Laparoscopic cervico-isthmic anastomosis for old traumatic disjunction between the cervix and the uterine corpus: a case report and literature review.

BACKGROUND: Old traumatic disjunction between the cervix and the uterine corpus is very rare case. In most cases, it is not immediately noticed until the onset of other symptoms, such as amenorrhea, periodic abdominal pain and so on. Scanty cases of anastomosis surgery via laparoscope have been reported. CASE PRESENTATION: We report here a 23-year-old young woman with the primary amenorrhea due to traumatic cervico-isthmic disjunction. The patient had a closed pelvic fracture at the age of 4 and has experienced periodic lower abdominal pain since the age of 17 years. A complete disjunction between the cervix and the uterine corpus was diagnosed. Laparoscopic cervico-isthmic anastomosis was performed to restore the continuity of the endometrial cavity and cervical canal. After this surgery, normal menstruation was resumed without cyclic abdominal pain. CONCLUSION: Laparoscopic cervico-isthmic anastomosis could reconstruct the uterine outflow tract successfully, alleviate symptoms, and achieve a good short-term outcome.

Hysteroscopy-assisted Transvaginal Repair without Scar Defect Resection: A Novel Technique for the Treatment of Uterine Niche.

STUDY OBJECTIVE: To describe hysteroscopy-assisted transvaginal repair technique without scar defect resection for uterine niche. DESIGN: Surgical video article (Supplemental Videos 1-3). Stepwise narrated video demonstration of the novel technique. A total of 15 women diagnosed as having niche in the uterus were enrolled in our study. Patients provided a signed consent and there are no conflicts of interest. SETTING: Niche in the uterus is defined as an indentation in the myometrium at the uterine incision owing to healing defects [1]. Surgical treatment options for niche include hysteroscopic, laparoscopic, and vaginal surgery [2]. Compared with hysteroscopic surgery, regular vaginal surgery may effectively increase the residual myometrium thickness, reducing the risk of subsequent pregnancy [3-5]. However, regular vaginal surgery removes the original scar defect followed by suture, which can lead to a new niche after the surgery and may postpone conception because of the new uterine incision [6]. Here we describe a new technique of hysteroscopy-assisted transvaginal repair for the niche, which does not remove the original scar defect [7]. This surgery may be beneficial for those who plan conceive as soon as possible after the operation. INTERVENTIONS: Hysteroscopy-assisted vaginal surgery without scar defect resection was selected as ideal surgical approach. Hysteroscopy was used for abnormal structures in the niche [8,9]. Opening the peritoneum through the vaginal wall confirmed the position of the niche, and a 2-0 absorbable suture was used to interruptedly suture the upper and lower margins of the scar defect and close the niche (or reduce its size), rather than resection. Hysteroscopy was used again to assess the status of the niche after suture and confirm repair. If unsatisfactory, suture procedure was repeated to close the remaining part of the niche. CONCLUSION: Our novel technique, described and demonstrated in this video article, is an efficacious and viable approach to treat uterine niche. Chinese experts recommend at least a 1-year gap between conventional scar defect resection with suturing and conception, because of the new uterine incision [6]. In contrast, this novel procedure avoids removal of the original scar defect and the surrounding scar tissue by directly repairing the lower uterine segment. Meanwhile, hysteroscopy can treat abnormal structures in the niche and improve effectiveness. Given that the integrity of the uterine myometrium is retained, this technique may help shorten contraception time after operation. Further studies with larger sample size, longer follow-up time, and more postoperative follow-up indicators, such as fertility outcomes, are needed to comprehensively evaluate the restorative effect of this novel technique.

Transcytosis mechanisms of cell-penetrating peptides: Cation-independent CC12 and cationic penetratin.

Cell-penetrating peptides (CPPs) can aid in intracellular and in vivo drug delivery. However, the mechanisms of CPP-mediated penetration remain unclear, limiting the development and further application of CPPs. Flow cytometry and laser confocal fluorescence microscopy were performed to detect the effects of different endocytosis inhibitors on the internalization of CC12 and penetratin in ARPE-19 cells. The co-localization of CPPs with the lysosome and macropinosome was detected via an endocytosis tracing experiment. The flow cytometry results showed that chlorpromazine, wortmannin, cytochalasin D, and the ATP inhibitor oligomycin had dose-dependent endocytosis-inhibitory effects on CC12. The laser confocal fluorescence results showed that oligomycin had the most significant inhibitory effect on CC12 uptake; CC12 was co-located with the lysosome, but not with the macropinosome. For penetratin, cytochalasin D and oligomycin had obvious inhibitory effects. The laser confocal fluorescence results indicated that oligomycin had the most significant inhibitory effect on penetratin uptake; the co-localization of penetratin with the lysosome was higher than that with the macropinosome. Cation-independent CC12 and cationic penetratin may be internalized into cells primarily through caveolae and clathrin-mediated endocytosis, and they are typically dependent on ATP. The transport of penetratin could be partly achieved through the direct transmembrane pathway, as the positive charge of penetratin interacts with the negative charge of the cell membrane, and partly through the endocytic pathway.

Estrogen-ERα signaling and DNA hypomethylation co-regulate expression of stem cell protein PIWIL1 in ERα-positive endometrial cancer cells.

BACKGROUND: We previously identified PIWIL1 as an oncogene involved in endometrial carcinogenesis. However, the mechanism of Piwil1 mediated regulation of tumorigenesis remains poorly understood. METHODS: The expression levels of target genes in endometrial cancer cells were detected by quantitative reverse transcription-PCR (RT-qPCR) and western blotting. Up- or down-regulation of ERα or PIWIL1 was achieved by transient transfection with expressing plasmids or short hairpin RNA (shRNA). Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to demonstrate the ERα bound to the half estrogen response element (half-ERE) located in PIWIL1 promoter. The expression of PIWIL1 and ERα in endometrial carcinoma tissues were investigated using immunohistochemistry and RT-qPCR. The proliferation ability of cancer cells were evaluated by MTT. Methylation status of the PIWIL1 promoter was detected by bisulfite sequencing PCR (BSP). RESULTS: In the present study, we found that PIWIL1 mediated E2-stimulated cancer cell proliferation. In ERα-positive endometrial cancer cells, we demonstrated that estrogen-ERα signaling significantly up-regulated the expression of PIWIL1, which was mediated by binding of the ERα onto the PIWIL1 promoter. Furthermore, we found that a half-ERE in the PIWIL1 promoter was essential for ERα binding. The PIWIL1 promoter was hypomethylated in ERα-positive endometrial cancer cells. Treatment with 5-aza-deoxycytidine (5-aza-dC) could up-regulate PIWIL1 expression. CONCLUSIONS: These findings uncover a novel molecular mechanism by which estrogen-ERα signaling and DNA hypomethylation co-regulate PIWIL1 expression. These findings provide novel insights into the hormonal regulation of PIWIL1 in endometrial cancer and the PIWIL1's role in estrogen-stimulated endometrial carcinogenesis. Video Abstract. (MP4 41319 kb).

Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer.

Prostaglandin E2 (PGE2), a derivative of arachidonic acid, has been identified as a tumorigenic factor in many cancers in recent studies. Prostaglandin E synthase 2 (PTGES2) is an enzyme that in humans is encoded by the PTGES2 gene located on chromosome 9, and it synthesizes PGE2 in human cells. In our study, we selected 119 samples from endometrial cancer patients, with 50 normal endometrium tissue samples as controls, in which we examined the expression of PTGES2. Both immunohistochemistry (IHC) and Western blot analyses demonstrated that synthase PTGES2, which is required for PGE2 synthesis, was highly expressed in endometrium cancer tissues compared with normal endometrium. Stable PTGES2-shRNA transfectants were generated in Ishikawa and Hec-1B endometrial cancer cell lines, and transfection efficiencies were confirmed by RT-PCR and Western blot analyses. We found that PGE2 promoted proliferation and invasion of cells in Ishikawa and Hec-1B cells by cell counting kit-8 tests (CCK8) and transwell assays, respectively. PGE2 stimulation enhanced the expression of SUMO-1, via PGE2 receptor subtype 4 (EP4). Further analysis implicated the Wnt/ß-catenin signaling pathway function as the major mediator of EP4 and SUMO-1. The increase in SUMO-1 activity prompted the SUMOlyation of target proteins which may be involved in proliferation and invasion. These findings suggest SUMO-1 and EP4 as two potential targets for new therapeutic or prevention strategies for endometrial cancers.

Stem cell protein Piwil1 endowed endometrial cancer cells with stem-like properties via inducing epithelial-mesenchymal transition.

BACKGROUND: Stem cell protein Piwil1 functions as an oncogene in various tumor types. However, the exact function and mechanism of Piwil1 in endometrial cancer remains unclear. METHODS: The expression of Piwil1 and its relationships with clinicopathological factors were investigated using immunohistochemistry. Up- or down-regulation of Piwil1 were achieved by stable or transient transfection with plasmids or short hairpin RNA (shRNA). Effects of Piwil1 on cancer cells viability, invasion and migration were evaluated by MTT, plate colony formation, transwell assay and nude mouse tumor xenograft assay. The stem-like properties of endometrial cancer cells was detected by spheroid formation assay. Effects of Piwil1 on expression levels of target genes were detected by qRT-PCR, western blotting and Immunofluorescence. RESULTS: Compared with atypical hyperplasia and normal tissues, Piwil1 was much higher in endometrial carcinoma tissues. We found that Piwil1 expression was significantly correlated with FIGO stage, lymphovascular space involvement, lymph node metastasis and level of myometrial invasion. Overexpression of Piwil1 functioned to maintain stem-like characteristics, including enhancing tumor cell viability, migration, invasion and sphere-forming activity. Conversely, Piwil1 knockdown inhibited cell viability, migration, invasion, sphere-forming activity in vitro and tumor formation in xenograft model in vivo. Furthermore, study of the expression of epithelial and mesenchymal markers showed that Piwil1 was responsible for an EMT-like phenotype associated with an increase in mesenchymal markers and suppression of E-cadherin. Moreover, Piwil1 augmented expression levels of CD44 and ALDH1 expression, two known endometrial CSC markers, as well as other stemness-associated genes. CONCLUSIONS: Our results suggested that stem cell protein Piwil1 play important roles in regulating EMT and the acquisition of stem-like properties of endometrial cancer cells. Therefore, it indicated that Piwil1 may represent a promising target for developing a novel treatment strategy for endometrial cancer.

Oncostatin M activates STAT3 to promote endometrial cancer invasion and angiogenesis.

Oncostatin M (OSM), a pleiotropic cytokine, can either promote or inhibit the growth of tumors derived from specific tissues. However, little is known about the activity and expression pattern of OSM in endometrial cancers (ECs). Herein we show that expression of OSM in human ECs was significantly higher than that in hyperplastic or normal tissues. In EC tissues, high OSM levels were positively correlated with tumor stage, histological grade, myometrial invasion, and lymph node metastasis. Additionally, we demonstrated that recombinant human OSM (rhOSM) promoted tumor angiogenesis in EC cell lines by activating STAT3 (signal transducer and activator of transcription 3) and enhanced both cell migration and cell invasion. rhOSM did not, however, influence the proliferation of EC cells in vitro. In contrast, in our in vivo xenograft model, overexpression of rhOSM promoted cell proliferation, tumor growth, and angiogenesis in nude mice. Collectively, these experiments suggest that OSM may be a tumor promoter that encourages EC progression. OSM may thus serve as a potential target of antiangiogenic therapy for endometrial cancer.

Bimanual microincision versus standard coaxial small-incision cataract surgery: meta-analysis of randomized controlled trials.

PURPOSE: This meta-analysis aimed to evaluate the outcomes of bimanual microincision cataract surgery (B-MICS) through a 1.2- to 1.5-mm incision versus standard coaxial small-incision cataract surgery (C-SICS) through a 2.8- to 3.2-mm incision. METHODS: A comprehensive literature search was performed according to the Cochrane Collaboration methodology to identify randomized controlled clinical trials comparing B-MICS with standard C-SICS. Main outcome measures were mean surgical time, mean phacoemulsification power, effective phacoemulsification time, best-corrected visual acuity, surgically induced astigmatism (SIA), mean laser flare photometry values, mean endothelial cell loss, mean increased central corneal thickness, and intraoperative and postoperative complications. RESULTS: We identified 14 randomized controlled clinical trials that included 1235 eyes diagnosed with cataracts. No statistically significant differences were detected between the 2 surgical procedures in terms of best-corrected visual acuity (p>0.05), SIA at postoperative 1 month (p = 0.09), laser flare photometry values (p = 0.38), mean endothelial cell loss (p = 0.53), increased central corneal thickness at postoperative 1 month (p = 0.64) or 3 months (p = 0.88), intraoperative complications (p = 0.68), and postoperative complications (p = 0.30); however, statistically significant differences were apparent for mean surgical time (p<0.00001), mean phacoemulsification power (p = 0.008), effective phacoemulsification time (p = 0.0009), SIA at postoperative 3 months (p = 0.02), and increased central corneal thickness at postoperative 1 day (p = 0.04). CONCLUSIONS: The meta-analysis shows that the 2 techniques have similar outcomes in terms of final visual acuity and complications. Bimanual MICS has the advantage of less SIA and phaco time whereas C-SICS has the advantage of quicker surgery and less likelihood of early-onset corneal edema.