Significant Increase In Incidence Research Articles

Abstract 4001: Unraveling the molecular mechanism of racial disparity in hepatocellular carcinoma (HCC): A link between type I interferon (IFN-I) signaling and HCC disparity

Abstract Among HCC patients, there is a statistically significant increase in incidence and mortality as well as a decrease in 5-year survival rates in African-American (hereafter referred to as black) patients compared to non-Hispanic white (hereafter referred to as white) patients. Currently, there is a gap in our understanding of the molecular mechanism underlying this racial disparity. The purpose of this study is to unravel this molecular mechanism. Gene expression profiles were analyzed by RNA-sequencing (RNA-Seq). Canonical pathway analysis of the differentially expressed genes was performed by Ingenuity Pathway Analysis (IPA). Differential expression of the genes was validated by qRT-PCR and immunohistochemistry. The role of the identified genes in regulating proliferation was determined by transient knockdown by siRNA in a patient-derived xenograft (PDX) cell line established from a black HCC patient followed by MTT assay. In TCGA database, RNA-Seq data from 377 HCC patients were available, of which 17 were black and 184 were white. 279 genes were identified, with a p-value<0.01, that are differentially regulated between black and white patients. IPA analysis identified Type I Interferon (IFN-I) signaling as the only pathway that showed statistically significant activation in black patients. RNA-Seq on HCC samples from 14 white and 18 black patients from the tissue bank at VCU Medical Center identified 283 differentially regulated genes and IPA analysis revealed that the only pathway that showed statistically significant activation in black patients is the IFN-I signaling pathway. Activation of the IFN-I signaling pathway in black patients was identified even after correction of the differential gene expression data for HCV status, indicating that the observed findings are independent of HCV infection. Four interferon stimulated genes (ISGs), ISG15, IFI6, MX1 and OAS1, showing significantly increased expression in black HCC patients in both the TCGA database and our own analysis, were chosen for further analysis by qRT-PCR in HCC patient-derived xenografts (PDX) samples from black and white patients, both HCV positive and negative. The levels of the four ISGs were very low in two HCV-negative white HCC PDX lines. In three HCV-negative black HCC PDX lines, their expression levels were significantly and robustly higher. In a HCV-positive black HCC PDX line, their expression was further higher. The results for OAS1, ISG15 and MX1 were validated at the protein level using immunohistochemistry. Transient knock down of IFI6 and ISG15 significantly decreased proliferation of a PDX line established from a black HCC patient. Persistent activation of the IFN-I signaling pathway might be a key determinant of racial disparity in black HCC patients. This pathway might be exploited to develop targeted treatment that work best for black HCC patients. Citation Format: Saranya Chidambaranathan-Reghupaty, Mikhail Dozmorov, Rachel Mendoza, Zhao Lai, Paul B. Fisher, Trevor Reichman, Devanand Sarkar. Unraveling the molecular mechanism of racial disparity in hepatocellular carcinoma (HCC): A link between type I interferon (IFN-I) signaling and HCC disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4001.

SUN-170 ACUTE KIDNEY INJURY AND VARICEAL REBLEEDING IN CIRRHOTIC PATIENTS

Acute kidney injury (AKI) is a common complication in cirrhotic patients with variceal bleeding. We evaluated the relationship between the incidence of AKI and variceal rebleeding according to the newly proposed criteria by the international club for ascites for diagnosis of AKI in cirrhosis. A prospective cohort study included 203 patients with cirrhosis admitted to the Liver Units in Zagazig university hospitals from July 2017 to Jan 2018 with history of follow up in outpatient clinics. Patients were classified into two major groups according to the presence or absence of AKI (Group I: AKI, Group II: Non AKI). Each group was subdivided into two subgroup according to the incidence of re-bleeding of varices. Patients were followed-up with a pre-defined protocol including endoscopic treatment regularly performed every 3-4 weeks until the gastro-esophageal varices were eradicated. After eradication, surveillance endoscopy was performed every 3 months for 9 months. Ninety-one patients (45%) fulfilled the ICA-AKI criteria and most (65%) initially had stage 1 AKI. Higher Child-Pugh score, low systemic blood pressure, blood transfusion before endoscopy were independent predictors of AKI. 28% of patient with AKI progressed to higher stages with decompensated liver status, hyponatremia, higher demand of blood transfusion, increased frequency of infection, and elevated serum creatinine levels at diagnosis of AKI. Significant increase in incidence of variceal rebleeding was noticed in patients with AKI at presentation. The stage of AKI significantly correlates with the rate of variceal rebleeding at 1 and 3 months of follow up. The occurrence of AKI was associated with higher incidence of gastro esophageal rebleeding in cirrhotic patients.

TIPS Is Not Associated with a Higher Risk of Developing HCC in Cirrhotic Patients: A Systematic Review and Meta-analysis.

Background and Aims: The association between portal-systemic shunt and hepatocellular carcinoma (HCC) development in patients who have cirrhosis is still controversial. This systematic review with meta-analysis was performed to systematically clarify the potential role of portal-systemic shunt in the development of HCC.Methods: The PubMed, Embase, and Cochrane Library databases were searched for potentially eligible literature. Meta-analysis with random-effects model was performed to combine the incidence rates of HCC after portal-systemic shunt. Finally, seven studies were included. In the present review, we mainly focused on 859 patients (365 in the transjugular intrahepatic portal-systemic shunt (TIPS) group and 494 in the non-TIPS group) from five studies to analyze incidence rates after TIPS.Results: At the end of follow-up, there were 66 (18%, 66/365) patients who developed HCC after TIPS intervention and 63 (13%, 63/494) patients who developed HCC after non-TIPS treatments. Pooled estimates with random-effects model did not demonstrate a significant increase of incidence of HCC after TIPS (risk ratio: 1.37 [confidence interval (CI): 0.96 to 1.97]; p = 0.08) compared with non-TIPS treatments. Subgroup analyses for those patients with transplanted liver also did not detect a significant difference between the TIPS group and non-TIPS group (risk ratio: 1.10 [CI: 0.59 to 2.07]; p = 0.75).Conclusions: Current evidence suggests that portal-systemic shunt is not associated with a higher risk of HCC development in cirrhotic patients.

Increasing Incidence rates of Oropharyngeal Squamous Cell Carcinoma in Germany and Significance of Disease Burden Attributed to Human Papillomavirus.

Increasing incidences of head and neck cancers and rising proportions of these associated with human papillomavirus (HPV), especially in the oropharynx, have been reported in international studies. So far, the trends and contribution of HPV to the number of newly diagnosed cases of oropharyngeal squamous cell carcinomas (OPSCC) in Germany are uncertain. We investigated HPV association and incidence rates in a cohort of consecutively included patients with OPSCC in Giessen 2000-2017, and compared our results with regional (Giessen and the federal state of Hesse), national (Germany), and international (United States) databases. Regional data show a significant increase in the overall incidence rates of oropharyngeal cancers and in the incidence of HPV-associated cancers of the subsites tonsils and oropharynx, whereas other oropharyngeal subsites show no significant change. Analysis of national databases shows a significant incidence increase in Germany and in the United States. The rise in incidence is predominantly attributable to male patients in the US population, whereas in Germany rising OPSCC incidence is more associated with females. There is a significant elevation of OPSCC incidence rates in Germany, which corresponds to the recognized incidence increase of HPV-related oropharyngeal cancers based on experimental data from consecutively included patients of our cohort. Our investigation shows different patterns of this increase in Germany and in the United States, which demonstrates spatial heterogeneity and the need for population-based investigations regarding the role of HPV in oropharyngeal cancer.

PSAscreening and molecular markers

Prostate cancer (PCA) is the most common type of cancer in men. The significant increase in incidence is most likely caused by the overdiagnosis of prostate cancer by widespread prostate-specific antigen (PSA) screening. This article reviews the three largest randomized trials of PSA-based prostate cancer screening and the benefits and disadvantages of general PSA screening. It gives an overview about the strategies to avoid the harms from overdetection and overtreatment without missing clinically relevant tumors. This review article is based on aliterature search in the PubMed database on PSA-based screening, molecular serum markers and risk-adapted PSA screening. In contrast to the CAP and PLCO trial, the ERSPC study reports areduced relative and absolute mortality risk. Furthermore, the use of the PSA was associated with significantly lower risk of metastatic disease. In order to avoid unnecessary biopsy and overtreatment including treatment of insignificant prostate cancer, anumber of tests have been proposed to improve the specificity of the PSA screening including the PHI, the 4Kscore and the risk-adapted PSA screening. The assessment of a baseline PSA level in the fifth decade allows subsequent risk-adapted PSA screening intervals. This concept is currently evaluated by the largest prospective multicenter trial, the PROBASE-trial. Neither acomplete rejection of aPSA-based screening nor ageneral PSA testing is afinal solution to this dilemma. Arisk-adapted PSA screening according to abaseline PSA as well as serum markers may reduce unnecessary diagnostic and therapeutic interventions and its attendant morbidities without adecrease in sensitivity.

Incidence and trends of pancreatic cancer (PC) in Girona: A population-based study from the Girona Cancer Registry (1994-2015).

225 Background: PC is the third leading-cause of cancer death in Spain. In this study we aim to investigate PC’s incidence and trends during 1994-2015 in Girona. Methods: Data were extracted from the population-based Girona Cancer Registry. Incident PC cases were classified using the ICD-O-3 Third Edition. Age-adjusted incidence rates (ASRE) to the European standard population and world standard population (ASRW) were obtained. Trends were assessed using the estimated annual percentage of change (EAPC) of the ASRE13. Results: We identified 1590 PC incident cases, 45.8% females and 54.2%. Patients > 64 years old represented a 72.6% of cases. According to histology, epithelial tumors stand for a 44% of cases and neuroendocrine neoplasms represented only the 3% of all cases, being most of PC tumors’ histology non-specified. Cases detected only by death certificates (DCO) were 7.7% in males and 7.4% in females. For the whole study population, crude rate (CR) cancer incidence was 11.26 cases per 100,000 inhabitants/year (12.17 men; 10.34 women). Regarding the ASR, results show an ASRE13 of 12.99 (95% CI 12.36;13.65) and ASRW of 5.58 (95% CI 5.8;13.655.91). Age-specific rates reflected a drastic increase with age, having the population over 85 years the highest rate (74.5 cases per 100,000 inhabitants/year). We also found a significant increase in incidence of PC cases over the study period, with an EAPC of 1.41% per year, present in both men (EAPC = 1.30%) and women (EAPC = 1.37%). Conclusions: Incidence rates of PC in Girona are within the European average, and likewise they have been increasing for the last two decades. There is an increase of incidence in the elderly population reflected in age-specific rates, reason whereby we believe there are a high proportion of unspecific histologies. These results can be used as baseline for further research.

Abstract TP329: Continuous Intracerebroventicular Injection of Brain-derived Neurotrophic Factor Increases Stroke Onset via Elevation of Blood Pressure in Hypertensive Rats

Introduction: Increasing evidences describe that Brain-derived neurotrophic factor (BDNF) is neuroprotective against cerebrovascular injuries and we previously revealed BDNF preservation on cerebral vessels was associated with inhibition of stroke onset in hypertensive rats. As BDNF was reported to increase blood pressure (BP) in hypertension, however, the upregulation might show conflicting results regarding stroke onset. In this study, we pursued the role of BDNF on stroke onset induced by high-salt diet (HSD) in hypertensive rats. Methods: In experiment 1, spontaneously hypertensive stroke-prone rats (SHRSP) were fed an 8% (n=22) or 0.3% (n=8) sodium diet from 11 weeks of age through 28 days. In experiment 2, SHRSP were treated with continuous intracerebroventricular injection of 2.1μg/day BDNF (n=10) or the vehicle (PBS; n=10) and fed an 8% sodium diet from 11 weeks of age through 24 days. Results and Conclusions: In experiment 1, stroke onset (95%) and mortality (55%) were frequently seen in the rats with HSD, whereas the rats with normal-salt diet were healthy. The expression level of BNDF was upregulated in the cerebral hemisphere and the increase were seen in reactive astrocytes at somatosensory cortex, whereas it was downregulated in endothelial cells. In experiment 2, in comparison with vehicle group, SHRSP with BDNF showed significant increase of incidence of stroke signs (60% vs. 89%), mortality (20% vs. 67%), BP at 2 weeks (214±6 vs. 244±12 mmHg), heart rate (366±20 vs. 457±17 beat/min) and decrease of body weight at 2 week (253±6 vs. 212±11 g), symptom score (5.6±0.3 vs. 2.8±0.8), and gastrocnemius muscle/BW (57±1 vs. 53±1 mg/g). Conclusion Despite the consistent observations of protective roles of BDNF in endothelial cells against the stroke, the present study demonstrated that endogenous BDNF was produced in reactive astrocytes in relation to stroke onset and additive application of exogenous BDNF by continuous intracerebroventricular injection enhanced the onset via elevation of BP in hypertensive rats. As BDNF is a potential candidate treatment not only for post-stroke but also stroke inhibition, we suggest that hypertensive patients need care for the elevation of BP in the clinical trials with BDNF.

End of Phase 1 Results from Zuma-6: Axicabtagene Ciloleucel (Axi-Cel) in Combination with Atezolizumab for the Treatment of Patients with Refractory Diffuse Large B Cell Lymphoma

Background Axi-cel is a US FDA-approved autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy for treatment of adult patients (pts) with relapsed or refractory large B cell lymphoma (LBCL) after ≥ 2 prior lines of therapy. The checkpoint proteins PD-1 and PD-L1 are expressed on CAR T cells and in the tumor microenvironment, and are upregulated after CAR T cell infusion (Cherkassky, et al. J Clin Invest. 2016; Galon, et al. ASCO 2017. #3025). This suggests that PD-L1 blockade could augment axi-cel activity. This end of Phase 1 analysis of ZUMA-6 examines the safety and preliminary efficacy of axi-cel in combination with the anti–PD-L1 antibody atezolizumab (atezo) in pts with refractory LBCL (NCT02926833). Methods Eligible pts (≥ 18 years) with refractory DLBCL must have received prior CD20-targeting and anthracycline-containing regimen and had ECOG ≤ 1 and adequate bone marrow and organ function. Pts received low-dose conditioning followed by axi-cel infusion (target dose of 2 × 106 cells/kg). Atezo was administered at 1200 mg every 21 days for 4 doses starting on Day 21, 14, and 1 post–axi-cel infusion for Cohorts 1, 2, and 3, respectively. Incidence of dose-limiting toxicities (DLTs) was the primary endpoint. Secondary endpoints included the frequency of adverse events (AEs), disease response, and pharmacokinetics. Results As of January 19, 2018, 12 pts have received axi-cel and ≥1 dose of atezo (3 in Cohort 1; 3 in Cohort 2, 6 in Cohort 3). Median age was 55 years (range, 30 – 66); median follow-up from axi-cel infusion was 4.4 months (range, 0.8 – 12.6). One pt in Cohort 3 experienced a DLT of Grade 4 thrombocytopenia and neutropenia lasting >30 days. All pts experienced at least 1 AE (92% Grade ≥ 3), with no apparent exacerbation or recurrence of axi-cel–related AE following atezo infusion. The most common grade ≥ 3 AEs were anemia (9/12, 75%), encephalopathy (5/12, 42%), and neutropenia (5/12, 42%). Grade ≥ 3 CRS and neurologic events occurred in 3 (25%) and 6 (50%) pts, respectively. The ORR in evaluable pts was 9/10 (90%), with 6 pts (60%) in CR and 3 (30%) in partial response (PR); 2/6 pts (33%) had converted to CR at month 6 and month 9 after initially achieving a PR. CAR T cell expansion (area under the curveD0-28) in pts with DLBCL was >2-fold higher in ZUMA-6 than the median observed in pts treated with axi-cel alone in ZUMA-1 (ZUMA-6: median, 823 cells/µL × days, range, 99 – 2301; ZUMA-1: median, 357 cells/µL × days, range, 5 – 11,507). Median CAR T cell levels remained higher than ZUMA-1 beyond 28 days. Conclusions PD-L1 blockade with atezo following axi-cel infusion has a manageable safety profile, with a low incidence of DLTs and no clinically significant increase in incidence of AEs. Encouraging efficacy results support the opening of Phase 2 of ZUMA-6 in which 22 pts will be treated according to the Cohort 3 schedule. Pharmacokinetic data suggest the potential for enhanced CAR T cell expansion.

Comparison of 3% vs. 23.4% Hypertonic Saline in Traumatic Brain Injury

Background: Hypertonic saline (HTS) is an effective treatment for patients with increased intracranial pressure (ICP) secondary to traumatic brain injury (TBI). The ideal concentration for use in these patients is not well defined. The aim of our study was to compare Glasgow coma scale (GCS) and mortality of patients after administration of 3% vs. 23.4% HTS in the initial resuscitation. Methods: We performed a retrospective analysis of patients admitted to the surgical intensive care unit (ICU) under the trauma service with a diagnosis of TBI who received HTS during initial resuscitation. Patient medical records were reviewed to collect data including in-hospital mortality, ICU length of stay, hospital length of stay, GCS at the time of admission and discharge, serum sodium and serum osmolality values at 24, 48 and 72 h after arrival, acute kidney injury and severe hypernatremia. Results: Patients >= 18 years of age admitted to trauma ICU with a diagnosis of TBI. Pregnant, incarcerated, or non-traumatic intracranial hemorrhage patients were excluded. Thirty-one patients were included in the study. The 3% arm included 21 patients, and 23.4% arm had 10 patients. All patients received 3% HTS continuous infusion following initial bolus. Median injury severity scores (ISS) were 22 vs. 25 in the 3% vs. 23.4% HTS groups, respectively (P = 0.37). There was no difference in in-hospital mortality between the two groups (52.4% vs. 50.0%, P = 0.45). There was a significant improvement in GCS at discharge, 8.3% vs. 44.4% in 3% HTS vs. 23.4% HTS arms, respectively (P = 0.029). Patients reaching goal serum sodium and serum osmolality at 24 h was significantly higher in the 23.4% group (33.3% vs. 70.0%; P = 0.028 and 35.7% vs. 77.8%; P = 0.026, respectively). Significant increase in incidence of severe hypernatremia in the 23.4% arm was noted (0.0% vs. 40.0%, P = 0.009). Conclusion: This study demonstrates no significant difference in in-hospital mortality for patients who received 3% vs. 23.4% HTS. Significantly higher percentage of patients receiving 23.4% HTS reached goal serum sodium and osmolality levels at 24 h with a concomitant significantly increased rate of severe hypernatremia. J Curr Surg. 2019;9(4):39-44 doi: https://doi.org/10.14740/jcs389 Â

Breast Cancer in Indian Women: Genetic Risk Factors and Predictive Biomarkers

AbstractBreast cancer is the most common cancer among Indian women with a significant increase in incidence in young women. To identify risk factors for breast cancer in young women, study of BRCA1 and BRCA2 germ line mutations was done in a cohort of 204 Indian breast cancer patients. The study showed a total of 18 mutations in 2.94% of the tested patients, 44% BRCA1 and 78% BRCA2 mutations were found unique to the Indian population. Association of low penetrance genes mainly CYP17, VDR gene and AR-CAG repeat polymorphisms with breast cancer risk showed CYP17 A2 and VDR Poly-A L as high risk alleles, the risk of developing breast cancer among women carrying three high-risk alleles is 4.68 (95% confidence interval [CI]: 0.77–28.0; p for trend = 0.10) compared with women carrying none. CYP17 A2 allele was also found associated with development of breast cancer at young age and can also serve as a target for therapy. Betel quid chewing has been found as a significant and independent risk factor for developing breast cancer in North East Indian women which induces genetic alterations leading to breast carcinogenesis. Studies to assess the predictive role of various tumor markers showed that expression of p-glycoprotein in pretreatment biopsy predicts a poor clinical response to neoadjuvant chemotherapy (NACT) in patients having locally advanced breast cancer. The chemotherapy-induced toxicity (vomiting and alopecia) correlated significantly with clinical and immunohistochemical response (reduction in bcl2/bax ratio) and were found to be a cost-effective and reliable predictor of response to NACT. Androgen receptor (AR) has been identified as independent predictive marker for response to NACT in locally advanced breast cancer cases and can serve as novel therapeutic target for triple negative breast cancers.

Role of Biofilm and its Effects in Orthodontic Treatment

The presence of biofilms can be attributed as the causative factor of many oral pathological conditions, including caries, periodontal disease, and candidiasis. It has been estimated that some 60% of human infections, including dental caries and periodontal disease, are due to microbial biofilms. Thus, in order to control the various disease processes that occur in the human oral cavity, an understanding of biofilms, their formation, and control of their development, is vital. Supragingival plaque control in orthodontic patients become more difficult with fixed nature of orthodontic appliances. The brackets, arch wires, and other orthodontic gadgets are main focalpoints for accumulation of plaque and also act as obstacle to plaque control and enhancing gingivitis. Hence, the prevalence of gingival inflammation in orthodontic patients is increased, along with significant increase in incidences of dental caries and their mild variant known as white spot lesions. Biofilm accumulation can also lead to premature debonding and eventually enamel decalcification and periodontal diseases. This review was conducted to understand the importance of biofilm and its implication in clinical orthodontic outcomes.

Effect of nonpharmacological methods on incidence of postspinal hypotension during cesarean delivery

Introduction Hypotension is caused by upward spread of anesthetic into the subarachnoid space; this results in venous pooling in the capacitance vessels of the lower limbs as a result of block of sympathetic tone and unopposed activity of parasympathetic tone. It also may be caused by aorto-caval syndrome and is accompanied by bradycardia, nausea, and vomiting. Hypotension may have deleterious effects on mother and fetus and may result in uteroplacental hypoperfusion, as placental perfusion is pressure dependent, and lack of autoregulation of placental blood vessels, if persisted, may threaten the life of the fetus. Aim The primary aim of the work is to compare incidence of intraoperative hypotension between the three groups. The secondary outcome is to assess Appearance, Pulse, Grimace, Activity, Respiration (Apgar) score, vasopressor consumption, and occurrence of complications (nausea, vomiting, and bradycardia). Patients and methods A total of 150 patients undergoing cesarean delivery under spinal anesthesia were included. Patients were divided into three equal groups, using simple randomization method, with 50 patients each: group S, in which the patient will sit for 1 min after induction of spinal anesthesia and then will lie down; group E, in which patient's legs will be elevated to 30° from the horizontal plane; and group C in which the patient will lie down immediately after induction of spinal anesthesia as a control group. Then, heart rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure were measured every 2 min until delivery of fetus and then every 5 min until the end of surgery. Sensory level was assessed before start of surgery, subsequently after lying down, and every 1 min using hot and cold test until it reaches T6 sensory level. Fetal well-being was assessed by Appearance, Pulse, Grimace, Activity, Respiration (Apgar) score measured by a pediatrician blinded to the study protocol at 1 and 5 min after delivery. Incidence of hypotension is defined as ‘at least one episode of decrease in systolic blood pressure to less than 90 mmHg or decrease in systolic pressure more than 20% from the baseline till the end of surgery’. It was treated immediately by 200 ml intravenous bolus fluids and injection of 5 mg ephedrine intravenous bolus every 2 min until elevation of blood pressure, and the total of ephedrine consumption was calculated. Duration of surgery and intraoperative complications was recorded as bradycardia, defined by heart rate below 60 beats/min, which was treated by 0.5 mg atropine sulfate, and nausea and vomiting, which were treated by ondansetron intravenous 4 mg after correction of hypotension. Results A total of 150 cesarean delivery patients between 22 and 34 years of age were included in the study. Regarding basic clinical and demographic data, it was found that the median age of all cesarean delivery patients was 30 years. The median BMI of all cesarean delivery patients was 32.5. Regarding the surgery duration, the median surgery duration of all cesarean delivery patients was 40 min. Regarding level of sensory block, most patients had sensory block at T6 (70%), and 30% at T4 in groups C, E, and S, correspondingly. Regarding primary outcome (incidence of hypotension mean arterial blood pressuer (MAP)<70 mmHg), there was a highly significant increase in incidence of hypotension in group C compared with other groups of patients, with highly significant statistical difference (P=0.0092). The incidence of hypotension in group C was 70%, in group E was 50%, whereas in group S was 40% (P=0.0092). Regarding secondary outcomes (ephedrine consumption, Apgar scores, and complications), there was a highly significant increase in ephedrine consumption in group C compared with other groups (P=0.000002). The median value of ephedrine consumption in group C was 7.5 mg, in group E was 2.5 mg, whereas no ephedrine was consumed in group S (P=0.000002). Moreover, there was a nonsignificant difference regarding Apgar score at 1 min (P>0.05). There was a highly significant increase in Apgar score at 5 min in group S compared with other groups (P=0.0047). There was a highly significant increase in bradycardia in group C compared with the other groups (P=0.0015). There was a highly significant increase in nausea in group C compared with the other groups (P=0.0008). There was a highly significant increase in vomiting in group C compared with the other groups (P=0.0008). Conclusion Incidence of hypotension in patients undergoing cesarean delivery under spinal anesthesia markedly decreased in patients who sat for 1 min after induction of spinal anesthesia and then lied down (group S) compared with patients who lied down immediately after induction of spinal anesthesia.

Lactate dehydrogenase and maternal and perinatal outcome in preeclamptic women

Background: Preeclampsia is a condition that is characterized by hypertension and proteinuria occurring after 28 weeks of gestation. It complicates 5%–8% of all pregnancies. Lactate dehydrogenase (LDH) is an intracellular enzyme and its level is increased in preeclamptic women due to cellular death. Preeclampsia is a multisystem disorder and leads to a lot of cellular death. It carries substantial risks for both fetus and mother with a subsequent increase in the perinatal and maternal morbidity and mortality. Aim: The present study was planned to estimate and compare the serum LDH levels in women with preeclampsia and normal pregnant women and to correlate LDH levels with maternal and perinatal outcome in preeclampsia. Materials and Methods: This observational prospective study was conducted on 200 antenatal women. Women were divided into two groups, namely Group I (n = 100) comprised of women with preeclampsia (study group) and it was further subdivided into three categories on the basis of LDH levels: A (n = 53): 800 IU and Group II (n = 100, control) comprised of normotensive pregnant women. LDH levels of both the groups were compared, and association of maternal and perinatal outcome was assessed in relation to LDH levels. Results: With increased severity of preeclampsia, rise in the LDH levels was observed. Severely preeclamptic women with LDH levels >800 IU/l showed a significant increase in incidence of eclampsia, abruption, hemolysis, elevated liver enzymes, and low platelet count syndrome, disseminated intravascular coagulation, and intensive care unit (ICU)/respiratory ICU transfer as compared to women who had lower levels

843: Perinatal outcomes by BMI class in women with hypertension or diabetes delivered by term cesarean

We have shown that in otherwise healthy women, body mass index (BMI) ≥40 kg/m2 is independently associated with adverse neonatal outcomes; however, delivery <39-40 weeks for this indication alone further increases morbidity. It is unclear if increasing BMI has additive adverse perinatal effects when added to common comorbidities like hypertension (HTN) and/or diabetes (DM). We sought to evaluate if increasing BMI class is associated with worsening perinatal outcomes in women with HTN and/or DM delivered by pre-labor elective repeat cesarean delivery (ERCD) and to identify the gestational age (GA) at birth between 37-39 weeks at which these morbidities are minimized. We performed a secondary analysis of a prospective cohort of women undergoing ERCD performed at 19 centers in the MFMU from 1999-2002. Women with HTN and/or DM and non-anomalous singletons delivered by term pre- labor ERCD were included. Women with comorbidities other than HTN or DM or non-elective CD were excluded. Primary outcome was composite neonatal morbidity; secondary outcomes included composite maternal morbidity and individual components of the composites (Table). Incidences of outcomes were calculated for women with HTN, DM, and HTN and/or DM and stratified by BMI class. Multivariable logistic regression was used to calculate adjusted ORs (with 95% CIs) with BMI <30 as reference. Mantel-Haenszel test was used to evaluate the relationship between BMI class and each comorbidity stratified by week GA at delivery. Of 13350 women who underwent ERCD, 786 with documented BMI and either HTN, DM, or HTN and/or DM were analyzed. There was no significant difference in composite neonatal morbidity (or individual components) by BMI class in women with HTN, DM, or HTN and/or DM (Figure/Table). However, there was increasing composite maternal morbidity (p=NS) and a significant increase in incidence of wound complications (p=0.04) with increasing BMI class in women with HTN and/or DM. There were no significant relationships between BMI class, HTN and/or DM, and any outcome across week GA at delivery (p=NS). While BMI ≥40 increases neonatal morbidity in healthy women, there appears to be no additive effect of increasing BMI class, regardless of GA at delivery, in women with HTN and/or DM.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Mortality of women with ductal carcinoma in situ of the breast: a population-based study from the Girona province, Spain (1994\u20132013)

PurposeWe aim to comprehensively describe the incidence and mortality trends of ductal carcinoma in situ (DCIS) in the Girona province, Spain (1994–2013) and to estimate the all-cause mortality excess risk of diagnosed women.MethodsAge-standardized rates of DCIS were estimated between 1994 and 2013. Standard mortality ratios (SMR) and absolute excess mortality were calculated overall and by tumor and patient characteristics. A sensitivity analysis was conducted excluding cases with a subsequent invasive breast cancer (sIBC).ResultsOf the 641 women included, 56 died (follow-up time: 8.4 person-years). Between 1994 and 2013, a significant increase in incidence and decrease in mortality was identified among women aged between 50 and 69 years old. Neoplasms and circulatory system disease were the most common causes of death. No excess risk of death was found overall, except for women aged < 50 years (SMR = 3.44, 95% CI 1.85; 6.40) and those with a sIBC (SMR = 2.51, 95% CI 1.26; 5.02), risk that lessened when cases with sIBC were excluded. Patients with sIBC also showed an excess risk (SMR = 2.29, 95% CI 1.03; 5.10).ConclusionsAmong women aged 50–69 years old, incidence of DCIS has significantly increased yet mortality has decreased. Overall, the all-cause mortality risk of women diagnosed with DCIS remains similar to that of the general population except for women diagnosed before age 50 and those with sIBC, who showed a significant increased risk. Differential management of these patients should be considered.

2198. Increased Global Incidence and Altered Demographic Profile of Hepatitis Delta Virus (HDV)

BackgroundA significant increase in the yearly incidence of hepatitis delta virus (HDV) diagnosis in hepatitis B virus (HBV) patient populations has been identified through analysis of global infectious disease datasets. Currently, HDV is classified as a non-notifiable infectious disease in many countries around the world. Kuschner et al. reported over 90% of HBV-positive patients are not being tested for HDV (2015). Together, the non-notifiable status of HDV and the noncompliance in testing potential HDV carriers presents a significant barrier in active surveillance of changes in the incidence of HDV. Therefore, a study was designed to evaluate the global incidence of HDV using datamining approaches.MethodsDatasets containing yearly HDV and HBV incidence were utilized in this study including the National Health and Nutritional Examination Survey (NHANES) datasets and 14 additional datasets obtained through data-mining of global infectious disease datasets. These global datasets of reported yearly HDV and HBV diagnoses and demographic data ranging between 1999 and 2016 were analyzed.ResultsEpidemiological analysis of infectious disease datasets from 15 countries identified a significant increase in the incidence of HDV relative to HBV-positive patients starting in 2011. Within the United States, analysis of NHANES datasets identified an increase in the incidence of HDV diagnosis among HBV-positive individuals from 5% in 1999–2010 to 58% in 2016. Comparative analysis of the yearly reported incidence of HDV and HBV in 14 additional countries identified a significant increase in the incidence of HDV in the same time period. Modeling of the collective spatiotemporal profile of the increase in HDV incidence is suggestive of a shared common intermittent exposure pattern of infection. The fastest growing demographic in the HDV-positive populations is in patients greater than 65 years of age.ConclusionOur analysis identified a significant increase in the incidence of HDV diagnoses spanning three continents starting in 2011 and may be suggestive of an alteration in HDV transmission pattern. Active surveillance of HDV in the United States and worldwide is warranted to further define these observed changes in HDV incidence.Disclosures All authors: No reported disclosures.

Anal cancer in high-income countries: Increasing burden of disease.

BackgroundPrevious studies have reported that anal cancer incidence has increased in individual countries; however, age-specific trends were not examined in detail. This study describes pooled and country-specific anal cancer incidence trends by sex, age (all ages, <60 and 60+ years) and histological subtype (all subtypes, squamous cell carcinoma [SCC] and adenocarcinoma [ADC]).MethodsFive-year incidence and population-at-risk data were obtained from IARC’s Cancer Incidence in Five Continents for the years 1988–1992 to 2008–2012. The standardised rate ratios (SRRs) for 2008–2012 vs 1988–1992 and the 5-year average percent change (AvPC) during the period were used to assess changes in the age-standardised incidence rates.ResultsDuring the study period, there were significant increases in the incidence of SCC in both men and women of all age groups with significant increasing trend, and these increases were highest in those aged <60 years (SRR = 2.34 [95% CI:2.11–2.58] in men and SRR = 2.76 [95% CI:2.54–3.00] in women). By contrast, there were significant decreases in the incidence of ADC in men and women of all ages (SRR = 0.60 [95% CI:0.54–0.67]) and (SRR = 0.63 [95% CI:0.56–0.71], respectively), with similar decreases in those aged <60 years and 60+ years. These competing trends still resulted in significant increases in the overall incidence of anal cancer in men and women of all ages groups with significant increasing trend. The SRRs in men of all ages, <60 years and 60+ years were 1.35 (95% CI:1.28–1.42), 1.77 (95% CI:1.62–1.92) and 1.08 (95% CI:1.00–1.15), respectively. The corresponding SRRs in women were 1.75 (95% CI:1.67–1.83), 2.31 (95% CI:2.14–2.48) and 1.38 (95% CI 1.31–1.46), respectively.ConclusionIncreases in the incidence of anal SCC has driven an overall increase in anal cancer incidence; this may be associated with changing sexual behaviours and increasing levels of HPV exposure in younger cohorts. The findings further reinforce the importance of HPV vaccination.

1646P - Carcinosarcoma: Clinical and epidemiological patterns in the United States

Background: Carcinosarcomas are rare tumors that comprise microscopic features of both epithelial tumors (carcinomas) and connective tissue tumors (sarcomas). Data about carcinosarcoma are relatively scarce. In this study, data about carcinosarcoma in the SEER’s database were explored and further analyzed and summarized. SEER incorporates clinical and epidemiological data from 18 cancer registries all over the United States and presented data can be extrapolated to generate evidence on this rarely occurring tumor. Methods: SEER*Stat Version 8.3.5 was used to obtain data from the SEER 18 Regs Nov 2017 Submission database. Cases diagnosed between 2000-2015 with carcinosarcoma (ICD-O-3 8980/3, 8981/3) were included. Both SEER*Stat and SPSS were used for further data analysis. Results: A total of 8365 patients were diagnosed with carcinosarcoma between 2000 and 2015, with a median age of 68. The disease occurred predominantly in females (n = 7578; 90.6%) and was more common in white race (n = 6231; 74.5%). Incidence rate was 6.2 per million (CI: 6.1-6.3) with a significant increase of incidence over time (annual percent change = 6.1%) The most common sites for occurrence were the corpus uteri (n = 4656; 55.7%) and ovary (n = 1100; 13.2%) followed by other part of the female genital system (n = 886; 10.6%). The disease was the only primary tumor in 5969 (71.4%) of cases, and the first of 2 or more primaries in 493 patients (8.3%). It occurred as a second or later multiple primary in the remaining percentage of patients (n = 1903; 22.7%). Median survival was 20.5 months, with 5-years and 10-years observed survival being 30.6% (CI: 29.3-31.9%) and 22.4% (CI: 21-23.8%) respectively. Relative survival at 5 years and 10 years was 34.5% (CI: 33.1-36%) and 29.5% (CI: 27.7-31.3%) respectively. Conclusions: Carcinosarcoma is a rare tumor that occurs with an incidence rate of 6.2 per million. It is predominantly a disease of females who represents 90.6% of cases with female genital system being the main site of occurrence. The disease occurred as a second (or later) primary in 22.7% of patients. It has a median survival of 20.5 months and a relative 5-years survival of 34.5%. Legal entity responsible for the study: Mohamed Alaa Gouda. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.

Effect of hemodialysis on blood ammonia level among cirrhotic patients undergoing hemodialysis

Background: Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known while their effects on blood ammonia are unknown and were explored here. Methods: Blood samples were obtained from 56 hemodialysis patients (immediately before and after dialysis). Blood levels of ammonia, creatinine, arterial blood gases, and electrolytes were measured. Results: There was significant fall in serum creatinine following hemodialysis with significant increase in blood ammonia. Moreover, cirrhotic patients with high-bicarbonate showed a significant more increase in ammonia and significant increase in incidence of hyper-ammonemia to that of non-cirrhotic and low-bicarbonate. Furthermore, the increase in serum bicarbonate showed a significant correlation to the change of blood ammonia following dialysis. Conclusion: The fall in blood creatinine concentration following hemodialysis is paradoxically accompanied by a rise in blood ammonia in hemodialysis subjects, contrasting the reported effect on breath ammonia. The mechanism of the post-hemodialysis rise in blood ammonia may be due alkalotic change in PH. The observed rise in blood ammonia level was directly related to the rise in blood bicarbonate and with aggravation of alkalotic state in cirrhotic patients. The rise in blood bicarbonate is associated with increased incidence of hyper-ammonemia among cirrhotic patients.

Incidence and Survival of Thyroid Cancer in Children, Adolescents, and Young Adults in Denmark: A Nationwide Study from 1980 to 2014.

Thyroid cancer constitutes a major and increasing proportion of head and neck cancers in children and adolescents. The purpose of this study was to determine the incidence and survival of thyroid cancer in Danish patients aged 0-24 years from 1980 to 2014. Patients aged 0-24 years registered with primary thyroid cancer in the Danish Cancer Registry or the Danish Pathology Data Bank during 1980-2014 were included. Crude incidence rates and age-adjusted incidence rates (AAIR) per 100,000, average annual percent change (AAPC), and overall survival (OS) were evaluated in relation to sex, histopathological tumor type, age at diagnosis, and year of diagnosis. A total of 297 thyroid cancer patients (72% female, 72% papillary carcinoma) were identified. The AAIR per 100,000 increased significantly from 0.36 in 1980 to 0.97 in 2014, with an AAPC of 2.9%. There was no significant increase in incidence among children and adolescents (0-17 years). However, among young adults (18-24 years), a significant increase in incidence was observed (AAPC 3.7%). The incidence of thyroid cancer increased with age from 0.05 among infants aged 0 years to 1.73 among young adults aged 24 years. Female patients and papillary carcinoma showed significant increase in incidence (AAPC 3.3% and 3.2%), whereas male patients and other histopathological tumor types showed no change. The 15-year OS was 99%. The lowest 15-year OS was observed among patients with medullary carcinomas at 96%. There was no significant difference in OS between groups based on histopathological tumor type, and there was no significant change in OS over time. In this nationwide study, no change in OS was observed, but a significant increase was seen in the incidence of thyroid cancer among young adults (aged 18-24 years), mainly attributed to an increase among females and patients with papillary carcinoma. No increase in incidence was seen among children and adolescents. These findings demonstrate the excellent prognosis for children and adolescents diagnosed with thyroid cancer.