaal wordt momenteel gewerkt aan prospectieve multicentrische vergelijkende studies om het mogelijke verschil aan te tonen ten opzichte van de ORC op het oncologische en/of functionele vlak, maar daarnaast meer duidelijkheid te verkrijgen ten aanzien van de kosteneffectiviteit van de RARC., The open radical cystectomy is considered the golden standard treatment for muscle invasive bladder cancer and recurrent high risk non-muscle invasive bladder cancer. Since 2000 there is an increase in the performance of laparoscopic and robotic assisted cystectomy with or without the creation of an intracorporal performed urine deviation. The results from literature mainly present retrospective studies reflecting comparison with historical open cystectomy series. In combination with few smaller prospective series there is ample evidence for RARC as a safe technique, accompanied with less blood loss and transfusion rates and shorter admission time, compared to the ORC. Concerning the functional and oncological results the RARC seems not inferior to the ORC. In addition, the RARC has a great ergonomic benefit. As a drawback the higher costs for purchase and use of the daVinci™ system can be mentioned. Nowadays, international and national studies are being developed to gain more evidence to show potential difference over the ORC as well as to clarify the concerns about the cost-effectiveness of the RARC.

Het doel van deze studie is evaluatie van de eerste ervaringen en perioperatieve complicaties met de robotgeassisteerde radicale cystectomie (RARC) en de intracorporele aanleg van de urinedeviatie volgens Bricker. 20 patienten ondergingen een RARC wegens een klinisch gelokaliseerd blaascarcinoom. Onderzocht zijn perien postoperatieve complicaties tot 30 dagen na de operatie, duur van de operatie, en het verloop en duur van de opname. De gemiddelde operatieduur was 377 (285-491) minuten, het bloedverlies bedroeg 202 (50-800) ml en de opnameduur was 15,3 (8-39) dagen. Er waren in totaal 11 (55%) chirurgische complicaties: 4 Clavien I-, 5 Clavien IIen 2 Clavien IIIb-complicaties. Er waren geen Clavien IV- of V-complicaties. Het is goed mogelijk om een RARC in een Nederlands perifeer ziekenhuis uit te voeren, inclusief de aanleg van de urinedeviatie volgens Bricker intracorporeel. Er is een duidelijk dalende trend in de operatieduur en het bloedverlies is gering.

The standard treatment for muscle-invasive bladder cancer (MIBC) is a radical cystectomy with pelvic lymph node dissection with or without neoadjuvant chemotherapy. In selected cases a bladder sparing approach is possible, for example a limited surgical excision combined with external beam radiotherapy and brachytherapy. To perform brachytherapy flexible catheters have to be implanted in the bladder wall. The implantation is done either by the open retropubic approach or the endoscopic surgical approach. The largest experience for brachytherapy is with low-dose rate and pulsed-dose rate, although some short-term experience with high-dose rate is also reported. The main advantage for this technique is the conservation of bladder function, with comparable local control rates as for cystectomy series in selected cases. The GEC-ESTRO/ACROP (Groupe Europeen de Curietherapie-European Society for Radiotherapy and Oncology / Advisory Committee on Radiation Oncology Practice) recommendations to perform bladder implantations and brachytherapy as a treatment option for MIBC are described.

Item does not contain fulltext OBJECTIVES: In muscle invasive bladder cancer (MIBC), careful clinical staging is essential for patient counseling and decision-making. Bimanual palpation (BP) is an integral part and guideline advice of clinical staging. Until now, however, the value of BP has never been studied. With this study, we aim to determine the accuracy of clinical staging through BP. METHODS: Detailed clinical data were collected from a population-based series of 1,409 patients with MIBC, diagnosed between 1989 and 2005, in the region of the Comprehensive Cancer Centre East in The Netherlands. Selected were all patients who underwent BP (n = 738). Preoperative tumor-stage (cT-stage) determined through BP was compared with post-cystectomy pT-stage. Contingency tables were made to determine the correlation between cT-stage and pT-stage. RESULTS: In 18 of 142 patients in whom BP showed an organ-confined tumor, the tumor was unresectable (pT4) at the time of surgery. Four out of 9 patients who had a suspected T4 tumor on BP but who underwent cystectomy anyway appeared to have operable tumors at cystectomy. In 87 patients (57.6%), accurate staging through BP was observed. In 17 patients (11.3%), clinical overstaging was found, and in 47 patients, (31.1%) clinical understaging. CONCLUSIONS: Frequently, pT-stage after cystectomy does not correlate with preoperative cT-stage based on BP. Discrepancy was observed in 42% of the patients: in 11%, clinical overstaging and in 31%, clinical understaging. Based on these data, some caution is suggested when interpreting the outcome of BP. Prospective data is needed for a more formal evaluation of the staging accuracy of BP.

Objectives. To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression. Methods. We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guerin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models. Results. pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P = 0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS. Conclusions. These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.

Contains fulltext : 137175.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The objective of this study was to evaluate the role of 3-T multiparametric magnetic resonance imaging (MP-MRI) and magnetic resonance-guided biopsy (MRGB) in early risk restratification of patients on active surveillance at 3 and 12 months of follow-up. MATERIALS AND METHODS: Within 4 hospitals participating in a large active surveillance trial, a side study was initiated. Pelvic magnetic resonance imaging, prostate MP-MRI, and MRGB were performed at 3 and 12 months (latter prostate MP-MRI and MRGB only) after prostate cancer diagnosis in 1 of the 4 participating hospitals. Cancer-suspicious regions (CSRs) were defined on prostate MP-MRI using Prostate Imaging Reporting And Data System (PI-RADS) scores.Risk restratification criteria for active surveillance discontinuance were (1) histopathologically proven magnetic resonance imaging suspicion of node/bone metastases and/or (2) a Gleason growth pattern (GGP) 4 and/or 5 and/or cancer multifocality (>/=3 foci) in MRGB specimens of a CSR on MP-MRI. RESULTS: From 2009 to 2012, a total of 64 of 82 patients were consecutively and prospectively included and underwent MP-MRI and a subsequent MRGB. At 3 and 12 months of follow-up, 14% (9/64) and 10% (3/30) of the patients were risk-restratified on the basis of MP-MRI and MRGB. An overall CSR PI-RADS score of 1 or 2 had a negative predictive value of 84% (38/45) for detection of any prostate cancer and 100% (45/45) for detection of a GGP 4 or 5 containing cancer upon MRGB, respectively. A CSR PI-RADS score of 4 or higher had a sensitivity of 92% (11/12) for detection of a GGP 4 or 5 containing cancer upon MRGB. CONCLUSIONS: Application of MP-MRI and MRGB in active surveillance may contribute in early identification of patients with GGP 4 or 5 containing cancers at 3 months of follow-up. If, during further follow-up, a PI-RADS score of 1 or 2 continues to have a negative predictive value for GGP 4 or 5 containing cancers, a PI-RADS standardized reported MP-MRI may be a promising tool for the selection of prostate cancer patients suitable for active surveillance.

There is accumulating evidence that some biochemical pathways observable by magnetic resonance spectroscopy, e.g., citrate acid and phospholipid metabolism, are altered in human prostate cancer. Four well-established human prostate cancer cell lines were therefore studied with magnetic resonance spectroscopy to compare differences in metabolic content with tumor biological behavior. Herein we demonstrate that, although each cell line has its own metabolic profile, relative creatine and citrate levels can be used to discriminate the androgen-dependent LNCaP cell line from the androgen-independent DU-145, TSU, and PC-3 cell lines.

The effects of repeated high-energy shock wave (HESW) tumor administration on tumor blood flow (TBF) were studied in NU-1 human kidney cancer xenografts. Deuteriated water was used as a magnetic resonance spectroscopic detectable tracer for measuring tumor blood flow. Tumors were exposed twice to 800 electromagnetically generated HESW, with a 24-h interval or sham exposed. No changes in TBF occurred after sham exposure to HESW. TBF levels 2 h after the first and second HESW application were, respectively, 46% and 37% lower than the mean preexposure TBF value and returned to normal levels within 16 h. There was statistically no difference found between the effects on tumor blood flow after the first and second HESW exposure. These observations are in agreement with earlier studies and provide a rationale to shorten the time interval between HESW monotreatments to 2 to 3 h.

Contains fulltext : 97259.pdf (Publisher’s version ) (Closed access) Prognostic factors for survival after recurrent MIBC are unknown and were evaluated using a population-based series of 1409 MIBC patients. 330 Patients who underwent RC or RT with curative intent and who suffered from recurrence were selected. Multivariable survival analyses were performed. Clinicopathological factors that predict survival after recurrence are recurrence location, treatment for recurrence and age at recurrence diagnosis. PURPOSE: We conducted this study to evaluate the prognostic factors for survival among patients with recurrent muscle-invasive bladder cancer (MIBC) after initial treatment with curative intent. PATIENTS AND METHODS: Clinical data were collected from a population-based series of 1409 patients with MIBC. We selected 330 patients who underwent radical cystectomy (RC) or radiotherapy (RT) for urothelial carcinoma with curative intent and who experienced recurrence. Multivariate survival analyses were performed with death from MIBC as the endpoint. Covariates were gender, time to recurrence, age at diagnosis of recurrence, recurrence multiplicity, localization, and treatment for recurrence. Analyses were performed separately for patients initially treated with RC (i-RC) or external beam radiotherapy (i-EBRT). RESULTS: Patients with recurrence after i-RC showed a 1- and 3-year survival of 17% and 6%, respectively. Localization and treatment for recurrence were significantly associated with survival. Patients with recurrence after i-EBRT showed a 1- and 3-year survival of 31% and 12%, respectively. Age at diagnosis of recurrence, localization, and treatment for recurrence were significantly associated with survival. CONCLUSION: This study confirms the extremely poor prognosis after recurrence of MIBC in patients initially treated with surgery or RT. Clinicopathologic factors that predict survival after disease recurrence are location of recurrence, treatment for recurrence, and age at diagnosis of recurrence. Improved diagnosis of primary MIBC to detect extravesical disease and more effective therapeutic approaches to target recurrent MIBC are needed.

Recently, we have shown that connecting live three-dimensional (3D) monitors to all three available Da Vinci® robot (Intuitive) generations improved the impression of shared perception for the whole surgical team. Standardized dry lab experiments revealed that delicate teamwork was faster (up to 40%) when using the 3D monitor [1]. We now studied whether introduction of 3D auxiliary monitor for the assistants at the operating table indeed had a positive impact for robot-assisted laparoscopic partial tumor-nephrectomies (RAL-PN). In order to exclude possible learning curve effects, we examined the data of 26 procedures of 1 experienced surgeon and team members where in every case the same standardized surgical procedure was performed.

Ondanks de inzet van de robot bij de radicale cystectomie (RARC) is er nog weinig bekend over de kosteneffectiviteit.

Contains fulltext : 81043.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete ablative response after intravesical apaziquone instillations. METHODS: Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2 urothelial cell carcinoma (UCC) of the bladder, with the exception of one marker lesion of 0.5-1.0 cm. Intravesical apaziquone was administered at weekly intervals for six consecutive weeks, without maintenance instillations. A histological confirmed response was obtained 2-4 weeks after the last instillation. Routine follow-up (FU) was carried out at 6, 9, 12, 18 and 24 months from the first apaziquone instillation. RESULTS: At 3 months FU 31 of 46 patients (67.4%) had a complete response (CR) to ablative treatment. Side-effects on the long-term were only mild. Two CR patients dropped out during FU. On intention-to-treat (ITT) analysis 49.5% of the CR patients were recurrence-free at 24 months FU, with a median duration of response of 18 months. Of 15 no response (NR) patients, only two received additional prophylactic instillations after TURBT. On ITT-analysis 26.7% of the NR patients were recurrence-free (log rank test, P = 0.155). The overall recurrence-free survival was 39% (18 of 46 patients) at 24 months FU. CONCLUSIONS: The CR of the marker lesion in 67% of patients was followed by a recurrence-free rate of 56.5% at 1-year FU, and 49.5% at 2-year FU. These long-term results are good in comparison with the results of other ablative studies.

Contains fulltext : 170222.pdf (Publisher’s version ) (Open Access) PURPOSE: Compare the efficacy and tolerability of dutasteride in combination with bicalutamide to bicalutamide monotherapy in the treatment of locally advanced and metastatic prostate cancer (PCa). METHODS: One-hundred-fifty PCa patients with locally advanced or metastatic disease were prospectively enrolled and randomly assigned to receive either bicalutamide monotherapy 150 mg once daily (79 patients) or bicalutamide 150 mg plus dutasteride 0.5 mg once daily (71 patients). Treatment response was assessed by serum PSA level measurement, and standard procedures for diagnosis of clinical progression were used during follow-up. Patient-reported quality of life (QoL) was assessed using validated questionnaires (EORTC QLQ-C30 and QLQ-PR25). RESULTS: At 3 years follow-up, PSA progression was found in 52 patients [65.8 %; 95 % confidence interval (CI) 55.4-76.3] in the monotherapy group compared to 38 patients (53.5 %; 95 % CI 41.9-65.1) in the combined therapy group (p = 0.134). At the time of analysis 37 men (46.8 %; 95 % CI 35.8-57.8) in the monotherapy group had died versus 30 men (42.3 %; 95 % CI 30.8-53.7) in the combined therapy group. Median survival time was 5.4 and 5.8 years, respectively (p = 0.694). There was no statistically significant difference in the presentation frequency of adverse events between groups (p = 0.683). QoL was good and comparable between the two groups. CONCLUSIONS: Both therapies were well tolerated with a good QoL. However, despite a trend toward higher efficacy of the combined therapy, progression-free survival and overall survival was not significantly different between the groups. Further research on this therapy should be performed.

Verder moet men zeker zijn van een op de juiste wijze afgenomen urinemonster en een zorgvuldige behandeling van dit monster naar en in het laboratorium (1).

Indien naar aanleiding van anamnese en lichamelijk onderzoek de verdenking bestaat op een urineweginfectie, kan dit aannemelijk worden gemaakt door urine-onderzoek met behulp van teststrips en sedimentonderzoek. Teststroken (strips) zijn meestal voorzien van een combinatie van een aantal testvelden voor zowel leukocyten, erytrocyten, eventueel vrij-hemoglobine, eiwit, nitriet, glucose, ketonen en pH. De bepalingen met deze strips moeten een hoge sensitiviteit hebben, met een hoge voorspellende waarde voor een negatief resultaat. Dit betekent dat in de praktijk monsters met een negatief resultaat niet voor nader sedimentonderzoek in aanmerking hoeven te komen.

The hypothesis that exposure of a solid tumor to high-energy shock waves (HESW) could lead to an increase of metastases was investigated in an animal model. The highly metastatic AT-6 Dunning R3327 rat prostate cancer subline was implanted in the hind limb of a Fisher-Copenhagen rat and was exposed to 6000 shock waves delivered by an experimental lithotripter, or sham-treated, as soon as the tumor had reached a volume of 175–225 mm3. The tumor-bearing leg was amputated 24 h later and the number of metastases was examined 12 weeks thereafter at autopsy. Metastases were seen in 82% of the animals exposed to HESW and in 25% of the sham-treated animals. There was no significant difference in weight of the lungs that contained metastases, between sham and treated animals. These results were confirmed in a second experiment. We conclude that the metastatic spread of tumors with a high metastatic potential may be enhanced by shock-wave exposure.

105 Background: To prevent overtreatment of insignificant and/or low-risk prostate carcinoma in the PSA screening era, active surveillance is emerging as a treatment strategy for selected patients. In our series we aim to establish whether MRI could aid in correct risk assessment for these patients within the framework of the Prostate Cancer Research International Active Surveillance (PRIAS) study. Methods: We included patients in our protocol based on contemporary criteria for active surveillance: - Diagnosis of prostate cancer by TRUS-guided biopsy. - PSA ≤10 ng/mL, PSA density 3+3=6 upon MRGB or T3 stage at MRI. Results: In 48 of 49 included patients at least one TSR was identified, with a median of 2 TSRs (range1-4) per patient. MRGB was obtained from every TSR, with a median of 4 MRGBs taken per patient. Five patients had a GS >3+3=6 upon MRGB and were excluded. Three patients were excluded due to suspicion of T3 stage on MRI. Five patient were excluded upon physician’s discretion due to multifocal prostate cancer upon MRGB. Combined multimodality MRI/MRGB in our active surveillance cohort thus excluded 27% (13/49) of patients who were incorrectly stratified as low-risk prostate carcinoma by contemporary criteria. Conclusions: Application of multimodality MRI and MRGB in an active surveillance protocol improves risk stratification, adding onto contemporary PSA and TRUS-guided biopsy criteria for low-risk prostate cancer. This approach might increase safety and reliability of active surveillance for prostate cancer and deserves ongoing prospective evaluation.

The effects of high energy shock waves (HESW) on tumor cell metabolism and tumor blood flow were studied in the NU-1 kidney cancer xenograft by multinuclear 1H/2H/31P magnetic resonance spectroscopy. Tumor xenografts were exposed to 800 HESW using an experimental electromagnetic shock wave emitter based on the Siemens Lithostar Plus, which is used for clinical lithotripsy. Exposure of tumors to 800 HESW resulted in a temporary decrease of tumor blood flow (TBF) determined by the 2H NMR monitoring of the 2HO1H wash-out after intratumoral injection. By concomitant recording of 31P and 1H NMR spectra, tumor pH, high-energy phosphates and lactate levels were followed. Tumor treatment with HESW transiently resulted in acidification, ATP decrease, P(i) increase and lactate increase. In contrast, HESW administration adjacent to the tumor did not significantly influence TBF, tumor pH, high-energy phosphates or lactate levels, showing that the observed alterations are caused by an interaction of HESW and tumor tissue. The most likely explanation for these observations is that HESW administration causes local vascular malfunctioning followed by a reduction in oxygen and nutrient supply to the tumor which leads to a decreased aerobic energy metabolism. The results of this study may be used to aid the design of HESW-based therapies.

In this study, it was investigated whether prostate tumor biological parameters correlate with metabolic profiles. 1H and 31P magnetic resonance spectra were acquired from perchloric acid extracts of seven Dunning R-3327 prostate tumor sublines. Several metabolic ratios, for example, phosphocholine/total phosphate, choline/total creatine, and inositol/total creatine, did not correlate specifically with one biological characteristic but, based on each of these ratios, the well-differentiated, nonmetastatic, and hormone-dependent sublines could be discriminated from the poorly differentiated or anaplastic, metastatic, and hormone-independent sublines. The glycerophosphoethanolamine/total phosphate, glycerophosphocholine/total phosphate, and phosphocreatine/total phosphate ratios correlated with differentiation grade, and the differences in glycerophosphorylglycerol/total phosphate ratio between metastatic and nonmetastatic sublines was highly significant. No correlation for hormonal sensitivity with any of the metabolites measured could be found, neither by 31P nor by 1H MRS. © 1994 Wiley-Liss, Inc.