Utility of neutrophil-to-lymphocyte ratio as an indicator of tumor immune status in non-small cell lung cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic biomarker in non-small cell lung cancer (NSCLC); however, the underlying biological rationale remains unclear. The present study aimed to explore the potential utility of NLR as a surrogate biomarker for immune response to cancer and to elucidate the underlying mechanism. METHODS: This retrospective study included the medical records of 120 patients with NSCLC who underwent surgery at the study institution in 2012. NLR in peripheral blood was determined from blood test within 30 days before surgery. Tumor immune status was evaluated using immunohistochemical staining to identify CD3+, CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs), and the relationship of NLR, with clinicopathologic characteristics including 5-year overall survival (OS), and the tumor immune status was investigated. The median values of NLR and TIL count were used as cutoff points. RESULTS: The 5-year OS was significantly better in patients with low NLR (<2.2) than in those with high NLR (≥2.2) (70.1% vs. 56.8%, P = 0.042) and in patients with high CD3+ TIL count (≥242) than in those with low CD3+ TIL count (<242) (70% vs. 56.8%, P = 0.019). Additionally, the CD3+ TIL count was negatively correlated with preoperative NLR (P = 0.005). CONCLUSION: NLR might potentially reflect the immune status of tumor microenvironment, explaining its impact on prognosis of patients with NSCLC.

Effective division of the intersegmental plane using a robotic stapler in robotic pulmonary segmentectomy.

PURPOSES: Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes. METHODS: RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period. RESULTS: The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS. CONCLUSIONS: The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective.

Impact of the neutrophil-to-lymphocyte ratio on patients with locally advanced non-small cell lung cancer who suffer radiation pneumonitis during the course of induction chemoradiotherapy followed by surgery.

PURPOSE: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery. METHODS: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis. RESULTS: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group. CONCLUSION: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC.

Pulmonary Vein Repair on Extracorporeal Life Support: A Potential Surgical Complication for 2-Staged Lung Transplantation: Case Report.

Double-lung transplantation (DLT) is favored for enhanced long-term survival despite the risk of major complications, particularly in elderly patients or those with comorbidities. Two-stage contralateral single-lung transplantation (SLT) leading to DLT is considered a valuable option to combine the advantages of less invasive SLT with DLT survival benefits. This study detailed the intraoperative challenges encountered during the procedure. A 54-year-old patient with chronic lung allograft dysfunction after right SLT underwent contralateral (left) SLT because of left lung dysfunction. During surgery, unexpected complications arose from robust adhesions on the right side, a consequence of prior transplantation, causing difficulty in manipulating the heart position. The deep bifurcation of the left pulmonary vein posed challenges, leading to damage to the left atrium, necessitating extracorporeal circulation. Despite these complexities, successful anastomosis was achieved. This case highlights the importance of recognizing potential surgical difficulties in contralateral lung transplantation, particularly in cases with adhesions, and emphasizes the need for caution when managing deep pulmonary veins. This 2-stage approach holds promise for patients with poor health but emphasizes the significance of addressing the potential challenges inherent in the surgical procedure.

Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation.

OBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction. METHODS: According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0-1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation. RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml. CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction.

Long-term outcomes of lung transplantation requiring renal replacement therapy: A single-center experience.

BACKGROUND: Life-long immunosuppressive therapy after lung transplantation (LT) may lead to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT). We aimed to investigate the characteristics and long-term outcomes of patients undergoing LT and requiring RRT. METHODS: This study was a single-center, retrospective cohort study. The patients were divided into the RRT (n = 15) and non-RRT (n = 170) groups. We summarized the clinical features of patients in the RRT group and compared patient characteristics, overall survival, and chronic lung allograft dysfunction (CLAD)-free survival between the two groups. RESULTS: The cumulative incidences of ESRD requiring RRT after LT at 5, 10, and 15 years were 0.8 %, 7.6 %, and 25.2 %, respectively. In the RRT group, all 15 patients underwent hemodialysis but not peritoneal dialysis, and two patients underwent living-donor kidney transplantation. The median follow-up period was longer in the RRT group than in the non-RRT group (P < 0.001). The CLAD-free survival and overall survival did not differ between the two groups. The 5-year survival rate even after the initiation of hemodialysis was 53.3 %, and the leading cause of death in the RRT group was infection. CONCLUSIONS: Favorable long-term outcomes can be achieved by RRT for ESRD after LT.

Postoperative Complications in Living Donors for Lung Transplantation.

Background: Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor's safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes. Methods: The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998-2009) and era 2 (2010-2022). Results: The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae (P = 0.01) and elevated liver enzyme levels (P = 0.028). Living donor surgery on the right side (P = 0.01), era 2 (P = 0.01), and the need for plasty (P = 0.04) were predictors of postoperative complications. Conclusions: Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent.

Augmented humoral response to third and fourth dose of SARS-CoV-2 mRNA vaccines in lung transplant recipients.

BACKGROUND: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs. METHODS: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses. RESULTS: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021). CONCLUSION: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection.

Effects of case volume on short- and long-term outcomes following cadaveric lung transplantation in Japan.

Background: Despite the low number of lung transplantations (LTs) in Japan, 10 LT facilities are accredited and good outcomes have been reported. A database review was conducted to clarify the impact of case volume at LT facilities in Japan on short- and long-term outcomes. Methods: All cadaveric LT cases treated between 2000 and 2021 in Japan were analyzed using the database of the Japanese Society of Lung and Heart-Lung Transplantation (JSLHT). The nine institutions represented were categorized into the low-volume (LV; <80 cumulative LT cases, <8 LTs/year, n=5) and high-volume (HV; ≥80 cumulative LT cases, ≥8 LTs/year, n=4) centers. Ninety-day and 1-year mortality, as well as 5- and 10-year survival data were evaluated. Results: A total of 658 cadaveric LTs were performed at the nine institutions. The 90-day rates of mortality at the HV and LV centers were 3.5% and 3.9%, respectively (P=0.801), while the 1-year mortality rates were 9.2% and 11.5%, respectively (P=0.199). Additionally, log-rank analysis of Kaplan-Meier curves showing case volume did not reveal a significant difference in long-term survival between the HV and LV centers (P=0.272), though the LV centers had wide differences for long-term outcomes (P=0.030). Conclusions: Case volume did not have effects on short- or long-term outcomes following LT in Japan, while there were large variations in long-term outcomes among the LV centers compared to those of the HV centers.