A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis.

BACKGROUND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-non-specific) and non-shared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC. APPROACH RESULTS: Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was identified as a novel PBC susceptibility gene locus through a GWAS and subsequent genome-wide meta-analysis involving 2,181 cases and 2,699 controls from the Japanese population (GWAS-lead variant: rs8098858, p=2.6×10-8). In-silico and in-vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells (Tfh) and plasmacytoid dendritic cells (pDCs). Infiltration of PTPN2-positive T-cells and pDCs were confirmed in the portal area of the PBC-liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in-vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758. CONCLUSIONS: PTPN2, a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC via an insufficient negative feedback loop caused by the PTPN2 risk allele of rs2292758 in IFN signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment.

Toxoplasma gondii IgG avidity for the diagnosis of primary infection in pregnant women: Comparison between chemiluminescent microparticle immunoassay and enzyme-linked immunosorbent assay.

INTRODUCTION: This study evaluated whether IgG avidity measured by chemiluminescent microparticle immunoassay (CMIA) compared with enzyme-linked immunosorbent assay (ELISA) was useful to detect primary T. gondii infection during pregnancy and to estimate the risk for congenital T. gondii infection. METHODS: One hundred six women with positive tests for T. gondii IgG and T. gondii IgM, comprising 21 women (19.8%) with low (<30%), 6 (5.7%) with borderline (30%-35%), and 79 (74.5%) with high (>35%) IgG avidity measured by ELISA were selected. Their stored sera were used for T. gondii IgG avidity measurements by CMIA. RESULTS: In CMIA, 72 (67.9%) women had low (<50%), 12 (11.3%) had borderline (50%-59.9%), and 22 (20.8%) had high (≥60%) IgG avidity. The ratio of low T. gondii IgG avidity index in CMIA was more than three-fold than that in ELISA. Eighteen (85.7%) of 21 women with ELISA low avidity also had CMIA low avidity, and 26 (96.3%) of 27 women with ELISA low or borderline avidity corresponded to CMIA low or borderline avidity, whereas 21 (26.6%) of 79 women with ELISA high avidity were diagnosed with CMIA low avidity. All three cases with congenital T. gondii infection showed coincidentally low IgG avidity in both methods. A positive correlation in IgG avidity indices was found between of ELISA and CMIA. CONCLUSIONS: CMIA for T. gondii avidity measurements compared with ELISA was clinically useful to detect pregnant women at a high risk of developing congenital T. gondii infection.

Effectiveness of Laparoscopic Adenomyomectomy on Perinatal Outcomes.

Objectives: The objective of this study was to observe the influence of laparoscopic adenomyomectomy on perinatal outcomes. Materials and Methods: The retrospective cohort study included 43 pregnant cases with adenomyosis who did not undergo laparoscopic surgery before pregnancy (nonsurgery group; 26 cases) and did (surgery group; 17 cases). To evaluate the impact of surgery on perinatal outcomes, nine obstetric complications including preterm delivery, hypertensive disorder of pregnancy, placental malposition, oligohydramnios, gestational diabetes mellitus, uterine rupture, abruptio placentae, and postpartum hemorrhage were selected. One obstetric complication was counted as one point (Maximum 9 points for one person). The obstetrical morbidity was compared by adding up the number of relevant events (0-9) between the two groups. Apgar score, umbilical artery pH (UApH), neonatal intensive care unit (NICU) admission, and neonatal death were also examined. Results: The surgery group had a significantly lower prevalence of fetal growth restriction compared to the nonsurgery group (nonsurgery vs. surgery; 26.9%, 7/26 vs. 0%, 0/17: P = 0.031). No differences were found in the morbidity of the nine obstetric complications (19.2%, 45/234 vs. 13.7%, 21/153), gestational weeks (mean ± standard deviation, 37.2 ± 2.4 vs. 36.4 ± 3.2), birth weight (2573.6 ± 557.9 vs. 2555.4 ± 680.8 g), Apgar score (1, 5 min; 8.0 ± 0.7 vs. 7.7 ± 1.2, 8.9 ± 0.6 vs. 8.5 ± 1.8), UApH (7.28 ± 0.08 vs. 7.28 ± 0.06), NICU admission (26.9%, 7/26 vs. 41.2%, 7/17), and neonatal death (0%, 0%) between both groups. Conclusion: Laparoscopic adenomyomectomy may not increase obstetric complications, although attention must be paid to uterine rupture during pregnancy.

Anti-ß2-glycoprotein I/HLA-DR Antibody and Adverse Obstetric Outcomes.

Anti-ß2-glycoprotein I/HLA-DR (anti-ß2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-ß2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-ß2GPI/HLA-DR antibody levels (normal, <73.3 U) were measured in 462 women with RPL, 124 with fetal growth restriction (FGR), 138 with hypertensive disorders of pregnancy (HDP), 71 with preterm delivery before 34 gestational weeks (preterm delivery (PD) ≤ 34 GWs), and 488 control women who experienced normal delivery, by flow cytometry analysis. The adjusted odds ratios (aORs) of anti-ß2GPI/HLA-DR antibody positivity for adverse obstetric outcomes and RPL were evaluated on the basis of comparisons between the control and each patient group, using multivariable logistic regression analysis. The following were the positivity rates for the anti-ß2GPI/HLA-DR antibody in the patient and control groups: RPL, 16.9%; FGR, 15.3%; HDP, 17.4%; PD ≤ 34 GWs, 11.3%; and the control, 5.5%. It was demonstrated that anti-ß2GPI/HLA-DR antibody positivity was a significant risk factor for RPL (aOR, 3.3 [95% confidence interval {CI} 1.9-5.6], p < 0.001), FGR (2.7 [1.3-5.3], p < 0.01), and HDP (2.7 [1.4-5.3], p < 0.01) although not for PD ≤ 34 GWs. For the first time, our study demonstrated that the anti-ß2GPI/HLA-DR antibody is involved in the pathophysiology underlying FGR and HDP, as well as RPL.

Anti-ß2-glycoprotein I/HLA-DR antibody in infertility.

To evaluate whether anti-ß2-Glycoprotein I/HLA-DR (anti-ß2GPI/HLA-DR) antibody is associated with pathophysiology of infertility, 224 women with infertility were enrolled from July 2020 to December 2021 in this prospective study. The serum levels of anti-ß2GPI/HLA-DR antibody (normal < 73.3 U) were determined in 224 women with infertility. Backgrounds, causes and clinical factors were compared between women with and without anti-ß2GPI/HLA-DR antibody. Forty (17.9 %) of the 224 women tested positive for anti-ß2GPI/HLA-DR antibody. The prevalence of endometriosis was higher in women with anti-ß2GPI/HLA-DR antibody than in women without the antibody (32.5 %, 13/40 vs. 17.4 %, 32/184; P = 0.048). Logistic regression analyses revealed that, among clinical factors and diseases, endometriosis was associated with anti-ß2GPI/HLA-DR antibody positivity in infertile women (adjusted-odds ratio [OR] 3.01, 95 % confidence interval [CI] 1.30-6.99; P = 0.010). Twenty-three (15.5 %) of 148 women who underwent assisted reproductive technology (ART) tested positive for anti-ß2GPI/HLA-DR antibody. The prevalence of recurrent implantation failure (RIF) defined as three or more implantation failures following in vitro fertilization and embryo transfers was higher in women with ART who tested positive for the antibody (43.5 %, 10/23) than in women with ART who tested negative (20.8 %, 26/125; P = 0.032). Logistic regression analyses revealed that RIF was associated with anti-ß2GPI/HLA-DR antibody positivity in women with ART (adjusted-OR 2.92, 95 % CI 1.05-8.11; P = 0.040). Anti-ß2GPI/HLA-DR antibody may be associated with the pathophysiology of infertility, endometriosis and RIF; and can be a potential therapeutic target in infertility.

Awareness of Infectious Disease Screening During Early Pregnancy and Knowledge About its Vertical Transmission in Japan: A Report from the Pregnant Women Health Initiative.

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.

Hysteroscopic resection with temporary balloon catheter occlusion of bilateral internal iliac arteries for managing retained products of conception after spontaneous abortion: Two cases report.

Retained products of conception (RPOC) is a condition in which trophoblastic tissue remains in the uterus after pregnancy, causing massive hemorrhage in some cases. Though RPOC is commonly treated by intrauterine curettage or hysteroscopic resection uterine artery embolization or hysterectomy may be performed in case of massive bleeding. We experienced two cases of RPOC after surgery for missed abortion that failed to respond to conservative treatment and required surgical treatment. They were treated by hysteroscopic resection with temporary balloon catheter occlusion of bilateral internal iliac arteries for fertility preservation. After the balloon catheters were inflated, the reduction of blood flow to RPOC was observed under transvaginal ultrasound. In both cases, good visualization was maintained throughout the surgery with minimal bleeding. They were discharged the next day and resumed menstruation 1 month after surgery. This paper demonstrates the usefulness of this procedure as a minimally invasive and fertility-preserving surgery.

Influence of laparoscopic surgery for endometriosis and its recurrence on perinatal outcomes.

Purpose: It is unknown whether surgery for endometriosis or recurrence of endometriosis affects obstetric outcomes. Methods: A total of 208 pregnant women with a history of endometriosis were analyzed. Patients who had endometriomas >3 cm and no history of laparoscopic surgery for endometriosis were defined as non-surgery group (n = 60), while those who had a history of surgery for endometriosis (n = 148) were defined as surgery group. We investigated the obstetric outcomes in 208 patients according to with or without postoperative recurrence of endometriosis and the time from surgery to pregnancy. Results: Among 177 cases of on-going pregnancy, in surgery group, there were lower prevalence of placenta previa compared with non-surgery group (8.5% vs. 23.4%; p = 0.020). Subgroup analysis revealed a decreased prevalence of placenta previa in postoperative non-recurrence group (6.0%: p = 0.007) compared with non-surgery (23.4%) and postoperative recurrence group (28.6%). Placenta previa was more prevalent in the patients who got pregnant more than 2 years after surgery (20.0%) than the patients who got pregnant within 2 years (2.4%: p = 0.002). Multivariate analysis revealed that the surgery was associated with a reduction in placenta previa (OR: 0.32, 95% CI [0.11-0.90]; p = 0.032). Conclusions: Pregnancy within two years after laparoscopic surgery for endometriosis may reduce placenta previa.

The first case of congenital syphilis diagnosed by 16S ribosome-RNA gene sequence analysis.

Syphilis infection during pregnancy causes perinatal complications and mother-to-child transmission if untreated. A newborn was delivered by emergent cesarean section due to non-reassuring fetal status at 34 weeks of gestation. The mother tested negative for rapid plasma reagin (RPR) and Treponema pallidum hemagglutination (TPHA) in early pregnancy. The newborn had a severe inflammatory reaction, thrombocytopenia, and elevated IgM as well as disseminated intravascular coagulation and multiple organ failure. The 16S ribosomal RNA gene sequence analysis of the amniotic fluid detected Treponema pallidum. The newborn tested positive for RPR, TPHA, and IgM fluorescent treponemal antibody-absorption in the blood, and thus, congenital syphilis was diagnosed. This is the first case that 16S ribosomal RNA gene sequencing of the amniotic fluid led to an early diagnosis of congenital syphilis in a newborn. The 16S rRNA gene sequencing may be a useful method for the early detection of the primary causative microbe of congenital infection.

Influence of Uterine Cavity Breach in Laparoscopic Myomectomy on the Risk of Obstetric Complications.

Objectives: Prepregnancy myomectomy is effective for the treatment of infertility or prevention of obstetric complications and is usually performed with laparoscopy. However, pregnancies following myomectomy have risks of obstetric complications, especially in cases with uterine cavity breaches, but the evidence remains unclear. We investigated how uterine cavity breach in laparoscopic myomectomy influenced the occurrence of obstetric complications. Patients and Methods: One hundred and eighty women who underwent a cesarean section from 2014 to 2020 in pregnancies following laparoscopic myomectomy were included. They were divided into two groups: 25 women in the uterine cavity breach group and 155 in the nonbreach group. Obstetric complications, including placenta accreta spectrum (PAS), uterine rupture, placental malposition, abruption placenta, preterm delivery, threatened premature labor, premature rupture of membranes, and massive intrapartum hemorrhage, were assessed. Results: Multivariate analysis revealed that the frequency of PAS in the breach group (24.0%) was statistically significantly higher than in the nonbreach group (5.2%, P < 0.05). Conclusion: This study demonstrated that women who experienced uterine cavity breach in laparoscopic myomectomy had an increased risk of PAS in subsequent pregnancies.

Perinatal outcomes associated with the positional relationship between the placenta and the adenomyosis lesion.

INTRODUCTION: Although various perinatal complications have been reported to be increased in the pregnant patients with adenomyosis, it is not clear what type of patients with adenomyosis is more likely to cause obstetric complications. In this study, we focused on the positional relationship between the placenta and adenomyosis lesion in evaluating perinatal prognosis of pregnant patients with adenomyosis. MATERIAL AND METHODS: This retrospective cohort study was carried out between 1 January 2005 and 31 December 2019 in a single institution. Adenomyosis was diagnosed by magnetic resonance imaging (MRI) and/or transvaginal ultrasonography (TVUS). To evaluate the influence of adenomyosis on perinatal outcomes, we classified the positional relationship between the placenta and the adenomyosis lesion into two groups and examined the perinatal prognosis of the patients with adenomyosis by analyzing their clinical records. Group I (n = 9) was defined when the placenta was not overlaid on adenomyosis lesion. Group II (n = 11) was defined when a part of the placenta was overlaid on adenomyosis lesion. RESULTS: Twenty pregnant patients with adenomyosis were analyzed. There were no differences in clinical backgrounds between group I and group II. There was a significant increase in the obstetric morbidity in group II than that of Group I(group I: 6.3%, 4/63 vs group II: 18.6%, 26/77; P < 0.001). In group II, fetal growth restriction (FGR) was more frequent (0%, 0/9 vs 45.5%, 5/11; P = 0.042) and the birth weight was significantly lower than that in group I (2951.1 g ± 326.5 g vs 2318.9 ± 656.1 g; P = 0.037). There was a trend of lighter weight of the placenta in group II (550.6 ± 66.5 g vs 437.5 ± 117.8 g; P = 0.063) and the volume of bleeding during delivery was a higher trend in group II than that in group I (845.1 ± 367.1 g vs 1356 ± 604.8 g; P = 0.083). Group II was furtherly subdivided into group IIa (less than half the major axis of the placenta overlaid on adenomyosis lesion) and group IIb (more than half the major axis of placenta overlaid on adenomyosis lesion). The obstetric morbidity tended to be higher in group IIb than in group IIa (group IIa: 22.9%, 8/35 vs group IIb: 42.9%, 18/42); P = 0.09). In group IIb, the frequency of FGR was significantly higher (group IIa: 0%, 0/5 vs IIb: 83.3%, 5/6; P = 0.020) and the birth weight was significantly lower than those in group IIa (2656.8 ± 231.9 g vs 2037 ± 780.1 g; P = 0.040). All cases of FGR, hypertensive disorder of pregnancy (HDP), and oligohydramnios were observed in group IIb. CONCLUSION: Placental localization near adenomyosis may increase the risk of perinatal complications.

Combination of conservative treatment and temporary bilateral laparoscopic uterine artery clipping with hysteroscopic transcervical resection for cervical pregnancy: A retrospective study.

INTRODUCTION: We investigated whether temporary bilateral laparoscopic uterine artery clipping with hysteroscopic transcervical resection (LUA clipping-TCR) is an effective minimally invasive treatment for the management of cervical pregnancy. MATERIALS AND METHODS: This study is a retrospective clinical case series conducted at Teine Keijinkai Hospital from January 2014 to June 2019. Nine cervical pregnancies among 164 ectopic pregnancies were retrospectively examined. The intervention involved performing LUA clipping-TCR on villous tissue. Information on patient characteristics, clinical data, and surgical details was collected from medical records and surgical videos. RESULTS: The mean (range) age of the patients was 33 years (29-41 years); and mean gestational sac diameter, 12.8 mm (5-24 mm). Five patients had a history of intrauterine procedures. Three patients had a positive fetal heartbeat. The mean (range) preoperative serum hCG level (mIU/mL), surgical time (min), uterine artery blocking time (min), and amount of surgical blood loss (ml) were 14,040 (2880-41,367), 82 (62-120), 42 (21-68), and 57 (10-200), respectively. The mean decrease in serum hCG level (second postoperative day) and duration until resumption of menstruation were 79.7 % (70-86.7 %) and 46 days (35-80 days), respectively. The hospitalization period was 2-3 days, with no evidence of persistent ectopic pregnancy. Live birth was achieved in four cases. DISCUSSION: Our results confirm previous findings and provide new evidence that LUA clipping-TCR is effective for cervical pregnancy management and fertility preservation, respectively. Future large-scale prospective studies to compare different cervical pregnancy management methods are required.

Analysis of risk factors of postlaparoscopic shoulder pain.

AIM: Postlaparoscopic shoulder pain (SP), mainly caused by pneumoperitoneum with CO2 , sometimes suffers patients. This study was aimed to analyze the backgrounds of SP after gynecologic laparoscopy to clarify the risk of SP. METHODS: We analyzed answers of questionnaire about the degree of SP from 696 patients undergoing gynecologic laparoscopic surgery since 2014-2018. The questionnaire asks the degree of SP with numeric rating scale from 0 to 10, before and 3 days after operation. We defined cases in which postoperative score elevated more than three compared to preoperative score as SP(+). Analyzed backgrounds were age, parity, body mass index, operative method, operative duration and amount of hemorrhage. Statistics was performed by Fisher exact analysis as univariate analysis, and with logistic regression as multivariate analysis. All laparoscopic surgeries were performed under 10-12 mmHg in pressure of pneumoperitoneum with CO2 . RESULTS: Univariate analysis revealed categories 'less than 50 years old', and 'over 2 h' and 'over 3 h' in operative duration resulted significant high rate of SP(+). For these three factors, multivariate analysis resulted that "less than 50 years old' and 'over 3 h in operative duration' were significantly high. CONCLUSION: This study suggests that 'less than 50 years' old and 'over 3 h in operative duration' were risk factors of postlaparoscopic SP. To protect from SP after laparoscopy, some countermeasures should be necessary especially for these patients.

Second-Generation meta-Phenolsulfonic Acid-Formaldehyde Resin as a Catalyst for Continuous-Flow Esterification.

A second-generation m-phenolsulfonic acid-formaldehyde resin (PAFR II) catalyst was prepared by condensation polymerization of sodium m-phenolsulfonate and paraformaldehyde in an aqueous H2SO4 solution. This reusable, robust acid resin catalyst was improved in both catalytic activity and stability, maintaining the characteristics of the previous generation catalyst (p-phenolsulfonic acid-formaldehyde resin). PAFR II was applied in the batchwise and continuous-flow direct esterification without water removal and provided higher product yields in continuous-flow esterification than any other commercial ion-exchanged acid catalyst tested.

Complications Related to the Initial Trocar Insertion of 3 Different Techniques: A Systematic Review and Meta-analysis.

This systematic review aimed to investigate complications related to initial trocar insertion among 3 different laparoscopic techniques: Veress needle (VN) entry, direct trocar entry (DTE), and open entry (OE). A literature search was completed, and complications were assessed. Major vessel injury, gastrointestinal injury, and solid organ injury were defined as major complications. Minor complications were defined as subcutaneous emphysema, extraperitoneal insufflation, omental emphysema, trocar site bleeding, and trocar site infection. Arm-based network meta-analyses were performed to identify the differences in complications among the 3 techniques. Seventeen studies were included in the quantitative analysis. DTE resulted in fewer major complications when compared with VN entry although the difference was not significant (p = .23) as well as significantly fewer minor complications (p < .001). There were no significant differences in minor complications when comparing OE and DTE (p = .74). Fewer major complications were observed with OE compared with VN entry although the difference was not significant (p = .31). There were significantly fewer minor complications for patients who underwent OE (p = .01). DTE patients experienced the least number of minor complications followed by VN entry and OE. In conclusion, major complications are extremely rare, and all 3 insertion methods can be performed without mortality.

Successful treatment of uterine artery pseudoaneurysm with laparoscopic temporary clamping of bilateral uterine arteries, followed by hysteroscopic surgery.

Surgical strategies for the treatment of uterine artery pseudoaneurysm (UAP) include transarterial embolization and ultrasound-guided low-dose thrombin injection. Such strategies, however, have limitations and include the risk of ischemic damage to the uterus. We report a case of UAP treated with a new hysteroscopic and laparoscopic technique. A 29-year-old G1P0 woman with spontaneous abortion was transferred to the present institution because of hemorrhagic shock. We diagnosed ruptured UAP on transvaginal ultrasound with color Doppler. Emergency laparoscopic temporary clamping of the bilateral uterine arteries was done to reduce the bleeding, and transcervical resection to stop the hemorrhaging and to collect the pseudoaneurysm tissue. After surgery, blood flow to the myometrium was monitored on ultrasound. By postoperative day 48, normal menstruation had restarted, and no intrauterine adhesions were observed. On pathology of the UAP, a dilated spiral artery without its characteristic elastic fibers was identified. This surgical approach may help preserve fertility and allow for pathological diagnosis of UAP.

Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population.

A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.

Effect of sleep disorders on threatened premature delivery.

AIM: The present observational study aimed to clarify the effects of sleep disorders on threatened premature delivery, especially preterm uterine contraction. METHODS: The participants included 122 healthy singleton pregnant women. The Pittsburgh sleep quality index was used to evaluate the quality of sleep during the previous month at the initial examination and at 16, 24, and 32 weeks of gestation; scores >5 indicate poor sleep. Threatened premature delivery was defined as preterm uterine contraction >6 times/h and requiring tocolytic therapy before 37 weeks of gestation. We analyzed the relationship between poor sleep and threatened premature delivery. RESULTS: Poor sleep affected 27% (n=33) at the initial examination, 34% (n=41) at 16 weeks, 37% (n=45) at 24 weeks, and 41% (n=50) at 32 weeks of gestation. There were 23 patients (19%) with threatened premature delivery. Poor sleep affected 35% and 25% of patients with threatened and non-threatened premature delivery at the initial examination, respectively, 52% and 29% at 16 weeks, 48% and 34% at 24 weeks, and 43% and 40% at 32 weeks of gestation. CONCLUSIONS: Sleep disorders at 16 weeks of gestation were the most significantly associated with threatened premature delivery.

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma.

Cancer vaccine therapy is one of the most attractive therapies as a new treatment procedure for pancreatic adenocarcinoma. Recent technical advances have enabled the identification of cytotoxic T lymphocyte (CTL) epitopes in various tumor-associated antigens (TAAs). However, little is known about which TAA and its epitope are the most immunogenic and useful for a cancer vaccine for pancreatic adenocarcinoma. We examined the expression of 17 kinds of TAA in 9 pancreatic cancer cell lines and 12 pancreatic cancer tissues. CTL responses to 23 epitopes derived from these TAAs were analyzed using enzyme-linked immunospot (ELISPOT), CTL, and tetramer assays in 41 patients, and factors affecting the immune responses were investigated. All TAAs were frequently expressed in pancreatic adenocarcinoma cells, except for adenocarcinoma antigens recognized by T cells 1, melanoma-associated antigen (MAGE)-A1, and MAGE-A3. Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAAs, namely, MAGE-A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines. The frequency of lymphocyte subsets correlated well with TAA-specific immune response. Overall survival was significantly longer in patients with TAA-specific CTL responses than in those without. P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA-specific CTLs may improve the prognosis of these patients.

Rare case of peritoneal complete hydatidiform mole.

A 23-year-old woman, gravida 1, para 1, was transferred to our hospital with acute lower abdominal pain and vital signs consistent with shock. Her urine concentration of human chorionic gonadotrophin was 8000 mIU/mL. Transvaginal ultrasound revealed an echo-free space with mosaic echo pattern in the right adnexal area and no gestational sac in the uterus. With a preoperative diagnosis of ruptured ectopic pregnancy, emergency laparotomy was performed. The rectouterine pouch was filled with many clots containing small amounts of villous tissue. After removal of the conceptus, which was infiltrating into the peritoneum of the Pouch of Douglas, bleeding was controlled by Argon laser. Histological examination of the conceptus by immunohistochemical staining with p57(kip2) showed features of complete hydatidiform mole. This case demonstrates that the peritoneum in the Pouch of Douglas is a possible site of ectopic complete hydatidiform mole occurrence and that immunohistochemical stain is useful to confirm the diagnosis of ectopic complete hydatidiform mole.