Clinicopathological implications of histological mapping in radical prostatectomy specimens.

OBJECTIVE: The present study aims to elucidate the clinicopathological implications of histological mapping in radical prostatectomy specimens. METHODS: This study included 76 prostatic cancers with histological mapping. The examined characteristics from the histological mappings were the largest tumor dimension, distance from the tumor core to resection margin, tumor dimension from the apex to base, tumor volume, tumor surface area, and proportion of the tumor. In addition, these histological parameters from the histological mapping were compared between patients with positive surgical margin (PSM) and negative surgical margin (NSM). RESULTS: Patients with PSM were significantly correlated with a higher Gleason score and pT stage than those with NSM. Among the histological characteristics from mappings, there were significant correlations between PSM and the largest tumor dimension, tumor volume, tumor surface area, and proportion of tumor (P < 0.001, P < 0.001, P < 0.001, and P = 0.017, respectively). The distance from the tumor core to the resection margin was significantly longer with PSM than with NSM (P = 0.024). According to the linear regression test, the tumor volume, tumor surface area, and largest tumor dimension were significantly correlated with Gleason score and grade (P = 0.019, P = 0.036, and P = 0.016, respectively). There were no significant differences in the histological factors between the apical and non-apical involved subgroups. CONCLUSION: Various clinicopathological characteristics assessed from the histological mappings, such as the tumor volume, tumor surface area, and proportion of the tumor, can be useful for interpreting PSM after radical prostatectomy.

Understanding Brain-Skeletal Muscle Crosstalk Impacting Metabolism and Movement.

Metabolism and movement, among the critical determinants in the survival and success of an organism, are tightly regulated by the brain and skeletal muscle. At the cellular level, mitochondria -that powers life, and myosin - the molecular motor of the cell, have both evolved to serve this purpose. Although independently, the skeletal muscle and brain have been intensively investigated for over a century, their coordinated involvement in metabolism and movement remains poorly understood. Therefore, a fundamental understanding of the coordinated involvement of the brain and skeletal muscle in metabolism and movement holds great promise in providing a window to a wide range of life processes and in the development of tools and approaches in disease detection and therapy. Recent developments in new tools, technologies and approaches, and advances in computing power and machine learning, provides for the first time the opportunity to establish a new field of study, the 'Science and Engineering of Metabolism and Movement'. This new field of study could provide substantial new insights and breakthrough into how metabolism and movement is governed at the systems level in an organism. The design and approach to accomplish this objective is briefly discussed in this article.

Roles of NF-κB activation in benign prostatic hyperplasia and association between NF-κB and HIF-1α.

OBJECTIVE: The aim of this study was to elucidate the role of NF-κB activation in benign prostatic hyperplasia (BPH) using immunohistochemistry. METHODS: Immunohistochemical staining for NF-κB was performed and evaluated, dividing into glands and stroma in 101 human BPH tissues. To evaluate the impacts of NF-κB activation on BPH progression, correlations between NF-κB expression and clinical findings, hormone receptors, and HIF-1α were evaluated. RESULTS: NF-κB expression was found in 37.6% and 30.7% in glands and stroma of BPH, respectively. Total and T-zone volumes in transrectal ultrasonography were significantly higher in patients with NF-κB activation than those without NF-κB activation in the stroma. However, NF-κB activation of stroma was not correlated with HIF-1α expression and microvessel density. In subgroup analysis based on NF-κB activation, androgen and progesterone receptors of stroma were highly expressed in HIF-1α negative cases than in HIF-1α positive cases. In cases without NF-κB activation, patients with HIF-1α positivity showed a high frequency of diffuse fibrosis than those with HIF-1α negativity (P = 0.001). CONCLUSION: Taken together, our result showed that NF-κB activation of stroma was significantly correlated with low total and T-zone volumes in transrectal ultrasonography. Diffuse fibrosis was frequently found in patients with NF-κB inactivation and HIF-1α positivity.

The Prevalence of Lower Urinary Tract Symptoms and Overactive Bladder in South Korea: A Cross-Sectional, Population-Based Study.

PURPOSE: Lower urinary tract symptoms (LUTS) affect over half of the adults' population worldwide, with an increasing prevalence among the older age groups. Therefore, with the increasing elderly population, LUTS is an important disease, highlighting the need for accurate data on its prevalence. This present study aimed to investigate the prevalence of LUTS in South Korea. METHODS: The study targeted individuals aged at least 19 years nationwide. We conducted computer-assisted telephone interviews, 80% mobile random digital dialing (RDD) sampling frame, and 20% landline RDD sampling frame between April and May 2020. Questionnaires included The International Prostate Symptom Score (IPSS), the overactive bladder symptom score (OABSS), and the characteristics of respondents. Current International Continence Society definitions were used for individual LUTS and OAB. RESULTS: There were 2,000 respondents, 1,009 (50.4%) were women and 546 (27.3%) were aged ≥60 years. Based on our IPSS questionnaire survey results, 77.9% of the respondents had LUTS; 63.7% had mild symptoms (1-7), 11.7% had moderate symptoms (8-19), and 2.4% had severe symptoms (20-35). The prevalence and severity of LUTS increased with age with 22.1% of respondents aged 60 years and above complaining of moderate or severe LUTS. According to the survey through OABSS, the prevalence of OAB was 9.6%, males were 10.3% and females were 9.0%. CONCLUSION: Based on our survey results, 77.9% of the Korean adult population (over the age of 19) experienced at least one LUTS, and the severity increased with age. The prevalence and severity of OAB increased with age, especially after 40 years; the prevalence of OAB was 9.6%, and 13.4% of them were over 60 years old.

A Multicenter, Open-Label, Observational Study Evaluating the Quality of Life After Using a Hydrophilic-Coated Catheter (SpeediCath) With Self-Intermittent Catheterization.

PURPOSE: We evaluated the change in patient quality of life after the use of a hydrophilic-coated catheter (SpeediCath) in adults requiring intermittent catheterization (IC). METHODS: This was a multicenter, open-label, observational study using the Patient Perception of Intermittent Catheterization (PPIC) questionnaire and the Intermittent Self-Catheterization questionnaire (ISC-Q) and safety at 12 and 24 weeks in adult patients who had already used other type of catheters prior to switching to SpeediCath or in patients undergoing self-IC for the first time for any reason. RESULTS: Among a total of 360 subjects, 215 (59.7%) were women, and the mean age was 62.0±13.2 years. At 24 weeks, the satisfaction rate after using SpeediCath was 84.1%, and 80% of patients responded that they could easily perform IC. In total, 81.6% of patients were willing to continue using SpeediCath. The mean ISC-Q score was 54.90±18.65 at 24 weeks. Men found less interference in their daily life by performing IC than women and found it easier to handle the catheter before it was inserted into the urethra. At week 12, the mean change in ISC-Q was significantly greater in patients <65 years (20.24±23.55) than in those ≥65 years (7.57±27.70, P=0.049), but there was no difference at 24 weeks. The most common adverse events were urinary tract infection in 9.72%, gross hematuria in 2.78%, and urethral pain in 1.39%. CONCLUSION: The use of a SpeediCath provided good quality of life for patients who needed self-IC regardless of age or sex.

p62/SQSTM1-induced caspase-8 aggresomes are essential for ionizing radiation-mediated apoptosis.

The autophagy-lysosome pathway and apoptosis constitute vital determinants of cell fate and engage in a complex interplay in both physiological and pathological conditions. Central to this interplay is the archetypal autophagic cargo adaptor p62/SQSTM1/Sequestosome-1 which mediates both cell survival and endoplasmic reticulum stress-induced apoptosis via aggregation of ubiquitinated caspase-8. Here, we investigated the role of p62-mediated apoptosis in head and neck squamous cell carcinoma (HNSCC), which can be divided into two groups based on human papillomavirus (HPV) infection status. We show that increased autophagic flux and defective apoptosis are associated with radioresistance in HPV(-) HNSCC, whereas HPV(+) HNSCC fail to induce autophagic flux and readily undergo apoptotic cell death upon radiation treatments. The degree of radioresistance and tumor progression of HPV(-) HNSCC respectively correlated with autophagic activity and cytosolic levels of p62. Pharmacological activation of the p62-ZZ domain using small molecule ligands sensitized radioresistant HPV(-) HNSCC cells to ionizing radiation by facilitating p62 self-polymerization and sequestration of cargoes leading to apoptosis. The self-polymerizing activity of p62 was identified as the essential mechanism by which ubiquitinated caspase-8 is sequestered into aggresome-like structures, without which irradiation fails to induce apoptosis in HNSCC. Our results suggest that harnessing p62-dependent sequestration of ubiquitinated caspase-8 provides a novel therapeutic avenue in patients with radioresistant tumors.

Clinicopathological Significance of Papillary Thyroid Carcinoma Located in the Isthmus: A Meta-Analysis.

BACKGROUND: The thyroid isthmus is located directly anterior to the trachea and is covered by the strap muscles. Several studies have suggested that papillary thyroid carcinoma (PTC) in the isthmus is more aggressive and is associated with a poor prognosis. The purpose of this meta-analysis was to assess the clinicopathological characteristics and recurrence rates of PTC in the isthmus compared to PTC at other sites. METHODS: Relevant articles were obtained by searching the PubMed database. A meta-analysis was performed using 11 eligible studies. RESULTS: The rate of extrathyroidal extension was 0.502 (95% confidence interval [CI]: 0.239-0.764) and 0.454 (95% CI: 0.331-0.582) for isthmus PTC and PTC at other site, respectively; however, the difference in the rates was not statistically significant. Lymphovascular invasion did not significantly differ between isthmus PTC (0.179 [95% CI: 0.102-0.297]) and PTC at other sites (0.114 [95% CI: 0.066-0.188]). The rate of central lymph node (LN) metastasis was significantly higher in isthmus PTC (0.527 [95% CI: 0.435-0.617]) than in PTC at other sites (0.352 [95% CI: 0.280-0.432]). No significant difference was observed between the two groups in terms of lateral cervical LN metastasis rate. Isthmus PTC was more likely to have a prominent recurrence rate (0.046 [95% CI: 0.022-0.094]) than PTC at other sites (0.010 [95% CI: 0.001-0.070]); however, the difference was not statistically significant (because of the small number of included studies). CONCLUSIONS: The results of this meta-analysis indicated that isthmus PTC was associated with an increased risk of central LN metastasis. Isthmus PTC seems to have a slightly higher recurrence rate than PTC at other sites. Therefore, considering the potential of the isthmus location as an unfavorable factor, more attention should be focused on isthmus PTC, and a more aggressive approach such as prophylactic central LN dissection might provide better outcomes in PTC management.

Photodynamic Therapy as a Potent Radiosensitizer in Head and Neck Squamous Cell Carcinoma.

Despite recent advances in therapeutic modalities such as radiochemotherapy, the long-term prognosis for patients with advanced head and neck squamous cell carcinoma (HNSCC), especially nonviral HNSCC, remains very poor, while survival of patients with human papillomavirus (HPV)-associated HNSCC is greatly improved after radiotherapy. The goal of this study is to develop a mechanism-based treatment protocol for high-risk patients with HPV-negative HNSCC. To achieve our goal, we have investigated molecular mechanisms underlying differential radiation sensitivity between HPV-positive and -negative HNSCC cells. Here, we found that autophagy is associated with radioresistance in HPV-negative HNSCC, whereas apoptosis is associated with radiation sensitive HPV-positive HNSCC. Interestingly, we found that photodynamic therapy (PDT) directed at the endoplasmic reticulum (ER)/mitochondria initially induces paraptosis followed by apoptosis. This led to a substantial increase in radiation responsiveness in HPV-negative HNSCC, while the same PDT treatment had a minimal effect on HPV-positive cells. Here, we provide evidence that the autophagic adaptor p62 mediates signal relay for the induction of apoptosis, promoting ionizing radiation (XRT)-induced cell death in HPV-negative HNSCC. This work proposes that ER/mitochondria-targeted PDT can serve as a radiosensitizer in intrinsically radioresistant HNSCC that exhibits an increased autophagic flux.

Characteristics of an Impaired PDT Response.

A concurrent human papilloma virus (HPV) infection potentiates the efficacy of ionizing radiation for treatment of head and neck cancer by promoting apoptosis. Studies in cell culture indicated an opposite effect for photodynamic therapy (PDT) when this leads to mitochondrial and ER photodamage. The explanation for this difference in PDT efficacy remains to be established. While apoptosis was impaired in HPV(-) cells, such cells can be killed via photodamage directed at the ER: this leads to a nonapoptotic death pathway termed paraptosis. No differences in photosensitizer uptake or reactive oxygen species (ROS) production were observed in HPV(+) vs. HPV(-) tumors. We now provide evidence that death pathways initiated by ER/mitochondrial photodamage leading to either paraptosis or apoptosis are impaired in an HPV(+) head and neck cell line. These results illustrate the complex determinants of PDT efficacy, a topic that has yet to be fully explored.

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.

Effects of HPV Status on Responsiveness to Ionizing Radiation vs Photodynamic Therapy in Head and Neck Cancer Cell lines.

Efficacy of ionizing radiation (I/R) was compared with phototoxic effects of photodynamic therapy (PDT) in vitro using two cell lines derived from patients with head and neck squamous cell carcinoma (HNSCC). A cell line derived from a donor with a human papilloma virus (HPV) infection was more responsive to I/R but significantly less responsive to PDT than a cell line derived from an HPV-free patient. Cell death after I/R in the HPV(+) cell line was associated with increased DEVDase activity, a hallmark of apoptosis. The HPV(-) line was considerably less responsive to I/R, with DEVDase activity greatly reduced, suggesting an impaired apoptotic program. In contrast, the HPV(-) cells were readily killed by PDT when the ER was among the targets for photodamage. While DEVDase activity was enhanced, the death pathway appears to involve paraptosis until the degree of photodamage reached the LD99 range. These data suggest that PDT-induced paraptosis can be a death pathway for cells with an impaired apoptotic program.

The Effects of Bariatric Surgery on Type 2 Diabetes in Asian Populations: a Meta-analysis of Randomized Controlled Trials.

BACKGROUND: To evaluate the effects of bariatric surgery on patients with type 2 diabetes through comparing Asian and non-Asian populations according to follow-up time. METHODS: In this meta-analysis of randomized controlled trials (RCTs), we searched PubMed databases for relevant articles. A meta-analysis was undertaken of 37 eligible RCTs. RESULTS: Diabetes remission rates among Asian populations were similar to those of non-Asian populations at 1 year (95% confidence interval (CI) 0.519 [0.417, 0.619] vs 0.571 [0.316, 0.794], respectively) but were found to be higher in Asian populations at 2 years compared to non-Asian populations (95% CI 0.672 [0.469, 0.826] vs 0.563 [0.220, 0.855], respectively). Asian populations showed greater reductions in HbA1c (- 3.512 [- 2.726, - 4.299], - 3.001 [- 1.433, - 4.569], and - 3.345 [- 2.267, - 4.423]) than non-Asian populations (- 2.129 [- 1.821, - 2.438], - 2.301 [- 1.881, - 2.722], and - 2.107 [- 1.941, - 2.273]) at 1, 2, and 5 years, respectively. Asian populations also showed greater reductions of fasting plasma glucose than non-Asian populations, and these effects were prominent at 3- and 5-year follow-up (Asian populations, - 83.297 [- 73.264, - 93.331]; non-Asian populations, - 54.288 [- 37.409, - 71.166] at 3 years; Asian populations, - 99.014 [- 82.239, - 115.788]; non-Asian populations, - 45.756 [- 21.892, - 69.621] at 5 years). CONCLUSIONS: Bariatric surgery is more successful in diabetes remission and glucose outcome improvement in Asian populations with type 2 diabetes than in non-Asian populations, even over long-term follow-up periods. Bariatric surgery can be considered an effective treatment option and may present an appropriate opportunity to improve the prognosis for Asian patients with type 2 diabetes.

Diagnostic and prognostic implications of parafibromin immunohistochemistry in parathyroid carcinomaT.

The aim of the present study was to elucidate the diagnostic and prognostic implications of parafibromin immunohistochemistry (IHC) in parathyroid carcinoma (PC). We performed a meta-analysis to examine the rate of loss of parafibromin expression from 18 eligible studies. In addition, a diagnostic test accuracy review was conducted to investigate the diagnostic role of parafibromin in PC. The rates of loss of parafibromin expression were 0.522 (95% CI: 0.444-0.599), 0.291 (95% CI: 0.207-0.391), 0.027 (95% CI: 0.011-0.064), and 0.032 (95% CI: 0.008-0.119) in PC, atypical parathyroid adenoma (APA), parathyroid adenoma (PA), and parathyroid hyperplasia, respectively. In the diagnostic test accuracy review for diagnosis of PC, the pooled sensitivity and specificity of parafibromin IHC was 0.53 (95% CI: 0.46-0.59) and 0.96 (95% CI: 0.95-0.97), respectively. The diagnostic odds ratio and the area under curve on summary receiver operating characteristic curve was 25.31 (95% CI: 8.91-71.87) and 0.7954, respectively. In addition, the meta-analysis demonstrated that loss of parafibromin expression was significantly correlated with worse disease-free survival (hazard ratio: 2.832; 95% CI: 1.081-7.421). Loss of parafibromin IHC expression was significantly higher in PC than in APA, PA, and parathyroid hyperplasia. Parafibromin IHC could be useful for diagnosis and prediction of prognosis of PC in daily practice.

Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis.

BACKGROUND: Although the correlation between low claudin-1 expression and worse prognosis has been reported, details on the prognostic implications of claudin-1 expression in various malignant tumors remain unclear. The present study aimed to elucidate the prognostic roles of claudin- 1 immunohistochemistry (IHC) in various malignant tumors through a meta-analysis. METHODS: The study included 2,792 patients from 22 eligible studies for assessment of the correlation between claudin-1 expression and survival rate in various malignant tumors. A subgroup analysis based on the specific tumor and evaluation criteria of claudin-1 IHC was conducted. RESULTS: Low claudin-1 expression was significantly correlated with worse overall survival (OS) (hazard ratio [HR], 1.851; 95% confidence interval [CI], 1.506 to 2.274) and disease-free survival (DFS) (HR, 2.028; 95% CI, 1.313 to 3.134) compared to high claudin-1 expression. Breast, colorectal, esophageal, gallbladder, head and neck, and lung cancers, but not cervical, liver or stomach cancers, were significantly correlated with worse OS. Breast, colorectal, esophageal, and thyroid cancers with low claudin-1 expression were associated with poorer DFS. In the lower cut-off subgroup (< 25.0%) with respect to claudin-1 IHC, low claudin-1 expression was significantly correlated with worse OS and DFS. CONCLUSIONS: Taken together, low claudin-1 IHC expression is significantly correlated with worse survival in various malignant tumors. More detailed criteria for claudin-1 IHC expression in various malignant tumors are needed for application in daily practice.

Effects of Variant Histology on the Oncologic Outcomes of Patients With Upper Urinary Tract Carcinoma After Radical Nephroureterectomy: A Propensity Score-Matched Analysis.

PURPOSE: To determine the prognostic effect of upper tract urothelial carcinoma (UTUC) with variant histology (VH) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: The data of 1173 patients who received RNU for UTUC without neoadjuvant chemotherapy in 11 institutions between 2002 and 2016 were retrospectively reviewed. A matched propensity score analysis was performed. Clinicopathologic variables, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between patients with pure UTUC and patients with UTUC and VH. Univariate and multivariate Cox proportional regression models were used to determine the independent variables associated with oncologic outcomes. RESULTS: UTUC with VH was observed in 93 patients (7.9%). After propensity score matching, UTUC with VH showed no difference in clinicopathologic features compared to pure UTUC; however, it was associated with shorter RFS, CSS, and OS (log rank, P = .011, P = .002, P = .006, respectively). Additionally, the multivariate analysis revealed that VH was independently associated with a poor RFS [hazard ratio (HR) = 1.92; 95% confidence interval (CI), 1.27-2.89; P = .002], CSS (HR = 4.47; 95% CI, 1.99-10.1; P = .001), and OS (HR = 3.00; 95% CI, 1.55-5.78; P = .001). However, the Kaplan-Meier method revealed that differences in RFS, CSS, and OS were not significant in patients who received adjuvant chemotherapy (log rank, P = .562, P = .060, P = .153, respectively). CONCLUSION: UTUC with VH was independently associated with poor oncologic outcomes in patients with UTUC after RNU. Although patients with UTUC and VH had a poor prognosis compared to patients with pure UTUC, adjuvant chemotherapy would be helpful in improving the survival rates of these patients.

Prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy: A prospective multicenter study.

OBJECTIVES: To estimate the prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy and to identify the high-risk groups. METHODS: From January 2015 to March 2016, rectal swabs of 557 men who underwent transrectal ultrasound-guided prostate needle biopsy were obtained from five institutions. Clinical variables, including demographics, rectal swab culture results and infectious complications, were evaluated. Univariable and multivariable analyses were used to identify the risk factors for fluoroquinolone resistance of rectal flora and infectious complications. RESULTS: The incidence of fluoroquinolone-resistant and extended-spectrum beta-lactamase production was 48.1 and 11.8%, respectively. The most common fluoroquinolone-resistant bacteria was Escherichia coli (81% of total fluoroquinolone-resistant bacteria, 39% of total rectal flora), and 16 (2.9%) patients had infectious complications. Univariable and multivariable analysis of clinical parameters affecting fluoroquinolone resistance showed no factor associated with fluoroquinolone resistance of rectal flora. The clinical parameter related to infectious complications after prostate biopsy was a history of operation within 6 months (relative risk 6.60; 95% confidence interval 1.99-21.8, P = 0.002). CONCLUSIONS: These findings suggest that a risk-based approach by history taking cannot predict antibiotic resistance of rectal flora, and physicians should consider targeted antibiotic prophylaxis or extended antibiotic prophylaxis for Korean patients undergoing transrectal ultrasound-guided prostate biopsy because of high antibiotic resistance of rectal flora.

Potential Biomarkers for Diagnosis of Overactive Bladder Patients: Urinary Nerve Growth Factor, Prostaglandin E2, and Adenosine Triphosphate.

PURPOSE: This study aimed to investigate potential biomarkers for the diagnosis of overactive bladder (OAB). METHODS: A total of 219 subjects were enrolled and divided into 2 groups: OAB subjects (n=189) and controls without OAB symptoms (n=30). Three-day voiding diaries and questionnaires were collected, and urinary levels of nerve growth factor (NGF), prostaglandin E2, and adenosine triphosphate were measured and normalized to urine creatinine (Cr). Baseline characteristics and urinary levels of markers were analyzed. A receiver-operator characteristic (ROC) curve was used to analyze the diagnostic performance of urinary markers. Urinary levels of markers according to subgroup and pathogenesis of OAB were evaluated. Correlation analyses were used to analyze the relationship between urinary levels of markers and voiding diary parameters and questionnaires. RESULTS: There was no difference between the 2 groups with regards to age, sex ratio, or urine Cr (P>0.05). The urinary levels of NGF/Cr were higher in OAB subjects than in controls (P<0.001). Urinary NGF/Cr was a sensitive biomarker for discriminating OAB patients (area under the curve=0.741; 95% confidence interval, 0.62-0.79; P=0.001) in the ROC curve. The urinary levels of NGF/Cr were significantly higher in OAB subjects than in controls regardless of subgroup or pathogenesis. Correlation analysis demonstrated urinary urgency was significantly related to urinary NGF/Cr level (correlation coefficient, 0.156). Limitations include a relatively wide variation of urinary markers. CONCLUSIONS: Urinary NGF is a potential biomarker that could serve as a basis for adjunct diagnosis of OAB.

Clinicopathological Significance and Prognosis of Medullary Thyroid Microcarcinoma: A Meta-analysis.

BACKGROUND: The objective of the present meta-analysis was to evaluate the clinicopathological significance and prognosis of micro-MTC compared to macro-MTC. METHODS: Relevant articles were obtained by searching the PubMed and MEDLINE databases. A meta-analysis was performed using 15 eligible studies. In addition, subgroup analysis based on heredity was performed in patients diagnosed with micro-MTC. RESULTS: The rate of extrathyroidal extension of micro-MTC [0.118 (95% CI 0.073-0.185)] was significantly lower than that of macro-MTC [0.303 (95% CI 0.224-0.395)]. Micro-MTC [0.229 (95% CI 0.161-0.314)] had a significantly lower rate of cervical lymph node (LN) metastasis compared to macro-MTC [0.595 (95% CI 0.486-0.694)]. The rate of multifocality was not significantly different between micro-MTC and macro-MTC [0.394 (95% CI 0.244-0.566) vs. 0.320 (95% CI 0.234-0.421), respectively]. The rate of distant metastasis did not differ significantly between micro-MTC [0.082 (95% CI 0.017-0.314)] and macro-MTC [0.068 (95% CI 0.009-0.376)]. Patients with micro-MTC showed significantly higher disease-free survival rates [hazard ratio [HR] 0.406 (95% CI 0.288-0.575), I 2 = 40.563%] compared to patients with macro-MTC. CONCLUSION: Micro-MTC has aggressive features, such as multifocality and distant metastasis, similar to macro-MTC and a non-negligible rate of extrathyroidal extension and cervical LN metastasis. We suggest that treatment of micro-MTC should be approached with a similar focus as that of macro-MTC. Considering that less extrathyroidal extension and cervical LN metastasis occur in patients with micro-MTC compared to macro-MTC, we propose that treatment of micro-MTC, which has a relatively low disease burden status, should be viewed as an opportunity for improving prognosis.

Surgical Outcomes of Primary and Recurrent Female Urethral Diverticula.

OBJECTIVE: To evaluate the surgical outcomes of female urethral diverticulectomy. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 68 patients with symptomatic urethral diverticula (UD) with at least 1 year of follow-up data following transvaginal urethral diverticulectomy conducted by a single surgeon. The presence of UD was confirmed by a preoperative magnetic resonance imaging (MRI). According to MRI findings, the UDs were classified as simple, U-shaped, or circumferential. Cure was defined as the absence of residual diverticulum on a postoperative MRI with a resolution of symptoms. RESULTS: There were 27 cases (39.7%) of simple, 16 cases (23.5%) of U-shaped, and 25 cases (36.8%) of circumferential diverticula. The initial cure rate for UD was 77.9%. According to configuration, the cure rates for simple, U-shaped, and circumferential diverticula were 100%, 75.0%, and 64.0%, respectively (P = .043). Of the 15 patients with UD recurrence, 4 did not require reoperation because of symptom resolution. Of the 11 cases that underwent a second operation, 8 patients were cured: 7 via a Martius labial fat pad interposition (MLFI) procedure and 1 via simple excision without MLFI. The overall cure rate was 92.6%. The circumferential configuration was an independent factor for a lower cure rate (odds ratio, 7.97; 95% confidence interval, 1.14-55.69). CONCLUSION: Transvaginal diverticulectomy is an effective treatment for female UD. The success rate of an initial surgery was significantly lower for UDs with circumferential configurations than for simple or U-shaped UDs. Regardless of the initial configuration, MLFI is a good treatment option for recurrent or persistent diverticula.