Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study.

SUMMARY: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

Hypoxia-inducible Factor-1α and mTOR as a Potential Therapeutic Target in Endometriosis: An Immunohistochemical Study.

BACKGROUND AND STUDY AIM: We aim to study the immunohistochemical expression of both hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) in endometriosis to provide new evidence for a targeted endometriosis therapy. PATIENTS AND METHODS: This study comprised 106 endometriotic cases diagnosed clinically and histopathologically. The immunohistochemical method was done to determine the expression of HIF-1α and mTOR. RESULTS: Endometriotic glands showed significant cytoplasmic expression of both markers in patients with poor ovulation, severe endometriosis, and infertile for >2 years ( P <0.001). Also, patients with intense and worst pain show significant immunohistochemical expression of both markers ( P <0.001). There is a significant correlation between mTOR and HIF-1α expression in endometriotic tissue samples as P <0.001. CONCLUSIONS: Our data suggest that both mTOR and its downstream target HIF-1α transcription factor are both disrupted in patients with endometriosis, which is consistent with aberrant activation of these pathways and their possible contribution to the pathogenesis of endometriosis. These results could offer a promising novel opportunity to be blocked therapeutically. As new management options need to be refined in particular in severe cases and infertile patients with endometriosis, therefore future studies are warranted to investigate treating endometriosis with mTOR inhibitors; the latter are already in clinical trials in phase III and IV, treating solid tumors as well as non-neoplastic disorders.

Progesterone/Oestradiol ratio can Better Predict Intracytoplasmic Sperm Injection Outcomes than Absolute Progesterone Level.

BACKGROUND: Several parameters were proposed to predict the impact of premature luteinization on intracytoplasmic sperm injection (ICSI) outcomes such as isolated progesterone (P) level, progesterone to oocyte ratio, and progesterone/estradiol ratio (P/E2). AIM: The aim of this study is to compare the predictive value of P/E2 ratio and isolated P level on the ovulation triggering day for pregnancy outcomes in fresh GnRH antagonist ICSI cycles. SETTINGS AND DESIGN: A retrospective cohort study conducted in a university-affiliated in vitro fertilization center between January 2017 and April 2019. METHODS: The study included women who underwent their first- or second-ranked GnRH antagonist ICSI cycles with day-3 embryo transfer. P/E2 ratio was calculated as (P [ng/mL] × 1000)/E2 (pg/mL). Cutoff values of ≥1.5 ng/ml for high P (HP) and ≥0.55 for HP/E2 ratio were chosen based on the literature. STATISTICAL ANALYSIS: A receiver operating curve was performed to detect the predictability of serum P/E2 and P for the ongoing pregnancy rate. First, patients were divided according to either P level (low P < 1.5 ng/mL and HP ≥1.5 ng/mL) or P/E2 ratio (low P/E2 <0.55 and HP/E2 ≥ 0.55). Patients were further divided into four subgroups: (Group A: HP and HP/E2 ratio, Group B: low P and low P/E2 ratio, Group C: HP only, and Group D: HP/E2 only). A multivariate regression analysis models were used to account for the effect of the cycle confounders on the likelihood of pregnancy. RESULTS: A total of 402 ICSI cycles were analyzed. The area under the curve was 0.67 and 0.59 for P/E2 and P, respectively. P/E2 showed a significant association with ongoing pregnancy (adjusted odds ratios [aOR]: 0.409, 95% confidence interval [CI] 0.222-0.753, P = 0.004) while HP revealed no significant predictive value (aOR: 0.542, 95% CI 0.284-1.036, P = 0.064) after the multivariate analysis. CONCLUSIONS: P elevation may not present as an independent predictor for cycle outcomes. P/E2 ratio has a better prognostic value than P alone in predicting pregnancy of GnRH antagonist cycles.

Effect of Metformin on Premature Luteinization and Pregnancy Outcomes in Intracytoplasmic Sperm Injection-Fresh Embryo Transfer Cycles: A Randomized Double-Blind Controlled Trial.

BACKGROUND: Premature luteinization (PL) is not unusual in in vitro fertilization (IVF) and could not be wholly avoided by using either gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonist regimens. The study aims to evaluate metformin's efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was conducted in a tertiary university IVF center. We recruited infertile women who were scheduled to perform their first or second ICSI trial. Eligible women were recruited and randomized in a 1:1 ratio into two groups. Metformin was administered in a dose of 1500 mg per day since the start of contraceptive pills in the cycle antecedent to stimulation cycle until the day of ovulation triggering, while women in the placebo group received a placebo for the same regimen and duration. The primary outcome was the incidence of PL, defined as serum progesterone (P) on the triggering day ≥1.5 ng/mL. Secondary outcomes comprised the live birth, ongoing pregnancy, implantation, and good-quality embryos rates. RESULTS: The trial involved 320 eligible participants (n=160 in each group). Both groups had comparable stimulation days, endometrial thickness, peak estradiol levels, number of oocytes retrieved, and number of mature oocytes. Metformin group experienced lower level of serum P (P<0.001) and incidence of PL (10 vs. 23.6%, P=0.001). Moreover, lower progesterone/estradiol (P/E) ratio and progesterone to mature oocyte index (PMOI) (P=0.002 and P=0.002, respectively) were demonstrated in women receiving metformin. Metformin group generated a better rate of goodquality embryos (P=0.005) and ongoing pregnancy (43.8 vs. 31.8%, P=0.026). A similar trend, though of borderline significance, was observed in the live birth rate in favor of metformin administration (38.15 vs. 27.5%, P=0.04). CONCLUSION: Metformin could be used in patients with potential PL to improve fresh cycle outcomes by preventing PL (Registration number: NCT03088631).

Multiparametric transvaginal ultrasound in the diagnosis of endometrial cancer in post-menopausal bleeding: diagnostic performance of a transvaginal algorithm and reproducibility amongst less experienced observers.

OBJECTIVE: (a) To comparatively evaluate the performance of grayscale ultrasound features, power Doppler (PD) blood flow characteristics, and gel infusion sonography (GIS) in diagnosing endometrial cancer during real-time examination, (b) to compare the performance of real-time diagnosis of endometrial cancer by experienced observers with offline analysis by blinded observers using similar sonographic criteria during review of cine loop clips. METHODS: 152 females with post-menopausal bleeding (PMB) had ET ≥ 4 mm at first-line ultrasound were included. Two experienced radiologists evaluated endometrial patterns at real-time evaluation (grayscale ultrasound, PD, and GIS), then examinations were stored as video clips for later evaluation by two less-experienced radiologists. The reference standard was hysteroscopy (HY) and/or hysterectomy with the histopathological examination. The area under (AUC) the receiver operating characteristic (ROC) curve was calculated to assess the diagnostic performance for the prediction of endometrial cancer. RESULTS: Among 152 females with ET ≥ 4 mm at first line TVUS, 88 (57.9%) patients had endometrial cancer on final pathologic analysis. Real-time ultrasound criteria (ET ≥ 5 mm with the presence of irregular branching endometrial blood vessels or multiple vessels crossing EM or areas with densely packed color-splash vessels with non-intact or interrupted EMJ at the grayscale ultrasound and/or GIS) correctly diagnosed 95% of endometrial cancers with 92% diagnostic efficiency.There is comparable accuracy of real-time evaluation (96%) and offline analysis (92%) after the exclusion of poor quality videos from the analysis. The diagnostic criteria showed good to an excellent agreement between real-time ultrasound and offline analysis. CONCLUSION: When real-time ultrasound is performed with good technique, utilizing multiple parameters, it is possible to diagnose endometrial cancer with a high degree of accuracy and reproducibility. ADVANCES IN KNOWLEDGE: when real-time ultrasound is performed with good technique, utilizing multiple parameters, it is possible to diagnose endometrial cancer with a high degree of accuracy and reproducibility.

The safety and effectiveness of Bakri balloon in the management of postpartum hemorrhage: a systematic review.

Background: Postpartum hemorrhage (PPH) is a direct cause of maternal death all over the world. A Bakri balloon is recommended by American College of Obstetricians and Gynecologists (ACOG) and World Health Organization (WHO) as a treatment line for PPH unresponsive to uterotonics. We carried out a systematic review to assess the safety and effectiveness of Bakri balloon in the management of PPH.Methods: We searched PubMed, SCOPUS, central Cochrane, and Web of Science, from 2001 to 2018 for randomized controlled trials (RCTs) and observational studies to assess the safety and effectiveness of Bakri balloon on refractory PPH.Results: Twenty-eight articles were included for analysis. The primary indication for the use of a Bakri balloon tamponade was PPH. Only 67.9% (19/28) quantified the estimate blood loss necessary to use the balloon. Uterine atony was the underlying cause of PPH in 75% (21/28) of studies. Most of the studies on Bakri balloon are followed by vaginal birth (3/4). Bakri balloon displacement from the uterine cavity was reported by five publications, with the overall rate being 9% (95% CI: 5-15%). Hysterectomy was necessary for 1% (95% CI: 0-8%) of the women who required the balloon.Conclusions: Bakri balloon seems to be a less effective tool for management of PPH either after vaginal or cesarean delivery.

Vitamin D receptor and cellular retinol-binding protein-1 immunohistochemical expression in normal, hyperplastic and neoplastic endometrium: Possible diagnostic and therapeutic implications.

BACKGROUND: We conducted this study to assess the effect of VDR and CRBP-1 immunohistochemical expression on the endometrium and to explore their role in endometrial cancer carcinogenesis. METHODS: This study comprised two hundred paraffin-embedded endometrial tissue samples diagnosed as 42 and 63 proliferative and secretory endometrium respectively, 45 endometrial hyperplasias with atypia and 50 endometrial carcinomas (25 low-grade and 25 high-grade endometrial carcinomas). The immunohistochemical method was done to determine the expression of VDR and CRBP-1. RESULTS: VDR was strongly expressed in 8 (17.8%) cases with endometrial hyperplasia, 15 (60%) cases with low-grade endometrial carcinoma, and 22 (88%) cases with high-grade endometrial carcinoma. While CRPB1 overexpression was noted in cases with proliferative endometrium, secretory endometrium and endometrial hyperplasia with atypia, 37 (88.1%), 56 (88.9%) and 3 (6.7%) cases respectively and all malignant cases showed negative expression. CONCLUSIONS: Increased VDR expression and reduced CRBP-1 expression are associated with malignant features of the endometrium with a significant statistical difference of immunoreactivity between groups of normal endometrium, hyperplastic changes & carcinoma. Our data suggested that increased VDR expression is partly associated with endometrial cancers through a premalignant phase. Also, increased VDR and reduced CRBP-1 expression are associated with the progression of endometrial carcinoma with higher grades.

Revisiting debates of premature luteinization and its effect on assisted reproductive technology outcome.

The impact of the prematurely elevated serum progesterone on the late follicular phase, commonly known as premature luteinization (PL), is a matter of continuing debate. Available evidence supports that serum progesterone ≥ 1.5 ng/ml on the day of ovulation triggering could reduce the pregnancy potential in fresh in vitro fertilization (IVF) cycles by jeopardizing endometrial receptivity. Causes of PL during ovarian stimulation are unclear. Recent studies point toward the daily follicle-stimulating hormone dosage, duration of controlled ovarian stimulation, number of oocytes retrieved, and peak estradiol level as factors affecting the incidence of PL. Emerging data show additional influence on embryo quality. The prevention of PL has been challenging. The key elements in preventing PL include individualization of ovarian stimulation according to patient's ovarian reserve, proper ovulation trigger timing, and use of medications such as corticosteroids and metformin. Embryo cryopreservation with deferred embryo transfer is the established strategy to overcome PL, yet it is an extra burden to the IVF laboratory and increased cost for patients. Herein, we review the up-to-date knowledge of this frequent IVF problem including causes, proposed diagnostic criteria, and its impact on endometrial receptivity, embryo quality, and pregnancy outcomes. The preventive measures and rescue strategies are also discussed.

The accuracy of multi-detector computed tomography and laparoscopy in the prediction of peritoneal carcinomatosis index score in primary ovarian cancer.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare the accuracy of MDCT and laparoscopy in the prediction of peritoneal carcinomatosis index score. Reproducibility of MDCT interpretation was also assessed. METHODS: This prospective study included 85 ovarian cancer patients underwent MDCT and diagnostic laparoscopy before cytoreductive surgery. We calculated the accuracy of diagnostic modalities in the calculation of the peritoneal cancer index score (PCI). Radiologist interobserver agreement was calculated using kappa statistics. RESULTS: Nine hundred-thirty (84.2%) of the 1105 regions had peritoneal deposits at exploratory laparotomy. Computed tomography (CT) and laparoscopy sensitivity were 94.9%, 98.3%, specificity 86.7%, 80.4%, PPV 97.9 %, 96.8%, NPV 72.2%, 88.8 %, and accuracy 93.8 %, 95.7%, respectively. However, computed tomography (CT) diagnostic performance is less accurate than laparoscopy in pelvic and small intestinal regions; no statistically significant differences were evident regarding total PCI score compared to surgery (p> 0.05). CT and laparoscopy correctly depicted peritoneal carcinomatosis in 88.2%, 90.6% of patients, respectively. Optimal cytoreduction was achieved in 68 (80%) patients. CONCLUSION: Both CT and laparoscopy seems to be effective tools for assessment of peritoneal carcinomatosis using the PCI score. Dedicated MDCT protocol with routine use of a standardized PCI form may provide better comprehensive multi-regional analysis that may help surgeons referring patients to the best treatment option. Laparoscopy is a valuable tool in cases with a high risk of suboptimal cytoreduction related to disease extent.

Accuracy of radiologic- laparoscopic peritoneal carcinomatosis categorization in the prediction of surgical outcome.

OBJECTIVE: To evaluate the agreement between multiple detector CT (MDCT) and laparoscopy in the preoperative categorization of peritoneal carcinomatosis, and to determine the impact of this categorization on the prediction of cytoreduction status. METHODS: This prospective study included 80 consecutive females with primary ovarian cancer eligible for cytoreductive surgery (CRS). MDCT and diagnostic laparoscopy were performed prior to surgery for assessment of peritoneal carcinomatosis extent. Based on PCI (peritoneal cancer index) score, carcinomatosis was categorized into three groups. Categorization agreement between CT and laparoscopy was assessed and compared with the intraoperative-histopathologically proven PCI. Impact of PCI categorization on cytoreduction status was also evaluated. RESULTS: The overall agreement between CT and laparoscopy in preoperative peritoneal carcinomatosis categorization was good (K =0.71-0.79) in low category group and excellent in both moderate and large group (interclass correlation coeeficient = 0.89-0.91). (p<0.01) Optimal cytoreduction was achieved in 62/80 (77.5%) patients, PCI < 20 was detected in 48/62 (77.4%), pre-operative PCI < 20 correctly predicted optimal cytoreductive surgery (OCS) in 40/48 (83.3%) cases. Suboptimal cytoreduction was performed in 18/80 (22.5%) patients. PCI > 20 was detected in (10/18) 55.6%, preoperative CT and laparoscopy PCI > 20 correctly predicted SCS in 8/10 (80%) cases. The area under receiver operating characteristic curve showed that PCI cut-off <20 was the best predictor of OCS with an accuracy 85%, sensitivity 97%, specificity 40%, negative predictive value 76%, and positive predictive value 93%. CONCLUSION: Both laparoscopy and CT are equally effective in pre-operative peritoneal carcinomatosis categorization. PCI < 20 is accurate in the prediction of optimal cytoreduction. More than half of patients with suboptimal cytoreduction had PCI > 20 and interval debulking surgery can be recommended. ADVANCES IN KNOWLEDGE: Both laparoscopy and CT are equally effective in pre-operative peritoneal carcinomatosis categorization. PCI < 20 is accurate in the prediction of optimal cytoreduction. More than half of patients with suboptimal cytoreduction had PCI > 20 and interval debulking surgery can be recommended.

Human uterine leiomyoma contains low levels of 1, 25 dihdroxyvitamin D3, and shows dysregulated expression of vitamin D metabolizing enzymes.

OBJECTIVES: To evaluate tissue concentration of 1, 25 dihydroxyvitamin D3, and gene expression level of CYP27B1 that codes for 1-α hydroxylase (vitamin D activating enzyme), and CYP24A1 that codes for 24-hydroxylase (vitamin D catabolizing enzyme) in human uterine leiomyoma (ULM), its adjacent myometrium (Myo-F), and normal myometrium (Myo-N). STUDY DESIGN: Levels of 1, 25 dihydroxyvitamin D3 were measured using HPLC and Diode detectors whereas CYP27B1, and CYP24A1 expressions were assessed using Real-Time PCR in ULM, Myo-F, and Myo-N. Non-parametric statistics were used. RESULTS: ULMs contained significantly less 1, 25 dihydroxy vitamin D3 compared to Myo-F (3.0, IQR: 1.0-9.0 versus 6.0, IQR: 3.0-13.0 µg/ kg, P value is 0.03). No significant difference was detected between ULM and Myo-N, or Myo-F and Myo-N. Intratumoral level of the active form of vitamin D did not differ according to the type of ULM (submucous or interstitial/subserous), or to the ULM volume. CYP27B1 was expressed in ULM (2.17, IQR: 0.65-4.9), Myo-F (4.94, IQR: 1.04-22.59), and Myo-N (0.99, IQR: 0.49-1.71) to a comparable level. CYP24A1 expression was significantly higher in ULM compared to Myo-N (2.00, IQR: 0.69-10.77 versus 0.22, IQR: 00- 0.96, respectively, P value is 0.04). CONCLUSIONS: Human ULMs contain significantly lower 1, 25 dihydroxyvitamin D3 than its adjacent myometrium. ULM, Myo-F, and Myo-N express CYP27B1 and CYP24A1. ULMs express significantly higher level of CYP24A1 than normal myometrium indicating that over expression of 24-hydroxylase is a mechanism by which ULMs sustain a relative state of hypovitaminosis D.

Exome Sequencing Landscape Analysis in Ovarian Clear Cell Carcinoma Shed Light on Key Chromosomal Regions and Mutation Gene Networks.

Previous studies have reported genome-wide mutation profile analyses in ovarian clear cell carcinomas (OCCCs). This study aims to identify specific novel molecular alterations by combined analyses of somatic mutation and copy number variation. We performed whole exome sequencing of 39 OCCC samples with 16 matching blood tissue samples. Four hundred twenty-six genes had recurrent somatic mutations. Among the 39 samples, ARID1A (62%) and PIK3CA (51%) were frequently mutated, as were genes such as KRAS (10%), PPP2R1A (10%), and PTEN (5%), that have been reported in previous OCCC studies. We also detected mutations in MLL3 (15%), ARID1B (10%), and PIK3R1 (8%), which are associations not previously reported. Gene interaction analysis and functional assessment revealed that mutated genes were clustered into groups pertaining to chromatin remodeling, cell proliferation, DNA repair and cell cycle checkpointing, and cytoskeletal organization. Copy number variation analysis identified frequent amplification in chr8q (64%), chr20q (54%), and chr17q (46%) loci as well as deletion in chr19p (41%), chr13q (28%), chr9q (21%), and chr18q (21%) loci. Integration of the analyses uncovered that frequently mutated or amplified/deleted genes were involved in the KRAS/phosphatidylinositol 3-kinase (82%) and MYC/retinoblastoma (75%) pathways as well as the critical chromatin remodeling complex switch/sucrose nonfermentable (85%). The individual and integrated analyses contribute details about the OCCC genomic landscape, which could lead to enhanced diagnostics and therapeutic options.

Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma.

Somatic mutations in the ARID1A tumor-suppressor gene have been frequently identified in ovarian clear cell carcinoma (CCC) cases. BAF250a encoded by ARID1A is a member of the SWI/SNF complex, but the expression and mutation status of other SWI/SNF subunits have not been explored. The current study aimed to elucidate the biological and clinical significance of the SWI/SNF complex subunits, by assessing the expression and mutation status of SWI/SNF subunits, and distinct genomic aberrations associated with their expression. Of 82 CCC specimens, 38 samples presented no BAF250a expression, and 50 samples exhibited the loss of at least one subunit of the SWI/SNF complex. Cases which lack at least one SWI/SNF complex component exhibited significantly more advanced stages, faster growth and stronger nuclear atypia compared with SWI/SNF-positive samples (p<0.05). Although BAF250a expression is not related to poor prognosis, the group presenting the loss of at least one SWI/SNF complex subunit exhibited significantly shorter overall and progression-free survivals (p<0.05). A multivariate analysis suggested that the expression status of the SWI/SNF complex serves as an independent prognostic factor (p<0.005). The cases positive for all SWI/SNF subunits demonstrated significantly greater DNA copy number alterations, such as amplification at chromosomes 8q.24.3 and 20q.13.2-20q.13.33 (including ZNF217) and deletion at chromosomes 13q12.11-13q14.3 (including RB1), 17p13.2-17p13.1 (including TP53) and 19p13.2-19p13.12. In conclusion, the CCCs exhibiting the loss of one or multiple SWI/SNF complex subunits demonstrated aggressive behaviors and poor prognosis, whereas the CCCs with positive expression for all SWI/SNF components presented more copy number alterations and a favorable prognosis.

Clinical efficacy of neoadjuvant chemotherapy with irinotecan (CPT-11) and nedaplatin followed by radical hysterectomy for locally advanced cervical cancer.

OBJECTIVE: To investigate the clinical efficacy of neoadjuvant chemotherapy (NAC) with irinotecan (CPT-11) and nedaplatin (NED) followed by radical hysterectomy. METHODS: Patients with locally advanced cervical cancer (stage Ib2-IIb) were treated with NAC followed by surgery, primary surgery or primary radiotherapy. NAC was usually performed using transuterine arterial chemotherapy (TUAC) or intravenous CPT-11/NED. Survival rates were analysed in the three treatment groups; response rates and adverse events associated with NAC, TUAC and CPT-11/NED were compared, along with previously reported adverse events of chemoradiotherapy. RESULTS: A total of 165 patients with cervical cancer were recruited. Of these, 70 were treated with NAC followed by surgery (48 with CPT-11/NED, 18 with TUAC and four with other types of chemotherapy), 73 were treated with primary surgery and 22 with primary radiotherapy (including chemoradiotherapy). There were no significant differences in progression-free survival or overall survival rates between the three treatment groups. The response rates for the NAC regimen of CPT-11/NED and TUAC were high (75% and 78%, respectively). The frequency of severe thrombocytopenia was lower in patients receiving CPT-11/NED compared with TUAC, and the incidence of severe anaemia, vomiting and cystitis was lower in patients receiving CPT-11/NED compared with chemoradiotherapy. CONCLUSIONS: The use of CPT-11/NED as a NAC regimen shows favourable activity, with lower toxicity compared with NAC using TUAC or chemoradiotherapy, for the treatment of locally advanced cervical cancer.

Stem cell applications for pathologies of the urinary bladder.

New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient's quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context.

A novel diagnostic criterion for lymph node metastasis in cervical cancer using multi-detector computed tomography.

OBJECTIVES: The sensitivity of the current 10mm cut-off diameter that is used to diagnose lymph node (LN) metastasis is too low. This is the first study to develop a new criterion to diagnose LN metastasis in a region-by-region manner using multi-detector computed tomography (MDCT). METHODS: 1) The short-axis diameter of the LNs in MDCT images from 1-mm slices obtained immediately prior to surgery was compared with the pathological diagnosis in 78 uterine cervical cancer patients undergoing primary surgery. For the region-by-region analysis, we divided para-aortic and pelvic spaces into 13 regions. 2) In 28 cases in which patients received neoadjuvant chemotherapy (NAC) followed by surgery, we compared MDCT images before and after NAC. RESULTS: 1) The optimal cut-off in the region-by-region analysis was 5mm, yielding 71% sensitivity and 79% specificity. 2) NAC significantly decreased LN size (p<0.0001). NAC decreased the number of swollen LN regions (>5mm) from 51% (81/158) to 26% (41/158). CONCLUSIONS: The new criterion developed using MDCT could be effective for accurately assessing LN status. It also facilitates the assessment of NAC efficacy regarding the eradication of LN metastases.