A patient's perspective on the side effects of tyrosine kinase inhibitors in the treatment of advanced and metastatic gastrointestinal stromal tumors.

Aim: To provide the gastrointestinal stromal tumor patient's perspective on side effects of tyrosine kinase inhibitors and compare this with that of healthcare professionals. Materials & methods: Semi-structured interviews were conducted with 19 patients with an advanced or metastatic gastrointestinal stromal tumor, as well as six healthcare professionals, and five patients participated in a focus group. Thematic analysis was used to interpret the data. Results: Most participants (n = 29) reported gastrointestinal symptoms followed by tiredness (n = 25), edema (n = 22), muscle cramps (n = 21), skin problems (n = 21), eye problems (n = 11) and trouble sleeping (n = 10). Patients, but not healthcare professionals, reported cognitive problems or symptoms of depression. Conclusion: These results underline the importance of including the patient's perspective, as there is a gap in symptom reporting between patients and healthcare professionals.

In this study, the authors report on the side effects of targeted therapies used in the treatment of gastrointestinal stromal tumors from the patient's perspective and draw comparisons with reports from healthcare professionals. The authors conducted interviews with both patients and healthcare professionals. Most participants reported gastrointestinal symptoms followed by tiredness, fluid retention, muscle cramps, skin problems, eye problems and trouble sleeping. Gastrointestinal stromal tumor patients reported cognitive problems and symptoms of depression, which were not reported by healthcare professionals. In conclusion, the authors' results highlight the importance of including the patient's perspective, as there is a gap in symptom reporting between patients and healthcare professionals.

International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

Health-related quality of life scores of metastatic pancreatic cancer patients responsive to first line chemotherapy compared to newly derived EORTC QLQ-C30 reference values.

BACKGROUND: Metastatic pancreatic cancer (mPC) and its treatments significantly impact health-related quality of life (HRQoL). POLO, a randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy of olaparib as maintenance therapy in germline BRCA mutated mPC patients who had not progressed during ≥16 weeks of first-line platinum-based chemotherapy. HRQoL was assessed using the EORTC QLQ-C30. To enhance score interpretation, we derived reference values for treatment-naïve mPC patients from the literature. METHODS: A targeted literature review identified EORTC QLQ-C30 baseline values in treatment-naïve mPC patients. Reference values were calculated by deriving means from studies meeting inclusion criteria, with scores from 0 to 100 (higher scores indicate better QoL/functioning but worse symptoms). For POLO patients, means were calculated using pooled baseline data across study arms. RESULTS: Four studies met inclusion criteria. Depending on the specific scale, sample sizes ranged from n = 466 to n = 639. Compared to newly derived reference values, POLO patients reported markedly better HRQoL scores at baseline across most scales, with eight scales showing differences of ≥10 points. POLO patients' HRQoL scores were often close to or better than general population norm data. CONCLUSIONS: This is the first study to systematically derive EORTC QLQ-C30 reference values for mPC. POLO patients had better HRQoL scores than those in the literature and similar to general population data. Comparatively high HRQoL of POLO patients are likely due to effects of prior first-line treatment and resolution of chemotherapy-related symptoms, response shift, or a combination. Newly derived reference values can enhance interpretation of mPC patients' HRQoL. TRIAL REGISTRATION: The POLO trial was registered on 9 July 2014 with ClinicalTrials.gov as NCT02184195.

Evaluation of increased fiber, decreased amino acids, or decreased electrolyte balance as dietary approaches to slow finishing pig growth rates.

In swine production, pig movement restrictions or packing plant closures may create the need to slow growth rates of finishing pigs to ensure they remain at a marketable body weight when packing plant access is restored. Although dietary formulations can be successful at slowing pig growth, precision is needed regarding how to best formulate diets to achieve growth rate reductions. Thus, the objective was to evaluate three dietary experimental approaches aimed at slowing growth rates in finishing pigs. These approaches consisted of either increasing neutral detergent fiber (NDF), reducing essential amino acids, or reducing the dietary electrolyte balance through the addition of acidogenic salts. A total of 94 mixed-sex pigs (72.4 ± 11.2 kg BW) across two replicates were individually penned and assigned to 1 of 8 dietary treatments (n = 11-12 pigs/treatment): 1) Control diet representative of a typical corn-soybean meal-based finisher diet (CON); 2) diet containing 15% NDF from soybean hulls (15% NDF); 3) diet containing 20% NDF from soybean hulls (20% NDF); 4) diet containing 25% NDF from soybean hulls (25% NDF); 5) diet formulated as per CON but with 50% of the soybean meal replaced with corn (89% Corn); 6) diet containing 97% corn and no soybean meal or synthetic amino acids (97% Corn); 7) diet containing 2% anhydrous calcium chloride (2% CaCl2); and 8) diet containing 4% anhydrous calcium chloride (4% CaCl2). Over 28 d, pig body weights and performance were recorded weekly. At d 28, all pigs were ultrasound scanned and switched to the CON diet to evaluate compensatory gain from d 28 to 35. Overall, increased NDF did not impact any growth performance parameter (P > 0.05). Amino acid restriction reduced average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F) linearly (linear P < 0.001). Similarly, ADG, ADFI, and G:F were linearly reduced with increased CaCl2 inclusion (linear P < 0.001). ADG differed during the compensatory gain period (P < 0.001), with 4% CaCl2-fed pigs having a 47% increase in ADG compared with CON-fed pigs. Conversely, 15% and 25% NDF-fed pigs had reduced ADG compared with CON-fed pigs during the compensatory gain period. Gain efficiency differed from day 28 to 35 (P < 0.001), with 4% CaCl2-fed pigs having a 36% increase in G:F compared with CON-fed pigs. Altogether, these data demonstrate that both amino acid restriction and CaCl2 inclusion are effective at slowing pig growth, albeit at greater inclusion rates.

Developing Symptom Lists for People with Cancer Treated with Targeted Therapies.

BACKGROUND: Targeted therapies (TTs) have revolutionised cancer treatment with their enhanced specificity of action. Compared with conventional therapies, TTs are delivered over a longer period and often have unusual symptom profiles. Patient-reported outcome measures such as symptom side-effect lists need to be developed in a time-efficient manner to enable a rapid and full evaluation of new treatments and effective clinical management OBJECTIVE: The aim of this study was to develop a set of TT-related symptoms and identify the optimal method for developing symptom lists. PATIENTS AND METHODS: Symptoms from TT treatment in the context of Chronic Myeloid Leukaemia (CML), HER2-positive breast cancer, or Gastrointestinal Stromal Tumours (GIST) were identified through literature reviews, interviews with healthcare professionals (HCPs) and patients, and patient focus groups. The symptom set was then pilot tested in patients across the three cancer diagnoses: The number of items derived from each source (literature, patients, or HCPs) were compared. RESULTS: A total of 316 patients and 86 HCPs from 16 countries participated. An initial set of 209 symptoms was reduced to 61 covering 12 symptom categories. Patient interviews made the greatest contribution to the item set. CONCLUSIONS: Symptom lists should be created based on input from patients. The item set described will be applicable to the assessment of new TTs, and in monitoring treatment.

Psychometric properties of the updated EORTC module for assessing quality of life in patients with lung cancer (QLQ-LC29): an international, observational field study.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) assesses quality of life (QOL) in patients with lung cancer and was the first EORTC module developed for use in international clinical trials. Since its publication in 1994, major treatment advances with possible effects on QOL have occurred. These changes called for an update of the module and its international psychometric validation. We aimed to investigate the scale structure and psychometric properties of the updated lung cancer module, QLQ-LC29, in patients with lung cancer. METHODS: This international, observational field study was done in 19 hospitals across 12 countries. Patients aged older than 18 years with a confirmed diagnosis of lung cancer and no other previous primary tumour, and who were mentally fit with sufficient language skills to understand and complete the questionnaire were included. Patients were asked during a hospital visit to fill in the paper versions of the core questionnaire EORTC QLQ-C30 plus QLQ-LC29, and investigators selected half of these patients to complete the questionnaire again 2-4 weeks later. Our primary aim was to assess the scale structure and psychometric properties of EORTC QLQ-LC29. We analysed scale structure using confirmatory factor analysis; reliability using Cronbach's α value (internal consistency) and intra-class coefficient (test-retest reliability); sensitivity using independent t tests stratified by Karnofsky performance status; and responsiveness to change over time by ANOVA. This study is registered with ClinicalTrials.gov, NCT02745691. FINDINGS: Between April 12, 2016, and Sept 26, 2018, 523 patients with a confirmed diagnosis of either non-small-cell lung cancer (n=442) or small-cell lung cancer (n=81) were recruited. Confirmatory factor analysis provided a solution composed of five multi-item scales (coughing, shortness of breath, fear of progression, hair problems, and surgery-related symptoms) plus 15 single symptom or side-effect items: χ2=370·233, root mean square error of approximation=0·075, and comparative-fit index=0·901. Cronbach's α for internal consistencies of all multi-item scales were above the threshold of 0·70. Intra-class coefficients for test-retest reliabilities ranged between 0·82 and 0·97. Three (shortness of breath, fear of progression, and hair problems) of the five multi-item scales showed responsiveness to change over time (p values <0·05), as did nine of 15 single symptom items. Four (coughing, shortness of breath, fear of progression, and surgery-related symptoms) of the five multi-item scales and ten of the 15 single symptom items were sensitive to known group differences (ie, lower vs higher Karnofsky performance status). INTERPRETATION: Results determined the psychometric properties of the updated lung cancer module, which is ready for use in international clinical studies. FUNDING: EORTC Quality of Life Group.

International validation of the EORTC CAT Core: a new adaptive instrument for measuring core quality of life domains in cancer.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) has developed computerised adaptive tests (CATs) for the 14 functional and symptom domains of the EORTC QLQ-C30 quality of life questionnaire. This is expected to optimise measurement precision, relevance to patients and flexibility. Here, we present the first international validation of the EORTC CAT Core. METHODS: A heterogeneous sample of 699 cancer patients scheduled for chemotherapy and/or radiotherapy was recruited across seven European countries. The EORTC CAT Core and all QLQ-C30 items were administered to participants before and after initiating treatment. Correlations between CAT and QLQ-C30 scores and floor/ceiling effects were calculated. Using several grouping variables, relative validity (cross-sectional known groups difference), responsiveness (changes over time) and relative sample size requirements of the CAT compared to the QLQ-C30 were estimated. RESULTS: Correlations of the CAT and QLQ-C30 ranged from 0.81 to 0.93 across domains. The mean relative reduction in floor and ceiling effects using the CAT was 42% (range 3-99%). Analyses of known groups validity and responsiveness indicated that, across domains, mean sample size requirements for the CAT were 72% and 70%, respectively, of those using the QLQ-C30. CONCLUSIONS: The EORTC CAT Core measures the same domains as the QLQ-C30 with reduced floor/ceiling effects. The CAT generally facilitated the use of smaller samples (about 30% smaller on average) without loss of power compared to the QLQ-C30. Based on this study, the EORTC QLG will release the EORTC CAT Core for general use.

Exploring the patient experience of locally advanced or metastatic pancreatic cancer to inform patient-reported outcomes assessment.

PURPOSE: Pancreatic cancer and its treatments impact patients' symptoms, functioning, and quality of life. Content-valid patient-reported outcome (PRO) instruments are required to assess outcomes in clinical trials. This study aimed to: (a) conceptualise the patient experience of pancreatic cancer; (b) identify relevant PRO instruments; (c) review the content validity of mapped instruments to guide PRO measurement in clinical trials. METHODS: Qualitative literature and interviews with clinicians and patients were analysed thematically to develop a conceptual model of patient experience. PRO instruments were reviewed against the conceptual model to identify gaps in measurement. Cognitive debriefing explored PRO conceptual relevance and patients' understanding. RESULTS: Patients in the USA (N = 24, aged 35-84) and six clinicians (from US and Europe) were interviewed. Pre-diagnosis, pain was the most frequently reported symptom (N = 21). Treatments included surgery, radiation, chemotherapy, and immunotherapy. Surgery was associated with acute pain and gastrointestinal symptoms. Chemotherapy/chemoradiation side effects were cyclical and included fatigue/tiredness (N = 21), appetite loss (N = 15), bowel problems (N = 15), and nausea/vomiting (N = 15). Patients' functioning and well-being were impaired. The literature review identified 49 PRO measures; the EORTC QLQ-C30/PAN26 were used most frequently and mapped with interview concepts. Patients found the EORTC QLQ-C30/PAN26 to be understandable and relevant; neuropathic side effects were suggested additions. CONCLUSIONS: This is the first study to develop a conceptual model of patients' experience of metastatic/recurrent pancreatic cancer and explore the content validity of the EORTC QLQ-C30/PAN26 following therapeutic advances. The EORTC QLQ-C30/PAN26 appears conceptually relevant; additional items to assess neuropathic side effects are recommended. A recall period should be stated throughout to standardise responses.

Psychometric evaluation of a patient-reported outcome measure in pancreatic exocrine insufficiency (PEI).

BACKGROUND/OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is commonly caused by chronic pancreatitis (CP) or cystic fibrosis (CF). There are no PEI-specific patient-reported assessments of symptoms and impacts. The PEI Questionnaire (PEI-Q) was developed through qualitative research with PEI patients and expert clinical input. This study evaluated the psychometric properties of the PEI-Q. METHODS: 162 PEI patients (CF = 71 and CP = 91), 62 diarrhoea-specific irritable bowel syndrome (IBS-D) patients and 60 healthy controls completed the 26-item PEI-Q and the Gastrointestinal Quality of Life Index (GIQLI) at baseline. PEI patients completed the measures again two weeks later to assess the test-retest reliability of the PEI-Q. Analyses supported item reduction and scoring algorithm development, followed by psychometric evaluation. RESULTS: Over 90% of PEI patients completed at least 23 of the 26 items at baseline. Item responses and clinical relevance supported retention of 18 items. Factor analysis supported a three-factor solution (abdominal symptoms, bowel movements, impacts) with adequate model fit. PEI-Q scores had good internal consistency (Cronbach's alpha: 0.77-0.82) and test-retest reliability (ICC: 0.73-0.87). Correlations between PEI-Q and GIQLI supported convergent validity. Known-groups and receiver operating characteristic analyses demonstrated that PEI-Q scores discriminated (p < 0.001) between differing PEI severities, and PEI patients and controls. CONCLUSIONS: The PEI-Q has good validity and reliability. Results indicate that the PEI-Q could be used to aid identification and diagnosis of PEI, assist in the management of patients already diagnosed with PEI, ensuring correct and optimum treatment as well as enhance patient-clinician communication.

Effects of dietary chromium propionate on growth performance, metabolism, and immune biomarkers in heat-stressed finishing pigs1.

Study objectives were to determine the effects of chromium (Cr) propionate (Cr propionate 0.04%; 0.5 g/kg of feed to deliver 200 parts per billion Cr/d; KemTRACE Cr, Kemin Industries, Inc., Des Moines, IA) on growth performance, metabolism, and health biomarkers in heat-stressed and nutrient-restricted pigs. Crossbred barrows (n = 96; 105 ± 1 kg BW) were enlisted in an experiment conducted in two replicates, blocked by initial BW, and randomly assigned to one of six dietary-environmental treatments: (i) thermoneutral (TN) and fed ad libitum a control diet (TNCtl), (ii) TN and fed ad libitum a Cr supplemented diet (TNCr), (iii) TN and pair-fed a control diet (PFCtl), (iv) TN and pair-fed a Cr supplemented diet (PFCr), (v) heat stress (HS) and ad libitum fed a control diet (HSCtl), or (vi) HS and ad libitum fed a Cr supplemented diet (HSCr). The study consisted of three experimental periods (P). During P0 (5 d), all pigs were housed in TN conditions (21.3 ± 0.1 °C, 56.8 ± 0.3% relative humidity [RH]) and fed the control diet ad libitum. During P1 (5 d), pigs were fed their respective dietary treatments ad libitum and kept in TN conditions. During P2 (35 d), HSCtl and HSCr-treated pigs were fed ad libitum and exposed to progressive cyclical HS conditions (27 to 31 °C, 50 ± 0.3% RH), while TNCtl, TNCr, PFCtl, and PFCr pigs remained in TN conditions and were fed ad libitum or pair-fed to their respective HSCtl and HSCr counterparts to eliminate the confounding effects of dissimilar feed intake. Overall, HS pigs had increased (P < 0.01) rectal temperature, skin temperature, and respiration rate (0.3 °C, 3.8 °C, and 32 breaths per minute, respectively) relative to TN pigs. Overall, HS decreased ADFI and ADG (20 and 21%, respectively; P < 0.01) compared with TN controls. Final BW tended to be increased in HSCr (2.7 kg, P = 0.06) compared with HSCtl pigs. Similarly, ADG tended to be increased during P2 in HSCr relative to HSCtl-treatment (0.77 vs. 0.72 kg/d; P = 0.10). There were no effects of Cr on most production parameters, but ADFI tended to be increased in Cr relative to Ctl-fed pigs (3.19 vs. 3.09 kg/d; P = 0.08). No effects of Cr supplementation were detected on circulating glucose, insulin, NEFA, cholesterol, triglycerides, or lipopolysaccharide binding protein. However, blood neutrophils were increased in HSCr (37%; P < 0.01) relative to HSCtl pigs. In summary, these results suggest Cr supplementation may benefit growth performance during HS.

International phase IV validation study of an EORTC quality of life questionnaire for testicular cancer patients: the EORTC QLQ-TC26.

BACKGROUND: Given the high cure-rate for testicular cancer (TC) and the patients' young age, comprehensive evaluation of health-related quality of life (HRQOL) is an important consideration in this patient population. The EORTC QLQ-TC26 questionnaire module has been developed to supplement the EORTC QLQ-C30 in assessing TC-specific HRQOL in clinical trials and routine clinical practice. This international, multicentre phase IV validation study evaluated the psychometric properties of the new module. METHODS: This international, multicentre phase IV validation study enrolled testicular cancer patients from seven European countries. Patients completed the EORTC quality of life core questionnaire EORTC QLQ-C30 and the QLQ-TC26 at two consecutive time points and a debriefing questionnaire regarding the QLQ-TC26 after baseline assessment. Psychometric evaluation included examination of the hypothesized module scale structure, internal consistency and test-retest reliability, known-groups validity, responsiveness to change over time and cross-cultural acceptability. RESULTS: Data from 313 patients (mean age 38.6, SD 9.5) were analysed. All items exhibited a high completion rate with less than 2.4% missing values except for the sexuality items (up to 8.8%). The confirmatory factor analysis supported the hypothesised scale structure of the QLQ-TC26. Test-retest reliability was good for 8 of 12 scales (intraclass correlation: R t1|t2 ranged from 0.71-0.91) and four scales did not meet the acceptable criteria. Internal consistency was good for all twelve scales (Cronbach alpha = 0.79-0.90), except Communication (alpha = 0.67) and Sexual Functioning (alpha = 0.62). The module was able to distinguish clearly between patients with differing clinical status. Responsiveness to change over time was acceptable. CONCLUSION: The EORTC QLQ-TC26 is a valid, reliable and well-accepted condition-specific questionnaire, supplementing the EORTC QLQ-C30, for the assessment of testicular cancer patients' HRQOL in clinical trials.

Recurrent Acute Pancreatitis: International State-of-the-Science Conference With Recommendations.

Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research.

Understanding the quality of life (QOL) issues in survivors of cancer: towards the development of an EORTC QOL cancer survivorship questionnaire.

BACKROUND: The number of cancer survivors is growing steadily and increasingly, clinical trials are being designed to include long-term follow-up to assess not only survival, but also late effects and health-related quality of life (HRQOL). Therefore it is is essential to develop patient-reported outcome measures (PROMs) that capture the full range of issues relevant to disease-free cancer survivors. The objectives of this project are: 1) to develop a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire that captures the full range of physical, mental and social HRQOL issues relevant to disease-free cancer survivors; and 2) to determine at which minimal time since completion of treatment the questionnaire should be used. METHODS: We reviewed 134 publications on cancer survivorship and interviewed 117 disease-free cancer survivors with 11 different types of cancer across 14 countries in Europe to generate an exhaustive, provisional list of HRQOL issues relevant to cancer survivors. The resulting issue list, the EORTC core questionnaire (QLQ-C30), and site-specific questionnaire modules were completed by a second group of 458 survivors. RESULTS: We identified 116 generic survivorship issues. These issues covered body image, cognitive functioning, health behaviors, negative and positive outlook, health distress, mental health, fatigue, sleep problems, physical functioning, pain, several physical symptoms, social functioning, and sexual problems. Patients rated most of the acute symptoms of cancer and its treatment (e.g. nausea) as no longer relevant approximately one year after completion of treatment. CONCLUSIONS: Compared to existing cancer survivorship questionnaires, our findings underscore the relevance of assessing issues related to chronic physical side effects of treatment such as neuropathy and joint pain. We will further develop a core survivorship questionnaire and three site-specific modules for disease-free adult cancer survivors who are at least one year post-treatment.

Intestinal Fatty Acid Binding Protein as a Marker of Necrosis and Severity in Acute Pancreatitis.

OBJECTIVES: The aim of this study was to study intestinal fatty acid binding protein (i-FABP) as a potential biomarker in predicting severity of acute pancreatitis (AP). METHODS: In a prospective multicenter cohort study, plasma levels of i-FABP were measured in 402 patients with AP. Severity of AP was determined based on the 1992 Atlanta Classification. RESULTS: Admission levels of plasma i-FABP were significantly higher in patients with pancreatic necrosis, in patients having systemic complications, in patients treated invasively, in patients treated in the intensive care unit, in patients with severe AP, and in deceased patients. Plasma i-FABP levels on admission yielded an area under curve (AUC) of 0.732 in discriminating patients with or without pancreatic necrosis and AUC of 0.669 in predicting severe AP. Combination of levels of i-FABP and venous lactate on the day of admission showed higher discriminative power in severe AP-AUC of 0.808. CONCLUSIONS: Higher i-FABP levels on admission were associated with pancreatic necrosis, systemic complications, and severe AP. Low levels of i-FABP had a high negative predictive value for pancreatic necrosis and severe AP. Combination of levels of i-FABP and venous lactates on admission were superior to either of markers used alone in predicting severe AP.

Surgeons' assessment versus risk models for predicting complications of hepato-pancreato-biliary surgery (HPB-RISC): a multicenter prospective cohort study.

BACKGROUND: Several studies advise the use of risk models when counseling patients for hepato-pancreato-biliary (HPB) surgery, but studies comparing these models to the surgeons' assessment are lacking. The aim of this study was to assess whether risk prediction models outperform surgeons' assessment for the risk of complications in HPB surgery. METHODS: This prospective study included adult patients scheduled for HPB surgery in three centers in the UK and the Netherlands. Primary outcome was the rate of postoperative major complications. Surgeons assessed the risk prior to surgery while blinded for the formal risk scores. Risk prediction models were retrieved via a systematic review and risk scores were calculated. For each model, discrimination and calibration were evaluated. RESULTS: Overall, 349 patients were included. The rate of major complications was 27% and in-hospital mortality 3%. Surgeons' assessment resulted in an AUC of 0.64; 0.71 for liver and 0.56 for pancreas surgery (P = 0.020). The AUCs for nine existing risk prediction models ranged between 0.57 and 0.73 for liver surgery and between 0.51 and 0.57 for pancreas surgery. CONCLUSION: In HPB surgery, existing risk prediction models do not outperform surgeons' assessment. Surgeons' assessment outperforms most risk prediction models for liver surgery although both have a poor predictive performance for pancreas surgery. REGISTRATION INFORMATION: REC reference number (13/SC/0135); IRAS ID (119370). TRIALREGISTER.NL: NTR4649.

Factors Influencing Global Health Related Quality of Life in Elderly Cancer Patients: Results of a Secondary Data Analysis.

Cancer treatment for elderly patients is often complicated by poor physical condition, impaired functioning and comorbidities. Patient reported health related quality of life (HRQOL) can contribute to decisions about treatment goals and supportive therapy. Knowledge about factors influencing HRQOL is therefore needed for the development of supportive measures and care pathways. An exploratory secondary data analysis on 518 assessments of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC QLQ-C30) and the elderly module (EORTC QLQ-ELD14) was performed to identify factors predictive for global HRQOL. Preliminary simple and multivariable regression analyses were conducted resulting in a final model comprising sociodemographic and disease specific variables and scales of the QLQ-C30 and QLQ-ELD14. Age, sex and disease related variables explained only part of the variance of global HRQOL (adjusted R2 = 0.203). In the final model (adjusted R2 = 0.504) fatigue, social function, burden of illness and joint stiffness showed possible influence on global HRQOL. Fatigue, social function and burden of illness seem to have the largest impact on global HRQOL of elderly cancer patients. Further prospective studies should examine these domains. Actionable symptoms should be given special attention to initiate targeted supportive measures aiming to maximize HRQOL of older cancer patients.

Phase I-III development of the EORTC QLQ-ANL27, a health-related quality of life questionnaire for anal cancer.

BACKGROUND AND PURPOSE: There is currently no health-related quality of life (HRQoL) measure specific to anal cancer. Our objective was to develop an anal cancer HRQoL module to supplement the EORTC QLQ-C30 questionnaire using EORTC Quality of Life Group Guidelines. MATERIALS AND METHOD: In order to generate a list of HRQoL issues facing anal cancer patients treated with chemoradiotherapy (CRT), we systematically reviewed the literature and conducted semi-structured interviews with patients and health care professionals (HCPs). Our list was then operationalised into questions using the EORTC Item Library. The provisional question list was pilot tested alongside the EORTC QLQ-C30 with patients from 11 centres across 8 countries. RESULTS: From our literature review and interviews with 43 patients, we generated a list of 197 issues. The list was then refined to 134 issues and reviewed by 34 HCPs and 10 patients. This review resulted in the retention of 65 issues which were used in the draft questionnaire tested by 100 patients. Our analyses led to the modification and removal of questions resulting in a 27 item questionnaire, the EORTC QLQ-ANL27. CONCLUSION: We have developed a 27 item questionnaire to supplement the EORTC QLQ-C30, for use with patients treated for anal cancer. This has been pilot tested and is now available upon request for use in clinical trials as well as clinical practice in 8 languages (http://groups.eortc.be/qol/).

Describing Peripancreatic Collections According to the Revised Atlanta Classification of Acute Pancreatitis: An International Interobserver Agreement Study.

OBJECTIVES: Severe acute pancreatitis is associated with peripancreatic morphologic changes as seen on imaging. Uniform communication regarding these morphologic findings is crucial for accurate diagnosis and treatment. For the original 1992 Atlanta classification, interobserver agreement is poor. We hypothesized that for the revised Atlanta classification, interobserver agreement will be better. METHODS: An international, interobserver agreement study was performed among expert and nonexpert radiologists (n = 14), surgeons (n = 15), and gastroenterologists (n = 8). Representative computed tomographies of all stages of acute pancreatitis were selected from 55 patients and were assessed according to the revised Atlanta classification. The interobserver agreement was calculated among all reviewers and subgroups, that is, expert and nonexpert reviewers; interobserver agreement was defined as poor (≤0.20), fair (0.21-0.40), moderate (0.41-0.60), good (0.61-0.80), or very good (0.81-1.00). RESULTS: Interobserver agreement among all reviewers was good (0.75 [standard deviation, 0.21]) for describing the type of acute pancreatitis and good (0.62 [standard deviation, 0.19]) for the type of peripancreatic collection. Expert radiologists showed the best and nonexpert clinicians the lowest interobserver agreement. CONCLUSIONS: Interobserver agreement was good for the revised Atlanta classification, supporting the importance for widespread adaption of this revised classification for clinical and research communications.

Health-related Quality of Life and Functional Outcomes in 5-year Survivors After Pancreaticoduodenectomy.

OBJECTIVE: Our aim was to assess quality of life (QOL) and functionality in a large cohort of patients ≥5-years after pancreaticoduodenectomy (PD). BACKGROUND: Long-term QOL outcomes after PD for benign or malignant disease are largely undocumented. METHODS: We administered the EORTC QLQ-C30 questionnaire to patients who underwent PD for neoplasms from 1998 to 2011 and compared their scores with an age- and sex-matched normal population. Clinical relevance (CR) of differences was scored as small (5-10), moderate (10-20), or large (>20) based on validated interpretation of clinically important differences. RESULTS: Of 305 PD survivors, 245 (80.3%) responded, of whom 157 (64.1%) underwent PD for nonmalignant lesions. Median follow-up was 9.1 years (range 5.1 -21.2 yrs). New-onset diabetes developed in 10.6%; 50.4% reported taking pancreatic enzymes; 54.6% reported needing antacids. Compared with the age- and sex-adjusted controls, PD survivors demonstrated higher global QOL (78.7 vs 69.7, CR small, P < 0.001), physical (86.7 vs 77.9, CR small, P < 0.001) and role-functioning scores (86.3 vs 74.1, CR medium, P < 0.001). Using linear regression and adjusting for socioeconomic variables, there were no differences in QOL or functional scores in the benign versus malignant subgroups. Older age at operation was associated with worse physical-functioning (-0.4/yr, P = 0.008). Taking pancrelipase (-6.8, P = 0.035) or antacids (-6.3, P = 0.044) were both associated with lower social-functioning scores. CONCLUSIONS: Patients who had a PD demonstrated better global QOL, physical- and role-functioning scores at 5-years when compared with age- and sex-matched controls. Approximately half of the patients required pancreatic enzyme replacement, while only 11% developed new-onset diabetes.

Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency (PEI) to Inform the Development of a Patient-Reported Outcome (PRO) Instrument.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) affects patients with chronic pancreatitis (CP) and cystic fibrosis (CF) who produce insufficient digestive pancreatic enzymes. Common symptoms include steatorrhoea, diarrhea, and abdominal pain. OBJECTIVE: The objective of the study was to develop and test the content validity of a patient-reported outcome (PRO) instrument assessing PEI symptoms and their impact on health-related quality of life. METHODS: Instrument development was supported by a literature review, expert physician interviews (n = 10: Germany 4, UK 3, France 3), and exploratory, qualitative, concept-elicitation interviews with patients with CF and CP with PEI (n = 61: UK 29, Germany 18, France 14) and expert physicians (n = 10). Cognitive debriefing of the draft instrument was then performed with patients with PEI (n = 37: UK 24, Germany 8, France 5), and feasibility was assessed with physicians (n = 3). For all interviews, verbatim transcripts were qualitatively analysed using thematic analysis methods and Atlas.ti computerized qualitative software. All themes were data driven rather than a priori. RESULTS: Patient interviews elicited symptoms and impacts not reported in the literature. Six symptom concepts emerged: pain, bloating, bowel symptoms, nausea/vomiting, eating problems, and tiredness/fatigue. Six impact domains were also identified. A 45-item instrument was developed in English, French, and German for testing in cognitive debriefing patient interviews. Following cognitive debriefing, 18 items were deleted. CONCLUSION: Rigorous qualitative patient research and expert clinical input supported development of a PEI-specific PRO with the potential to aid management and monitoring of unmet needs among patients with PEI. The next step is to perform psychometric evaluation of the resulting instrument.