Thoracoscopic Anatomical Sublobar Resection Including Subsegmentectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC. METHODS: We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy. RESULTS: No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups. CONCLUSIONS: Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option.

Complex video-assisted thoracoscopic surgery lobectomy for locally advanced lung cancer: a prospective feasibility study.

PURPOSE: The limitations regarding indications for video-assisted thoracoscopic surgery lobectomy requiring complex surgery remain unclear. A prospective cohort study was conducted to elucidate the safety and feasibility of complex thoracoscopic lobectomy for patients with locally advanced non-small-cell lung cancer. METHODS: We planned to enroll patients who were suspected of needing thoracoscopic lobectomy or more with complex surgery, including tracheo-bronchoplasty, pulmonary arterioplasty, and combined resection of adjacent organs. Between February 2016 and January 2019, 28 consecutive patients were prospectively enrolled. RESULTS: After excluding 1 patient due to disease progression, 27 patients were included in this study. Three patients underwent thoracoscopic lobectomy without complex surgery. Of the remaining 24 patients, complex thoracoscopic lobectomy was successfully completed in 21 (88%), and the 3 conversions were due to surgery for the great vessels. All 27 patients achieved complete resection. Six patients (22%) suffered grade 2 complications, and the in-hospital, 30-day, and 90-day mortality rates were all 0%. At a median follow-up time of 900 days, the 3-year overall and disease-free survival rates were 75% and 54%, respectively. CONCLUSIONS: Complex thoracoscopic lobectomy was shown to be safe and feasible in select patients with locally advanced non-small-cell lung cancer excluding invasion to the great vessels. CLINICAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trials Registry, 000,019,441 (JAPAN). Institutional Review Board number: 46-15-0003 (accepted at September 7, 2015).

Long-term outcomes of video-assisted thoracoscopic surgery lobectomy vs. thoracotomy lobectomy for stage IA non-small cell lung cancer.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) lobectomy is performed widely for patients with clinical stage I non-small cell lung cancer (NSCLC) because of its superior short-term outcomes to those of thoracotomy lobectomy. However, the long-term outcomes of VATS lobectomy vs. thoracotomy lobectomy remain controversial. METHODS: We reviewed the clinical data of 202 consecutive patients who underwent lobectomy for clinical stage IA NSCLC at our institution between January, 2008 and December, 2013. Stage IA NSCLC was confirmed pathologically in 162 of these patients, 60 of whom underwent VATS lobectomy and 102 of whom underwent thoracotomy lobectomy. We compared the perioperative clinical factors and outcomes of these two groups, using a propensity score-matched analysis. RESULTS: In an analysis of 58 matched cases, the VATS group showed less blood loss, a shorter duration of chest tube placement, a shorter postoperative hospital stay, and a lower peak C-reactive protein value, despite a longer operative time. The VATS group also had significantly longer survival than the thoracotomy group [5-year overall survival, 100% vs. 87%, respectively (p = 0.01); 5-year disease-free survival, 100% vs. 86% (p = 0.03)]. CONCLUSIONS: These findings suggest that VATS may have better long-term as well as short-term outcomes than thoracotomy for patients with early-stage NSCLC.

Thymothymectomy with pulmonary partial resection using the subxiphoid approach: how to do it?

An open approach by sternotomy is still selected for locally advanced anterior mediastinal tumors. Technical and instrumental improvements to video-assisted thoracic surgery (VATS) have enabled the treatment of anterior mediastinal tumor in the last decade, and the indications of VATS for an anterior mediastinal tumor are thus expanding. Recently, a single-port thymectomy procedure using the subxiphoid approach has gained popularity worldwide because of its low invasiveness. Improvements to the thoracoscopic instruments and the development of a single-port device are expanding the adoption of single-port VATS in the thoracic surgical field, including resection of anterior mediastinal tumors. We, herein, report a case of thymothymectomy with pulmonary partial resection using the subxiphoid approach. This approach is useful for extended operation for anterior mediastinal tumors and provides favorable results regarding postoperative pain and cosmetic outcomes.

Intermolecular Interaction between Phosphatidylcholine and Sulfobetaine Lipid: A Combination of Lipids with Antiparallel Arranged Headgroup Charge.

Intermolecular interactions between lipid molecules are important when designing lipid bilayer interfaces, which have many biomedical applications such as in drug delivery vehicles and biosensors. Phosphatidylcholine, a naturally occurring lipid, is the most common lipid found in organisms. Its chemical structure has a negatively charged phosphate linkage, adjacent to an ester linkage in a glycerol moiety, and a positively charged choline group, placed at the terminus of the molecule. Recently, several types of synthetic lipids that have headgroups with the opposite charge to that of phosphatidylcholine have emerged; that is, a positively charged ammonium group is present adjacent to the ester linkage in their glycerol moiety and a negatively charged group is placed at their terminus. These types of lipids constitute a new class of soft material. The aim of this study was to determine how such lipids, with antiparallel arranged headgroup charge, interact with naturally occurring phosphatidylcholines. We synthesized 1,2-dipalmitoyl-sn-glycero-3-sulfobetaine (DPSB) to represent a reversed-head lipid; 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) was used to represent a naturally occurring phospholipid. The intermolecular interaction between these lipids was investigated using surface pressure-area (π-A) isotherms of the lipid monolayer at the air/water interface. We found that the extrapolated area and excess free energy of the mixed monolayer deviated negatively when compared with the ideal values from additivity. Moreover, differential scanning calorimetry of the lipid mixture in aqueous dispersion showed that the gel-to-liquid crystal transition temperature increased compared with that of each pure lipid composition. These results clearly indicate that DPSB preferably interacts with DPPC in the mixture. We believe that the attraction between the oppositely charged headgroups of these lipids reinforces the intermolecular interaction. Our results provide insight into the intermolecular interaction between phospholipids and reversed-head lipids, which may prove useful for the design of lipid-based materials in the future.

Blockade of glucose-6-phosphate dehydrogenase induces immunogenic cell death and accelerates immunotherapy.

BACKGROUND: Enhanced glucose metabolism has been reported in many cancers. Glucose-6-phosphate dehydrogenase (G6PD) is a rate-limiting enzyme involved in the pentose phosphate pathway, which maintains NADPH levels and protects cells from oxidative damage. We recently found that low G6PD expression correlates with active tumor immunity. However, the mechanism involving G6PD and tumor immunity remained unclear. METHODS: We conducted in vitro studies using G6PD-knocked down malignant melanoma cells, pathway analysis using the GEO dataset, in vivo studies in combination with immune checkpoint inhibitors (ICIs) using a mouse melanoma model, and prognostic analysis in 42 melanoma patients and 30 lung cancer patients who were treated with ICIs. RESULTS: Inhibition of G6PD, both chemically and genetically, has been shown to decrease the production of NADPH and reduce their oxidative stress tolerance. This leads to cell death, which is accompanied by the release of high mobility group box 1 and the translocation of calreticulin to the plasma membrane. These findings suggested that inhibiting G6PD can induce immunogenic cell death. In experiments with C57BL/6 mice transplanted with G6PD-knockdown B16 melanoma cells and treated with anti-PD-L1 antibody, a significant reduction in tumor size was observed. Interestingly, inhibiting G6PD in only a part of the lesions increased the sensitivity of other lesions to ICI. Additionally, out of 42 melanoma patients and 30 lung cancer patients treated with ICIs, those with low G6PD expression had a better prognosis than those with high G6PD expression (p=0.0473; melanoma, p=0.0287; lung cancer). CONCLUSION: G6PD inhibition is a potent therapeutic strategy that triggers immunogenic cell death in tumors, significantly augmenting the efficacy of immunotherapies.

Expression of vascular endothelial growth factor receptor in thymic epithelial tumors.

Thymic epithelial tumors (TETs) are rare and the major symptoms are not obvious until the tumor progresses to a relatively large size and compresses the surrounding organs. As its growth is aggressive and it metastasizes to distant organs, it is important to find novel effective therapies. Lenvatinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is approved as a drug therapy for thymic carcinoma (TC); however, although it is a molecular targeted therapy, there are no obvious predictors of therapeutic efficacy. The present study aimed to assess the association between clinicopathological factors and the protein expression of VEGFR, which is associated with tumor aggressiveness and the efficacy of VEGFR inhibitors. The VEGFR-2 protein expression was evaluated in 144 patients with TETs who underwent surgical resection. The present study assessed whether the expression of VEGFR-2 protein was associated with TET classification and pathological stage, progression-free survival and overall survival (OS). A total of 94 cases (65.2%) were positive for VEGFR-2 protein. The expression of VEGFR-2 was higher in the more aggressive type B3 thymoma and TC (88.5%) than in types A, AB, B1 and B2 thymoma (60.2%). The 5-year OS rate for the overall population was 53.1%. The 5-year OS rates of patients with negative VEGFR-2 staining score values (66.5%) were significantly longer than in patients with positive VEGFR-2 staining score values (42.5%; P=0.000078). Furthermore, the pathological stage was the only factor significantly associated with OS in multivariate analysis. The results of the present study suggest the possibility that the indications for VEGF inhibitor therapy could be extended to type B3 thymoma.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Function and evolution of nodulation genes in legumes.

Root nodule (RN) symbiosis has a unique feature in which symbiotic bacteria fix atmospheric nitrogen. The symbiosis is established with a limited species of land plants, including legumes. How RN symbiosis evolved is still a mystery, but recent findings on legumes genes that are necessary for RN symbiosis may give us a clue.

Pedunculated solitary fibrous tumor of the pleura manifesting as a migrating chest mass: report of a case.

We report the case of solitary fibrous tumor of the pleura, which appeared to change its location. A computed tomography (CT) scan done at a previous hospital showed a tumor in the posterior mediastinum, suggesting that it was neurogenic. However, on the initial preoperative CT scan, the tumor seemed to have moved anteriorly, but when contrast material was injected; the tumor appeared in its original position. Video-assisted thoracoscopic surgery (VATS) revealed a pedunculated and free-moving tumor, originating from the visceral pleura. We diagnosed this unusual migrating tumor as a pedunculated solitary fibrous tumor of the pleura.

Middle lobe preservation and fixation: right upper and lower sleeve bilobectomy. How to do it.

We herein report the case of a 65-year-old female with primary lung cancer who underwent a right upper and lower sleeve bilobectomy. The radiological findings revealed that the tumor was located in the superior segment of the right lower lobe and had invaded the posterior segment of the upper lobe and the truncus intermedius. We performed a right upper and lower sleeve bilobectomy. A latissimus dorsi flap was utilized to separate the thoracic cavity into upper and lower portions, and the preserved middle lobe was fixed in the upper portion to prevent torsion. Postoperative radiography showed good expansion of the middle lobe.

Extended Bronchoplasty Anastomosed between the Left Main and the Superior Segmental Bronchi for Locally Advanced Left Upper Lobe Lung Cancer with Invasion of the Basal Segment.

We report a case of extended bronchoplasty in which anastomosis between the left main and the superior segmental bronchi with resection of the left upper lobe and basal segment was required to avoid pneumonectomy for locally advanced lung cancer. The main tumor located at the left upper lobe invaded the basal segment, and involved both the basal pulmonary artery and left secondary carina. Regarding anastomosis, the bronchi were cut in a deep wedge shape and a wall flap was made by part of the lower lobar bronchus. The patient's postoperative course was uneventful and he has been alive without recurrence for more than 3 years after surgery.

Prognostic value of systemic inflammatory markers and the nutrition status in thymic epithelial tumors with complete resection.

BACKGROUND: Recent studies have shown that several systemic inflammatory markers and the nutrition status, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), are useful prognostic factors in several malignant tumors. The present study explored the prognostic value of the NLR, MLR, PLR, and PNI in thymic epithelial tumor (TET) patients who underwent complete resection. METHODS: A total of 158 TET patients who underwent complete resection were involved in the analysis. Their NLR, MLR, PLR, and PNI values were obtained from a blood examination within one month before the initiation of treatment. A receiver operating characteristic curve analysis was conducted to determine the optimal cutoff values. RESULTS: The enrolled patients were stratified by cutoffs of 4.35 for the NLR, 0.22 for the MLR, 130.18 for the PLR, and 44.02 for the PNI. A univariate analysis revealed that high-grade malignant TET, including type B2 and B3 thymoma, thymic carcinoma, and thymic neuroendocrine tumor; an advanced Masaoka stage; a high NLR; a high MLR; and a low PNI were significant predictors of a poor disease-free survival (DFS). A multivariate analysis confirmed that an advanced Masaoka stage (HR = 5.5557, p = 0.0007) and a high MLR (HR = 3.3371, p = 0.0264) were independent predictors of a poor DFS. CONCLUSIONS: Our study demonstrated that the pretreatment MLR was an independent predictor of the DFS in patients with TETs who underwent complete resection.

A large intrathoracic goiter with tracheal stenosis: Complete resection using a robot-assisted thoracoscopic approach.

Growing intrathoracic goiters may compress surrounding organs and deteriorate the cardiopulmonary function. Treating such cases requires carefully considering how to maintain oxygenation and resect the tumor with minimal invasiveness without complications. We herein report a surgically resected case of a large intrathoracic goiter-compressed trachea extending from the right lower pole of the thyroid gland to the carina. We secured the airway by intubation preparing for extracorporeal membrane oxygenation and successfully performed surgical complete resection using a robot-assisted thoracoscopic and cervical approach. Intrathoracic goiter is a tumor with abundant neovascularity, and the right vagus nerve is displaced in the thoracic cavity, but a robot-assisted thoracoscopic approach using CO2 insufflation improved visualization at the narrow apex area of the thoracic cavity. Robot-assisted thoracoscopic surgery is a useful surgical procedure enabling safe and minimally invasive surgery without recurrent laryngeal nerve palsy or tracheal injury for intrathoracic giant goiters extending into the thoracic cavity.

A single-center analysis of 71 patients with thymic carcinoma: the chronological changes in the surgical procedure and prognosis.

Background: Effective treatments for thymic carcinoma (TC) have not been established due to its rarity and the prognosis has not yet been improved. In the present study, data of patients who underwent treatment for TC at our single institution were retrospectively reviewed to investigate the chronological changes in the clinical characteristics, surgical procedure, and prognosis. Methods: A total of 71 patients were included in this study. To investigate the chronological changes, the patients were divided into two groups at January 2009, when minimally invasive surgery (MIS) for thymic epithelial tumors (TETs) was introduced. Results: Among the 71 TC patients, 24 patients underwent surgery through December 2008 (earlier period), and 21 underwent surgery from January 2009 (later period). The patients in the later group were more likely to be diagnosed by chest computed tomography (CT) scan without subjective symptom. The rates of MIS and complete resection were significantly higher and the number of the patients at the early stage were significantly greater in the later group. The 5-year overall survival (OS) rate of the patients who underwent surgery at earlier and later groups were 58.7% and 92.8% respectively (P<0.01). Conclusions: The prognosis of TC has improved over time, thanks to early detection by CT screening and complete surgical resection.

Comparison of the efficacy of novel two covering methods for spontaneous pneumothorax: a multi-institutional study.

OBJECTIVES: The postoperative recurrence rate after thoracoscopic bullectomy for primary spontaneous pneumothorax (PSP) is not satisfactory. This retrospective study was conducted to elucidate an effective technique for improving the postoperative recurrence rate. METHODS: The present study included 373 patients who underwent thoracoscopic bullectomy for PSP at three hospitals from January 2013 to May 2020. We compared the recurrence rate according to two methods that were used to cover the staple line after thoracoscopic bullectomy. Group A (146 patients) was treated with an absorbable polyglycolic acid (PGA) sheet plus fibrin glue and oxidised regenerated cellulose (ORC). Group B (227 patients) was treated with ORC alone. RESULTS: There was no significant difference in preoperative characteristics of the patients. The postoperative recurrence rate of pneumothorax was 3.4% (5/146) in Group A and 17.2% (39/227) in Group B, respectively. Among 23 patients (Group A, n=3 and Group B, n=20) who received reoperation for recurrent pneumothorax, the site of recurrence was around the stapler line of the first operation in 1 of 5 (20%) patients in Group A and 28 of 39 (71.8%) patients in Group B. The 1-year recurrence-free rate was 97.4% (median follow-up period, 73 days (range, 2-3952 days)) in Group A and 80.9% (median follow-up period, 71 days (range 2-2648 days)) in Group B. CONCLUSIONS: Coverage with a PGA sheet may prevent the postoperative recurrence of PSP. A large-scale prospective randomised study should be conducted to clarify the most effective treatment for PSP.

Hemoptysis after coil embolization for pulmonary arteriovenous malformation: Histopathological confirmation of bronchial epithelium extension.

Coil embolization is widely performed for pulmonary arteriovenous malformations (PAVMs). We describe herein 2 cases of hemoptysis during long-term follow-up after coil embolization for PAVMs. For both cases, lobectomy was performed and histopathological examinations revealed chronic inflammation and bronchial epithelium extension into the sac of the PAVM. In addition, we performed a systematic review of previous reports of hemoptysis after embolization for PAVMs.

The usefulness of fluorodeoxyglucose-positron emission tomography as a preoperative diagnostic tool for thymic epithelial tumors.

BACKGROUND: To investigate the usefulness of 18F-fluorodeoxy glucose-positron emission tomography (18F-FDG PET) for the preoperative imaging diagnosis of malignant grade in thymic epithelial tumors (TETs) and the correlation between the maximum standardized uptake value (SUVmax) and tumor size in TETs. METHODS: We retrospectively investigated 51 patients with TETs performed 18F-FDG PET. The SUVmax was compared between thymic carcinomas and thymomas. We also evaluated the difference in the SUVmax limited to small TETs. In addition, the correlation between the SUVmax and the tumor size was evaluated. RESULTS: The mean SUVmax of thymic carcinomas (n=12) and thymomas (n=39) was 5.71±2.6 and 3.08±1.4, respectively. The SUVmax of thymic carcinomas was significantly higher than that of thymomas (P<0.001). The mean SUVmax of these small thymic carcinomas (n=3) and thymomas (n=13) was 2.97±0.24 and 1.79±0.47, respectively. The SUVmax of the small thymic carcinomas was significantly higher than that of the thymomas (P=0.001). We found a positive correlation between the SUVmax and the maximum tumor size of TETs (correlation coefficient: 0.632, P<0.001). CONCLUSIONS: 18F-FDG PET might be useful for evaluating the preoperative malignancy of TETs. Of note, the maximum tumor size should be considered when performing assessments by 18F-FDG PET.

Type A thymoma with simultaneous solitary intrapulmonary metastasis: A case report.

A 79-year-old woman was referred to our facility because of an abnormal chest shadow. Chest computed tomography (CT) showed a solitary right middle lung nodule with a maximum diameter of 3 mm and anterior mediastinal nodule with a maximum diameter of 21 mm. The lung nodule was suspected of being a primary lung cancer rather than a metastatic tumor because there were no primary malignant tumors, apart from an anterior mediastinal tumor visible on diagnostic imaging, including F18 fluorodeoxyglucose-positron emission tomography, and a solitary lung nodule. Partial lung resection by video-assisted thoracoscopic surgery (VATS) was performed, and the intraoperative frozen section of the tumor tissue resulted in a diagnosis of carcinoid tumor. As a result, right middle lobectomy by VATS was performed. The final histological diagnosis of the permanent specimen was intrapulmonary type A thymoma. VATS thymectomy was performed three months later. The histological diagnosis was type A thymoma with intrapulmonary metastasis (Masaoka stage IVb). Additional therapy was not performed because complete resection was achieved. Follow-up CT was performed once every six months after the operation. The patient has been followed up for one year without any further recurrence.