Effect of Resected Lung Volume on Pulmonary Function and Residual Lung Volume in Patients Undergoing Segmentectomy: A Retrospective Study.

PURPOSE: We elucidated the effects of planned resection volume on postoperative pulmonary function and changes in residual lung volume during segmentectomy. METHODS: This study included patients who underwent thoracoscopic segmentectomy between January 2017 and December 2022 and met eligibility criteria. Pre- and post-resection spirometry and computed tomography were performed. Three-dimensional reconstructions were performed by using computed tomography images to calculate the volumes of the resected, remaining, and nonoperative side regions. Based on the resected region volume, patients were divided into the higher and lower volume segmentectomy groups. Changes in lung volume and pulmonary function before and after the surgery were comparatively analyzed. RESULTS: The median percentage of resected lung volume was 10.9%, forming the basis for categorizing patients into the two groups. Postoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) ratios to preoperative measurements in both groups did not differ significantly (FEV1, p = 0.254; FVC, p = 0.777). Postoperative FEV1 and FVC ratios to their predicted postoperative values were significantly higher in the higher volume segmentectomy group than in the lower volume segmentectomy group (FEV1, p = 0003; FVC, p < 0.001). The higher volume segmentectomy group showed significantly greater post-to-preoperative lung volume ratio in overall, contralateral, ipsilateral, residual lobe and residual segment than the lower volume segmentectomy group. CONCLUSIONS: Postoperative respiratory function did not differ significantly between the higher- and lower-volume segmentectomy groups, indicating improved respiratory function because of substantial postoperative residual lung expansion. Our findings would aid in determining the extent of resection during segmentectomy.

Pulmonary artery occlusion post immunotherapy for hilar node-positive lung cancer.

We present the case of a patient who developed pulmonary artery occlusion following immune-checkpoint inhibitor (ICI) therapy for non-small cell lung cancer. A 69-year-old man with squamous cell carcinoma (yc-T1cN0M0), initially diagnosed at c-stage IVA (T3N1M1b), in the upper lobe of the left lung, was scheduled to undergo salvage lung resection after ICI therapy. However, he exhibited an occlusion of the lingular pulmonary artery near the clinically metastatic hilar lymph node. To avoid severe adhesions, the patient underwent successful wedge resection without dividing pulmonary vessels and was discharged without complications. Surgeons should be prepared for pulmonary artery changes following ICI therapy.

Number of lymph nodes dissected and upstaging rate of the N factor in robot-assisted thoracic surgery versus video-assisted thoracic surgery for patients with cN0 primary lung cancer.

PURPOSE: The accuracy of lymph node (LN) dissection in robotic surgery for lung cancer remains controversial. We compared the accuracy of LN dissection in robot-assisted thoracic surgery (RATS) vs. video-assisted thoracic surgery (VATS). METHODS: The subjects of this retrospective analysis were 226 patients with cN0 primary lung cancer who underwent robot-assisted or video-assisted thoracic lobectomy with LN dissection, in our department, between April, 2016 and February, 2021. We compared the numbers of all LNs and mediastinal LNs dissected, the time required for LN dissection, complications, and upstaging rates of the N factor between the groups. Furthermore, we performed an inverse probability of treatment weighting-adjusted analysis to reduce potential bias between the groups. RESULTS: The number of dissected LNs was higher in the RATS group in both the unweighted and weighted analyses. The time required for lymph node dissection was also longer in RATS. There was no significant difference in complications or in the upstaging rate of the N factor between the groups. CONCLUSION: More LNs were dissected with RATS. Thus, the usefulness of robot-assisted surgery for LN dissection needs to be investigated further.

Clinical effect of soft coagulation for air leak treatment during pulmonary lobectomy.

BACKGROUND: Soft coagulation using the VIO soft coagulation system is used to treat minor lung air leaks during pulmonary resection in Japan. We previously reported that it has a similar effect as the air leak treatment with fibrin glue. We evaluated the efficacy of soft coagulation using the VIO soft coagulation system for lung air leakage during pulmonary resection. METHODS: Intraoperative air leaks from the interlobar lung parenchyma were observed in 42 of the 283 patients who underwent video-assisted thoracoscopic surgery lobectomy between 2016 and 2018. We retrospectively reviewed these 42 patients who were treated using the VIO soft coagulation system for air leaks. We classified the air leaks in to grades using the Macchiarini scale score and evaluated the surgical outcomes of air leak treatment. RESULTS: Air leaks from the interlobar lung parenchyma having Macchiarini scale scores 1, 2, and 3 occurred in 8, 17, and 17 patients, respectively. In all the 8 patients with score 1 air leaks (100%), the air leaks could be controlled using the VIO soft coagulation system alone, and none had delayed pneumothorax requiring intervention. Of the score 2 and 3 air leaks, 52.9% and 35.3% were controlled using the VIO soft coagulation system alone, respectively. CONCLUSIONS: Macchiarini scale score 1 air leaks from the interlobar lung parenchyma could be well controlled using the VIO soft coagulation system. Therefore, soft coagulation with this system may be an alternative method for treating minor air leaks during pulmonary resection surgery.

Pulmonary vessels and bronchus anatomy of the left upper lobe.

PURPOSES: The bronchopulmonary vascular bifurcation patterns in the upper lobe of the left lung are diverse. Therefore, it is important for general thoracic surgeons to understand the detailed anatomy of the pulmonary segments when performing thoracoscopic anatomical pulmonary resection. This study aimed to analyze the bronchovascular patterns of the left upper lobe and summarize the anatomical information associated with pulmonary anatomical pulmonary resection. METHODS: We reviewed the anatomical patterns of pulmonary vessels and the left lung bronchus of 539 patients using computed tomography imaging data including those obtained using three-dimensional computed tomography. We herein report the anatomic structure in the left upper lobe. RESULTS: Regarding the superior division bronchi, a pattern of trifurcation into B1+2, B3, lingular division bronchus was observed in nine patients (1.7%). A pattern of proximal bifurcation of B4 was found in eight patients (1.5%). Regarding the lingular veins (LV), patterns of LV drainage into the left lower pulmonary vein were observed in 22 patients (4.1%). Regarding the pulmonary artery, mediastinal lingular arteries (MLA) were found in 161 patients (29.9%). CONCLUSION: The bifurcation patterns of the bronchovascular region in the upper lobe of the left lung were clarified. These results should be carefully noted when performing anatomical pulmonary resection.

Salvage Surgery for Bronchopleural Fistula Due to Durvalumab and Chemoradiation.

Herein we describe a case of salvage lobectomy for a bronchopleural fistula secondary to durvalumab after chemoradiotherapy in initially unresectable non-small cell lung cancer. A 75-year-old man with adenocarcinoma, c-stage IIIB (T4N2M0) in the upper lobe of the right lung, received durvalumab after chemoradiotherapy. Fourteen months after durvalumab was discontinued, pneumonitis developed followed by peripheral bronchopleural fistula, and he unavoidably underwent salvage right upper lobectomy. The postoperative course was uneventful, and air leakage ceased. After chemoradiotherapy and durvalumab, refractory air leakage may develop that may require salvage surgery.

Anatomy of the left subsuperior segment for segmentectomy.

PURPOSE: The subsuperior segmental bronchi (B*) forms the subsuperior segment (S*) between the superior (S6) and basal segment (S7, S8, S9, S10) of the lung. However, the anatomical planes of S* remains undefined. The present study clarified the anatomical features of S*. METHODS: We reviewed the anatomical patterns of pulmonary vessels and the left lung bronchus in 539 patients using three-dimensional computed tomography. We report the anatomic structure in S*. RESULTS: A total of 537 patients were analyzed. B* was observed in 129 (24.0%) patients. The intersegmental vein between S6 and S* was complete in all cases. The absence of intersegmental veins of S* was observed in 77 (14.3%) patients, reaching 59.7% of B* cases. Twenty-two (4.1%) cases of B* diverged from the trunk of the basal bronchus, and about half of the B* branched to the dorsolateral (n = 77, 14.3%) or dorsal (n = 2, 0.37%) direction. CONCLUSION: Our study revealed the branching patterns of B* and anatomical intersegmental veins of S*. Our results provide useful information regarding anatomical segmentectomy including or adjusting to the left S*.

Unexpected haemorrhage from lateral thoracic artery following the removal of a pleural drainage tube.

Pulmonologists must be aware of the possible arterial bleeding even during the removal of a safely inserted drain.

MCL1 inhibition enhances the efficacy of docetaxel against airway-derived squamous cell carcinoma cells.

MCL1 is an anti-apoptotic BCL2 family member that is often overexpressed in various malignant tumors. However, few reports have described the role of MCL1 in squamous cell carcinoma (SqCC) derived from airways including the lung. In this study, we examined whether MCL1 could be a novel druggable target for airway-derived SqCC, for which effective molecular targeted drugs are unavailable. We searched the Kaplan-Meier Plotter database and found that high MCL1 mRNA expression was significantly associated with shorter survival in patients with lower airway (lung) or upper airway (head and neck) derived SqCC. We also explored the Expression Atlas database and learned that authentic lung SqCC cell lines expressing both TP63 and KRT5 mRNA were extremely sparse among the publicly available "lung SqCC cell lines", with an exception being HARA cells. HARA cells were highly dependent on MCL1 for survival, and MCL1-depleted cells were not able to grow, and even declined in number, upon docetaxel (DTX) exposure in vitro and in vivo. Similar in vitro experimental findings, including those in a 3D culture model, were also obtained using Detroit 562 pharyngeal SqCC cells. These findings suggested that combined treatment with MCL1 silencing plus DTX appears highly effective against airway-derived SqCC.

Vessel sealing system for video-assisted lung resection for cancer reduces chylothorax and bleeding.

BACKGROUND: The objective of this study was to analyze the efficacy of the LigaSureTM vessel sealing system for lung cancer resection with node dissection, as this has not been sufficiently evaluated. METHODS: From 2004 to 2018, 948 patients underwent anatomical pulmonary resection with node dissection for non-small cell lung carcinoma (NSCLC) via the video-assisted thoracoscopic surgery (VATS) approach. Medical records of these patients were reviewed retrospectively. Univariate and multivariate analyses were conducted to determine the risk factors for chylothorax and blood loss. RESULTS: Of the 948 patients, 318 (33.5%) who underwent anatomical lung resection with node dissection by conventional methods without vessel sealing system and 630 (66.5%) who underwent lung resection with node dissection with the vessel sealing system were included. The median intraoperative blood loss was 100 mL. Postoperative chylothorax occurred in 9 (2.8%) patients in the conventional method group with 2 (0.3%) patients in the vessel sealing system group (P=0.001). Patients in the vessel sealing group who developed chylothorax were cured by conservative treatment. Univariate and multivariate analyses identified male sex [odds ratio (OR) 2.053; 95% confidence interval (CI): 1.494-2.820; P<0.001] and the use of vessel sealing system (OR 0.342; 95% CI: 0.256-0.457; P<0.001) as independent predictors of intraoperative blood loss. The univariate and multivariate analyses identified the use of the vessel sealing system (OR 0.108; 95% CI: 0.023-0.504; P=0.005) as an independent predictor of chylothorax incidence. CONCLUSIONS: Vessel sealing system for lung cancer resection could decrease chest tube duration, amount of intraoperative bleeding, and incidence of chylothorax in patients who undergo lung resection with node dissection.

Treatment of air leakage using the VIO soft coagulation system: a mouse pulmonary air leak model.

PURPOSE: We aimed to compare the efficacy of the VIO soft coagulation system (VSCS) for the treatment of air leaks by sealing with fibrin glue, and also assess the histological alterations that occur after soft coagulation. METHODS: A mouse pulmonary air leak model was designed. The pulmonary fistula was subsequently coagulated with the VSCS or sealed with fibrin glue with polyglycolic acid (PGA) sheets. The burst pressure at air leak recurrence was measured in each group, and the results were compared. We also evaluated the histological alterations in the mouse pulmonary air leak model after soft coagulation with the VSCS. RESULTS: The burst pressure in the soft coagulation group (80 W/Effect 5) (median 42.8; range 35.4-53.8 cmH2O) was similar to that in the fibrin glue group (median 41.5; range 34.6-43.9 cmH2O) (p = 0.21). Histological examinations revealed that the visceral pleura remained torn, the structure of the pulmonary alveolus was maintained, and the coagulated fistula was covered with a fibrin membrane in the soft coagulation group. CONCLUSIONS: The pressure resistance following soft coagulation was equivalent to that after sealing using fibrin glue with PGA sheets. The air leaks were likely controlled by covering the fistula with a fibrin membrane after soft coagulation with the VSCS.

Spontaneous pneumothorax during nintedanib therapy in patients with systemic sclerosis-associated interstitial lung disease.

Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc). Nintedanib, an antifibrotic drug, has recently been approved for treating SSc-ILD. Although there have been no reports suggesting the development of pneumothorax with nintedanib use, its safety in patients with impaired lung function is unclear. We observed the development of refractory spontaneous pneumothorax during nintedanib therapy in two patients with SSc-ILD and impaired lung function. Nintedanib use for SSc-ILD, an extensive disease, may therefore increase the risk of pneumothorax. In addition, pneumothorax is more likely to be refractory in these cases; initiation of nintedanib treatment and follow-up should be considered carefully.

Efficacy of Automatic Retention Pressure of a Double-Lumen Tube Cuff: An Artificial Intubation Model.

BACKGROUND: The movement of a double-lumen endotracheal tube (DLT) out of its appropriate position during thoracic surgery can result in the loss of one-lung ventilation (OLV), especially during pulmonary resection and node dissection. Our study aimed to validate the efficacy of automatic retention pressure control of the DLT bronchial cuff in maintaining OLV in an artificial intubation model. MATERIALS AND METHODS: A 35-Fr left-sided DLT was intubated to the left main bronchus in an intubation simulator and connected to an anesthesia machine. The inspiratory volume, respiratory rate, and inspiratory-expiratory ratio were set at 500 mL, 12 times/min, and 1:2, respectively. A 1-kg right main bronchial traction in the lateral right was provided after OLV was established. SmartCuff (Smiths Medical, Minneapolis, Minnesota, USA) was used to maintain cuff pressure. The efficacy of retention pressure with SmartCuff (Group S) and without SmartCuff (Group WS) was compared. The primary outcome was the rate of tidal volume (TV) reduction following bronchial traction in the two groups. RESULTS: The TVs were 289.8 ± 28.9 mL and 242.8 ± 31.9 mL in Group S and Group WS, respectively (P = 0.003). The rate of TV reduction after bronchial traction was significantly lower in Group S (29 ± 5%) than in Group WS (43 ± 6%) (P < 0.001). CONCLUSIONS: Automatic retention pressure control of the DLT bronchial cuff improves the rate of TV reduction during right main bronchial traction in an artificial intubation model. Continuous retention cuff pressure may be useful in maintaining OLV during thoracic surgery.

Lung adenocarcinoma with tumor resolution and dystrophic calcification after salvage surgery following immune checkpoint inhibitor therapy: A case report.

A clinical trial of immune checkpoint inhibitors for advanced non-small cell lung cancer reported an overall survival plateau with a long tail to the survival curve, suggesting that immune checkpoint inhibitors prolong survival. However, little evidence supports the efficacy of immune checkpoint inhibitors as neoadjuvant chemotherapy. We performed salvage surgery on a patient who was treated with an anti-programmed cell death protein-1 (PD-1) antibody and whose tumor size had not changed over time. A 69-year-old Japanese female with advanced lung adenocarcinoma was initially administered pembrolizumab therapy; however, owing to the development of various immune-related adverse events (irAEs), the patient was switched to chemotherapy following steroid therapy. The tumor continued to shrink and calcification within the tumor increased. We performed salvage surgery following which the tumor cells disappeared and necrosis and calcification were detected in the tumor. We concluded that if calcification develops within the tumor and tumor shrinkage is maintained after treatment with anti-PD-1 drugs, the calcification may be dystrophic owing to drug-induced tumor necrosis, and salvage surgery might be beneficial in removing the tumor. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: If calcification develops within the tumor and tumor shrinkage is maintained after treatment with anti-PD-1 drugs, the calcification may be dystrophic owing to tumor necrosis caused by drug effects, and salvage surgery might be beneficial in removing the tumor. WHAT THIS STUDY ADDS: This study showed the efficacy of immune checkpoint inhibitors as neoadjuvant chemotherapy to be followed by salvage surgery for unresectable advanced lung adenocarcinoma.

Cerebral infarction after left upper lung lobectomy with central vascular ligation.

BACKGROUND: Thrombus of the pulmonary vein (PV) stump is reportedly more frequent after left upper lobectomy than after other lobectomies, risking postoperative cerebral infarction (PCI). We have performed central vascular ligation before vascular dissection to improve the safety of surgical stapling. The effects of central vascular ligation in terms of PV stump thrombus and PCI are uncertain. METHODS: This study retrospectively reviewed the records of patients who underwent left upper lobectomy at a single center (Hokkaido Cancer Center, Sapporo, Japan) between November 1, 2008 and July 31, 2018. Relationships between PCI, PV stump thrombus and background characteristics were investigated and analyzed. RESULTS: All 208 cases of left upper lobectomy underwent central vascular ligation of the PV during this study. PCI occurred in 8 of the 208 patients. PV stump thrombus was detected in 14 of the 132 patients. In comparison with no-PCI cases, PCI cases showed significantly higher rates of comorbidity with cardiovascular disease (P=0.02), double cancer within 5 years (P=0.04), intraoperative hyperthermic chemotherapy (P=0.02), postoperative intrapleural inflammation (P=0.02) and postoperative PV stump thrombus (P=0.04). Presence of both comorbid cardiovascular disease (odds ratio, 18.4) and intraoperative hyperthermic chemotherapy (odds ratio, 30.4) was associated with higher risk of PV stump thrombus than presence of none of these factors. Cerebral infarction within 30 days postoperatively was seen in only 2 of the 208 cases (1.0%). CONCLUSIONS: Central ligation of the PV may prevent postoperative early cerebral infarction. Further study of the effectiveness of this method for preventing PV stump thrombus is needed.

Pericyte-myofibroblast transition in the human lung.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease that includes fibroblastic foci (FF). It has been increasingly appreciated that the origin of collagen-overproducing cells such as pathological myofibroblasts in FF is pericytes. However, neither pericytes derived from the lung nor FF in the IPF lung have not been fully characterized. Human lung pericytes (HuL-P) examined in this study expressed two representative pericyte markers; platelet-derived growth factor receptor ß (PDGFRB) and chondroitin sulfate proteoglycan 4 (CSPG4), and were able to migrate and cover endothelial tubes in 3D conditions, indicating that they retain characteristics of pericytes. Moreover HuL-P cells transitioned to myofibroblast-like cells in the presence of transforming growth factor (TGF)-ß signaling or to pericyte-like cells in the absence of TGF-ß signaling (pericyte-myofibroblast transition). On the other hand, the FF detected in this study were invariably localized between peripheral lung epithelia and capillary endothelia, the basement membranes of which are physiologically fused. The localization is highly specific in that the only cells that exist between the gap are pericytes. As expected, FF were immunohistochemically positive for PDGFRB and CSPG4, suggesting that pericytes are activated to form FF. We also found that HuL-P cells were difficult to eradicate by dual silencing of Bcl-xL plus MCL1. It would be more sensible to suppress pericyte-myofibroblast transition than to kill activated myofibroblasts for the treatment of IPF.

EGFR-independent EGFR-mutant lung adenocarcinoma cells depend on Bcl-xL and MCL1 for survival.

Although most EGFR-mutant lung adenocarcinomas initially respond to EGFR inhibitors, disease progression almost inevitably occurs. We previously reported that two EGFR-mutant lung adenocarcinoma cell lines, HCC827 and H1975, contain subpopulations of cells that display an epithelial-to-mesenchymal phenotype and can thrive independently of EGFR signaling. In this study, we explored to what extent these two sublines, HCC827 GR2 and H1975 WR7, depended on the anti-apoptotic BCL2 family members, Bcl-xL and/or MCL1, for survival. Although HCC827 GR2 cells were hardly affected by Bcl-xL or MCL1 knockdown alone, dual inhibition of Bcl-xL and MCL1 caused the cells to undergo apoptosis, resulting in decreased viability. In H1975 WR7 cells, not only dual inhibition, but also MCL1 silencing alone, induced the cells to undergo apoptosis. Interestingly, the two sublines markedly declined in number when autophagy flux was suppressed, because they depend, in part, on active autophagy for survival. However, autophagy inhibition was inferior to dual inhibition of Bcl-xL plus MCL1 for GR2 cells, or MCL1 inhibition alone, for decreasing the viability of WR7 cells. Collectively, these findings suggest that inhibiting Bcl-xL plus MCL1, or MCL1 alone, may represent a new approach to treat EGFR-independent EGFR-mutant cancer cells.

Pulmonary vessels and bronchial anatomy of the left lower lobe.

PURPOSE: To identify and clarify the comprehensive anatomic patterns in the left lower lobe (LLL). METHODS: Using computed tomography (CT) imaging data, including that obtained using three-dimensional CT, we reviewed the anatomic patterns of the pulmonary vessels and bronchi in the left lungs of 539 patients, focusing on the LLL. RESULTS: The two-stem type in A6 was observed in 131 (24.7%) patients and the three-stem type in A6 was observed in 11 (2.1%) patients. The independent two-stem type in B6 was observed in four (0.75%) patients. The B7 with independent branching from the basal bronchi was observed in 42 (7.9%) patients. B* was observed in 129 (24.0%) patients and B* was accompanied by A* in all patients. An extrapericardial common trunk of the left pulmonary veins was identified in five patients (0.93%). CONCLUSION: We identified various bronchovascular patterns in the LLL of a large number of patients. Our results provide useful information for anatomic pulmonary resection, especially segmentectomy.

[Paraffinoma with Spinal Paralysis 40 Years After Pleural Plombage for Tuberculosis].

Paraffin had been used for pleural plombage in the treatment of tuberculosis. However, paraffin use has been reported to cause late postoperative complications. A 79-year-old man was presented with an extramedullary tumor and spinal paralysis. Forty-seven years ago, he had undergone pleural plombage using paraffin for the treatment of pulmonary tuberculosis. Since the extramedullary tumor was found to be paraffinoma, paraffin in the vertebral canal and thoracic cavity was removed surgically. All the paraffin in the vertebral canal and thoracic cavity was removed. After surgery, the patient remains well, without spinal paralysis.