Pregnancy-associated gynecological cancer in New South Wales, Australia 1994-2013: A population-based historical cohort study.

INTRODUCTION: Pregnancy-associated gynecological cancer (PAGC) refers to cancers of the ovary, uterus, fallopian tube, cervix, vagina, and vulva diagnosed during pregnancy or within 12 months postpartum. We aimed to describe the incidence of, and perinatal outcomes associated with, invasive pregnancy-associated gynecological cancer. MATERIAL AND METHODS: We conducted a population-based historical cohort study using linked data from New South Wales, Australia. We included all women who gave birth between 1994 and 2013, with a follow-up period extending to September 30, 2018. Three groups were analyzed: a gestational PAGC group (women diagnosed during pregnancy), a postpartum PAGC group (women diagnosed within 1 year of giving birth), and a control group (women with control diagnosis during pregnancy or within 1 year of giving birth). We used generalized estimation equations to compare perinatal outcomes between study groups. RESULTS: There were 1 786 137 deliveries during the study period; 70 women were diagnosed with gestational PAGC and 191 with postpartum PAGC. The incidence of PAGC was 14.6/100 000 deliveries and did not change during the study period. Women with gestational PAGC (adjusted odds ratio [aAOR] 6.81, 95% confidence interval [CI] 2.97-15.62) and with postpartum PAGC (aOR 2.65, 95% CI 1.25-5.61) had significantly increased odds of a severe maternal morbidity outcome compared with the control group. Babies born to women with gestational PAGC were more likely to be born preterm (aOR 3.11, 95% CI 1.47-6.59) and were at increased odds of severe neonatal complications (aOR 3.47, 95% CI 1.45-8.31) compared with babies born to women without PAC. CONCLUSIONS: The incidence of PAGC has not increased over time perhaps reflecting, in part, the effectiveness of cervical screening and early impacts of human papillomavirus vaccination programs in Australia. The higher rate of preterm birth among the gestational PAGC group is associated with adverse outcomes in babies born to these women.

The Novel Use of IL-28 as an Effective Radiosensitizer in Pancreatic Cancer.

BACKGROUND/AIM: Pancreatic cancer is the second most common gastrointestinal cancer in the world, yet the five-year survival outcome rate of less than 5% urges for improvement in medical interventions of pancreatic cancer. Currently, high dose radiation therapy (RT) is used as an adjuvant treatment; however, the high level of RT required to treat advanced neoplasms leads to high incidence rates of side effects. In recent years, the utilization of cytokines as radiosensitizing agents has been studied, in order to reduce the amount of radiation required. However, few studies have examined IL-28 regarding its potential as a radiosensitizer. This study is the first to utilize IL-28 as a radiosensitizing agent in pancreatic cancer. MATERIALS AND METHODS: MiaPaCa-2, a widely used pancreatic cancer cell line was used in this study. Clonogenic survival and cell proliferation assays were used to evaluate growth and proliferation of MiaPaCa-2 cells. Caspase-3 activity assay was used to evaluate apoptosis of MiaPaCa-2 cells and RT-PCR was used to study the possible molecular mechanisms. RESULTS: Our results showed that IL-28/RT enhanced RT-induced inhibition of cell proliferation and promoted apoptosis of MiaPaCa-2 cells. Furthermore, compared to RT alone, we found that IL-28/RT up-regulated the mRNA expression of TRAILR1 and P21, while down-regulating mRNA expression of P18 and survivin in MiaPaCa-2 cells. CONCLUSION: IL-28 has the potential to be used as a radiosensitizer for pancreatic cancer and warrants further investigation.

Pregnancy associated cancer, timing of birth and clinical decision making-a NSW data linkage study.

BACKGROUND: The incidence of pregnancy-associated cancer (PAC), comprising cancer diagnosed during pregnancy or within one year postpartum, is increasing. We investigated the obstetric management and outcomes of women with PAC and their babies. METHODS: A population-based observational study of all women who gave birth between 1994 and 2013 in New South Wales, Australia. Women were stratified into three groups: those diagnosed during pregnancy (gestational cancer group), those diagnosed within one year of giving birth (postpartum cancer group), and a no-PAC group. Generalized estimating equations were used to examine the association between PAC and adverse maternal and neonatal outcomes. RESULTS: One million seven hundred eighty-eight thousand four hundred fifty-onepregnancies were included-601 women (614 babies) were in the gestational cancer group, 1772 women (1816 babies) in the postpartum cancer group, and 1,786,078 women (1,813,292 babies) in the no-PAC group. The overall crude incidence of PAC was 132.7/100,000 women giving birth. The incidence of PAC increased significantly over the twenty-year study period from 93.5/100,000 in 1994 to 162.5/100,000 in 2013 (2.7% increase per year, 95% CI 1.9 - 3.4%, p-value < 0.001). This increase was independent of maternal age. The odds of serious maternal complications (such as acute abdomen, acute renal failure, and hysterectomy) were significantly higher in the gestational cancer group (adjusted odds ratio (AOR) 5.07, 95% CI 3.72 - 6.90) and the postpartum cancer group (AOR 1.55, 95% CI 1.16 - 2.09). There was no increased risk of perinatal mortality in babies born to women with PAC. However, babies of women with gestational cancer (AOR 8.96, 95% CI 6.96 - 11.53) or postpartum cancer (AOR 1.36, 95% CI 1.05 - 1.81) were more likely to be planned preterm birth. Furthermore, babies of women with gestational cancer had increased odds of a severe neonatal adverse outcome (AOR 3.13, 95% CI 2.52 - 4.35). CONCLUSION: Women with PAC are more likely to have serious maternal complications. While their babies are not at increased risk of perinatal mortality, they are more likely to experience poorer perinatal outcomes associated with preterm birth. The higher rate of birth intervention among women with gestational cancers reflects the complexity of clinical decision-making in this context.

The MOHMQuit (Midwives and Obstetricians Helping Mothers to Quit Smoking) Trial: protocol for a stepped-wedge implementation trial to improve best practice smoking cessation support in public antenatal care services.

BACKGROUND: Smoking during pregnancy is the most important preventable cause of adverse pregnancy outcomes, yet smoking cessation support (SCS) is inconsistently provided. The MOMHQUIT intervention was developed to address this evidence-practice gap, using the Behaviour Change Wheel method by mapping barriers to intervention strategies. MOHMQuit includes systems, leadership and clinician elements. This implementation trial will determine the effectiveness and cost-effectiveness of MOHMQuit in improving smoking cessation rates in pregnant women in public maternity care services in Australia; test the mechanisms of action of the intervention strategies; and examine implementation outcomes. METHODS: A stepped-wedge cluster-randomised design will be used. Implementation of MOHMQuit will include reinforcing leadership investment in SCS as a clinical priority, strengthening maternity care clinicians' knowledge, skills, confidence and attitudes towards the provision of SCS, and clinicians' documentation of guideline-recommended SCS provided during antenatal care. Approximately, 4000 women who report smoking during pregnancy will be recruited across nine sites. The intervention and its implementation will be evaluated using a mixed methods approach. The primary outcome will be 7-day point prevalence abstinence at the end of pregnancy, among pregnant smokers, verified by salivary cotinine testing. Continuous data collection from electronic medical records and telephone interviews with postpartum women will occur throughout 32 months of the trial to assess changes in cessation rates reported by women, and SCS documented by clinicians and reported by women. Data collection to assess changes in clinicians' knowledge, skills, confidence and attitudes will occur prior to and immediately after the intervention at each site, and again 6 months later. Questionnaires at 3 months following the intervention, and semi-structured interviews at 6 months with maternity service leaders will explore leaders' perceptions of acceptability, adoption, appropriateness, feasibility, adaptations and fidelity of delivery of the MOHMQuit intervention. Structural equation modelling will examine causal linkages between the strategies, mediators and outcomes. Cost-effectiveness analyses will also be undertaken. DISCUSSION: This study will provide evidence of the effectiveness of a multi-level implementation intervention to support policy decisions; and evidence regarding mechanisms of action of the intervention strategies (how the strategies effected outcomes) to support further theoretical developments in implementation science. TRIAL REGISTRATION: ACTRN12622000167763, registered February 2nd 2022.

Safer Baby Bundle: study protocol for the economic evaluation of a quality improvement initiative to reduce stillbirths.

INTRODUCTION: Stillbirth continues to be a public health concern in high-income countries, and with mixed results from several stillbirth prevention interventions worldwide the need for an effective prevention method is ever present. The Safer Baby Bundle (SBB) proposes five evidence-based care packages shown to reduce stillbirth when implemented individually, and therefore are anticipated to produce significantly better outcomes if grouped together. This protocol describes the planned economic evaluation of the SBB quality improvement initiative in Australia. METHODS AND ANALYSIS: The implementation of the SBB will occur over three state-based health jurisdictions in Australia-New South Wales, Queensland and Victoria, from July 2019 onwards. The intervention is being applied at the state level, with sites opting to participate or not, and no individual woman recruitment. The economic evaluation will be based on a whole-of-population linked administrative dataset, which will include the data of all mothers, and their resultant children, who gave birth between 1 January 2016 and 31 December 2023 in these states, covering the preimplementation and postimplementation time period. The primary health outcome for this economic evaluation is late gestation stillbirths, with the secondary outcomes including but not limited to neonatal death, gestation at birth, mode of birth, admission to special care nursery and neonatal intensive care unit, and physical and mental health conditions for mother and child. Costs associated with all healthcare use from birth to 5 years post partum will be included for all women and children. A cost-effectiveness analysis will be undertaken using a difference-in-difference analysis approach to compare the primary outcome (late gestation stillbirth) and total costs for women before and after the implementation of the bundle. ETHICS AND DISSEMINATION: Ethics approval for the SBB project was provided by the Royal Brisbane & Women's Hospital Human Research Ethics Committee (approval number: HREC/2019/QRBW/47709). Approval for the extraction of data to be used for the economic evaluation was granted by the New South Wales Population and Health Services Research Ethics Committee (approval number: 2020/ETH00684/2020.11), Australian Institute of Health and Welfare Human Research Ethics Committee (approval number: EO2020/4/1167), and Public Health Approval (approval number: PHA 20.00684) was also granted. Dissemination will occur via publication in peer reviewed journals, presentation at clinical and policy-focused conferences and meetings, and through the authors' clinical and policy networks.This study will provide evidence around the cost effectiveness of a quality improvement initiative to prevent stillbirth, identifying the impact on health service use during pregnancy and long-term health service use of children.

Green nanotechnology of MGF-AuNPs for immunomodulatory intervention in prostate cancer therapy.

Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent.

Gestational breast cancer in New South Wales: A population-based linkage study of incidence, management, and outcomes.

BACKGROUND: The incidence of gestational breast cancer (GBC) is increasing in high-income countries. Our study aimed to examine the epidemiology, management and outcomes of women with GBC in New South Wales (NSW), Australia. METHODS: A retrospective cohort study using linked data from three NSW datasets. The study group comprised women giving birth with a first-time diagnosis of GBC while the comparison group comprised women giving birth without any type of cancer. Outcome measures included incidence of GBC, maternal morbidities, obstetric management, neonatal mortality, and preterm birth. RESULTS: Between 1994 and 2013, 122 women with GBC gave birth in NSW (crude incidence 6.8/ 100,000, 95%CI: 5.6-8.0). Women aged ≥35 years had higher odds of GBC (adjusted odds ratio (AOR) 6.09, 95%CI 4.02-9.2) than younger women. Women with GBC were more likely to give birth by labour induction or pre-labour CS compared to women with no cancer (AOR 4.8, 95%CI: 2.96-7.79). Among women who gave birth by labour induction or pre-labour CS, the preterm birth rate was higher for women with GBC than for women with no cancer (52% vs 7%; AOR 17.5, 95%CI: 11.3-27.3). However, among women with GBC, preterm birth rate did not differ significantly by timing of diagnosis or cancer stage. Babies born to women with GBC were more likely to be preterm (AOR 12.93, 95%CI 8.97-18.64), low birthweight (AOR 8.88, 95%CI 5.87-13.43) or admitted to higher care (AOR 3.99, 95%CI 2.76-5.76) than babies born to women with no cancer. CONCLUSION: Women aged ≥35 years are at increased risk of GBC. There is a high rate of preterm birth among women with GBC, which is not associated with timing of diagnosis or cancer stage. Most births followed induction of labour or pre-labour CS, with no major short term neonatal morbidity.

Stillbirth in Australia 2: Working together to reduce stillbirth in Australia: The Safer Baby Bundle initiative.

The rate of late gestation stillbirth in Australia is unacceptably high. Up to one third of stillbirths are preventable, particularly beyond 28 weeks' gestation. The aim of this second paper in the Stillbirth in Australia series is to highlight one key national initiative, the Safer Baby Bundle (SBB), which has been led by the Centre of Research Excellence in Stillbirth in partnership with state health departments. Addressing commonly identified evidence practice gaps, the SBB contains five elements that, when implemented together, should result in better outcomes than if performed individually. This paper describes the development of the SBB, what the initiative aims to achieve, and progress to date. By collaborating with Departments of Health and other partners to amplify uptake of the SBB, we anticipate a reduction of at least 20% in Australia's stillbirth rate after 28 weeks' gestation is achievable.

Comparison of group O Rh(D)- red blood cell use in pregnant women across hospitals of various sizes and obstetric capabilities prior to the introduction of patient blood management guidelines.

BACKGROUND: O Rh(D)- red blood cell (RBC) units can generally be transfused to most patients regardless of their ABO blood type and are frequently used during emergency situations. Detailed usage patterns of O Rh(D)- RBC units in obstetric populations have not been well characterised. With the introduction of patient blood management guidelines, historical usage patterns are important for providing comparative data. AIMS: To determine how the use of O Rh(D)- RBC units in pregnant women differs between hospitals of different sizes and obstetric capabilities prior to patient blood management guidelines. METHODS: Data from 67 New South Wales public hospital blood banks were linked with hospital and perinatal databases to identify RBC transfusions during pregnancy, birth and postnatally between July 2006 and December 2010. RBC transfusions were divided into O Rh(D)- or other blood types. Hospitals were classified according to birth volume, obstetric capability and location, with transfusions classified by timing and diagnosis. RESULTS: Of the 12 078 RBC units transfused into pregnant women, 1062 (8.8%) were O Rh(D)-. Higher use of O Rh(D)- RBC units was seen in antenatal transfusions, preterm deliveries and in regional or smaller hospitals. There was wide variation in rates of O Rh(D)- RBC transfusion among hospitals. CONCLUSIONS: The rate of O Rh(D)- RBC unit use in obstetrics was lower during the period assessed than the nationally reported usage. It is encouraging that O Rh(D)- RBCs were more commonly used in emergency or specialised situations, or in facilities where holding a large blood inventory is not feasible.

Piloting a Telephone Based Health Coaching Program for Pregnant Women: A Mixed Methods Study.

Objectives Get Healthy in Pregnancy (GHiP) is a telephone based lifestyle coaching service for pregnant women, in New South Wales, Australia. GHiP had two service options; a telephone-based health coaching program consisting of up to 10 calls and information only (including one call). This study sought to compare the outcomes of the two GHiP options, to determine the characteristics of women likely to use the service and to explore the feedback from women and health professionals. Methods A pragmatic stratified clustered randomised controlled trial was conducted. Two metro and three rural hospitals were randomised into health coaching or information only arms. Self-reported measures of height and weight and health behaviours (dietary and physical activity) were collected at baseline and 36 weeks gestation. Process evaluation included descriptive analysis of routine program data, and semi-structured interviews with participants and health professionals. Results Of 3736 women screened, 1589 (42.5%) were eligible to participate, and of those eligible, 923 (58.1%) were recruited. More women in the health coaching arm gained weight within the target range for their BMI at 36 weeks gestation (42.9%) compared with information only (31.9%). Women found GHiP to be useful and supportive and midwives and doctors said that it facilitated conversations about weight with pregnant women. Conclusions for Practice Telephone-based lifestyle programs integrated with routine clinical care show promise in helping pregnant women achieve healthy gestational weight gain, but in this case was not significantly different from one information telephone call. Strong positive feedback suggests that scaled-up service delivery would be well received. TRIAL REGISTRATION: ACTRN12615000397516 (retrospectively registered).

Association between interleukin­33 and ovarian cancer.

Ovarian cancer is the leading cause of cancer­ associated mortality in the female reproductive system. Interleukin (IL)­33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL­33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL­33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL­33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase­3 activity kit were all used to evaluate the direct effects of IL­33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcription­polymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL­33; however, the relative caspase­3 activity in cancer cells was decreased in the presence of IL­33. Molecular mechanism studies revealed that the pro­proliferative effect of IL­33 on cancer cells was associated with decreased levels of p27, and the anti­apoptotic effect of IL­33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factor­related apoptosis­inducing ligand receptor 1 (TRAILR1). Therefore, IL­33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an anti­tumor effort in pancreatic cancer, the results of the present study indicated that IL­33 exhibited a significant onco­promoting effect on ovarian cancer. Accordingly, the inhibition of IL­33 may be a promising therapeutic strategy for ovarian cancer.

IL-33 notably inhibits the growth of colon cancer cells.

Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.

First 100 consecutive robotic inguinal hernia repairs at a Veterans Affairs hospital.

The utilization of robotics in general surgery has increased significantly including usage in the Veterans Affairs (VA) system. We implemented a robotic inguinal hernia repair (RIHR) program in our VA hospital and report on initial experience with safety and outcomes. The first 100 consecutive RIHR at a VA hospital were reviewed and compared against the results of contemporaneous open inguinal hernia repair (OIHR). Data were collected for operative characteristics, surgical complications and pain related outcomes. Overall, operative times for OIHR were less than RIHR (83.7 vs. 109.7 min, p < 0.0001); however, there was no difference in operative time for bilateral repairs (121.5 vs. 121.9 min, p = ns). Complication rates were similar between the groups. RIHR patients had less pain at POD 1 than OIHR patients (p = 0.05). RIHR were less likely to have multiple post-op visits for pain than OIHR patients (p = 0.003). RIHR can be implemented in the VA system with acceptable surgical outcomes. RIHR may be associated with less post-operative pain in the early post-operative period.

Uptake of external cephalic version for term breech presentation: an Australian population study, 2002-2012.

BACKGROUND: The safety, efficacy, and cost-effectiveness of external cephalic version (ECV) for term breech presentation has been demonstrated. Clinical guidelines recommend ECV for all eligible women, but the uptake of this procedure in the Australian healthcare setting is unknown. This study aimed to describe ECV uptake in New South Wales, the most populous state of Australia, during 2002 to 2012. METHODS: Data from routine hospital and birth records were used to identify ECVs conducted at ≥36 weeks' gestation. Women with ECV were compared to women who were potentially eligible for but did not have ECV. Eligibility for ECV was based on clinical guidelines. For those with ECV, birth outcomes following successful and unsuccessful procedures were examined. RESULTS: In N = 32,321 singleton breech pregnancies, 10.5% had ECV, 22.3% were ineligible, and 67.2% were potentially eligible but did not undergo ECV. Compared to women who were eligible but who did not attempt ECV, those who had ECV were more likely to be older, multiparous, overseas-born, public patients at delivery, and to deliver in tertiary hospitals in urban areas (p < 0.01). Fewer women who underwent ECV smoked during pregnancy, fewer were morbidly obese, and fewer had a hypertensive disorder of pregnancy, compared to those who were eligible. Caesarean section occurred in 25.9% of successful compared to 95.6% of unsuccessful ECVs. Infant outcomes did not differ by ECV success. CONCLUSIONS: The majority of women with a breech presentation did not receive ECV. It is unclear whether this is attributable to issues with service provision or low acceptability among women. Policies to improve access to and information about ECV appear necessary to improve uptake among women with term breech presentation. Improved data collection around the diagnosis of breech presentation, ECV attempts, and outcomes may help to identify specific barriers to ECV uptake.

Induction of labour practices in New South Wales hospitals: Before and after a statewide policy.

Midwifery Unit Managers completed surveys in 2008 and 2014 to determine methods of induction of labour. There was an increase in balloon catheter use for cervical ripening (rate difference 37%, P = 0.007). Currently, all respondent hospitals have an oxytocin protocol; district hospitals had a significant increase in use of post-maturity protocols (rate difference = 40%, P = 0.01) but there was no change in use of prostaglandin protocols.

Unveil the mysterious mask of cytokine-based immunotherapy for melanoma.

Melanoma is the leading cause of death among all skin cancers and its incidence continues to rise rapidly worldwide in the past decades. The available treatment options for melanoma remain limited despite extensive clinical research. Melanoma is an immunogenic tumor and great advances in immunology in recent decades allow for the development of immunotherapeutic agents against melanoma. In recent years, immunotherapy utilizing cytokines has been particularly successful in certain cancers and holds promise for patients with advanced melanoma. In this review, an overview of the current status and emerging perspectives on cytokine immunotherapy for melanoma are discussed in details. Such a study will be helpful to unveil the mysterious mask of cytokine-based immunotherapy for melanoma.

IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer.

IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.

Laparoscopic Versus Open Resection for Gastrointestinal Stromal Tumors (GISTs).

PURPOSE: Primary gastrointestinal stromal tumors (GISTs) are typically treated with open resection. There is growing interest in laparoscopic GIST resection; however, data is limited. We report our experience with GIST resections using both open and laparoscopic techniques. MATERIALS AND METHODS: Twenty-nine GIST patients underwent definitive intent resection at the University of Missouri from 1990 to 2010. Patients who underwent laparoscopic resection (n = 7) were matched on the basis of tumor size, age, tumor location, and National Comprehensive Cancer Network (NCCN) risk stratification with seven patients who underwent open resection. The two groups were compared with respect to age, gender, BMI, tumor size, tumor site, mitotic rate, surgical margins, NCCN risk stratification, estimated blood loss, hospital stay, surgical complications, disease recurrence, and overall survival. RESULTS: The cohorts did not differ with respect to age, gender, BMI, tumor location, tumor size, or positive margins (p > 0.05). Patients who underwent open resection had more NCCN high-risk patients, but the difference was not statistically significant (p = 0.08). There was significantly less estimated blood loss (median 15 vs. 150 mL, p < 0.05) and significantly shorter hospital stay (median 4 vs. 7 days, p < 0.05) for the laparoscopy group. There were no recurrences in the laparoscopy group, but there was one in the open group with a median follow-up of 55 and 63 months, respectively (p > 0.05). Five-year disease-free survival was 100 % for the laparoscopic group and 83 % for the open resection group. CONCLUSIONS: Laparoscopic resection for appropriately selected GISTs is feasible and associated with significantly less blood loss and shorter hospitalizations compared to open resection. Further studies are needed to better define its role for GIST.

Long-term childhood outcomes of breech presentation by intended mode of delivery: a population record linkage study.

INTRODUCTION: There is a lack of information on long-term outcomes by mode of delivery for term breech presentation. We aimed to compare childhood mortality, cerebral palsy, hospitalizations, developmental, and educational outcomes associated with intended vaginal breech birth (VBB) with planned cesarean section. MATERIAL AND METHODS: Population birth and hospital records from New South Wales, Australia, were used to identify women with non-anomalous pregnancies eligible for VBB during 2001-2012. Intended mode of delivery was inferred from labor onset and management. Death, hospital, and education records were used for follow up until 2014. Cox proportional hazards regression and modified Poisson regression were used for analysis. RESULTS: Of 15 281 women considered eligible for VBB, 7.7% intended VBB, 74.2% planned cesarean section, and intention was uncertain for 18.1%. Intended VBB did not differ from planned cesarean section on infant mortality (Fisher's exact p = 0.55), childhood mortality (Fisher's exact p = 0.50), cerebral palsy (Fisher's exact p = 1.00), hospitalization in the first year of life [adjusted hazard ratio (HR) 1.04; 95% CI 0.90-1.20], hospitalization between the first and sixth birthdays (HR 0.92; 95% CI 0.82-1.04), being developmentally vulnerable [adjusted relative risk (RR) 1.22; 95% CI 0.48-1.69] or having special needs status (RR 0.95; 95% CI 0.48-1.88) when aged 4-6, or scoring more than 1 standard deviation below the mean on tests of reading (RR 1.10; 95% CI 0.87-1.40) and numeracy (RR 1.04; 95% CI 0.81-1.34) when aged 7-9. CONCLUSIONS: Planned VBB confers no additional risks for child health, development or educational achievement compared with planned cesarean section.

Contribution of changing risk factors to the trend in breech presentation at term.

BACKGROUND: Recent population-wide changes in perinatal risk factors may affect rates of breech presentation at birth, and have implications for the provision of breech services and training in breech management. AIMS: To investigate whether changes in maternal and pregnancy characteristics explain the observed trend in breech presentation at term. MATERIALS AND METHODS: All singleton term (≥37 week) births in New South Wales during 2002-2012 were identified through birth and associated hospital records. Annual rates of breech presentation were determined. Logistic regression modelling was used to predict expected rates of breech presentation and these were compared with observed rates over time. A priori predictors included maternal age, country of birth, parity, smoking during pregnancy, diabetes, pregnancy hypertension, placenta praevia, previous singleton term breech, previous caesarean section, infant sex, gestational age, birthweight and congenital anomalies. Hospital and Medicare data were used to assess concomitant trends in external cephalic version. RESULTS: Among 914 147 singleton term births, 3.1% were breech at delivery. Rates of breech presentation declined from 3.6% in 2002 to 2.7% in 2012 (test for trend P < 0.001), but was predicted to increase from 3.6% in 2002 to 4.3% in 2012 because of increased maternal age, nulliparity, maternal diabetes, history of breech presentation and previous caesarean section. However, use of external cephalic version appears to have increased over time. CONCLUSIONS: Breech presentation at delivery has decreased in New South Wales. Increased use of external cephalic version likely accounts for this decline, as changes in risk factors do not.