Outcomes of conception subsequent to methotrexate treatment for an unruptured ectopic pregnancy.

OBJECTIVE: To assess the risk of adverse pregnancy outcomes in subsequent pregnancies among women treated with methotrexate for ectopic pregnancy. METHODS: In a retrospective single-center study, data were assessed for women treated with methotrexate for ectopic pregnancy at Asaf Harofe Medical Center, Zerifin, Israel, between May 2004 and May 2014. RESULTS: Overall, 226 women were treated with methotrexate for ectopic pregnancy and subsequently conceived. The median time from treatment to conception was 10 months (range 1-120 months), and 127 women conceived within 12 months of treatment. Except for early missed abortion-which affected 23 (10.2%) pregnancies-adverse pregnancy outcomes such as fetal malformations were rare. The frequency of early abortion was lowest for women who conceived within 6 months of treatment with methotrexate (3/93, 3.2%), increased between 6 and 23 months (15/83, 18.1%), and remained high thereafter (7/50, 14.0%; P=0.006). CONCLUSION: The frequency of fetal malformation in a subsequent pregnancy was low among women treated with methotrexate for ectopic pregnancy. The frequency of early missed abortion was lowest during the first 6 months after treatment with methotrexate.

Evaluation of Clinical and Pathologic Risk Factors May Reduce the Rate of Multimodality Treatment of Early Cervical Cancer.

OBJECTIVE: To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. METHODS: This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. RESULTS: We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10 mm received RT, and 87% of patients with tumors depth of invasion >10 mm and lymph-vascular space invasion received RT. CONCLUSIONS: This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation.

Infertility Following Retained Products of Conception: Does the Timing of Surgical Intervention Matter?

BACKGROUND: Despite the large volume of evidence on the management of retained products of conception (RPOC), there are virtually no data regarding the optimal time frame of surgical intervention in case of RPOC. OBJECTIVES: To examine whether the time interval between spontaneous vaginal delivery or pregnancy termination and the uterine evacuation due to pathologically confirmed RPOC influences the reproductive outcome. METHODS: We retrospectively reviewed all the records of women who were admitted to our department due to pathologically confirmed RPOC following either spontaneous vaginal delivery or pregnancy termination between January 2000 and December 2010. Based on the median time from delivery or pregnancy termination until the operative intervention in the study group, patients were stratified into two groups: early intervention (< 3 weeks) and late intervention (> 3 weeks). Reproductive outcomes were compared between the two study groups. RESULTS: Reproductive outcomes were analyzed in 172 patients with pathologically confirmed RPOC. Of them, 95 (55.2%) were included in the early intervention group and 77 (44.8%) in the late intervention group. There were no significant differences in the conception rate, mean time to conception, and the occurrence rate of a new infertility problem in women with early surgical intervention compared to those with late surgical intervention (P > 0.05). Furthermore, there was no significant difference between the groups in the pregnancy outcomes following RPOC. CONCLUSIONS: Early surgical intervention in women with pathologically confirmed RPOC following spontaneous vaginal delivery or pregnancy termination yields the same reproductive outcomes as late surgical intervention.

Comparison of Reproductive Outcomes following Retained Products of Conception after Vaginal Delivery versus First-Trimester Abortion.

OBJECTIVE: To compare the reproductive outcomes of women with pathologically confirmed retained products of conception (RPOC) following spontaneous vaginal delivery versus first-trimester pregnancy termination. METHODS: We retrospectively reviewed all cases of women who underwent uterine re-evacuation due to pathologically confirmed RPOC between January 1, 2000 and December 31, 2010. Reproductive outcomes were compared between women with RPOC following spontaneous vaginal delivery and those who underwent dilatation and curettage (D&C) due to first-trimester abortion. RESULTS: The study group consisted of 176 patients with pathologically confirmed RPOC. Of those, 83 (47.1%) were admitted after spontaneous vaginal delivery and 93 (52.9%) following D&C due to first-trimester abortion. There were no significant differences in the conception rate, the mean time to conception and the rate of a new infertility problem between women with RPOC after vaginal delivery compared to those following pregnancy termination (p > 0.05). Furthermore, there were no significant differences between the groups in pregnancy outcomes following RPOC. CONCLUSION: Pathologically confirmed RPOC harbors the same reproductive outcomes following spontaneous vaginal delivery and first-trimester pregnancy termination.

Prevalence and risk factors of inadequate cervical dilation following laminaria insertion in second-trimester abortion--case control study.

OBJECTIVE: The objective was to explore the prevalence of and risk factors for inadequate cervical dilation following insertion of a single set of laminaria in women scheduled for dilation & evacuation (D&E) at 14-24 weeks' gestation. STUDY DESIGN: We retrospectively reviewed all cases of women who underwent pregnancy termination by D&E at 14-24 weeks' gestation between January 2003 and December 2013. All cases in which the surgical procedure was cancelled due to failure to achieve adequate cervical dilation after a single set of laminaria inadequate cervical dilation were included. The control group was women who underwent D&E following adequate cervical dilation after a single set of laminaria, and were matched according to gestational week in a ratio of 1:3. RESULTS: The overall dilation failure rate was 3.2%, with 4.0% among the induced-abortion patients and 1.5% among the patients with fetal demise (p=.002). Patients who had inadequate cervical dilation had lower rates of gravidity (p=.002) and previous spontaneous vaginal delivery (p<.001), along with higher rates of primigravidity, nulliparity (p<.001), previous cesarean section/s (p=.041), previous abdominal surgeries (p=.001) and previous cervical procedures (p=.003), compared to controls. A multivariable logistic regression analysis revealed two risk factors for inadequate cervical dilation following laminaria insertion, namely, previous cesarean section (p=.002) and previous cervical procedure (p<.001), whereas increased gravidity was found to protect against inadequate cervical dilation (p=.002). CONCLUSIONS: Previous cesarean section/s, cervical procedures and primigravidity were found to be risk factors for failure to achieve adequate cervical dilation after a single set of laminaria. Women who are scheduled for D&E, and in whom one of these risk factors exists, might benefit from additional interventions to achieve better cervical preparation.

Intrauterine adhesions after hysteroscopic treatment for retained products of conception: what are the risk factors?

OBJECTIVE: To assess the prevalence and risk factors for intrauterine adhesions (IUAs) after hysteroscopic treatment of retained products of conception (RPOC). DESIGN: Retrospective cohort study. SETTING: Gynecologic endoscopy unit. PATIENT(S): A total of 167 women referred to our institution from 2009 to 2013. INTERVENTION(S): Operative hysteroscopy for treatment of RPOC and office hysteroscopic follow-up to assess for IUA. MAIN OUTCOME MEASURE(S): We investigated demographic characteristics, obstetrics parameters, and surgical variables to evaluate which factors could be associated with IUA formation. RESULT(S): Of 167 women treated for RPOC, 84 (50.3%) had undergone a follow-up hysteroscopic evaluation after the operative hysteroscopy and were included in the study. Intrauterine adhesions were found in 16 cases (19.0%), of which only 3 (3.6%) were severe adhesions. Multivariate analysis showed that the presence of IUA was associated with RPOC after cesarean section (5 of 10 [50.5%] developed IUA, vs. 7 of 49 [14.3%] after vaginal delivery). Intrauterine adhesions were also found in 4 of 23 women (17.4%) undergoing hysteroscopy for RPOC after abortion. Patient age, gravidity, parity, and the interval between the index pregnancy and treatment for RPOC were not associated with postoperative IUA. CONCLUSION(S): Hysteroscopic treatment for RPOC had a 3.6% incidence of severe intrauterine adhesions formation in this descriptive series. Women with RPOC occurring after delivery by cesarean section are particularly at risk for development of IUA.

Infertility following retained products of conception: is it the surgical procedure or the presence of trophoblastic tissue?

OBJECTIVE: To compare the reproductive outcome of women who underwent re-evacuation of the uterine cavity due to suspected retained products of conception (RPOC) and in whom trophoblastic tissue was confirmed by histopathologic examination to those with negative pathologic findings. STUDY DESIGN: We retrospectively reviewed all cases of women who underwent uterine re-evacuation due to suspected RPOC between January 2000 and December 2010. Reproductive outcomes were compared between women in whom trophoblastic tissue was confirmed by histopathologic examination and those with negative pathologic findings. RESULTS: A total of 240 patients underwent uterine re-evacuation due to suspected RPOC, of whom 162 (67.5%) had pathological examination positive for RPOC, and 78 (32.5%) had pathologically negative RPOC. The rate of a new infertility problem following resection of a positive pathologic finding was significantly higher compared with a negative finding (P=0.029). The mean time to conception was significantly longer after resection of a positive pathologic finding compared with a negative finding (P<0.001). A significantly higher rate of hypomenorrhea/amenorrhea was found following resection of a positive pathologic finding compared with a negative finding (P=0.017). CONCLUSION: RPOC-associated infertility is primarily related to the presence of trophoblastic tissue rather than the surgical intervention per se in the gravid uterus.

Integration of PET/CT into the preoperative evaluation of patients with early cervical cancer does not decrease the proportion of patients with positive lymph nodes found after surgery.

PURPOSE: The aim of this study was to evaluate whether preoperative positron emission tomography/computed tomography (PET/CT) in patients with early-stage cervical carcinoma reduced the proportion of patients with metastatic lymph nodes identified after surgery. PATIENTS AND METHODS: This is a multicenter case-control study of 599 patients with early cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy at 1 of 10 gynecological oncology units in Israel. The patients were divided into 2 groups according to whether or not they underwent a preoperative PET/CT. The primary outcome was the proportion of patients with nodal involvement. The 2 groups were compared with regard to the clinical and histological variables. RESULTS: Of the 599 patients who underwent surgery, 180 (36%) had preoperative PET/CT study. There were no significant differences between the PET/CT and control groups with regard to clinical and histological risk factors. The proportion of patients with involved nodes was similar in the control and PET/CT groups (20.8% vs 19%; P = 0.73) as well as the proportion of patients receiving adjuvant radiotherapy/chemoradiation (58.3% vs 55.1%; P = 0.55). CONCLUSIONS: Preoperative PET/CT in patients with early cervical cancer does not reduce proportion of patients with metastatic nodal involvement and the employment of multimodality treatment. Prospective clinical trials comparing management based on PET/CT findings are warranted.

A comparison of reproductive outcomes following hysteroscopic management versus dilatation and curettage of retained products of conception.

OBJECTIVE: To compare the reproductive outcome of women who underwent blind dilatation and curettage (D&C) with those who underwent hysteroscopic resection of pathologically confirmed retained products of conception (RPOC). METHODS: Medical records of women who underwent either D&C or hysteroscopic resection of RPOC at Assaf Harofeh Medical Center, Israel, between 2000 and 2010 were retrospectively reviewed. RESULTS: A total of 177 women with pathologically confirmed RPOC underwent either D&C (n=94, 53.1%) or hysteroscopy (n=83, 46.9%). Mean time to conception was significantly shorter after hysteroscopy than after D&C (7.4±7 vs 12.9±16.8 months, P=0.037). Rate of occurrence of a newly diagnosed infertility problem was significantly higher following D&C than hysteroscopy (23 [24.5%] vs 10 [12.0%]; P=0.034). Etiology of the new problem was mechanical, including tubal occlusion and intrauterine adhesions. Logistic regression comparing both methods revealed that hysteroscopic resection was associated with a significant reduction in the occurrence of a new infertility problem compared with D&C (OR 0.42; 95% CI, 0.18-0.96, P=0.04). CONCLUSION: Hysteroscopic removal of RPOC is associated with a shorter mean time to further conception and a lower rate of occurrence of newly diagnosed infertility problems than D&C.

Intercoat (Oxiplex/AP gel) for preventing intrauterine adhesions after operative hysteroscopy for suspected retained products of conception: double-blind, prospective, randomized pilot study.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of Oxiplex/AP gel (Intercoat) in reducing intrauterine adhesion formation after hysteroscopic treatment because of retained products of conception (RPOC). DESIGN: Prospective double-blind, randomized, controlled pilot study (Canadian Task Force classification I). SETTING: Tertiary medical center. PATIENTS: All women who underwent hysteroscopic treatment because of RPOC at our institution between September 2009 and June 2012 were invited to participate. After operative hysteroscopy, participants were randomized to either have their uterine cavity filled with Oxiplex/AP gel (study group, n = 26) or not (control group, n = 26). INTERVENTIONS: Diagnostic office hysteroscopy to assess for adhesion formation was performed after 6 to 8 weeks. Findings were graded according to the American Fertility Society classification. Rates of subsequent pregnancy in the 2 groups were assessed. MEASUREMENTS AND MAIN RESULTS: Intraoperative complication rates were similar between the 2 groups. There were no postoperative complications after Oxiplex/AP gel application. Moderate to severe adhesions developed in 1 woman (4%) in the study group and 3 (14%) in the control group (p = .80). During follow-up of 20 months (range, 2-33 months), 7 women (27%) in the treatment group conceived, compared with 3 (14%) in the control group (p = .50). CONCLUSION: Intrauterine application of Oxiplex/AP gel after hysteroscopic removal of RPOC is safe. In this small sample, the difference in the rate of intrauterine adhesions was not statistically significant. A larger study would enable further establishment of the safety and efficacy of use of this gel.

Clinical, surgical, and histopathologic outcomes following failed medical abortion.

OBJECTIVE: To address the consequences of surgical curettage following failed medical abortion. METHODS: A retrospective case-control study was performed in a tertiary gynecologic department. The case group comprised 104 women who underwent surgical curettage following failed medical abortion; the control group included 104 women who underwent early surgically induced abortion. Clinical characteristics and surgical findings were examined. The extent of inflammation was quantified following immunohistochemical staining for cell-surface markers characteristic of T lymphocytes, B lymphocytes, and macrophages. The extent of necrosis was evaluated morphologically. RESULTS: Abnormal findings during surgical curettage were significantly more prevalent among women in the case group than in the control group (10.6% versus 1.9%; P=0.019). The most frequent abnormality in the case group was the presence of intimately adherent products of conception, necessitating sharp curettage. The extent of inflammation (represented by increased numbers of T and B lymphocytes) was greater in the case group than in the control group (P=0.046 and P=0.001, respectively), as was the extent of necrosis (P<0.05). CONCLUSION: Curettage following failed medical abortion harbors particular difficulties, which may be attributed to an inflammatory response. The long-term consequences of curettage following failed medical abortion warrant further investigation.

Coagulopathy associated with dilation and evacuation for second-trimester abortion.

OBJECTIVE: To characterize the clinical and laboratory features of coagulopathy following second-trimester surgical abortions. DESIGN. Retrospective study. SETTING: Gynecologic unit of a university-affiliated medical center. POPULATION: 1249 consecutive women underwent late second-trimester (16-24 weeks) surgical abortions between January 2002 and June 2010. Of those, 20 women (1.6%) were diagnosed with excessive bleeding accompanied by coagulopathy. METHODS: Women were divided into two groups based on whether the abortion was performed for fetal demise (n=14) or pregnancy termination (n=6). MAIN OUTCOME MEASURES: Gestational age, indication for abortion, blood clotting tests, number of blood products and coagulation factors administered. RESULTS: Women who had pregnancy termination began to bleed significantly earlier than those with fetal demise (p<0.05). A significantly higher number of women with fetal demise had a gradual deterioration of the clotting test, compared with women who had pregnancy termination (p<0.05). In women with fetal demise, early bleeding was associated with a more severe clinical presentation. CONCLUSIONS: Coagulopathy following surgical abortion manifests differentially in women who have fetal demise and those who have pregnancy termination, implying a different pathophysiology. Women with fetal demise suffering from excessive bleeding following surgical abortion accompanied with mild clotting test abnormalities should be carefully monitored to diagnose and treat an impending disseminated intravascular coagulation.

Fertility performance and obstetric outcomes among women with previous cesarean scar pregnancy.

OBJECTIVES: The purpose of this study was to assess fertility performance and obstetric outcomes after treatment of cesarean scar pregnancy. METHODS: We conducted a retrospective study in a large tertiary hospital in Israel. The study included 18 women with a diagnosis of cesarean scar pregnancy between 2000 and 2009. RESULTS: The incidence of cesarean scar pregnancy among our parturient patients was 1 per 3000 for the general obstetric population and 1 per 531 among those with at least 1 cesarean delivery. Sixteen were treated primarily with methotrexate. Two were treated primarily by surgery, and 2 more were treated by surgery after failed methotrexate treatment. After cesarean scar pregnancy treatment, 7 women conceived spontaneously, and 1 conceived by in vitro fertilization-intracytoplasmic sperm injection. The remaining 10 (55%) did not wish to conceive again. Two of the women who became pregnant (25%) had recurrent cesarean scar pregnancy. CONCLUSIONS: This study shows encouraging results for fertility performance and obstetric outcomes after treatment of cesarean scar pregnancy. Nevertheless, the risk of recurrent cesarean scar pregnancy is not negligible.

Inadvertent rupture of benign cystic teratoma does not impair future fertility.

OBJECTIVE: We sought to investigate the reproductive outcomes of women who underwent laparoscopic removal of benign cystic teratoma with or without intraoperative spillage. STUDY DESIGN: The reproductive outcomes of reproductive age women following laparoscopic removal of benign cystic teratoma from 1997 through 2007 were investigated by a telephone questionnaire. RESULTS: In all, 128 reproductive age women underwent benign cystic teratoma removal, and reproductive outcomes were available for 45. Among those 45 women, intraoperative spillage occurred in 16 (35.6%). The rate of spontaneous pregnancies was significantly lower for the nonspillage compared to the intraoperative spillage groups (20/29 [68.9%] vs 16/16 [100%], respectively; P = .01). However, the median time from surgery to the first pregnancy was similar (22 and 18.5 months, respectively; P = .9). From the 9 remaining women in the nonspillage group, 4 conceived with ovulation induction, 2 conceived with in vitro fertilization, and 3 were infertile. CONCLUSION: Intraoperative spillage of benign cystic teratomas does not lead to long-term infertility.

Twin tubal pregnancy: a rising complication?

OBJECTIVE: To present four cases of twin tubal pregnancies and discuss possible etiologies. Twin tubal pregnancies are a rare event, with incidence rates estimated as 1 out of 725-1,580 of tubal pregnancies. DESIGN: Case series. SETTING: Department of obstetrics and gynecology at a tertiary health care facility. PATIENT(S): All women with twin tubal pregnancy diagnosed and treated in the department during the years 2007-2009, according to electronic files and histologic reports. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Artificial reproductive technique preceding twin tubal pregnancies RESULT(S): We diagnosed four twin pregnancies of 163 tubal pregnancies, an incidence of 2.4%. Of the four cases, two conceived after gonadotropin stimulation and intrauterine insemination. The third conceived following in vitro fertilization and intracytoplasmic sperm injection. The fourth was a spontaneous conception diagnosed as monochorial monoamniotic twin tubal pregnancy. CONCLUSION(S): Twin tubal pregnancies may not be as rare as previously thought. Three of the four cases identified during a 2-year period followed artificial reproductive technique. We hope that this report will promote the study of the epidemiology of this event, improve diagnosis, and encourage the development of treatment modalities.

Oophoropexy to prevent adnexal torsion: how, when, and for whom?

STUDY OBJECTIVE: To assess the efficacy of oophoropexy in obviating recurrent torsion and its possible long-term effects. DESIGN: Case series and review of the literature (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: Women who underwent oophoropexy for recurrent torsion of normal adnexa between 2003 and 2008. MEASUREMENTS AND MAIN RESULTS: Retrieved information included the indication for oophoropexy, surgical methods, recurrence, and follow-up. Seven women underwent oophoropexy during the study period because of recurrent torsion of normal adnexa. One additional patient had experienced 3 torsion events of cystic adnexa. Surgical methods included suturing of the ovary to the pelvic sidewall or to the round ligament and plication of the utero-ovarian ligaments. Recurrence occurred in 1 of 6 patients for whom follow-up was available. All 6 patients reported spontaneous menstruation, and 2 conceived spontaneously and gave birth. Ultrasound at long-term follow-up (9-58 months) demonstrated normal ovaries. CONCLUSION: Oophoropexy seems to be efficacious in preventing recurrent torsion. It is our impression that plication of the utero-ovarian ligaments has advantages over other approaches insofar as surgical feasibility and anatomical conservation.

Does intraoperative spillage of benign ovarian mucinous cystadenoma increase its recurrence rate?

OBJECTIVE: To report a higher than estimated recurrence rate of benign mucinous cystadenomas after complete resection of the first one, and to assess potential risk factors for recurrence after complete surgical excision. STUDY DESIGN: We retrospectively reviewed all cases of women who underwent either laparoscopic or laparotomic removal of benign mucinous adnexal cysts by either adnexectomy or cystectomy in our institution between 1996 and 2006. RESULTS: Included were the data of 42 women who fulfilled study entry criteria. Three of them (7.1%) underwent a second operation because of a recurrence of the lesion. A significantly higher rate of women who had cyst recurrence had undergone cystectomy as opposed to adnexectomy (P < .05). Intraoperative rupture of cysts during cystectomy was also significantly associated with cyst recurrence (P < .03). CONCLUSION: Mucinous cystadenoma recurrence is apparently not as rare as reported in the literature. Intraoperative cyst rupture and cystectomy instead of adnexectomy emerged as being two risk factors for recurrence.

Maternal adnexal torsion in pregnancy is associated with significant risk of recurrence.

STUDY OBJECTIVES: To investigate the phenomenon of recurrent adnexal torsion during the same pregnancy, describe its risk factors, and suggest possible management of this entity. DESIGN: Retrospective case-control study (Canadian Task Force classification II-3). SETTING: Gynecologic endoscopy unit in a university hospital. PATIENTS AND INTERVENTIONS: Pregnant women with surgically proved adnexal torsion were retrospectively identified from 1993 to 2007. Details of clinical presentation, method of conception, preoperative ultrasound findings, and operative findings were analyzed. INTERVENTION: Comparison of characteristics of patients with recurrent episodes of adnexal torsion during the same pregnancy vs a single episode of torsion. MEASUREMENTS AND MAIN RESULTS: Thirty-three pregnant women with 38 episodes of adnexal torsion were included in the study. Seventeen pregnancies (51.5%) were spontaneously conceived. Twenty-eight women had a single episode of torsion, and 5 women (15.1%) had recurrent episodes of torsion during the same pregnancy. No significant differences were found between the 2 groups in age, method of conception, and gestational age at time of torsion. However, ultrasound studies demonstrated that multicystic ovaries were significantly more common in women with recurrent torsion compared with women with a single episode of torsion (80% vs 25%; p =.02). The interval between the first and second episodes of torsion ranged from 1 to 4 weeks. CONCLUSION: Pregnant women are at risk for recurrent torsion, especially when the ovaries are enlarged and ultrasound studies demonstrate multiple cysts. Cyst aspiration may prevent recurrent torsion during the same pregnancy.

Expression of stem cell markers in the human fetal kidney.

In the human fetal kidney (HFK) self-renewing stem cells residing in the metanephric mesenchyme (MM)/blastema are induced to form all cell types of the nephron till 34(th) week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms' tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms' tumor xenografts (NCAM, ACVRIIB, DLK1/PREF, GPR39, FZD7, FZD2, NTRK2) are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers (CD34, CD133, c-Kit, CD90, CD105, CD24) in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules (<10% of HFK cells) and were mostly present within the EpCAM(neg) and EpCAM(dim) fractions, indicating putative stem/progenitor markers. In contrast, single markers such as CD24 and CD133 as well as double-positive CD24(+)CD133(+) cells comprise >50% of HFK cells and predominantly co-express EpCAM(bright), indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem/progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM(+)EpCAM(-) and to a lesser extent in NCAM(+)EpCAM(+) fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells (NCAM(+)EpCAM(+)FZD7(+)), MM stem cells (NCAM(+)EpCAM(-)FZD7(+)) or both (NCAM(+)FZD7(+)). These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies.

Diagnosis and treatment of pediatric vaginal and genital tract abnormalities by small diameter hysteroscope.

The vaginal speculum can be safely and efficaciously replaced by the less traumatic small diameter continuous flow hysteroscopic vaginoscopy for diagnosis and treatment of genital tract lesion in children and adolescents.