Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

[EX Q]: Context: The aim of this study was to determine the clinical significance and prognostic impact of extranodal metastasis (EM) in gastric carcinoma.', 'The study included 1023 patients who underwent gastrectomy with lymphadenectomy for primary gastric carcinoma between January 1993 and December 1996. EM was defined as the presence of tumour cells in extramural soft tissue that was discontinuous with either the primary lesion or locoregional lymph nodes.', "EM was detected in 146 (14.3 per cent) of the 1023 patients and in 1060 (3.0 per cent) of the 35 811 nodules that were retrieved as 'lymph nodes' from adipose connective tissues. The incidence of EM was significantly higher in patients with tumours that were large (diameter 10 cm or more), infiltrative, deeply invading or undifferentiated and in those with lymph node, peritoneal or liver metastases, or lymphatic or vascular involvement. After curative operation overall survival was significantly worse for patients with EM than those without (P < 0.001). Multivariate analysis identified EM as an independent prognostic factor (hazard ratio 1.82 (95 per cent confidence interval 1.23 to 2.71); P = 0.003).
Answer: EM is an independent prognostic factor and should therefore be included in the tumour node metastasis (TNM) staging system.
[EX A]: Is extranodal metastasis an indicator of poor prognosis in patients with gastric carcinoma?

[EX Q]: Context: Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients.', 'Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (± SD) = 56.2 (±12.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period.', 'Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors.
Answer: The association of reduced hyperemic flow with increased risk of adverse clinical outcomes suggests that micro-vascular function may be an important prognostic marker in patients with HF.
[EX A]: Is reactive hyperemia associated with adverse clinical outcomes in heart failure?

[EX Q]: Context: Cancer pain is still inadequately treated in up to 60% of cancer patients. Based on the additional effect on the N-Methyl-d-Aspartate receptor, we expected that methadone (Met) could provide better pain relief than fentanyl (Fen) in cancer pain with a neuropathic pain component.', 'A randomised controlled trial was performed with 52 strong opioids naive patients with head-and-neck cancer with substantial pain (pain Numerical Rating Scale [NRS]\xa0>\xa04) and a neuropathic pain component (Douleur Neuropathique [DN4]\xa0>\xa04). Twenty-six patients were treated with Met and 26 with Fen. Patients were evaluated at 1, 3 and 5 weeks. The primary outcomes were reduction in average pain, clinical success (defined as 50% average pain decrease)\xa0and reduction in pain interference. Secondary outcomes were global perceived effect (GPE) and side-effects.', 'Reduction in NRS was higher with the use of Met at 1, 3 and 5 weeks (pain change 2.9, 3.1 and 3.1) compared to Fen (1.4, 1.7 and 2.0). This difference was significant at 1 (p\xa0=\xa00.011) and at 3 weeks (p\xa0=\xa00.03). Clinical success (>50% improvement) was higher with Met at 1 week (15% versus 50%, p\xa0=\xa00.012). The change in pain interference, the GPE and side-effect profile were not significantly different between the groups.
Answer: This is the first study to compare the effects of Met to Fen in cancer patients with a neuropathic pain component. Based on the results of this study, Met should be considered in the treatment of oncological pain with a neuropathic component.
[EX A]:
Is methadone superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer?