Jiaqing Xiang

Pattern of Lymph Node Metastases in Patients with Squamous Cell Carcinoma of the Thoracic Esophagus Who Underwent Three-Field Lymphadenectomy

Background/Aims: Lymph nodes in patients with squamous cell carcinoma of the thoracic esophagus might be involved with metastases at cervical, mediastinal, and abdominal sites. The range of lymph node dissection is still controversial. The pattern of lymph node metastasis and factors that are correlated with lymph node metastasis affect the surgical procedure of lymph node dissection. The purpose of the present study was to explore the pattern of lymph node metastasis and factors that are correlated with lymph node metastasis in patients with esophageal cancer who underwent three-field lymphadenectomy. Methods: Lymph node metastases in 230 patients who underwent radical esophagectomy with three-field lymphadenectomy were analyzed. The metastatic sites of lymph nodes were correlated with tumor location by chi-square test. Logistic regression was used to analyze clinicopathological factors related to lymph node metastasis. Results:Lymph node metastases were found in 133 of the 230 patients (57.8%). The average number of resected lymph nodes was 25.3 ± 11.4 (range 11–71). The proportions of lymph node metastases were 41.6, 19.44, and 8.3% in neck, thoracic mediastinum, and abdominal cavity, respectively, for patients with upper thoracic esophageal carcinomas, 33.3, 34.7, and 14%, respectively, in those with middle thoracic esophageal carcinomas, and 36.4, 34.1, and 43.2%, respectively, for patients with lower thoracic esophageal carcinomas. We did not observe any significant difference in lymph node metastatic rates among upper, middle, and lower thoracic carcinomas for cervical or thoracic nodes. The difference in lymph node metastatic rates for nodes in the abdominal cavity was significant among upper, middle, and lower thoracic carcinomas. The lower thoracic esophageal cancers were more likely to metastasize to the abdominal cavity than tumors at other thoracic sites. A logistic regression model showed that depth of tumor invasion and lymphatic vessel invasion were factors influencing lymph node metastases. Conclusions: Based on our data, cervical and mediastinal node dissection should be performed independent of the tumor location. Abdominal node dissection should be conducted more vigorously for lower thoracic esophageal cancers than for cancers at other locations. Patients with deeper tumor invasion or lymphatic vessel invasion were more likely to develop lymph node metastases.

Multicenter analysis of lung cancer patients younger than 45 years in Shanghai.

The treatment, prognosis, and outcomes of young lung cancer patients have not been fully explored. In addition, there is a pressing need to characterize this subgroup of patients, because there is a trend of increasing incidence in younger patients from Europe and Japan.

Precise Diagnosis of Intraoperative Frozen Section Is an Effective Method to Guide Resection Strategy for Peripheral Small-Sized Lung Adenocarcinoma

PURPOSE This study investigated the accuracy of intraoperative frozen section (FS) diagnosis for predicting the final pathology (FP) of peripheral small-sized lung adenocarcinoma and evaluated its usefulness in sublobar resection. PATIENTS AND METHODS The records of 803 patients with clinical stage I peripheral lung adenocarcinoma who underwent sublobar resection for FS diagnosis to guide surgical strategy were reviewed. The surgical extension was mainly based on FS. The FS were stratified into atypical adenomatous hyperplasia, adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma. The diagnostic accuracy of FS, the reasons for the discrepancy between FS and FP, and the clinical influence of the FS errors were evaluated. To assess the survival of patients with different subtypes after surgery, 301 patients were identified for prognosis evaluation. RESULTS The total concordance rate between FS and FP was 84.4%. When atypical adenomatous hyperplasia, AIS, and MIA were classified together as a low-risk group, the concordance rate was 95.9%. Most discrepant cases were the underestimation of AIS and MIA. The diagnostic accuracy of FS for tumors ≤ 1 cm and larger than 1 cm in diameter was 79.6% and 90.8%, respectively (P < .01). The FS errors had significant clinical impact on 0.9% of the 803 patients due to insufficient resection. The 5-year recurrence-free survival rate (100%) was significantly better for the patients with AIS/MIA than for patients with invasive adenocarcinoma (74.1%, P < .01). CONCLUSION Frozen pathology has a high concordance rate with FP. Precise diagnosis by intraoperative FS is an effective method to guide resection strategy for peripheral small-sized lung adenocarcinoma.

Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

BackgroundDespite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As2O3) with cisplatin (DDP) on A549 and H460 non-small cell lung cancer (NSCLC) cells were explored.MethodsA549 and H460 human lung cancer cells were treated with As2O3 and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, clonogenic assay, and flow cytometry (FCM). Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot.ResultsMTT and clonogenic assay showed As2O3 within 10-2 μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As2O3 exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI) for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As2O3 with DDP. FCM showed As2O3 did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As2O3 and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As2O3 and/or DDP. FCM and TUNEL staining illustrated that the combination of As2O3 and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As2O3 and/or DDP treatments compared with controls. The expression of caspase-3 in cells treated with the combination of As2O3 and DDP did not differ from that in cells treated with a single agent.ConclusionAs2O3 exerted synergistic effects with DDP on NSCLC cells, and the synergistic effects were partly due to the induction of caspase-independent apoptosis.

A clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer

OBJECTIVE Controversy remains over the appropriate postoperative management for patients with stage Ia non-small cell lung cancer who underwent complete surgical resection as a result of a heterogeneous prognosis. We aimed to identify the predictive factors for recurrence in these patients to aid in the decision making. METHODS We reviewed 344 patients with stage Ia non-small cell lung cancer to analyze the associations between recurrence-free survival and the following clinicopathologic variables: age, gender, smoking history, family history, preoperative serum carcinoembryonic antigen level, type of surgical resection, tumor location, tumor histology, lymphovascular invasion, tumor differentiation, and pathologic T status. RESULTS Cox multivariate survival analysis revealed that central tumor location (P=.019), stage T1b (P=.006), high histologic grade (including large cell carcinoma, solid predominant, micropapillary predominant, and invasive mucinous adenocarcinoma, P=.007), poor differentiation (P=.022), and lymphovascular invasion (P=.035) were independently associated with recurrence-free survival. A nomogram for predicting the probability of 3-year recurrence-free survival was developed using the 5 variables. This model shows good calibration, reasonable discrimination (concordance index=0.733), and small overfitting (2.6%) demonstrated by bootstrapping. CONCLUSIONS We developed a clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer. This model can help with the selection of appropriate postoperative therapeutic strategies for these patients.

Risk factors for predicting the occult nodal metastasis in T1–2N0M0 NSCLC patients staged by PET/CT: Potential value in the clinic

BACKGROUND AND OBJECTIVE The aims of our study were to evaluate the occult nodal metastasis in clinical stage I patients by PET/CT, further investigate the potential risk factors for nodal involvement, since a successful prediction could be helpful in selection appropriate candidates for SABR or limited surgery. METHODS We retrospectively reviewed the records of 189 patients who diagnosed as clinical stage I NSCLC by (18)F-FDG PET/CT from January 2004 to July 2011. All patients underwent lobectomy and systematic lymph node dissection and preoperative (18)F-FDG PET/CT scanning. The prevalence of occult nodal metastasis in patients as clinical N0 was analyzed according to clinicopathological factors such as tumor location, tumor size, tumor subtype, grade of differentiation and primary tumor SUV(max). Risk factors for occult nodal metastasis were defined by univariate and multivariate analysis. RESULTS Occult nodal metastasis was detected in 18.0% (34/189) of the patients. SUV(max) of the primary tumor and tumor size were independent predictors of occult nodal metastasis for patients with clinical N(0)NSCLC by FDG PET/CT. Accordingly we divided our patients into three groups: group 1 (low-risk group) ∼T ≤ 3 cm and SUV(max) ≤ 4.3; group 2 (moderate-risk group) ∼T ≤ 3 cm and SUV(max) > 4.3 or SUV(max) ≤ 4.3 and T > 3 cm; group 3 (high-risk group) ∼T > 3 cm and SUV(max) > 4.3. The occult lymph node metastasis rate in groups 1, 2, 3 was 1/82 (1.2%), 19/75 (25.3%) and 14/32 (43%) respectively. CONCLUSIONS T(1-2N0M0) NSCLC patients by PET/CT showing larger tumor size and high SUV(max) constitute a high-risk group for occult nodal metastasis. The combined information of primary tumor SUV(max) and tumor size before treatment have potential values in the clinic. These findings would be helpful in selection of SABR or limited surgery candidates.

Recurrent TERT promoter mutations in non-small cell lung cancers

INTRODUCTION The recurrent TERT promoter mutations have been recently described in diverse human cancers. We previously showed that over 60% of non-small cell lung cancer from East Asian harbored well-known oncogenic mutations in EGFR and KRAS. Here, we sought to determine the incidence, clinicopathologic characteristics, and association with known oncogenic mutations. PATIENTS AND METHODS A total of 467 patients treated surgically for primary lung cancer were examined for mutations in TERT promoter using polymerase chain reaction (PCR) followed by Sanger sequencing. Immunohistochemical (IHC) staining was performed to detect the expression of TERT. Clinical characteristics including gender, age, smoking status, tumor size, differentiation, lymph node metastasis, TNM stage, overall survival and relapse-free survival were analyzed. RESULTS Of 467 patients with non-small cell lung cancer, the TERT promoter mutation was detected in 12 patients. Of the 12 patients, 3 with C228T, 2 with C250T, 2 with C216T, 1 with C228A, 1 with C229G, 1 with G267C, 1 with C295T and 1 with G233C. Compared to the TERT mutation negative group, patients with TERT promoter mutation were significantly associated with older age (≥ 60 years, p = 0.039). No significant difference was found in overall survival (OS) or relapse-free survival (RFS) between TERT with mutation and TERT without mutation. CONCLUSIONS TERT promoter mutations are recurrent mutated in 2.57% of NSCLCs and are highly enriched in older patients. It may play an important role in the pathogenesis of NSCLC and may serve as a potential target for therapy.

Relationship between tumor size and disease stage in non-small cell lung cancer

BackgroundWhether tumor size and stage distribution are correlated remains controversial. The objective is to assess the relationship between tumor size and disease stage distribution in non-small cell lung cancer (NSCLC).MethodsWe conducted a retrospective analysis of 917 cases of NSCLC that were resected in the Cancer Hospital of Fudan University and Shanghai Sixth Hospital between January 2000 and February 2009. Tumor sizes were grouped into five categories: ≤20 mm, 21 to 30 mm, 31 to 50 mm, 51 to 70 mm and ≥71 mm.ResultsAge and tumor size affected stage distribution: patients 60 years or older had a higher percentage of N0M0 disease than patients younger than 60 years (61.67% vs. 44.85%, p < 0.01). The smaller the tumor, the more likely the disease was N0M0 status (p < 0.05). For tumors ≤20 mm in diameter, the proportion of cases with N0M0 status was 70.79%, compared to 58.88% for 21 to 30 mm, 48.03% for 31 to 50 mm, 47.55% for 51 to 70 mm, 33.33% for ≥71 mm. The mean (± SD) tumor size of cases with N0M0 status was 37.17 ± 21.34 mm, compared to 45.75 ± 23.19 mm for cases with other status.ConclusionsThere is a statistically significant relationship between tumor size and distribution of disease stage of primary NSCLC tumors: the smaller the tumor, the more likely the disease is N0M0 status.

Thoracic recurrent laryngeal lymph node metastases predict cervical node metastases and benefit from three‐field dissection in selected patients with thoracic esophageal squamous cell carcinoma

Recurrent laryngeal nerve lymph nodes (RLN LNs) are considered sentinel nodes for cervical LN metastases of esophageal cancer. Surgery is the treatment of choice, but whether three‐field lymph node dissection (3FL), which includes cervical LN dissection, or 2FL, which does not, should be performed is controversial.

Clusterin Immunoexpression and its Clinical Significance in Patients with Non-Small Cell Lung Cancer

Clusterin is an enigmatic glycoprotein with a nearly ubiquitous tissue distribution. It plays important roles in various pathophysiological processes, including tissue remodeling, reproduction, lipid transport, complement regulation, and apoptosis. Clusterin appears to have two main isoforms that result from alternative splicing. The secreted and nuclear forms of clusterin have been reported to play different roles in human malignancies. The purpose of this study was to examine clusterin immunoexpression and its clinical significance in a group of Chinese patients with non-small cell lung cancer (NSCLC). Tissue samples from the primary tumors of 121 patients with completely resected NSCLC were obtained. Clusterin protein expression was evaluated by immunohistochemical staining with an antibody against all clusterin isoforms. Staining patterns were observed and graded based on intensity and density and were correlated with clinical and pathological data. Both cytoplasmic and nuclear clusterin immunostaining patterns were observed. Clusterin staining was observed only in the cytoplasm in 70 patients (57.9%), only in the nucleus in 27 patients (22.3%), and in both the cytoplasm and nucleus in 16 patients (13.2%). A significant association was observed between positive cytoplasmic clusterin expression and histologic type as indicated by adenocarcinomas that were more likely to have clusterin staining only in the cytoplasm. Clusterin immunostaining was neither associated with recurrence-free survival (RFS) nor overall survival of patients by univariate or multivariate analysis. For patients undergoing chemotherapy, those with only cytoplasmic clusterin staining had worse survival than other patients. In conclusion, both cytoplasmic and nuclear immunostaining patterns of clusterin were detected in the tumors of patients with NSCLC. Adenocarcinomas were more likely to have only cytoplasmic staining. The immunoexpression of clusterin was not associated with prognosis, and cytoplasm-only immunostaining of clusterin was inversely correlated with chemosensitivity in this group of patients.