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.

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.

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.

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.

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.

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.

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.

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.

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.

International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. METHODS: A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. RESULTS: Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. CONCLUSION: The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.

Use of the lung cancer-specific Quality of Life Questionnaire EORTC QLQ-LC13 in clinical trials: A systematic review of the literature 20 years after its development.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) covers 13 typical symptoms of lung cancer patients and was the first module developed in conjunction with the EORTC core quality-of-life (QL) questionnaire. This review investigates how the module has been used and reported in cancer clinical trials in the 20 years since its publication. Thirty-six databases were searched with a prespecified algorithm. This search plus an additional hand search generated 770 hits, 240 of which were clinical studies. Two raters extracted data using a coding scheme. Analyses focused on the randomized controlled trials (RCTs). Of the 240 clinical studies that were identified using the LC13, 109 (45%) were RCTs. More than half of the RCTs were phase 3 trials (n = 58). Twenty RCTs considered QL as the primary endpoint, and 68 considered it as a secondary endpoint. QL results were addressed in the results section of the article (n = 89) or in the abstract (n = 92); and, in half of the articles, QL results were presented in the form of tables (n = 53) or figures (n = 43). Furthermore, QL results had an impact on the evaluation of the therapy that could be clearly demonstrated in the 47 RCTs that yielded QL differences between treatment and control groups. The EORTC QLQ-LC13 fulfilled its mission to be used as a standard instrument in lung cancer clinical trials. An update of the LC13 is underway to keep up with new therapeutic trends and to ensure optimized and relevant QL assessment in future trials.

Systematic review of the quality of life issues associated with anal cancer and its treatment with radiochemotherapy.

PURPOSE: Radiochemotherapy is the standard of care for the treatment of anal carcinoma achieving good loco-regional control and sphincter preservation. This approach is however associated with acute and late toxicities including haematological, skin, bowel function and genito-urinary complications. This paper systematically reviews studies addressing the quality of life (QoL) implications of anal cancer and radiochemotherapy. The paper also evaluates how QoL is assessed in anal cancer. METHODS: Medline, EMBASE, CINAHL, PsycInfo, Web of Science and the Cochrane Library were searched for publications (1996-2014) reporting the effects on patients of anal cancer and radiochemotherapy. RESULTS: Of the 152 papers reporting treatment-related effects on patients, only 11 provided a formal assessment of QoL. In the absence of an anal cancer-specific measure, QoL was assessed using generic cancer instruments such as the core EORTC quality of life questionnaire (EORTC QLQ-C30) or colorectal cancer tools such as the EORTC QLQ-CR29. Bowel function, particularly diarrhoea, and sexual problems were the most commonly reported QoL concerns. The review of QoL issues of anal cancer patients treated with radiochemotherapy is limited by the QoL assessment measures used. It is argued that certain treatment-related toxicities, for example skin-induced radiation problems, are overlooked or inadequately represented in existing measures. CONCLUSIONS: This review emphasises the need to develop an anal cancer-specific QoL measure and to incorporate QoL as an outcome of future trials in anal cancer. The results of this review are informative to clinicians and patients in terms of treatment decision-making.

Timing of enteral nutrition in acute pancreatitis: meta-analysis of individuals using a single-arm of randomised trials.

INTRODUCTION: In acute pancreatitis, enteral nutrition (EN) reduces the rate of complications, such as infected pancreatic necrosis, organ failure, and mortality, as compared to parenteral nutrition (PN). Starting EN within 24 h of admission might further reduce complications. METHODS: A literature search for trials of EN in acute pancreatitis was performed. Authors of eligible trials were requested to provide the data of all patients in the EN-arm of their trials. A meta-analysis of individual patient data was performed. The cohort of patients with EN was divided into patients receiving EN within 24 h or after 24 h of admission. Multivariable logistic regression, adjusting for predicted disease severity and trial, was used to study the effect of timing of EN on a composite endpoint of infected pancreatic necrosis, organ failure, or mortality. RESULTS: Observational data from 165 individuals from 8 randomised trials were obtained; 100 patients with EN within 24 h and 65 patients with EN after 24 h of admission. In the multivariable model, EN started within 24 h of admission compared to EN started after 24 h of admission, reduced the composite endpoint from 45% to 19% (adjusted odds ratio [OR] of 0.44; 95% confidence interval [CI] 0.20-0.96). Within the composite endpoint, organ failure was reduced from 42% to 16% (adjusted OR 0.42; 95% CI 0.19-0.94). CONCLUSIONS: In this meta-analysis of observational data from individuals with acute pancreatitis, starting EN within 24 h after hospital admission, compared with after 24 h, was associated with a reduction in complications.

Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus.

BACKGROUND AND OBJECTIVE: The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the disease make a revision necessary. METHODS: A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained. RESULTS: The revised classification of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images. CONCLUSIONS: This international, web-based consensus provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.

Implementation of enhanced recovery programme after pancreatoduodenectomy: a single-centre UK pilot study.

INTRODUCTION: Data on enhanced recovery programmes after pancreatoduodenectomy (ERP-PD) is limited. The aim of this pilot study was to evaluate the feasibility, safety and clinical outcomes of ERP-PD when implemented at a high-volume UK university referral centre. METHODS: This was an observational single-surgeon case-control study (before-and-after pathway). A total of 20 consecutive patients were prospectively enrolled for the ERP-PD and compared with 24 consecutive patients previously treated during an equal time frame. RESULTS: Patients in the ERP-PD group had a significant shorter time to remove naso-gastric tube (median of 5 vs. 7 days, p = 0.0001), start liquid diet (median of 2 vs. 5 days, p < 0.0001), start solid food (median of 4 vs. 9 days, p < 0.0001), pass stools (median of 6 vs. 7 days, p = 0.002), and had shorter length of stay (median of 8.5 days vs. 13 days, p = 0.015) compared to the pre-pathway group. Postoperative complications were overall less frequent but not significantly different in the ERP-PD group (p = 0.077). No difference in mortality and readmission rates was found. CONCLUSIONS: Our findings support the feasibility and safety of ERP-PD. Improved patients' outcomes, significant bed day savings and increase National Health Service productivity are anticipated with implementation of ERP-PD on a larger scale.

A systematic review of health-related quality of life instruments in patients with cancer cachexia.

PURPOSE: Assessing the health-related quality of life (HRQOL) of cancer patients with cachexia is particularly important because treatments for cachexia are currently aimed at palliation and treatment efficacy must be measured in ways other than survival. The aim of this systematic review was to evaluate HRQOL assessment in cancer patients with cachexia. METHODS: Using guidance from the Centre for Reviews and Dissemination, relevant databases were searched from January 1980 to January 2012 with terms relating to cancer, cachexia and HRQOL for papers including adult cancer patients with cachexia or documented weight loss at baseline. RESULTS: We found one cachexia-specific instrument, the Functional Assessment of Anorexia/Cachexia Therapy, but the tool has not been fully validated, does not cover all the relevant domains and the consensus-based standards for the selection of health status measurement instruments checklist highlighted a number of weaknesses in the methodological quality of the validation study. Sixty-seven studies assessed HRQOL in cachectic or weight-losing cancer patients. Most used generic cancer HRQOL instruments, limiting the amount of useful information they provide. A modified version of the Efficace minimum data checklist demonstrated that the quality of reporting on HRQOL tool use was inadequate in many of the studies. A negative relationship between HRQOL and weight loss was found in 23 of the 27 studies which directly examined this. CONCLUSION: There is a pressing need for a well-designed HRQOL tool for use with this patient group in both clinical trials and clinical practice.

Postoperative chyle leak after major pancreatic resections in patients who receive enteral feed: risk factors and management options.

BACKGROUND: Chyle leak complicates 1.3-10.8 % of pancreatic resections. Universal use of parenteral nutrition following pancreatic resection may reduce the incidence of chyle leak. However, this denies the majority of patients who do not develop chyle leak the benefits of enteral nutrition (EN). The present study aimed to identify risk factors for chyle leak following pancreatic resection within a single institution where EN was used universally. METHODS: All patients who underwent pancreatic resection between January 2007 and December 2010 were identified retrospectively. The patients had been treated according to a common unit protocol of enteral feeding; those developing chyle leak were switched to a medium-chain triglyceride (MCT) regimen. Clinical progress and recovery after surgery was evaluated. Multivariate analysis was performed to identify factors associated with chyle leak. RESULTS: A total of 245 patients underwent major pancreatic resection (231 pancreatoduodenectomy, 14 total pancreatectomy). Chyle leak complicated 40 cases (16.3 %). After multivariate analysis, both extensive lymphadenectomy (P = 0.002) and postoperative portal/mesenteric venous thrombosis (PVT) (P = 0.009) were independently linked with a higher incidence of chyle leak. The development of chyle leak was not associated with poorer survival or prolonged duration of hospital stay. It was associated with a significantly increased duration of abdominal drainage and reduced likelihood of early hospital discharge (P = 0.026). CONCLUSIONS: Universal use of enteral feeding is associated with a high rate of chyle leak following pancreatic resection. Patients undergoing extensive lymphadenectomy or those who develop PVT postoperatively are at increased risk. Development of chyle leak was not associated with additional morbidity or mortality following implementation of an MCT regimen. The implication is that reactive management of chyle leak with conversion to a MCT predominant diet is safe.

Cross-cultural development of an EORTC questionnaire to assess health-related quality of life in patients with testicular cancer: the EORTC QLQ-TC26.

OBJECTIVE: Testicular cancer (TC) is the most common cancer in young men, and its incidence is increasing. The low mortality rate makes quality of life (QOL) an important issue in this patient group. This study aimed to develop a supplementary module of the EORTC QLQ-C30 questionnaire to assess TC-specific aspects of QOL. METHODS: Questionnaire development was conducted according to guidelines from the EORTC Quality of Life Group. Phase I comprised generation of QOL issues relevant to TC patients through a literature search and interviews with patients and experts. Phase II included operationalization and assessment of item relevance. In phase III, items were pre-tested in a cross-cultural sample to assess issues such as understandability and intrusiveness of items. RESULTS: In phase I and II, an initial list of 69 QOL issues possibly relevant to TC patients was refined through patient and expert interviews. The remaining 37 issues were operationalized into items and assessed for relevance and priority in an expert sample (n = 28) and a patient sample (n = 62) from Austria, Canada and the Netherlands. After revision of the item list, 26 items were considered eligible for pre-testing in phase III, in which 156 patients from Australia, Austria, Italy and Spain participated. All items passed criteria for pre-testing, thus forming the new EORTC QLQ-TC26. CONCLUSION: The newly developed EORTC QLQ-TC26 is now available in several languages to assess QOL in TC patients receiving treatment and in TC survivors. Phase IV of questionnaire development will comprise international field testing, including extensive analysis of psychometric characteristics of the EORTC QLQ-TC26.

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.