Enhancing identification of early-stage lung adenocarcinomas through solid component analysis of three-dimensional computed tomography images.

OBJECTIVES: As the role of segmentectomy expands in managing early-stage lung adenocarcinoma, precise preoperative assessments of tumor invasiveness via computed tomography become crucial. This study aimed to evaluate the effectiveness of solid component analysis of three-dimensional (3D) computed tomography images and establish segmentectomy criteria for early-stage lung adenocarcinomas. METHODS: This retrospective study included 101 cases with adenocarcinoma diagnoses, with patients undergoing segmentectomy for clinical stage 0 or IA between 2012 and 2017. The solid component volume (3D-volume) and solid component ratio (3D-ratio) of tumors were calculated using 3D computed tomography. Additionally, based on two-dimensional (2D) computed tomography, the solid component diameter (2D-diameter) and solid component ratio (2D-ratio) were calculated. The area under the receiver-operating characteristic curve (AUC) was calculated for each method, facilitating predictions of mortality and recurrence within 5 years. The AUC of each measurement was compared with those of invasive component diameter (path-diameter) and invasive component ratio (path-ratio) obtained through pathology analysis. RESULTS: The predictive performance of 3D-volume did not differ significantly from that of path-diameter, whereas 2D-diameter exhibited less predictive accuracy (AUC: 3D-volume, 2D-diameter, and path-diameter: 0.772, 0.624, and 0.747, respectively; 3D-volume vs. path-diameter: p = 0.697; 2D-diameter vs. path-diameter: p = 0.048). Results were similar for the solid component ratio (AUC: 3D-ratio, 2D-ratio, path-ratio: 0.707, 0.534, and 0.698, respectively; 3D-ratio vs. path-ratio: p = 0.882; 2D-ratio vs. path-ratio: p = 0.038). CONCLUSION: Solid component analysis using 3D computed tomography offers advantages in prognostic prediction for early-stage lung adenocarcinomas.

Lobar shifting after lobectomy other than left upper lobectomy has a beneficial impact on postoperative pulmonary function.

PURPOSE: Occasionally, lobes displace after lobectomy, which is referred to as "lobar shifting". This study aimed to evaluate the effect of lobar shifting on postoperative pulmonary function. METHODS: We analyzed the records of 761 patients who underwent lobectomy between 2012 and 2022. The patients were categorized based on three-dimensional computed tomography (3D-CT) images into those with (shift group: n = 510) and those without (non-shift group: n = 251) their postoperative subject bronchus shifting toward the head or dorsal side. The preservation rate of forced expiratory volume in one second (FEV1.0) was compared between the two groups. Several factors were investigated to identify the cause of lobar shifting. RESULTS: FEV1.0 preservation rates, excluding left upper lobectomy, were significantly better in the shift group than in the non-shift group (all patients: 87.9% vs. 84.9%, p < 0.001; right upper lobectomy: 90.1% vs. 85.4%, p = 0.002; right lower lobectomy: 90.0% vs. 84.5%, p = 0.002; left upper lobectomy: 82.0% vs. 83.9%, p = 0.43; left lower lobectomy: 90.0% vs. 85.2%, p = 0.01). Factors that correlated with lobar shifting included age (p < 0.001), adhesions (p < 0.001), and lobulation (p = 0.001). CONCLUSIONS: Lobar shifting may benefit postoperative pulmonary function, excluding after left upper lobectomy. Morphological factors contribute to lobar shifting.

Factors affecting the short-term outcomes of robotic-assisted thoracoscopic surgery for lung cancer.

PURPOSE: Robotic-assisted thoracoscopic surgery (RATS) is a relatively new approach to lung cancer surgery. To promote the development of RATS procedures, we investigated the factors related to short-term postoperative outcomes. METHODS: We analyzed the records of patients who underwent RATS lobectomy for primary lung cancer at our institution between June, 2018 and January, 2023. The primary outcome was operative time, and the estimated value of surgery-related factors was calculated by linear regression analysis. The secondary outcome was surgical morbidity and the risk was assessed by logistic regression analysis. RESULTS: The study cohort comprised 238 patients. Left upper lobectomy had the longest mean operative time, followed by right upper lobectomy. Postoperative complications occurred in 13.0% of the patients. Multivariate analysis revealed that upper lobectomy, the number of staples used for interlobular fissures, and the number of cases experienced by the surgeon were significantly associated with a longer operative time. The only significant risk factor for postoperative complications was heavy smoking. CONCLUSION: Patients with well-lobulated middle or lower lobe lung cancer who are not heavy smokers are recommended for the introductory period of RATS lobectomy. Improving the procedures for upper lobectomy and dividing incomplete interlobular fissures will promote the further development of RATS.

Safety and efficacy of new staple-line reinforcement in lung resection: a prospective study of 48 patients.

PURPOSE: To evaluate the safety and efficacy of new staple-line reinforcement (SLR) in pulmonary resection through a prospective study and to compare the results of this study with historical control data in an exploratory study. METHODS: The subjects of this study were 48 patients who underwent thoracoscopic lobectomy. The primary endpoint was air leakage from the staple line. The secondary endpoints were the location of air leakage, duration of air leakage, and postoperative pulmonary complications. RESULTS: The incidence of intraoperative air leakage from the staple line was 6.3%. Three patients had prolonged air leakage as a postoperative pulmonary complication. No malfunction was found in patients who underwent SLR with the stapling device. When compared with the historical group, the SLR group had a significantly lower incidence of air leakage from the staple line (6.3% vs. 28.5%, P < 0.001) and significantly shorter indwelling chest drainage time (P = 0.049) and length of hospital stay (P < 0.001). CONCLUSIONS: The use of SLR in pulmonary resection was safe and effective. When compared with conventional products, SLR could control intraoperative air leakage from the staple line and shorten time needed for indwelling chest drainage and the length of hospital stay.

Console and bedside surgeon fused robot-assisted thoracic surgery.

In the last decade, even thoracic surgery has seen an increase in the use of robotic surgical systems, and robot-assisted thoracic surgery (RATS) is considered one of the main issues. While RATS is associated with solo manipulative freedom and high-definition optical systems, several disadvantages, such as the lack of tactile sensation and difficult learning curves for the whole team, have been raised. Therefore, to overcome these issues, we developed a 'fusion surgery' approach combining a robotic procedure with manual maneuvers, where the table surgeon retracts the lung and staples the pulmonary vasculature and bronchus. Herein, we introduce our 'fusion surgery' procedure and elaborate on its advantage from technical and educational perspectives.

Comparable efficacy and safety of COVID-19 vaccines for patients receiving tegafur-uracil as postoperative adjuvant chemotherapy.

PURPOSE: Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. METHODS: The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. RESULTS: The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. CONCLUSIONS: The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. CLINICAL TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).

Sarcomatoid mesothelioma originating from mesothelioma in situ: are methylthioadenosine phosphorylase loss and CDKN2A homozygous deletion poor prognostic factors for preinvasive mesothelioma?

The diagnosis of mesothelioma in situ (MIS) is challenging with conventional diagnostic approaches. Although recent advances in genomic-based assays have made it possible to diagnose MIS, the prognosis, treatment indications, and prognostic factors remain unclear. Previous reports have shown that MIS progresses to invasive mesothelioma; however, to the best of our knowledge, progression to sarcomatoid mesothelioma has not yet been reported. A 73-year-old man was diagnosed with MIS associated with methylthioadenosine phosphorylase (MTAP) loss and a CDKN2A homozygous deletion. Strikingly, pathological examination revealed that the MIS lesion had progressed to sarcomatoid mesothelioma. In analyses of previously reported cases and our case, MIS with a CDKN2A homozygous deletion or MTAP loss progressed to invasive mesothelioma earlier than that without them, indicating that a CDKN2A homozygous deletion and MTAP loss could be poor prognostic factors. Genomic analyses might be useful for predicting the prognosis of MIS and contributing to an optimal treatment.

Comparison of oncological outcomes between trisegmentectomy and lobectomy for non-small cell lung cancer in the left upper division.

Background: The left upper lobe is one of the largest lobes in the lungs and is divided into two anatomical units: the upper division (segments 1+2 and segment 3) and lingula (segments 4 and 5). This anatomical classification is similar to that used for the right upper and middle lobes. Although bilobectomy is not recommended for right upper or middle lobe tumors close to the interlobar plane, lobectomy is often performed for tumors located close to the intersegmental plane in the left upper division. To aid in establishing trisegmentectomy as a standard treatment for clinical N0 non-small cell lung cancer (NSCLC) in the left upper lobe, we aimed to re-assess its feasibility based on oncological outcomes according to tumor location. Methods: We retrospectively analyzed the data of patients with clinical N0 NSCLC in the left upper division who underwent left upper lobectomy or trisegmentectomy between April 2006 and December 2020. After propensity score matching, oncological outcomes were compared between the trisegmentectomy and lobectomy groups. To verify whether trisegmentectomy was indicated regardless of tumor distance from the intersegmental plane, we compared the recurrence-free survival (RFS) rates following trisegmentectomy between patients with tumors ≤20 and >20 mm from the intersegmental plane. Results: After propensity score matching, 46 patients were included in each group. There was no significant difference in the 5-year RFS rate between the lobectomy and trisegmentectomy groups (75.5% vs. 84.0%, P=0.41). In the trisegmentectomy cohort, the 5-year RFS rate did not significantly differ according to tumor distance from the intersegmental plane (≤20 or >20 mm) measured using three-dimensional computed tomography (79.4% vs. 81.2%, P=0.69). Multivariate analysis indicated that tumor distance from the intersegmental plane was not a significant predictor of RFS (hazard ratio: 1.75, 95% confidence interval: 0.52-5.91, P=0.37). Conclusions: Our analysis suggests that oncological outcomes (i.e., RFS rates) following trisegmentectomy for clinical N0 NSCLC in the left upper division are not significantly inferior to those following lobectomy, even if the tumor is located close to the intersegmental plane.

Cellular cannibalism and consequent thrombocytopenia in a patient with bone marrow metastasis of malignant pleural mesothelioma: A case report.

Cellular cannibalism is a tumor activity where a cell is engulfed by another cell. This process promotes tumor cell survival under unfavorable conditions. The current report describes an extremely rare case of thrombocytopenia resulting from cellular cannibalism in a patient with bone marrow metastasis due to malignant pleural mesothelioma (MPM). A 77-year-old male presented with hemothorax and thrombocytopenia. He was diagnosed with MPM of the sarcomatoid cell type. However, his disease progressed rapidly and he died 11 days after admission. Bone marrow aspiration revealed metastatic MPM cells that had engulfed other blood cells. Accordingly, the observed thrombocytopenia was attributed to cellular cannibalism by metastatic MPM tumor cells. To the best of our knowledge, this is the first reported case of thrombocytopenia due to cellular cannibalism in a patient with this type of malignancy (MPM). The results suggested that although MPM rarely metastasizes to the bone marrow, bone marrow aspiration could be useful in such cases.

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.

EWSR1-CREM fusion in pulmonary mesenchymal neoplasm showing distinctive clear cell morphology.

EWSR1-CREM gene fusions were recently discovered in several mesenchymal and epithelial tumors, including myxoid mesenchymal tumors of the central nervous system, rare cases of soft tissue clear cell sarcoma and angiomatoid fibrous histiocytoma, and hyalinizing clear cell carcinoma, which implicates the potential phenotypic diversities of tumors harboring an EWSR1-CREM fusion. We herein present an exceedingly indolent pulmonary mesenchymal tumor showing distinctive clinicopathological features. This tumor histologically displayed a small nest and alveolar pattern consisting of monomorphic clear cells intermingled with dilated anastomosing vasculature. Immunophenotypically, tumor cells were positive for vimentin and focally positive for synaptophysin, but negative for many immunohistochemical panels including keratins, EMA, desmin, mesothelial markers, melanotic markers, smooth muscle actin, inhibin and S-100 protein. Interestingly, RNA sequencing identified an in-frame EWSR1-CREM fusion, which was confirmed by subsequent real-time/reverse transcription polymerase chain reaction and fluorescence in situ hybridization assay. Clinical follow-up showed no evidence of recurrence and metastasis. Our pathological findings further expand the phenotypic spectrum of tumors associated with EWSR1-CREM fusions, implying the emergence of a possible novel tumor entity.

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.