Adhesion barriers in gynecologic surgeries and cesarean section: An Asia-Pacific expert panel consensus recommendation.

Adhesions arising from gynecologic surgeries and cesarean sections pose substantial clinical, social, and economic challenges, leading to issues like pelvic pain, infertility, bowel obstruction, and recurring surgeries. Preventing adhesions is a pressing unmet need, hindered by difficulties in assessing postoperative adhesions and understanding barriers. To bridge adhesion prevention gaps, statements on clinical practices were synthesized to present Asia-Pacific expert perspectives on gynecologic surgery and cesarean section adhesion prevention. An expert panel of eight physicians from various healthcare settings in the Asia-Pacific region was convened and a comprehensive literature search on topics related to adhesion prevention in gynecologic surgeries and cesarean sections was performed. Information from full-text publications was used to develop draft consensus statements, with each statement assigned the highest available evidence level based on a systematic literature review and graded using the Oxford Center for Evidence-based Medicine criteria. A modified Delphi process, involving two rounds of online voting and discussions with an extended group of 109 experts, was employed to reach a consensus on six topics related to adhesion barriers. A set of 15 consensus statements were synthesized. Key topics include adhesion incidence in Asia, cesarean section complications, barrier application status, adhesion formation and prevention, absorbable barriers' effectiveness, recommendations, and future considerations. The statements provide guidance for healthcare professionals, especially in the Asia-Pacific region, to tackle the challenges posed by postoperative adhesions and improve patient outcomes. Further research is needed to enhance understanding and prevention of adhesions in this region.

Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

Stem Cell Biomarkers and Tumorigenesis in Gastric Cancer.

Stomach cancer has a high mortality, which is partially caused by an absence of suitable biomarkers to allow detection of the initiation stages of cancer progression. Thus, identification of critical biomarkers associated with gastric cancer (GC) is required to advance its clinical diagnoses and treatment. Recent studies using tracing models for lineage analysis of GC stem cells indicate that the cell fate decision of the gastric stem cells might be an important issue for stem cell plasticity. They include leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5+), Cholecystokinin receptor 2 (Cckr2+), and axis inhibition protein 2 (Axin2+) as the stem cell markers in the antrum, Trefoil Factor 2 (TFF2+), Mist1+ stem cells, and Troy+ chief cells in the corpus. By contrast, Estrogen receptor 1 (eR1), Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), SRY (sex determining region Y)-box 2 (Sox2), and B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) are rich in both the antrum and corpus regions. These markers might help to identify the cell-lineage identity and analyze the plasticity of each stem cell population. Thus, identification of marker genes for the development of GC and its environment is critical for the clinical application of cancer stem cells in the prevention of stomach cancers.

Cryptocaryone Promotes ROS-Dependent Antiproliferation and Apoptosis in Ovarian Cancer Cells.

Cryptocaryone (CPC) is a bioactive dihydrochalcone derived from Cryptocarya plants, and its antiproliferation was rarely reported, especially for ovarian cancer (OVCA). This study aimed to examine the regulation ability and mechanism of CPC on three histotypes of OVCA cells (SKOV3, TOV-21G, and TOV-112D). In a 24 h MTS assay, CPC showed antiproliferation effects to OVCA cells, i.e., IC50 values 1.5, 3, and 9.5 µM for TOV-21G, SKOV3, and TOV-112D cells. TOV-21G and SKOV3 cells showed hypersensitivity to CPC when applied for exposure time and concentration experiments. For biological processes, CPC stimulated the generation of reactive oxygen species and mitochondrial superoxide and promoted mitochondrial membrane potential dysfunction in TOV-21G and SKOV3 cells. Apoptosis was detected in OVCA cells through subG1 accumulation and annexin V staining. Apoptosis signaling such as caspase 3/7 activities, cleaved poly (ADP-ribose) polymerase, and caspase 3 expressions were upregulated by CPC. Specifically, the intrinsic and extrinsic apoptotic caspase 9 and caspase 8 were overexpressed in OVCA cells following CPC treatment. Moreover, CPC also stimulated DNA damages in terms of γH2AX expression and increased γH2AX foci. CPC also induced 8-hydroxy-2'-deoxyguanosine DNA damages. These CPC-associated principal biological processes were validated to be oxidative stress-dependent by N-acetylcysteine. In conclusion, CPC is a potential anti-OVCA natural product showing oxidative stress-dependent antiproliferation, apoptosis, and DNA damaging functions.

Generation of Human Stomach Cancer iPSC-Derived Organoids Induced by Helicobacter pylori Infection and Their Application to Gastric Cancer Research.

There is considerable cellular diversity in the human stomach, which has helped to clarify cell plasticity in normal development and tumorigenesis. Thus, the stomach is an interesting model for understanding cellular plasticity and for developing prospective anticancer therapeutic agents. However, many questions remain regarding the development of cancers in vivo and in vitro in two- or three-dimensional (2D/3D) cultures, as well as the role of Helicobacter pylori (H. p.) infection. Here, we focus on the characteristics of cancer stem cells and their derived 3D organoids in culture, including the formation of stem cell niches. We define the conditions required for such organoid culture in vitro and examine the ability of such models for testing the use of anticancer agents. We also summarize the signaling cascades and the specific markers of stomach-cancer-derived organoids induced by H. p. infection, and their stem cell niches.

Antiosteoporosis effects of a marine antimicrobial peptide pardaxin via regulation of the osteogenesis pathway.

Antimicrobial peptides (AMPs) are known to play an important role in natural immunity. Moreover, the diverse biological activities of AMPs showed great potency in treating many diseases. Thus, in this study, we used an AMP, that is, pardaxin, from a marine fish (Pardachirus marmoratus), which has been reported to possess antibacterial and antitumor activities. We first investigated the mechanisms of pardaxin in promoting osteogenic differentiation in vitro and in vivo. As per our data, it was determined that pardaxin could stimulate bone morphogenetic protein-2 (BMP-2) and downstream cascade. The activation of BMP-2 could further induce the phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Additionally, the activation of p-Akt and p-ERK could prompt the elevation and translocation of runt-related transcription factor 2 (runx-2), which is associated with osteoblast differentiation. The translocation of runx-2 initiated transcription and translation of osteogenesis-related markers, including alkaline phosphatase (ALP), osterix, and osteocalcin. Pardaxin significantly facilitated preosteoblast cells in mineralization and reversed dexamethasone- (DM-) induced zebrafish bone formation deficiency by activating the osteogenesis pathway. Therefore, we suggest that pardaxin could be a possible candidate for osteoporosis treatment and a promising therapeutic agent.

Deletion of Jdp2 enhances Slc7a11 expression in Atoh-1 positive cerebellum granule cell progenitors in vivo.

BACKGROUND: The cerebellum is the sensitive region of the brain to developmental abnormalities related to the effects of oxidative stresses. Abnormal cerebellar lobe formation, found in Jun dimerization protein 2 (Jdp2)-knockout (KO) mice, is related to increased antioxidant formation and a reduction in apoptotic cell death in granule cell progenitors (GCPs). Here, we aim that Jdp2 plays a critical role of cerebellar development which is affected by the ROS regulation and redox control. OBJECTIVE: Jdp2-promoter-Cre transgenic mouse displayed a positive signal in the cerebellum, especially within granule cells. Jdp2-KO mice exhibited impaired development of the cerebellum compared with wild-type (WT) mice. The antioxidation controlled gene, such as cystine-glutamate transporter Slc7a11, might be critical to regulate the redox homeostasis and the development of the cerebellum. METHODS: We generated the Jdp2-promoter-Cre mice and Jdp2-KO mice to examine the levels of Slc7a11, ROS levels and the expressions of antioxidation related genes were examined in the mouse cerebellum using the immunohistochemistry. RESULTS: The cerebellum of Jdp2-KO mice displayed expression of the cystine-glutamate transporter Slc7a11, within the internal granule layer at postnatal day 6; in contrast, the WT cerebellum mainly displayed Sla7a11 expression in the external granule layer. Moreover, development of the cerebellar lobes in Jdp2-KO mice was altered compared with WT mice. Expression of Slc7a11, Nrf2, and p21Cip1 was higher in the cerebellum of Jdp2-KO mice than in WT mice. CONCLUSION: Jdp2 is a critical regulator of Slc7a11 transporter during the antioxidation response, which might control the growth, apoptosis, and differentiation of GCPs in the cerebellar lobes. These observations are consistent with our previous study in vitro.

Psychiatric problems of anxiety and depression disorder are associated with medical service utilization and survival among patients with cervical cancer.

OBJECTIVE: There are few nationwide studies regarding the long-term analysis of cervical cancer patients in Taiwan. Thus, this study aimed to evaluate medical service utilization, and survival among cervical cancer patients initially diagnosed with or without anxiety and/or depressive disorders. MATERIALS AND METHODS: This was a retrospective longitudinal study using data from the National Health Insurance Research Database from 1996 to 2010. The study subjects were cervical cancer patients identified by ICD-9-CM codes 180.X, while subjects with anxiety and/or depressive disorders were identified using the following codes: 300.0X-300.9X (minus 300.4X) for anxiety disorder, and 296.2X, 296.3X, 300.4, and 311.X for depressive disorder. The cervical patients with anxiety or/and depression disorder were classified as anxiety/depression (AD) group or the non-disorder (ND) group. Propensity score matching (PSM) was used to adjust for differences between the AD and ND groups. T-tests were used to evaluate differences in medical utilization and the Kaplan-Meier method was used to evaluate survival conditions between the two groups. Statistical analyses were performed using SPSS Statistics 20.0. RESULTS: A total of 3664 patients were identified, with 862 (23.5%) having anxiety, 149 (4.1%) with depression, and 349 (9.5%) having both anxiety and depression. In total, 1360 cervical cancer patients had anxiety/depression disorders. After PSM, the AD group had significantly more outpatient department (OPD) visits than the ND group (p < 0.001) but the survival status was better in the AD group than the ND group (p < 0.001). CONCLUSIONS: Cervical cancer patients with anxiety/depression disorders visited the OPD more frequently than those without anxiety/depression disorders but had better survival status. Gynecologists should also consider cancer patients' mental status during follow-up, referring patients to psychiatric professionals for appropriate psychiatric care if appropriate.

Identifying the Therapeutic Significance of Mesenchymal Stem Cells.

The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in immune disorders. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and conceal themselves from the innate immune system. These signatures are the reason for the uprising in the sciences of cellular therapy in the last decades. Irrespective of their therapeutic role in immune disorders, some factors limit beneficial effects such as inconsistency of cell characteristics, erratic protocols, deviating dosages, and diverse transfusion patterns. Conclusive protocols for cell culture, differentiation, expansion, and cryopreservation of MSCs are of the utmost importance for a better understanding of MSCs in therapeutic applications. In this review, we address the immunomodulatory properties and immunosuppressive actions of MSCs. Also, we sum up the results of the enhancement, utilization, and therapeutic responses of MSCs in treating inflammatory diseases, metabolic disorders and diabetes.

Human umbilical cord matrix-derived stem cells expressing interferon-ß gene inhibit breast cancer cells via apoptosis.

Human umbilical cord mesenchymal stem cells (hUCMSCs) derived from the umbilical cord matrix have been reported to be used as anti-tumor gene carrier for attenuation of tumor growth, which extends the half-life and lowers the unexpected cytotoxicity of the gene in vivo. Interferon-ß (IFNß) is known to possess robust anti-tumor effects on different types of cancer cell lines in vitro. The present study was aimed to investigate the anti-tumor effect of IFNß gene-transfected hUCMSCs (IFNß-hUCMSCs) on breast cancer cells with emphasis on triple negative breast carcinoma. Our findings revealed that the co-culture of IFNß-hUCMSCs with the human triple negative breast carcinoma cell lines MDA-MB-231 or Hs578T significantly inhibited growth of both carcinoma cells. In addition, the culture medium conditioned by these cells also significantly suppressed the growth and induced apoptosis of both carcinoma cells. Further investigation showed that the suppressed growth and the apoptosis induced by co-culture of IFNß-hUCMSCs or conditioned medium were abolished by pretreating anti-IFNß neutralizing antibody. These findings indicate that IFNß-hUCMSCs triggered cell death of breast carcinoma cells through IFN-ß production, thereby induced apoptosis and suppressed tumor cell growth. In conclusion, we demonstrated that IFNß-hUCMSCs inhibited the growth of breast cancer cells through apoptosis. With potent anti-cancer activity, it represents as an anti-cancer cytotherapeutic modality against breast cancer.

HPV knowledge and factors associated with intention to use condoms for reducing HPV infection risk among adolescent women in Taiwan.

Human papillomavirus (HPV) is a frequent cause of sexually transmitted infection worldwide, and has a key role in the etiology of cervical cancer. Young people are the most vulnerable age group for acquiring HPV infection, but this particular age group in Taiwan knows little about it. This study investigated Taiwanese adolescent women's knowledge of HPV and factors associated with intention to use condoms for reducing HPV-related diseases among adolescent women. A descriptive cross-sectional design was used, and a convenience sample of 384 adolescent women aged 15 to 16 years in Southern Taiwan was recruited. Data were collected using a self-administered questionnaire and analyzed with descriptive statistics, t-test or ANOVA, and multiple regression analysis. Only 26.6% of the participants were aware of HPV. The percentage of correct answers for knowledge about HPV was 35.4%. Factors associated with intention to use condoms for HPV prevention were discussion of sexual issues, attitude, subjective norm, perceived behavioral control, and HPV knowledge. These variables accounted for 55.8% of the variance in scores for intention to use condoms for HPV prevention. These findings could be used in future HPV prevention education and campaigns. Future intervention programs might be particularly focused on insufficient HPV knowledge among adolescent females.

Parity and risk of death from gallbladder cancer among a cohort of premenopausal parous women in Taiwan.

Little epidemiologic research has been done on the etiology of gallbladder cancer (GC). This cohort study was undertaken to examine whether there is an association between parity and risk of death from GC. The study cohort consisted of 1,292,462 women who had a first and singleton childbirth between 1 January 1978 and 31 December 1987. We tracked each woman from the time of their first childbirth to 31 December 2009, and their vital status was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) of death from GC associated with parity. There were 257 GC deaths during 34,980,246 person-years of follow-up. The mortality rate of GC was 0.73 cases per 100,000 person-years. As compared with women who had given birth to only one child, the adjusted HR was 1.20 (95% CI = 0.79-1.83) for women who had two children, 1.47 (95% CI = 0.95-2.29) for women who had three children, and 1.68 (95% CI = 0.99-2.85) for women with four or more births. There was a significant increasing trend in the adjusted HRs for GC with increasing parity. The findings suggested that premenopausal women of higher parity may increase the risk of death from GC.

Risk evaluation for the development of cervical intraepithelial neoplasia: development and validation of risk-scoring schemes.

Cervical cancer screening guidelines do not comprehensively define what constitutes high risk. This study developed and validated simple risk-scoring schemes to improve Papanicolaou smear screening for women at high risk. Four cumulative risk score (CRS) schemes were derived respectively for the development of cervical intraepithelial neoplasia grade 1 (CIN1) and grade 2 or worse (CIN2+) using community-based case-control data (n = 1523). By calculating the area under the receiver operating characteristic (AU-ROC) curve, these schemes were validated in a Papanicolaou smear follow-up cohort (n = 967) and a hospital-based cytology screening population (n = 217). A high DNA load of high-risk human papillomavirus (HR-HPV) was the main predictor for CIN1 and CIN2+, although age, married status combined with the number of sexual partners, active and passive smoking and age at sexual debut also affected associated lesions. In the training set, only the HPV-testing-contained CIN2+ CRS scheme presented an excellent discrimination for identifying CIN2+ (AU-ROC = 0.866). Using a CRS cutoff value of 4 to identify CIN2+, the sensitivity and specificity of predicting CIN2+ for the 3- and 5-year follow-ups were 100% and 90.8%, and 83.3% and 90.4%, respectively, in the validation cohort. In the hospital-based validation population, the CRS scheme showed comparable discrimination for CIN2+ detection (sensitivity 88.2% and specificity 84.6%). Women with CRS ≥ 4 had a 5.4% and 9.1% of 3- and 5-year cumulative incidence, respectively, and a 40.5-fold hazard ratio of developing CIN2+. In conclusion, combined with HR-HPV testing and verified risk factors, a simple CRS scheme could effectively improve the implementation of CIN2+ screening.

Statin use and the risk of breast cancer: a population-based case-control study.

OBJECTIVE: The aim of this study was to investigate whether the use of statins was associated with breast cancer risk. BACKGROUND: Experimental studies have shown that statins have potential protective effects against cancer. METHODS: We conducted a population-based case-control study in Taiwan. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of breast cancer for the period between 2004 and 2011. The controls were matched to cases by age, sex and index date. Adjusted odds ratios (ORs) and 95% CIs were estimated by using multiple logistic regression. RESULTS: We examined 565 breast cancer cases and 2260 controls. The unadjusted OR for any statin prescription was 1.19 (95% CI = 0.95 - 1.49) and the adjusted OR was 1.13 (95% CI = 0.84 - 1.51). Compared with no use of statins, the adjusted ORs were 1.02 (95% CI = 0.61 - 1.69) for the group with cumulative defined daily doses (DDDs) below 44.67 DDDs, 1.21 (95% CI = 0.83 - 1.76) for the group with cumulative dose between 44.68 DDDs and 308 DDDs, and 1.10 (95% CI = 0.66 - 1.83) for the group with the highest cumulative dose (> 308 DDDs). CONCLUSIONS: The present data do not provide evidence to support either beneficial or harmful associations between statin use and breast cancer risk.

Statin use and the risk of esophageal cancer: a population-based case-control study.

OBJECTIVE: The aim of this study was to investigate whether the use of statins was associated with esophageal cancer risk. METHODS: A population-based case-control study was conducted in Taiwan. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of esophageal cancer for the period between 2004 and 2010. The controls were matched to cases by age, sex and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. RESULTS: A total of 197 esophageal cancer cases and 788 controls were examined. The unadjusted ORs for any statin prescription was 0.86 (95% CI = 0.56 - 1.34) and the adjusted OR was 0.96 (95% CI = 0.59 - 1.58). Compared with no use of statins, the adjusted ORs were 0.77 (95% CI = 0.39 - 1.55) for the group having been prescribed statins with cumulative defined daily dose (DDDs) below 115 and 1.16 (95% CI = 0.63 - 2.14) for the group with cumulative statin use of 115 DDDs or more. CONCLUSIONS: The present data do not provide evidence to support either beneficial or harmful associations between statin use and esophageal cancer risk.

Traffic air pollution and risk of death from ovarian cancer in Taiwan: fine particulate matter (PM2.5) as a proxy marker.

The relationship between mortality attributed to ovarian cancer and exposure to ambient air pollutants was examined using an ecological design. The study areas consisted of 61 municipalities in Taiwan. Air quality data for recorded concentrations of fine particulate matter (PM2.5) from study municipalities for 2006-2009 were obtained as a marker of traffic emissions. These were used as a proxy for polycyclic aromatic hydrocarbons (PAH) exposure. Age-standardized mortality rates for ovarian cancer were calculated for the study municipalities for the years 1999-2008. A weighted multiple regression model was employed to calculate the adjusted risk ratio (RR) in relation to PM2.5 levels. After adjusting for urbanization level and fertility rate, the adjusted RR values (95% confidence interval [CI]) for ovarian cancer were 1.2 (1.02-1.41) for the municipalities with PM2.5 levels between 30.48 µg/m3 and 39.41 µg/m3 and 1.2 (1.03-1.39) for the municipalities with PM2.5 levels between 39.48 µg/m3 and 51.1 µg/m3, compared to the municipalities with PM2.5 levels less than 30.39 µg/m3. Results showed that individuals who resided in municipalities with higher levels of PM2.5, a proxy measure of PAH, were at an increased risk of death from ovarian cancer compared to those subjects living in municipalities with the lowest PM2.5. The findings of this study warrant further investigation into the role of exposure to air pollutants in the etiology of ovarian cancer development.

Mortality from breast, endometrial and ovarian cancers among grand multiparous women in Taiwan.

OBJECTIVE: This study was undertaken to examine whether there is a protective effect of grand multiparity on the risks of death from hormone-dependent cancers. METHODS: The study cohort consisted of 144 922 women with at least five children (grand multiparous (GM) women) in the Birth Register between 1 January 1978 and 31 December 1987. Standardised mortality ratios (SMRs) for cancers of the breast, endometrium and ovary were calculated by dividing the numbers of observed cancer deaths to the expected numbers of deaths based on the rates of national female population. RESULTS: Among the 144 922 GM women, a total of 394, 18 and 72 deaths were caused by cancers of the breast, endometrium and ovary, respectively. The SMRs among GM women were 0.73 (95% confidence intervals (CI) 0.66-0.80) for breast cancer, 0.54 (95% CI 0.29-0.79) for endometrial cancer and 0.64 (95% CI 0.49-0.79) for ovarian cancer. CONCLUSIONS: This study provides evidence that grand multiparity may confer a protective effect on the risk of death from cancers of the breast, endometrium and ovary.

Lower serum apelin levels in women with polycystic ovary syndrome.

We tested differences in serum apelin levels between women with polycystic ovary syndrome (PCOS) and those with a healthy regular menstrual cycle, finding that apelin levels were higher in normal women and that apelin was positively correlated with apolipoprotein A levels.

Parity, age at first birth, and risk of death from liver cancer: Evidence from a cohort in Taiwan.

BACKGROUND AND AIM: The present study was undertaken to examine whether there is an association between parity and age at first birth and risk of liver cancer. METHODS: The study cohort consisted of 1,292,462 women who had a first and singleton childbirth between 1 January 1978 and 31 December 1987. We tracked each woman from the time of their first childbirth to 31 December 2007, and their vital status was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate the relative risks (RR) of death from liver cancer associated with parity and age at first birth. RESULTS: There were 826 liver cancer deaths during 32,464,186.58 person-years of follow-up. The mortality rate of liver cancer was 2.54 cases per 100,000 person-years. The adjusted RR was 1.59 (95% confidence interval [CI] = 1.36-1.86) for women who gave birth between 26 and 30, 2.41 (95% CI = 1.81-3.20) for women who gave birth between 31 and 35, and 6.26 (95% CI = 4.27-9.19) for women who gave birth after 35 years of age, respectively, when compared with women who gave birth at less than 25 years of age. The adjusted RR was 0.72 (95% CI = 0.59-0.87) for women who had two to three children, and 0.63 (95% CI = 0.47-0.84) for women with four or more births, respectively, when compared with women who had given birth to only one child. CONCLUSIONS: The present study suggests that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of liver cancer.