Does repetitive dilatation and curettage or hysteroscopic biopsy in patients treated with progestins for endometrial hyperplasia or carcinoma affect subsequent fetomaternal outcomes? A population-based study using the National Health Insurance Research Database of Taiwan.

OBJECTIVE: To investigate the impact of repeated dilatation and curettage or hysteroscopic biopsy on fetomaternal outcomes in patients receiving progestin treatment for endometrial hyperplasia or early-stage carcinoma. METHOD: This was a population-based study using the Taiwan National Health Insurance Research Database between 2009 and 2017 of women who gave birth and had a history of endometrial hyperplasia and early-stage carcinoma treated with progestins. Logistic regression analysis was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) reflecting the association between repeated procedures and fetomaternal outcomes. RESULTS: A total of 6956 women with 8690 deliveries were identified. Compared with those who had two or fewer procedures, women who received more than two procedures had a significantly higher risk for cervical insufficiency (aOR, 5.09 [95 CI, 2.31-11.24]). Furthermore, women who had more than two procedures were prone to have adverse neonatal outcomes, including Apgar score < 7 at 1 min (aOR, 1.97 [95% CI, 1.13-3.43]) and 5 min (aOR, 3.11 [95% CI, 1.33-7.23]) and preterm delivery <32 weeks (aOR, 2.86 [95% CI, 1.50-5.45]). CONCLUSION: Undergoing more than two procedures was associated with subsequent maternal cervical insufficiency, preterm delivery <32 weeks, and low neonatal Apgar score. Health care providers should be aware of the potential risks and balance the benefits and harms of repeated procedures.

A novel technique of sutureless omentopexy during dual-incision laparoscopic peritoneal dialysis catheter insertion to prevent catheter dysfunction due to omental wrapping.

BACKGROUND: Omental wrapping (OW) is the leading cause of obstruction of the peritoneal dialysis (PD) catheter, which interferes with dialysis treatment. Routinely or selectively performing omentopexy during laparoscopic PD catheter placement has been suggested to prevent OW. However, most of the published techniques for performing this adjunctive procedure require additional incisions and suturing. Herein, we aimed to report our experience in performing omentopexy with a sutureless technique during dual-incision PD catheter insertion. We also performed a comparative analysis to assess the benefit/risk profile of routine omentopexy in these patients. METHODS: This retrospective study enrolled 469 patients who underwent laparoscopic PD catheter insertion. Their demographic characteristics and operative details were collected from the database of our institution. Omentopexy was performed by fixing the inferior edge of the omentum to the round ligament of the liver using titanium clips. For analysis, the patients were divided into the omentopexy group and the non-omentopexy group. We also reviewed the salvage management and outcomes of patients who experienced OW. RESULTS: The patients were categorized into the omentopexy (n = 81) and non-omentopexy (n = 388) groups. The patients in the non-omentopexy group had a higher incidence of OW, whereas no patient in the omentopexy group experienced this complication (5.2% vs. 0.0%, p = 0.033). The median operative time was 27 min longer in patients who underwent omentopexy than in those who did not [100 (82-118) min vs. 73 (63-84) min, p < 0.001]. One patient had an intra-abdominal hematoma after omentopexy and required salvage surgery to restore catheter function. The complication rate of omentopexy was 1.2% (1/81). CONCLUSION: Sutureless omentopexy during laparoscopic PD catheter insertion is a safe and reliable technique that does not require additional incisions and suturing. Routinely performing omentopexy provides clinical benefits by reducing the risk of catheter dysfunction due to OW.

Effects of Icodextrin Solution (Adept®) on Ovarian Cancer Cell Proliferation in an In Vitro Model.

Background and objective: Anti-adhesion barriers are currently used during ovarian cancer surgery to decrease adhesion-related morbidity. Adept® (4% icodextrin) solution, a liquid anti-adhesion material, has been widely used during gynecologic surgeries, though the risk of this barrier for oncologic surgery is controversial. The aim of this study was to determine the effect of Adept® solution on the proliferation of ovarian cancer cells. Materials and methods: We assessed the dose- and time-dependent effects of icodextrin on the growth and proliferation of OVCAR-3 and A2780 human ovarian tumor cell lines in vitro. Cell growth was determined by cell number counting. Expressions of cell cycle-regulation proteins (cyclin D1 and cyclin B1) were determined using Western blot analysis. Results: Adept® did not significantly increase ovarian cancer cell growth when tested at various concentrations (0, 1, 5, 10, 15, and 20%, equal to 0, 0.04, 0.2, 0.4, 0.6 and 0.8% icodextrin) and different time points (1-3 days) compared to control cells. Moreover, the protein levels of cyclin D1 and B1 were not overexpression-elevated in icodextrin-treated ovarian cancer cells, either with an increasing concentration or with an increasing treated time. These results demonstrated that Adept® does not activate the growth or proliferation of ovarian cancer cells in either a dose- or time-dependent manner. Conclusions: This study supports the use of Adept® solution as a safe anti-adhesion barrier for ovarian cancer surgery, though further in vivo studies are necessary.

Comparison of Prolift, Perigee-Apogee, Prosima, and Elevate transvaginal mesh systems in pelvic organ prolapse surgery: Clinical outcomes of a long-term observational study.

OBJECTIVES: To evaluate and compare the long-term clinical outcomes of four different transvaginal mesh systems. METHODS: This retrospective study included 695 patients classified into four groups (Prolift, n = 132; Perigee-Apogee, n = 186; Prosima, n = 60; Elevate; n = 317), with a median follow-up time of 5.8 years (range 0.5-12.2 years). The outcomes were objective anatomic success (Pelvic Organ Prolapse [POP] Quantification system stage ≤1), mesh exposure, and urologic functional assessments. RESULTS: For anatomic outcomes, we stepwise analyzed the short-term (within 3 years) and long-term (after 3 years) results. Prolift had the highest long-term success rate (9 years: 82.1%, P = .007). Elevate had a comparable short-term success rate (3 years: 87.5%), but its long-term success rate significantly decreased over time (5 years: 78.6%, 9 years: 66.8%, P = .007). Prosima had the lowest short-term success rate (P = .027). For the long-term mesh exposure rate (9-year cumulative), Elevate had the lowest with 11.1%; next were Perigee-Apogee (18.8%) and Prolift (24.6%); and Prosima had the highest with 39.4%, with a significant difference. In terms of urinary functional results, we observed no significant differences in voiding dysfunction, de novo stress urinary incontinence, or de novo overactive bladder symptoms among the four mesh groups, whether combined with midurethral sling surgery or not. CONCLUSION: Different vaginal mesh designs have various advantages and features. Prolift provided the best long-term anatomic success but had a high mesh exposure rate. Elevate gave comparable short-term success but had a decreased long-term success rate. However, Elevate is superior with the lowest long-term mesh exposure rate. Prosima had the worst anatomic correction and highest mesh exposure rates. This study provides a comprehensive long-term comparative result for POP patients and surgeons.

Laparoscopic pectopexy: the learning curve and comparison with laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: In addition to laparoscopic sacrocolpopexy (LS), laparoscopic pectopexy (LP) is a novel surgical method for correcting apical prolapse. The descended cervix or vaginal vault is suspended with a synthetic mesh by fixing the bilateral mesh ends to the pectineal ligaments. This study was aimed at developing a learning curve for LP and to compare it with results with LS. METHODS: We started laparoscopic/robotic pectopexy in our department in August 2019. This retrospective study included the initial 18 consecutive women with apical prolapse receiving LP and another group undergoing LS (21 cases) performed by the same surgeon. The medical and video records were reviewed. RESULTS: The age was older in the LP group than in the LS group (65.2 vs 53.1 years). The operation time of LP group was significantly shorter than that of the LS group (182.9 ± 27.2 vs 256.2 ± 45.5 min, p < 0.001). The turning point of the LP learning curve was observed at the 12th case. No major complications such as bladder, ureteral, bowel injury or uncontrolled bleeding occurred in either group. Postoperative low back pain and defecation symptoms occurred exclusively in the LS group. During the follow-up period (mean 7.2 months in LP, 16.2 months in LS), none of the cases had recurrent apical prolapse. CONCLUSIONS: Laparoscopic pectopexy is a feasible surgical method for apical prolapse, with a shorter operation time and less postoperative discomfort than LS. LP may overcome the steep learning curve of LS because the surgical field of LP is limited to the anterior pelvis and avoids encountering the critical organs.

Case Report: Vaccine-Induced Immune Thrombotic Thrombocytopenia in a Pancreatic Cancer Patient After Vaccination With Messenger RNA-1273.

Vaccination plays an important role during the COVID-19 pandemic. Vaccine-induced thrombotic thrombocytopenia (VITT) is a major adverse effect that could be lethal. For cancer patients, cancer-related thromboembolism is another lethal complication. When cancer patients receive their COVID-19 vaccines, the following thromboembolic events will be more complicated. We presented a case recently diagnosed with pancreatic cancer, who had received the mRNA-1273 (Moderna) vaccination 12 days prior. Ischemic stroke and VITT were also diagnosed. We aggressively treated the patient with steroids, immunoglobulin, and plasma exchange. The titer of anti-platelet factor four and d-dimer level decreased, but the patient ultimately died. The complicated condition of VITT superimposed cancer-related thromboembolism was considered. To our knowledge, only one case of mRNA-1273 related VITT was reported, and this case study was the first to report a cancer patient who was diagnosed with VITT after mRNA-1273 vaccination. Therefore, when the need for vaccination among cancer patients increased under the current COVID-19 pandemic, the possible risk of VITT for cancer patients should be carefully managed. Further studies of the risk evaluation of the COVID-19 vaccine in cancer patients might be required in the future.

Impact of the Time Interval Between Primary Debulking Surgery and Start of Adjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer.

AIM: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC). METHODS: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O'Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival. RESULTS: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (<23 days), intermediate (23-43 days) and late (>43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10-0.83, p=0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group. CONCLUSION: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3-6 weeks post-operatively. Initiating chemotherapy early (<23 days) did not appear to benefit PFS.

Effects of uterine artery occlusion during myomectomy on ovarian reserve: Serial follow-up of sex hormone levels, ultrasound parameters and Doppler characteristics.

AIM: To evaluate the influence of uterine artery occlusion at myomectomy (UAO + M) on ovarian reserve based on serum sex hormone levels, ultrasound and color Doppler examinations. METHODS: In this cohort study, nine women with symptomatic uterine myomas underwent UAO + M were recruited. Each woman was assessed preoperatively and 3, 6 months postoperatively, through a serial of hormonal, ultrasound parameters and Doppler examination for ovarian stromal blood flow. The data were analyzed using generalized estimating equations. RESULTS: There was no significant difference in serum anti-Müllerian hormone (AMH) or follicle-stimulating hormone (FSH) levels before and 3, 6 months after UAO + M. The ovarian volume, antral follicle count (AFC) and ovarian stromal blood flow had significant changes in the right ovary. Ovarian volume and AFC significantly reduced at 3 months and recovered at 6 months postoperatively (P = 0.046, P = 0.019, respectively). Peak systolic velocity and end diastolic velocity significantly decreased at 3 months and leveled off at 6 months (P < 0.001, P = 0.001, respectively). Resistance index significantly increased at 3 months and decreased at 6 months (P = 0.037). A similar trend in ultrasound and Doppler findings was observed in the left ovary, but no statistical significance was found. CONCLUSION: UAO + M had no detrimental effect on ovarian reserve 6 months postoperatively based on AMH and FSH levels. AFC, ovarian volume and stromal blood flow were transiently decreased in 3 months and recovered in 6 months.

Oncostatin m modulates the mesenchymal-epithelial transition of lung adenocarcinoma cells by a mesenchymal stem cell-mediated paracrine effect.

Mesenchymal stem cells (MSC) are strongly associated with tumor progression and have been used as novel cell-based agents to deliver anticancer drugs to tumors. However, controversies about the direct involvement of MSCs in tumor progression suggest that MSCs mediate tumor progression in a cancer type-dependent manner. In this report, we analyzed the functional interactions between human MSCs and lung adenocarcinoma (LAC) cells to determine the therapeutic potential of MSCs in lung cancer. We showed that MSCs effectively inhibited the migration, invasion, and cell-cycle progression of several LAC cell lines. MSCs also enhanced the mesenchymal-epithelial transition (MET) pathway, as evidenced by the reduction of several epithelial-mesenchymal transition-related markers in LAC cells cocultured with MSCs or in MSC-conditioned medium (MSC-CM). By cytokine array analysis, we determined that Oncostatin M (OSM), a differentiation-promoting cytokine, was elevated in the MSC-CM derived from primary MSC cultures. Furthermore, OSM treatment had the same effects as MSC-CM on LAC, whereas neutralizing antibodies to OSM reversed them. Notably, short hairpin RNAs against STAT1, an important downstream target of OSM, hindered the OSM-dependent induction of MET. In vivo xenograft tumor studies indicated that OSM inhibited tumor formation and metastasis of LAC cells, whereas neutralizing OSM in the MSC-CM hampered its inhibitory effects. In conclusion, this study showed that OSM is a paracrine mediator of MSC-dependent inhibition of tumorigenicity and activation of MET in LAC cells. These effects of OSM may serve as a basis for the development of new drugs and therapeutic interventions targeting cancer cells.

Pituitary adenylate cyclase-activating polypeptide prevents cell death in the spinal cord with traumatic injury.

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a potent factor in the regulation of neurotransmission, neuroprotection, neurogenesis and anti-inflammation. We here examined the neuroprotective effect of PACAP on injury to the spinal cord tissue of adult rats, induced by dropping a 10 g NYU impactor from the height of 25 mm (moderate injury) or 50 mm (severe injury). PACAP was found to effectively attenuate cell apoptosis in the spinal cord with moderate injury. However, treatment with PACAP had a lesser effect on decreasing DNA fragmentation in the lesion center of the spinal cord with severe contusion injury. Yet, greater extended neural fibers and motor neurons were observed in the rostral and caudal regions of the PACAP-treated spinal cord when compared to that seen in the PBS-treated control. Our findings indicate the beneficial effect of PACAP for the treatment of spinal cord injury (SCI).