Comparative Study of Postoperative Analgesic Effects of Intraoperative Levobupivacaine Local Infiltration Anesthesia and Transversus Abdominis Plane Block Following Gynecologic Laparoscopy.

Objectives: We aim to assess the postoperative analgesic effect of intraoperative levobupivacaine local infiltration anesthesia (LA) and transversus abdominis plane (TAP) block in gynecologic laparoscopy. Materials and Methods: We conducted a retrospective analysis on the data of 260 patients treated by gynecologic laparoscopy (adnexal surgery, hysterectomy, and myomectomy) between January 2019 and December 2020 at Minoh City Hospital, Osaka Japan. Patients were divided into two groups: intraoperative LA group and TAP block group. We assessed clinical characteristics, surgical results, postoperative numerical rating scale (NRS) pain scores, and the frequency of analgesic use up to 24 h after surgery in overall and by each type of surgery. Pearson's χ2 test, Fisher's exact test, and Wilcoxon/Kruskal-Wallis test were used for statistical analysis. Multiple regression analysis was used for multivariate analysis. Results: NRS pain score was statistically significantly higher in the LA group than in the TAP group 1 h after surgery in overall (P = 0.04), with NRS difference of 0.4 which was not clinically significant. No significant differences were observed in NRS pain scores at 3, 6, 12, and 24 h after surgery or in the frequency of analgesic use up to 24 h after surgery in overall and by type of surgery. Endometriosis was associated with increased postoperative pain at 1 h after surgery in adnexal surgeries (P = 0.04) and suggestive for all surgeries. Younger age was related to more frequency of analgesic use up to 24 h after surgery in overall, adnexal surgeries, and hysterectomy. Conclusion: Intraoperative levobupivacaine LA may have similar postoperative analgesic effects as TAP block in gynecologic laparoscopy.

Usefulness of Disposable Skin Biopsy Punch for Cervical Occlusion after Cervical Conization.

Cervical occlusion is a rare but serious complication after conization of the uterine cervix. We report on a 69-year-old woman with cervical intraepithelial neoplasia (CIN) 2, who successfully underwent follow-up biopsy of an occluded cervical canal after conization using a disposable skin biopsy punch. The disposable skin biopsy punch was inserted into a slight dimple, which was considered a uterine os, in the direction of the cervical canal, and a sample of tissue was obtained from the occluded portion. This procedure was performed without anesthesia and was completed uneventfully. Histological examination of the excised tissue revealed CIN 3. In addition, the procedure resulted in recanalization of the occluded cervical canal. The occlusion was limited in the external portion of the cervical os and attributed to adhesion of scar tissue during the healing process. Our experience suggests that a disposable skin biopsy punch can be used for follow-up biopsy and recanalization in patients with cervical occlusion after conization as a less invasive approach.

The Role of Preoperative and Postoperative Transversus Abdominis Plane and Rectus Sheath Block in Patients Undergoing Total Laparoscopic Hysterectomy.

PURPOSE: This study was performed to assess the efficacy of a preoperative and postoperative transversus abdominis plane (TAP) and rectus sheath (RS) block compared with no TAP and RS block in patients undergoing total laparoscopic hysterectomy (TLH). DESIGN: Prospective observational cohort study. METHODS: From January 2014 to December 2017, 195 women undergoing TLH were categorized into three groups based on their perioperative analgesia: no TAP + RS block (n = 88), preoperative TAP + RS block + systemic analgesia (n = 68), and postoperative TAP + RS block + systemic analgesia (n = 39). We evaluated use of nonsteroidal anti-inflammatory drugs (NSAIDs) and NSAID consumption within the first 12 hours postoperatively and the numerical rating scale score at 0, 12, and 24 hours postoperatively. FINDINGS: Women with a preoperative TAP + RS block had a significantly lower utilization rate of NSAIDs within the first 12 hours postoperatively (54.4% vs 75.0%; P = .007), lower postoperative flurbiprofen dose (45.5 vs 62.0 mg; P = .048), and lower numerical rating scale score at 12 hours postoperatively (1.63 vs 2.20; P = .002) compared with women with no TAP + RS block. CONCLUSIONS: A preoperative TAP + RS block provided superior postoperative analgesia in patients undergoing TLH and reduced analgesic consumption during the first 12 hours postoperatively.

Broad ligament hernia successfully repaired by single-incision laparoscopy: A case report.

A 52-year-old woman with a history of two parturitions presented with lower abdominal pain. Multi-detector CT of the abdomen showed discontinuity of the sigmoid colon near the broad ligament on the left side. We assigned a provisional diagnosis of an internal hernia progressing through a defect in the broad ligament. SILS revealed a total broad ligament defect on the left side but no signs of ischemic, necrotic bowel. We successfully repaired the broad ligament defect with suturing. At the 2-month follow-up, the patient remained well with no signs of recurrence. This case appears to be the first report of a broad ligament hernia successfully diagnosed and repaired by SILS.

Artificial neural networks to predict future bone mineral density and bone loss rate in Japanese postmenopausal women.

OBJECTIVE: Predictions of the future bone mineral density and bone loss rate are important to tailor medicine for women with osteoporosis, because of the possible presence of personal risk factors affecting the severity of osteoporosis in the future. We investigated whether it was possible to predict bone mineral density and bone loss rate in the future using artificial neural networks. RESULTS: A total of 135 women over 50 years old residing in T town of Wakayama Prefecture, Japan were analyzed to establish a statistical model. Artificial neural networks models were constructed using the two variables of bone mineral density and bone loss rate. The multiple correlation coefficients between the actual and measured values for lumbar and femoral bone mineral densities in 2003 showed R2 = 0.929 and R2 = 0.880, respectively, by linear regression analyses, while the values for bone loss rates in lumbar and femoral bone mineral densities were R2 = 0.694 and R2 = 0.609, respectively. Statistical models by artificial neural networks were superior to those by multiple regression analyses. The prediction of future bone mineral density values estimated by artificial neural networks was considered to be useful as a tool to tailor medicine for the early diagnosis of and intervention for women osteoporosis with women.

Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6).

PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m2, respectively; level 2: 100 and 1000 mg/m2) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity. RESULTS: A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m2 irinotecan and 1000 mg/m2 gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1-6.0 months) and 17.4 months (95% CI 9.9-21.9 months), respectively, while the 1-year survival rate was 58.6%. CONCLUSIONS: Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

Transumbilical extraction of 151-300-g myomas without morcellator versus conventional laparoscopic myomectomy with power morcellator.

STUDY OBJECTIVE: The aim of this study was to compare the surgical outcomes, particularly the specimen retrieval time, between two methods of laparoscopic myomectomy: transumbilical retrieval of the myoma without a morcellator and conventional retrieval of the myoma using a power morcellator via the left lower quadrant. DESIGN: Retrospective study. SETTING: Public hospital. PATIENTS: Seventy-four women undergoing laparoscopic myomectomy. INTERVENTIONS: Laparoscopic myomectomy followed by myoma retrieval via transumbilical extraction or electric motorized morcellator extraction. MEASUREMENTS AND MAIN RESULTS: Seventy-four patients undergoing laparoscopic myomectomy followed by myoma retrieval via transumbilical extraction or electric motorized morcellator extraction were studied. Significant differences were observed in the average weight of the retrieved myomas between the transumbilical and morcellator groups (141.0 vs. 262.8 g, respectively; p < 0.001). Therefore, we chose 27 patients whose total specimen weight was 151-300 g; 13 patients were in the transumbilical extraction group and 14 were in the electric motorized morcellator group. No significant differences were observed in patient characteristics between the two groups. The operative time, blood loss volume, and myoma retrieval time were similar between the two groups. CONCLUSION: Laparoscopic myomectomy with transumbilical extraction for myoma retrieval is a feasible method for specimens weighing up to 300 g.

Postoperative administration of dienogest for suppressing recurrence of disease and relieving pain in subjects with ovarian endometriomas.

To assess the effect of dienogest on recurrence of ovarian endometriomas and severity of pain after laparoscopic surgery, a retrospective study of 81 patients was performed at three institutions in Osaka, Japan. Patients had a six-month minimum follow-up after laparoscopic surgery for ovarian endometriomas performed between June 2012 and August 2014. Patients who chose to receive 2 mg dienogest daily and those who were managed expectantly postoperatively were included. Recurrence was defined as the presence of endometriomas of more than 2 cm. A visual analog scale (VAS) was used to score the intensity of pelvic pain. The cumulative recurrence rate and absolute VAS score changes between the baseline and at 6, 12, 18 and 24 months after the start of administration were evaluated in both groups. The recurrence rate was 16.5% and 24.0% in the expectant management group at 12 and 24 months, respectively. No recurrences occurred in the dienogest treatment group. The rate of VAS score reduction was significantly higher in the dienogest than in the expectant management group. Dienogest is effective on the recurrence of ovarian endometrioma and relieving pelvic pain after laparoscopic surgery.

Assessment of age-specific safety of laparoscopic surgery in elderly patients with ovarian tumors.

AIM: We assessed the age-specific safety of laparoscopic surgery in elderly patients with ovarian tumors. MATERIAL AND METHODS: We performed a retrospective analysis of 55 elderly patients treated by laparoscopic salpingo-oophorectomy under the diagnosis of an ovarian tumor between January 2009 and December 2014. We divided patients into three groups: "young-elderly" (aged 65-74), "old-elderly" (aged 75-84), and "super-elderly" (aged 85-105) and assessed clinical characteristics, surgical results and postoperative course. Statistical significance of categorical variables was examined by the Student's t-test, Mann-Whitney U test, or Fisher's exact test. Multiple regression analysis was used for multivariate analysis. RESULTS: Of a total of 55 patients who underwent laparoscopic surgery, there were 36 patients in the young-elderly group, 17 in the old-elderly group, and two in the super-elderly group. Statistical analysis was performed between the young-elderly and the old-elderly groups because of the small number in the super-elderly group. More frequent comorbidities were found in the patients in the old-elderly than in the young-elderly group (Fisher's exact test, P = 0.007). There were no significant differences in operative time, estimated blood loss and postoperative hospital stay between the young-elderly and old-elderly groups. Intraoperative complications only occurred in the young-elderly group. Postoperative complications occurred in all groups. CONCLUSIONS: Although patients in the old-elderly group had a significantly higher risk for surgery, they had equivalent surgical results to the young-elderly group for laparoscopic salpingo-oophorectomy.

Endometrial adenocarcinoma arising in a Turner's syndrome patient with spontaneous menstruation: a case report.

BACKGROUND: Women with Turner's syndrome exhibit anovulation, and the majority do not spontaneously menstruate. We present an unusual case of endometrial adenocarcinoma developing in a Turner's syndrome patient who was exhibiting spontaneous menstruation while not receiving regular hormone therapy. CASE: The patient's karyotype from blood lymphocytes was a mosaic of 45,XO/ 46,XX. Menarche and sexual development were normal. Her menstrual cycle had been regular for one year, but then became noticeably irregular. At age 26 she was referred to our hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was detected during performance of diagnostic endometrial curettage. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy was conducted. The final histological diagnosis was endometrial adenocarcinoma, Grade 1, pT1a N0 M0. Fluorescence in situ hybridization analysis of the right and left ovaries revealed a mosaic karyotype of 45,XO/ CONCLUSION: Previous reports regarding Turner's syndrome detected spontaneous menstruation in only 16% of patients; however, spontaneous menstruation was observed in 8 of 10 (80%) Turner's syndrome cases that developed endometrial carcinoma without receiving regular hormone therapy (p < 0.0001). Hormone therapy may be indicated for an irregular menstrual cycle in Turner's syndrome patients.

Increases in urinary creatinine and blood pressure during early pregnancy in pre-eclampsia.

BACKGROUND: It is important to predict the development of pre-eclampsia (PE) during early pregnancy to prevent its occurrence later on. In this study, we studied urinary biochemical parameters and blood pressure (BP) during and after pregnancy to find useful parameters for predicting PE. METHODS: A case-control study was performed in 25 PE patients and 172 normotensive pregnant women. Twelve biochemical parameters were measured in spot urine, and the systolic and diastolic BPs were measured using an automated device during pregnancy and six to eight weeks after birth. RESULTS: A multiple logistic regression analysis showed that the combinations of urinary creatinine (Cr) and systolic BP (SBP) in the first trimester of pregnancy (8.9 +/- 2.6 weeks), and of urinary inorganic phosphorus (IP)/Cr and SBP in the second trimester of pregnancy (19.0 +/- 1.6 weeks) were useful for predicting PE. The area under the curve in the receiver operator characteristic curve of the combination of urinary Cr and SBP in the first trimester was 0.85 (95% confidence interval [CI] 0.74-0.96), and that of the combination of urinary IP/Cr and SBP in the second trimester was 0.91 (95% CI: 0.86-0.97). When used 249 mg/dL in urinary Cr and 128 mmHg in SBP as their cut-off points, the combination in the first trimester increased the accuracy (sensitivity 75% and specificity 95%) in predicting PE, as compared with that of urinary Cr (29%, 99%) or SBP (50%, 98%). CONCLUSIONS: Combination of urinary Cr and SBP in early pregnancy and that of urinary IP/Cr and SBP in mid-pregnancy are useful for the prediction of PE.

[A case of metastatic rectal cancer from serous adenocarcinoma of the ovary].

A 51-year-old woman was hospitalized with constipation and bloody feces. Under diagnosis of a primary rectal cancer with peritonitis, an ileostomy was scheduled. Since peritoneal dissemination was found, histologically she was diagnosed as metastatic rectal cancer from serous adenocarcinoma of the ovary. Chemotherapy with paclitaxel and carboplatin was performed, and complete disappearance on assessable examination was seen. Eight months after the first operation, she underwent total hysterectomy, oophorectomy and low anterior resection of rectum. No viable cancer tissue could be found. After the second operation, she has been doing well without any recurrence for 1 year and half.

Epidermal growth factor enhances invasive activity of BeWo choriocarcinoma cells by inducing alpha2 integrin expression.

The trophoblast, an important component of the mammalian placenta, has several essential biological roles in the maintenance of pregnancy. First, trophoblast cells must attach to the uterine endometrium, and then they must invade to a depth at which the vascular network exists. Here, we investigated the effects of epidermal growth factor (EGF) on alpha2 integrin expression, adhesiveness to collagen, and invasive activity using human BeWo choriocarcinoma cells. EGF induced the expression of alpha2 integrin mRNA and protein, as shown by Northern blotting, Western blotting, and flow cytometry. Human chorionic gonadotropin (hCG) secretion was enhanced by the addition of EGF, which suggests that the BeWo cells functionally differentiated similarly to normal trophoblasts. EGF also dose-dependently stimulated the invasiveness of BeWo cells. Antibody against alpha2 integrin inhibited this effect, suggesting that it may be mediated by an increase of cell surface integrin. EGF had no effect on the adhesiveness of BeWo cells to collagen, whereas it stimulated the chemokinetic activity in a dose-dependent manner. The increase of chemokinetic activity was suppressed by antibody against alpha2 integrin. These results suggest that EGF may induce alpha2 integrin expression in trophoblast cells, thereby enhancing their invasiveness into the endometrium via an increase of their chemokinetic activity.

Involvement of Oct-1 in transcriptional regulation of beta-casein gene expression in mouse mammary gland.

Mouse beta-casein gene promoter contains a region termed block C which is crucial for its gene transcription induced by lactogenic hormones. Nuclear extracts from mouse mammary glands contain at least two binding complexes (DS1 and DS2) which specifically bind to double-stranded block C region DNA. The binding sequence of these complexes was identified to be 5'-AAATTAGCATGT-3' which contains a sequence element related to the consensus octamer motif's complement ATTTGCAT. In the present study, we demonstrate that this sequence element indeed is the binding site for octamer-binding transcription factors (Octs) and Octs represent the double-stranded DNA binding proteins specifically binding to the block C region. Formation of the specific double-stranded binding complexes can be completely blocked by Oct binding motif oligonucleotides and anti-rOct-1 antiserum. We also show that Oct-1B represents at least partial, if not all, double-stranded binding protein, DS1, in mammary nuclear extract. Oct-1B may function as a transcriptional activator on casein gene promoter. The Oct binding activity to beta-casein gene promoter in the mammary gland is affected under influence of hormones both in vitro and in vivo. The DS1 binding activity can be induced by the combination of lactogenic hormones insulin, hydrocortisone and prolactin in organ culture of virgin mouse mammary gland. The binding activity in vivo can be induced by injection of progesterone or its combination with estradiol in virgin mice.

Inhibition of phosphorylation of BAD and Raf-1 by Akt sensitizes human ovarian cancer cells to paclitaxel.

We studied the roles of the phosphatidylinositol 3-kinase (PI-3K)-Akt-BAD cascade, ERK-BAD cascade, and Akt-Raf-1 cascade in the paclitaxel-resistant SW626 human ovarian cancer cell line, which lacks functional p53. Treatment of SW626 cells with paclitaxel activates Akt and ERK with different time frames. Interference with the Akt cascade either by treatment with PI-3K inhibitor (wortmannin or LY294002) or by exogenous expression of a dominant negative Akt in SW626 cells caused decreased cell viability following treatment with paclitaxel. Interference with the ERK cascade by treatment with an MEK inhibitor, PD98059, in SW626 cells also caused decreased cell viability following treatment with paclitaxel. Treatment of cells with paclitaxel also stimulated the phosphorylation of BAD at both the Ser-112 and Ser-136 sites. The phosphorylation of BAD at Ser-136 was blocked by treatment with wortmannin or cotransfection with the dominant negative Akt. On the other hand, the phosphorylation of BAD at Ser-112 was blocked by PD98059. We further examined the role of BAD in the viability following paclitaxel treatment using BAD mutants. Exogenous expression of doubly substituted BAD2SA in SW626 cells caused decreased viability following treatment with paclitaxel. Moreover, because paclitaxel-induced apoptosis is mediated by activated Raf-1 and the region surrounding Ser-259 in Raf-1 conforms to a consensus sequence for phosphorylation by Akt, the regulation of Raf-1 by Akt was examined. We demonstrated an association between Akt and Raf-1 and showed that the phosphorylation of Raf-1 on Ser-259 induced by paclitaxel was blocked by treatment with wortmannin or LY294002. Furthermore, interference with the Akt cascade induced by paclitaxel up-regulated Raf-1 activity, and expression of constitutively active Akt inhibited Raf-1 activity, suggesting that Akt negatively regulates Raf-1. Our findings suggest that paclitaxel induces the phosphorylation of BAD Ser-112 via the ERK cascade, and the phosphorylation of both BAD Ser-136 and Raf-1 Ser-259 via the PI-3K-Akt cascade, and that inhibition of either of these cascades sensitizes ovarian cancer cells to paclitaxel.

Regulation of the PRL promoter by Akt through cAMP response element binding protein.

Regulation of the PI3K-protein kinase B/Akt (serine/threonine kinase) cascade by PRL-releasing peptide (PrRP) and insulin in GH3 rat pituitary tumor cells was investigated. PrRP and insulin rapidly and transiently stimulated the activation of Akt, and the PI3K inhibitor wortmannin blocked the PrRP- or insulin-induced activation of Akt. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase I, which specifically blocks signaling mediated by the betagamma subunits of G proteins, completely blocked the PrRP-induced Akt activation, suggesting that Gi/Go proteins are involved in PrRP-induced Akt activation, as they are in the activation of ERK by PrRP. Moreover, to determine whether a PI3K-Akt cascade regulates rat PRL (rPRL) promoter activity, we transfected the intact rPRL promoter ligated to the firefly luciferase reporter gene into GH3 cells. PrRP and insulin activated the rPRL promoter activity. Pretreatment with wortmannin or cotransfection with a dominant-negative Akt partially but significantly inhibited the induction of the rPRL promoter by PrRP or insulin. Cotransfection with a constitutively active Akt induced the rPRL promoter activity and cotransfection with a dominant-negative cAMP response element-binding protein (CREB) completely abolished the response of the rPRL promoter to the constitutively active Akt. Furthermore, either treatment with PrRP and insulin or transfection with the constitutively active Akt induced the phosphorylation of CREB. These results suggest that PrRP and insulin activate a PI3K-Akt cascade that is necessary to elicit rPRL promoter activity via a CREB-dependent mechanism.