BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

Objective:The study aimed was to explore the safety and efficacy of neoadjuvant immunochemotherapy for non-small cell lung cancer (NSCLC).Methods:We retrospectively collected data of all patients who received neoadjuvant immunochemotherapy and chemotherapy for NSCLC followed by surgery in our unit between January 2019 to September 2021.Results:Forty-four patients were diagnosed with NSCLC in a stageⅠ(2 cases), ⅡA(7 cases), ⅡB(11 cases), ⅢA (15 cases), ⅢB (1 case). The average age was 63 years old(range 44-71 years old). Squamous cell carcinoma accounted for 65.91% of all patients. Central lung cancer accounted for the vast majority, with 39 patients (88.64%). There were 19 cases in the neoadjuvant immunochemotherapy group and 25 cases in the neoadjuvant chemotherapy group; the average interval between the end of neoadjuvant therapy and the day of operation was 34 days, including( 33.74±10.66 )days in the immunochemotherapy group and (33.88±11.9) days in the chemotherapy group, and there was no significant difference between the two groups. No grade 3 or more adverse events occurred in all patients. There were 13 cases (63.16%) reached PR (partial response)+ CR (complete response) according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) in the neoadjuvant immunity group and 11 cases (44.00%) in the neoadjuvant chemotherapy group. There was no significant difference between the two groups. In the neoadjuvant immunochemotherapy group, 9 cases (47.37%) achieved down-staging, In the neoadjuvant chemotherapy group, 8 cases (32.00%) achieved down-staging, there was no significant difference between the two groups. Seven patients (36.84%) in neoadjuvant immunochemotherapy group showed pCR (pathologic complete remission), but there were no patients who reached pCR in the neoadjuvant chemotherapy group., the difference was statistically significant ( P=0.001). Four patients (21.05%) in the neoadjuvant immunochemotherapy group reached mPR (major pathologic response), 6 patients (24.00%) in the neoadjuvant chemotherapy group reached mPR, and the difference was no statistically significant( P= 0.817). Conclusion:The safety of neoadjuvant immunochemotherapy was satisfactory; Compared with neoadjuvant chemotherapy, neoadjuvant immunochemotherapy did not increase the preoperative grade 3 adverse events and prolong the waiting time before operation; neoadjuvant immunochemotherapy had obvious advantages in pCR, which provided the possibility for the cure of tumor.

Objective To assess the accuracy of CT features of lung nodules (≤3 cm) in predicting the accuracy of the pathological subtype and degree of infiltration of adenocarcinoma. Methods We retrospectively analyzed the clinical data of 333 patients with non-cavitary pulmonary nodules diagnosed as adenocarcinoma by surgery and pathology in the China-Japan Friendship Hospital from 2011 to 2018, including 108 males and 225 females, aged 16-82 (59.57±10.16) years. The basic clinical data and CT characteristics of the patients were recorded. Results When the average CT value was ≥507 Hu, the maximum diameter of the lung window was ≥14.5 mm, and the solid component ratio was ≥5.0%, it indicated more likely the invasive adenocarcinoma (IAC). The higher the average CT value of the nodule, the larger the maximum diameter of the lung window, and the more solid components, the higher the degree of infiltration. CT morphological features (including burrs, lobes, vascular signs, bronchial signs, pleural stretch or depression signs) were more common in IAC. Among them, burrs were more common in acinar adenocarcinoma and papillary adenocarcinoma. In invasive adenocarcinoma, the higher the risk of recurrence of the pathological subtype, the greater the average CT value. When the average CT value of IAC was >−106 Hu, and the proportion of solid components was ≥70.5%, the histological subtypes were more inclined to micropapillary/solid predominant adenocarcinoma. Conclusion The evaluation of CT features of lung nodules can improve the predictive value of histopathological types of lung adeno-carcinoma, thereby optimizing clinical treatment decisions and obtaining more ideal therapeutic effects.

Objective    To investigate the predictive value of preoperative radiological features on spread through air spaces (STAS) in stage cⅠA lung adenocarcinoma with predominant ground-glass opacity, and to provide a basis for the selection of surgical methods for these patients. Methods    The clinical data of 768 patients with stage cⅠA lung adenocarcinoma undergoing operation in our hospital from 2017 to 2018 were reviewed, and 333 early stage lung adenocarcinoma patients with predominant ground-glass opacity were selected. There were 92 males and 241 females, with an average age of 57.0±10.0 years. Statistical analysis was performed using SPSS 22.0. Results    STAS-positive patients were mostly invasive adenocarcinoma (P=0.037), and had more micropapillary component (P<0.001) and more  epidermal growth factor receptor (EGFR) gene mutations (P=0.020). There were no statistically significant differences between the STAS-positive and STAS-negative patients in other clinicopathological features. Univariate analysis showed that the maximum diameter of tumor in lung window (P=0.029), roundness (P=0.035), maximum diameter of solid tumor component in lung window (P<0.001), consolidation/tumor ratio (CTR, P<0.001), maximum area of the tumor in mediastinum window (P=0.001), tumor disappearance ratio (TDR, P<0.001), average CT value (P=0.001) and lobulation sign (P=0.038) were risk factors for STAS positive. Multivariate logistic regression analysis showed that the CTR was an independent predictor of STAS (OR=1.05, 95%CI 1.02 to 1.07, P<0.001), and the area under the receiver operating characteristic (ROC) curve was 0.71 (95%CI 0.58 to 0.85, P=0.002). When the cutoff value was 19%, the sensitivity of predicting STAS was 66.7%, and the specificity was 75.2%. Conclusion    CTR is a good radiological feature to predict the occurrence of STAS in early lung adenocarcinoma with predominant ground-glass opacity. For the stage cⅠA lung adenocarcinoma with predominant ground-glass opacity and CTR ≥19%, the possibility of STAS positive is greater, and sublobar resection needs to be carefully considered.

Objective:To analyze the law of distant metastasis in patients with small lung adenocarcinoma with different CT findings, and to explore the feasibility of different preoperative examination methods for small lung adenocarcinoma with different imaging characteristics.Methods:Clinicopathological data of cT1a-cN0 lung adenocarcinoma patients admitted to the respiratory center of China-Japan Hospital from January 2017 to December 2018 were retrospectively collected. A total number of 785 patients were included, including 289 males and 496 females. SPSS 22.0 was used for statistical analysis.Results:A total number of 785 patients were included in this study, including 287 pure ground-glass nodule (GGN) patients, 111 GGN predominant patients, 221 solid predominant patients and 166 solid nodule patients. Among the included patients, 8 had distant metastasis, including 6 with bone metastasis, 1 with brain metastasis and 1 with brain and adrenal metastasis. No distant metastasis was observed in the patients with pure GGN and GGN predominant nodule, while 1 solid predominant patients had distant metastasis, and 7 patients with solid nodules had distant metastasis. The probability of distant metastasis was 0.5% for the solid predominant patients and 4.2% for the solid nodule patients. Univariate analysis results showed that CEA level ( P=0.030), the largest diameter of the lung window tumor ( P=0.003), the largest diameter of the solid component of the lung window tumor ( P<0.001), the largest area of the lung window tumor ( P=0.002), mediastinal window tumor maximum area ( P<0.001), CTR ( P<0.001), TDR ( P<0.001), and pleural indentation sign ( P=0.037) were risk factors for distant metastases. Multivariate analysis showed that CEA ( OR=1.019, 95% CI: 1.002-1.037, P=0.028) and TDR ( OR=0.000, 95% CI: 0.000-0.310, P=0.001) were independent risk factors of distant metastasis. Conclusion:For patients with pure GGN and GGN predominant nodule, preoperative examination could not be required, but for pure solid nodules, it is necessary to perform relevant preoperative examination including skull MRI before surgery to exclude distant metastasis.

Objective    To investigate the mediastinal lymph node metastasis of cT1a-cN0M0 lung adenocarcinoma, so as to provide a theoretical basis for intraoperative lymph node dissection in patients with early stage lung adenocarcinoma. Methods    Clinicopathological features of lung adenocarcinoma patients who received operation in our hospital from 2017 to 2018 were collected. A total of 667 patients including 241 male and 426 female patients at age of 59 (16, 87) years were included. There were 234 patients with pure ground glass nodules, 98 patients with ground glass-predominant tumor, 199 patients with consolidation-predominant tumor and 136 patinets with solid tumor in the study. Postoperative N1 lymph node metastasis occurred in 30 patients and N2 lymph node metastasis occurred in 52 patients. Results    The result of univariate analysis showed that male (P=0.014), higher carcino-embryonic antigen levels (P<0.001), larger nodal diameter (P<0.001), larger consolidation tumor ratio (P<0.001), smaller tumor disappearance ratio (P<0.001), solid nodules (P<0.001), cavitary sign (P=0.005), lobulation sign (P=0.002), spicule sign (P=0.003), pleural indentation sign (P=0.001), bronchus sign (P=0.025) were risk factors for mediastinal lymph node metastasis. In terms of pathology, the N2 positive group had larger size of pathological tissue (P<0.001), more N1 lymph node metastasis (P<0.001), higher pathology T stage (P<0.001), more spread through air space (P=0.001), more pleural invasion (P<0.001), and more lymphovascular invasion (P<0.001). Multivariate analysis showed that lymphovascular invasion (OR=6.9, 95%CI 2.3-20.7, P=0.001), larger consolidation tumor ratio (OR=109.6, 95%CI 3.8-3 124.3, P=0.006), cavitary sign (OR=3.1, 95%CI 1.1-8.3, P=0.028) and N1 lymph node metastasis (OR=15.7, 95%CI 6.7-36.4, P<0.001) were independent risk factors for mediastinal lymph node metastasis. Conclusion    For lung adenocarcinoma, mediastinal lymph node metastasis will not occur in ground glass nodule and ground glass-predominant tumor patients. The probability of mediastinal lymph node metastasis increases with the increase of solid components and presence of cavitary sign. Therefore, different types of lymph node resection can be considered for patients with different imaging findings.

Objective:To evaluate the effect of interstitial lung disease(ILD) on postoperative morbidity and mortality in pulmonary resection for lung cancer patients.Methods:We retrospectively analyzed 971 patients undergoing pulmonary operation from January 2010 to January 2018 in our hospital. Clinical data including age, sex, history of chronic obstructive pulmonary disease(COPD), smoking history, smoking index, American Society of Anesthesiologists(ASA) classification, forced expiratory volume in 1 s(FEV1) % predict, surgical procedure, video assisted thoracoscopic surgery(VATS) or not, intraoperative blood transfusion, anesthesia time, operation time/one-lung ventilation time, blood loss, histology, postoperative morbidity, 60-days mortality, onset of acute exacerbation of interstitial lung disease(AE-ILD), drainage, extubation time, and postoperative stay were collected and analyzed.Results:There were 80(8.2%) and 891(91.8%) patients in ILD and non-ILD group, respectively. AE-ILD occurred in 5 patients, with a 60-day mortality of 80%. A multivariate regression analysis identified that the sex( P=0.023), ILD( P=0.001), COPD( P=0.027) were independent risk factors for postoperative morbidity. ILD( P=0.023) and postoperative morbidity( P=0.001) were independent risk factors for 60-day mortality in multivariate analysis. Conclusion:Patients with ILD had a higher incidence of postoperative morbidity and 60-day mortality. Based on the obvious postoperative morbidity and mortality, special attention and management should be taken in ILD patients.

Objective     To investigate the significance of neoadjuvant chemotherapy in the treatment of limited-disease small cell lung cancer (LD-SCLC). Methods     We retrospectively analyzed the clinical data of 55 LD-SCLC patients who underwent surgery in the Department of Thoracic Surgery, China-Japan Friendship Hospital from May 2007 to August 2016. There were 42 males and 13 females with a mean age of 57 years. All patients underwent clinical staging before treatment. According to the different treatments, the patients were divided into two groups, a preoperative neoadjuvant chemotherapy group and a direct surgery group. The comparison of long-term survival rates was made between the two groups. Results     Among the 55 patients, median survival time was 27 months. The 1-, 3-, 5-year survival rate was 89.1%, 45.0%, 33.8% respectively. Treatment methods and clinical N stage were significantly different in prognosis (P<0. 05). The results of Cox proportional hazards regression model showed that clinical N stage was prognostic factor of LD-SCLC patients (P<0. 05). Conclusion     Patients with clinical stage Ⅰ and Ⅱ SCLC are better to receive direct surgery. For patients with clinical stage Ⅲ, it is recommended to reach partial response or complete response with neoadjuvant chemotherapy before surgery. The status of lymph node metastasis is closely related to survival, thus identifying the accurate clinical stage is crucial before treatment.

Objective To investigate the effects of 5-aza-2'-deoxycytidine (5-Aza-dC) alone or combined with trichostatin A(TSA) on cell proliferation, promoter methylation and mRNA expression level of PDX-1 gene in pancreatic β cells induced by high glucose toxicity. Method NIT-1 cells were treated in vitro by high glucose (33.3 mmol/L), then divided into five groups, control group, HG grpup, 5-Aza-dC treatment group, TSA interfere group and 5-Aza-dC + TSA group. Proliferation of NIT-1 cells, insulin secretion, promoter methylation and mRNA expression of PDX-1 gene were detected respectively. Results 5-Aza-dC and TSA alone or in combination could promote cell proliferation and recover insulin secretion in NIT-1 cells , could also reduce PDX-1 gene methylation and enhance expression of PDX-1 mRNA. Compared with single-treatment group , combined group was significantly different (all P < 0.05). Conclusion 5-Aza-dC and TSA could activate the expression of PDX-1 and, then recover insulin secretion in NIT-1 cells induced by high glucose. Combination of them had synergistic effect.

ObjectiveTo evaluate the efficacy,safety and clinical value of anterior urethral fusion to treat diphallia.MethodsA 17-year-old male patient with complete penile diphallia was treated in March 2011.The physical examination showed two completely separated mature penis; urethrography,and urethroscope showed the two urethras were completely separated and entered the bladder respectively.Two anterior urethras were incised respectively at ventral sides ( from the meatus to bulbar urethra) and then two incised anterior urethras were splintered by a continuous suture with 4-0 polyglactin sutures in side and side.Two penises were splintered into one.The nocturnal penile tumescence test and the penis vibration thresholds were assessed before,and after surgery..ResultsThe patient was followed up for 12 months.There was no hematoma,urinary fistula,urinary incontinence and other complications postoperatively.The penis was recovered with normal appearance; urination and morning erection of penile were normal.6 months after surgery,there was no significant difference in the nocturnal penile tumescence and penis vibration thresholds detection ( P ＞ 0.05).ConclusionThe operation of anterior urethral fusion is a safe and efficient surgical treatment to treat partial complete penile diphallia with less complication and no worse effect on urination and erection of penile.