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Despite significant advancements in three-dimensional (3D) cell culture technology and the acquisition of extensive data, there is an ongoing need for more effective and dependable data analysis methods. These concerns arise from the continued reliance on manual quantification techniques. In this study, we introduce a microphysiological system (MPS) that seamlessly integrates 3D cell culture to acquire large-scale imaging data and employs deep learning-based virtual staining for quantitative angiogenesis analysis. We utilize a standardized microfluidic device to obtain comprehensive angiogenesis data. Introducing Angio-Net, a novel solution that replaces conventional immunocytochemistry, we convert brightfield images into label-free virtual fluorescence images through the fusion of SegNet and cGAN. Moreover, we develop a tool capable of extracting morphological blood vessel features and automating their measurement, facilitating precise quantitative analysis. This integrated system proves to be invaluable for evaluating drug efficacy, including the assessment of anticancer drugs on targets such as the tumor microenvironment. Additionally, its unique ability to enable live cell imaging without the need for cell fixation promises to broaden the horizons of pharmaceutical and biological research. Our study pioneers a powerful approach to high-throughput angiogenesis analysis, marking a significant advancement in MPS.
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Angiogênese , Aprendizado Profundo , Técnicas de Cultura de CélulasRESUMO
The development of organs-on-a-chip has resulted in advances in the reconstruction of 3D cellular microenvironments. However, there remain limitations regarding applicability and manufacturability. Here, we present an injection-molded plastic array 3D universal culture platform (U-IMPACT) for various biological applications in a single platform, such as cocultures of various cell types, and spheroids (e.g., tumor spheroids, neurospheres) and tissues (e.g., microvessels). The U-IMPACT consists of three channels and a spheroid zone with a 96-well plate form factor. Specifically, organoids or spheroids (~500 µm) can be located in designated areas, while cell suspensions or cell-laden hydrogels can be selectively placed in three channels. For stable multichannel patterning, we developed a new patterning method based on capillary action, utilizing capillary channels and the native contact angle of the materials without any modification. We derived the optimal material hydrophilicity (contact angle of the body, 45-90°; substrate, <30°) for robust patterning through experiments and theoretical calculations. We demonstrated that the U-IMPACT can implement 3D tumor microenvironments for angiogenesis, vascularization, and tumor cell migration. Furthermore, we cultured neurospheres from induced neural stem cells. The U-IMPACT can serve as a multifunctional organ-on-a-chip platform for high-content and high-throughput screening.
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INTRODUCTION: The indications for immune checkpoint inhibitors (ICIs) are expanding for various cancers because of their durable responses and tolerable safety profiles. Immune-related adverse events (irAEs), including neurological adverse events (nAEs), are associated with ICIs therapy. However, there have been few studies on whether re-challenge with ICIs can be clinically acceptable after neurological AE has improved. PATIENT CONCERNS: A 69-year-old woman with recurrent ovarian cancer undergoing palliative chemotherapy was admitted to our hospital with sudden development of diplopia, dizziness, and gait instability. The patient was administered ICI therapy with anti-angiogenic agents for 9 weeks for 3 cycles. DIAGNOSIS: We performed neurological examination, brain imaging, nerve conduction studies, and serology tests. The patient was diagnosed with Guillain-Barré syndrome variant, an immune-mediated polyneuropathy characterized by a triad of ataxia, areflexia, and ophthalmoplegia. INTERVENTION: After prompt discontinuation of pembrolizumab, the patient was taken intravenous methylprednisolone (2 mg/kg) was administered for 5 days, and her symptoms were partially resolved. With the addition of immunoglobulin 0.4 g/kg for 5 days, her symptoms gradually improved. OUTCOMES: The patient's neurological symptoms improved after immunosuppressive therapy, without sequelae. The NCV showed normal nerve conduction. Unfortunately, because there was little evidence for pembrolizumab rechallenge, pembrolizumab therapy was permanently discontinued, and the tumors eventually progressed.
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Inibidores de Checkpoint Imunológico , Imunoterapia , Idoso , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Recidiva Local de Neoplasia/etiologiaRESUMO
The development of a scalable and highly reproducible in vitro tumor microenvironment (TME) platform still sheds light on new insights into cancer metastasis mechanisms and anticancer therapeutic strategies. Here, we present an all-in-one injection molded plastic array three-dimensional culture platform (All-in-One-IMPACT) that integrates vascularized tumor spheroids for highly reproducible, high-throughput experimentation. This device allows the formation of self-assembled cell spheroids on a chip by applying the hanging drop method to the cell culture channel. Then, when the hydrogel containing endothelial cells and fibroblasts is injected, the spheroid inside the droplet can be patterned together in three dimensions along the culture channel. In just two steps above, we can build a vascularized TME within a defined area. This process does not require specialized user skill and minimizes error-inducing steps, enabling both reproducibility and high throughput of the experiment. We have successfully demonstrated the process, from spheroid formation to tumor vascularization, using patient-derived cancer cells (PDCs) as well as various cancer cell lines. Furthermore, we performed combination therapies with Taxol (paclitaxel) and Avastin (bevacizumab), which are used in standard care for metastatic cancer. The All-in-One IMPACT is a powerful tool for establishing various anticancer treatment strategies through the development of a complex TME for use in high-throughput experiments.
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Microfluídica , Neoplasias , Humanos , Células Endoteliais , Reprodutibilidade dos Testes , Esferoides Celulares , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
Breast cancer remains a leading cancer burden among women worldwide. Acquired resistance of cyclin-dependent kinase (CDK) 4/6 inhibitors occurs in almost all hormone receptor (HR)-positive subtype cases, comprising 70% of breast cancers, although CDK4/6 inhibitors combined with endocrine therapy are highly effective. CDK4/6 inhibitors are not expected to cooperate with cytotoxic chemotherapy based on the basic cytotoxic chemotherapy mode of action that inhibits rapidly proliferating cells. The palbociclib-resistant preclinical model developed in the current study investigated whether the combination of abemaciclib, CDK4/6 inhibitor with eribulin, an antimitotic chemotherapy could be a strategy to overcome palbociclib-resistant HR-positive breast cancer. The current study demonstrated that sequential abemaciclib treatment following eribulin synergistically suppressed CDK4/6 inhibitor-resistant cells by inhibiting the G2/M cell cycle phase more effectively. The current study showed the significant association of the pole-like kinase 1 (PLK1) level and palbociclib resistance. Moreover, the cumulative PLK1 inhibition in the G2/M phase by each eribulin or abemaciclib proved to be a mechanism of the synergistic effect. The synergistic antitumor effect was also supported by in vivo study. The sequential combination of abemaciclib following eribulin merits further clinical trials to overcome resistance to CDK4/6 inhibitors in HR-positive breast cancer.
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In vitro models are becoming more advanced to truly present physiological systems while enabling high-throughput screening and analysis. Organ-on-a-chip devices provide remarkable results through the reconstruction of a three-dimensional (3D) cellular microenvironment although they need to be further developed in terms of multiple liquid patterning principle, material properties, and scalability. Here we present a 3D anchor-based microfluidic injection-molded plastic array culture platform (Anchor-IMPACT) that enables selective, space-intensive patterning of hydrogels using anchor-island for high-throughput angiogenesis evaluation model. Anchor-IMPACT consists of a central channel and an anchor-island, integrating the array into an abbreviated 96-well plate format with a standard microscope slide size. The anchor-island enables selective 3D cell patterning without channel-to-channel contact or any hydrogel injection port using an anchor structure unlike conventional culture compartment. The hydrogel was patterned into defined regions by spontaneous capillary flow under hydrophilic conditions. We configured multiple cell patterning structures to investigate the angiogenic potency of colorectal cancer cells in Anchor-IMPACT and the morphological properties of the angiogenesis induced by the paracrine effect were evaluated. In addition, the efficacy of anticancer drugs against angiogenic sprouts was verified by following dose-dependent responses. Our results indicate that Anchor-IMPACT offers not only a model of high-throughput experimentation but also an advanced 3D cell culture platform and can significantly improve current in vitro models while providing the basis for developing predictive preclinical models for biopharmaceutical applications.
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Inibidores da Angiogênese/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Neovascularização Patológica/tratamento farmacológico , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Neovascularização Patológica/metabolismoRESUMO
PURPOSE: The aim of this study was to compare short-term oncologic outcomes and toxicity of focal or partial low-dose-rate brachytherapy (focal/partial LDR-BT) with whole gland low-dose-rate brachytherapy (whole LDR-BT) in localized prostate cancer patients. MATERIAL AND METHODS: Medical records of eligible patients who underwent focal/partial LDR-BT and whole LDR-BT between 2015 and 2017 at our institution were reviewed retrospectively. Clinical characteristics and pathologic outcomes were compared between focal/partial LDR-BT group and whole LDR-BT group. Biochemical recurrence-free survival was analyzed using Kaplan-Meier method and difference between two groups was assessed with log-rank test. Genitourinary and rectal toxicity were also evaluated between the two groups. RESULTS: Of the 60 patients analyzed, 30 focal/partial LDR-BT patients and 30 whole LDR-BT brachytherapy patients were included. Relative to the whole LDR-BT group, the focal/partial LDR-BT group had significantly higher initial PSA level (p = 0.002), smaller number of implanted seeds (p < 0.001), and shorter follow-up duration (p < 0.001). There was no significant difference between the two groups with regard to prostate volume, biopsy Gleason score, and risk group stratification. The 3-year biochemical recurrence-free survival estimates for focal/partial LDR-BT group and whole LDR-BT group were 91.8% and 89.6%, respectively, which was not significantly different (p = 0.554). Genitourinary symptoms were significantly worse in whole LDR-BT group than in focal/partial LDR-BT group. The incidence of rectal toxicity was similar between two groups. CONCLUSIONS: Our findings indicate that the focal/partial LDR-BT is comparable to the whole LDR-BT with respect to short-term biochemical recurrence and toxicities.
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After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later by macrophages. Axonal debris clearing is an early step of the repair process that facilitates regeneration. We show here that Schwann cells promote distal cut axon disintegration for timely clearing. By combining cell-based and in vivo models of nerve lesion with mouse genetics, we show that this mechanism is induced by distal cut axons, which signal to Schwann cells through PlGF mediating the activation and upregulation of VEGFR1 in Schwann cells. In turn, VEGFR1 activates Pak1, leading to the formation of constricting actomyosin spheres along unfragmented distal cut axons to mediate their disintegration. Interestingly, oligodendrocytes can acquire a similar behavior as Schwann cells by enforced expression of VEGFR1. These results thus identify controllable molecular cues of a neuron-glia crosstalk essential for timely clearing of damaged axons.
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Actinas/metabolismo , Axônios/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Células de Schwann/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligodendroglia/metabolismo , Fator de Crescimento Placentário/genética , Fator de Crescimento Placentário/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismoRESUMO
Angiogenic sprouting, which is the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from the cellular microenvironment, such as spatially controlled gradients of angiogenic factors. However, current in vitro models are less scalable for in-depth studies of angiogenesis. In this study, a plastic-based microfluidic chip is developed to reconstruct in vitro 3D vascular networks. The main disadvantages of the preexisting system are identified, namely, the low productivity and difficulty of experiments, and a breakthrough is suggested while minimizing disadvantages. The selection of plastic materials contributes to the productivity and usability of in vitro devices. By adopting this material, this chip offers simple fluid patterning, facilitating the construction of a cell-culture microenvironment. Compared with previous systems, the chip, which can form both inward and outwardly radial vascular sprouting, demonstrates the growth of functional, morphologically integral microvessels. The developed angiogenic model yields dose-dependent results for antiangiogenic drug screening. This model may contribute significantly not only to vascular studies under normal and pathological conditions, but also to fundamental research on the ocular neovascularization. Furthermore, it can be applied as a tool for more practical, extended preclinical research, providing an alternative to animal experiments.
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Microfluídica/métodos , Modelos Biológicos , Neovascularização Fisiológica , Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Olho/irrigação sanguínea , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/química , Dispositivos Lab-On-A-Chip , Microvasos/fisiologia , Neovascularização Fisiológica/efeitos dos fármacos , Impressão TridimensionalRESUMO
BACKGROUND: Robot-assisted partial nephrectomy (RPN) and focal therapy (FT) have both been successfully employed in the management of small renal masses. However, despite this being the era of minimally invasive surgery, few comparative studies exist on RPN and FT. The aim of our study is to review perioperative, renal functional and oncologic outcomes of FT and RPN in cT1 renal masses. METHODS: Literature published in Medline, EMBASE, and Cochrane Library databases up to April 22, 2018, was systematically searched. We included literature comparing outcomes of FT (radiofrequency ablation, cryoablation, microwave ablation, and irreversible electroporation) and RPN. Studies that reported only on laparoscopic partial nephrectomy or open partial nephrectomy, and review articles, editorials, letters, or cost analyses were excluded. In total, data from 1166 patients were included. RESULTS: From 858 total articles, 7 nonrandomized, observational studies were included. Compared with RPN, FT was associated with a significantly lower decrease of estimated glomerular filtration rate (weighted mean difference [WMD] -8.06âmL/min/1.73âm; confidence interval [CI] -15.85 to -0.26; P = .04), and lower estimated blood loss (WMD -49.61âmL; CI -60.78 to -38.45; Pâ<â.001). However, patients who underwent FT had a significantly increased risk of local recurrence (risk ratio [RR] 9.89; CI 4.24-23.04; Pâ<â.001) and distant metastasis (RR 6.42; CI 1.70-24.33; Pâ=â.006). However, operative times, lengths of stay, and complication rates were revealed to be similar between FT and RPN. CONCLUSION: RPN has a substantial advantage in preventing cancer recurrence. However, in the era of minimally invasive surgery, FT has advantages in renal function preservation and less bleeding. Long-term follow-up for survival rates and comparative analysis of microwave ablation and irreversible electroporation are needed to extend FT for patients with significant morbidities and for those who need sufficient renal function preservation with minimal bleeding.
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Técnicas de Ablação/métodos , Eletroquimioterapia/métodos , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Técnicas de Ablação/efeitos adversos , Eletroquimioterapia/efeitos adversos , Taxa de Filtração Glomerular , Humanos , Rim/patologia , Tempo de Internação/estatística & dados numéricos , Recidiva Local de Neoplasia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION AND OBJECTIVES: Retrograde urethrogram (RUG) and voiding cystourethrogram (VCUG) are currently the gold standard imaging technique for diagnosis of urethral stricture and determination of stricture location. However, RUG and VCUG have multiple limitations. These techniques require exposure to ionizing radiation, the quality is operator and patient dependent, there is a moderate degree of invasiveness with urethral catheterization, can have artifacts because of patient positioning that underestimates stricture length. The development of novel imaging modalities without ionizing radiation to accurately evaluate the presence, location, length, and lumen cross-sectional area (CSA) of the urethral stricture would be of great value. The objective of this study was to develop a novel endoluminal ultrasound (ELUS) imaging technique that permits the accurate quantitation of urethral stricture. METHODS: Urethral strictures were created in rabbits (n = 5) by electrocautery and an ELUS technique was developed for subsequent luminal imaging. A 3.2F 40 MHz ultrasound (US) probe was introduced transurethrally and infused with US contrast agent. Images were recorded as the catheter was pulled back at a constant speed to acquire tomographic images. Lumen CSA over the entire urethral length was calculated using a custom methodology and validated in our laboratory. RESULTS: Urethral luminal CSA over the entire length of urethra before and after experimental stricture development was quantified including the length of stenosis. Intra- and interobserver variability (r = 0.99 for both) was excellent. CONCLUSIONS: Feasibility of ELUS as a quantitative technique to determine healthy urethral lumen and stricture CSA was demonstrated. The translational potential for a nonionizing imaging modality to better describe CSA, length, location, and uninvolved urethral CSA of the stricture is a significant improvement over current methodology.
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Ultrassonografia/métodos , Uretra/diagnóstico por imagem , Estreitamento Uretral/diagnóstico por imagem , Animais , Meios de Contraste , Estudos Transversais , Masculino , Variações Dependentes do Observador , Coelhos , Tomografia Computadorizada por Raios XRESUMO
Microphysiological systems have emerged in the last decade to provide an alternative to in vivo models in basic science and pharmaceutical research. In the field of vascular biology, in particular, there has been a lack of a suitable in vitro model exhibiting a three-dimensional structure and the physiological function of vasculature integrated with organ-on-a-chip models. The rapid development of organ-on-a-chip technology is well positioned to fulfill unmet needs. Recently, functional integration of vasculature with diverse microphysiological systems has been increasing. This recent trend corresponds to emerging research interest in how the vascular system contributes to various physiological and pathological conditions. This innovative platform has undergone significant development, but adoption of this technology by end-users and researchers in biology is still a work in progress. Therefore, it is critical to focus on simplification and standardization to promote the distribution and acceptance of this technology by the end-users. In this review, we will introduce the latest developments in vascularized microphysiological systems and summarize their outlook in basic research and drug screening applications.
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Dispositivos Lab-On-A-Chip , Microvasos/fisiologia , Neovascularização Fisiológica , Animais , Humanos , Microvasos/fisiopatologia , Neoplasias/irrigação sanguíneaRESUMO
PURPOSE: To evaluate associations between pathologic factors and erythroblast transformation-specific (ETS)-related gene (ERG) expression in prostate cancer patients. Using next-generation sequencing, we identified target genes and regulatory networks. METHODS: ERG expression in 60 radical prostatectomies was compared with pathological findings by association rule mining with the Apriori algorithm. Whole-exome and RNA sequencing were performed on three formalin-fixed, paraffin-embedded ERG-positive and negative prostate cancer samples. A network diagram identifying dominant altered genes was constructed using Cytoscape open-source bioinformatics platform and GeneMania plugin. RESULTS: Pathologic conditions positive for perineural invasion, apical margins, and Gleason score 3 + 4 = 7 were significantly more likely to be ERG-positive than other pathologic conditions (p = 0.0008), suggesting an association between ERG positivity, perineural invasion, apical margins, and Gleason score 3 + 4 = 7 (Firth's logistic regression: OR 42.565, 95% CI 1.670-1084.847, p = 0.0232). Results of whole-exome and RNA sequencing identified 97 somatic mutations containing common mutated genes. Regulatory network analysis identified NOTCH1, MEF2C, STAT3, LCK, CACNA2D3, PCSK7, MEF2A, PDZD2, TAB1, and ASGR1 as pivotal genes. NOTCH1 appears to function as a hub, because it had the highest node degree and betweenness. NOTCH1 staining was found 8 of 60 specimens (13%), with a significant association between ERG and NOTCH1 positivity (p = 0.001). CONCLUSIONS: Evaluating the association between ERG expression and pathologic factors, and identifying the regulatory network and pivotal hub may help to understand the clinical significance of ERG-positive prostate cancer.
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Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Exoma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Próstata/patologia , Prostatectomia/métodos , Regulador Transcricional ERG/genéticaRESUMO
PURPOSE: This study identified noninvasive factors that predict overactive bladder (OAB) after readjustable mid-urethral sling surgery (Remeex system) in women with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 130 women with SUI due to ISD [Valsalva leak-point pressure (VLPP) <60 cm H2O] who underwent the Remeex procedure between February 2011 and March 2017. Patients were classified according to OAB symptoms before and 6 months after the Remeex procedure: Group 1, without preoperative and postoperative OAB (n=46); Group 2, without preoperative OAB and with postoperative OAB (de novo OAB, n=15); Group 3, with preoperative OAB and without postoperative OAB (n=25); Group 4, with preoperative and postoperative OAB (n=44). Noninvasive clinical and urodynamic factors were evaluated as predictors of de novo OAB. RESULTS: The four groups significantly differed with respect to age (p=0.036), peak urinary flow rate (PUFR) one month after surgery (post-PUFR, p=0.001), and postvoid residual (PVR) one month after surgery (post-PVR, p=0.005). No significant differences were detected for body mass index, diabetes, multiparity, menopause, previous hysterectomy, previous incontinence surgery, previous pelvic organ prolapse surgery, pyuria, preoperative PUFR, preoperative PVR, maximal cystometric capacity, VLPP, maximum urethral closure pressure, detrusor pressure at PUFR, and detrusor overactivity (p>0.05). Post-PUFR decreased significantly compared with preoperative PUFR in Groups 1, 2, and 4 (p=0.002, p=0.001, and p=0.001, respectively). Pairwise comparisons of post-PUFR and post-PVR revealed statistically significant differences between Group 2 and other groups (p<0.0125). Multivariate logistic regression analyses showed that post-PUFR was the only significant predictor of de novo OAB (odds ratio = 0.823, 95% confidence interval 0.727-0.931, p=0.002). CONCLUSIONS: Reduced PUFR after the Remeex procedure is a promising predictor of risk for de novo OAB. This metric is noninvasive and easy to measure.
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Bexiga Urinária Hiperativa/patologia , Bexiga Urinária Hiperativa/cirurgia , Incontinência Urinária por Estresse/patologia , Incontinência Urinária por Estresse/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Menopausa/fisiologia , Pessoa de Meia-Idade , Paridade/fisiologia , Prolapso de Órgão Pélvico/patologia , Prolapso de Órgão Pélvico/cirurgia , Pressão , Estudos Retrospectivos , Slings Suburetrais , Urodinâmica/fisiologiaRESUMO
The aim of the present study was to determine whether oncologic outcomes and adverse events associated with active on/off intermittent antiandrogen monotherapy (daily bicalutamide, 50 mg per day) are comparable with those of standard external beam radiation therapy (EBRT) or combined androgen blockade (CAB) therapy in prostate cancers with positive surgical margins after radical prostatectomy. Two hundred twenty-three patients with positive surgical margins post-radical prostatectomy who underwent active surveillance (AS, n = 32), EBRT without hormone therapy (n = 55), intermittent antiandrogen monotherapy without EBRT (IAAM, n = 50), or CAB without EBRT (n = 86), between 2007 and 2014, were reviewed retrospectively. Pathologic outcomes, biochemical recurrence rates, radiological disease progression, and adverse events were collected from medical records. Biochemical recurrence rates, biochemical recurrence-free survival rates, and radiological recurrence were not different between the groups (P = 0.225, 0.896, and 0.284, respectively). Adverse event rates and severities were lower for IAAM compared with EBRT or CAB (both P < 0.05), but were comparable to those for AS (P = 0.591 and 0.990, respectively). Grade ≥3 adverse events were not reported in the IAAM or AS groups. Erectile dysfunction and loss of libido rates were lower in the IAAM group compared with the EBRT and CAB groups (P = 0.032). Gastrointestinal complications were more frequently reported in the EBRT group (P = 0.008). Active on/off IAAM treatment might be an appropriate treatment option for patients with positive surgical margins after radical prostatectomy. Furthermore, regarding oncologic outcomes, IAAM was comparable to standard EBRT but had a milder adverse event profile.
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Anilidas/administração & dosagem , Antineoplásicos/administração & dosagem , Recidiva Local de Neoplasia , Nitrilas/administração & dosagem , Neoplasias da Próstata/terapia , Compostos de Tosil/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Neoplasia Residual , Nitrilas/efeitos adversos , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Compostos de Tosil/efeitos adversosRESUMO
INTRODUCTION: Internal urethrotomy (IU) in patients with urethral contracture following perineal repair of pelvic fracture urethral injuries (PRPFUI) is troublesome. We evaluated the clinical factors affecting the surgical outcome of IU for urethral contracture after PRPFUI. MATERIALS AND METHODS: We retrospectively reviewed the records of 35 patients who underwent IU for urethral contracture after PRPFUI between March 2004 and June 2013. Ages of patients ranged from 18 to 50, and their follow-up duration was more than 1year after IU. The urethral contracture was confirmed by retrograde urethrogram or cysto-urethroscopy. Success was defined as greater than 15mL/s of peak urinary flow rate at 1year after IU without any clinical evidence of urethral contracture. Success rates were investigated according to the number of IU. Age, body mass index, urethral defect length before PRPFUI, time interval between the original urethral injury and the PRPFUI or between a previous operation and the PRPFUI, time interval between the PRPFUI and the urethral contracture, number of PRPFUI performed, and the type of urethral lengthening procedure were compared between patients with and without success according to the number of IU. RESULTS: Among the 35 patients, the overall success rate of IU was 37% (13/35) during the mean follow-up period of 53 months (range: 17-148 months). There were 8 and 5 patients with success in first and second IU, respectively. However, there was no success after third IU. Urethral defect length before PRPFUI was significantly shorter in patients with success who underwent first and second IU (p<0.05). There were significant differences of success between patients with and without previous repeated failures of PRPFUI in first and second IU (p<0.05). CONCLUSIONS: Short urethral defect length and no previous surgical failures before PRPFUI are good prognostic factors for IU following PRPFUI. Only one or two IUs will be helpful in patients with urethral contracture following PRPFUI.
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Anastomose Cirúrgica/métodos , Contratura , Fraturas Ósseas/cirurgia , Ossos Pélvicos/cirurgia , Períneo/cirurgia , Uretra/lesões , Doenças Uretrais , Urografia , Adulto , Contratura/cirurgia , Feminino , Seguimentos , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Períneo/diagnóstico por imagem , Complicações Pós-Operatórias , República da Coreia/epidemiologia , Estudos Retrospectivos , Uretra/diagnóstico por imagem , Uretra/cirurgia , Doenças Uretrais/diagnóstico por imagem , Doenças Uretrais/etiologia , Doenças Uretrais/cirurgia , Adulto JovemRESUMO
OBJECTIVES: To investigate the renal function outcomes and contralateral kidney volume change measured by using a 3-dimensional reconstructive method after open partial nephrectomy (PN) or open radical nephrectomy (RN) according to the endophytic degree of tumors. MATERIALS AND METHODS: We included 214 PN and 220 RN patients. According to the endophytic degree of the tumors, we divided patients into 3 groups. Patients were assessed for renal function and kidney volume change both preoperatively and postoperatively at 6 months. Kidney volume was calculated by using personal computer-based software. Subgroup analyses was performed for tumor >4cm. RESULTS: Larger and complex tumors were more frequent in the RN group than PN group. Among patients with exophytic and mild endophytic tumors, the mean postoperative renal function was well preserved in PN group and the mean contralateral kidney volume significantly increased in the RN compared to the PN group (PN, 145.55 to 149.98mL; 3.0% versus RN, 143.93 to 169.64mL;17.9% p=0.006). However, in fully endophytic tumors, compensatory hypertrophy of the contralateral kidney was similar between PN and RN (PN, 138.16 to 159.64mL; 15.5% versus RN, 138.65 to 168.04mL; 21.2% p=0.416) and renal functional outcomes were similar between both groups. These results were also confirmed in tumors >4cm in size. CONCLUSIONS: In fully endophytic tumors, especially large tumors, the postoperative renal function and contralateral kidney volume were similar; therefore, we should consider RN preferentially as surgical option for these tumors.
Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Rim/patologia , Nefrectomia/métodos , Adulto , Idoso , Carcinoma de Células Renais/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tamanho do Órgão , Período Pós-Operatório , Estudos Prospectivos , Recuperação de Função Fisiológica , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga TumoralRESUMO
ABSTRACT Objectives To investigate the renal function outcomes and contralateral kidney volume change measured by using a 3-dimensional reconstructive method after open partial nephrectomy (PN) or open radical nephrectomy (RN) according to the endophytic degree of tumors. Materials and Methods We included 214 PN and 220 RN patients. According to the endophytic degree of the tumors, we divided patients into 3 groups. Patients were assessed for renal function and kidney volume change both preoperatively and postoperatively at 6 months. Kidney volume was calculated by using personal computer-based software. Subgroup analyses was performed for tumor >4cm. Results Larger and complex tumors were more frequent in the RN group than PN group. Among patients with exophytic and mild endophytic tumors, the mean postoperative renal function was well preserved in PN group and the mean contralateral kidney volume significantly increased in the RN compared to the PN group (PN, 145.55 to 149.98mL; 3.0% versus RN, 143.93 to 169.64mL;17.9% p=0.006). However, in fully endophytic tumors, compensatory hypertrophy of the contralateral kidney was similar between PN and RN (PN, 138.16 to 159.64mL; 15.5 % versus RN, 138.65 to 168.04mL; 21.2% p=0.416) and renal functional outcomes were similar between both groups. These results were also confirmed in tumors >4cm in size. Conclusions In fully endophytic tumors, especially large tumors, the postoperative renal function and contralateral kidney volume were similar; therefore, we should consider RN preferentially as surgical option for these tumors.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Rim/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodos , Tamanho do Órgão , Período Pós-Operatório , Carcinoma de Células Renais/fisiopatologia , Tomografia Computadorizada por Raios X , Estudos Prospectivos , Resultado do Tratamento , Estatísticas não Paramétricas , Recuperação de Função Fisiológica , Carga Tumoral , Gradação de Tumores , Taxa de Filtração Glomerular , Rim/fisiopatologia , Rim/diagnóstico por imagem , Neoplasias Renais/fisiopatologia , Pessoa de Meia-IdadeRESUMO
Urachal anomalies are relatively uncommon and result from incomplete obliteration of the urachus perinatally. In children, most urachal diseases including urachal cysts and sinuses are benign, and these can sometimes become secondarily infected. Malignant involvement of the urachus is rarely reported, one in 5 million people, accounting for 0.35% to 0.7% of all bladder cancers. There are only five cases of urachal cancer diagnosed at the age of twenties in English written literature. Age at the diagnosis of urachal carcinoma is important to understand pathogenetic transition from benign to malignancy. A 26-year-old man visited our clinic with gross hematuria starting a few months before. CT scan showed a 4.0 × 6.8 cm sized lobulated cystic mass over the bladder dome. Cystoscopy showed a ball-shaped extrinsic mass from the bladder dome with intact bladder mucosa. With an impression of urachal cancer, laparoscopic partial cystectomy with wide excision of urachus was performed. Final diagnosis was well differentiated mucinous urachal adenocarcinoma invading bladder muscle, staged as pT3a based on Sheldon's staging system. To our best knowledge, this case is the youngest Korean case of urachal carcinoma (the fourth youngest ever in English written literature).
RESUMO
A retained urethral catheter is a rare iatrogenic complication of which few cases have been reported in the literature. In this study, we describe a case of a forgotten urethral Foley catheter causing urethracutaneous fistula on scrotum. An 80-year-old man was referred for a small pus-draining cutaneous opening on the lower part of the scrotum. The distal segment of a broken Foley catheter was found, and it was located from urinary bladder to bulbous urethra with its tip penetrating the urethral mucosa. This catheter was removed using flexible cystoscopic forceps, and urethracutaneous fistula was well resolved with conservative therapy.