Histopathology of prostate tissue after vascular-targeted photodynamic therapy for localized prostate cancer

Low-risk prostate adenocarcinoma is classically managed either with active surveillance or radical therapy (such as external radiotherapy or radical prostatectomy), but both have significant side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy proposed as an alternative approach for localized, low-volume, and low-Gleason score (≤6) carcinomas. We report histological modifications observed in prostate biopsies of 56 patients, performed 6 months after VTP using the photosensitizer TOOKAD® Soluble (WST11) and low-energy laser administered in the tumor area transperineally by optic fibers. In 53 patients, we observed sharply demarcated hyaline fibrotic scars, with or without rare atrophic glands, sometimes reduced to corpora amylacea surrounded by giant multinuclear macrophages. Mild chronic inflammation, hemosiderin, and coagulative necrosis were also observed. When residual cancer was present in a treated lobe (17 patients), it was always located outside the scar, most often close to the prostate capsule, and it showed no therapy-related modification. Histopathological interpretation of post-WST11 VTP prostate biopsies was straightforward, in contrast with that of prostate biopsies after radio or hormonal therapy, which introduces lesions difficult to interpret. VTP resulted in complete ablation of cancer in the targeted area

Mesalazine: A Novel Etiology For Drug-Induced Urinary Calculi

We report the case of a 23-year-old woman treated by mesalazine for ulcerative colitis and who subsequently presented recurrent renal colic due to mesalazine urinary stones. This is the second case described in the literature.Mesalazine stones are soft, friable and have an orange-beige color. They are not visible on non-contrast computed tomography (CT). Their diagnosis is based on morpho-constitutional analysis and CT-urography. Patients treatedby mesalazine who present renal colic should undergo CT-urography in order to make the diagnosis

Rectal metastasis of prostate cancer: about a case

Prostate adenocarcinomas present a high risk of metastasis. We report a case of an atypical prostate cancer metastasis. A male patient presented a prostatic adenocarcinoma treated by surgery. A biological recurrence was discovered during the follow-up by an increased rate of Prostate Specific Antigen (PSA) and was treated by hormonotherapy. Several months later, there was a re-increase of the PSA rate. The CT scan showed a radiation proctitis aspect. An intermittent hormonotherapy was decided. Six months later, he presented abdominal pain. Examinations were performed and showed a rectal carcinosarcoma with prostate origins. A surgical management was realised. The outcomes were an early recurrence. A symptomatic treatment was decided. There are not any rectal localisations reported in the literature. Only loco-regional invasions of the rectum are described and no histological modification of metastasis compared to the primitive tumor has been reported. So, we report a metastasis of a prostate adenocarcinoma which transformed into a carcinosarcoma. KEYWORDS: Adenocarcinoma; Carcinosarcoma; Metastasis; Prostate; Rectal neoplasm

Transcutaneous tibial nerve stimulation: 2 years follow-up outcomes in the management of anticholinergic refractory overactive bladder

PURPOSE: To evaluate long-term use, efficacy and tolerability of transcutaneous tibial nerve stimulation (TTNS) in the treatment of refractory overactive bladder (OAB). METHODS: We performed a prospective observational study and included all patients treated in a single center for OAB persisting after first-line anticholinergic treatment, with ≥ 24 months follow-up. The protocol consisted of daily stimulation at home. The primary outcome was treatment persistence. Amelioration was defined as an improvement in urinary symptom profile (USP) score. RESULTS: We assessed 84 consecutive patients. After a mean follow-up of 39.3 months and a mean treatment use of 8.3 months, almost two-thirds of patients (71.8%) had discontinued TTNS. Treatment continuation was > 12 months for 28 patients (33.3%) and > 18 months for 16 patients (19%). TTNS was successful following 3 months of treatment in 60 (71%) patients. Mean USP score stayed significantly lower than baseline until 12 months of treatment, but was not significant anymore after 18 months. Discontinuation therapy reasons were a lack of sufficient symptom relief for 59 (70%) patients, compliance difficulty for 5 (6%) patients and becoming asymptomatic for 6 (8%) patients. No serious adverse events occurred. CONCLUSIONS: The present study confirms the utility of TTNS as a treatment option for patients with resistant OAB. In the long-term use, few patients continued with therapy, mostly because of a decreased effectiveness with time

Androgen Deprivation Therapy Potentiates the Efficacy of Vascular Targeted Photodynamic Therapy of Prostate Cancer Xenografts

WST11 vascular targeted photodynamic therapy (VTP) is a local ablation approach relying upon rapid, free radical-mediated destruction of tumor vasculature. A phase III trial showed that VTP significantly reduced disease progression when compared with active surveillance in patients with low-risk prostate cancer. The aim of this study was to identify a druggable pathway that could be combined with VTP to improve its efficacy and applicability to higher risk prostate cancer tumors. Transcriptome analysis of VTP-treated tumors (LNCaP-AR xenografts) was used to identify a candidate pathway for combination therapy. The efficacy of the combination therapy was assessed in mice bearing LNCaP-AR or VCaP tumors. Gene set enrichment analysis identifies the enrichment of androgen-responsive gene sets within hours after VTP treatment, suggesting that the androgen receptor (AR) may be a viable target in combination with VTP. We tested this hypothesis in mice bearing LNCaP-AR xenograft tumors by using androgen deprivation therapy (ADT), degarelix, in combination with VTP. Compared with either ADT or VTP alone, a single dose of degarelix in concert with VTP significantly inhibited tumor growth. A sharp decline in serum prostate-specific antigen (PSA) confirmed AR inhibition in this group. Tumors treated by VTP and degarelix displayed intense terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining 7 days after treatment, supporting an increased apoptotic frequency underlying the effect on tumor inhibition. Improvement of local tumor control following androgen deprivation combined with VTP provides the rationale and preliminary protocol parameters for clinical trials in patients presented with locally advanced prostate cancer.

Positron Emission Tomography/Computed Tomography with Gallium-68-labeled Prostate-specific Membrane Antigen Detects Relapse After Vascular-targeted Photodynamic Therapy in a Prostate Cancer Model

BACKGROUND: Evaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques. OBJECTIVE: We assessed whether positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen (Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP). DESIGN, SETTING, AND PARTICIPANTS: A total of 1×10 LNCaP cells were grafted subcutaneously in the flanks of 6-8-wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150mW/cm) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and ⁶⁸Ga-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Local tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance. RESULTS AND LIMITATIONS: Four weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p=0.01). CONCLUSIONS: In a preclinical prostate cancer model, we show that Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials. PATIENT SUMMARY: Positron emission tomography/computed tomography with gallium-68-labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer

Potentiating vascular-targeted photodynamic therapy through CSF-1R modulation of myeloid cells in a preclinical model of prostate cancer

Vascular-targeted photodynamic therapy (VTP) induces rapid destruction of targeted tissues and is a promising therapy for prostate cancer. However, the resulting immune response, which may play an important role in either potentiating or blunting the effects of VTP, is still incompletely understood. Myeloid cells such as myeloid-derived suppressor cells (MDSCs) and macrophages are often found in tumors and are widely reported to be associated with cancer angiogenesis, tissue remodeling, and immunosuppression. These cells are also known to play a critical role in wound-healing, which is induced by rapid tissue destruction. In this study, we investigated the effects of VTP on the recruitment of tumor-infiltrating myeloid cells, specifically MDSCs and tumor-associated macrophages (TAMs), in the Myc-Cap and TRAMP C2 murine prostate cancer models. We report that VTP increased the infiltration of myeloid cells into the tumors, as well as their expression of CSF1R, a receptor required for myeloid differentiation, proliferation, and tumor migration. As anti-CSF1R treatment has previously been used to deplete these cells types in other murine models of prostate cancer, we hypothesized that combining anti-CSF1R with VTP therapy would lead to decreased tumor regrowth and improved survival. Importantly, we found that targeting myeloid cells using anti-CSF1R in combination with VTP therapy decreased the number of tumor MDSCs and TAMs, especially M2 macrophages, as well as increased CD8 T cell infiltration, decreased tumor growth and improved overall survival. These results suggest that targeting myeloid cells via CSF1R targeting is a promising strategy to potentiate the anti-tumor effects of VTP

Post-treatment MRI aspects of photodynamic therapy for prostate cancer

OBJECTIVES: Photodynamic therapy is a new focal therapy for prostate cancer. METHODS: In this technique, a photosensitising agent is introduced intravenously, then activated by local laser illumination to induce tumour necrosis. Treatment efficacy is assessed by magnetic resonance imaging (MRI). RESULTS AND CONCLUSIONS: We illustrate specific post-treatment MRI aspects at early and late follow-up with pathological correlations. TEACHING POINTS: Dynamic phototherapy is a new and promising focal therapy for prostate cancer. One-week MRI shows increased volume of the treated lobe and large, homogeneous necrosis area. Six-month MRI shows significant changes of the prostate shape and signal. Six-month MRI becomes "base line" appearance for further follow-up or monitoring

Évaluation du drainage par sonde double J après urétéroscopie pour maladie lithiasique

Objectives During ureteroscopy for urolithiasis, postoperative ureteral drainage with double J stent is frequently used. It may reduce acute postoperative pain and late ureteral stenosis. Double J stent can have negative impact on life quality. After uncomplicated intervention, double J stent is not mandatory. Objective of our study was to evaluate pain and complications after ureteroscopy with or without stent. Methods We retrospectively analyzed ureteroscopy performed between May 2014 and January 2017. Interventions were compared regarding ureteral drainage with double J stent or not. Our primary outcome was early postoperative pain evaluated with an oral pain scale form 1 to 10 on day one after intervention. Clinical characteristics, per- and postoperative data were collected. We also looked for risks factors of complications. Results Three hundred and sixty-six interventions were included, 259 (70.8%) with and 107 (29.2%) without double J stent. Stone burden was higher in stented group (18.3 vs 9.4 mm, P < 0.0001). Patients without postoperative stents had more ureteral preparation with double J stent (78.5% vs 62.5%, P = 0.0032) and had more ambulatory interventions (75.7% vs 52.5%, P < 0.0001). Postoperative pain was not different (22% vs 17.75%, P = 0.398). Complication rate was similar (29% vs 20.5%, P = 0.1181), so was rehospitalization rate (0.8% vs 0.9%, P = 1). In multivariate analysis, complications factors were unprepared ureter, experienced surgeons and access sheath. Conclusion Not stenting after ureteroscopy do not increase pain or complications. Stenting should not be used after uncomplicated interventions for centimetric stones

Double-J ureteral stent under local anesthesia for women

INTRODUCTION: Ureteral stent placement is a key urologic procedure used to manage ureteral obstructions. It is usually performed under general anesthesia (GA) with its inherent risks. The objective was to evaluate safety, feasibility and tolerance of ureteral stent placement under local anesthesia (LA) in women. MATERIALS AND METHODS: From January 2010 to January 2013, we prospectively and consecutively reviewed all female patients who had an urgent retrograde ureteral stent placement under LA. Only primary stent placements were included in the study. Pain was assessed after surgery by Visual Analog Scale (VAS) and pain and comfort assessment during stent placement were reported. We compared outcomes and tolerance with patients under general anesthesia (GA) matched by age and operatives indications during the same period. RESULTS: We included 36 patients (18 under LA and 18 under GA) with a mean age of 59.4 +/- 22.4 years. The mean operative time was 24.4 +/- 12.9 min and 18.8 +/- 6.5 min in LA group and GA group (p = 0.110), respectively. One patient needed GA due to a poor tolerance. The mean perioperative VAS scores under LA and GA were 5.89 +/-2.95 and 2.06 +/- 2.67 (p < 0.0001), respectively. There were no intraoperative complications in either group. The procedure was painful for 16 (88.8%) patients from the LA group and 9 (50%) patients would not accept to undergo this intervention under LA again. CONCLUSION: Ureteral stent placement under LA in women can be performed safely and effectively. However, this procedure is painful and should be proposed only to selected cases