TGF-ß1 Neutralization Improves Pregnancy Outcomes by Restoring Endometrial Receptivity in Mice with Adenomyosis.

The objective of this research is to study the effects of TGF-ß1 inhibition on endometrial receptivity and pregnancy outcomes in mice with adenomyosis. Experiments were done using a mouse model of adenomyosis which took place in a hospital-affiliated laboratory. The mouse model used for this research is ICR mouse. Adenomyosis was induced by oral gavage of tamoxifen (TAM) from postnatal days (PNDs) 1 to 4 in ICR mice. Bilateral intrauterine injection of anti-TGF-ß1-neutralizing antibody or isotype IgG or PBS was performed at PND42. The mice were then either sacrificed or mated at PND64 followed by sacrificing at gestational day (GD) 4 or proceeding to delivery. Implantation numbers, rate of dams with live birth, live birth numbers, survival at 1 week old, and pup mortality rate after weaning were recorded. Collagen was demonstrated by Masson's trichrome and Van Gieson's stains. Uterine expression of a receptivity marker, leukemia inhibitory factor (LIF), was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry (IHC). Anti-TGF-ß1 treatment increased the mean implantation numbers, fecundity rate, the rate of dams with live birth, pup survival rate at 1 week old, and pup mortality rate after weaning. Collagen expression in uteri with adenomyosis was attenuated by anti-TGF-ß1 treatment. Increased LIF expression by anti-TGF-ß1 treatment was detected by qRT-PCR, Western blot, and IHC. The results suggest that inhibition of TGF-ß1 improves pregnancy outcomes by restoring endometrial receptivity in mice with adenomyosis.

The Effects of Anti-TGF-ß1 on Epithelial-Mesenchymal Transition in the Pathogenesis of Adenomyosis.

Adenomyosis is defined as the presence of endometrial glands and stroma in the myometrium. The mechanisms associated with the pathogenesis of adenomyosis remain unclear. Epithelial-mesenchymal transition (EMT) is characterized by losing cell polarity and cell-cell adhesion together with gaining migratory and invasive properties of stromal cells to become mesenchymal stem cells. Transforming growth factor-ß1 (TGF-ß1), an anti-inflammatory cytokine secreted by multiple cell types, plays a crucial role in embryogenesis and tissue homeostasis. The induction of EMT and ultimate fibrosis by TGF-ß1 is suggested to play a critical role in the pathogenesis of adenomyosis. Thus, this study aims to demonstrate the occurrence of EMT in and the effects of anti-TGF-ß1 on the pathogenesis of adenomyosis. ICR mice were fed with 1 µg/g body weight of tamoxifen (TAM) by in the first 4 postnatal days (PNDs). Subsequently, the right and left uterine horns were correspondingly injected with or without 10 µg of anti-TGF-ß1 neutralizing antibody on PND42 followed by sacrifice on PND64. E-cadherin, vimentin, and α-smooth muscle actin (α-SMA) expression in the uteri was evaluated by qRT-PCR, Western blot, and immunohistochemistry. Clusters of endometrial glands and increased numbers of vimentin-positive stromal cells in the disrupted α-SMA-positive myometrium were observed in the uteri from TAM-treated mice. Numbers of stromal cells in the myometrium and the disrupted myometrial continuity were reduced by anti-TGF-ß1. Moreover, uterine expression of E-cadherin and vimentin/α-SMA was increased and decreased by anti-TGF-ß1 treatment, respectively. Anti-TGF-ß1 successfully inhibits EMT and the development of adenomyosis in mouse uteri.

Laparoendoscopic Single-Site Supracervical Hysterectomy with Manual Morcellation: A Retrospective Study.

STUDY OBJECTIVE: To evaluate the feasibility, efficiency, and safety of manual morcellation in laparoendoscopic single-site (LESS) supracervical hysterectomy. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: A teaching hospital. PATIENTS: One hundred and ninety patients with symptomatic uterine leiomyomas and/or adenomyosis who underwent LESS supracervical hysterectomy. INTERVENTIONS: Manual morcellation through the umbilical wound. MEASUREMENTS AND MAIN RESULTS: Time of operation, blood loss volume, specimen weights, rate of morcellation, requirement for blood transfusion, hospital length of stay, and prevalence of postoperative cyclic spotting were recorded. The median weight of the uterine corpus was 245 g (range, 100-1960 g). The median total operation time was 69 minutes (range, 36-183 minutes). The median volume of blood loss was 50 mL (range, 10-850 mL). The median level of hemoglobin reduction was 1 g/dL (range, -1 to 3.2 g/dL). The incidence of intraoperative blood transfusion was 3.2%, and the mean manual morcellation rate was 38.9 ± 15 g/minute. The incidence of postoperative cyclic spotting was 10.5%. CONCLUSION: Safe and effective LESS surgery requires a minimal surgical incision compared with conventional laparoscopic surgery and laparotomy. Manual morcellation was found to be effective and safe in removing solid tumors in this population.

Total synthetic protoapigenone WYC02 inhibits cervical cancer cell proliferation and tumour growth through PIK3 signalling pathway.

Flavonoids have been intensively explored for their anticancer activity. In this study, a total synthetic flavonoid protoapigenone, known as WYC02, was analysed for its potential anticancer activity on human cervical cancer cells as well as the underlying mechanisms for these effects. The site-moiety maps are used to explore the binding site similarity, pharmacophore and docking pose similarity. The effect of WYC02 on cell viability, migration, invasion and apoptosis as well as the underlying mechanisms was analysed in vitro using human cervical cancer cells. The effect of WYC02 on in vivo tumour growth was assessed in a tumour xenograft study. WYC02 inhibited cell proliferation, MMPs activity, migration and invasion in cervical cancer cells. We speculated that WYC02 might inhibit the activities of PIK3 family proteins, including PIK3CA, PIK3CB, PIK3CD and PIK3CG. Indeed, WYC02 decreased the expression of PIK3 family proteins, especially PIK3CG, through ubiquitination and inhibited the activities of PIK3CG and PIK3 downstream molecules AKT1 and MTOR in cervical cancer cells. Furthermore, PIK3 signalling pathway was involved in the inhibitory effect of WYC02 on cervical cancer cell proliferation and tumour growth in vitro and in vivo. WYC02 inhibits cervical cancer cell proliferation and tumourigenesis via PIK3 signalling pathway and has the potential to be developed as a chemotherapeutic agent in cervical cancer.

Progesterone receptor is involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin-stimulated breast cancer cells proliferation.

Sex hormones are pivotal for both normal and neoplastic development of breast tissues. TCDD, with sex hormonal activity, executes multiple biological activities primarily through AhR. However, the detailed mechanisms how TCDD affects human breast cell are mostly unexplored. We analyzed the biological effects and underlying mechanisms of TCDD on MCF-7 cells. PR, other than AhR, was involved in TCDD-stimulated MCF-7 cell proliferation. TCDD inactivated Akt-FoxO3a pathway, increased cdc25C/cdc2 activity, decreased P21/P27 activity, and enriched G2/M phase, in a PR- and AhR-dependent manner. In conclusion, our study demonstrated for the first time that PR was involved in TCDD-stimulated breast cell proliferation.

Outcome of laparoscopic repair of ureteral injury: follow-up of twelve cases.

STUDY OBJECTIVE: To review the feasibility of laparoscopic repair in cases of ureteral injuries occurring during gynecologic laparoscopy. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: Institution-specific retrospective review of data from a tertiary referral medical center. PATIENTS: Patients suffering from iatrogenic ureteral injuries diagnosed during or after surgery, and cases with deliberate ureteral resection and repair because of underlying disease. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective review of all (10 345) laparoscopic gynecologic surgeries performed in our institute between February 2004 and November 2008. Twelve cases (median: 45.5 years, range: 27-63) of ureter transections were diagnosed and repaired laparoscopically by endoscopists. Of these, 10 had previous surgeries, pelvic adhesions, or a large pelvic-abdominal mass. One patient had undergone a segmental resection and laparoscopic ureteroureterostomy for deep infiltrative endometriosis. Of the remaining 11 iatrogenic ureteral transections, 10 were repaired via laparoscopic ureteroureterostomy, whereas 1 had undergone a laparoscopic ureteroneocystostomy. One injury was recognized on the second postoperative day, but intraoperative recognition was attained in 11 cases. The median duration of double J stenting was 73 days. Three patients had development of strictures (between 42 and 79 days after surgery) treated with restenting, but 1 had to undergo an ureteroneocystostomy for ureter disruption when trying to restent. One patient had development of leakage of the anastomotic site but recovered with a change of the double J stent. Only 1 case required another laparotomy for ureteroneocystostomy. Laparoscopic primary repair of ureteral injury was successful for 11 of 12 patients. All the patients were well and symptom free at the conclusion of the study period. CONCLUSION: Early recognition and treatment of ureteral injuries are important to prevent morbidity. Laparoscopic ureteroureterostomy could be considered in transections of the ureter where technical expertise is available. To the best of our knowledge, this is the largest series, to date, of ureteral repairs via laparoscopy.

Resectoscopic treatment of ectopic pregnancy in previous cesarean delivery scar defect with vasopressin injection.

OBJECTIVE: To describe resectoscopic treatment with vasopressin injection as an effective surgical intervention for ectopic pregnancy in previous cesarean delivery scar (PCDS) defect. DESIGN: Case report. SETTING: University hospital. PATIENT(S): Two women with ectopic pregnancy in PCDS defect. INTERVENTION(S): The patients underwent transvaginal ultrasound examination, followed by operative hysteroscopy with vasopressin injection for evacuating the ectopic pregnancy in PCDS defect. MAIN OUTCOME MEASURE(S): Conservation of the uterus. RESULT(S): Successful resectoscopic treatment of ectopic pregnancy in PCDS defect. CONCLUSION(S): Resectoscopic treatment of ectopic pregnancy in PCDS defect is a safe and efficient technique that has the advantage of a rapid return to normal levels of ß-hCG. Intracervical vasopressin administration could decrease intraoperative bleeding and provide a clear view during the operation.

Abdominal wall endometriomas.

OBJECTIVE: Abdominal wall endometriosis is rare, with an incidence of 0.03-0.47% following cesarean delivery. STUDY DESIGN: The study reviewed abdominal wall endometriomas during an 8-year period in the Department of Obstetrics and Gynecology of the Kaohsiung Municipal Hsiao-Kang Hospital. RESULTS: Of 166 patients with endometriosis treated surgically in the hospital during an 8-year period, 20 (12%) had abdominal wall endometriomas. The mean interval between the prior operation and the appearance of the first symptoms was 39.3 months. Preoperative diagnosis was correct in 14 patients (70%). CONCLUSION: Abdominal wall endometrioma is more common than generally assumed in patients visiting the hospital. In patients with a palpable subcutaneous mass near surgical scars associated with cyclic or constant pain, a thorough history and physical examination are sufficient to establish the presence of endometriomas. A surgical-wide excision with clear margins is the single treatment of choice.

The roles of laparoscopy in treating ovarian cancer.

Great advances in technology offer meticulous options of minimally invasive surgery to empower the gynecologists to manage patients of early ovarian cancer. Laparoscopy affords improved visualization of the pelvic peritoneum, diaphragm and the deep pelvic structures, and offers many advantages in the avoidance of long abdominal incision, including shorter hospital stay and a more rapid recovery time. Most studies showed that laparoscopy did not compromise the survival and recurrence prognosis in comparison with open abdominal approach of staging surgery. Contrarily, laparoscopy precludes the advantage of open surgery, such as manual examination of the full extent of the bowel and palpation of lymph nodes. Besides, laparoscopy technically hampers the removal of large ovarian mass, and laparoscopic cancer surgery has a potential risk of trocar site metastasis. As the trend shows that laparoscopy has been playing an important role in treating early ovarian cancer, we could expect laparoscopy to become an attractive surgical option in the future for ovarian cancers.

Resectoscopic treatment combined with sonohysterographic evaluation of women with postmenstrual bleeding as a result of previous cesarean delivery scar defects.

OBJECTIVE: The objective of this study was to assess the detection rate of previous cesarean delivery scar (PCDS) defect by transvaginal ultrasonography (TVU) and to evaluate the effectiveness of resectoscopic surgery to correct this anatomic defect. STUDY DESIGN: In all, 57 women were included in our study. A diagnosis of a PCDS defect was established by TVU. We used resectoscopy to remove the flaplike fibrotic tissue that appeared underneath the pouchlike defect. RESULTS: A total of 22 patients received resectoscopic treatment. The detection rate of PCDS defects was 88% by TVU. The duration of postmenstrual bleeding shortened significantly after resectoscopic therapy. CONCLUSION: TVU examination performed during the period of postmenstrual bleeding allows us to readily identify this anatomic defect. Resectoscopy, in our opinion, should be considered the first choice to correct this defect because it is minimally invasive and yields good therapeutic results.

A transient blocking uterine perfusion procedure to decrease operative blood loss in laparoscopic myomectomy.

BACKGROUND: To evaluate the feasibility and effectiveness of reversible ligating clips to block uterine arteries and reduce operative blood loss during laparoscopic myomectomy (LM). METHODS: Twenty consecutive women with symptomatic uterine fibroids desiring to preserve the uteri underwent laparoscopic surgery with ligation of the uterine arteries with ligating clips, followed by myomectomy and removal of the clips. RESULT: Laparoscopic uterine artery ligation with reversible ligating clips was successfully performed in all patients. The median main fibroid diameter and fibroid weight were 7.3 cm (interquartile range [IQR] 7.0-9.0) and 210 g (IQR 150-295 g), respectively. The median operating time was 120 minutes (IQR 100-148 minutes) and blood loss was 100.0 mL (IQR 56.3-137.5 mL). The median number of fibroids removed was 1 (IQR 1-4.3). The median post-operative hospital stay was 3 days (IQR 2-3 days) and no patient developed complications. Menstrual bleeding problems and bulk-related symptoms were controlled in 90.0% and 100% of women, respectively after 6 months of follow-up. One woman conceived spontaneously 4 months after surgery and delivered a baby girl at 38 weeks gestation via cesarean section. CONCLUSIONS: Blocking uterine perfusion before LM is valuable and feasible for the management of women with symptomatic fibroids. The procedure controlled operative blood loss without affecting the uterine blood supply after surgery.

Diagnostic laparoscopy in ascites of unknown origin: Chang Gung Memorial Hospital 20-year experience.

BACKGROUND: Ascites may appear with well-recognized disease but, in some situations, ascites is of unknown cause in spite of comprehensive study. The aim of this study was to assess the diagnostic accuracy of laparoscopy in patients with ascites of unknown origin, and evaluate the role of laparoscopy in this population after the advent of ultrasonography and computed tomography. METHODS: We collected 20 years' data of diagnostic laparoscopy from retrospective chart review at Chang Gung Memorial Hospital in Linkou and Taipei. We compared the first 10 years' data with the latter 10 years, in respect of surgical technique evolution and the different contributions of ascites. RESULTS: One hundred and seventy six patients who underwent laparoscopy for ascites of unknown origin were enrolled. They included: (1) carcinomatosis peritonei in 99 cases (56.2%); (2) tuberculous peritonitis in 31 cases (17.6%); (3) cirrhosis in 19 cases (10.8%); and (4) miscellaneous diagnoses in 27 cases (15.4%). Comparing the first 10 years' data with the latter 10 years', the distribution was nearly the same. Carcinomatosis peritonei accounted for the majority of cases and, with the evolution of anti-tuberculosis medicine, the number of tuberculosis cases is decreasing. Liver cirrhosis cases increased during the latter 10 years. CONCLUSION: Laparoscopy in combination with biopsy can clarify the causes of unexplained ascites in the majority of cases: it failed to reveal any gross abnormality in only 15% of cases. Therefore, laparoscopy is a valuable tool for the detection of the cause of unexplained ascites.

Oxytocin infusion in laparoscopic myomectomy may decrease operative blood loss.

STUDY OBJECTIVE: To evaluate the influence of oxytocin on operative blood loss during laparoscopic myomectomy (LM). DESIGN: Prospective clinical study (Canadian Task Force classification I). SETTING: Tertiary care university hospital. PATIENTS: Sixty women scheduled for myomectomy because of symptomatic uterine myomas. INTERVENTION: Two ampules of oxytocin (10 u/mL/amp) were added to 1000 mL of saline solution running at the rate of 40 mU/min during the course of LM. MEASUREMENTS AND MAIN RESULTS: Blood loss and blood transfusion rate were significantly greater in the group without oxytocin infusion (group B) than in the group with oxytocin infusion (group A), with 445.0 +/- 268.6 mL (95% CI 344.7-545.3) versus 269.5 +/- 225.8 mL (95% CI 185.2-353.8)/(p <.05), and 36.7% versus 6.7% (p <.05), respectively. There was no significant difference in average age, body weight, or numbers of vaginal delivery and cesarean sections between the 2 groups. There was no significant difference in mean total myoma weight, main myoma size, postoperative stay, and complications between the 2 groups. CONCLUSION: Oxytocin infusion combined with skillful surgical techniques may decrease operative blood loss and blood transfusion during LM.

Inhibition of ovarian cancer growth and implantation by paclitaxel after laparoscopic surgery in a mouse model.

OBJECTIVE: We used an established experimental model to evaluate the influence of intraperitoneal chemotherapy on the generation of laparoscopy-associated metastases and the effectiveness of chemotherapy. STUDY DESIGN: Twenty-four nude mice underwent laparoscopy with carbon dioxide insufflation and the instillation of a tumor cell suspension with or without paclitaxel into the peritoneal cavity. Mice were allocated to 1 of the following groups (8 mice to each group): (1) controls; (2) paclitaxel given during the operation; (3) paclitaxel given after the operation. Mice were killed 30 days after the procedure, and the peritoneal cavity and port sites were examined for the presence of tumors. RESULTS: Tumor implantation and port-site metastases were reduced more by the intraoperative intraperitoneal administration of paclitaxel during the operation than by administration after the operation. CONCLUSION: Intraoperative intraperitoneal administration of paclitaxel may decrease significantly the occurrence of port-site metastasis and intraperitoneal dissemination in an animal study.

A prospective comparison of morcellator and culdotomy for extracting of uterine myomas laparoscopically in nullipara.

We compare the removal of uterine myomas in 78 nulliparous women identified by ultrasound during laparoscopic myomectomy through culdotomy or by use of a power morcellator. Patients were divided into two groups. The culdotomy group was significantly longer. There were no significant differences in tumor size, total specimen weight, patient body weight, total operating time, blood loss, and postoperative stay between each group. Uterine myomas can be removed successfully through either port site in nullipara; however, because of reduced removal time, the power morcellator is preferred.

Ectopic pregnancy in an inguinal herniorrhaphy scar.

An ectopic pregnancy may occur in unusual sites. In the following case, an ectopic pregnancy was discovered in the first trimester within an inguinal herniorrhaphy scar from an inguinal herniorrhaphy performed about 20 years previously. Early diagnosis of the ectopic pregnancy by sonography enabled laparoscopic management and preservation of the woman's fertility.