Surgical outcomes and perioperative risk factors of patients with interstitial lung disease after pulmonary resection.

BACKGROUND: Patients of interstitial lung disease (ILD) combined with pulmonary lesions are increasingly common in clinical practice. Patients with ILD are at significantly higher risk for complications after pulmonary resection (including lobectomy and sublobar resection), especially acute exacerbations of ILD (AE-ILD). The purpose of this study is to summarize the short-term and long-term outcomes after pulmonary resection in ILD patients and to analyze the clinical factors affecting surgical safety. METHODS: From January 2004 to January 2022, a total of 78 patients who were diagnosed with ILD and underwent pulmonary resection at our center were enrolled in this study. Clinical data, pathological findings, surgical procedures, and intraoperative safety of these patients were collected retrospectively. Postoperative 90-day complications and mortality, long-term surgical outcomes from postoperative 90 days to 24 months, and changes in ILD condition were investigated. Logistic regression analysis was used to identify the risk factors associated with postoperative complications. RESULTS: The median age of patients was 66.5 (range 33-86) years, 82.1% (64/78) of patients were male, and 78.2% (61/78) of patients had comorbidities. Idiopathic ILD and secondary ILD accounted for 86% and 14%, thoracotomy and video-assisted thoracoscopic surgery accounted for 12.8% and 87.2%, and lobectomy and sublobar resection accounted for 37.2% and 62.8%, respectively. Postoperative 90-day complications occurred in 25.6% (20/78) of patients, with pulmonary complications and AE-ILD occurring in 15.4% and 9.0% of patients, respectively. The postoperative 90-day mortality rate was 5.1% (4/78), and the cause of death was AE-ILD. Exacerbation of ILD or other complications occurred in 12.8% (10/78) of patients from postoperative 90 days to 24 months. Univariate logistic regression analysis showed that comorbidity, extent of resection, systemic lymph node dissection, operation time, intraoperative blood loss, and pathology of pulmonary lesion were associated with postoperative 90-day complications. In multivariate logistic regression analysis, age-adjusted Charlson Comorbidity Index and intraoperative blood loss were identified as independent risk factors of postoperative 90-day complications. CONCLUSIONS: Patients with ILD have a significantly higher risk of postoperative 90-day complications and mortality after pulmonary resection, especially pulmonary complications and AE-ILD. After postoperative 90 days, the risk of deterioration of pulmonary status remains high, including exacerbation of ILD and complications associated with long-term use of glucocorticoids and immunosuppressant. Age, comorbidity and intraoperative blood loss are high risk factors for postoperative 90-day complications.

Thymoma negatively affects the neurological outcome of myasthenia gravis after thymectomy: a propensity score matching study.

BACKGROUND: Thymoma and myasthenia gravis (MG) interact with each other. This study aimed to evaluate the effects of thymoma on neurological outcome of MG patients after thymectomy using the propensity score matching (PSM) method. METHODS: Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Clinical and follow-up data were collected. Statistical analysis was performed using SPSS 23.0 software. PSM was performed to eliminate selection bias. RESULTS: A total of 456 patients were included in this study. Thymoma was present in 138 (30.3%) patients. The median follow-up time was 72 (range, 12-135) months. At the last follow-up, a lower proportion of thymomatous MG patients achieved complete stable remission (CSR) compared with non-thymomatous MG patients (P = 0.011), and the effective rate [CSR + pharmatologic remission (PR) + minimal manifestations (MM)] of thymomatous MG patients was also lower (P = 0.037). Considering time to CSR, Kaplan-Meier analysis showed thymomatous MG patients had lower cumulative CSR rate than non-thymomatous MG patients (log-rank, P = 0.019). After PSM, 105 pairs of patients were matched successfully. For the matched patients, thymomatous MG patients had a lower CSR rate and a lower effective rate (P = 0.002, 0.039, respectively), and K-M analysis still showed thymomatous MG patients had lower cumulative CSR rate (log-rank, P = 0.048). Multivariate Cox analysis demonstrated that thymoma (HR: 0.592, 95% CI 0.389-0.900, P = 0.014), older age at the time of surgery (HR: 0.971, 95% CI 0.953-0.990, P = 0.003), and preoperative course of MG > 12 months (HR: 0.474, 95% CI 0.317-0.708, P = 0.000) were negative predictive factors for CSR. CONCLUSIONS: Thymoma had a negative effect on the neurological outcome of MG after thymectomy. MG patients with old age and a preoperative course of longer than one year had a lower probability of achieving CSR.

Two-stage minimally invasive pulmonary resections with intraoperative localization technique for bilateral multiple primary lung cancers: A case report.

Multiple primary lung cancers (MPLCs) are becoming more and more common and these patients can benefit from minimally invasive surgery. Here, we report a case of a patient diagnosed with synchronous MPLCs who underwent bilateral thoracoscopic pulmonary resections in a two-stage strategy, and achieved a good surgical outcome and high quality of life. A 66-year-old female was found to have one major ground-glass nodule (GGN) in the right upper lobe and eight minor GGNs in the left upper and lower lobes. The patient underwent right upper lobe resection and systematic mediastinal lymph node dissection via single-utility port thoracoscopic surgery in September 2018. Pathology was lepidic predominant adenocarcinoma pT1bN0M0, IA2. Regular high-resolution computed tomography examination during 36 months after right upper lobectomy showed gradually increasing diameter and solid component of multiple GGNs in left lung. The patient underwent thoracoscopic multiple pulmonary resections using an intraoperative localization technique in a hybrid operating room in October 2021 and all eight nodules in the left lung were resected. Two segmentectomies and four wedge resections were performed, and the pathological results of the eight nodules included four adenocarcinomas, three adenocarcinomas in situ, and one alveolar epithelial hyperplasia. The two operations were successful with no intra- or postoperative 90-day complications. During more than 20 months of follow-up after the second operation, the patient had well recovered pulmonary function and physical status with a Karnofsky performance status score of 90 and no local recurrence or metastasis. A two-stage surgical strategy for synchronous MPLCs is therefore feasible. The surgical strategy, timing of intervention, and extent of pulmonary resection should be individually designed according to the location and characteristics of each nodule. Intraoperative localization of small GGNs is very important to ensure that all nodules are completely and accurately resected during the operation.

Postoperative clinical outcomes of patients with thymic epithelial tumors after over-3-year follow-up at a single-center.

BACKGROUND: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation. METHODS: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0. RESULTS: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications. CONCLUSIONS: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy.

Analysis of influencing factors of perioperative myasthenic crisis in 387 myasthenia gravis patients without thymoma in a single center.

OBJECTIVE: To study the influencing factors of myasthenic crisis in non-thymoma myasthenia gravis (MG) patients during perioperative period. METHODS: We retrospectively analyzed a total of 387 non-thymoma MG patients who underwent extended thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from February 2011 to December 2021, recorded ASA score, Osserman classification, preoperative course, pyridostigmine dosage, operation method, operation time, and intraoperative blood loss, then analyzed the factors associated with postoperative myasthenic crisis by univariate and multivariate logistic regression. RESULTS: Osserman classification IIB + III + IV (P < 0.001), history of myasthenic crisis (P = 0.013), pyridostigmine dosage greater than 240 (P < 0.001), ASA score 2 and 3 (P = 0.001) are independent risk factors for myasthenic crisis. CONCLUSION: Patients with poor Osserman classification, history of myasthenic crisis before surgery, larger preoperative dosage of pyridostigmine, and higher ASA scores should be highly alert to the occurrence of postoperative myasthenic crisis.

Surgical safety analysis and clinical experience sharing of myasthenia gravis patients aged 65 and over.

BACKGROUND: To evaluate the surgical safety in myasthenia gravis (MG) patients aged 65 and over. METHODS: A total of 564 patients with MG who underwent surgery in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were included in the study and divided into two groups taking the age of 65 as the boundary. Perioperative data of patients were recorded and statistically analyzed. RESULTS: Compared with young patients, FEV1, FEV1% and MVV in lung function of elderly MG patients were worse (p < 0.001, p < 0.001, p = 0.002). Postoperative drainage time was longer (p < 0.001), combined with more drainage volume (p = 0.002). The American Society of Anesthesiologists (ASA) score of elderly MG patients was higher (p < 0.001). Complications were more likely to occur (p = 0.008) after surgery and Clavien-Dindo classification (CDC) of postoperative complications was also higher (p = 0.003). Meanwhile, postoperative myasthenic crisis (POMC) was more likely to occur (p = 0.038). Logistic regression showed that lower DLCO% (p = 0.049) was an independent risk factor for postoperative complications. CONCLUSIONS: Surgical indications should be considered in each elderly MG patient on an individual basis. Moreover, most elderly MG patients safely survive the perioperative period and benefit from surgery through individualized consideration.

Analysis of influencing factors of postoperative myasthenic crisis in 564 patients with myasthenia gravis in a single center.

OBJECTIVE: To study the influencing factors of myasthenic crisis in patients with myasthenia gravis during perioperative period. METHODS: A total of 564 myasthenia gravis (MG) patients who underwent standard expanded resection of thymoma/thymoma in the Department of Thoracic Surgery of Beijing Hospital from January 2011 to March 2022 were retrospectively included in the study. Clinical indicators such as gender, age, thymoma, American Society of Anesthesiologists (ASA) score, operation time, intraoperative blood loss, and some others were recorded. RESULTS: Osserman-stages IIB + III + IV (odds ratio [OR] 16.091, 95% confidence interval [CI] 5.170-50.076, p value < 0.001), the dosage of pyridostigmine bromide more than 240 mg (OR 6.462, 95% CI 3.110-13.427, p value < 0.001), ASA score 2 and 3 (OR 3.203, 95% CI 1.461-7.020, p value = 0.004), low diffusion lung capacity for carbon monoxide (DLCO%) (OR 0.981, 95% CI 0.963-1.000 p value = 0.049), and blood loss greater than 1000 ml (OR 16.590, 95% CI 1.911-144.011, p value = 0.011) were independent risk factors for myasthenic crisis. CONCLUSIONS: Patients with poor Osserman stages, higher preoperative dosage of pyridostigmine bromide, higher ASA score, poor pulmonary function (low DLCO%), and more intraoperative bleeding should be highly vigilant for the occurrence of postoperative myasthenic crisis.

Clinical characteristics of myasthenia gravis (MG) patients developing other autoimmune diseases after thymectomy from one single center cohort.

BACKGROUND: Myasthenia gravis (MG) patients are reported to have a high risk of other autoimmune diseases (ADs), and thymectomy may increase the risk further. A cohort of MG patients in which thymectomy was performed were investigated to analyze the prevalence, types and features of the new onset ADs. METHODS: Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Patients with a postoperative follow-up period shorter than a year or incomplete clinical records were excluded. Clinical and follow-up data were collected. Statistical analyses were performed using SPSS version 22.0. RESULTS: A total of 445 patients were included in this study. The median follow-up period was 72 months (range, 12-135 months). A total of 63 (14.2%) MG patients had concurrent ADs. The incidence rate was higher than the background prevalence of population (5%), and also higher than that of a former Chinese MG cohort (11.6%). A total of 47 patients (10.6%) were diagnosed with ADs before thymectomy, and 19 (4.3%) developed a new AD after thymectomy. The most common types of new onset ADs after thymectomy were Hashimoto's thyroiditis and rheumatoid arthritis (RA), which were different from those before thymectomy (hyperthyroidism and Hashimoto's thyroiditis). The incidence rate of new onset RA (1.35%) was higher than the frequency of RA before thymectomy (0.45%), and also higher than the incidence rate in a Chinese MG cohort (0.5%). There was a higher proportion of female patients (p = 0.026) with postoperative ADs. A younger age at operation may increase the risk of nonthymoma MG patients (p = 0.040) developing ADs. The postoperative treatment effect of MG was similar between patients with and without new onset ADs (p > 0.05). CONCLUSIONS: We observed a higher incidence rate of autoimmune diseases, especially rheumatoid arthritis, in MG patients after thymectomy. The most common types of ADs after thymectomy were different from those before thymectomy. New onset ADs tended to occur in female and young nonthymoma MG patients. The postoperative effect of MG was not related with the new occurrence of ADs.

Surgical treatment of intermediate to high grade thymic neuroendocrine neoplasms: case series of five patients and literature review.

Background: Thymic neuroendocrine neoplasms (Th-NENs) are extremely rare. Th-NENs are divided into four pathological subtypes: typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC). The latter three subtypes are highly aggressive with poor prognosis. There are limited reports on the optimal surgical strategies for Th-NENs. This study aims to report a case series of Th-NENs after surgical treatment and review the literatures. Methods: We report a case series of five patients diagnosed with Th-NENs and summarize their clinical characteristics. Literatures related to surgical treatment of Th-NENs were reviewed. Results: There were three males and two females, and mean age was 53.6 years. No myasthenia gravis or neuroendocrine symptoms were found. Three patients were diagnosed with AC and the other two were diagnosed with LCNEC. Two patients were stage II-b, one patient was stage III-a, and two patients were stage IV-b. One patient received preoperative chemotherapy, one patient received preoperative chemoradiotherapy, and three patients underwent surgery directly. Two patients underwent extended thymectomy via video-assisted thoracoscopic surgery (VATS), two patients underwent extended thymectomy via median sternotomy, and one patient underwent resection of anterior mediastinal tumor, sternal metastases, superior vena cava and partial right atrium via median sternotomy and cardiopulmonary bypass. R0 resection was achieved in 80% (4/5) of patients. There was no postoperative 90-day complication and death. One patient had no recurrence. One patient had lymph node metastases and was still alive after somatostatin analogue therapy. One patient had no recurrence of Th-NENs but died of other tumors. Two patients had distant metastases. Median overall survival (mOS) was 49 (range, 4-134) months. A total of 22 original studies related to surgical treatment of Th-NENs were retrieved. Conclusions: Th-NENs is a very rare and extremely aggressive malignancy. Early diagnosis and surgical resection are the most important methods to improve prognosis. Radical resection and lymph node dissection are recommended for accurate staging and better prognosis. Currently, there are few clinical data on Th-NENs and several important surgical issues remain unresolved. In the future, multi-center, large-sample database and clinical studies are urgently needed to explore better treatment modality.

Localization of small peripheral pulmonary nodules for surgical resection: a new intraoperative technique in hybrid operating room.

OBJECTIVE: The purpose of this study was to introduce a new feasible and effective intraoperative localization technique for small peripheral pulmonary nodules in hybrid operating room. METHODS: Between June 2020 and June 2021, the intraoperative localization was performed in 27 patients for 35 small pulmonary nodules at our institution. The procedure was undergone under thoracoscopic observation. After making the VATS ports, a titanium clip was clipped at the visceral pleura as near the pulmonary nodule as possible to be a marker for the nodule. VATS resection was performed next. RESULTS: A total of 27 patients were included in this study, including 6 males and 21 females. The median age was 58 years (range 34-78 years). All surgeries were performed by two-port VATS. A total of 35 pulmonary nodules underwent intraoperative localization. The mean diameter of nodules was 10.6 ± 3.7 mm. The distance of nodules to visceral pleura was 8.3 ± 8.7 mm. The mean localization time was 23.3 ± 3.3 min. The median time of C-arm scanning was 3 (range 2-4) times. The median times for clipping were 2 (range 1-3) times. All the nodules were localized successfully and resected precisely. No VATS were converted to thoracotomy. There were no complications related to localization procedures. CONCLUSIONS: This new intraoperative localization technique was feasible, safe and effective. And also the intraoperative procedure could avoid extra suffering for patients.

[Successful Rescue of Acute Exacerbation of Idiopathic Pulmonary Fibrosis after Surgery for Lung Cancer: Case Report].

Idiopathic Pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease with unknown cause, which is closely related to lung cancer. A serious complication called Acute exacerbation of IPF (AE-IPF) is prone to occur after lung resection. It progresses rapidly without effective treatment and has a poor prognosis. A typical case of AE-IPF after lung cancer surgery was reported, and its clinical characteristics, imaging features, diagnosis and treatment were summarized.
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Myasthenia gravis affects overall survival in patients with thymoma: an analysis of multicentre database using propensity score matching.

OBJECTIVES: About one-third of patients with thymoma have myasthenia gravis (MG). It remains controversial whether MG affects the prognosis of patients with thymoma. The aim of this study was to evaluate the effect of MG on the prognosis of patients with thymoma in a multicentre database. METHODS: Patients with thymoma who underwent thymectomy were identified from 2 prospectively collected databases in 2 medical centres from 2010 to 2018. Kaplan-Meier curves and the log-rank test were used to assess overall survival and recurrence-free survival, and a Cox proportional hazards model was used to determine significant contributors to survival. Propensity score matching was performed to eliminate selection bias. RESULTS: A total of 514 patients with thymoma were included in this study, of whom 320 patients were MG-free and 194 had MG. Patients with MG were younger (median age 50 vs 54 years, P = 0.001) and had smaller tumours (4.4 ± 2.0 vs 4.9 ± 2.3 cm, P = 0.020). Pathological analysis showed that type B tumours especially B2-B3 (B2 + B3 + mix B tumours, 55.2%) are more common in patients with MG, while type AB (37.2%) was the most common in patients without MG. A larger proportion of Masaoka III-IV stage tumour (25.7% vs 11.0%, P < 0.001) was seen in patients with thymoma and MG. Multivariable Cox regression analysis demonstrated that MG (hazard ratio [HR] = 3.729, 95% confidence interval [CI]: 1.398-9.947, P = 0.009), incomplete resection (HR = 5.441, 95% CI: 1.500-19.731, P = 0.010) and Masaoka stage III + IV (HR = 3.390, 95% CI: 1.196-9.612, P = 0.022) were negative prognostic factors of overall survival. Meanwhile, MG (HR =3.489, 95% CI: 1.403-8.680, P = 0.007) and Masaoka stage III + IV (HR = 6.582, 95% CI: 2.575-16.828, P < 0.001) were negative prognostic factors of recurrence-free survival. Propensity-matched analysis compared 148 patient pairs. K-M survival analysis demonstrated that MG was associated with worse overall survival and recurrence-free survival in propensity score-matched patients (log-rank, P = 0.034 and 0.017, respectively). CONCLUSIONS: Thymoma patients with MG have smaller tumours and a higher percentage of late-stage tumours, which are mainly of WHO B types, especially B2-B3 types. In addition, MG is significantly associated with worse overall survival and recurrence-free survival in thymoma.

Simultaneous bilateral pulmonary resection via single-utility port VATS for multiple pulmonary nodules: A single-center experience of 16 cases.

BACKGROUND: The detection rate of bilateral multiple pulmonary nodules (BMPNs) is increasing due to widespread use of chest computed tomography (CT) screening. However, there is no consensus on the treatment options for BMPNs and whether simultaneous bilateral pulmonary resection is safe remains controversial. The purpose of this study was to evaluate the feasibility and safety of simultaneous bilateral pulmonary resection for BMPNs. METHODS: A total of 16 consecutive patients with BMPNs who underwent simultaneous bilateral pulmonary resection in Beijing Hospital from June 2013 to July 2020 were enrolled in this study. Clinical characteristics, imaging and pathological features, and perioperative outcomes were retrospectively reviewed. RESULTS: There were 10 males and six females included in the study with a mean age of 61.9 (range: 39-78) years. A total of 35 nodules were resected in 16 patients including 12 patients with bilateral primary lung cancer, three patients with primary lung cancer on one side and a benign nodule on the contralateral side, and one patient with bilateral benign nodules. All patients underwent bilateral pulmonary resection via single-utility port video-assisted thoracoscopic surgery (VATS). Nine, four, two, and one patients underwent lobectomy with contralateral segmentectomy or wedge resection, segmentectomy with contralateral wedge resection, bilateral segmentectomy and bilateral wedge resection, respectively. All operations were accomplished successfully without intraoperative blood transfusion, conversion to thoracotomy, major complication and postoperative 90-day death. The mean operation time was 220.1 ± 65.6 minutes, median thoracic drainage duration was four days (range: 2-8 days), mean pleural drainage was 1387.5 ± 694.7 mL, and median postoperative hospital stay was seven days (range: 5-18 days). There were three cases (18.8%) of minor complications, including one case of pulmonary air leakage, one case of atrial fibrillation, and one case of poor healing of surgical site. A total of 50% (8/16) of the patients had severe postoperative pain and required additional analgesia. CONCLUSIONS: For selected patients, simultaneous bilateral pulmonary resection via single-utility port VATS is a safe and feasible minimally invasive procedure for BMPNs. Adequate postoperative analgesia via a multimodal analgesia strategy should be used to prevent postoperative pain. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The incidence of major complication after minimally invasive bilateral pulmonary resection is low for patients with good pulmonary function, but there is a relatively high incidence of minor complications and pain at the surgical site. Adequate postoperative analgesia via multimodal analgesia strategy should be used to prevent postoperative pain. WHAT THIS STUDY ADDS: For the treatment of bilateral multiple pulmonary nodules, simultaneous bilateral pulmonary resection via single-utility port video-assisted thoracoscopic surgery is safe and feasible for selected patients.

Two polymorphic mutations in promoter region of DNA polymerase ß in relatively higher percentage of thymic hyperplasia patients.

BACKGROUND: DNA polymerase ß is one of the key enzymes involved in the repair of DNA damage, and its high or low expression is closely related to tumorigenesis. In a previous study on lung cancer, we found three genetic mutations in the promoter region of the Polb gene could be detected in the Han Chinese population. The purpose of this study was to explore the relationship between these mutations and thymic hyperplasia. METHODS: Genomic DNA was extracted from 59 thymic hyperplasia patients by the salting out method and used for amplification of the promoter region of the Polb gene. The Polb gene mutation and its frequency were analyzed systematically by comparing them with the deposited wild-type gene sequence in the NCBI database. The three typical mutated sequences in the promoter region of Polb gene, -196G > T, -168C > A and -188_-187insCGCCC, were then amplified and ligated to pGL4.10 vector, so as to get the vectors used for the infection of 293T cells to explore their transcription activities by dual-luciferase reporter system. RESULTS: Two types of mutations, -168C>A and-188_-187insCGCCC, were found in a significantly higher percentage in patients with thymic hyperplasia than in normal healthy people after sequencing analysis of 59 patients and 60 healthy controls. These results suggest that the two mutations may be closely related to thymic hyperplasia. in vitro functional experiments showed that-168C>A could significantly increase promoter activity, whereas -188_-187insCGCCC could significantly reduce promoter activity, suggesting that these two mutations may affect the expression level of the Polb gene in cells. CONCLUSIONS: Two types of mutations in the promoter region of the Polb gene, -168C>A and-188_-187insCGCCC, are associated with thymic hyperplasia and may become a new risk factor for this disease. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Genetic mutations in the Polb gene are reported to be associated with different kinds of cancers. However, their relationship with thymic hyperplasia is still unclear. WHAT THIS STUDY ADDS: For the first time, we report that two nucleotide mutations in the promoter region of the Polb gene are closely related with thymic hyperplasia after sequencing 59 patients and 60 healthy controls in the Han Chinese population.

Effects of avitinib on the pharmacokinetics of osimertinib in vitro and in vivo in rats.

BACKGROUND: Avitinib is one type of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study was to investigate the effect of avitinib on the pharmacokinetics of osimertinib, one FDA approved third-generation TIKI, both in vitro and in vivo. METHODS: The in vitro metabolic stability and inhibitory effect of avitinib on osimertinib were assessed with rat liver microsomes (RLM) to determine its IC50 values. For the in vivo study, 18 Sprague-Dawley rats were randomly divided into three groups: the avitinib multiple dose group (30 mg/kg avitinib once daily for seven days), the avitinib single dose group (PEG200 once daily for six days and a dose of 30 mg/kg avitinib in PEG200 on day 7) and the control group (equal amounts of PEG200 once daily for seven days). Next, all rats were given osimertinib at a dosage of 10 mg/kg. UPLC/MS-MS was used for the determination of the concentration of osimertinib in plasma. RESULTS: In vitro analysis revealed that the IC50 value of osimertinib in rat liver microsomes was 27.6 µM. When rats were pretreated with avitinib, the values of AUC and MRT of the osimertinib were increased, and its Cmax and Tmax were significantly extended, whereas the values of CLz/F were significantly decreased (P < 0.05). CONCLUSIONS: Both in vitro and in vivo results demonstrated that a drug-drug interaction between avitinib and osimertinib occurred and more attention should be paid when avitinib and osimertinib are synchronously administered in clinic. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Osimertinib is the only market available third-generation EGFR-TKI and it has been reported that some drugs could have drug-drug interactions with it. WHAT THIS STUDY ADDS: For the first time, we systematically investigated the effect of avitinib, one newly developed third-generation EGFR-TKI, on the pharmacokinetics of osimertinib both in vitro and in vivo using a rat model.

miR-208b-5p inhibits invasion of non-small cell lung cancer through the STAT3 pathway by targeting interleukin-9.

Previous studies reported a dysregulation of micro (mi)R-208b-5p expression level in various types of human cancer; however, the role of miR-208-5p in non-small cell lung cancer (NSCLC) remains unclear. Therefore, the present study aimed to determine whether miR-208b-5p could regulate NSCLC progression. A total of 62 pairs of primary tumor and adjacent normal tissues were collected from patients with NSCLC. miR-208b-5p expression level was determined by reverse transcription-quantitative polymerase chain reaction. Furthermore, miR-208b-5p mimics was transfected into NSCLC A549 and H1299 cells in order to upregulate miR-208b-5p expression. Dual-luciferase reporter assay was utilized to investigate the associations between miR-208b-5p and IL9 mRNA. The results demonstrated that miR-208b-5p expression decreased in NSCLC tissues and cell lines. Furthermore, miR-208b-5p overexpression inhibited A549 and H1299 cell proliferation and invasiveness. miR-208b-5p was demonstrated to bind directly to the 3' untranslated region of interleukin-9 (IL-9) and therefore decreased its expression. In the NSCLC-derived cell lines, miR-208b-5p inactivated IL-9/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Furthermore, enhanced IL-9 level decreased the miR-208b-5p-mediated suppression of epithelial-mesenchymal transition in NSCLC cells by inactivating the STAT3 signaling pathway. In conclusion, the findings from this study demonstrated that miR-208b-5p inhibited migration and invasion of NSCLC cells. The anti-tumor activity of miR-208b-5p may be mediated by IL-9 and STAT-3 pathway.

Surgical outcomes of 215 patients with thymic epithelial tumors: A single-center experience.

OBJECTIVES: To evaluate the oncological prognosis and neurological outcomes for patients with thymic epithelial tumors (TETs) after thymectomy. METHODS: Consecutive patients with TETs who underwent thymectomy at Beijing Hospital from January 2011 to December 2018 were retrospectively enrolled into the study. Clinical, pathological, and perioperative data was collected. Patients were followed-up by telephone interview and outpatient records. Statistical analyses were performed using SPSS version 19.0. RESULTS: A total of 215 patients (115 men and 100 women) were included in this study of which 133 patients (61.9%) had TETs associated with myasthenia gravis (MG), and 82 patients (38.1%) had thymic tumors without MG. A total of 194 (90.2%) patients were successfully followed-up. The median follow-up period was 42 months. The five-year overall survival (OS) rate was 88.6%. MG was the first cause of death for patients with MG (6/10). Prognosis in MG patients was similar to those without MG. Multivariate Cox regression analysis demonstrated that TNM stage III + IV was an independent risk factor for OS. Incomplete resection and younger age were risk factors for tumor recurrence. For patients with MG, the cumulative complete stable remission (CSR) rate increased with the postoperative follow-up period, and the five-year CSR rate was 44.7%. Univariate Cox analysis indicated that age, preoperative MG duration and preoperative medication might correlate with CSR. Multivariate Cox analysis only indicated older age as a negative factor of achieving CSR. CONCLUSIONS: MG had little influence on OS and tumor recurrence of thymic tumors. The new TNM staging system was an independent prognostic factor. Incomplete resection and younger age were risk factors for tumor recurrence. Older age was a negative factor of achieving CSR for thymoma patients with MG after extended thymectomy. KEY POINTS: Significant findings of the study MG was not a prognostic factor for thymic tumors. The new TNM staging system was useful for prediction of prognosis. Incomplete resection and younger age were risk factors for tumor recurrence. Older age led to a lower probability of achieving CSR for thymomatous MG. What this study adds This study had a relatively large sample size of patients with thymic epithelial tumors in a single center. We evaluated not only the oncological prognosis, but also neurological outcomes after thymectomy, which was a more comprehensive assessment of surgical effect for thymic epithelial tumors.

[Surgical Treatment of Lung Cancer Combined with Interstitial Lung Disease].

BACKGROUND: Interstitial lung disease (ILD) is a group of diffuse lung diseases that mainly involve the interstitial and alveolar cavities and result in loss of alveolar-capillary functional units, leading to restrictive ventilatory dysfunction and diffusion impairment. There was an increased incidence of lung cancer on the basis of ILD, and perioperative risk of patients with lung cancer combined with ILD (LC-ILD) was significantly increased. The aim of this study is to summarize the safety and experience of surgical treatment of LC-ILD. METHODS: A retrospective analysis was performed on 23 patients with LC-ILD who underwent pneumonectomy in Beijing Hospital from January 2012 to December 2019, and their clinical manifestations, image feature, pathology, surgical safety, perioperative complications and treatment experience were summarized. RESULTS: A total of 23 patients were included in this study, including 20 males (87.0%) with an average age of (69.1±7.8) years, and 19 cases (82.6%) were smokers. Of the ILD types, 14 cases (60.9%) were idiopathic pulmonary fibrosis, 7 cases (30.4%) were idiopathic nonspecific interstitial pneumonia, and 2 (8.7%) were interstitial lung disease associated with connective tissue diseases. The pathology of lung cancer included adenocarcinoma (30.4%, 7/23), small cell carcinoma (30.4%, 7/23), squamous cell carcinoma (26.1%, 6/23), small cell carcinoma mixed with squamous cell carcinoma (4.3%, 1/23) and large cell neuroendocrine carcinoma (8.7%, 2/23). Surgical approaches included video assisted thoracoscopy (69.6%, 16/23) and anterolateral thoracotomy (30.4%, 7/23), with lobectomy (52.2%, 12/23), double lobectomy (4.3%, 1/23), and sublobectomy (39.1%, 9/23). There were 11 cases (47.8%) of postoperative complications, including 8 cases (34.8%) of pulmonary complications, 4 cases (17.4%) of acute exacerbation of ILD (AE-ILD), 6 cases (26.1%) of atrial fibrillation, and 1 case (4.3%) of acute left ventricular dysfunction. The 90-day mortality is 8.7% (2/23) and the cause of death was acute exacerbation of ILD. CONCLUSIONS: Most of LC-ILD were elderly patients with multiple comorbidities and decreased pulmonary function, leading to significantly increased surgical risk. The ILD should be fully evaluated and controlled before surgery, intraoperative trauma should be minimized, and special attention should be paid to pulmonary complications and AE-ILD after surgery. Postoperative AE-ILD has a poor prognosis and glucocorticoids may be effective. Early diagnosis and treatment is the key to treatment of AE-ILD.

Simple method for distinguishing the intersegmental plane in thoracoscopic lung segmentectomy.

Here, we introduce a simple method for delineating the intersegmental border in thoracoscopic pulmonary segmentectomy which can be widely reproduced because it is less time-consuming, fault-tolerant, and does not require any special chemical reagents or equipment. This method provides clear and accurate demarcation lines between the inflated and deflated lung parenchyma. KEY POINTS: A method with an effective and simple application which can be popularized. This modified targeted bronchus inflation method provides a clear and accurate intersegmental plane.

Surgical effect and prognostic factors of myasthenia gravis with thymomas.

BACKGROUND: To evaluate the surgical effect and prognostic factors of extended thymectomy for myasthenia gravis (MG) patients with thymomas. METHODS: Patients with MG with thymomas who underwent extended thymectomy at Peking University People's Hospital and Beijing Hospital between January 2010 and December 2018 were retrospectively enrolled. Patients were followed up by telephone or outpatient record review . Statistical analyses were performed using SPSS version 19.0. RESULTS: A total of 194 patients were included in this study. According to the Osserman classification, there were 56 type I, 52 type IIa, 67 type IIb, 14 type III, and five type IV. Video-assisted thoracoscopic surgery (VATS) thymectomies were performed in 137 patients, and transthymectomies in 57 patients. The average operation time was 136.6 ± 46.5 minutes, average blood loss was 129.3 ± 287.4 mL, and average postoperative stay was 8.3 ± 7.4 days. A total of 170 patients (87.6%) were successfully followed up. The median follow-up period was 45 months, and the five-year overall survival (OS) rate was 81.9%. Cox regression analysis demonstrated that age, Masaoka stage, and recurrence were prognostic factors of OS. Tumor recurrence tended to occur in patients with Masaoka stage III + IV, and age was a protective factor. A total of 20 patients experienced postoperative myasthenic crisis (POMC). Univariate analysis indicated that presence of bulbar symptoms, surgical procedure, and blood loss were risk factors for POMC, but multivariate analysis only indicated the presence of bulbar symptoms as an independent risk factor. A total of 162 patients were evaluated for post intervention MG status. A total of 55 patients achieved complete stable remission; the overall effective rate was 84.5%. Older patients and those with B-type thymomas had a lower probability of achieving complete stable remission. Efficacy was similar in patients who underwent VATS or the transsternal procedure. CONCLUSIONS: Age, Masaoka stage, and recurrence were prognostic factors of OS. Presence of bulbar symptoms was an independent risk factor for POMC. Age and World Health Organization classification influence the postoperative effect of MG. KEY POINTS: Significant findings of the study Age, Masaoka stage, and recurrence were prognostic factors of OS for MG with thymomas. The presence of bulbar symptoms was an independent risk factor for POMC. Age and World Health Organization classification may influence the postoperative effect of MG. What this study adds Our study had a relatively large sample size of MG patients with thymomas only. We emphasize the analysis of the postoperative effect of MG and overall survival for these patients, which is a complement to previous studies.