Reducing Changeover Time Between Surgeries Through Lean Thinking: An Action Research Project.

Background: Maximizing the utilization of the operating room suite by safely and efficiently changing over patients is an opportunity to deliver more value to patients and be more efficient in the operating suite. Lean Thinking is a concept that focuses on the waste inadvertently generated during organization and development of an activity, which should maximize customer value while minimizing waste. It has been widely applied to increase process efficiency and foster continuous improvement in healthcare and in the operating room environment. The objective of this paper is to provide insight on how healthcare professionals can be engaged in continuous improvement by embracing Lean Thinking and ultimately reducing changeover time between surgeries. Methods: Using an action research approach, Lean methodology such as Gemba walks, Process Mapping, Root-Cause-Analysis, and the Single Minute Exchange of Dies (SMED) system was applied to understand the causes of variability and wastes concerning changeovers and improve processes in the context of gynecological- and general surgery. Data were collected and analyzed through observations and video recordings. Problem and issue have been raised to management team attention and included in the annual balanced scorecard of the hospital. This initiative has been also made relevant to the team working in the operating suite and related processes before and after the entry of the patient in the operating suite. Results: Improved patient flow and inter-professional collaboration through standardized and safer work enabled effective parallel processing and allowed the hospital to reduce changeover time between operations by 25% on average, without changes in terms of infrastructure, technology or resources. Conclusion: Lean thinking allowed the team to re-evaluate how the whole operating suite performs as a system, by starting from a sub-process as changeover. It is fundamental in order to improve further and obtain sustainable results over time, to act on a system level by defining a common goal between all stakeholders supported by a management and leading system such as visual/weekly management, optimizing planning, implementing standard-works to be followed by every associate and guaranteeing the role of the surgeon as process driver who pull performances.

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice.

Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.

Prognostic Relevance of Progesterone Receptor Levels in Early Luminal-Like HER2 Negative Breast Cancer Subtypes: A Retrospective Analysis.

Introduction: In luminal-like early breast cancer (BC), the lack of Progesterone Receptor (PR) expression generally correlates with more aggressive behavior but the clinical validity of low PR levels remains a debated issue. Methods: The main aim of this retrospective analysis was to assess the survival outcome (Breast cancer specific survival, BCSS) in a cohort of 687 luminal-like HER2 negative early BC patients treated at our Institutions from January 2000 to December 2018, using a sub-classification of tumors in subgroup 1 (PR high/Ki67 low), subgroup 2 (PR high/Ki67 high), subgroup 3 (PR low/Ki67 low), subgroup 4 (PR low/Ki67 high) according to PR and Ki67 values. Results: At a median follow-up of 7 years, BCSS rates were 96.3%, 89%, 86.8% and 85% in the subgroup 1, 2, 3, 4 respectively. Overall, a statistically significant difference in BCSS rates was observed among the 4 subgroups (p=0.0036). On univariate analysis, post-menopause, older age (≥ 50 years), low PR and high Ki67 expression, poorly differentiated grade and size ≥ 2 cm as well as luminal B-like tumors (subgroups 2, 3, 4) were significantly associated with a worse BCSS. Multivariate analysis identified grade, size and subgroup classification of BC as independent prognostic markers of poorer outcome. In particular, subgroups 4, 3 and 2 displayed a significantly higher risk of BC-related death (HR=4.11; p=0.008; HR=3.43; p=0-007; HR=2.57; p=0.020, respectively) when compared to subgroup 1. Conclusions: Our results support the usefulness of PR and Ki67 levels as prognostic markers, corroborating their crucial role in the decision-making process of patients with luminal-like HER2 negative early BC. Clinical application of these parameters should be assessed prospectively.

Immunotherapy for head and neck cancer: Present and future.

Immunotherapy has changed the treatment landscape of Head and Neck cancer (HNC). Different immune checkpoint inhibitors targeting PD-1/PD-L1 axis have been approved for different disease settings and many others, alone or in combination, are currently under investigation. Otherwise, as in other cancer types, efficacy, and resistance mechanisms, are not clearly understood. Considering the heterogeneity of the benefit reported in clinical trials, cost-efficacy analysis and the development of an effective patient selection are encouraged. Different pathways involving innate immunity, regulatory T lymphocytes and microbiome are emerging as new potential biomarkers, supported by preclinical and translational data. In this review we report current evidence on immunotherapy in HNC with updates from the main 2021 oncology events as ASCO, AACR and ESMO meetings. We focus on clinical trials results of single agent and combination immunotherapy in different clinical scenario, from (neo)adjuvant to metastatic setting, describing also novel evidence about efficacy and resistance biomarkers.

HER2-Low Status Does Not Affect Survival Outcomes of Patients with Metastatic Breast Cancer (MBC) Undergoing First-Line Treatment with Endocrine Therapy plus Palbociclib: Results of a Multicenter, Retrospective Cohort Study.

BACKGROUND: Approximately 45-50% of breast cancers (BCs) have a HER2 immunohistochemical score of 1+ or 2+ with negative in situ hybridization, defining the "HER2-low BC" subtype. No anti-HER2 agents are currently approved for this subgroup in Europe, where treatment is still determined by HR expression status. In this study, we investigated the prognostic significance of HER2-low status in HR+/HER2- metastatic BC (MBC) patients treated with endocrine therapy (ET) plus palbociclib as first line. METHODS: We conducted a retrospective study including 252 consecutive HR+/HER2- MBC patients who received first-line ET plus palbociclib at six Italian Oncology Units between March 2016 and June 2021. The chi-square test was used to assess differences in the distribution of clinical and pathological variables between the HER-0 and HER2-low subgroups. Survival outcomes, progression-free survival (PFS) and overall survival (OS), were calculated by the Kaplan-Meier method, and the log-rank test was performed to estimate the differences between the curves. RESULTS: A total of 165 patients were included in the analysis: 94 (57%) and 71 (43%) patients had HER2-0 and HER2-low disease, respectively. The median age at treatment start was 64 years. No correlation between patients and tumor characteristics and HER2 status was found. Median PFS (mPFS) for the entire study cohort was 20 months (95% CI,18-25 months), while median OS (mOS) was not reached at the time of analysis. No statistically significant differences, in terms of PFS (p = 0.20) and OS (p = 0.1), were observed between HER2-low and HER2-0 subgroups. CONCLUSIONS: In our analysis, HR+ MBC patients with low HER2 expression who received first-line treatment with ET plus Palbociclib reported no statistically different survival outcomes compared to HER2-0 patients. Further prospective studies are needed to confirm the clinical role of HER2 expression level.

Thoracic ultrasound confirmation of correct lung exclusion before one-lung ventilation during thoracic surgery.

INTRODUCTION: Fiberoptic bronchoscopy is the standard method for verifying the correct position of a double-lumen endotracheal tube (DLET) prior to one-lung ventilation. However, it must be performed by a specially trained anesthesiologist and is often resource consuming. The aim of this study was to compare this approach with thoracic ultrasound done by a nurse anesthetist in terms of sensitivity, specificity, and cost-effectiveness. METHODS: We conducted a prospective cross-over case-control study involving 51 adult patients consecutively undergoing thoracic surgery with one-lung ventilation. After orotracheal intubation with a DLET, correct exclusion of the lung being operated on exclusion was assessed first by a certified anesthesiologist using standard fiberoptic bronchoscopy and then by a trained nurse anesthetist using thoracic ultrasound. The nurse was blinded as to the findings of the anesthesiologist's examination. RESULTS: The two approaches proved to be equally sensitive and specific, but the ultrasound examination was more rapid. This factor, together with the fact that ultrasound was performed by a nurse instead of a physician, and the costs of materials and sterilization, had a significant economic impact amounting to a net saving of €37.20 ± 5.40 per case. CONCLUSIONS: Although fiberoptic bronchoscopy is still the gold standard for checking the position of a DLET, thoracic ultrasound is a specific, sensitive, cost-effective alternative, which can be used to rapidly verify the proper function of the tube based on the demonstration of correct lung exclusion.