Segmentectomy versus lobectomy: does FEV1.0 change accurately reflect the postoperative cardiopulmonary function?

OBJECTIVE: The postoperative respiratory function has been compared between lobectomy and segmentectomy based on the resting spirometric change in many previous studies. However, spirometric change has only been assessed in static conditions, and it is unclear whether it accurately reflects the cardiopulmonary function. METHODS: We used spirometry and a 6-min walk test to evaluate patients who underwent lobectomy and segmentectomy and examined the changes in heart rate (HR), respiratory rate (RR), and saturation of percutaneous oxygen (SpO2) before and after walking between the two groups. RESULTS: The present study included 24 patients who underwent segmentectomy and 21 who underwent lobectomy. There was no significant difference in the reduction of the median forced expiratory volume in 1 s (FEV1.0) after surgery. In the 6-min walk test, the increase in HR and RR after surgery has no significant differences between lobectomy and segmentectomy (HR: p = 0.372 and RR: p = 0.131). However, the two groups showed a significant difference in the reduction of SpO2 (p < 0.001). In addition, correlation analysis found that the more the number of resected segments, the more the reduction of SpO2 with a statistical significance (p = 0.002). CONCLUSIONS: Patients who received segmentectomy showed to suppress the reduction of SpO2 with a statistical difference after the 6-min walk test in comparison to those who received lobectomy. These results suggest that segmentectomy has less impact on the cardiopulmonary function and the 6-min walk test is useful for evaluating the postoperative cardiopulmonary function.

Resected stage I anaplastic lymphoma kinase-positive lung adenocarcinoma has a negative impact on recurrence-free survival.

BACKGROUND: The clinical and prognostic implications of anaplastic lymphoma kinase (ALK) status in resected lung cancers remain unclear. In this study we analyzed the prognostic and predictive significance of ALK-positive among patients with completely resected lung adenocarcinoma. METHODS: We retrospectively reviewed 197 patients with lung adenocarcinoma who underwent complete surgical resection and had been tested for their ALK status. We investigated the impact of an ALK-positive status on the recurrence-free survival (RFS) and overall survival (OS) and examined the predictive factors for an ALK-positive status. RESULTS: ALK positivity was noted in 36 (18%) out of 197 patients, and when limited to stage I patients, in 24 (19%) out of 124. In the pathological-stage I population, while the OS exhibited no significant difference between ALK-positive and ALK-negative patients (5-year OS rate, 81.2% vs. 89.8%, p = 0.226), the RFS of ALK-positive patients was significantly worse than that of ALK-negative patients (5-year RFS rate, 55.9% vs. 78.8%, p = 0.018). A multivariate analysis showed that ALK-positive status (hazard ratio [HR] 3.431, p = 0.009) was an independent prognostic factor for the RFS. Regarding the relationship between clinicopathological factors and an ALK-positive status, a high-grade histological subtype, including solid and micropapillary subtypes (odds ratio [OR] 5.464, p < 0.001), and never-smokers (OR 4.292, p = 0.018) were associated with ALK-positive. CONCLUSION: A high-grade histological subtype and never-smokers were associated with ALK positivity, and the RFS of ALK-positive patients was worse than that of ALK-negative patients among patients with completely resected stage I lung adenocarcinoma.

The difference in postoperative pulmonary functional change between upper and lower thoracoscopic lobectomy.

OBJECTIVES: Through 3-dimensional lung volumetric and morphological analyses, we aimed to evaluate the difference in postoperative functional changes between upper and lower thoracoscopic lobectomy. METHODS: A total of 145 lung cancer patients who underwent thoracoscopic upper lobectomy (UL) were matched with 145 patients with lung cancer who underwent thoracoscopic lower lobectomy (LL) between April 2012 and December 2018, based on their sex, age, smoking history, operation side, and pulmonary function. Spirometry and computed tomography were performed before and 6 months after the operation. In addition, the postoperative pulmonary function, volume and morphological changes between the 2 groups were compared. RESULTS: The rate of postoperative decreased and the ratio of actual to predicted postoperative forced expiratory volume in 1 s were significantly higher after LL than after UL (P < 0.001 for both). The tendency above was similar irrespective of the resected side. The postoperative actual volumes of the ipsilateral residual lobe and contralateral lung were larger than the preoperatively measured volumes in each side lobectomy. Moreover, the increased change was particularly remarkable in the middle lobe after right LL. The change in the D-value, representing the structural complexity of the lung, was better maintained in the left lung after LL than after UL (P = 0.042). CONCLUSIONS: Pulmonary function after thoracoscopic LL was superior to that after UL because the upward displacement and the pulmonary reserves of the remaining lobe appeared more robust after LL.

Prognostic significance of preoperative haemoglobin A1c level in patients with lung adenocarcinoma.

OBJECTIVES: We investigated the influence of the preoperative haemoglobin A1c (HbA1c) value on the prognosis and pathology of patients with lung adenocarcinoma who underwent surgery. METHODS: We reviewed the medical records of 400 lung adenocarcinoma patients who underwent lobectomy with mediastinal lymph node dissection between 2009 and 2013 using a prospectively maintained database. We stratified 400 patients into 4 groups according to the preoperative HbA1c value as follows: HbA1c ≤ 5.9 (n = 296), 6.0 ≤ HbA1c ≤ 6.9 (n = 70), 7.0 ≤ HbA1c ≤ 7.9 (n = 21) and HbA1c ≥ 8.0 (n = 12). We compared the recurrence-free survival and overall survival (OS) among these 4 groups. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. RESULTS: The median follow-up period was 61.2 months. On comparing the recurrence-free survival and OS rates among these 4 groups, we found that these rates among patients in the HbA1c ≥ 8.0 group were significantly poorer compared with the other 3 groups (5-year recurrence-free survival: HbA1c ≤ 5.9, 70.4%; 6.0 ≤ HbA1c ≤ 6.9, 69.7%; 7.0 ≤ HbA1c ≤ 7.9, 70.7%; ≥8.0 HbA1c, 18.8%; P = 0.002; and 5-year OS: HbA1c ≤ 5.9, 88.7%; 6.0 ≤ HbA1c ≤ 6.9, 80.6%; 7.0 ≤ HbA1c ≤ 7.9, 90.2%; ≥8.0 HbA1c, 66.7%; P = 0.046). Patients in the HbA1c ≥ 8.0 group had significantly more tumours with vascular invasion (P = 0.041) and experienced distant metastasis significantly more often (P = 0.028) than those with other values. A multivariate analysis revealed that preoperative HbA1c ≥ 8.0 [hazard ratio (HR) 2.33; P = 0.026] and lymph node metastasis (HR 3.94; P < 0.001) were significant independent prognostic factors for recurrence. CONCLUSIONS: Our results revealed that preoperative HbA1c ≥ 8.0 is associated to poor prognosis due to the occurrence of distant metastasis and we should carefully follow these patients after surgery. CLINICAL REGISTRATION NUMBER: Hyogo Cancer Center, G-57.

Cluster analysis of emphysema for predicting pulmonary complications after thoracoscopic lobectomy.

OBJECTIVES: Despite significant advances in surgical techniques, including thoracoscopic approaches and perioperative care, the morbidity rate remains high after lung resection. This study focused on a low attenuation cluster analysis, which represented the size distribution of pulmonary emphysema and assessed its utility for predicting postoperative pulmonary complications after thoracoscopic lobectomy. METHODS: From April 2013 to September 2018, lung cancer patients who received spirometry and computed tomography (CT) before surgery and underwent thoracoscopic lobectomy were included. The cumulative size distribution of the low attenuation area (LAA, defined as ≤-950 Hounsfield unit on CT) clusters followed a power-law characterized by an exponent D-value, a measure of the complexity of the alveolar structure. D-value and LAA% (LAA/total lung volume) were calculated using preoperative 3-dimensional CT software. The relationship between pulmonary complications and patient characteristics, including D-value and LAA%, was investigated. RESULTS: Among 471 patients, there were 61 respiratory complication cases (12.9%). Receiver operation characteristic curve analysis revealed that the best predictive cut-off value of D-value and LAA% for pulmonary complications was 2.27 and 16.5, respectively, with an area under the curve of 0.72 and 0.58, respectively. D-value was significantly correlated with % forced expiratory volume in 1 s. Per univariate analysis, gender, smoking history, forced expiratory volume in 1 s/forced vital capacity, LAA% and D-value were risk factors for predicting postoperative pulmonary complications. In the multivariate analysis, D-value remained a significant predictive factor. CONCLUSION: Preoperative assessment of emphysema cluster analysis may represent the vulnerability of the operated lung and could be the novel predictor for pulmonary complications after thoracoscopic lobectomy.

Pleural invasion, epidermal growth factor receptor mutation and carcinoembryonic antigen level affect pleural lavage cytology-positive status in non-small-cell lung cancer.

OBJECTIVES: Pleural invasion (pl) is strongly associated with the pleural lavage cytology (PLC) status. We analysed tumours with pl and evaluated the relationship between the PLC status and pl. METHODS: We retrospectively reviewed 428 surgically treated patients who had been diagnosed with non-small-cell lung cancer with pl and had their PLC status examined between 2000 and 2016. We investigated the influence of a PLC-positive status on the prognosis and searched for the factors predictive of a PLC-positive status. RESULTS: Seventy-eight (18%) patients were PLC positive. The recurrence-free survival of PLC-positive patients was significantly worse than that of PLC-negative patients in pl1 and pl2, but not in pl3 (5-year recurrence-free survival rate, PLC positive versus PLC negative: pl1, 22.0% vs 60.0%, P = 0.002; pl2, 30.4% vs 59.7%, P = 0.015; pl3, 50.0% vs 59.6%, P = 0.427). A multivariable analysis showed that the degree of pl (pl2-3 versus pl1) [odds ratio (OR) 5.34, P < 0.001] was an independent predictive factor for PLC positivity. Epidermal growth factor receptor (EGFR) mutation positivity (OR 5.48, P = 0.042) and carcinoembryonic antigen (CEA) ≥5 ng/ml (OR 3.78, P = 0.042) were associated with a PLC-positive status in patients with pl2-3. We found that the PLC-positive rate in patients with pl2-3 was 35.6%; however, if the tumour was EGFR mutation positive and had CEA ≥5 ng/ml, the PLC-positive rate increased to 77%. CONCLUSIONS: If a tumour was suspected of being pl2-3 and had EGFR mutation positivity and CEA ≥5 ng/ml, the PLC-positive rate was extremely high. CLINICAL TRIAL REGISTRATION NUMBER: Hyogo Cancer Center, G-138.

Thoracoscopic left S1 + 2 segmentectomy as a good resolution for preserving pulmonary function.

OBJECTIVES: Segmentectomies such as S1 + 2, S1 + 2+3 and S4 + 5 segmentectomy are used to treat patients with non-small-cell lung cancer (NSCLC) in the left upper lobe. However, the preservable lung volume and changes after such segmentectomies remain unknown. We compared the residual pulmonary function after thoracoscopic segmentectomy or lobectomy in the left upper lobe and examined the efficacy of S1 + 2 segmentectomy regarding postoperative pulmonary function. METHODS: Patients with left upper lobe NSCLC who underwent thoracoscopic segmentectomy or lobectomy were included. Spirometry and computed tomography were performed before and 6 months after resection, and the ipsilateral preserved lobe volume was calculated using 3-dimensional computer tomography. The percentage of postoperative/preoperative forced expiratory volume in 1 s and actual/predicted regional forced expiratory volume in 1 s (preservation rate) in the residual lobe were compared. RESULTS: Eighty-eight patients underwent lobectomy and 70 patients underwent segmentectomy (23 S1 + 2, 35 S1 + 2+3 and 12 S4 + 5 segmentectomies). The percentage of postoperative/preoperative forced expiratory volume in 1 s was 97 in S1 + 2, 82 in S1 + 2+3, 86 in S4 + 5 segmentectomy and 73 in left upper lobectomy, indicating that segmentectomy could be a meaningful approach to preserve pulmonary function. The preservation rate was 83% in S1 + 2 and 62% in S1 + 2+3 segmentectomy and was significantly higher in S1 + 2 than in S1 + 2+3 segmentectomy (P < 0.001). CONCLUSIONS: Postoperative pulmonary function and the preservable lung volume of the residual lobe after thoracoscopic S1 + 2 segmentectomy were well-preserved among other segmentectomies and lobectomy. Thoracoscopic S1 + 2 segmentectomy is a good alternative for preserving postoperative function.

DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC.

BACKGROUND: The mammalian Notch family ligands delta-like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. METHODS: We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum-based adjuvant chemotherapy. RESULTS: DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum-based adjuvant chemotherapy. Among patients with DLL3 expression-positive tumors, no difference was found in the five-year overall survival (OS) or recurrence-free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five-year OS: 58.3% vs. 35.7% P = 0.36, five-year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3-negative tumors, significantly greater five-year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five-year OS: 90.0% vs. 26.9% P<0.01, five-year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3-negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01-0.41, P < 0.01), although it was not a factor among patients with DLL3-positive tumors (HR: 0.73, 95% CI: 0.23-2.27, P = 0.58). CONCLUSIONS: Our results revealed that DLL3 is a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DLL3 was a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression-negative LCNEC, platinum-based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression-positive LCNEC. WHAT THIS STUDY ADDS: Our results suggest that DLL3 expression-positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti-DLL3 therapies if these effects are confirmed by ongoing clinical research.

Pneumatocele triggered by continuous positive airway pressure after lung resection.

A pneumatocele is a cystic change of the lung that is caused by a check valve in the bronchiole due to infection, trauma and positive-pressure ventilation. We herein report a case of pneumatocele triggered by using of continuous positive airway pressure (CPAP) for sleep apnea syndrome (SAS) after pulmonary resection. A 69-year-old man underwent right upper lobectomy for lung cancer and developed interstitial pneumonia (IP) 10th postoperative day (POD). He was treated with steroid pulse therapy (solmedrol 500 mg × 3 days), and thereafter with oral steroid therapy (predonin 30mg/day). Well responded to the steroid therapy, IP was improved. However, he noticed bloody sputum 29th POD, and chest computed tomography showed a giant cystic lesion on the dorsal right lower lobe. We resected the cyst and the pathological findings revealed that the cystic lesion was pneumatocele, and CPAP was strongly suspected of triggering this disease.