Treatment patterns and clinical outcomes of resectable clinical stage III non-small cell lung cancer in a Japanese real-world setting: Surgery cohort analysis of the SOLUTION study.

BACKGROUND: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non-small cell lung cancer (NSCLC) in real-world settings. METHODS: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first-line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow-up data were obtained using medical records from diagnosis to March 1, 2018. RESULTS: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3-year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3-year progression-free survival (PFS) and disease-free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29-0.81]), PFS (0.62 [0.39-0.96]), and DFS (0.62 [0.39-0.97]) versus surgery alone. CONCLUSIONS: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC.

Tips for using forceps during uniportal video-assisted thoracoscopic surgery.

Uniportal video-assisted thoracoscopic surgery is usually performed using an ultrasonic coagulation cutting device in the dominant hand and a long suction device in the non-dominant hand. However, countertraction with forceps is often needed for dissection of a vessel sheath. Moreover, in uniportal video-assisted thoracoscopic surgery, which requires the simultaneous use of multiple instruments, the instruments tend to interfere with each other during the procedure because of the need to share a single incisional port. In this video tutorial, we present tips for using thoracoscopic forceps with bent tips and a 30° video thoracoscope in uniportal video-assisted thoracoscopic surgery.

Simple smoke ventilation method for uniportal video-assisted thoracoscopic surgery.

Fogging of the thoracoscopic lens affects a surgeon's ability to maintain a clear operating field. In uniportal video-assisted thoracoscopic surgery, the thoracoscopic lens tends to fog when the surgeon does not hold a suction instrument. Thus, a suction instrument needs to be held by the surgeon's nondominant hand to remove surgical smoke, mist, and moisture. Here, we describe a simple, easy and cost-effective surgical smoke ventilation technique for uniportal video-assisted thoracoscopic surgery using a suction catheter to solve the problem. We present this technique and comment on its advantages, including decreased cost and improved surgical visualization.

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.

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*.

Risk factors for atelectasis of the middle lobe after right upper lobectomy: preoperative bronchial diameter and stapling of the fissure.

BACKGROUND: Atelectasis of the middle lobe after right upper lobectomy is often seen. However, the risk factors for atelectasis are uncertain. Therefore, we assessed cases in our institution and investigated risk factors for atelectasis of the middle lobe following right upper lobectomy. METHODS: We identified 354 cases in which right upper lobectomy had been performed in our institution between January 2009 and December 2018, and 342 were included in this retrospective analysis. We divided patients into two groups according to the presence of postoperative atelectasis of the middle lobe, and then preoperative clinical variables and perioperative variables were compared between the two groups. Multivariable analyses for postoperative atelectasis of the middle lobe were performed using the logistic regression model. RESULTS: Middle lobe atelectasis was detected in 59 cases (17.3%). Multivariable analysis demonstrated that the preoperative diameter of the middle lobe bronchus [P=0.012; confidence interval (CI), 0.525-0.930] and stapling of the fissure between the upper and middle lobes (P=0.004; CI, 1.997-37.050) were independent risk factors for postoperative atelectasis of the middle lobe. CONCLUSIONS: A small preoperative diameter of the middle lobe bronchus and stapling of the fissure between the upper and middle lobes are risk factors for middle lobe atelectasis following right upper lobectomy.

Simple lung retraction method for uniportal video-assisted thoracoscopic surgery.

In conventional multiportal video-assisted thoracoscopic surgery, devices such as cotton-tipped applicators are used instead of graspers to avoid injuring the fragile lung tissue while stabilizing the lung and securing the surgical visual field. However, in uniportal video-assisted thoracoscopic surgery, which requires the simultaneous use of multiple instruments, the instruments tend to interfere with each other during the procedure because they share a single incisional port. Here, we describe a simple, easy and cost-effective lung retraction technique using cotton swabs to solve the problem. We present this technique and comment on its advantages, including decreased cost and improved surgical visualization.

[Thoracoscopic Pulmonary Resection in Lung Cancer Patients with Pleural Adhesion].

When a presence of significant pleural adhesion is identified at the beginning of surgery, multiple factors determine the outcome of the surgery, particularly when it is performed thoracoscopically. These factors include identification of adhesion at the beginning of the surgery, as well as procedures involved in dissection and additional incisions. If the adhesion is partial, the lack of observation during creation of the surgical field can lead to damage being caused outside the field of view due to traction. Thus, it is important to focus observations. At our department, we started performing thoracoscopic surgery in 1992. Currently, over 80% of annual surgical cases are performed thoracoscopically. We will review our thoracoscopic surgery cases that involved pleural adhesion and discuss the tools and techniques used, as well as providing additional tips for ensuring successful thoracoscopic surgery.

Single-Port vs Conventional Three-Port Video-Assisted Thoracoscopic Pulmonary Wedge Resection: Comparison of Postoperative Pain and Surgical Costs.

PURPOSE: Single-port video-assisted thoracoscopic (VATS) pulmonary wedge resection was reported in 2004. We started using single-port VATS (SPVATS) pulmonary wedge resection in 2017 and compared results between conventional three-port VATS (VATS group) and SPVATS (SPVATS group). METHODS: We identified 145 consecutive patients with VATS group and SPVATS group. Perioperative characteristics including pain and the number of stapler cartridges used were examined as the surgical outcomes, retrospectively. RESULTS: In all, 66 cases of SPVATS group and 79 cases of VATS group pulmonary wedge resection were compared. The rate of epidural anesthesia (p <0.0001) was significantly higher and operative time (p <0.0001) was significantly longer with VATS group than with SPVATS group. The number of stapler cartridges used, duration of drain insertion, and rate of postoperative complications did not differ significantly between groups. Average numerical rating scale (NRS) score on postoperative day 1 and postoperative day 7 (p <0.0001 each), maximum NRS score on postoperative day 7 (p = 0.0082) and amount of 25 mg tramadol (p = 0.0062) were significantly lower in SPVAS group than in VATS group. CONCLUSION: Our results suggest that SPVATS pulmonary wedge resection offers better pain control and cost-effectiveness than three-port VATS pulmonary wedge resection. These findings should contribute to the body of evidence for SPVATS.

Primary capicua transcriptional repressor-rearranged sarcoma of the lung.

A 60-year-old man had a malignant left lower lung tumour with no metastases and underwent video-assisted thoracoscopic left lower lobectomy and lymphadenectomy. Pathological examination led to a diagnosis of capicua transcriptional repressor (CIC)-rearranged sarcoma. He has had 3.5 years of recurrence-free survival. CIC-rearranged sarcoma is a Ewing-like sarcoma that shows pathological findings similar to Ewing sarcoma. Most of CIC-rearranged sarcoma is CIC-double homeobox 4 protein (DUX4) fusion. Pulmonary CIC-rearranged sarcoma is extremely rare and has an unfavourable prognosis. However, complete resection can produce prognosis of long-term survival, and thus, surgery is an important option.

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.

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.

Impact of somatic mutations on prognosis in resected non-small-cell lung cancer: The Japan Molecular Epidemiology for lung cancer study.

BACKGROUND: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS). METHODS: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. RESULTS: Of 876 patients, 172 had ≥2 somatic mutations. Median follow-up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488-2.695), age (≥70 vs <70 years, HR = 1.583, 95% CI: 1.229-2.049), gender (male vs female, HR = 1.503, 95% CI: 1.045-2.170) and pathological stage (II vs I, HR = 3.386, 95% CI: 2.447-4.646; ≥III vs I, HR = 6.307, 95% CI: 4.680-8.476) were significantly associated with RFS, while EGFR mutation (yes vs no, HR = 0.482, 95% CI: 0.309-0.736), number of coexisting mutations (≥2 vs 0 or 1, HR = 1.695, 95% CI: 1.143-2.467), age (≥70 vs <70 years, HR = 1.932, 95% CI: 1.385-2.726), and pathological stage (II vs I, HR = 2.209, 95% CI: 1.431-3.347; ≥III vs I, HR = 5.286, 95% CI: 3.682-7.566) were also significant for OS. CONCLUSION: A smaller number of coexisting mutations, earlier stage, and younger age were associated with longer RFS and OS, while EGFR mutations were significantly associated with improved OS.

Patient outcomes post-pulmonary resection for synchronous bone-metastatic non-small cell lung cancer.

BACKGROUND: The efficacy of curative-intent pulmonary resection for non-small cell lung cancer (NSCLC) patients with certain types of oligometastases, particularly brain and adrenal metastases, has previously been described. We investigated the outcomes of curative-intent pulmonary resection for NSCLC patients with synchronous isolated bone metastases, which have been less clear to date. METHODS: We retrospectively reviewed the clinical and pathological records of 41 patients with NSCLC and synchronous isolated bone metastases who underwent radical treatments (surgery and/or chemotherapy and/or radiotherapy) for both their primary tumors and bone metastases at the National Hospital Organization, Hokkaido Cancer Center, between 2008 and 2013. RESULTS: Nine of the 41 patients underwent pulmonary primary tumor resection; the rate of clinical N0-1 disease among these 9 patients (100%) was significantly higher than that among the 32 patients who did not undergo resection (34.4%). The five-year overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates of the nine patients who underwent pulmonary resection were 66.7%, 55.6%, and 44.4%, respectively. On multivariate analysis, the predictors of longer OS among all 41 patients were primary site resection [hazard ratio (HR) =4.18, 95% CI, 1.20-14.6, P=0.025] and epidermal growth factor receptor (EGFR) mutation (HR =3.30, 95% CI, 1.08-10.1, P=0.036). The former was also a predictor of longer PFS (HR =3.75, 95% CI, 1.27-11.0, P=0.016). CONCLUSIONS: Patients with clinical N0-1 NSCLC and synchronous isolated bone metastases may achieve longer survival rates following primary lung tumor resection.

Pulmonary Staple-Stump Granuloma After Segmentectomy: Two Case Reports and Comparison with Cases of Stump Recurrence.

BACKGROUND Correctly diagnosing a staple-line mass after pulmonary resection for lung malignant tumor can be difficult. Differential diagnoses of recurrence, infectious mass, granuloma, and so on must be considered, despite their rarity. We report two cases of pulmonary staple-stump granuloma after segmentectomy for lung cancer. CASE REPORT Case 1 involved a 70-year-old man with small nodule in the left upper lobe identified on computed tomography (CT). Video-assisted thoracoscopic (VATS) left upper division segmentectomy was performed. Histopathological examination revealed squamous carcinoma. Follow-up CT 1 year postoperatively showed a shadow at the staple-stump, with growth evident later. CT-guided biopsy found no malignancy. However, complete left upper lobectomy was performed because of the gradually enlarging lesion. Histopathological examination revealed epithelioid granuloma. Case 2 involved a 60-year-old with suspected lung cancer in the right upper lobe. VATS right upper division segmentectomy (S2) was performed. CT at 30 months postoperatively showed a shadow at the staple line, with subsequent growth. VATS right upper lobectomy was performed. Intraoperative rapid diagnosis revealed epithelioid granuloma. These two cases were compared with five cases of staple-stump recurrence in our institution. All cases of recurrence grew concentrically or radially from the staple line with the mass surrounding the staple line. On the other hand, cases of granuloma extended along the long axis of the staple line, and 3-dimensional CT (3DCT) may help to understand the morphology. CONCLUSIONS Although preoperative differentiation of staple-line granuloma is difficult and pathological diagnosis is important, characteristic radiologic features and 3DCT may facilitate diagnosis.

Intraoperative diagnosis with abnormal branching of the left A8 pulmonary artery from the left main pulmonary artery.

BACKGROUND: Safety is of vital importance for lung resection. The dissection of pulmonary vessels is associated with vascular injury and bleeding, and identification of the vessels is necessary. The most common abnormal branching pattern of the left pulmonary artery is the mediastinal lingular artery. However, a mediastinal basal pulmonary artery is very rare. A case of abnormal branching from the left pulmonary artery to S8 which was diagnosed intraoperatively, and, thus, its dissection was avoided, is reported. CASE PRESENTATION: A 76-year-old woman with rheumatoid arthritis was diagnosed with left upper lung adenocarcinoma and visited our hospital. Contrast CT was not performed due to renal dysfunction, and abnormal branching of the left pulmonary artery was not identified. Video-assisted thoracoscopic left upper lobectomy and lymphadenectomy were performed. After the upper pulmonary vein was dissected and tissue around it was detached carefully, a pulmonary mediastinal branch from the left main pulmonary artery was identified descending between the upper pulmonary vein and upper bronchus. It was possible to separate the interlobar fissure safely and preserve A8. On retrospective examination, non-contrast CT showed A8. CONCLUSIONS: Although preoperative identification of left pulmonary mediastinal branches was difficult by non-contrast CT, a careful surgical procedure preserved the left pulmonary mediastinal A8.

Visceral subpleural hematoma of the left diaphragmatic surface following left upper division segmentectomy.

BACKGROUND: Pulmonary visceral subpleural hematoma is rare. We report visceral subpleural hematoma of the left diaphragmatic surface following left upper division segmentectomy. This very rare case was difficult to distinguish from thoracic abscess. CASE PRESENTATION: A 68-year-old man with hypertension had undergone video-assisted thoracoscopic left upper division segmentectomy for suspected lung carcinoma. Deep vein thrombosis of the lower leg was identified and edoxaban, a so-called novel oral anticoagulant, was started on postoperative day 7. The chest drainage tube was removed on postoperative day 12 because of persistent air leakage, but fever appeared the same day. Computed tomography revealed a cavity with mixed air and fluid, so antibiotics were started on suspicion of abscess. Computed tomography-guided drainage was attempted, but proved unsuccessful. Fever continued and surgical investigation was therefore performed. Visceral subpleural hematoma was identified under the diaphragmatic surface of the left basal lung. We excised the pleura, then performed drainage and applied running sutures. The parenchyma and visceral pleura were covered with polyglycolic acid sheet and fibrin glue. Edoxaban was restarted on postoperative day 12 of video-assisted thoracoscopic surgery and no recurrence of hematoma has been revealed. CONCLUSIONS: Visceral subpleural hematoma after thoracic surgery is extremely rare. Furthermore, correct diagnosis was difficult and surgery offered a good diagnostic and therapeutic procedure.

[Surgical Treatment of T3 Lung Cancer with Invasion of Chest Wall and Other Adjacent Organs].

We conducted a retrospective investigation in patients who underwent surgery for T3 lung cancer with invasion of chest wall and other adjacent organs. Fifty patients who underwent surgery for T3 lung cancer with invasion of adjacent organs were investigated. The chest wall was the most frequently invaded organ, followed by the pericardium and mediastinal pleura. In cases of chest wall invasion, patients underwent en bloc resection and, when a complete resection was judged feasible, extrapleural resection. Six patients with superior sulcus tumor underwent surgery after preoperative treatment. The 5-year-survival was 55.7%. A significant difference in 5-year survival was observed between complete resection and incomplete resection in patients with lung cancer with chest wall invasion( p<0.047).

Long-Term Outcomes after Video-Assisted Thoracoscopic Pericardiectomy for Pericardial Effusion.

PURPOSE: Chronic or recurrent pericardial effusion is often associated with malignant disease. However, there have been few reports of the long-term outcomes after video-assisted thoracoscopic (VATS) pericardiectomy. We have performed it since 1992, and report our procedure and outcomes. METHODS: Patients who underwent VATS pericardiectomy were investigated. RESULTS: In all, 29 patients (12 men; median age: 61 (23-88) years) were evaluated; 8 had no malignancies and 21 did. Preoperative performance status (PS) scores were as follows: 1, 11 patients; 2, 10 patients; 3, 5 patients; and 4, 2 patients. One patient with malignancy died intraoperatively. PS improved significantly after the procedure (p = 0.0163). Median survival times were 5360 days in the nonmalignant group, 160 days in the malignant group, 209 days in breast cancer patients, and 62 days in other malignancy patients. The nonmalignant group had significantly longer survival than the malignant group (p = 0.0015). Most cases had uneventful postoperative courses. No recurrent pericardial effusions have been observed. CONCLUSION: In cases of nonmalignant pericardial effusion, long-term survival is expected following VATS pericardiectomy. Malignant pericardial effusion has a poor prognosis, but most cases maintain good PS. However, early postoperative death may occur, and it is important to select patients carefully.

Multiplex Ultrasensitive Genotyping of Patients with Non-Small Cell Lung Cancer for Epidermal Growth Factor Receptor (EGFR) Mutations by Means of Picodroplet Digital PCR.

Epidermal growth factor receptor (EGFR) mutations have been used as the strongest predictor of effectiveness of treatment with EGFR tyrosine kinase inhibitors (TKIs). Three most common EGFR mutations (L858R, exon 19 deletion, and T790M) are known to be major selection markers for EGFR-TKIs therapy. Here, we developed a multiplex picodroplet digital PCR (ddPCR) assay to detect 3 common EGFR mutations in 1 reaction. Serial-dilution experiments with genomic DNA harboring EGFR mutations revealed linear performance, with analytical sensitivity ~0.01% for each mutation. All 33 EGFR-activating mutations detected in formalin-fixed paraffin-embedded (FFPE) tissue samples by the conventional method were also detected by this multiplex assay. Owing to the higher sensitivity, an additional mutation (T790M; including an ultra-low-level mutation, <0.1%) was detected in the same reaction. Regression analysis of the duplex assay and multiplex assay showed a correlation coefficient (R2) of 0.9986 for L858R, 0.9844 for an exon 19 deletion, and 0.9959 for T790M. Using ddPCR, we designed a multiplex ultrasensitive genotyping platform for 3 common EGFR mutations. Results of this proof-of-principle study on clinical samples indicate clinical utility of multiplex ddPCR for screening for multiple EGFR mutations concurrently with an ultra-rare pretreatment mutation (T790M).