Cost analysis of four types of surgeries for pelvic organ prolapse in a Japanese population.

INTRODUCTION AND HYPOTHESIS: To compare the perioperative costs analysis between laparoscopic/transvaginal and the mesh/non-mesh surgeries for pelvic organ prolapse (POP) in Japan. MATERIALS AND METHODS: From April 2013 to April 2017, 890 patients who underwent POP surgeries were enrolled in this study. Regarding transvaginal native tissue repair (TV-NTR: transvaginal hysterectomy with colpocleisis), transvaginal mesh surgery (TVM), laparoscopic native tissue repair (L-NTR: laparoscopic hysterectomy and uterosacral ligament colposuspension), and laparoscopic sacrocolpopexy (LSC), a retrospective observational study was performed. Patients' age, operation time, blood loss, perioperative complications, length of hospital stay, pre-/postoperative quality of life (QOL) scores, were reviewed from the medical records. The net income, which was calculated by using the income (the operation/anesthesia fee) and the costs (the labor and consumables costs for operation/anesthesia), was evaluated. RESULTS: The operation fees of the L-NTR ($4250) and the LSC ($4833) groups were higher than that of the TV-NTR ($2652) and the TVM ($2913) groups. The labor costs and consumables costs of operation were higher in the LSC ($1589) and the L-NTR ($1500) groups than the TV-NTR ($180) and the TVM ($178) groups. The consumables costs for anesthesia in the four groups were equal. The operation hours were significantly shorter in the TV-NTR and the TVM groups than the L-NTR and the LSC groups. CONCLUSIONS: We found that TVM operation was an economically excellent and the most efficient POP operation with shorter operation time and less consumables.

Guideline for Gynecological Practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition.

Nine years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 4th Revised Edition was published in 2020. The 2020 Guidelines includes 4 additional clinical questions (CQ), which brings the total to 99 CQ (12 on infectious disease, 29 on oncology and benign tumors, 29 on endocrinology and infertility and 29 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Laparoscopic uterosacral ligament colpopexy for apical support in addition to hysterectomy for pelvic organ prolapse.

AIM: To evaluate the perioperative complications and the anatomical outcomes of our laparoscopic uterosacral ligament (USL) colpopexy, which is a novel laparoscopic technique for the management of uterine prolapse. The objective was to report on outcome after 2 years of a technique using laparoscopic USL colpopexy. METHODS: A total of 152 uterine prolapse patients underwent laparoscopic USL colpopexy from May 2013 to April 2015. We described the surgical technique and performed a retrospective analysis of this laparoscopic technique. Patients underwent standardized assessment and examination using pelvic organ prolapse quantification (POP-Q) score. The dependent values of Ba point (bladder), C point (vaginal cuff) and Bp point (rectum) were recorded preoperatively, and at 1, 3, 6, 12 and 24 months of postoperative examination. Pre/postoperative data were compared using the Kaplan-Meier method. RESULTS: Mean age, operative time and amount of hemorrhage were 68.2 ± 7.5 years, 118.3 ± 36.4 min and 60.5 ± 73.3 mL, respectively. Overall recurrent prolapse, which was defined as POP-Q stage II or higher, was noted in 29 patients (19%). However, only 2 patients presented recurrent rectocele among 51 patients with preoperative POP-Q stage II of uterine prolapse alone (recurrence rate; 3.9%). The pre/postoperative average POP-Q scores were -0.2/-2.7 cm (P < 0.05) at Ba point, -1.9/-5.1 cm (P < 0.05) at C point and -2.4/-2.3 cm (P = 0.06) at Bp point. CONCLUSION: Laparoscopic visualization of uterosacral ligaments may result in safe colpopexy. Our results show this will be a useful procedure for apical support as native tissue repair.

Aiming for complete safety of first trocar insertion of laparoscopic surgery: usefulness of preoperative ultrasonography of umbilical region.

AIM: Vascular or intestinal injuries at the time of the first trocar insertion can cause serious complications during laparoscopic surgeries. In this study, we evaluate the usefulness of ultrasound scans of the umbilical region as well as intraumbilical conditions to help prevent serious complications. METHODS: The subjects included 430 cases who underwent laparoscopic gynecologic surgeries. The umbilical ultrasound scan was performed after tracheal intubation to observe the intestinal movements associated with respiration. Structures of the umbilical region as well as peristalsis and the movement of the intestinal tract were observed. Then, the thickness of the subcutaneous fat (between the umbilical skin surface and the rectus fascia) and the preperitoneal fat (between the rectus fascia and the peritoneum) were measured. The relationship between body mass index (BMI), insertion time of the first trocar and ultrasound measurements were analyzed. RESULTS: The anatomical structures of the umbilical region (the subcutaneous tissue and the preperitoneal fat) were clearly observed in all cases. The BMI score had a significant relationship with subcutaneous fat thickness (r = 0.547), but remarkably not with preperitoneal fat thickness (r = 0.174). There was no significant relationship between BMI and insertion time. However, insertion time of the first trocar had a significant relationship with preperitoneal fat thickness (r = 0.534). CONCLUSIONS: Preoperative ultrasonography of the umbilical region is asimple process, and it is helpful inpreventing serious complications caused by the first trocar insertion. We have found that preperitoneal fat thickness seems to be an important factor in predicting the potential difficulty of the first trocar insertion.

Pharmacokinetic and Pharmacodynamic Markers of Mycophenolic Acid Associated with Effective Prophylaxis for Acute Graft-Versus-Host Disease and Neutrophil Engraftment in Cord Blood Transplant Patients.

Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is frequently used to prevent acute graft-versus-host disease (aGVHD) in patients receiving hematopoietic stem cell transplantation (HSCT). However, optimal doses of MMF and target MPA concentrations in HSCT patients have not been defined. In this study, relationships between pharmacokinetic or pharmacodynamic markers of MPA and successful aGVHD prevention and neutrophil engraftment were evaluated to inform individualized MPA treatments in HSCT patients. We recruited 35 patients undergoing cord blood transplantation (CBT) who were treated with MMF. Area under the concentration-time curves from 0 to 24 hours (AUC0-24) for free MPA and MPA acyl glucuronide (AcMPAG) at 1 week after the start of MMF treatments were significantly higher in patients with gastrointestinal (GI) aGVHD at stage ≥I than those at stage 0. Patients with faster neutrophil engraftment had higher free MPA AUC0-24 at 1 week after the start of MMF treatments compared with those with slower neutrophil engraftment. Inosine-5'-monophosphate dehydrogenase activity in peripheral blood mononuclear cells and single nucleotide polymorphisms in genes that were previously associated with MPA pharmacokinetics and pharmacodynamics were not an independent predictor for the clinical outcomes. Receiver-operating characteristic model analyses showed that cutoff values of AUC0-24 for successful GI aGVHD prevention were .689 and 15.6 µg⋅hour⋅mL-1 for free MPA and AcMPAG, respectively. In addition, the cut-off value of free MPA AUC0-24 for neutrophil engraftment by day 25 was .405 µg⋅hour⋅mL-1. In conclusion, free MPA AUC0-24 may be a better predictor of the prevention of GI aGVHD and neutrophil engraftment compared with that of total MPA in patients receiving CBT. Hence, monitoring of the free MPA AUC0-24 between .405 and .689 µg⋅hour⋅mL-1 could be considered informative of individualized MPA treatments in CBT patients.

Novel technique for adhesion barrier insertion by using cut-off surgical glove fingers in laparoscopic surgery.

AIM: Laparoscopic surgery causes fewer postoperative adhesions than laparotomy and adhesion barriers are used to lessen the chance of adhesion. Sodium hyaluronate and carboxymethylcellulose (SH-CMC), a bioresorbable membrane, is effective in preventing adhesions. However, its properties make it difficult to insert the film into the abdominal cavity and to place it into the target area during laparoscopic surgeries. Here we report a novel technique for applying SH-CMC during laparoscopic surgeries by using cut-off surgical glove fingers. METHODS: In our dry-box experiment, we found that SH-CMC became more flexible after moisturizing for 30 s. Therefore, for this procedure, we moisturizing both sides of the SH-CMC sheet (7.35 × 6.35 cm) on wet gauze (for 30 s). The film was rolled into cut-off surgical glove fingers and inserted into the abdominal cavity through a 12-mm trocar. The film was then removed from the glove finger and unrolled onto the target area (glove-finger method). RESULTS: The dry-box experiment revealed that moisturizing both sides of SH-CMC for 30 s/side, 15 min after package removal, made the film more flexible. Ninety of 96 attempts with SH-CMC were successful among the 24 patients who underwent total laparoscopic hysterectomy with our glove-finger method. CONCLUSION: Our glove-finger method can realize the smooth application of SH-CMC to the target area during laparoscopic surgeries.

Laparoscopic fixation of the vaginal cuff to the uterosacral ligaments at the time of hysterectomy.

INTRODUCTION AND HYPOTHESIS: Transvaginal ipsilateral uterosacral ligament colpopexy for pelvic organ prolapse (POP), which was reported by Shull et al. (Shull's colpopexy) in 2000, is one of the most frequently performed non-mesh pelvic floor reconstructive surgical procedures. Despite its excellent anatomical outcomes, ureteral injury and difficulty in uterosacral ligament detection (especially in patients with severe POP) are typical issues with this procedure. METHOD: This video demonstrates the procedure in a 58-year-old woman, gravida 2 para 2, with POP-Q stage II uterine prolapse and stage I cystocele. At the beginning of the operation, the bilateral uterosacral ligaments were confirmed and separated from the ureters after entering the retroperitoneal space. The inferior hypogastric nerve and pelvic nerve plexus were also separated from the uterosacral ligament. After total laparoscopic hysterectomy, three ipsilateral delayed absorbable monofilament sutures were placed between the uterosacral ligament and the vaginal cuff. Retroperitonealization was then performed using a continuous suture with closure of the Douglas pouch. CONCLUSION: Laparoscopic Shull's colpopexy for POP is a secure procedure with the advantages of laparoscopy (magnification and sharing the operative field). This may become one of the most useful operations for apical support as native tissue repair.

How to reduce the operative time of laparoscopic sacrocolpopexy?

OBJECTIVE: Laparoscopic sacrocolpopexy (LSC) has been reported to achieve lower recurrence rates, shorter recovery time, and less dyspareunia. However, as a pelvic organ prolapse (POP) surgery, LSC is problematic because it requires specific techniques and it takes a comparatively longer operative time. In this study, we present our surgical techniques of LSC and their effectiveness for shortening operative times and raising safety. METHODS: Thirty-four women with stage 2 or greater POP who underwent LSC in our hospital between September 2014 and October 2015 were enrolled in this study. The notable points of our operative procedures are as follows: (1) fixing the sigmoid colon to the left lateral abdominal wall for a clearer visualization of the sacral promontory, (2) making a retroperitoneal tunnel (not opening the peritoneum) from the sacral promontory to the Douglas pouch, (3) dissection of the vaginal wall after transvaginal hydrodissection, (4) fixation of mesh to the vaginal wall by using absorbable tacks, and (5) limiting usage of posterior mesh for the patients with posterior vaginal wall descent. RESULTS: The median operative time was 140 (range, 90-255) minutes, and blood loss was 50 (range, 10-1600) mL. The operative time decreased as the surgical techniques improved through experience. No major intra- or postoperative complications occurred. The mean follow-up period was 4 (range, 1 -14) months, and only one patient presented a recurrent grade 2 cystocele. CONCLUSION: Our unique procedures will help shorten operative times and reduce complications of LSC.

Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients.

Monitoring of pharmacodynamics in addition to pharmacokinetics is one of strategies to individualize mycophenolate mofetil therapy. The purpose of this study was to develop sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for evaluation of the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). Concentrations of mycophenolic acid glucuronide (MPAG), mycophenolic acid acyl-glucuronide, as well as unbound MPA and MPAG, were determined, and inosine-5'-monophosphate dehydrogenase activity was calculated by measuring concentrations of produced xanthosine-5'-monophosphate (XMP) and intracellular adenosine-5'-monophosphate after incubation of peripheral blood mononuclear cell (PBMC) lysates. A metal-free Mastro(TM) column and two gradient patterns were used to improve the quantification limit of XMP to 0.1 µM. In the clinical MPA concentration range, the linearity of the calibration curve, inter- and intra-day precision and accuracy satisfied the relevant US Food and Drug Administration guidelines. The MPA concentrations in hematopoietic stem cell transplant (HSCT) patients determined by the enzyme assay and the present LC-MS/MS method showed a good correlation (r(2) = 0.95, p < 0.001). In this study, we report sensitive and validated LC-MS/MS methods to evaluate the pharmacokinetics and pharmacodynamics of MPA, which are sufficiently sensitive to assess small quantities of PBMC lysates collected shortly after HSCT.

Retrospective study of tension-free vaginal mesh operation outcomes for prognosis improvement.

AIM: The aim of this study is to look at the weak points of tension-free vaginal mesh (TVM) operation for pelvic organ prolapse by reviewing recurrent cases. METHODS: Five hundred and twenty-six transobturator TVM operations were performed at the University of Occupational and Environmental Health hospital from August 2006 to December 2011. Thirty-seven patients with pelvic organ prolapse quantification (POP-Q) stage II or higher after their initial operations were diagnosed as recurrent and were enrolled in the present study. The patients' characteristics, procedures of the initial and second operations, and the recurrence rates in the pelvic organs were retrospectively reviewed. RESULTS: The median age, parity and body mass index of the patients were 66.5 years (range, 48-80), 2.2-times (range, 1-5) and 24.1 kg/m(2) (range, 17.6-32.1), respectively. The mean/median follow-up periods of the whole group were 29.7/35.9 months and the recurrent prolapse rate was 7.0% (37/526 cases). We performed reoperations in eight cases (8/526 cases; 1.5%). The median recurrent period after the initial operations was 6.9 months (range, 1-24). All recurrent cases showed severe prolapse with POP-Q stage III to IV before the initial operations. The uterus showed the most frequent recurrent prolapse after anterior posterior TVM or anterior TVM. CONCLUSION: Because the uterus is the most recurrent organ after TVM operations, TVM operations may not be sufficient for apical suspension.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan.

Prenatal spontaneous disruption of the dividing membrane in monochorionic diamniotic twins detected at the time of fetoscopic laser photocoagulation.

Spontaneous antepartum rupture of the dividing membrane occurring in monochorionic diamniotic twins (MD twin) is an extremely rare complication and difficult to diagnose prenatally. We present a case of pseudo-monoamniotic twins derived from an MD twin gestation, which was suspected by ultrasound and was confirmed by antepartum fetoscopy. A 28-year-old woman, gravida 1, para 1 at 24 weeks of gestation was referred because of suspected polyhydroamnios in an MD twin. Ultrasound suggested twin-twin transfusion syndrome stage III, spontaneous rupture of the dividing membranes and cord entanglement. Fetoscopic laser photocoagulation (FLP) was performed using the Nd:YAG laser on 12 placental vascular connections. Fetoscopy revealed the spontaneous rupture of the dividing membrane and cord entanglement. The remainder of the pregnancy was managed as a monoamniotic twin gestation. Elective cesarean section was performed at 32 weeks of gestation following antenatal steroids and concordantly grown healthy male infants were delivered.

Interleukin-6 is neither necessary nor sufficient for preterm labor in a murine infection model.

OBJECTIVE: The aim of this study was to investigate the role of interleukin 6 (IL-6) in a murine model of bacterially induced preterm delivery. METHODS: On day 14.5 of a 19-20-day gestation, female mice underwent one of two interventions. In experiment 1, pregnant right uterine horns were injected at laparotomy with 0.5-20 microg of recombinant human IL-6 (rhIL-6). In experiment 2, IL-6-deficient (IL-6(-/-)) and wild-type control (IL-6(+/+)) mice underwent intrauterine inoculation with 10(5) to 10(8) heat-killed Escherichia coli organisms. Preterm delivery and maternal survival rates were recorded. RESULTS: In experiment 1, doses as high as 20 microg of IL-6 per mouse resulted in up-regulation of acute phase reactants but did not cause preterm delivery or other adverse maternal or fetal effects. In experiment 2, in bacterially inoculated mice, the absence of maternal and fetal IL-6 had no effect on preterm delivery rates. CONCLUSION: IL-6 was neither sufficient nor necessary for preterm delivery in these murine models.

Shiga toxin 1 and 2 induce apoptosis in the amniotic cell line WISH.

OBJECTIVE: The aim of this study was to evaluate the toxicity of Shiga toxin (Stx) 1 and 2 on amniotic cells in vitro. METHODS: WISH cells, which were derived from human amniotic cells, and Vero cells were cultured with or without Stxs. After 24 hours of culture, cell viability was measured by Cell Counting Kit-8, and extracted DNA was electrophoresed on a 1% agarose gel. The morphologic changes were observed by Papanicolaou staining, and the apoptotic index (percentage of apoptotic nuclei per total nuclei) was calculated. Quantification of apoptotic cells was also measured by an enzyme-linked immunosorbent assay. RESULTS: The viability of WISH cells decreased in proportion to the concentrations of Stxs. Cellular ladder formation was observed by DNA electrophoresis of Stx-treated WISH cells, and the typical morphologic changes were observed by Papanicolaou staining. The proportion of apoptotic cells increased in response to Stxs. CONCLUSIONS: Stxs injured WISH cells directly and induced apoptosis in vitro. WISH cells were as sensitive as Vero cells to Stxs and cell death occurred by apoptosis.