Neo-adjuvant chemo/immunotherapy in the treatment of stage III (N2) non-small cell lung cancer: a phase I/II pilot study.

In a previous randomized study, we showed that adjuvant immunotherapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 (rIL-2) significantly improved survival in resected N2-Non Small Cell Lung Cancer (NSCLC) patients. The present study assesses feasibility, safety and potential efficacy of combined neo-adjuvant chemotherapy and immunotherapy with peripheral blood mononuclear cells (PBMC) and rIL-2 in resectable N2-NSCLC patients. Eighty-two consecutive N2-NSCLC patients underwent neo-adjuvant chemotherapy with cisplatin and gemcitabine. Out of the 82 patients, 23 were also subjected to leukapheresis prior to neo-adjuvant chemotherapy while the remaining 59 did not. Collected PBMC were analyzed for viability and phenotype and then stored frozen in liquid nitrogen. Thawed PBMC were infused intravenously, 5 days before surgery. After the infusion, rIL-2 was administered subcutaneously until surgery. Only patients with a partial or complete response to neoadjuvant chemotherapy underwent surgery: 13 patients in the experimental immunotherapy group (A) and 32 in the reference group (B). The two groups were homogeneous for all major prognostic factors. Median leukapheresis yield was 10 billion PBMC, (range 3–24 billions). Two to six billion PBMC were infused. The phenotypic analysis showed that similar proportions of CD4 and CD8 cells were present in leukapheresis products, and thawed PBMC, as well as in T lymphocytes isolated from the removed tumours. No severe adverse effects were observed following immunotherapy. No significant differences in overall survival (OS) and event-free survival (EFS) were seen between the two groups. However, the 5-year OS in group A was almost twice as much compared to group B (59% vs 32%). After adjustment for major prognostic factors, a statistically significant 66% reduction in the hazard of death was seen in patients receiving immunotherapy. The OS benefit was more evident in patients with adenocarcinoma than in those with squamous cell carcinoma. This study supports the favorable toxicity profile and potential efficacy of combining neo-adjuvant chemotherapy and immunotherapy with PBMC and rIL-2 in the treatment of N2-NSCLC patients

Disciplinary problems among high achiever students: the types and the causes

This qualitative study has been done to 24 teachers and 72 students from various secondary schools in Penang, Malaysia, in order to investigate the effect of between class ability grouping (BCAG) on high achiever secondary school students. Studies reported that BCAG triggered correspondence bias among teachers, which eventually affect them to show different perception and expectations towards high achiever classes (HAC) and low achiever classes (LAC) students. Symbolic interaction theories explained that individuals tend to be affected by others’ expectation, and therefore behave in a way they were expected to. Therefore, according to the previous studies on BCAG, it was assumed that HAC students would achieve better and would not be significantly involved in disciplinary problems. After semi-structured interview had been conducted in order to collect the data, and two-cycled analyses method, namely In-Vivo and Thematic Analyses had been operated in order to analyze the massive amount of qualitative data, the it was discovered that HAC students were involved with disciplinary problems, such as being disrespectful to teachers, paying less attention in the classroom, neglecting assignments and doing external work during classes. Other findings of this study showed that the disciplinary problems among HAC are related to their self-esteem types due to locus of control difference, as well as bigger issues apart from the competition among themselves. School management system, BCAG itself, reciprocal envy between HAC and LAC students, as well as their inclination towards tuition centers contributed to disciplinary problems among HAC students

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Pleural lavage cytology predicts recurrence and survival, even in early non-small cell lung cancer

PURPOSE: The TNM staging remains the best prognostic descriptor of lung cancer; however, new independent prognostic factors are needed, particularly for early stage disease. METHODS: An evaluation of the pleural lavage cytology (PLC) was performed in 436 consecutive NSCLC patients who underwent surgical resection; clinical, pathological and follow-up data were available for 414 patients. RESULTS: The PLC was positive in 15 patients (3.6 %). The overall five-year survival was 35.9 % in PLC-positive and 57.8 % in PLC-negative patients (p = 0.004). To compare groups with the same prognostic characteristics, the analysis was restricted to p-stage I patients, but the survival remained worse in the PLC-positive patients (42.9 vs 69.4 %; p = 0.001). Recurrence was also observed more frequently in PLC-positive cases: 69.2 vs 34.5 %, OR 4.28 (95 % CI 1.29-14.18; p = 0.01). Among the PLC-positive patients, no difference between the local (44.4 %) and distant (55.6 %) relapse patterns was found (p = 0.82). The multivariate analysis identified four independent prognostic factors: age (p < 0.001), disease stage (p < 0.001), gender (p = 0.025) and PLC status (p = 0.012). CONCLUSIONS: PLC is an independent prognostic factor for NSCLC. PLC-positive NSCLC patients have a worse overall survival and a higher recurrence rate, even in stage I disease. PLC-positive patients should be considered a high risk category, who should potentially be eligible for adjuvant therapy regardless of their p-stage

Eosinophil Granulocytes Account for Indoleamine 2,3-Dioxygenase-Mediated Immune Escape in Human Non-Small Cell Lung Cancer

Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is supposed to play a role in tumor immune escape. Its expression in solid tumors has not yet been well elucidated: IDO can be expressed by the tumor cells themselves, or by ill-defined infiltrating cells, possibly depending on tumor type. We have investigated IDO expression in 25 cases of non-small cell lung cancer (NSCLC). Using histochemistry and immunohistochemistry, we found that IDO was expressed not by tumor cells, but by normal cells infiltrating the peritumoral stroma. These cells were neither macrophages nor dendritic cells, and were identified as eosinophil granulocytes. The amount of IDO-positive eosinophils varied in different cases, ranging from a few cells to more than 50 per field at x200 magnification. IDO protein in NSCLC was enzymatically active. Therefore, at least in NSCLC cases displaying a large amount of these cells in the inflammatory infiltrate, IDO-positive eosinophils could exert an effective immunosuppressive action. On analyzing the 17 patients with adequate follow-up, a significant relationship was found between the amount of IDO-positive infiltrate and overall survival. This finding suggests that the degree of IDO-positive infiltrate could be a prognostic marker in NSCLC

Neo-Adjuvant Chemo/Immunotherapy in the Treatment of Stage III (N2) Non-Small Cell Lung Cancer: A Phase I/II Pilot Study

In a previous randomized study, we showed that adjuvant immunotherapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 (rIL-2) significantly improved survival in resected N2-Non Small Cell Lung Cancer (NSCLC) patients. The present study assesses feasibility, safety and potential efficacy of combined neo-adjuvant chemotherapy and immunotherapy with peripheral blood mononuclear cells (PBMC) and rIL-2 in resectable N2-NSCLC patients. Eighty-two consecutive N2-NSCLC patients underwent neo-adjuvant chemotherapy with cisplatin and gemcitabine. Out of the 82 patients, 23 were also subjected to leukapheresis prior to neo-adjuvant chemotherapy while the remaining 59 did not. Collected PBMC were analyzed for viability and phenotype and then stored frozen in liquid nitrogen. Thawed PBMC were infused intravenously, 5 days before surgery. After the infusion, rIL-2 was administered subcutaneously until surgery. Only patients with a partial or complete response to neoadjuvant chemotherapy underwent surgery: 13 patients in the experimental immunotherapy group (A) and 32 in the reference group (B). The two groups were homogeneous for all major prognostic factors. Median leukapheresis yield was 10 billion PBMC, (range 3–24 billions). Two to six billion PBMC were infused. The phenotypic analysis showed that similar proportions of CD4 and CD8 cells were present in leukapheresis products, and thawed PBMC, as well as in T lymphocytes isolated from the removed tumours. No severe adverse effects were observed following immunotherapy. No significant differences in overall survival (OS) and event-free survival (EFS) were seen between the two groups. However, the 5-year OS in group A was almost twice as much compared to group B (59% vs 32%). After adjustment for major prognostic factors, a statistically significant 66% reduction in the hazard of death was seen in patients receiving immunotherapy. The OS benefit was more evident in patients with adenocarcinoma than in those with squamous cell carcinoma. This study supports the favorable toxicity profile and potential efficacy of combining neo-adjuvant chemotherapy and immunotherapy with PBMC and rIL-2 in the treatment of N2-NSCLC patients