Can MRI Help Inform Which Men With a History of Multifocal High-Grade Prostatic Intraepithelial Neoplasia or Atypical Small Acinar Proliferation Remain at an Elevated Risk for Clinically Significant Prostate Cancer?

PURPOSE: We investigated the association of MRI findings in men with a previous diagnosis of atypical small acinar proliferation (ASAP) or multifocal high-grade intraepithelial neoplasia (HGPIN) with pathologic findings on repeat biopsy. MATERIALS AND METHODS: We retrospectively reviewed patients with ASAP/multifocal HGPIN undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative registry. We included men with and without an MRI after the index biopsy demonstrating ASAP/multifocal HGPIN but before the repeat biopsy. Men with an MRI prior to the index biopsy were excluded. We compared the proportion of men with ≥ GG2 CaP (Grade Group 2 prostate cancer) on repeat biopsy among the following groups with the χ2 test: no MRI, PIRADS (Prostate Imaging-Reporting and Data System) ≥ 4, and PIRADS ≤ 3. Multivariable models were used to estimate the adjusted association between MRI findings and ≥ GG2 CaP on repeat biopsy. RESULTS: Among the 207 men with a previous diagnosis of ASAP/multifocal HGPIN that underwent a repeat biopsy, men with a PIRADS ≥ 4 lesion had a higher proportion of ≥ GG2 CaP (56%) compared with men without an MRI (12%, P < .001). A lower proportion of men with PIRADS ≤ 3 lesions had ≥ GG2 CaP (3.0%) compared with men without an MRI (12%, P = .13). In the adjusted model, men with a PIRADS 4 to 5 lesion had higher odds (OR: 11.4, P < .001) of ≥ GG2 CaP on repeat biopsy. CONCLUSIONS: MRI is a valuable diagnostic tool to triage which men with a history of ASAP or multifocal HGPIN on initial biopsy should undergo or avoid repeat biopsy without missing clinically significant CaP.

Amniotic bladder therapy: six-month follow up treating interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by chronic pelvic pain and usually accompanies lower urinary tract symptoms. We have previously reported that amniotic bladder therapy (ABT) provides symptomatic improvement in refractory IC/BPS patients for up to 3 months. Herein, we evaluated the durability of ABT up to 6 months. MATERIALS AND METHODS: Consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized amniotic membrane. Clinical evaluation and patient-reported outcome measurements including Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB) were assessed. RESULTS: Twenty-five consecutive recalcitrant IC/BPS patients were included in the study with an average age of 47.4 ± 14.4 years (29-67 years). After ABT, the IC/BPS symptoms improved gradually up to 3 months in all patients with an average improvement in ICSI, ICPI, BPIC-SS and OAB score of 72.8%, 71.9%, and 66.6%, (p < 0.001) respectively, at 3 months. At 4 months after ABT, 7 patients experienced a rebound in symptoms and requested another injection which resulted in a significant improvement in IC/BPS symptoms after 2, 4, and 8 weeks (p < 0.01). For the 18 patients who received only one injection, the IC/BPS symptoms were still significantly lower at 5 and 6 months compared to baseline (p < 0.01), suggesting a possible durable effect based on the ICSI, ICPI, BPIC-SS, and OAB questionnaire scores. CONCLUSIONS: ABT provided an improvement in pain and lower urinary tract symptoms up to 6 months post-treatment in some refractory IC/BPS patients.

A preliminary report assessing the feasibility and effectiveness of amniotic bladder therapy in patients with chronic radiation cystitis.

INTRODUCTION: Chronic radiation cystitis (CRC) can develop between 6 months and 20 years after radiation therapy that presents with symptoms of urinary frequency, urgency, bladder pain, and nocturia. Amniotic membrane (AM) is known to contain pro-regenerative properties and could thereby be a potential therapeutic modality for radiation-induced tissue injury of the bladder. MATERIALS AND METHODS: CRC patients recalcitrant to previous treatments received amniotic bladder therapy (ABT) comprised of intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 mL 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, and SF-12 Health Survey) were repeated at preop and 2, 4, 8 and 12 weeks post-injection. RESULTS: Five consecutive female patients aged 64.4 ± 20.1 years with a median CRC disease duration of 10 years were included. After ABT, BPIC-SS scores improved from baseline to 12 weeks (36.6 ± 1.1 to 12.6 ± 3.1) and this was associated with an improvement in ICSI, ICPI, OAB, and SF-12 scores. One patient had an acute urinary tract infection at 2 weeks but was successfully treated with oral antibiotics. No other adverse events related to micronized AM injections were observed. Uroflow assessments showed increases in voided volume for all five patients. CONCLUSIONS: This data provides additional evidence for the potential benefit of ABT in patients with chronic inflammatory conditions of bladder such as CRC.

Treatment of chronic post-radiation cystitis with trans-urethral amniotic bladder therapy appears durable at 9 months: A clinical study.

PURPOSE: Chronic radiation cystitis (CRC) develops after radiation therapy and can present with symptoms like urinary frequency, urgency, pelvic pain, and nocturia. We have previously reported that amniotic bladder therapy (ABT) provides symptomatic improvement in refractory CRC patients for up to 3 months. Herein, we evaluated the durability of ABT up to 6 months. MATERIALS AND METHODS: CRC patients recalcitrant to previous treatments received ABT comprised of intra-detrusor injections of 100 mg micronized AM diluted in 10 mL 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, SF-12 Health Survey) were repeated at pre-op and 2, 4, 8, 12, 16, 20, 24, and 36 weeks post-injection. RESULTS: Five consecutive patients with a mean age of 64.4 ± 20.1 years with a median CRC duration of 10 years were included and followed for 6 months. After ABT, the lower urinary tract symptoms improved as early as 2 weeks and were maintained up to 20 weeks. BPIC significantly improved from 36.6 ± 1.1 at baseline to 12.6 ± 1.5 at 16 weeks and 13.8 ± 2.9 at 20 weeks. At 24 and 36 weeks, the improvement was maintained in four (80%) of the five patients (BPIC = 13.8 ± 1.0). Uroflow assessment showed voiding volume improved two-fold in four of the five patients at 24 weeks compared to baseline. CONCLUSION: Our data suggest that a significant number of CRC patients may have durable benefit after ABT. Despite this, some of them can show symptoms rebound at 24 weeks.

Early three-month report of amniotic bladder therapy in patients with interstitial cystitis/bladder pain syndrome.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by symptomatic frequency and urgency, as well as chronic pelvic pain. Disruption of the urothelial barrier is closely associated with IC/BPS. As amniotic membranes (AM) offer capabilities of wound healing in many other fields of medicine, likewise amniotic bladder therapy (ABT) may offer capability of urothelial healing in IC/BPS. METHODS: Under general anesthesia, 10 consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 ml 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder Assessment Tool, and SF-12 Health Survey) were repeated at pre-op and 2, 4, 8 and 12 weeks post-op. RESULTS: Ten females (47.4 ± 14.4 years) who had recalcitrant IC/BPS for 7.8 years (5.2-12.1 years) received injection of micronized AM uneventful in all cases. After treatment, voiding symptoms and bladder pain significantly improved from pre-injection to 3 months. BPIC-SS significantly decreased from 37.4 ± 0.70 at baseline to 12.2 ± 2.90 at 3 months (p < 0.001). This corresponded to a significant improvement in their overall physical and mental quality of life. No adverse events occurred related to micronized AM injections, such as UTIs or acute urinary retention. CONCLUSION: ABT could be an innovative treatment option for IC/BPS patients in terms of improving clinical symptoms based on preliminary outcomes at 3 months. Further studies are warranted to confirm the usefulness of ABT in patients with IC/BPS and to determine the duration of the effect.

A Novel Interaction between Chemokine and Phosphoinositide Signaling in Metastatic Prostate Cancer.

Prostate cancer commonly metastasizes to bone due to its favorable microenvironment for cell growth and survival. Currently, the standard of care for metastatic prostate cancer is medical castration in conjunction with chemotherapeutic agents and newer anti-androgen/androgen receptor therapies. While these therapies aim to improve the quality of life in patients with advanced disease, resistance to these therapies is inevitable prompting the development of newer therapies to contain disease progression. The CXCL12/CXCR4 axis has previously been shown to be involved in prostate cancer cell homing to bone tissue, and new investigations found a novel interaction of Phosphatidyl Inositol 4 kinase IIIa (PI4KA) downstream of chemokine signaling. PI4KA phosphorylates at the 4th position on phosphatidylinositol (PI), to produce PI4P and is localized to the plasma membrane (PM). At the PM, PI4KA provides precursors for the generation of PI(4,5)P2, and PI(3,4,5)P3 and helps maintain PM identity through the recruitment of lipids and signaling proteins. PI4KA is recruited to the PM through evolutionarily conserved adaptor proteins, and in PC cells, CXCR4 binds with adaptor proteins to recruit PI4KA to the PM. The objective of this review is to summarize our understanding of the role that phosphatidyl inositol lipid messengers in cancer cells.