Huikang Xie

Reduced miR-3127-5p expression promotes NSCLC proliferation/invasion and contributes to dasatinib sensitivity via the c-Abl/Ras/ERK pathway.

miR-3127-5p is a primate-specific miRNA which is down-regulated in recurrent NSCLC tissue vs. matched primary tumor tissue (N = 15) and in tumor tissue vs. normal lung tissue (N = 177). Reduced miR-3127-5p expression is associated with a higher Ki-67 proliferation index and unfavorable prognosis in NSCLC. Overexpression of miR-3127-5p significantly reduced NSCLC cells proliferation, migration, and motility in vitro and in vivo. The oncogene ABL1 was a direct miR-3127-5p target, and miR-3127-5p regulated the activation of the Abl/Ras/ERK pathway and transactivated downstream proliferation/metastasis-associated molecules. Overexpression of miR-3127-5p in A549 or H292 cells resulted in enhanced resistance to dasatinib, an Abl/src tyrosine kinase inhibitor. miR-3127-5p expression levels were correlated with dasatinib sensitivity in NSCLC cell lines without K-Ras G12 mutation. In conclusion, miR-3127-5p acts as a tumor suppressor gene and is a potential biomarker for dasatinib sensitivity in the non-mutated Ras subset of NSCLC.

Tumor Spread through Air Spaces Affects the Recurrence and Overall Survival in Patients with Lung Adenocarcinoma >2 to 3 cm

Objectives: Tumor spread through air spaces (STAS) is a novel invasive pattern in lung adenocarcinoma (ADC). The effects of the combination of STAS and tumor size on survival have not been well studied. Methods: A total of 383 patients with ADC 3 cm or smaller (stage IA) and 161 patients with stage IB ADC were identified from 2009 to 2010. Recurrence‐free survival (RFS) and overall survival (OS) were compared between patients as stratified by STAS and tumor size. A validation cohort was included in this study. Results: STAS was observed in 116 ADCs 3 cm or smaller (30.3%). In cases involving ADCs 3 cm or smaller, patients with STAS had worse RFS (p = 0.006) and OS rates (p < 0.001) than those without STAS. Furthermore, comparable RFS (p = 0.091) and OS (p = 0.443) rates were observed in patients with ADCs 3 cm or smaller with STAS present and those with stage IB ADC. Multivariate analysis revealed STAS to be an independent prognostic factor in ADCs 3 cm or smaller (RFS, p = 0.043; OS, p = 0.009). Among patients with ADCs larger than 2 to 3 cm, STAS still stratified the prognosis. Moreover, the unfavorable prognosis of patients with ADCs larger than 2 to 3 cm with STAS present was similar to that of patients with stage IB ADC. Among patients with ADCs 2 cm or smaller, STAS failed to stratify the prognosis significantly. Similar results were obtained in the validation cohort. Conclusions: These results provide preliminary evidence that STAS could be considered as a factor in a staging system to predict prognosis more precisely, especially in ADCs larger than 2 to 3 cm.

Preoperative nomogram for identifying invasive pulmonary adenocarcinoma in patients with pure ground-glass nodule: A multi-institutional study.

Purpose To construct a preoperative nomogram to differentiate invasive pulmonary adenocarcinomas (IPAs) from preinvasive lesions in patients with solitary pure ground-glass nodules (GGN). Methods A primary cohort of patients with pathologically confirmed pulmonary solitary pure GGN after surgery were retrospectively studied at five institutions from January 2009 to September 2015. Half of the patients were randomly selected and assigned to a model-development cohort, and the remaining patients were assigned to a validation cohort. A nomogram predicting the invasive extent of the solitary GGNs was constructed based on the independent risk factors. Predictive performance was evaluated by concordance index (C-index) and calibration curve. Results Out of 898 cases included in the study, 501 (55.8%) were preinvasive lesions and 397 (44.2%) were IPAs. In the univariate analysis, lesion size (p < 0.001), lesion margin (p = 0.041), lesion shape (p < 0.001), mean computed tomography (CT) value (p = 0.018), presence of pleural indentation (p = 0.017), and smoking status (p = 0.014) were significantly associated with invasive extent. In multivariate analysis, lesion size (p < 0.001), lesion margin (p = 0.042), lesion shape (p < 0.001), mean CT value (p = 0.014), presence of pleural indentation (p = 0.026), and smoking status (p = 0.004) remained the predictive factors of invasive extent. A nomogram was developed and validation results showed a C-index of 0.94, demonstrating excellent concordance between predicted and observed results. Conclusions We established and validated a novel nomogram that can identify IPAs from preinvasive lesions in patients with solitary pure GGN.

Is neoadjuvant chemotherapy mandatory for limited-disease small-cell lung cancer?

OBJECTIVES The present study attempted to evaluate the role of neoadjuvant chemotherapy combined with surgery in limited-disease small-cell lung cancer (LD-SCLC). METHODS A retrospective analysis was performed on 106 LD-SCLC patients who underwent complete resections from February 2000 to February 2012 in Shanghai Pulmonary Hospital. Among these cases, two cycles of neoadjuvant chemotherapies were administered to all pathologically confirmed patients [Group Neoadjuvant (Group N)]. For those without pathology, operations followed by adjuvant chemotherapies were performed [Group Adjuvant (Group A)]. Prognostic features and overall survival (OS) were compared using the log-rank test and calculated using the Kaplan-Meier method. RESULTS Group N included 47 cases and Group A included 59 cases. A total of 57 patients were male and 49 were female, with a mean age of 56.1 ± 10.2 years. A total of 41 patients were at pathological stage (p-Stage) IIIa, and 65 patients were at I or II. The overall 5-year survival rate (5-YS) was 28%. The 5-YS for p-Stage I-II (n = 65) was significantly better than that of p-Stage III (n = 41) (35 vs 20%, P = 0.034). For p-Stage IIIa (pN2 positive), the 5-YS of Group N was significantly better than that of Group A (34 vs 12%, P = 0.020). The median overall survival for Group N and Group A in IIIa (pN2 positive) LD-SCLC patients were 46 and 15 months (P = 0.009), respectively. Multivariate analysis for survival showed mediastinal lymph node involvement; surgery and histopathology of SCLC were both significant independent predictors of long-term survival. CONCLUSIONS Neoadjuvant chemotherapy combined with surgery provided reasonable options for pIIIa-N2 LD-SCLC patients, which can give them a better chance of survival.

Relationship of Lymph Node Micrometastasis and Micropapillary Component and Their Joint Influence on Prognosis of Patients With Stage I Lung Adenocarcinoma

This study aimed to investigate the relationship between lymph node micrometastasis and histologic patterns of adenocarcinoma, with a particular focus on their joint effect on prognosis. We retrospectively reviewed 235 patients with stage I adenocarcinoma from January 2009 to December 2009. Lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin (AE1/AE3) and thyroid transcription factor-1. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis on prognosis. Lymph node micrometastasis was observed in 35 patients (15%). Patients with micrometastasis had significantly worse recurrence-free survival (P<0.001) and overall survival (P<0.001) compared with those without micrometastasis. Micropapillary component was confirmed as an independent predictor of increased frequency of micrometastasis (P<0.001). Among 62 patients with adenocarcinoma with a micropapillary component, 23 (37%) had lymph node micrometastasis. Micropapillary-positive/micrometastasis-positive patients had significantly worse survival compared with micropapillary-positive/micrometastasis-negative patients (RFS, P=0.039; OS, P=0.002) and micropapillary-negative patients (recurrence-free survival, P<0.001; overall survival, P<0.001). Moreover, the presence of micrometastasis correlated with a higher risk of locoregional recurrence (P=0.031) rather than distant recurrence (P=0.456) in micropapillary-positive patients. In summary, lymph node micrometastasis was more frequently observed in adenocarcinoma with a micropapillary component. Moreover, lymph node micrometastasis could provide helpful prognostic information in patients with resected stage I lung adenocarcinoma with a micropapillary component; thus, immunohistochemical detection of micrometastatic tumor cells in lymph nodes should be recommended.

Visceral pleural invasion in lung adenocarcinoma ≤3 cm with ground-glass opacity: a clinical, pathological and radiological study

BACKGROUND Visceral pleural invasion (VPI) had been demonstrated as an aggressive sign in non-small cell lung cancers (NSCLC). However, its incidence and clinical relevance in early lung cancer showing ground glass nodules (GGNs) has not been clarified. METHODS All consecutive surgically treated patients with solitary GGNs between 2009 and 2013 were reviewed retrospectively. Inclusion criteria were defined as lesions ≤3 cm with pleura abutting on computed tomography (CT) scan and pathologically confirmed NSCLC. RESULTS Out of 156 enrolled patients, 38 had pathologically confirmed VPI. The incidence of VPI was 41.5% (27/65) if the tumor diameter was larger than 2.0 cm and 14.3% (13/91) if diameter was smaller than 2.0 cm (P<0.001). Further, the incidence was 17.4% (12/69) in pure GGNs and 32.2% (28/87) in part-solid GGNs (P=0.040). The tumor size and the nodule nodule-pleural relationship were significant predictors of positive VPI. In cases with pleural indentation, attachment, and closeness, the incidence was 38.1%, 25.5%, and 5.3%, respectively (P=0.001). All cases were PL0 and PL1, with no PL2 cases observed. CONCLUSIONS Although VPI was visible in both pure/mix GGNs, it was more common in larger (>2 cm) GGNs. The radiographic findings of nodule abutment or a pleural tag did not reliably predict or exclude VPI. In patients with GGNs, a low rate of PL2 invasion may be observed.

Clinical and radiological features of synchronous pure ground‐glass nodules observed along with operable non‐small cell lung cancer

It is common to observe synchronous pure ground‐glass nodules (PGN) along with operable primary tumor on initial CT scans while clinical and radiological features of these PGNs remain unclear.

Radical mediastinal nodal removal improves disease-free survival for pulmonary low-grade malignant tumors

PURPOSE To investigate the prognostic role of radical lymph node dissection in treatment for pulmonary Low Grade Malignant Tumors (LGMTs); specifically, on the extent of nodal removal and its impact on long-term survival. METHODS A total of 93 LGMTs cases underwent surgical resection and were histopathologically confirmed. Overall survival rates and disease-free survival were respectively calculated according to the extent of lymph node resection and histopathological grades of tumors. Risk factors of nodal involvement and survival predictors were calculated via multivariate analysis. Life table, Kaplan-Meier, and Cox regression models were used for the statistical analysis. RESULTS Thirty-eight cases of carcinoid, 17 adenoid cystic carcinomas, and 38 mucoepidermoid carcinomas were included in the current study. Twenty-one cases were high-grade and 72 were low-grade. A total of 813 lymph nodes were removed, at an average of 8.7±5.4 nodes per patient. The numbers of harvested nodes were 11.8±4.5, in the study group via radical nodal removal and 4.0±2.4 nodes per patient in the nodal sampling group. Eleven cases showed lymph nodal involvement (5 mediastinal and 6 hilar lymph node metastasis). No significant differences of overall survival was found among the different histological types (p=0.939), or the extent of nodal removal (p=0.971). Meanwhile, there was a significant difference of disease-free survival (DFS) rates according to the extent of nodal removal (5-YS: 97% of radical nodal dissection vs. 78% of nodal sampling, p=0.038). Overall survival and disease-free survival were closely associated with histological grading (OS: 78% of high grade vs. 97% of low grade, p=0.001; DFS: 57% of high grade vs. 97% of low grade, p<0.0001). CONCLUSIONS Radical lymph node dissection improved disease-free survival for pulmonary low-grade malignant tumors, although no obvious improvement on overall survival was noticed. Histological grade was the most important prognostic factor in LGMTs.

Wedge resection for localized infectious lesions: high margin/lesion ratio guaranteed operational safety

OBJECTIVE This study aims to elucidate the risk factors of pulmonary complications for localized infectious lesions with limited resection. METHODS We retrospectively investigated 139 cases for which wedge resection had been performed for localized pulmonary infectious lesions. Patients included 85 males and 54 females with a median age of 53 years (range: 21-74 years old). Forty-six patients had focal organizing pneumonia (OP), sixty patients had lung abscess, twenty-three patients had aspergilloma, five patients had lung abscess combining aspergillus fumigatus, and five patients had lung abscess combined with tuberculosis granuloma. Information regarding perioperative manipulations, surgical complications, and follow-ups were collected for further analysis. RESULTS Prominent pneumonia developed in eight cases post-operation. In follow-up, one patient had a recurrence of lung abscess five months post-operation and underwent a left upper lobectomy and one patient died two months after discharge because of respiratory failure that resulted from pneumonia. Univariate and multivariate analysis showed a significant difference in the margin/lesion ratio (distance between staple margins to lesion/the maximum tumor diameter) between patients with pulmonary complications and those without complications (P=0.01). The best cut-off value of margin/lesion ratio to complication was 0.985, and a margin/lesion ratio less than 0.985 was associated with high post-operative complications. CONCLUSIONS The present case series shows that partial resection for localized pulmonary infection is an acceptable surgical manipulation. A high margin/lesion ratio achievement may guarantee operational safety.

Simultaneous video-assisted thoracoscopic surgery sleeve lobectomy and thymectomy

Thymic carcinoid tumour associated with pulmonary squamous cell carcinoma is very rare. We present a case of synchronous lung cancer and mediastinal tumour treated with simultaneous video-assisted thoracoscopic surgery (VATS) sleeve lobectomy and thymectomy. A 67-year old man presented with cough and bloody sputum. Chest computed tomography showed an anterior mediastinal mass with a right hilar nodule. A right upper sleeve lobectomy and a thymectomy were performed via a VATS approach. Thymic carcinoid tumour associated with pulmonary squamous cell carcinoma was diagnosed, and the patient received adjuvant radiochemotherapy.