Alternative polyadenylation determines the functional landscape of inverted Alu repeats.

Inverted Alu repeats (IRAlus) are abundantly found in the transcriptome, especially in introns and 3' untranslated regions (UTRs). Yet, the biological significance of IRAlus embedded in 3' UTRs remains largely unknown. Here, we find that 3' UTR IRAlus silences genes involved in essential signaling pathways. We utilize J2 antibody to directly capture and map the double-stranded RNA structure of 3' UTR IRAlus in the transcriptome. Bioinformatic analysis reveals alternative polyadenylation as a major axis of IRAlus-mediated gene regulation. Notably, the expression of mouse double minute 2 (MDM2), an inhibitor of p53, is upregulated by the exclusion of IRAlus during UTR shortening, which is exploited to silence p53 during tumorigenesis. Moreover, the transcriptome-wide UTR lengthening in neural progenitor cells results in the global downregulation of genes associated with neurodegenerative diseases, including amyotrophic lateral sclerosis, via IRAlus inclusion. Our study establishes the functional landscape of 3' UTR IRAlus and its role in human pathophysiology.

Deadenylation kinetics of mixed poly(A) tails at single-nucleotide resolution.

Shortening of messenger RNA poly(A) tails, or deadenylation, is a rate-limiting step in mRNA decay and is highly regulated during gene expression. The incorporation of non-adenosines in poly(A) tails, or 'mixed tailing', has been observed in vertebrates and viruses. Here, to quantitate the effect of mixed tails, we mathematically modeled deadenylation reactions at single-nucleotide resolution using an in vitro deadenylation system reconstituted with the complete human CCR4-NOT complex. Applying this model, we assessed the disrupting impact of single guanosine, uridine or cytosine to be equivalent to approximately 6, 8 or 11 adenosines, respectively. CCR4-NOT stalls at the 0, -1 and -2 positions relative to the non-adenosine residue. CAF1 and CCR4 enzyme subunits commonly prefer adenosine but exhibit distinct sequence selectivities and stalling positions. Our study provides an analytical framework to monitor deadenylation and reveals the molecular basis of tail sequence-dependent regulation of mRNA stability.

Identification of genes associated with the regulation of cold tolerance and the RNA movement in the grafted apple.

In grafted apple, rootstock-derived signals influence scion cold tolerance by initiating physiological changes to survive over the winter. To understand the underlying molecular interactions between scion and rootstock responsive to cold, we developed transcriptomics and metabolomics data in the stems of two scion/rootstock combinations, 'Gala'/'G202' (cold resistant rootstock) and 'Gala'/'M9' (cold susceptible rootstock). Outer layers of scion and rootstock stem, including vascular tissues, were collected from the field-grown grafted apple during the winter. The clustering of differentially expressed genes (DEGs) and gene ontology enrichment indicated distinct expression dynamics in the two graft combinations, which supports the dependency of scion cold tolerance on the rootstock genotypes. We identified 544 potentially mobile mRNAs of DEGs showing highly-correlated seasonal dynamics between scion and rootstock. The mobility of a subset of 544 mRNAs was validated by translocated genome-wide variants and the measurements of selected RNA mobility in tobacco and Arabidopsis. We detected orthologous genes of potentially mobile mRNAs in Arabidopsis thaliana, which belong to cold regulatory networks with RNA mobility. Together, our study provides a comprehensive insight into gene interactions and signal exchange between scion and rootstock responsive to cold. This will serve for future research to enhance cold tolerance of grafted tree crops.

Heterologous vaccination utilizing viral vector and protein platforms confers complete protection against SFTSV.

Severe fever with thrombocytopenia syndrome virus was first discovered in 2009 as the causative agent of severe fever with thrombocytopenia syndrome. Despite its potential threat to public health, no prophylactic vaccine is yet available. This study developed a heterologous prime-boost strategy comprising priming with recombinant replication-deficient human adenovirus type 5 (rAd5) expressing the surface glycoprotein, Gn, and boosting with Gn protein. This vaccination regimen induced balanced Th1/Th2 immune responses and resulted in potent humoral and T cell-mediated responses in mice. It elicited high neutralizing antibody titers in both mice and non-human primates. Transcriptome analysis revealed that rAd5 and Gn proteins induced adaptive and innate immune pathways, respectively. This study provides immunological and mechanistic insight into this heterologous regimen and paves the way for future strategies against emerging infectious diseases.

Prediction of anti-vascular endothelial growth factor agent-specific treatment outcomes in neovascular age-related macular degeneration using a generative adversarial network.

To develop an artificial intelligence (AI) model that predicts anti-vascular endothelial growth factor (VEGF) agent-specific anatomical treatment outcomes in neovascular age-related macular degeneration (AMD), thereby assisting clinicians in selecting the most suitable anti-VEGF agent for each patient. This retrospective study included patients diagnosed with neovascular AMD who received three loading injections of either ranibizumab or aflibercept. Training was performed using optical coherence tomography (OCT) images with an attention generative adversarial network (GAN) model. To test the performance of the AI model, the sensitivity and specificity to predict the presence of retinal fluid after treatment were calculated for the AI model, an experienced (Examiner 1), and a less experienced (Examiner 2) human examiners. A total of 1684 OCT images from 842 patients (419 treated with ranibizumab and 423 treated with aflibercept) were used as the training set. Testing was performed using images from 98 patients. In patients treated with ranibizumab, the sensitivity and specificity, respectively, were 0.615 and 0.667 for the AI model, 0.385 and 0.861 for Examiner 1, and 0.231 and 0.806 for Examiner 2. In patients treated with aflibercept, the sensitivity and specificity, respectively, were 0.857 and 0.881 for the AI model, 0.429 and 0.976 for Examiner 1, and 0.429 and 0.857 for Examiner 2. In 18.5% of cases, the fluid status of synthetic posttreatment images differed between ranibizumab and aflibercept. The AI model using GAN might predict anti-VEGF agent-specific short-term treatment outcomes with relatively higher sensitivity than human examiners. Additionally, there was a difference in the efficacy in fluid resolution between the anti-VEGF agents. These results suggest the potential of AI in personalized medicine for patients with neovascular AMD.

Antisense Expression of Apple TFL1-like Gene (MdTFL1) Promotes Early Flowering and Causes Phenotypic Changes in Tobacco.

Apples (Malus × domestica Borkh.) require up to several years for flowering and bearing fruits. The transition from vegetative to reproductive phase is controlled by floral regulators such as TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT). TFL1 mediates the maintenance of vegetative phase, unlike the antagonistic function of FT to promote the transition into reproductive phase. In this study, we isolated apple TFL1-like gene (MdTFL1) to elucidate various phenotypic traits triggered by the antisense expression of MdTFL1 in tobacco apart from its floral induction function. Early flowering was observed in the tobacco line with MdTFL1 knockout, indicating the reduced time for transition to vegetative phases. Quantitative reverse-transcription PCR showed upregulation of genes involved in the regulation of floral induction, including NtAP1, NtSOC1, NFL1, and NtFTs, and downregulation of carotenoid cleavage dioxygenases (CCDs) and CEN-like genes in transgenic lines. Interestingly, transgenic tobacco expressing antisense MdTFL1 exhibited distinct morphological changes in lateral shoot outgrowth, internode length, and the development of leaves, flowers, and fruits. The results suggested that using the antisense expression of MdTFL1 gene is one of the approaches to shorten the vegetable phase and proposed improvement of plant architecture in horticultural crops.

The m6A(m)-independent role of FTO in regulating WNT signaling pathways.

FTO and ALKBH5 are the two enzymes responsible for mRNA demethylation. Hence, the functional study of FTO has been focused on its mechanistic role in dynamic mRNA modification, and how this post-transcriptional regulation modulates signaling pathways. Here, we report that the functional landscape of FTO is largely associated with WNT signaling pathways but in a manner that is independent of its enzymatic activity. Re-analyses of public datasets identified the bifurcation of canonical and noncanonical WNT pathways as the major role of FTO. In FTO-depleted cells, we find that the canonical WNT/ß-Catenin signaling is attenuated in a non-cell autonomous manner via the up-regulation of DKK1. Simultaneously, this up-regulation of DKK1 promotes cell migration via activating the noncanonical WNT/PCP pathway. Unexpectedly, this regulation of DKK1 is independent of its RNA methylation status but operates at the transcriptional level, revealing a noncanonical function of FTO in gene regulation. In conclusion, this study places the functional context of FTO at the branch point of multiple WNT signaling pathways and extends its mechanistic role in gene regulation.

Collagen type VI­α1 and 2 repress the proliferation, migration and invasion of bladder cancer cells.

The bladder cancer (BCa) microenvironment comprises heterogeneous tumor cell populations, the surrounding stroma and the extracellular matrix (ECM). Collagen, the scaffold of the tumor microenvironment, regulates ECM remodeling to promote tumor infiltration, angiogenesis, invasion and migration. The present study examined how collagen type VI­α (COL6A) 1 and 2 function during BCa pathogenesis and progression, with the aim of facilitating the development of precision therapeutics, risk stratification and molecular diagnosis. COL6A1 and COL6A2 mRNA expression in non­muscle invasive BCa (NMIBC) and MIBC tissue samples was measured using reverse transcription­quantitative PCR. In addition, the tumor­suppressive effects of COL6A1 and COL6A2 in human BCa EJ cells (MGH­U1) were assessed. Compared with normal controls, COL6A1 and COL6A2 mRNA expression was downregulated in both NMIBC and MIBC tissue samples (P<0.05, respectively). COL6A1 and COL6A2 effectively inhibited the proliferation of human BCa EJ cells (MGH­U1) and induced cell cycle arrest at the G1 phase. Additionally, COL6A1 and COL6A2 served roles in MAPK and AKT signaling by increasing p38 MAPK phosphorylation and decreasing AKT phosphorylation. Finally, COL6A1 and COL6A2 inhibited wound healing and invasion by suppressing the activity of matrix metalloproteinase (MMP)­2 and MMP­9. In conclusion, COL6A1 and COL6A2 may act as classical collagens by forming a physical barrier to inhibit BCa tumor growth and invasion.

Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs.

DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs.

RNA demethylation by FTO stabilizes the FOXJ1 mRNA for proper motile ciliogenesis.

Adenosine N6-methylation (m6A) is one of the most pervasive mRNA modifications, and yet the physiological significance of m6A removal (demethylation) remains elusive. Here, we report that the m6A demethylase FTO functions as a conserved regulator of motile ciliogenesis. Mechanistically, FTO demethylates and thereby stabilizes the mRNA that encodes the master ciliary transcription factor FOXJ1. Depletion of Fto in Xenopus laevis embryos caused widespread motile cilia defects, and Foxj1 was identified as one of the major phenocritical targets. In primary human airway epithelium, FTO depletion also led to FOXJ1 mRNA destabilization and a severe loss of ciliated cells with an increase of neighboring goblet cells. Consistently, Fto knockout mice showed strong asthma-like phenotypes upon allergen challenge, a result owing to defective ciliated cells in the airway epithelium. Altogether, our study reveals a conserved role of the FTO-FOXJ1 axis in embryonic and homeostatic motile ciliogenesis.

Preharvest Application of Chitosan Improves the Postharvest Life of 'Garmrok' Kiwifruit through the Modulation of Genes Related to Ethylene Biosynthesis, Cell Wall Modification, and Lignin Metabolism.

The influence of the preharvest application of chitosan on physicochemical properties and changes in gene expression of 'Garmrok' kiwifruit during postharvest cold storage (0 °C; RH 90-95%; 90 days) was investigated. Preharvest treatment of chitosan increased the fruit weight but had no significant effect on fruit size. The chitosan treatment suppressed the ethylene production and respiration rate of kiwifruit during the cold storage. The reduction of ethylene production of chitosan-treated kiwifruit was accompanied with the suppressed expression of ethylene biosynthesis genes. Moreover, preharvest application of chitosan diminished weight loss and delayed the changes in physicochemical properties that include firmness, soluble solids content, titratable acidity, total sugars, total acids, total phenols, and total lignin. As a result, the preharvest application of chitosan delayed the maturation and ripening of fruit. Expression of genes related to cell wall modification was down-regulated during the early maturation (ripening) period, while those related to gene expression for lignin metabolism were up-regulated at the later stages of ripening. These results demonstrate that the preharvest application of chitosan maintained the fruit quality and extends the postharvest life of 'Garmrok' kiwifruit, possibly through the modulation of genes related to ethylene biosynthesis, cell wall modification, and lignin metabolism.

MS1-Level Proteome Quantification Platform Allowing Maximally Increased Multiplexity for SILAC and In Vitro Chemical Labeling.

Quantitative proteomic platforms based on precursor intensity in mass spectrometry (MS1-level) uniquely support in vivo metabolic labeling with superior quantification accuracy but suffer from limited multiplexity (≤3-plex) and frequent missing quantities. Here we present a new MS1-level quantification platform that allows maximal multiplexing with high quantification accuracy and precision for the given labeling scheme. The platform currently comprises 6-plex in vivo SILAC or in vitro diethylation labeling with a dedicated algorithm and is also expandable to higher multiplexity (e.g., nine-plex for SILAC). For complex samples with broad dynamic ranges such as total cell lysates, our platform performs highly accurately and free of missing quantities. Furthermore, we successfully applied our method to measure protein synthesis rate under heat shock response in human cells by 6-plex pulsed SILAC experiments, demonstrating the unique biological merits of our in vivo platform to disclose translational regulations for cellular response to stress.

Comparison of the Efficacy Between Transurethral Coagulation and Transurethral Resection of Hunner Lesion in Interstitial Cystitis/Bladder Pain Syndrome Patients: A Prospective Randomized Controlled Trial.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by chronic pelvic pain related to the bladder with no effective treatment options. OBJECTIVE: To evaluate the efficacy and safety of transurethral resection (TUR) and transurethral coagulation (TUC) as treatments for Hunner lesion (HL) in IC/BPS. DESIGN, SETTING, AND PARTICIPANTS: A single-center, prospective, randomized controlled trial involving 126 patients with HL in IC/BPS. INTERVENTION: TUR or TUC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was recurrence-free time after surgery. Secondary outcomes included change of the number of frequency, nocturia, urgency episodes in voiding diaries, O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), pelvic pain and urgency/frequency (PUF) symptom scale, and visual analog scale (VAS) for pain and risk factors for recurrence. RESULTS AND LIMITATIONS: There were no differences in the recurrence-free time between treatment groups, a difference of 12.2 mo (95% confidence interval [CI], 11.1-17.6) for TUR, and a difference of 11.5 mo (95% CI, 9.03-16.1; p=0.735) for TUC. No difference was found in decreased mean daytime frequency, nocturia, urgency episodes, ICSI, ICPI, PUF symptom scale, and VAS for pain between both groups over 12 mo. Regardless of treatment types, there were significant improvements in all symptom questionnaires and pain compared with baseline (all, p < 0.05). Treatment type (TUR or TUC), age, sex, previous history of hydrodistension, and number of HLs did not affect recurrence. Incidence of bladder injury was higher in the TUR group (7.9%) than in the TUC group (3.4%). CONCLUSIONS: There was no difference in the recurrence-free time and effect on urinary symptoms, including pain between TUC and TUR, for HL. Taking into account procedure-related complications, the surgeon can choose the method with which he/she is most familiar and comfortable. PATIENT SUMMARY: In patients with bladder pain syndrome with Hunner lesions, both endoscopic resection and coagulation of the lesions are effective treatments.

A Computational Framework for Genome-wide Characterization of the Human Disease Landscape.

A key challenge for the diagnosis and treatment of complex human diseases is identifying their molecular basis. Here, we developed a unified computational framework, URSAHD (Unveiling RNA Sample Annotation for Human Diseases), that leverages machine learning and the hierarchy of anatomical relationships present among diseases to integrate thousands of clinical gene expression profiles and identify molecular characteristics specific to each of the hundreds of complex diseases. URSAHD can distinguish between closely related diseases more accurately than literature-validated genes or traditional differential-expression-based computational approaches and is applicable to any disease, including rare and understudied ones. We demonstrate the utility of URSAHD in classifying related nervous system cancers and experimentally verifying novel neuroblastoma-associated genes identified by URSAHD. We highlight the applications for potential targeted drug-repurposing and for quantitatively assessing the molecular response to clinical therapies. URSAHD is freely available for public use, including the use of underlying models, at ursahd.princeton.edu.

Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation.

RNA tails play integral roles in the regulation of messenger RNA (mRNA) translation and decay. Guanylation of the poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, the most common of which is guanosine. A single guanosine residue is sufficient to impede the deadenylase CCR4-NOT complex, which trims the tail and exposes guanosine at the 3' end. Consistently, depletion of TENT4A and TENT4B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of posttranscriptional gene regulation.

IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment.

Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.

Change of Ultrasound Estimated Bladder Weight and Bladder Wall Thickness After Treatment of Bladder Outlet Obstruction With Dutasteride.

OBJECTIVES: To investigate the change of bladder wall hypertrophy to relieve bladder outlet obstruction (BOO) by treatment with 5α-reductase inhibitor. METHODS: Men who have BOO confirmed by urodynamic study (BOO index ≥40) were treated with dutasteride 0.5 mg once a day for 6 months. We measured ultrasound estimated bladder weight (UEBW), UEBW divided by body surface area (UEBW/BSA), and bladder wall thickness (BWT) before and after treatment. Changes in LUTS parameters were assessed by using the International Prostate Symptom Score, uroflowmetry, residual urine volume, prostate volume, serum prostate-specific antigen (PSA), and LUTS outcome scores (LOS). Correlation between the change of LUTS parameters and UEBW, UEBW/BSA, and BWT were evaluated. We assessed the changes of bladder wall hypertrophy according to the results of benefit, satisfaction, and willingness to continue (BSW) questionnaire. RESULTS: Thirty patients completed the 6-month study. The mean UEBW was 47.10 ± 7.79 g before and 50.07 ± 5.39 g after dutasteride treatment (P = 0.259). The mean UEBW/BSA was 26.47 ± 4.30 g/m2 before and 28.2 ± 3.53 g/m2 after treatment (P = 0.253), and there was no definite change in mean BWT after treatment (P = 0.301). Most LUTS parameters including LOS significantly improved. Increased BOO index value was related to decreased BWT (ρ = 0.361, P = 0.049). There was no definite change in mean UEBW, UEBW/BSA, and BWT according to the results of the BSW questionnaire. CONCLUSIONS: There was no change in UEBW, UEBW/BSA and BWT despite improving most clinical parameters suggesting BOO. The changes of bladder wall hypertrophy parameters still have limitations to directly reflect the relief of BOO.

Tension-Free Vaginal Tape-SECUR Procedure for the Treatment of Female Stress Urinary Incontinence: 3-Year Follow-Up Results.

OBJECTIVES: To assess the efficacy and complications associated with the use of the tension-free vaginal tape (TVT)-Secur system device for the treatment of female stress urinary incontinence (SUI) based on a 3-year follow-up. METHODS: Women with SUI were randomly allocated to either the U- or H-type groups depending on the TVT-Secur approach used. Patients were questioned about continence and satisfaction 1, 2, and 3 years after surgery. Patients were assessed postoperatively by questionnaires including Sandvik, Incontinence Quality of Life (I-QoL), Bristol Female Lower Urinary Tract Symptoms-Scored Form (BF-LUTS), incontinence visual analogue scale (I-VAS), and benefit, satisfaction, and willingness to continue questionnaire. Cure was regarded as no leakage on the Sandvik questionnaire. RESULTS: A total of 115 patients with SUI were included in this study (U-type: 53, H-type: 62). A total of 102 patients were followed-up for 3 years (U-type: 47, H-type: 55). The overall cure rate at the 1-, 2-, and 3-year follow-ups was 87.8, 83.0, and 79.4%, respectively, and there was no difference in the cure rate between the U-and H-type approaches. Approximately 83.4 and 83.3% of patients were satisfied with the surgical outcome at the 1- and 3-year follow-ups. I-QoL, BFLUTS-SF, and I-VAS were improved from baseline regardless of the approach used at the 1- and 2-year follow-ups. Complications included intraoperative vaginal wall perforation (three cases), voiding difficulties such as immediate postoperative retention, and urgency episodes. CONCLUSIONS: Both U- and H-type approaches of TVT-Secur for the treatment of female SUI remains efficacious, safe, and satisfactory for up to 3 years after surgery.

Risk factors for contralateral patent processus vaginalis determined by transinguinal laparoscopic examination.

Concurrent contralateral inguinal exploration in children with unilateral hernia or hydrocele is a subject of debate. The aim of the present study was to investigate the incidence of contralateral patent processus vaginalis (CPPV) using transinguinal laparoscopy (inguinoscopy). In addition, the risk factors of CPPV were evaluated in order to facilitate the selection of appropriate candidates for contralateral examination. A total of 119 patients who presented with unilateral hydrocele, inguinal hernia or cryptorchidism between 2001 and 2008 underwent inguinoscopy during the ipsilateral surgery. All data were collected prospectively. The incidence of CPPV was investigated and the risk factors affecting the presence of CPPV were analyzed. Among these patients, 29 individuals (24.4%) had CPPV confirmed by inguinoscopy. No surgical complications were observed during the inguinoscopy. Cases with suspicious ultrasound findings were at a higher risk of CPPV than cases with normal findings (odds ratio, 13.800; P=0.004). A history of contralateral disease was also found to be a significant risk factor (odds ratio, 4.008; P=0.019). The present study identified that the significant risk factors for CPPV were suspicious findings on ultrasound examination and a history of contralateral disease. Therefore, it is concluded that performing inguinoscopy in children with these risk factors is beneficial.

Treatment outcomes of transurethral macroplastique injection for postprostatectomy incontinence.

PURPOSE: We investigated the efficacy of transurethral injection of Macroplastique bulking agent (Uroplasty) for male stress urinary incontinence (SUI) after prostate surgery. MATERIALS AND METHODS: This retrospective review included men with SUI treated by transurethral injection for symptoms resulting from prostate surgery. Patients were evaluated at 1 month and 6 months after injection by determining the number of pads used per day and changes in incontinence symptoms. Treatment success was defined as use of 1 pad or fewer per day combined with subjective symptom improvement. RESULTS: The study population comprised 30 men with a mean age of 66.1±5.3 years. Of the 30 patients, 24 (80.0%) underwent prostate cancer surgery and the remaining 6 (20.0%) underwent surgery for benign prostatic hyperplasia. The preinjection pad number was 2.9±1.9 pads per day. After injection treatment, the mean follow-up period was 9.3±12.7 months and the success rate was 43% (13/30) at 1 month and 32% (6/19) at 6 months. Injection was more likely to result in a successful outcome in patients with no preinjection radiation treatment history and higher abdominal leak point pressure (ALPP) than in those with a previous history of radiation treatment and lower ALPP, although this result was not statistically significant. Acute urinary retention occurred in 5 patients (17%). CONCLUSIONS: Transurethral Macroplastique injection treatment is a relatively non-invasive treatment method for male SUI with a success rate of 43% at 1 month and 32% at 6 months. Patients with a higher ALPP and no previous history of radiation therapy may experience better treatment outcomes.