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37 Background: While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery(CRS) and heated intraperitoneal chemotherapy(HIPEC), liver resection(LR) is increasingly performed concomitantly with CRS/HIPEC. As this practice continues to expand, identification of preoperative factors associated with poor outcomes is paramount. Methods: Patients from the US HIPEC Collaborative(2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival(OS). Results: 658 patients were included. Average age was 54 years and 45% were male; 83 (15%) underwent liver resection of colorectal (58%) or invasive appendiceal (42%) metastases. Liver resection patients had more complications (81 vs 60%; p = 0.001), greater number of complications (2.3 vs 1.5; p < 0.001), and required more reoperations (22 vs 11%; p = 0.007) and readmissions (39 vs 25%; p = 0.014) than non-liver resection patients. Liver resection patients had decreased OS (2-year OS 62% vs 79%, p < 0.001), which persisted on multivariable Cox regression when accounting for PCI and histology type. Preoperative factors associated with decreased OS on multivariable analysis in patients undergoing liver resection included age < 60 years (HR:3.61), colorectal histology (HR:3.84), and multiple liver tumors (HR:3.45) (all p < 0.05). When assigning one point for each factor, there was an incremental decrease in 2-yr survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%; p < 0.001). Conclusions: As concurrent liver resection with CRS/HIPEC has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC with liver resection. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in overall survival.

184 Background: Patient age is often a significant factor in preoperative selection for major abdominal surgery. Its association with postoperative outcomes in patients undergoing cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) remains ill-defined. Methods: The US HIPEC Collaborative database(2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC. Age was categorized into < 65 or >65yrs. Primary outcomes were postoperative major complications, readmission, 30-day mortality, and non-home discharge(NHD). Analysis was stratified by disease histology: non-invasive(appendiceal LAMN/HAMN), and invasive(appendiceal/colorectal adenocarcinoma). Results: Of 1090pts identified, 22% were >65yrs(n = 240), 59% were female(n = 646), 25% had non-invasive(n = 276) and 51% had invasive(n = 555) histology. Median PCI was 13(IQR7-20). Patients >65yrs had a higher rate of major complications(37vs26%, p = 0.02), readmission(28vs22%,p = 0.05), 30-day mortality(3vs1%,p = 0.02), and NHD(12vs5%,p < 0.01) compared to those < 65yrs. On multivariable analysis accounting for extent of disease as measured by PCI, for non-invasive histology, age >65yrs was an independent predictor for NHD(OR:2.54,95%CI:1.08-5.99,p = 0.03), but not major complications. For invasive histology, even when accounting for PCI, age >65yrs was an independent predictor for both NHD(OR:2.54,95%CI:1.08-5.98,p = 0.03) and major complications(OR:2.04,95%CI:1.16-3.59,p = 0.05). Age was not associated with hospital readmission or 30-day mortality for any histology. Conclusions: Regardless of histology, patients >65yrs are nearly at three-fold increased risk for non-home discharge after CRS/HIPEC. For invasive histology, age >65yrs is also associated with increased major complication rates, but the procedure seems to be better tolerated when performed for indolent biology. These data inform preoperative counseling and risk stratification. Early planning for discharge disposition in this high-risk population can potentially translate to cost savings.

AbstractDespite the identification of acquired genetic mutations associated with Myeloproliferative Neoplasms (MPNs) there is a paucity of information relating to modifiable risk factors that may lead to these mutations. The MOSAICC Study was an exploratory case‐control study of polycythemia vera (PV), essential thrombocythemia (ET), and Myelofibrosis (MF). MPN patients and population controls (identified by General Practitioners) and non‐blood relative/friend controls were recruited from 2 large UK centers. Participants completed a telephone‐based questionnaire analyzed by unconditional logistic regression analysis adjusting for potential confounders. Risk factors for MPNs identified included increasing childhood household density [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.16–5.62], low childhood socioeconomic status (OR 2.30, 95%CI 1.02–5.18) and high pack years smoking (OR 2.19, 95%CI 1.03–4.66) and current smoking restricted to JAK2 positive PV cases (OR 3.73, 95%CI 1.06–13.15). Obesity was linked with ET (OR 2.59, 95%CI 1.02–6.58) confirming results in previous cohort studies. Receipt of multiple CT scans was associated with a strongly increased risk of MPN although with wide confidence intervals (OR 5.38, 95%CI 1.67–17.3). Alcohol intake was inversely associated with risk of PV (OR 0.41, 95%CI 0.19–0.92) and ET (OR 0.48, 95%CI 0.24–0.98). The associations with childhood household density, high pack years smoking and alcohol were also seen in multivariate analysis. This is the largest case control study in MPNs to date and confirms the previously reported associations with obesity and cigarette smoking from cohort studies in addition to novel associations. In particular, the role of smoking and JAK2 mutation cases merits further evaluation.

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, encouraging patients to ask questions to facilitate their consultation with their physician. Aim: The aim of this study was to develop a QPL specific to adults with gastroesophageal reflux disease (GERD), created by esophageal experts. Methods: The QPL content (78 questions) was derived through a modified Delphi method consisting of 2 rounds. In round 1, 18 esophageal experts provided 5 answers to the prompt “What you wish your patients would ask” and “What questions do patients often not ask, that I wish they would ask?” In round 2, the experts rated each question on a 5-point Likert scale, and responses rated as “essential” or “important,” determined by an a priori threshold of ≥4.0, were accepted for the QPL. Results: Twelve esophageal experts participated. Of 143 questions from round 1, 110 (76.9%) were accepted for inclusion in the QPL, meeting a median value of ≥4.0, and, subsequently, it reduced to 78, minimizing redundancy. Median values ranged between 4.0 and 5.0, with the highest agreement median (5.0) for questions asking dosing and timing of proton pump inhibitor therapy, and surveillance in Barrett’s. Questions were categorized into the following categories: “What does this illness mean,” “lifestyle modifications,” “general treatment,” “treatment with proton pump inhibitors,” “What I should expect for my future,” and “Barrett’s.” The largest number of questions covered lifestyle modifications (21.8%), with the highest agreement median (5.0) for “How helpful are lifestyle modifications in GERD?” Conclusions: A preliminary GERD-specific QPL, the first of its kind, was developed by esophageal experts. Modification after more patient consultation and feedback is planned in subsequent versions to create a GERD-QPL for eventual use in clinical gastroenterology.

AbstractIntroductionWe aimed to expand on the global surgical discussion around splenic trauma in order to understand locally and clinically relevant factors for operative (OP) and non‐operative management (NOM) of splenic trauma in a South African setting.MethodsA retrospective cohort study was performed using 2013–2017 data from the Pietermaritzburg Metropolitan Trauma Service. All adult patients (≥15 years) were included. Those managed with OP or NOM for splenic trauma were identified and analyzed descriptively. Multiple logistic regression analysis identified patients and clinical factors associated with management type.ResultsThere were 127 patients with splenic injury. Median age was 29 [19–35] years with 42 (33%) women and 85 (67%) men. Blunt injuries occurred in the majority (81, 64%). Organ Injury Scale (OIS) grades included I (25, 20%), II (43, 34%), III (36, 28%), IV (15, 11%), and V (8, 6%). Nine patients expired. On univariate analysis, increasing OIS was associated with OP management, need for intensive care unit (ICU) admission, and hospital and ICU duration of stay, but not mortality. In patients with a delayed compared to early presentation, ICU utilization (62% vs. 36%, p = 0.008) and mortality (14% vs. 4%, p = 0.03) were increased. After adjusting for age, sex, presence of shock, and splenic OIS, penetrating trauma (adjusted odds ratio, 5.7; 95%CI, 1.7–9.8) and admission lactate concentration (adjusted odds ratio, 1.4; 95%CI 1.1–1.9) were significantly associated with OP compared to NOM (p = 0.002; area under the curve 0.81).ConclusionsWe have identified injury mechanism and admission lactate as factors predictive of OP in South African patients with splenic trauma. Timely presentation to definitive care affects both ICU duration of stay and mortality outcomes. Future global surgical efforts may focus on expanding non‐operative management protocols and improving pre‐hospital care in patients with splenic trauma.

AbstractObjectiveTo address knowledge gaps regarding burdens associated with not adequately controlled chronic hypoparathyroidism.DesignGlobal patient and caregiver survey.Study PopulationsPatients with chronic hypoparathyroidism not adequately controlled on conventional therapy and their caregivers.MeasurementsHealth‐related quality of life (HRQoL) and health status were evaluated using the 36‐item Short Form version 2 (SF‐36 v2.0) and Five‐Level EuroQoL 5 Dimensions (EQ‐5D‐5L) instruments, respectively. Hypoparathyroidism‐associated symptoms were assessed by a disease‐specific Hypoparathyroidism Symptom Diary and caregiver burden via the Modified Caregiver Strain Index (MCSI).ResultsData were obtained from 398 patients and 207 caregivers. Patients' self‐rated hypoparathyroidism‐related symptom severity was none (3%), mild (32%), moderate (53%) or severe (12%). Per the Hypoparathyroidism Symptom Diary, patients reported moderate, severe or very severe symptoms of physical fatigue (73%), muscle cramps (55%), heaviness in limbs (55%) and tingling (51%) over a 7‐day recall period. Impacts (rated ‘somewhat’ or ‘very much’) were reported by 84% of patients for ability to exercise, 78% for sleep, 75% for ability to work and 63% for family relationships. Inverse relationships were observed between patient self‐rated overall symptom severity and HRQoL and health status assessment scores—the greater the symptom severity, the lower the SF‐36 and EQ‐5D‐5L scores. Caregiver burden increased with patient self‐rated symptom severity: none, 1.7 MCSI; mild, 5.4 MCSI; moderate, 9.5 MCSI; and severe, 12.5 MCSI.ConclusionPatients with not adequately controlled hypoparathyroidism reported substantial symptoms and impacts. Greater patient symptom severity was associated with decreased patient HRQoL and health status assessments and increased caregiver burden.

Abstract BACKGROUND The Tumor Treating Fields (TTF) mechanism of action is hypothesized act upon mitosis by disrupting the cell spindle apparatus. However, biomarkers and human tissue correlation of the effect of the TTF device are lacking. CASE: A 41 year-old previously healthy woman was found to have a right frontoparietal glioblastoma after she developed subacute onset of left hemiparesis and headache. The tumor was IDH wild type MGMT promoter unmethylated and TERT mutated. Chromosomal Microarray (CMA) was performed and demonstrated genome wide aneuploidy primarily characterized by hyperdiploidy. She underwent a gross total resection of the enhancing portion of the tumor and subsequent standard chemoradiotherapy (60 Gy IMRT with concomitant temozolomide) followed by initiation of the TTF device and adjuvant temozolomide. Six months after diagnosis, after 72 days of using the TTF device with 75% compliance and completion of the third cycle of temozolomide the patient had radiographic recurrence. She underwent a repeat resection. Pathology demonstrated recurrent tumor. Genetic analysis no longer demonstrated chromosomal losses or gains: the tumor was diploid. DISCUSSION This case may be a demonstration of effect of the TTF device applying a selective pressure to cells with multiple chromosomal gains and losses as the efficiency of mitosis in these cells may already be severely compromised. We are currently performing CMA on all patients with available tissue treated with the TTF device at our institution, with a planned retrospective analysis to explore this hypothesis further. CONCLUSION Repeat resection with detailed genetic analysis of GBM recurrence after therapies may help generate hypotheses regarding mechanisms of resistance, and in this case, mechanisms of action of the TTF.

OBJECTIVES: Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy ). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE). METHODS: Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy. RESULTS: One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than in T2DM; however, triopathies (all 3 complications together) were seen in 10% of T1DM and 3% of T2DM ( P = 0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36% vs 10%; P = 0.006) and number of diabetic complications (1.0 vs 0.5; P = 0.009); however, 39% of diabetic patients with delayed GE did not have any diabetic complications. DISCUSSION: In diabetic patients with symptoms of Gp, delayed GE was associated with the presence of retinopathy and the total number of diabetic complications. Only 10% of patients with T1DM and 3% of those with T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have any diabetic complications. Thus, the presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.

Abstract Background: Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients; however, there are concerns that ESAs increase mortality in some patients. Within the framework of an international collaboration we thus conducted a patient-level meta-analysis to assess the effects of ESAs on mortality in cancer patients. Methods: We performed a meta-analysis, based on the intention-to-treat principle, of cancer patients enrolled in randomized controlled trials comparing epoetin alfa, epoetin beta or darbepoetin alfa plus red blood cell transfusions as needed versus transfusion alone, for prophylaxis or treatment of anemia while or after receiving anticancer therapy. Patient-level data were obtained and analyzed by independent statisticians at two academic departments. Primary endpoints were on-study mortality and overall survival in patients receiving chemotherapy, defined as all patients from studies in which =/> 70% of study population received chemotherapy, and in all cancer patients regardless of anticancer therapy. On-study mortality was defined as death from any cause between date of randomization and 28 days after end of active study phase. Overall survival was defined as death from any cause between date of randomization and longest follow up available. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated per study and meta-analyzed with fixed-effects and random-effects models. Stratified multivariable Cox-regression analyses were conducted to assess the impact of baseline imbalances. Tests for interactions were used to identify differences in effect across pre-specified subgroups. All analyses were pre-specified in a peer-reviewed protocol (Bohlius et al. 2008). An independent steering committee consisting of clinicians and methodologists agreed on all analyses and interpretations. Independent investigators and representatives from manufacturers contributing data offered advice, but had no decision-making authority. Results: Data from 13,933 cancer patients enrolled in 53 studies were included in the analysis; 38 trials including 10,441 patients used mainly chemotherapy. Including all cancer patients ESAs increased on-study mortality by 17% (HR 1.17; 95% CI 1.06–1.30), with little evidence for a difference between chemotherapy and other trials (p for interaction=0.42), and worsened overall survival by 6% (HR 1.06; 95% CI 1.00–1.12). In the chemotherapy population on-study mortality was increased by 10% (HR 1.10, 95% CI 0.98–1.24) and overall survival was worsened by 4% (HR 1.04; 95% CI 0.97–1.11). Adjusting for known prognostic factors had little effect on the overall estimates. There was no conclusive evidence for effect modification by patient level characteristics such as age, sex, Hb and Hct at baseline, Hb ceiling, type and stage of tumor or study level characteristics (anticancer treatment, ESA treatment schedules, study design and quality) for the outcomes tested. Conclusion: ESA treatment in cancer patients increased on-study mortality by 17% and worsened overall survival by 6%. For patients undergoing chemotherapy the increase was less pronounced, but could not be excluded. In clinical practice, risks of ESAs must be balanced against benefits of ESAs depending on the clinical circumstances of the individual patient.

Abstract Introduction The Classic Myeloproliferative Neoplasms (MPNs), characterised by an over production of one or more cells of the myeloid lineage, are classified into polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF). Despite the identification of numerous genetic mutations, a paucity of information relating to medical and lifestyle factors contributing to the aetiology of these diseases remains. Methods The MOSAICC Study was an exploratory case-control study of MPNs. MPN patients were recruited between two sites, Belfast and Southampton, in preparation for a planned UK-wide investigation. Population controls (identified by General Practitioners) and non-blood relative/friend controls were also recruited. Participants completed a telephone-based questionnaire seeking information on a range of medical, environmental, lifestyle and occupational risk factors. Risk factors were assessed using unconditional logistic regression with adjustment for potential confounders. Results Risk factors identified included smoking [≥25 pack years vs. never: odds ratio (OR) 3.14, 95% confidence interval (CI) 1.26-7.87], increasing childhood household density [>2 vs <1 Child(ren)/room: OR 3.29, 95% CI 1.31-8.30], history of heart disease (OR 3.31, 95% CI 1.23-8.87), CT scans (≥3 vs. none: OR 4.92, 95% CI 1.55-15.67), having an implant (OR 10.77, 95% CI 1.01-3.10), and pig ownership (OR 5.92, 95% CI 1.17-29.92). Alcohol was associated with a reduced risk of MPNs (OR 0.49, 95% CI 0.28-0.88) as was home working on car exhausts (OR 0.33, 95% CI 0.12-0.88), painting at home (OR 0.49, 95% CI 0.28-0.86) and short haul air travel (p for trend 0.012). Participants working in occupations with high exposure to environmental tobacco smoke had an excess risk of MPN (OR 2.45, 95% CI 1.12-5.37). Work-based radiation and solvent exposure also appeared to increase risk of MPNs (p<0.05). Conclusions This exploratory study has confirmed a reported association between cigarette smoking and MPNs. It has identified some potential novel risk factors including work-based radiation and solvent exposure. The findings of this study need to be replicated in a larger, adequately powered, study in order to identify important risk factors for the classic MPNs. Conflict of Interest The authors declare no conflict of interest. Acknowledgments: The MOSAICC Study team acknowledges the support of the National Institute for Health Research, through the Northern Ireland Cancer Research Network (NICRN) and for Southampton the Central South Coast Cancer Network (CSCCN). The team thank those who have participated in the MOSAICC study and the personnel who assisted in the recruitment of patients. Disclosures Mesa: CTI Biopharma: Research Funding; Promedior: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Incyte Corporation: Research Funding; Pfizer: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding; Gilead: Research Funding.