Objective: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 health-related quality of life questionnaire is one of the most widely used cancer-specific health-related quality of life questionnaires worldwide. General population norm data can facilitate the interpretation of QLQ-C30 data obtained from cancer patients. This study aimed at systematically collecting norm data from the general population to develop European QLQ-C30 norm scores and to generate comparable norm data for individual countries in Europe and North America. Methods: We collected QLQ-C30 data from the general population across 11 European Union (EU) countries, Russia, Turkey, Canada and United States (n >= 1000/country). Representative samples were stratified by sex and age groups (18-39, 40-49, 50-59, 60-69 and >= 70 years). After applying weights based on the United Nations population distribution statistics, we calculated QLQ-C30 domain scores to generate a 'European QLQ-C30 Norm' based on the EU countries. Further, we calculated QLQ-C30 norm scores for all 15 individual countries. Results: A total of 15,386 respondents completed the online survey. For the EU sample, most QLQ-C30 domains showed differences by sex/age, with men scoring somewhat better health than women, while age effects varied across domains. Substantially larger differences were seen in inter-country comparisons, with Austrian and Dutch respondents reporting consistently better health compared with British and Polish respondents. Conclusions: This study is the first to systematically collect EORTC QLQ-C30 general population norm data across Europe and North America applying a consistent data collection method across 15 countries. These new norm data facilitate valid intra-country as well as inter-country comparisons and QLQ-C30 score interpretation. (C) 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

In response to the growing need for flexibility in the measurement of patient-reported outcomes (PROs), the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) launched its new Item Library (IL) in October 2017, enabling registered users to create customized measures tailored to study- and population-specific needs in cancer clinical trials. The goal of this abstract is to present the structure and content of these guidelines, which provide guidance on the design and implementation of customized measures. Topics for the guidelines were drafted by a multidisciplinary EORTC QLG IL working group during an interactive dialogue session. Enquiries from registered users were also taken into account as key areas for focus, and a group leader moderated the discussion. These topics then underwent further revisions by the working group. Guidelines on the design and use of PROs, published by the Consolidated Standards of Reporting Trials PRO Extension, Food and Drug Administration, and European Medicines Agency were consulted in parallel for relevant guidance and to identify possible gaps. The guidelines address both EORTC-specific and more general gaps in the existing published guidance documents and contain six sections: background/rationale; general recommendations; implementation; translations; publications and referencing; and sharing. The implementation section is the most comprehensive and is structured to reflect the sequence of study planning, informing users on item selection; item ordering; response/time scale selection; naming; formatting; and scoring, analysis, and interpretation, including limitations. In response to users’ requirements, the subsections on item selection and scoring, analysis, and interpretation are the most detailed, and include examples to facilitate application. The guidelines provide detailed recommendations for use of the IL, from the early stage of item selection to the analysis and reporting of results, thereby responding directly to the needs of commercial and academic users while promoting scientific rigor.

Objective: The computer-adaptive test (CAT) of the European Organisation for Research and Treatment of Cancer (EORTC), the EORTC CAT Core, assesses the same 15 domains as the EORTC QLQ-C30 health-related quality of life questionnaire but with increased precision, efficiency, measurement range and flexibility. CAT parameters for estimating scores have been established based on clinical data from cancer patients. This study aimed at establishing the European Norm for each CAT domain based on general population data. Methods: We collected representative general population data across 11 European Union (EU) countries, Russia, Turkey, Canada and the United States (n >= 1000/country; stratified by sex and age). We selected item subsets from each CAT domain for data collection (totalling 86 items). Differential item functioning (DIF) analyses were conducted to investigate cross-cultural measurement invariance. For each domain, means and standard deviations from the EU countries (weighted by country population, sex and age) were used to establish a T-metric with a European general population mean = 50 (standard deviation = 10). Results: A total of 15,386 respondents completed the online survey (n = 11,343 from EU countries). EORTC CAT Core norm scores for all 15 countries were calculated. DIF had negligible impact on scoring. Domain-specific T-scores differed significantly across countries with small to medium effect sizes. Conclusion: This study establishes the official European Norm for the EORTC CAT Core. The European CAT Norm can be used globally and allows for meaningful interpretation of scores. Furthermore, CAT scores can be compared with sex-and age-adjusted norm scores at a national level within each of the 15 countries. (C) 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background The European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 was the first module to be used in conjunction with the core questionnaire, the QLQ-C30. Since the publication of the LC13 in 1994, major advances have occurred in the treatment of lung cancer. Given this, an update of the EORTC QLQ-LC13 was undertaken. Methods The study followed phases I to III of the EORTC Module Development Guidelines. Phase I generated relevant quality-of-life issues using a mix of sources including the involvement of 108 lung cancer patients. Phase II transformed issues into questionnaire items. In an international multicenter study (phase III), patients completed both the EORTC QLQ-C30 and the 48-item provisional lung cancer module generated in phases I and II. Patients rated each of the items regarding relevance, comprehensibility, and acceptance. Patient ratings were assessed against a set of prespecified statistical criteria. Descriptive statistics and basic psychometric analyses were carried out. Results The phase III study enrolled 200 patients with histologically confirmed lung cancer from 12 centers in nine countries (Cyprus, Germany, Italy, Israel, Spain, Norway, Poland, Taiwan, and the UK). Mean age was 64 years (39 - 91), 59% of the patients were male, 82% had non-small-cell lung cancer, and 56% were treated with palliative intent. Twenty-nine of the 48 questions met the criteria for inclusion. Conclusions The resulting module with 29 questions, thus currently named EORTC QLQ-LC29, retained 12 of the 13 original items, supplemented with 17 items that primarily assess treatment side-effects of traditional and newer therapies.

Background: Informal carers of cancer patients with cachexia face additional challenges to those encountered by informal carers in general because of the central role food and eating play in everyday life. Patient weight loss and anorexia, core features of cancer cachexia, are frequent causes of distress in caregivers. Identification of quality of life issues can inform the development of interventions for both caregivers and patients and facilitate communication with healthcare professionals. Aim: To identify quality of life issues that are relevant to carers of cancer patients with cachexia. Design: A systematic review and thematic synthesis of the qualitative literature were conducted. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources: PubMed, ISI Web of Knowledge, EMBASE, MEDLINE, CINAHL, PsycINFO and PsycARTICLES were searched for publications dated from January 1980 to February 2015 using search terms relating to cancer, cachexia, quality of life and carers. Papers written in the English language, featuring direct quotes from the carers of adult patients with any cancer diagnosis and cachexia or problems with weight loss or anorexia, were included. Results: Five themes were extracted from the 16 identified studies. These highlighted the impact on everyday life, the attempts of some carers to take charge, the need for healthcare professional’s input, conflict with the patient and negative emotions. Conclusion: The complexity of caring for a cancer patient with cachexia translates into a range of problems and experiences for informal carers. By addressing the impact of caring for a patient with cancer cachexia on carers, both caregiver and patient quality of life may improve.

Background: There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice. Methods: This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed. Results: Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach’s α -coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change. Conclusions: The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.

Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment.

Objectives To develop a model of the impact of cancer cachexia on patients by identifying the relevant health-related quality-of-life (HRQOL) issues, and to use the model to identify opportunities for intervention. Methods Standard systematic review methods were followed to identify papers which included direct quotes from cancer patients with cachexia or problems with eating or weight loss. Following thematic synthesis methodology, the quotes were coded, and themes and metathemes were extracted. The metathemes were used to develop a model of the patient's experience of cachexia. Results 18 relevant papers were identified which, in total, contained interviews with more than 250 patients. 226 patient quotes were extracted from the papers and 171 codes. 26 themes and 8 metathemes were formulated. The model developed from the metathemes demonstrated a direct link between eating and food problems and negative emotions and also a link mediated by the associated physical decline. These links provide opportunities for interventions. Conclusions There are a vast number of HRQOL issues associated with cancer cachexia as identified from patients’ own words. The model generated from these issues indicates that relationships, coping and knowledge of the condition are important components of new psychosocial interventions.

Introduction It is suggested that T-lymphocytes play a role in the pathogenesis of chronic pancreatitis (CP), but little is known about the composition of T-cell subsets in this disease and previous studies have been discordant.1–4 We therefore aimed to characterise T-helper (Th) and T-regulatory (Treg) lymphocytes in CP tissue and peripheral blood. Methods Peripheral blood mononuclear cells were isolated from 15 patients with CP (all male, median age 48.2 years) and 14 controls (10 male, four female, median age 56.1 years). Mononuclear cells were also isolated from the pancreatic tissue of four CP patients (all male, median age 41 years) using enzymatic and mechanical digestion, followed by density gradient centrifugation. The mononuclear cells were stimulated with PMA and ionomycin (not Treg cells), and analysed using a FACSAria flow cytometer. Live CD3+CD4+ Th1, Th2, Th17 and Treg cells were identified as IFN-γ+, IL-13+, IL-17+(IFN-γ±), and CD25+FoxP3+CD127lo/− respectively. Statistical analysis was performed using a Mann–Whitney U Test. Results The peripheral blood of CP patients comprised a significantly higher percentage of Th1 cells (15.2% vs 8.11%; p=0.03), Th2 cells (2.00% vs 1.17%; p=0.03), Th17 cells (1.23% vs 0.41%; p=0.003), dual secreting IFN-γ+IL-17+ Th17 cells (0.11% vs 0.03%; p=0.003) and Treg cells (6.30% vs 4.40%; p=0.05) compared to controls. CP patients who consume excess alcohol have significantly more Th1 cells than non-drinkers (23.7% vs 9.81%; p=0.01). The T-helper cell infiltrate in CP tissue was mainly composed of Th1 cells (26.1%–57.2%, median 41.5%). Th17 cells were also seen (0.95%–3.80%, median 2.1%), including IFN-γ+IL-17+ Th17 cells (0.22%–2.39%, median 0.37%). No discernible Th2 cells were identified and few or no Treg cells were seen in CP tissue. Conclusion This work is the first to demonstrate a significant increase in the number of Th17 cells in the peripheral blood of CP patients, and to clearly demonstrate that Th1 cells are the principal T-helper cell found in CP tissue along with appreciable numbers of Th17 cells. Interestingly there is no polarisation of the peripheral blood T-helper cell response in CP towards either a Th1 or Th2 phenotype. It appears therefore that the blood of CP patients is primed to respond non-specifically to inflammatory stimuli. Intriguingly CP patients who consume excess alcohol have more peripheral blood Th1 cells. Alcohol increases gut permeability causing high circulating levels of lipopolysaccharide which is known to generate Th1 cell responses.5 These combined features may contribute to the pathogenesis of CP. Competing interests None declared. References 1. Hunger RE. Gastroenterology 1997. 2. Ebert MP. Am J Gastro 1998. 3. Miyoshi H. Pancreas 2008. 4. Schmitz-Winnenthal H. Gastroenterology 2010. 5. Bode C. J Hepatol 1987.

Background: Quality of life measurement in cholangiocarcinoma and gallbladder cancer involves the assessment of patient-reported issues related to the symptoms, disease and treatment of these tumours. This study describes the development of the disease-specific quality of life (QoL) questionnaire for patients with cholangiocarcinoma and gallbladder cancer to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30 core cancer questionnaire. Methods: Phases 1–3 of the guidelines for module development published by the EORTC were followed, with adaptations for incorporation of questions from existing modules. Results: A total of 47 QoL issues (questions) were identified; 44 questions from the two related validated questionnaires, the EORTC QLQ-PAN26 (pancreatic module) and the EORTC QLQ-LMC21 (liver metastases module), two from the Functional Assessment of Cancer Therapy hepatobiliary module questionnaire in the literature search and one from healthcare professional interviews. Following phase 1 and 2 interviews with patients ( n =101) and health care professionals ( n =6), a 23-question provisional questionnaire was formulated. There were five questions from PAN26, 15 from LMC21 and three extra questions. In phase 3, the provisional item list was pre-tested in 52 patients in four languages and this resulted in a 21-item module. Conclusion: This is the only disease-specific QoL questionnaire for patients with cholangiocarcinoma and gallbladder cancer, and initial assessments show it to be accurate and acceptable to patients in reflecting QoL in these diseases.

BACKGROUNDDue to the aging of the population, the number of older patients diagnosed with a malignant disease is increasing. A multidisciplinary approach to the senior adult cancer patient is mandatory, to assure optimal diagnosis and therapeutic management.DESIGNEuropean Organisation for Research and Treatment of Cancer (EORTC) has currently defined senior adult oncology as one of its priorities and has established an active Elderly Task Force (ETF). Under the auspices of the EORTC, the ETF organized a workshop on clinical trial methodology in older cancer patients and in this article, we present the conclusions of this workshop.RESULTSBesides the 'classical' efficacy end points, quality of life, functional status and independence of the patient should be assessed in clinical trials in older patients. The participants of the workshop agreed on the use of a minimum dataset for the assessment of global health and functional status in older cancer patients. The panel also recommended that optimization of collaboration with pharmaceutical industry requires reporting of age-related data (subgroup analyses of clinical trials, age-related pooled analyses and obligatory post-marketing studies in vulnerable and frail older patients).CONCLUSIONThe identification of proper clinical outcomes and the validation of geriatric screening tools are needed for conducting sound and comparable clinical trials.

Introduction Mucosal-Associated Invariant T cells (MAIT) are recently described human T lymphocytes with possible functions in mucosal antibacterial host defence.1 MAIT express a highly conserved T cell receptor (TCR) alpha chain consisting of an invariant Vα7.2-Jα33 rearrangement.2 Recent evidence suggests a role for T lymphocytes in the pathogenesis of chronic pancreatitis (CP), but little is known about the composition of T cell subsets in this disease.34 Intestinal bacterial overgrowth is common in chronic pancreatitis patients.5 We hypothesised that this antigenic load may promote MAIT infiltration of the pancreas and used flow cytometry to study T lymphocytes in resected pancreatic tissue and blood of patients with chronic pancreatitis. Methods Fresh resected pancreatic tissue from five patients with CP (5 males, aged 35–62, median age 43) was diced finely, enzymatically digested and passed through a nylon mesh. Lymphocytes were then isolated using density gradient centrifugation. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of the CP patients and four control patients (2 male, 2 female, aged 31–75, median age 41) using widely established techniques. Isolated tissue lymphocytes and PBMCs were analysed with fluorochrome conjugated antibodies (anti- CD3; CD4; CD8; CD161; TCR Vα7.22 and a live/dead stain) according to standard techniques using a FACSAria. Results The ratio of CD4:CD8 T cells found in pancreatic tissue compared to blood in patients with CP trended towards a higher ratio in blood, however the trend was not statistically significant. Double negative (DN) and CD8 MAIT cells (TCR Vα7.2+ CD161) were identified in pancreatic tissue and blood in all patients. The proportion of DN MAIT cells was significantly higher in pancreatic tissue compared to blood in patients with CP: 19.4% (5.7–39.6%) versus 5.2% (1.9–11.1%); p<0.05. The proportion and ratio of CD4 and CD8 T cells was similar in peripheral blood of patients with CP compared to controls. Conclusion These preliminary data show that while the distribution of CD4 and CD8 lymphocytes in CP tissue and blood is similar, DN MAIT cells are over-represented in tissue. This suggests a specific role for DN MAIT cells in local immune responses in CP. Further analysis using a larger patient cohort and functional studies to assess the possible role of these cells in the regulation of pancreatic inflammation are required.

Computed tomographic enterography (CTE) is a useful technique for evaluating the small bowel and has the capability to include the colon for evaluation of patients with inflammatory bowel disease (IBD). The aims of this study are (1) to determine if CTE is a sensitive method for detecting Crohn colitis and ulcerative colitis and (2) to assess the accuracy of determining the extent and activity of colonic disease in patients with proven IBD. Seventy patients (35 patients with proven colitis at colonoscopy and 35 negative patients with a proven normal colon) having both a CTE examination and recent colonoscopy formed the retrospective study group. A radiologist evaluated the examinations in a blinded fashion for disease presence, activity, and extent. Sensitivity was 93% for the detection of moderate and severe disease in well- distended colons. Specificity was 91%. In good to excellent distended colons, mild, moderate, and severe disease was detected with a sensitivity of 67%, 90%, and 100%, respectively. Severe disease activity was commonly underestimated, and mild disease when detected was usually overestimated. The full extent of colonic disease at CTE was usually underestimated. CTE is a valid technique for detecting colitis in the colon in patients with IBD. Better methods for assessing disease activity and extent are needed.

In inoperable malignancy, pain relief with opioids is often inadequate. Nerve block procedures may improve symptom control. Our aim was to assess celiac plexus block (CPB) and thoracoscopic splanchnicectomy (TS) in patients receiving appropriate medical management (MM). Methods: Patients with confirmed irresectable malignancy of the pancreas or upper abdominal viscera who required opioid analgesia were randomized to MM alone, MM+CPB, or MM+TS. Randomization was stratified by treatment centre, tumour type and previous opioid medication. The primary endpoint was pain relief at 2 months. Results: 65 patients (58 pancreas cancer) were randomized, 18 withdrew or died within 2 months. Effective pain relief was achieved in only one third of subjects at 2 weeks, and just under half at 2 months (MM: 6/19 and 5/12 evaluable patients; CPB: 5/14 and 5/9; TS 4/14 and 4/11). There were no significant differences between the groups in pain scores or opioid consumption, and there was no correlation between continued use of opioids and effective pain relief. Discussion: Previous randomized studies have shown small differences in pain scores, but no difference in opioid consumption and quality of life. The absence of any benefit from interventions in the present study questions their value.

BACKGROUND:To estimate the clinical benefit of CT enterography (CTE) in patients with fistulizing Crohn's disease and describe the appearance of fistulas at CTE.METHODS:Crohn's patients who had undergone CTE, which diagnosed an abscess or fistula, were identified. A gastroenterologist reviewed clinical notes prior to and following CTE to assess the pre-CTE clinical suspicion for fistula/abscess, and post-CTE alteration in patient management. A radiologist reassessed all fistula-positive cases, which were confirmed by a non-CT reference standard, to describe their radiologic appearance.RESULTS:Fifty-six patients had CT exams identifying 19 abscesses and 56 fistulas. There was no or remote suspicion of fistula or abscess at pre-imaging clinical assessment in 50% of patients. Thirty-four patients (61%) required a change in or initiation of medical therapy and another 10 (18%) underwent an interventional procedure based on CT enterography findings. Among 37 fistulas with reference standard confirmation, 30 (81%) were extraenteric tracts, and 32 (86%) were hyperenhancing compared to adjacent bowel loops. Most fistulas (68%) contained no internal air or fluid.CONCLUSION:CTE detects clinically occult fistulas and abscesses, resulting in changes in medical management and radiologic or surgical intervention. Most fistulas appear as hyperenhancing, extraenteric tracts, usually without internal air or fluid.

This international study aimed to test the measurement properties of the updated European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module for colorectal cancer, the QLQ-CR29. The QLQ-CR29 was administered with the QLQ-C30, core questionnaire, to 351 patients from seven countries. Questionnaire scaling and reliability were established and clinical and psychometric validity examined. Patient acceptability and understanding were assessed with a debriefing questionnaire. Multi-trait scaling analyses and face validity refined the module to four scales assessing urinary frequency, faecal seepage, stool consistency and body image and single items assessing other common problems following treatment for colorectal cancer. Scales distinguished between clinically distinct groups of patients and did not correlate with QLQ-C30 scales, demonstrating construct validity. The QLQ-CR29 scores were reproducible over time in stable health. The EORTC QLQ-CR29 demonstrates sufficient validity and reliability to support its use to supplement the EORTC QLQ-C30 to assess patient-reported outcomes during treatment for colorectal cancer in clinical trials and other settings.