Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer.

BACKGROUND: There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer. METHODS: We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study. TILs were analysed using a standardised method based on H&E staining producing a percentage score for stromal and intratumoral compartments. We used Cox regression to estimate hazard ratios of the association between TILs and survival. RESULTS: The extent of stromal and intra-tumoral TILs were correlated in the primary tumours (n = 679, Spearman's rank correlation = 0.60, P < 0.001) with a similar correlation in secondary tumours (n = 224, Spearman's rank correlation = 0.62, P < 0.001). There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.29, P < 0.001) and intra-tumoral TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.19, P = 0.0094). The extent of stromal TILs differed between histotypes (Pearson chi2 (12d.f.) 54.1, P < 0.0001) with higher levels of stromal infiltration in the high-grade serous and endometriod cases. A significant association was observed for higher intratumoral TIL levels and a favourable prognosis (HR 0.74 95% CI 0.55-1.00 p = 0.047). CONCLUSION: This study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and intratumoral TIL levels are correlated and that their levels correlate with clinical variables such as tumour histological subtype. We have also shown that increased levels of both intratumoral and stromal TILs are associated with a better prognosis; however, this is only statistically significant for intratumoral TILs. This study suggests that a clinically useful immune prognostic indicator in epithelial ovarian cancer could be developed using this technique.

Decision-making in intensive care medicine - A review.

Decision-making by intensivists around accepting patients to intensive care units is a complex area, with often high-stakes, difficult, emotive decisions being made with limited patient information, high uncertainty about outcomes and extreme pressure to make these decisions quickly. This is exacerbated by a lack of clear guidelines to help guide this difficult decision-making process, with the onus largely relying on clinical experience and judgement. In addition to uncertainty compounding decision-making at the individual clinical level, it is further complicated at the multi-speciality level for the senior doctors and surgeons referring to intensive care units. This is a systematic review of the existing literature about this decision-making process and the factors that help guide these decisions on both sides of the intensive care unit admission dilemma. We found many studies exist assessing the patient factors correlated with intensive care unit admission decisions. Analysing these together suggests that factors consistently found to be correlated with a decision to admit or refuse a patient from intensive care unit are bed availability, severity of illness, initial ward or team referred from, patient choice, do not resuscitate status, age and functional baseline. Less research has been done on the decision-making process itself and the factors that are important to the accepting intensivists; however, similar themes are seen. Even less research exists on referral decision and demonstrates that in addition to the factors correlated with intensive care unit admission decisions, other wider variables are considered by the referring non-intensivists. No studies are available that investigate the decision-making process in referring non-intensivists or the mismatch of processes and pressure between the two sides of the intensive care unit referral dilemma.

Intensive care decision-making: Identifying the challenges and generating solutions to improve inter-specialty referrals to critical care.

INTRODUCTION: Decision-making regarding admission to UK intensive care units is challenging. Demand for beds exceeds capacity, yet the need to provide emergency cover creates pressure to build redundancy into the system. Guidelines to aid clinical decision-making are outdated, resulting in an over-reliance on professional judgement. Although clinicians are highly skilled, there is variability in intensive care unit decision-making, especially at the inter-specialty level wherein cognitive biases contribute to disagreement. METHOD: This research is the first to explore intensive care unit referral and admission decision-making using the Critical Decision Method interviewing technique. We interviewed intensive care unit (n = 9) and non-intensive care unit (n = 6) consultants about a challenging referral they had dealt with in the past where there was disagreement about the patient's suitability for intensive care unit. RESULTS: We present: (i) a description of the referral pathway; (ii) challenges that appear to derail referrals (i.e. process issues, decision biases, inherent stressors, post-decision consequences) and (iii) potential solutions to improve this process. DISCUSSION: This research provides a foundation upon which interventions to improve inter-specialty decision-making can be based.