Prognostic implication of PD-L1 in early-stage non-small cell lung cancer: a retrospective single-centre study.

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with localised and locally advanced non-small cell lung cancer has not been fully elucidated. This information could help to better interpret recent and upcoming results of phase III adjuvant or neoadjuvant anti-PD-1/PD-L1 immunotherapy studies. METHODS: In a cohort of 146 patients with early or locally advanced non-small cell lung cancer treated with curative intent (by surgery or radiotherapy), we investigated the prognostic value of PD-L1 expression and its correlation with other biological and clinical features. PD-L1 expression was stratified by quartiles. Primary endpoints were overall and disease-free survival. We also analysed the prognostic impact of the presence of actionable mutations, implemented treatment modality and completion of the treatment plan. Neither type of patient received neoadjuvant or adjuvant immunotherapy or target therapy. RESULTS: Of the 146 selected patients, 32 (21.9%) presented disease progression and 15 died (10.3%) at a median follow-up of 20 months. In a univariable analysis, PD-L1 expression ≥25% was associated with significantly lower disease-free survival (hazard ratio [HR]) 1.9, 95% confidence interval [CI] 1.0-3.9, p = 0.049). PD-L1 expression ≥50% did not lead to disease-free survival or overall survival benefits (HR 1.2 and 1.1, respectively; 95% CI 0.6-2.6 and 0.3-3.4, respectively; pnot significant). In a multivariate analysis, a stage >I (HR 2.7, 95% CI 1.2-6, p = 0.012) and having an inoperable tumour (HR 3.2, 95% CI 1.4-7.4, p = 0.005) were associated with lower disease-free survival. CONCLUSION: The population of patients with early-stage non-small cell lung cancer and PD-L1 expression ≥25% who were treated with curative intent during the pre-immunotherapy era exhibited a worse prognosis. This finding provides justification for the utilisation of adjuvant immunotherapy in this subgroup of patients, based on the current evidence derived from disease-free survival outcomes. However, for patients with PD-L1 expression <25%, opting to wait for the availability of the overall survival results may be a prudent choice.

Perioperative costs of local or regional anesthesia versus general anesthesia in the outpatient setting: a systematic review of recent literature

Abstract Background and objectives: In this systematic review, we carried out an assessment of perioperative costs of local or regional anesthesia versus general anesthesia in the ambulatory setting. Methods: A systematic literature search was conducted to find relevant data on costs and cost-effectiveness analyses of anesthesia regimens in outpatients, regardless of the medical procedure they underwent. The hypothesis was that local or regional anesthesia has a lower economic impact on hospital costs in the outpatient setting. The primary outcome was the average total cost of anesthesia calculated on perioperative costs (drugs, staff, resources used). Results: One-thousand-six-hundred-ninety-eight records were retrieved, and 28 articles including 27,581 patients were selected after reviewing the articles. Data on the average total costs of anesthesia and other secondary outcomes (anesthesia time, recovery time, time to home readiness, hospital stay time, complications) were retrieved. Taken together, these findings indicated that local or regional anesthesia is associated with lower average total hospital costs than general anesthesia when performed in the ambulatory setting. Reductions in operating room time and postanesthesia recovery time and a lower hospital stay time may account for this result. Conclusions: Despite the limitations of this systematic review, mainly the heterogeneity of the studies and the lack of cost-effectiveness analysis, the economic impact of the anesthesia regimes on healthcare costs appears to be relevant and should be further evaluated.

Contribution margin per hour of operating room to reallocate unutilized operating room time: a cost-effectiveness analysis

Abstract Background and objectives: Contribution margin per hour (CMH) has been proposed in healthcare systems to increase the profitability of operating suites. The aim of our study is to propose a simple and reproducible model to calculate CMH and to increase cost-effectiveness. Methods: For the ten most commonly performed surgical procedures at our Institution, we prospectively collected their diagnosis-related group (DRG) reimbursement, variable costs and mean procedural time. We quantified the portion of total staffed operating room time to be reallocated with a minimal risk of overrun. Moreover, we calculated the total CMH with a random reallocation on a first come-first served basis. Finally, prioritizing procedures with higher CMH, we ran a simulation by calculating the total CMH. Results: Over a two-months period, we identified 14.5 hours of unutilized operating room to reallocate. In the case of a random ''first come -first serve'' basis, the total earnings were 87,117 United States dollars (USD). Conversely, with a reallocation which prioritized procedures with a high CMH, it was possible to earn 140,444 USD (p < 0.001). Conclusion: Surgical activity may be one of the most profitable activities for hospitals, but a cost-effective management requires a comprehension of its cost profile. Reallocation of unused operating room time according to CMH may represent a simple, reproducible and reliable tool for elective cases on a waiting list. In our experience, it helped improving the operating suite cost-effectiveness.

Resection of thymic carcinoma after induction therapy and reconstruction of right ventricular outflow tract with pulmonary homograft.

Treatment of malignant epithelial thymic tumours, including thymoma and thymic carcinoma, is based on surgical resection, whenever possible. Mainstay of surgical treatment is complete resection with clear margins. This may require resection of adjacent structures, even major vessels. We describe a case of resection of the main pulmonary artery trunk and reconstruction with cadaveric homograft after induction chemo-radiotherapy for a locally advanced thymic carcinoma. Written informed consent was obtained from the patient.

A Risk Model to Predict the Delivery of Adjuvant Chemotherapy Following Lung Resection in Patients With Pathologically Positive Lymph Nodes.

To investigate factors associated with the ability to receive adjuvant chemotherapy in patients with pathological N1 and N2 stage after anatomic lung resections for non-small cell lung cancer (NSCLC). Multicenter retrospective analysis on 707 consecutive patients found pathologic N1 (pN1) or N2 (pN2) disease following anatomic lung resections for NSCLC (2014-2019). Multiple imputation logistic regression was used to identify factors associated with adjuvant chemotherapy and to develop a model to predict the probability of starting this treatment. The model was externally validated in a population of 253 patients. In the derivation set, 442 patients were pN1 and 265 pN2. 58% received at least 1 cycle of adjuvant chemotherapy. The variables significantly associated with the probability of starting chemotherapy after multivariable regression analysis were: younger age (p < 0.0001), Body Mass Index (BMI) (p = 0.031), Forced Expiratory Volume in 1 second (FEV1) (p = 0.037), better performance status (PS) (p < 0.0001), absence of chronic kidney disease (CKD) (p = 0.016), resection lesser than pneumonectomy (p = 0.010). The logit of the prediction model was: 6.58 -0.112 x age +0.039 x BMI +0.009 x FEV1 -0.650 x PS -1.388 x CKD -0.550 x pneumonectomy. The predicted rate of adjuvant chemotherapy in the validation set was 59.2 and similar to the observed 1 (59%, p = 0.87) confirming the model performance in external setting. This study identified several factors associated with the probability of initiating adjuvant chemotherapy after lung resection in node-positive patients. This information can be used during preoperative multidisciplinary meetings and patients counseling to support decision-making process regarding the timing of systemic treatment.

Perioperative costs of local or regional anesthesia versus general anesthesia in the outpatient setting: a systematic review of recent literature.

BACKGROUND AND OBJECTIVES: In this systematic review, we carried out an assessment of perioperative costs of local or regional anesthesia versus general anesthesia in the ambulatory setting. METHODS: A systematic literature search was conducted to find relevant data on costs and cost-effectiveness analyses of anesthesia regimens in outpatients, regardless of the medical procedure they underwent. The hypothesis was that local or regional anesthesia has a lower economic impact on hospital costs in the outpatient setting. The primary outcome was the average total cost of anesthesia calculated on perioperative costs (drugs, staff, resources used). RESULTS: One-thousand-six-hundred-ninety-eight records were retrieved, and 28 articles including 27,581 patients were selected after reviewing the articles. Data on the average total costs of anesthesia and other secondary outcomes (anesthesia time, recovery time, time to home readiness, hospital stay time, complications) were retrieved. Taken together, these findings indicated that local or regional anesthesia is associated with lower average total hospital costs than general anesthesia when performed in the ambulatory setting. Reductions in operating room time and postanesthesia recovery time and a lower hospital stay time may account for this result. CONCLUSIONS: Despite the limitations of this systematic review, mainly the heterogeneity of the studies and the lack of cost-effectiveness analysis, the economic impact of the anesthesia regimes on healthcare costs appears to be relevant and should be further evaluated.

Contribution margin per hour of operating room to reallocate unutilized operating room time: a cost-effectiveness analysis.

BACKGROUND AND OBJECTIVES: Contribution margin per hour (CMH) has been proposed in healthcare systems to increase the profitability of operating suites. The aim of our study is to propose a simple and reproducible model to calculate CMH and to increase cost-effectiveness. METHODS: For the ten most commonly performed surgical procedures at our Institution, we prospectively collected their diagnosis-related group (DRG) reimbursement, variable costs and mean procedural time. We quantified the portion of total staffed operating room time to be reallocated with a minimal risk of overrun. Moreover, we calculated the total CMH with a random reallocation on a first come-first served basis. Finally, prioritizing procedures with higher CMH, we ran a simulation by calculating the total CMH. RESULTS: Over a two-months period, we identified 14.5 hours of unutilized operating room to reallocate. In the case of a random "first come-first serve" basis, the total earnings were 87,117 United States dollars (USD). Conversely, with a reallocation which prioritized procedures with a high CMH, it was possible to earn 140,444 USD (p < 0.001). CONCLUSION: Surgical activity may be one of the most profitable activities for hospitals, but a cost-effective management requires a comprehension of its cost profile. Reallocation of unused operating room time according to CMH may represent a simple, reproducible and reliable tool for elective cases on a waiting list. In our experience, it helped improving the operating suite cost-effectiveness.

Dissemination of patient blood management practices in Swiss intensive care units: a cross-sectional survey.

BACKGROUND: Patient blood management (PBM) promotes the routine detection and treatment of anaemia before surgery, optimising the management of bleeding disorders, thus minimising iatrogenic blood loss and pre-empting allogeneic blood utilisation. PBM programmes have expanded from the elective surgical setting to nonsurgical patients, including those in intensive care units (ICUs), but their dissemination in a whole country is unknown. METHODS: We performed a cross-sectional, anonymous survey (10 October 2018 to 13 March 2019) of all ordinary medical members of the Swiss Society of Intensive Care Medicine and the registered ICU nurses from the 77 certified adult Swiss ICUs. We analysed PBM-related interventions adopted in Swiss ICUs and related them to the spread of PBM in Swiss hospitals. We explored blood test ordering policies, blood-sparing strategies and red blood cell-related transfusion practices in ICUs. RESULTS: A total of 115 medical doctors and 624 nurses (response rates 27% and 30%, respectively) completed the surveys. Hospitals had implemented a PBM programme according to 42% of physicians, more commonly in Switzerland's German-speaking regions (Odds Ratio [OR] 3.39, 95% confidence interval [CI] 1.23-9.35; p = 0.018) and in hospitals with more than 500 beds (OR 3.91, 95% CI 1.48-10.4; p = 0.006). The PBM programmes targeted the detection and correction of anaemia before surgery (79%), minimising perioperative blood loss (94%) and optimising anaemia tolerance (98%). Laboratory tests were ordered in 70.4% by the intensivist during morning rounds; the nurses performed arterial blood gas analyses autonomously in 48.4%. Blood-sparing techniques were used by only 42.1% of nurses (263 of 624, missing: 6) and 47.0% of physicians (54 of 115). Approximately 60% of respondents used an ICU-specific transfusion guideline. The reported haemoglobin threshold for the nonbleeding ICU population was 70 g/l and, therefore, was at the lower limit of current guidelines. CONCLUSIONS: Based on this survey, the estimated proportion of the intensivists working in hospitals with a PBM initiative is 42%, with significant variability between regions and hospitals of various sizes. The risk of iatrogenic anaemia is relevant due to liberal blood sample collection practices and the underuse of blood-sparing techniques. The reported transfusion threshold suggests excellent adherence to current international ICU-specific transfusion guidelines.

Urban-Rural Disparities in the Lung Cancer Surgical Treatment Pathway: The Paradox of a Rich, Small Region.

Introduction: Rural populations in large countries often receive delayed or less effective diagnosis and treatment for lung cancer. Differences are related to population-based factors such as lower pro capita income or increased risk factors or to differences in access to facilities. Switzerland is a small, rich country with peculiar geographic and urban characteristics.We explored the relationship between lung cancer diagnostic-surgical pathway and urban-rural residency in our region. Methods: We retrospectively analyzed the medical records of 280 consecutive patients treated for primary non-small cell lung cancer at our institution (2017-2021). This is a regional tertiary center for diagnosis and treatment, and data were extracted from a prospectively collected clinical database. We included anatomical lung resection. Collected variables included patients and surgical characteristics, risk factors, comorbidities, histology and staging, symptoms (vs. incidental diagnosis), general practitioner (GP) involvement, health insurance, and suspected test-treatment interval. The exposure was rurality, defined by the 2009 rural-urban residency classification from the Department of Land. Results: A total of 150 patients (54%) lived in rural areas. Rural patients had a higher rate of smoking history (93% vs. 82%; p = 0.007). Symptomatic vs. incidental diagnosis did not differ as well as previous cancer rate, insurance, and pathological staging. In rural patients, there was a greater burden of comorbidities (mean Charlson Comorbidity Index Age-Adjusted 5.3 in rural population vs. 4.8 in urban population, p = 0.05), and GP was more involved in the diagnostic pathway (51% vs. 39%, p = 0.04). The interval between the first suspected test and treatment was significantly shorter (56 vs. 66.5 days, p = 0.03). Multiple linear regression with backward elimination was run. These variables statistically predicted the time from the first suspected test and surgical treatment [F(3, 270), p < .05, R 2 = 0.24]: rurality (p = 0.04), GP involvement (p = 0.04), and presence of lung cancer-related symptoms (p = 0.02). Conclusions: In our territory with inhomogeneous population distribution and geographic barriers, residency has an impact on the lung cancer pathway. It seems paradoxical that rural patients had a shorter route. The more constant involvement of GP might explain this finding, having suggested more tests for high-risk patients in the absence of symptoms or follow-ups. This did not change the staging of surgical patients, but it might be essential for the organization of an effective lung cancer screening program.

Tracking the outcomes of surgical treatment of Stage 2 and 3 empyema: introduction and consolidation of minimally invasive approach.

BACKGROUND: We described the results of surgical treatment of empyema, tracing outcomes throughout the passage from the open thoracotomy (OT) approach to video-assisted thoracoscopic surgery (VATS) in a single institute. METHODS: We retrospectively analyzed the records of 88 consecutive patients treated for Stage 2 and 3 empyema (2010-2019). We divided the study period into three groups: OT period (2010-2013), early VATS (2014-2017, from the introduction of VATS program, until acme of learning curve), and late VATS (2018-2019). Groups were compared to investigate the outcomes evolution. RESULTS: Most relevant findings of the study were significant variation in postoperative length of stay (median [interquartile range]: 9 days [7.5-10], 10 [7.5-17.5], and 7 [5-10] for OT period, early VATS, and late VATS, respectively, p = 0.005), hospital admission referral to thoracic surgery interval (7.5 days [4.5-11], 6.5 [3-9], and 2.5 [1.5-5.5], p = 0.003), chest tube duration (5.5 days [5-7.5], 6 [4-6], 4 [3-5], p = 0.003), and proportion of operation performed by residents (3 [15%], 6 [16.7%], 14 [43.6%], p = 0.01). CONCLUSIONS: Our findings pictured the trajectory evolution of outcomes during introduction and consolidation of VATS treatment of empyema. During the early phase, we observed a decline in some indicators that improved significantly in the late VATS period. After a learning curve, all outcomes showed better results and we entered into a teaching phase.

Stage III N2 non-small cell lung cancer treatment: decision-making among surgeons and radiation oncologists.

BACKGROUND: Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease associated with a poor prognosis. A number of therapeutic options are available for patients with Stage III N2 NSCLC, including surgery [with neoadjuvant or adjuvant chemotherapy (CTx)/neoadjuvant chemoradiotherapy (CRT)] or CRT potentially followed by adjuvant immunotherapy. We have no clear evidence demonstrating a significant survival benefit for either of these approaches, the selection between treatments is not always straightforward and can come down to physician and patient preference. The very heterogeneous definition of resectability of N2 disease makes the decision-making process even more complex. METHODS: We evaluated the treatment strategies for preoperatively diagnosed stage III cN2 NSCLC among Swiss thoracic surgeons and radiation oncologists. Treatment strategies were converted into decision trees and analysed for consensus and discrepancies. We analysed factors relevant to decision-making within these recommendations. RESULTS: For resectable "non-bulky" mediastinal lymph node involvement, there was a trend towards surgery. Numerous participants recommend a surgical approach outside existing guidelines as long as the disease was resectable, even in multilevel N2. With increasing extent of mediastinal nodal disease, multimodal treatment based on radiotherapy was more common. CONCLUSIONS: Both, surgery- or radiotherapy-based treatment regimens are feasible options in the management of Stage III N2 NSCLC. The different opinions reflected in the results of this manuscript reinforce the importance of a multidisciplinary setting and the importance of shared decision-making with the patient.

European Society of Thoracic Surgeons electronic quality of life application after lung resection: field testing in a clinical setting.

OBJECTIVES: Technology has the potential to assist healthcare professionals in improving patient-doctor communication during the surgical journey. Our aims were to assess the acceptability of a quality of life (QoL) application (App) in a cohort of cancer patients undergoing lung resections and to depict the early perioperative trajectory of QoL. METHODS: This multicentre (Italy, UK, Spain, Canada and Switzerland) prospective longitudinal study with repeated measures used 12 lung surgery-related validated questions from the European Organisation for Research and Treatment of Cancer Item Bank. Patients filled out the questionnaire preoperatively and 1, 7, 14, 21 and 28 days after surgery using an App preinstalled in a tablet. A one-way repeated measures analysis of variance was run to determine if there were differences in QoL over time. RESULTS: A total of 103 patients consented to participate in the study (83 who had lobectomies, 17 who had segmentectomies and 3 who had pneumonectomies). Eighty-three operations were performed by video-assisted thoracoscopic surgery (VATS). Compliance rates were 88%, 90%, 88%, 82%, 71% and 56% at each time point, respectively. The results showed that the operation elicited statistically significant worsening in the following symptoms: shortness of breath (SOB) rest (P = 0.018), SOB walk (P < 0.001), SOB stairs (P = 0.015), worry (P = 0.003), wound sensitivity (P < 0.001), use of arm and shoulder (P < 0.001), pain in the chest (P < 0.001), decrease in physical capability (P < 0.001) and scar interference on daily activity (P < 0.001) during the first postoperative month. SOB worsened immediately after the operation and remained low at the different time points. Worry improved following surgery. Surgical access and forced expiratory volume in 1 s (FEV1) are the factors that most strongly affected the evolution of the symptoms in the perioperative period. CONCLUSIONS: We observed good early compliance of patients operated on for lung cancer with the European Society of Thoracic Surgeons QoL App. We determined the evolution of surgery-related QoL in the immediate postoperative period. Monitoring these symptoms remotely may reduce hospital appointments and help to establish early patient-support programmes.

Surgical treatment of pleural empyema in Coronavirus disease 19 patients: the Southern Switzerland experience.

We report the first surgical series of patients developing pleural empyema after severe bilateral interstitial lung disease in confirmed severe acute respiratory syndrome coronavirus 2 infection. The empyema results in a complex medical challenge that requires combination of medical therapies, mechanical ventilation and surgery. The chest drainage approach was not successful to relieve the symptomatology and to drain the excess fluid. After multidisciplinary discussion, a surgical approach was recommended. Even though decortication and pleurectomy are high-risk procedures, they must be considered as an option for pleural effusion in Coronavirus disease-positive patients. This is a life-treating condition, which can worsen the coronavirus disease manifestation and should be treated immediately to improve patient's status and chance of recovery.

Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Patients With Lung Cancer: The Potential Role of Interleukin-17 Target Therapy.

The coronavirus disease 2019 outbreak is evolving rapidly worldwide. The lungs are the target of the primary infection and patients with lung cancer seem to have a poor prognosis. To our knowledge, this is the first reported investigation of a possible role of interleukin-17 target therapy in patients with lung cancer and concomitant severe acute respiratory syndrome-coronavirus-2 infection.

Effect of postoperative haemoglobin variation on major cardiopulmonary complications in high cardiac risk patients undergoing anatomical lung resections.

OBJECTIVES: Recent evidence shows that permissive anaemia strategies are safe in different surgical settings. However, effects of variations in haemoglobin (Hb) levels could have a negative impact in high-risk patients. We investigated the combined effect of postoperative Hb concentration and cardiac risk status on major cardiopulmonary complications after anatomical lung resections. METHODS: We retrospectively analysed the records, collected in a prospective clinical database, of 154 consecutive patients undergoing anatomical lung resections at our institution (February 2017-February 2019). Hb levels were displayed as preoperative concentration, nadir Hb level before onset of complications and delta Hb (ΔHb). Cardiac risk was stratified according to the Thoracic Revised Cardiac Risk Index (ThRCRI). Univariable and multivariable logistic regression analyses were used to test the associations between patients, surgical variables and cardiopulmonary complications according to the European Society of Thoracic Surgeons definitions. RESULTS: Cardiopulmonary complications occurred in 63 patients (17%). In the fully adjusted multivariable model, higher values of ΔHb were associated with increased risk of complications [odds ratio (OR) 1.07; P < 0.001], along with higher ThRCRI classes (classes A-B versus C-D: OR 0.09; P < 0.001). Interaction terms with transfusion were not statistically significant, indicating that the harmful effect of ΔHb was independent. According to receiver operating characteristic curve analysis, a ΔHb of 29 g/l was found to be the best cut-off value for predicting complications. CONCLUSIONS: In our series, ΔHb, rather than nadir Hb, was associated with an increased risk of complications, particularly in patients with higher cardiac risk. Restrictive transfusion strategies should be carefully applied in patients undergoing lung resections and balanced according to individual clinical status.

Persistent postdischarge pain and chronic postoperative pain after breast cancer surgery under general anesthesia and single-shot paravertebral block: incidence, characteristics and impact on quality of life and healthcare costs.

Introduction: Breast surgery is associated with persistent postsurgical pain; usually related to poorly treated acute pain. Paravertebral block has been successfully employed in analgesic protocols for breast surgery; its impact on postdischarge pain (PDP) has not been investigated. The aim of this study was to assess characteristics of PDP after breast surgery, the development of chronic postoperative pain (CPP) and its impact on health care costs. Methods: We conducted a retrospective, observational study on a continuous cohort of adult female patients undergoing local breast cancer surgery under combined anesthesia. All patients were interviewed 6 months after hospital discharge. The survey was specifically conceived to assess incidence, features and duration of PDP. The overall cost of additional healthcare resources consumed with a specific relationship to persistent PDP was estimated. Results: A database of 244 patients was preliminarily analyzed. Of these, 188 were included in the following statistical analysis; 123 patients (65.2%) reported significant PDP, with a median intensity on NRS of 6 (IQR=2), more frequently described as burning and associated with paresthesia and/or hyperalgesia (87 patients, 46%). One hundred and six patients (56.5%) reported this pain as interfering with their normal daily activities, work and sleep. In 26.8% of cases (50 patients) symptoms lasted more than 1 month and in 28 patients (15.0%) pain became chronic. The majority of patients self-treated their pain with non-steroideal anti-inflammatory drugs, but in 50 patients (26.8%) this therapy was reported as ineffective. This additional consumption of healthcare resources led to a significant economical impact. Conclusion: PDP and CPP seem to be common complications after breast cancer surgery, even if a combined anesthesia technique with a thoracic paravertebral block is performed, leading to severe consequences on patients' quality of life and increasing consumption of healthcare resources after discharge. Trial number: NCT03618459 (www.clinicaltrials.gov).