Relationship Between Preoperative Inflammation Ratios Derived From Preoperative Blood Cell Count and Postoperative Pulmonary Complications in Patients Undergoing Lobectomy: A Single-Center Observational Study.

OBJECTIVE: Evaluation of the association of inflammatory cell ratios, especially neutrophil-to-lymphocyte ratio (NLR), based on preoperative complete blood counts, with postoperative complications in lobectomy surgery. DESIGN: This was a retrospective monocentric cohort study. SETTING: The study was conducted at Foch University Hospital in Suresnes, France. PARTICIPANTS: Patients having undergone a scheduled lobectomy from January 2018 to September 2021. INTERVENTIONS: There were no interventions. MEASUREMENTS AND MAIN RESULTS: The authors studied 208 consecutive patients. Preoperative NLR, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammation index, systemic inflammation response index, and aggregate inflammation systemic index were calculated. Median and (IQR) of NLR was 2.67 (1.92-3.69). No statistically significant association was observed between any index and the occurrence of at least one major postoperative complication, which occurred in 37% of the patients. Median postoperative length of stay was 7 (5-10) days. None of the ratios was associated with prolonged length of stay (LOS), defined as a LOS above the 75th percentile. CONCLUSIONS: The results suggested that simple available inflammatory ratios are not useful for the preoperative identification of patients at risk of postoperative major complications in elective lobectomy surgery.

Results of Lung Transplantation for Cystic Fibrosis With Selected Donors Over 65 Years Old.

Lung transplantation is limited by the shortage of suitable donors. Many programs have begun to use extended criteria donors. Donors over 65 years old are rarely reported, especially for young cystic fibrosis recipients. This monocentric study was conducted for cystic fibrosis recipients from January 2005 to December 2019, comparing two cohorts according to lung donor age (<65 years or ≥65 years). The primary objective was to assess the survival rate at 3 years using a Cox multivariable model. Of the 356 lung recipients, 326 had donors under 65 years, and 30 had donors over 65 years. Donors' characteristics did not differ significantly in terms of sex, time on mechanical ventilation before retrieval, and partial pressure of arterial oxygen/fraction of inspired oxygen ratio. There were no significant differences in post-operative mechanical ventilation duration and incidence of grade 3 primary graft dysfunction between the two groups. At 1, 3, and 5 years, the percentage of predicted forced expiratory volume in 1 s (p = 0.767) and survival rate did not differ between groups (p = 0.924). The use of lungs from donors over 65 years for cystic fibrosis recipients allows extension of the donor pool without compromising results. Longer follow-up is needed to assess the long-term effects of this practice.

Prospective Radiologic-Pathologic Correlation of Macroscopic Volume and Microscopic Extension of Nonsolid Lung Nodules on Thin-section CT Images for Sublobar Resection and Stereotactic Radiotherapy Planning.

INTRODUCTION: The objective of this study was to determine whether computed tomography (CT) could be a useful tool for nonsolid lung nodule (NSN) treatment planning, surgery or stereotactic body radiation therapy (SBRT), by assessing the macroscopic and microscopic extension of these nodules. METHODS: The study prospectively included 23 patients undergoing anatomic resection at the Foch Hospital in 2020/2021 for NSN with a ground-glass component of more than 50%. Firstly, for each patient, both the macroscopic dimensions of the NSN were assessed on CT and during pathologic analysis. Secondly, the microscopic extension was assessed during pathologic examination. Wilcoxon sign rank tests were used to compare these dimensions. Spearman correlation test and Bland-Altman analysis were used to evaluate the agreement between radiological and pathologic measurements. RESULTS: On CT, the median largest diameter and volume of NSN were 21 mm and 3780 cc, while on pathologic analysis, they were 15 mm and 1800 cc, respectively. Therefore, the largest diameter and volume of the NSN were significantly higher on CT than on pathological analysis. For microscopic extension, the median largest diameter and volume of NSN were 17 mm and 2040 cc, respectively. No significant difference was observed between the macroscopic size and the microscopic extension assessed during pathologic analysis. Moreover, correlation analysis and Bland-Altman plots showed that radiological and pathologic measurements could provide equivalent precision. CONCLUSION: Our study showed that CT did not underestimate the macroscopic size and microscopic extension of NSN and confirmed that CT can be used for NSN treatment planning.

A virtual crossmatch-based strategy for perioperative desensitisation in lung transplant recipients with pre-formed donor-specific antibodies: 3-year outcome.

BACKGROUND: Pre-formed donor-specific antibodies (DSAs) are associated with worse outcome after lung transplantation (LTx) and might limit access to LTx. A virtual crossmatch-based strategy for perioperative desensitisation protocol has been used for immunised LTx candidates since 2012 at Foch Hospital (Suresnes, France). We compared the outcome of desensitised LTx candidates with high DSA mean fluorescence intensity and those with low or no pre-formed DSAs, not desensitised. METHODS: For all consecutive LTx recipients (January 2012 to March 2018), freedom from chronic lung allograft dysfunction (CLAD) and graft survival were assessed using Kaplan-Meier analysis and Cox multivariate analysis. RESULTS: We compared outcomes for desensitised patients with high pre-formed DSAs (n=39) and those with no (n=216) or low pre-formed DSAs (n=66). The desensitisation protocol decreased the level of immunodominant DSA (class I/II) at 1, 3 and 6 months post-LTx (p<0.001, p<0.01 and p<0.001, respectively). Freedom from CLAD and graft survival at 3 years was similar in the desensitised group as a whole and other groups. Nevertheless, incidence of CLAD was higher with persistent high-level DSAs than cleared high-level (p=0.044) or no DSAs (p=0.014). Conversely, graft survival was better with cleared high DSAs than persistent high-level, low-level and no pre-formed DSAs (p=0.019, p=0.025 and p=0.044, respectively). On multivariate analysis, graft survival was associated with cleared high DSAs (hazard ratio 0.12, 95% CI 0.02-0.85 versus no DSAs; p=0.035) and CLAD with persistent DSAs (3.04, 1.02-9.17 versus no pre-formed DSAs; p=0.048). CONCLUSION: The desensitisation protocol in LTx recipients with high pre-formed DSAs was associated with satisfactory outcome, with cleared high pre-formed DSAs after desensitisation identified as an independent predictor of graft survival.

Hanging donor lungs give good short-, mid- and long-term results in lung transplantation.

BACKGROUND: Hanging donors are considered as marginal donors and frequently unsuitable for lung transplantation. However, there is no evidence of higher lung transplantation (LTx) morbidity-mortality with lungs providing by hanging donor. METHODS: Between January 2010 and July 2015, we performed a retrospective study at Foch hospital. We aimed to assess whether hanging donor grafts are suitable for lung transplantation. RESULTS: A total of 299 LTx were performed. Subjects were allocated to a hanging group (HG) (n = 20) and a control group (CG) (n = 279). Donor and recipient characteristics did not differ. Primary graft dysfunction (PGD) at 72 hours was comparable in both groups (P = .75). The median duration of postoperative mechanical ventilation (1 [range, 0-84] vs 1 [range, 0-410] day, P = .35), the hospital length of stay (31 days [20-84] vs 32 days [12-435], P = .36) did not differ between the two groups. No statistically significant difference was found in 1-year and 5-year survival between the HG (83% and 78%) and the CG (86% and 75%), P = .85. CONCLUSION: We believe that hanging donors should be considered as conventional donors with particular caution in the final evaluation of the graft and in perioperative management.

Impact of donor, recipient and matching on survival after high emergency lung transplantation in France.

INTRODUCTION: Since July 2007, the French high emergency lung transplantation (HELT) allocation procedure prioritises available lung grafts to waiting patients with imminent risk of death. The relative impacts of donor, recipient and matching on the outcome following HELT remain unknown. We aimed at deciphering the relative impacts of donor, recipient and matching on the outcome following HELT in an exhaustive administrative database. METHODS: All lung transplantations performed in France were prospectively registered in an administrative database. We retrospectively reviewed the procedures performed between July 2007 and December 2015, and analysed the impact of donor, recipient and matching on overall survival after the HELT procedure by fitting marginal Cox models. RESULTS: During the study period, 2335 patients underwent lung transplantation in 11 French centres. After exclusion of patients with chronic obstructive pulmonary disease/emphysema, 1544 patients were included: 503 HELT and 1041 standard lung transplantation allocations. HELT was associated with a hazard ratio for death of 1.41 (95% CI 1.22-1.64; p<0.0001) in univariate analysis, decreasing to 1.32 (95% CI 1.10-1.60) after inclusion of recipient characteristics in a multivariate model. A donor score computed to predict long-term survival was significantly different between the HELT and standard lung transplantation groups (p=0.014). However, the addition of donor characteristics to recipient characteristics in the multivariate model did not change the hazard ratio associated with HELT. CONCLUSIONS: This exhaustive French national study suggests that HELT is associated with an adverse outcome compared with regular allocation. This adverse outcome is mainly related to the severity status of the recipients rather than donor or matching characteristics.

Mutational Diversity of Lung Cancer and Associated Lymph Nodes. An Exploratory Prospective Study of 4 Resected cIIIA-N2.

Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected. Samples (tumour and paired LN) were analysed for PD1, PD-L1 and CD8 immunostaining. Somatic mutation testing was performed by deep targeted next generation sequencing (NGS), with the AmpliSeq™ Colon and Lung Cancer Panel (LifeTechnology). A total of 9 primary lung cancer samples and 10 LN stations were analysed. For each cancer, we found 2 mutations, with allelic ratios from 3% to 72%. Mutational patterns were heterogeneous for 2 primary tumours. In 3 cases, mutations observed in the primary tumour were not found in LN metastases (ALK, FGFR3, MET). Inversely, in 1 case, a KRAS mutation was found in LN but not in the primary tumour. All primary tumours were found PD-L1 positive while CD8+ T cells infiltrate varied. In the different examined LN samples, PD-L1 expression, CD8+ and PD1+ T cells infiltrate were not similar to the primary tumour. This preliminary prospective study shows the diversity of intra-tumour and LN mutations using routinely-used targeted NGS, concerning both mutated gene and allelic ratio. Further studies are needed to evaluate its prognostic impact.

Post-traumatic massive hand lymphedema fully cured by vascularized lymph node flap transfer.

Post-traumatic localized hand lymphedema is a rare situation and its diagnosis may be difficult, causing lack of care leading to failure of care. Our case study is of two young women with massive post-traumatic hand lymphedema who were treated for algodystrophy for 2 years, and whose bandages and physiotherapy were unsuccessful. Major social and psychological consequences due to difficulty with diagnosis and management resulting in inappropriate tests and therapeutic treatment were prescribed due to these issues. Noncontrast magnetic resonance lymphography revealed complete lymphatic vessel blockage in the hand and wrist. A vascularized lymph node flap harvested at the groin level was transferred to the elbow level 1 month after local dermolipectomy. These procedures resulted in the restoration of lymphatic flow. Both patients were definitely cured, and they returned to normal life within 6 months after surgery. Lymph node flap transfer associated with dermolipectomy may cure massive localized lymphedema in selected cases.

Ewing Sarcoma of the Chest Wall: Prognostic Factors of Multimodal Therapy Including En Bloc Resection.

BACKGROUND: Radiotherapy has long been the treatment of choice for local control of Ewing sarcoma of the chest wall (ESCW). However, there is debate regarding the use of surgery versus radiotherapy. The objective of this study was to identify risk factors that may affect long-term outcomes of nonmetastatic ESCW treated with preoperative chemotherapy (CT) followed by en bloc resection and adjuvant CT or chemoradiation. METHODS: Between 1996 and 2014, 30 patients with a median age of 25 years (SD ± 8.9 years) were treated at Marie-Lannelongue Hospital in Le Plessis-Robinson, France. Adjuvant therapy was used in 27 patients: CT for 6, chemoradiation for 20, and radiotherapy for 1. Patients' demographics, treatment data, tumor features, and outcomes were collected. RESULTS: In this cohort of patients who received multimodal therapy, including neoadjuvant CT and en bloc resection, there was no postoperative mortality. Eight patients (27%) experienced postoperative complications. Resection included at least one rib (n = 27) and the sternum (n = 1) or the spine (n = 8). Negative and microscopic disease resections were achieved in 28 and 2 patients, respectively. Tumor viability (TV) was ≤5% in 18 patients (60%). In patients with TV >5% at definitive histologic examination, adjuvant chemoradiation was associated with a better long-term outcome than was treatment with adjuvant CT alone. The 5-year overall survival and disease-free survival rates were 60.7% and 41.0%, respectively, with a median survival of 87 months. By univariate analysis, TV >5% and pleural extension at diagnosis were associated with poorer long-term survival (p < 0.05). CONCLUSIONS: Multimodality treatment of ESCW, including neoadjuvant CT followed by en bloc resection and adjuvant CT or chemoradiation, is associated with excellent long-term outcomes.

Can mathematics replace anatomy to establish recommendations in lung cancer surgery?

The greater the number of lymph node (LN) sampled (NLNsS) during lung cancer surgery, the lower the risk of underestimating the pN-status and the better the outcome of the pN0-patients due to stage-migration. Thus, regarding LN sampling "to be or not to be", number is the question. Recent studies advocate removing 10 LNs. The most suitable NLNsS is unfortunately impossible to establish by mathematics. A too high NLNsS variability exists, based on anatomy, surgery and pathology. The methodology may vary according to Inter-institutional differences in the surgical approach regarding LN inspection and number sampling. The NLNsS increases with the type of resection: sublobar, lobectomy or pneumonectomy. Concerning pathology, one LN may be divided into several pieces, leading to number overestimation. The pathological examination is limited by the number of slices analyzed by LN. The examined LNs can arbitrarily depend on the probability of detecting nodal metastasis. In fact, the only way to ensure the best NLNsS and the best pN-staging is to remove all LNs from the ipsilateral mediastinal and hilar LN-stations as they are discovered by thoroughly dissecting their anatomical locations. In doing so, a deliberate lack of harvest of LNs is unlikely, number turns out not to be the question anymore and a low NLNsS no longer means incomplete surgery. This prevents from judging as incomplete a complete LN dissection in a patient with a small NLNsS and from considering as complete a true incomplete one in a patient with a great NLNsS. Precise information describing the course of the operation and furnished in the surgeon's reports is also advisable to further improve the quality of LN-dissection, which ultimately might be beneficial in the long-term to patients. However, that procedure is of limited interest in pN-staging if LNs are not thoroughly examined and also described by the pathologist.