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.

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.

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.

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.

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.

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.

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).

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.

Examination on the necessity of pericardial fat tissue resection in extended thymectomy for myasthenia gravis.

BACKGROUND: Extended thymectomy with pericardial fat tissue resection has been a mainstay in the treatment for myasthenia gravies (MG), but few studies have examined the necessity of the pericardial fat tissue resection in extended thymectomy. METHODS: We pathologically examined the distribution of germinal centers in the resected thymus including the thymus-surrounding fat tissue. Patients who underwent extended thymectomy using subxiphoid thoracoscopy for generalized MG or thymoma with anti-acetylcholine receptor antibody (anti-AchR Ab) positivity from March 2015 to January 2021 were included in this study. RESULTS: A total of 20 patients underwent extended thymectomy (generalized nonthymomatous MG, n=5; generalized MG with thymoma, n=6; thymoma with anti-AchR Ab positivity, n=9). The resected specimens were divided to 6 parts and were pathologically examined to investigate the distribution of the geminal centers in all lesions. The number and distribution of germinal centers in the thymus varied depending on the patient, and no germinal centers were identified in the right or left pericardial fat tissues. CONCLUSIONS: It is necessary to resect the pericardial fat tissue in patients whose preoperative images show the presence of pericardial fat tissue hyperplasia or ectopic thymoma. However, extensive pericardial fat tissue resection might not be necessary for all MG patients who undergo extended thymectomy with opening of the bilateral pleural by video-assisted or robot-assisted thoracoscopic surgery (RATS) via a subxiphoid approach.

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.

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.

A simple and reliable method to preoperatively detect a common trunk of the left pulmonary vein.

BACKGROUND: It is difficult to detect a common trunk of the left pulmonary vein (PV) preoperatively, which may cause intraoperative accidental complications. The purpose of this study is to establish a simple and reliable method of detecting a common trunk in preoperative computed tomography (CT) images. METHODS: A total of 428 patients who underwent thin-section CT preoperatively for left lung cancer at 4 institutions were reviewed. The characteristic findings of a common trunk in the axial view were considered by confirming the preoperative CT findings of cases that had been verified to have a common trunk based on intraoperative findings. The CT images were reviewed independently by two evaluators. RESULTS: We found that the distance between the mediastinal side of the left lower bronchus and the junction of two left PVs was extremely short in the cases with a common trunk in the axial view. In a typical case, the axial section of the bronchus is close to the junction. Of the 416 patients that were evaluable among the 428 total patients, 26 (6.3%) were diagnosed as having a common trunk by both evaluators, and the diagnosis was coincident in 413 patients (99.2%). We were able to evaluate the surgical videos of 16 of the 26 patients, and a common trunk was confirmed in 15 patients (94%). CONCLUSIONS: We established a simple and reliable method of detecting a common trunk of the left PV in the axial view on chest CT that was routinely performed prior to lung cancer surgery.

Pericardial immunoglobulin G4-related inflammatory pseudotumor after right upper lobectomy for lung cancer.

A 75-year-old woman underwent thoracoscopic right upper lobectomy for lung cancer. A histopathological examination showed adenocarcinoma, pT1aN0M0 stage IA1. At six months after surgery, chest computed tomography (CT) revealed pericardial nodules that had not been detected before pulmonary resection. Postoperative CT performed two months later revealed that the nodules were growing and F18 fluorodeoxyglucose-positron emission tomography showed a maximum standardized uptake of 9.87. Blood tests revealed no elevated tumor markers, with the exception of a mildly elevated interleukin-2. Based on the above results, thoracoscopic biopsy was performed due to the suspected recurrence of lung cancer or malignant lymphoma. The histopathological examination of the nodule revealed immunoglobulin G4 (IgG4)-related inflammatory pseudotumor. The serum IgG4 levels were elevated (358 mg/dL, normal: 4.5-117.0 mg/dL). No additional treatment was required because all nodules were observed to have disappeared naturally on a follow-up CT scan performed two months after the surgical biopsy. The patient has been followed-up for two years without recurrence. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We report a case of pericardial immunoglobulin G4-related inflammatory pseudotumor that appeared after right upper lobectomy for lung cancer, and which naturally disappeared without any treatment. WHAT THIS STUDY ADDS: There was an immunoglobulin G4-related inflammatory pseudotumor which appeared as multiple nodules in the pericardial space, and this should be kept in mind when considering the differential diagnosis of intrapericardial nodules.

Long-term survivor of pulmonary combined large cell neuroendocrine carcinoma treated with nivolumab.

Several authors have previously reported that patients with pulmonary combined large cell neuroendocrine cancer ( LCNEC) have a poor prognosis and there is no consensus on the treatment strategy for combined LCNEC as well as LCNEC. Here, we report the case of a long-term survivor with pulmonary combined LCNEC. The patient was a 60-year-old man who underwent thoracoscopic right lower lobectomy. The final histopathology and staging of the tumor showed LCNEC combined with squamous cell carcinoma and T2aN0M0 stage IB. Multimodality treatments including chemotherapy, radiotherapy and surgery for several recurrences were performed after the pulmonary surgery. After immune checkpoint inhibitor (ICI) therapy with nivolumab, all the metastatic lesions shrunk and a partial response was maintained at five years after the first surgery. In our case, ICI after multimodality therapy combining cytotoxic anticancer drugs and radiotherapy was effective in LCNEC with metachronous multiple metastases. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Immune checkpoint inhibitor after multimodality therapy combining cytotoxic anticancer drugs and radiotherapy was effective in LCNEC with metachronous multiple metastases. The patient survived over five-years after the first surgery. WHAT THIS STUDY ADDS: Immune checkpoint inhibitor may be effective in some LCNEC patients.

Mixed-type primary germ cell tumor of the mediastinum in a young adult male with a sudden life threatening condition: A case report.

Primary germ cell tumors of the mediastinum are rare neoplasms. Above all, choriocarcinomas are highly aggressive with early haematogenous dissemination. Here, we report an extremely rare case of mixed-type primary germ cell tumor of the mediastinum which occurred in a 26-year-old man with multiple metastases of the lung caused by choriocarcinoma components, with diffuse pulmonary hemorrhaging. The patient developed a sudden life threatening condition a few days after a needle biopsy. KEY POINTS: Significant findings of the study: This was an extremely rare case of mixed-type germ cell tumor in a young adult male who developed a sudden life threatening condition due to choriocarcinoma components just a few days after a needle biopsy. What this study adds: Serious conditions may occur in patients with germ cell tumor containing choriocarcinoma components. At present, there is no other way to treat such patients than to promptly recognize complications and perform urgent multimodal intervention.

Talc pleurodesis for secondary pneumothorax in elderly patients with persistent air leak.

BACKGROUND: We herein report the usefulness of two types of talc pleurodesis for secondary pneumothorax of elderly patients with persistent air leak who have severe pulmonary emphysema. METHODS: We assessed 17 elderly patients with persistent air leak who received talc pleurodesis for secondary pneumothorax from April 2013 to March 2017. Thoracoscopic talc poudrage (TTP) (n=11) was performed in patients whose general condition was thought to sufficiently stable to tolerate for general anesthesia. Talc slurry pleurodesis (TSP) (n=6) via a chest tube was performed in patients whose general condition was thought to be insufficiently stable to tolerate general anesthesia. RESULTS: The median drainage period after pleurodesis was 6 days in patients who received TTP and 12 days in patients who received TSP. Complications associated with talc pleurodesis included atrial fibrillation (n=1) in the thoracoscopic poudrage group, while the slurry pleurodesis group showed chest pain (n=2), asthmatic attack (n=1), and pneumonia (n=1). All patients who received thoracoscopic poudrage were able to leave the hospital after removal of the chest tube. Five of the six patients who received slurry pleurodesis were able to leave the hospital, but one of them died of acute exacerbation of interstitial pneumonia (IP) on the 45th day after pleurodesis. The success rate was 94% (16/17). There were no cases of recurrence during the observation period. CONCLUSIONS: TTP was deemed likely to be safe and effective for patients able to tolerate general anesthesia. In patients with IP, especially those treated with steroids, the indication of talc pleurodesis should be cautiously considered.