Perspectives on surgical treatment for thymic epithelial tumors: a narrative review.

Background and Objective: Thymic epithelial tumors are relatively rare; thus, mostly retrospective studies and a few prospective randomized controlled trials have been conducted on the treatment and the biomarkers, with no standard therapy established. Indications for extended thymectomy, robot-assisted thoracic surgery, and multidisciplinary treatment are controversial. Here, we considered the prospects of surgical treatment and the possibility of immune checkpoint inhibitor (ICI) treatment for thymic epithelial tumors. Methods: This is a narrative review; PubMed was searched using a set of keywords related to thymoma and its proposed treatments over the last 5 years. Key Content and Findings: Thymic epithelial tumors are associated with autoimmune diseases. They are relatively rare, and their pathology remains unclear. Therefore, accumulating more case reports is important. Surgical resection is generally considered for both diagnosis and treatment. If the tumor has a strong tendency to invade surrounding areas, such as thymic carcinoma/thymoma, the diagnosis may be confirmed preoperatively by needle biopsy, and induction chemotherapy may be selected. Surgical resection is the most effective treatment, and complete resection is important. In cases where complete resection is difficult, multidisciplinary treatment is performed. Although there are various obstacles, using ICIs may prove effective for treatment both as preoperative and postoperative chemotherapy in the future, as shown for other cancers. Programmed cell death-ligand 1 (PD-L1) is an immunoinhibitory molecule that suppresses T cells activation, leading to tumor progression. Overexpression of PD-L1 in some cancers is associated with poor clinical outcomes. However, the role of PD-L1 expression as a prognostic factor remains controversial. Therefore, various biomarkers other than PD-L1 have been identified. Conclusions: We reviewed the latest treatments for thymic epithelial tumors. If new therapeutic agents such as ICIs and molecular-targeted drugs are developed, this review suggests that surgery will become more important not only as therapy but also as part of multidisciplinary treatment that includes tissue collection.

Prognostic impact of PD-L1 and TIGIT expression in non-small cell lung cancer following concurrent chemo-radiotherapy.

We investigated the effect of preoperative therapy for non-small cell lung cancer on programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), poliovirus receptor (CD155), and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) expression and prognosis with the cases of 28 patients received preoperative concurrent chemo-radiotherapy (cCRT) and 27 received preoperative drug therapy. The post-treatment PD-L1 expression was higher in cCRT group than in the drug therapy (50.0% vs 5.0%, p = 0.000), whereas that of CD155 did not significantly differ (40.0% vs 60.0%, p = 0.131). The PD-1 expression was not significantly different between the cCRT and drug therapy groups (51.1% vs 42.9%, p = 0.076), while the TIGIT was significantly higher in the cCRT group (41.5% vs 34.0%, p = 0.008). The patients who received cCRT resulted in elevated PD-L1and TIGIT values had a worse prognosis (p = 0.008). The PD-L1 and TIGIT expression after cCRT was significantly higher than after drug treatment. The cCRT population with high expression of both had a significantly poorer prognosis, indicating elevation of PD-L1 and TIGIT after cCRT as a negative prognostic factor. Combination therapy with anti-PD-L1 and anti-TIGIT antibodies after cCRT may contribute to an improved prognosis.

Relationship between anti-acetylcholine receptor antibodies and the development of post-thymectomy myasthenia gravis in patients with thymoma: a single-center experience.

BACKGROUND: Approximately 15-29.6% of patients with thymoma have myasthenia gravis (MG). Some of these patients develop MG after thymectomy despite having no history of MG or related symptoms. Few previous studies have examined the risk factors for the development of post-thymectomy MG in patients with thymoma. Herein, we retrospectively reviewed our institutional experience with patients with thymoma who developed MG after thymectomy. METHODS: Twenty-six patients with thymoma but without MG, who were tested preoperatively for anti-acetylcholine receptor antibody (anti-AChR-Ab) levels, underwent surgical resection at our hospital between 2013 and 2020. Patients with thymic carcinoma were excluded from the study. We evaluated the association of outcomes with preoperative anti-AChR-Ab levels and post-thymectomy MG. We performed a χ2 test for bivariate analysis of categorical data. Differences were considered significant at P<0.05. RESULTS: The characteristics of the 26 patients (median age: 62 years; 8 men, 18 women) were as follows: World Health Organization (WHO) classifications AB (n=8), B1 (n=9), B2 (n=6), B3 (n=1), and others (n=2) and Masaoka stage I (n=12), II (n=9), III (n=3), and IVa (n=2). Among the 26 patients, only five had high (>0.3 nmol/L) preoperative anti-AChR-Ab levels. Post-thymectomy MG occurred in two of the five patients (40%) with high preoperative anti-AChR-Ab levels. A high preoperative serum anti-AChR-Ab titer was significantly associated with post-thymectomy MG (P=0.0267). The anti-AChR-Ab titer was also measured postoperatively in four of the five (80%) patients with high preoperative levels. The anti-AChR-Ab titer decreased in two of these four patients, and neither developed postoperative MG. CONCLUSIONS: Preoperative and postoperative anti-AChR-Ab positivity might be associated with post-thymectomy MG. Therefore, regular measurement of anti-AChR-Ab levels after thymectomy is required.

Difficulty of treatment for pleural epithelioid hemangioendothelioma: a report of a case.

We herein report the case of a 62-year-old man who underwent extrapleural pneumonectomy (EPP) for pleural epithelial hemangioendothelioma (EHE) diagnosed by a pleural biopsy. Pre-operative computed tomography revealed diffuse pleural thickening and pleural effusion in the right thoracic cavity, although metastasis to neither the lymph nodes nor distant organs was detected. We decided to perform EPP based on surgical findings that the tumor had invaded the lung parenchyma. A pathological examination revealed tumor invasion of the lung parenchyma, blood vessel, pericardium, diaphragm and bronchial wall. Despite aggressive treatment, tumor recurrence was detected about 1 month after surgery. Although we controlled the tumor progression using pazopanib, the patient ultimately died 3.5 months after the operation. Pleural EHE is a very rare disease that has a poor prognosis due to its high malignant potential. It is important to formulate strategies matched to individual cases based on disease progression and invasiveness of treatment.

What is the best treatment strategy for primary spontaneous pneumothorax? A retrospective study.

BACKGROUND: Several treatment strategies are available for primary spontaneous pneumothorax (PSP). Surgical procedures are also performed in patients with PSP without an absolute indication for surgery. This study was performed to investigate the best treatment strategy for PSP by comparison of the recurrence rate. MATERIALS AND METHODS: From January 2006 to December 2013, 149 patients with PSP aged ≤50 years were treated in our institution. We reviewed the recurrence rate of PSP for each treatment strategy and evaluated the association between the recurrence rate of PSP with the clinicopathological characteristics. We also compared the surgery and non-surgery groups. RESULTS: A significant difference in the PSP recurrence rate was found between the surgery and non-surgery groups (22% vs. 52%, respectively; p < 0.001), patients aged ≥22 and < 22 years (16% vs. 44%, respectively; p < 0.001), and smokers and nonsmokers (13% vs. 43%, respectively; p < 0.001). There were also significant differences in the multivariate analysis (p < 0.001, p = 0.050, and p = 0.001, respectively). In the surgery group, the PSP recurrence rate was significantly different between patients aged ≥22 and < 22 years (7% vs. 38%, respectively; p < 0.001) and smokers and nonsmokers (5% vs. 33%, respectively; p = 0.002). No significant differences were found in the non-surgery group. CONCLUSIONS: In the surgical treatment of PSP, it is desirable that smokers stop using tobacco and that patients are ≥22 years old. Moreover, when surgery is being considered, the best timing seems to be when air leakage is present because the air leakage sites can be resected.

Salvage surgery combined with descending aorta resection for lung cancer.

BACKGROUND: Recent retrospective studies have shown that salvage surgery can improve survival with acceptable adverse events, and this procedure has been adapted for lung cancer. However, there are no reports demonstrating the efficacy of salvage surgery combined with aortic resection. CASE PRESENTATION: A 73-year-old man had received definitive concurrent chemoradiotherapy (carboplatin/paclitaxel, 70 Gy) for lung cancer originated from the left upper lobe and infiltrating the thoracic aorta (cT4N1M0 stage IIIA). Although the tumor has shrunk significantly (ycT4N0M0 stage IIIA), radiation pneumonitis occurred. Due to the steroid therapy, radiation pneumonitis was relieved; however, re-enlargement of the primary tumor was observed during steroid tapering. Nonetheless, the lymphatic and distant metastases were controlled. Moreover, aortic invasion was localized to the periphery of the third branch, and the tumor was considered to be resectable. Intraoperatively, we observed macroscopic evidence of aortic invasion in the periphery of the third branch; thus, left upper lobectomy combined with descending aorta resection was performed under partial extracorporeal circulation. The patient is currently active without any recurrence 21 months post-surgery. CONCLUSIONS: No clear consensus exists regarding salvage surgery combined with aortic resection for primary lung cancer. However, we believe that this surgery may improve the survival of carefully selected patients.

Prognostic factors of advanced or postoperative recurrent non-small cell lung cancer targeted with immune check point inhibitors.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) have been established as one of standard therapy, the prognostic factors of ICIs remain unclear, aside from the programed cell death-ligand 1 (PD-L1) expression of tumor cells. The aim of this study was to determine the prognostic factors of ICIs. METHODS: We analyzed the clinicopathological data of 44 cases of advanced NSCLC targeted with ICIs in our hospital, between February 2016 and February 2018, in order to determine the prognostic factors of ICIs. We also reviewed the literature regarding ICIs. RESULT: We retrospectively analyzed the 44 cases (26 nivolumab and 18 pembrolizumab cases). These patients were 38 men and 6 women, comprising 13 cases of adenocarcinoma, 29 squamous cell carcinoma and 2 unclassified types. Seven patients were using first-line therapy and while the others were using second-line therapy or later. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) mutations were negative in all the cases. The response rate and disease control rate were 20.5% and 51.3%, respectively. The median progression-free survival time and median survival time were 146 days and 257 days, respectively. We observed five severe adverse effects (AEs) (three cases of interstitial pneumonia, one of liver dysfunction and one of adrenal failure), that were resolved by steroid pulse therapy. In multivariate analyses, the Eastern Cooperative Oncology Group performance status (ECOG PS), pathological type, standardized uptake value (SUV) on positron emission tomography (PET), white blood cell (WBC) count, neutrophil, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and albumin were independently prognostic factors. There were no significant differences in the prognosis between nivolumab and pembrolizumab. CONCLUSIONS: ICIs were effective in 44 treated NSCLC cases. Our analysis suggests that while ICIs are effective in treating patients, candidates must be carefully selected and cautiously observed.

Fenestration without rib resection for postoperative bronchopleural fistula.

BACKGROUND: Fenestration is performed in patients with bronchopleural fistula to avoid a life-threatening situation. However, usually, this procedure is required 9-cm mean length of the incision with rib resection. CASE PRESENTATION: A 73-year-old man underwent right lower lobectomy with lymph node dissection (ND2a-2) for primary lung cancer (cT1cN2M0 Stage IIIA) with combined pulmonary fibrosis and emphysema. He developed a bronchopleural fistula on postoperative day 20, and we performed emergency fenestration without rib resection using a Lap-protector. The patient reported minimal pain postoperatively. As the rapid deterioration of the general condition due to the recurrence of the tumor was observed at the time of his 1-year postoperative follow-up, closing of the thoracic cavity was abandoned. However, using this fenestration, the control of infection in the thoracic cavity could be sufficiently performed without complications such as pain and pneumonia, and his routine activities were unaffected postoperatively. CONCLUSION: Compared with conventional method, fenestration without rib resection using a Lap-protector is a more convenient and painless technique for postoperative bronchopleural fistula.

Successful surgical treatment with tracheal resection for a symptomatic vascular ring in an adult.

Vascular rings are congenital anomalies of the aortic arch, which may cause compression of the trachea and esophagus. Compression symptoms usually present in infants and children. Adult presentations are quite rare, and compression symptoms may not be relieved by surgical correction due to tracheal remodeling and malacia caused by a long-standing compression. Here, we present an adult case of symptomatic vascular ring formed by the right aortic arch and persistent left ligamentum arteriosus. Respiratory symptoms were predominantly due to severe tracheal stenosis caused by tracheal wall thickening through remodeling during long-standing compression, and were relieved by surgery with transection of the persistent followed by resection and reconstruction of the trachea.

Extended pleurectomy decortication for thymoma with pleural dissemination.

Complete resection is the mainstay of treatment for thymoma. Even for advanced-stage thymoma with pleural dissemination, complete resection with extrapleural pneumonectomy may provide a favorable prognosis. Pleurectomy decortication, a lung-sparing surgery, has been preferably employed in recent years as an alternative surgical procedure for malignant pleural mesothelioma. However, little has been reported about pleurectomy decortication for other malignant tumors with pleural dissemination. Here, we present the first case of thymoma with pleural dissemination for which complete en bloc resection was achieved with extended pleurectomy decortication.

Effect of erlotinib plus bevacizumab on brain metastases in patients with non-small cell lung cancer.

BACKGROUND: The standard therapy for brain metastasis (BM) in non-small cell lung cancer (NSCLC) is radiation therapy (RT), although it is associated with complications such as leukoencephalopathy. In the current report, we retrospectively review data from eight patients who had NSCLC and harbored epidermal growth factor receptor (EGFR) mutations, and who were received erlotinib plus bevacizumab (E+B) as first-line therapy for BM. METHODS: Patients were given E+B as first therapy for BM until August 2017 at our institution. Patients receiving local therapy for BM, such as surgery or radiotherapy, were excluded. Patients were administered erlotinib orally (once daily at 150 mg/body) plus bevacizumab by intravenous infusion (15 mg/kg on day 1 of a 21- or 28-day cycle). RESULTS: Eight NSCLC patients who were diagnosed with BM received E+B, including 2 men and 6 women with a median age of 65 years (range, 46-84 years). Four patients had an L858R EGFR mutation, while the other four had an exon 19 deletion. Seven patients had a partial response to E+B treatment, and one had a complete response. The 2-year survival rate was 62.5%. Three patients who were pre-treated with gefitinib had an E+B treatment duration of less than 1 year. At the time of this analysis, four patients had BM-related neurologic symptoms and multiple BMs, and were still receiving E+B with no evidence of treatment failure after more than 1 year. CONCLUSIONS: E+B can be used as first-line therapy for BM, even in patients with BM-related neurologic symptoms and multiple BMs.

Complete resection of an anterior mediastinal tumor by total arch replacement and pulmonary artery trunk plasty with a pericardial patch: A case report.

INTRODUCTION: Patients with undiagnosed anterior mediastinal tumors commonly undergo surgery for diagnosis and treatment. However, determining the optimal therapeutic strategy is difficult for tumors with substantial invasion, such as lesions touching the aortic arch (AA). CASE PRESENTATION: A 76-year-old man of Asian descent presented to our hospital because chest computed tomography (CT) revealed an anterior mediastinal tumor. This tumor surrounded the left subclavian vein and touched the AA. We suspected the tumor to be malignant. We therefore decided to resect the tumor with preparation for total arch replacement (TAR). The operation was performed in three steps. First, we performed a mediastinal sternotomy. However, the tumor had invaded the subclavian vein, so we resected this vein after adding a transmanubrial approach. However, because of invading the AA we needed next step. Second, we shifted the patient to the right lateral decubitus position. We performed partial resection of the left upper lobe and exfoliated the distal AA. Third, we shifted the patient to the dorsal position and implanted an artificial cardiopulmonary device, after which we performed TAR, and pulmonary artery (PA) trunk plasty with a pericardial patch. The operation was successful, with no major adverse events. Pathologically, the tumor was diagnosed as diffuse large B-cell lymphoma. DISCUSSION: If oncologically complete resection is preferable for tumors with substantial invasion, complete resection should be attempted even if the surgery is difficult. CONCLUSION: We performed complete resection of an anterior mediastinal tumor with TAR and PA trunk plasty using a pericardial patch.

Outcomes of patients undergoing surgery for thymic carcinoma: a single-center experience.

BACKGROUND: Thymic carcinoma is uncommon, presents locally at an advanced stage, and behaves aggressively. The optimum treatment for advanced thymic carcinoma is controversial. We retrospectively reviewed our institutional experience with patients with thymic carcinoma. METHODS: We analyzed the clinical data of six patients who underwent total thymectomy for thymic carcinoma at our institution from 2006 to 2016. Variables analyzed included sex, age, histological classification, Masaoka staging, postoperative treatment, and recurrence. RESULTS: The clinical characteristics of the six patients with thymic carcinoma (median age, 56 years; five men and one woman) were as follows: squamous cell carcinoma (n=5); sarcomatoid carcinoma (n=1); Masaoka stages II (n=1), III (n=2), IVa (n=1), and IVb (n=2). Four patients underwent combined pulmonary resection (66.7%) as a component of en bloc resection due to suspicion of pulmonary invasion. Four patients (66.7%) received postoperative therapy, and complete resection was achieved for four patients. There were no perioperative deaths. One patient experienced a recurrence. CONCLUSIONS: Complete resection for thymic cancer improved the prognosis of our patients, indicating that robust studies will be required to confirm our findings.

Extremely Didactic Experience About the Postoperative Recurrence of Lung Cancer: a Case Report.

We often encounter the postoperative recurrence of lung cancer. It is generally diagnosed based on the clinical course and the results of imaging studies, such as computed tomography (CT) and positron emission tomography (PET). The organization diagnosis is often not done. We present the case of a patient who was treated for the postoperative recurrence of lung cancer that was later proven by biopsy to be a second lung cancer. It is possible that cases of a second cancer, like ours, are overlooked because they are incorrectly classified as postoperative recurrences of lung cancer based on the clinical course and imaging findings. However, when we encounter a case of suspected postoperative recurrence, we should also consider that it could be a second lung cancer.

Predictive factors of postoperative survival among patients with pulmonary neuroendocrine tumor.

BACKGROUND: Pulmonary neuroendocrine tumor (NET) occurs with 20% of all lung cancers, and there are a limited number of literatures about the molecular aberrations, treatment and prognosis; especially in resected cases, as the operation indication for large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is rare due to their aggressive behaviors. We investigated the relationship between postoperative survival and molecular expression patterns of pulmonary NET to establish a more effective treatment strategy. METHODS: In the present study, the curative surgical resection of pulmonary NET was reviewed retrospectively. A total of 105 patients with pulmonary NET, who underwent complete resection between 1978 and 2016, were subjected to analysis with respect to histological characterization and clinical behaviors of pulmonary NET using immunohistochemistry (IHC) of neuroendocrine markers and programmed cell death-ligand 1 (PD-L1). RESULTS: The pathological types included 67 SCLC, 18 LCNEC, 14 typical carcinoids (TCs) and 6 atypical carcinoids (ACs). The ACs had significantly worse prognosis than TCs. PD-L1 expression ratio in SCLC/LCNEC/TC/AC was 26.1%/50%/15.4%/20%, respectively. However, it was not significantly correlated with each prognosis. Therefore, the SCLC patients were analyzed, the overall 5-year survival of SCLC patients was found to be 47.3%. In the univariate analysis of the molecular expression of SCLC, neuroendocrine markers such as chromogranin-A (CGA) and synaptophysin (SYN) showed poor prognosis, albeit without significant differences. CONCLUSIONS: The neuroendocrine markers such as CGA and SYN might assist the prediction of prognosis and probably influence the decision for adjuvant chemotherapy or follow-up intervals after surgery in SCLC patients; however additional studies are essential.

Mediastinal Tracheostoma for Treatment of Tracheostenosis after Tracheostomy in a Patient with Mucopolysaccharidosis-Induced Tracheomalacia.

BACKGROUND: Treatment of tracheostenosis after tracheostomy in pediatric patients is often difficult. Mucopolysaccharidosis is a lysosomal storage disease that may induce obstruction of the airways. CASE PRESENTATION: A 16-year-old male patient underwent long-term follow-up after postnatal diagnosis of type II mucopolysaccharidosis. At 11 years of age, tracheostomy was performed for mucopolysaccharidosis-induced laryngeal stenosis. One week prior to presentation, he was admitted to another hospital on an emergency basis for major dyspnea. He was diagnosed with tracheostenosis caused by granulation. The patient was then referred to our institution. The peripheral view of his airway was difficult because of mucopolysaccharidosis-induced tracheomalacia. For airway management, a mediastinal tracheostoma was created with extracorporeal membrane oxygenation. To maintain the blood flow, the skin incision for the mediastinal tracheal hole was sharply cut without an electrotome. The postoperative course was uneventful, and the patient was weaned from the ventilator on postoperative day 19. He was discharged 1.5 months postoperatively. Although he was referred to another institution because of respiratory failure caused by his primary disease 6 months postoperatively, his airway management remained successful for 1.5 years postoperatively. CONCLUSION: Mediastinal tracheostomy was useful for treatment of tracheostenosis caused by granulation tissue formation after a tracheostomy.

Successful lung-sparing resection of synchronous pleural mesothelioma and contralateral lung cancer.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an uncommon malignant tumor, and its synchronous occurrence with primary lung cancer is extremely rare. Here, we report the first surgical case of synchronous MPM and contralateral lung adenocarcinoma. Extrapleural pneumonectomy (EPP) combined with surgery for contralateral lung cancer may not be tolerated, and a lung-sparing procedure including pleurectomy/decortication (P/D) can be an alternative to achieve complete resection. CASE PRESENTATION: A 69-year-old male with right MPM and lung adenocarcinoma in the left upper lobe presented. Two lesions were judged to be synchronous MPM and lung cancer that were both potentially resectable clinical stage I diseases, and complete resection of both tumors was successfully achieved with right P/D following left upper division segmentectomy. CONCLUSIONS: P/D, not EPP, is a less invasive surgical procedure for MPM with curative intent and can be performed in combination with contralateral lung resection.