Factors affecting gasless reduced-port laparoscopic myomectomy (GRP-LM) using a subcutaneous abdominal wall lifting method: a retrospective analysis of a large cohort of 966 cases in Japan.

OBJECTIVE: To evaluate the usefulness of gasless reduced-port laparoscopic myomectomy (GRP-LM) using a subcutaneous abdominal wall lifting method. METHODS: In GRP-LM, after lifting the abdominal wall by a subcutaneous abdominal wall lifting method, a 1.5-cm incision is made in the lateral abdomen, Lap Protector® is placed. The operation is performed by two surgeons, one who inserts multiple forceps from the Lap Protector and performs the operation, and an assistant who operates the laparoscope and uterine manipulator. The surgical outcome of GRP-LM and the factors that affect it were investigated. RESULTS: GRP-LM was performed in 966 patients. Complications (0.5%) and blood transfusions (0.3%) were remarkably rare, and there were no cases of conversion to open surgery. With regard to the correlation between the number of fibroids extracted and each factor, the number of fibroids extracted correlated with fibroid weight and operation time, but not with blood loss. The average number of sutures per case was 21, and the average suture and ligation time per suture was 77 s. Comparing the cost of GRP-LM with that of the conventional insufflation LM, a saving of $875 was possible with GRP-LM. CONCLUSION: GRP-LM is a suitable for multiple fibroids, and is cosmetic and economical, because it allows rapid and reliable suture and ligation, despite having only one port for the procedure.

Validate robot-assisted total laparoscopic hysterectomy with four equally-spaced ports without an assistant port.

To evaluate the usefulness of robot-assisted total laparoscopic hysterectomy with four equally-spaced ports (RA-TLH/4e) without an assistant port. In RA-TLH/4e, four da Vinci ports were placed horizontally at a height of 4 cm above the umbilicus with 8 cm equal spacing. Poor development of the surgical field or difficult forceps manipulations were handled with the endoscope and forceps movement (port-hopping). Patient background, surgical outcomes, complications, port-hopping frequency were compared in three groups: RA-TLH/4e, RA-TLH with four unequally-spaced ports (RA-TLH/4u), and conventional RA-TLH with five ports (RA-TLH/5). There were no significant differences in patient background or surgical outcomes among the three groups except for age, preparation time, and hospital stay, and no cases of laparotomy conversion or serious complications. RA-TLH/4e had fewer port-hoppings than RA-TLH/4u. The minimum abdominal width showed a weak negative correlation with port-hopping frequency in RA-TLH/4u, but not in RA-TLH/4e. RA-TLH/4e allowed for a reduction in personnel and costs compared to RA-TLH/5. The equal placement of four ports allowed sufficient port spacing even for patients with narrow abdominal widths. In addition, the port-hopping technique was able to fully compensate for the lack of an assistant port. RA-TLH/4e is a highly useful technique that not only excels in safety but also reduces costs.

Efficacy of uterine artery embolization (UAE) for uterine fibroids according to FIGO classification: a single-center experience.

OBJECTIVE: This study aims to retrospectively evaluate the outcomes of uterine artery embolization (UAE) for uterine fibroids (UFs), specifically submucosal UFs, according to the International Federation of Gynecology and Obstetrics (FIGO) classification of UFs. MATERIALS AND METHODS: Forty-two patients with symptomatic UFs underwent UAE with Embosphere® between July 2016 and November 2021. MRI was performed before, at 3 and 6 months after the UAE. At each examination, the volume of UF was measured, and the percentage volume reduction rate (VRR) was calculated. The technical success rate (TSR), symptom improvement rate (SIR), regrowth rate (RR) after 6 months, and adverse events (AEs) were examined; VRR was compared between patients with submucosal UFs (FIGO types 0-2, group A), those with submucosal contacts (FIGO type 3, group B), and those without submucosal UFs (FIGO types 4-7, group C). Statistical analysis was performed on the difference in VRR between groups A, B, and C at 3 and 6 months after UAE. The relationship with hormone levels before UAE and VRR was evaluated. RESULTS: Thirty-seven of the 42 patients were evaluated. Overall, VRR was 37.0% at 3 months and 52.1% at 6 months; TSR, SIR, and RR were 100%, 95.2%, and 5.4%, respectively; VRR at 6 months was 80.7% for group A (n = 7), 57.8% for group B (n = 13), and 37.1% for group C (n = 17). Significant differences were found between A and C (p < 0.001) and B and C (p = 0.023). Hormone levels before UAE had no effect on VRR. There was no significant AEs other than grade 3 pulmonary embolism in one patient. CONCLUSION: UAE was effective for submucosal FIGO types 0-3. UAE was especially useful as an option for FIGO type 3 with a low protrusion rate that is difficult to treat with transcervical resection.

Enhanced production of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells by caffeic acid phenethyl ester, a major component of Chinese propolis.

OBJECTIVES: We evaluated the immune-modulatory effects of Chinese propolis (CP) and its major constituent, caffeic acid phenethyl ester (CAPE), on the cytokine production of anti-CD3 antibody-stimulated mouse spleen cells. METHODS: Mouse spleen cells stimulated by anti-CD3 monoclonal antibody were co-cultured with CP, CAPE, and HC030031, a specific antagonist of the TRPA1 Ca2+-permeable cation channel. Cytokine production was assayed by enzyme-linked immunosorbent assay. Interleukin (IL)-2 mRNA expression was examined by reverse transcription-quantitative polymerase chain reaction. RESULTS: In stimulated spleen cells treated with 1/16,000 CP diluent, IL-2 production was markedly enhanced, while IL-4 and IL-10 productions were not significantly affected. In contrast, interferon (IFN)-γ, IL-6, and IL-17 productions were markedly reduced. These effects of CP were reproduced by the CAPE treatment. A time-course observation demonstrated that, compared to control cells, IL-2 mRNA expression and production were significantly enhanced in the spleen cells stimulated by CAPE; however, IL-2 production was markedly delayed compared to that in the untreated control cells. The enhancement of IL-2 production by CAPE was scarcely alleviated by the addition of HC030031. These effects of CAPE upon IL-2 mRNA production were abolished in spleen cells without anti-CD3 antibody stimulation. CONCLUSIONS: CAPE is an important regulator of CP for cytokine regulation in anti-CD3 antibody-stimulated spleen cells. The agent specifically reduced IFN-γ, IL-6, and IL-17 and slightly enhanced Th2 cytokine production while significantly enhancing IL-2 production at the transcriptional level.

Development and Efficacy of Gasless Reduced-Port Laparoscopic Surgery for Gynecological Diseases.

Objective: To evaluate the efficacy of gasless reduced-port laparoscopic surgery (GRP-LS) using a subcutaneous abdominal wall lifting method for gynecological diseases. Methods: This study included gasless laparoscopic surgeries performed at our hospital between September 1, 1993 and December 31, 2016. The new GRP-LS technique was compared with the conventional gasless three-port laparoscopic surgery (G3P-LS), based on patient background, operative results in patients treated for laparoscopic myomectomy (LM), laparoscopic ovarian cystectomy (LC), and laparoscopic salpingectomy (LT). Surgeons of the two techniques were categorized by the number of surgeries they had performed, and the number of surgeons and surgeries for each technique were compared. Results: GRP-LS was used in 2,338 cases and G3P-LS in 2,473 cases. GRP-LS was used in 980 LM cases, 804 LC cases, 240 LT cases, and 314 cases for other conditions. The operative time required for GRP-LS was significantly less for LM, LC, LT, and the procedure also had less blood loss for LM and LC than G3P-LS. G3P-LS required a transition to open surgery in 0.69% of cases, whereas GRP-LS showed a very low rate of 0.09%. Sixty-seven of the 78 GRP-LS surgeons (85.9%) had performed fewer than 50 GRP-LSs, and these surgeons performed about half of all surgeries. Eighty-three of the 93 GRP-LS surgeons (89.2%) had performed fewer than 50 G3P-LSs, and these surgeons performed 38.9% of all surgeries. Conclusions: GRP-LS is an effective surgery with few complications and less cosmetic damage and can be easily introduced to novice or inexperienced laparoscopic surgeons.

Does the use of a uterine manipulator in robotic surgery for early-stage endometrial cancer affect oncological outcomes?

BACKGROUND: To investigate the impact of the use of a uterine manipulator in robot-assisted surgery for early-stage endometrial cancer on oncological outcome. METHODS: Eighty six robotic surgeries and sixty seven open surgeries were performed for early-stage endometrial cancer. Disease-free survival and overall survival at 5 years, and surgical results and postoperative complications were compared between surgeries. In robotic surgery, a uterine manipulator was used in all cases. RESULTS: There was no significant difference in oncological outcome between surgeries. Robotic surgery showed significantly longer operative time, less blood loss, and shorter hospital stay compared to open surgery. In robotic surgery, complications occurred significantly less frequently, and no patients required conversion to laparotomy. There were no clear correlations of positive lavage cytology with The International Federation of Gynecology nd Obstetrics stage, recurrence, and site of recurrence in either surgery. CONCLUSIONS: The use of a uterine manipulator during robotic surgery for early-stage endometrial cancer did not influence recurrence or survival.

Introduction of gasless laparoscopic surgery as a minimally invasive procedure for endometrial cancer and its usefulness from the viewpoint of the learning curve.

BACKGROUND: We investigated the usefulness of gasless laparoscopic surgery (GLS) using a subcutaneous abdominal wall lifting method for endometrial cancer. METHODS: We studied 105 patients with early endometrial cancer who underwent GLS (55) or open surgery (50). A uterine manipulator was used in all GLS cases. We compared operative time, blood loss, number of lymph nodes removed, hospital stay, perioperative complications, cases converted to laparotomy, and recurrence and survival rates. We also studied the learning curve and proficiency of GLS. RESULTS: The GLS group had significantly longer operative time (265 vs. 191 min), reduced blood loss (184 vs. 425 mL), shorter hospital stay (9.9 vs. 17.6 days), and fewer postoperative complications (1.8 vs. 12.0%) than the open group. No case was converted to laparotomy. Disease-free and overall survival rates at 4 years postoperatively (GLS vs. open groups) were 98.0 versus 97.8 and 100 versus 95.7%, respectively, and there was no significant difference between the groups. Regarding the learning curve for GLS, two different phases were observed in approximately 10 cases. Operator 2, who was not accustomed to laparoscopic surgery, showed a significant reduction in operative time in the later phase 2. CONCLUSIONS: GLS for endometrial cancer results in less bleeding, shorter hospital stay, and fewer complications than open surgery. Recurrence and survival rates were not significantly different from those of open surgery. This technique may be introduced in a short time for operators who are skilled at open surgery but not used to laparoscopic surgery.

Single assistant versus dual assistant robotic surgery for robot-assisted laparoscopic hysterectomy using da Vinci Xi or X.

BACKGROUND: To verify the usefulness of single assistant robotic surgery (SA-RS) using da Vinci Xi or X performed for total hysterectomy. METHODS: The SA-RS group (S-group) includes surgeries in which the surgeon performed all surgical operations other than that of the uterine manipulator, while the dual assistant robotic surgery group (D-group) includes surgeries performed by the surgeon with two assistants. In S-group, the forceps and camera were replaced during surgery in cases of a large uterus with limited range of motion of the instrument. A comparative study of patient background, intraoperative and postoperative results and surgery-related cost was performed between the two groups. RESULTS: No significant differences were observed between the two groups. On the contrary, S-group showed a significant reduction in preparation time and wound closure time, and a savings of $768. CONCLUSION: SA-RS for total hysterectomy was possible, which is excellent in terms of cost, esthetics, and manpower.

Augmented secretion of IL-1α from mouse oral squamous cell carcinoma (OSCC) vcells caused by serum deprivation and hypoxia promotes immune suppressive activity of mesenchymal stromal cells.

OBJECTIVES: We have previously reported that mouse oral squamous carcinoma (OSCC), Sq-1979-1, produces interleukin (IL)-1α, which specifically enhances the immunosuppressive activity of co-cultured mesenchymal stromal 10T1/2 cells. This study assessed the conditions promoting the production of IL-1α in Sq-1979-1 cells, which could further enhance the immunosuppressive function of 10T1/2 cells, and evaluated its expression in OSCC tissues. METHODS: The expression of IL-1α was examined by RT-PCR, western blotting, and enzyme-linked immune sorbent assay (ELISA). The interferon (IFN)- γ-producing capability of anti-CD3 antibody-stimulated mouse spleen cells co-cultured with 10T1/2 cells and conditioned medium (CM) from Sq-1979-1 cells was examined by ELISA. The function of IL-1α was examined using an anti-IL1α antibody. Immunohistochemical analysis of the OSCC tissues was performed. RESULTS: The production of IL-1α from Sq-1979-1 cells was synergistically enhanced in lower serum (0.5% or 1.0% FBS) at the transcriptional level, and under hypoxia (1.0% oxygen) at the release level compared to that in the control medium supplemented with 10% FBS under normoxia. The IFN-γ-producing capability of stimulated spleen cells co-cultured with 10T1/2 cells was significantly reduced in the CMs prepared with the lower serum or under hypoxia. These functions of CMs were completely abolished by the anti-IL-1α antibody. The expression of IL-1α in OSCC tissues was prominent in the midst of a carcinomatous cellular lesion or a nearby necrotic lesion, where a supply deficiency could occur. CONCLUSION: s: IL-1α production by Sq-1979-1 cells was synergistically augmented under low serum and hypoxic conditions, which could promote the immunosuppressive activity of mesenchymal cells.

A case of a patient who underwent transcatheter arterial embolization for unruptured splenic aneurysm during pregnancy.

Here, we report the case of a 30-year-old female patient who underwent coil embolization for unruptured splenic artery aneurysm without any complication at 26 weeks of pregnancy with reduction in fetal radiation exposure. The patient did not suffer from rupture of splenic artery aneurysm during or after procedure. Pregnancy is a risk factor of splenic artery aneurysm rupture with a high mortality rate. Transcatheter arterial embolization at 26 weeks of pregnancy might be a better treatment alternative for a pregnant patient with splenic artery aneurysm with respect to the endurance of fetal radiation exposure to prevent aneurysm rupture.

Plasma estradiol levels and antidepressant effects of omega-3 fatty acids in pregnant women.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) reduce depressive symptoms through an anti-inflammatory effect, and injection of both omega-3 PUFAs and estradiol (E2) induces antidepressant-like effects in rats by regulating the expression of inflammatory cytokines. The aims of this study were to examine the association of increased E2 during pregnancy with depressive symptoms and with inflammatory cytokines in women who were and were not supplemented with omega-3 PUFAs. METHODS: Pregnant women with Edinburgh Postnatal Depression Scale scores ≥9 were recruited at 12-24 weeks of gestation. The participants were randomly assigned to receive 1800 mg omega-3 fatty acids (containing 1206 mg eicosapentaenoic acid [EPA]) or placebo for 12 weeks. E2, omega-3 PUFAs, high-sensitivity C-reactive protein, interleukin-6, and adiponectin were measured at baseline and at the 12-week follow-up. Multivariable regression analyses were conducted to examine the association of the changes of E2 and omega-3 PUFAs with the changes in depressive symptoms and with the changes of inflammatory cytokines at follow-up by intervention group. RESULTS: Of the 108 participants in the trial, 100 (92.6%) completed the follow-up assessment including blood sampling. Multivariable regression analyses revealed that the increase of EPA and E2 was significantly associated with a decrease in depressive symptoms among the participants assigned to the omega-3 group, but not among those assigned to the placebo group. Neither E2 nor any PUFAs were associated with a change in inflammatory cytokines. CONCLUSION: Supplementation with EPA and increased levels of E2 during pregnancy might function together to alleviate antenatal depression through a mechanism other than anti-inflammation.

Transcriptomic features of trophoblast lineage cells derived from human induced pluripotent stem cells treated with BMP 4.

INTRODUCTION: Early development of the human placenta remains poorly understood due to the lack of proper model systems. Previous reports have demonstrated that human induced pluripotent stem cells (hiPSCs) treated with bone morphogenetic protein 4 (BMP4) can differentiate into extraembryonic tissues as useful models of the early stage of trophoblast (TB) differentiation. In our previous study, we optimized the culture conditions of hiPSC-derived TB lineages, but the differentiated cells were heterogeneous. METHODS: In order to characterize the hiPSC-derived TB lineage cells, four types of hiPSCs were treated with 50 ng/mL of BMP4 for 10 days. Subsequently, cells that were positive for the pan-TB marker keratin 7(KRT7) were purified from the differentiated cells using flow cytometry and identified with a DNA microarray. RESULTS: Comparisons of our microarray data with the human transcriptome in a previous large-scale analysis showed that the gene expression patterns of KRT7+ cells were similar to the placenta. In total, 259 upregulated genes were commonly expressed in all four KRT7+ groups, including well-known TB markers. Among these upregulated genes, several with poorly investigated expression patterns and functions were confirmed as expressed in the primary placenta. While only XAGE2 and KCNQ2 were expressed in TB layers, XAGE2 was expressed throughout pregnancy and KCNQ2 was expressed only in cytotrophoblasts of the first trimester placenta. CONCLUSION: BMP4-treated KRT7+ cells were in the course of the human placental development. In addition, this approach allowed the identification of new genes that might be involved in placentation. However, further studies are needed to confirm their functions.

Ultrasound Elastography can Detect Placental Tissue Abnormalities.

BACKGROUND: In this prospective cohort study, we examined the utility of elastography to evaluate the fetus and placenta. PATIENTS AND METHODS: Pregnant women in their third trimester of pregnancy, by which time the placenta has formed, were included in this study. A total of 111 women underwent ultrasound examinations, including elastography. Elastographic evaluation was performed using two protocols. First, the placental index (PI) was measured, which quantitatively assesses the hardness of tissue. Second, regions of interest (ROI) were categorized into 3-step scores according to the frequency of the blue area (hardness of placental tissue score [HT score]), which is a qualitative method. After delivery, 40 of the 111 placentas were pathologically examined. RESULTS: The average PI was 44.3 (± 29.4) in the in utero SGA group, which was significantly higher than that in the normal group (8.8 (± 10.0); p < 0.01) during pregnancy. There was a significant correlation between the PI and z score for estimated fetal weight (EFW) (r = -0.55; p < 0.01). Moreover, a significant positive correlation was observed between the PI and the z score of birth weight (r = -0.39; p < 0.01). Pathological ischemia findings of the placenta were identified in 67% of the HT score 3 group, representing 6 of the 9 patients, and in 20% of the HT score 1 group, representing only 3 of the 15 patients. CONCLUSIONS: Placental hardness, as determined by elastography, correlates with both lower estimated fetal body weight and birth weight. These results suggest that ultrasound elastography in the placenta may be an additional marker of intrauterine fetal well-being.

Efficient production of trophoblast lineage cells from human induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) are potentially useful in both clinical applications and basic biological research. hiPSCs can differentiate into extra-embryonic cells in the presence of BMP4. However, the differentiation potential of hiPSCs can be affected by culture conditions or genetic variation. In this study, we investigated the effect of various BMP4 concentrations on the expression states of trophoblast markers and the optimal conditions for trophoblast induction. A high-fidelity gene expression assay using hiPSC lines showed that the expression levels of various trophoblast marker genes, such as KRT7, GCM1, CGB, and HLA-G, were upregulated by BMP4 in a dose-dependent manner in all types of hiPSCs used in this study. Treatment with high doses of BMP4 for prolonged periods increased the ratio of cells with trophoblast markers irrespective of the presence of bFGF. We found that the expression states of major pluripotency- and differentiation-related protein-coding genes in BMP4-treated cells depended on culture conditions rather than donor cell types. However, miRNA expression states were affected by donor cell types rather than BMP4 dose. Furthermore, the effect of the presence of bFGF on differentiation potential of KRT7-positive cells differed among iPSC types. Mechanistically, chromatin states around KRT7 promoter regions were comparable among the iPSC types used in this study, indicating that hiPSC chromatin state at these regions is not a parameter for cytotrophoblast differentiation potential. In conclusion, the optimal conditions for trophoblast differentiation from hiPSCs differ according to parental cell line.

Clinical efficacy of a combination of Percoll continuous density gradient and swim-up techniques for semen processing in HIV-1 serodiscordant couples.

To evaluate the clinical efficacy of a procedure comprising a combination of Percoll continuous density gradient and modified swim-up techniques for the removal of human immunodeficiency virus type 1 (HIV-1) from the semen of HIV-1 infected males, a total of 129 couples with an HIV-1 positive male partner and an HIV-1 negative female partner (serodiscordant couples) who were treated at Keio University Hospital between January 2002 and April 2012 were examined. A total of 183 ejaculates from 129 HIV-1 infected males were processed. After swim-up, we successfully collected motile sperms at a recovery rate as high as 100.0% in cases of normozoospermia (126/126 ejaculates), oligozoospermia (6/6), and asthenozoospermia (36/36). The recovery rate of oligoasthenozoospermia was 86.7% (13/15). In processed semen only four ejaculates (4/181:2.2%) showed viral nucleotide sequences consistent with those in the blood of the infected males. After using these sperms, no horizontal infections of the female patients and no vertical infections of the newborns were observed. Furthermore, no obvious adverse effects were observed in the offspring. This protocol allowed us to collect HIV-1 negative motile sperms at a high rate, even in male factor cases. We concluded that our protocol is clinically effective both for decreasing HIV-1 infections and for yielding a healthy child.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

BACKGROUND: Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. METHODS: The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. DISCUSSION: The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

[Uterine cancer].

It is thought that robotic surgery is highly useful for uterine malignant tumor such as endometrial cancer and cervical cancer. It is nothing but that robotic surgery enables us the correct and delicate movement of forceps, which is necessary for operative procedures at the deep and narrow space in the pelvic cavity and the perivascular lymphadenectomy. By our experience, significant reduction of blood loss and shortening of the hospital stay were accepted in the cases of endometrial cancer and cervical cancer. At present the robotic surgery in uterine cancer in Japan lags far behind the USA In order not to miss the trend in the world, it is required for the robotic surgery of uterine cancer to spread widely in Japan from now on. For this purpose, it is necessary to accumulate cases on the assumption that advanced medical care and also insurance adaptation.