Multiomics analysis revealed the mechanisms related to the enhancement of proliferation, metastasis and EGFR-TKI resistance in EGFR-mutant LUAD with ARID1A deficiency.

INTRODUCTION: Dysregulated ARID1A expression is frequently detected in lung adenocarcinoma (LUAD) and mediates significant changes in cancer behaviors and a poor prognosis. ARID1A deficiency in LUAD enhances proliferation and metastasis, which could be induced by activation of the Akt signaling pathway. However, no further exploration of the mechanisms has been performed. METHODS: Lentivirus was used for the establishment of the ARID1A knockdown (ARID1A-KD) cell line. MTS and migration/invasion assays were used to examine changes in cell behaviors. RNA-seq and proteomics methods were applied. ARID1A expression in tissue samples was determined by IHC. R software was used to construct a nomogram. RESULTS: ARID1A KD significantly promoted the cell cycle and accelerated cell division. In addition, ARID1A KD increased the phosphorylation level of a series of oncogenic proteins, such as EGFR, ErbB2 and RAF1, activated the corresponding pathways and resulted in disease progression. In addition, the bypass activation of the ErbB pathway, the activation of the VEGF pathway and the expression level changes in epithelial-mesenchymal transformation biomarkers induced by ARID1A KD contributed to the insensitivity to EGFR-TKIs. The relationship between ARID1A and the sensitivity to EGFR-TKIs was also determined using tissue samples from LUAD patients. CONCLUSION: Loss of ARID1A expression influences the cell cycle, accelerates cell division, and promotes metastasis. EGFR-mutant LUAD patients with low ARID1A expression had poor overall survival. In addition, low ARID1A expression was associated with a poor prognosis in EGFR-mutant LUAD patients who received first-generation EGFR-TKI treatment. Video abstract.

Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy.

Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse-free (P = 0.050) and tumor-specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.

Deep learning on tertiary lymphoid structures in hematoxylin-eosin predicts cancer prognosis and immunotherapy response.

Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models' discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis.

Preoperative prognostic prediction for stage I lung adenocarcinomas: Impact of the computed tomography features associated with the new histological grading system.

Objectives: This study aimed to identify the computed tomography (CT) features associated with the new International Association for the Study of Lung Cancer (IASLC) three-tiered grading system to improve the preoperative prediction of disease-free survival of stage I lung adenocarcinoma patients. Methods: The study included 379 patients. Ordinal logistic regression analysis was used to identify the independent predictors of IASLC grades. The first multivariate Cox regression model (Model 1) was based on the significant factors from the univariate analysis. The second multivariate model (Model 2) excluded the histologic grade and based only on preoperative factors. Results: Larger consolidation tumor ratio (OR=2.15, P<.001), whole tumor size (OR=1.74, P=.002), and higher CT value (OR=3.77, P=.001) were independent predictors of higher IASLC grade. Sixty patients experienced recurrences after 70.4 months of follow-up. Model 1 consisted of age (HR:1.05, P=.003), clinical T stage (HR:2.32, P<.001), histologic grade (HR:4.31, P<.001), and burrs sign (HR:5.96, P<.001). Model 2 consisted of age (HR,1.04; P=.015), clinical T stage (HR:2.49, P<.001), consolidation tumor ratio (HR:2.49, P=.016), whole tumor size (HR:2.81, P=.022), and the burrs sign (HR:4.55, P=.002). Model 1 had the best prognostic predictive performance, followed by Model 2, clinical T stage, and histologic grade. Conclusion: CTR (cut-off values of <25% and ≥75%) and whole tumor size (cut-off value of 17 mm) could stratify patients into different prognosis and be used as preoperative surrogates for the IASLC grading system. Integrating these CT features with clinical T staging can improve the preoperative prognostic prediction for stage I lung adenocarcinoma patients.

GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma.

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

Development and validation of a nomogram based on preoperative variables for predicting recurrence-free survival in stage IA lung adenocarcinoma.

BACKGROUND: This study aimed to establish a nomogram for predicting risk of recurrence and provide a model for decision-making between lobectomy and sublobar resection in patients with stage IA lung adenocarcinoma. METHODS: Patients diagnosed with stage IA lung adenocarcinoma (LUAD) between December 2010 and October 2018 from Cancer Hospital Chinese Academy of Medical Sciences were included. Patients were randomly assigned to training and validation cohorts, accounting for 70% and 30% of the total cases, respectively. We collected laboratory variables before surgery. Univariate and multivariate analyses were performed in the training cohort to identify variables significantly associated with recurrence-free survival (RFS) which were subsequently used to construct a nomogram. Validation was conducted in both cohorts. A receiver operating characteristic curve was used to determine the optional cutoff values of the scores calculated from the nomogram. Patients were then divided into low- and high-risk groups. Survival was performed to determine if the nomogram could guide the operation method. RESULTS: A total of 543 patients were included in this study. Gender, albumin level, carcinoembryonic antigen level and cytokeratin-19-fragment level were included in the nomogram. In both cohorts, the nomogram stratified the patients into high- and low-risk groups in terms of RFS. In particular, there was a significant difference in RFS between lobectomy and sublobar resection in the high-risk group. CONCLUSIONS: Gender, albumin level, carcinoembryonic antigen level and cytokeratin-19-fragment level are valuable markers in predicting recurrence and can guide surgical practice in patients with stage IA LUAD.

Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization.

Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection. We apply this method to plasma samples of 497 healthy controls and 780 patients of seven cancer types and develop an ensemble classifier by incorporating methylation, fragmentation, and CNA features. In the test cohort, our approach achieves an area under the curve value of 0.966 for overall cancer detection. Detection sensitivity for early-stage patients achieves 73% at 99% specificity. Finally, we demonstrate the feasibility to accurately localize the origin of cancer signals with combined methylation and fragmentation profiling of tissue-specific accessible chromatin regions. Overall, this proof-of-concept study provides a technical platform to utilize multimodal cfDNA features for improved cancer detection.

A strategy to reduce the false-positive rate after low-dose computed tomography in lung cancer screening: A multicenter prospective cohort study.

BACKGROUND: The ability of lung cancer screening to manage pulmonary nodules was limited because of the high false-positive rate in the current mainstream screening method, low-dose computed tomography (LDCT). We aimed to reduce overdiagnosis in Chinese population. METHODS: Lung cancer risk prediction models were constructed using data from a population-based cohort in China. Independent clinical data from two programs performed in Beijing and Shandong, respectively, were used as the external validation set. Multivariable logistic regression models were used to estimate the probability of lung cancer incidence in the whole population and in smokers and nonsmokers. RESULTS: In our cohort, 1,016,740 participants were enrolled between 2013 and 2018. Of 79,581 who received LDCT screening, 5165 participants with suspected pulmonary nodules were allocated into the training set, of which, 149 lung cancer cases were diagnosed. In the validation set, 1815 patients were included, and 800 developed lung cancer. The ages of patients and radiologic factors of nodules (calcification, density, mean diameter, edge, and pleural involvement) were included in our model. The area under the curve (AUC) values of the model were 0.868 (95% CI: 0.839-0.894) in the training set and 0.751 (95% CI: 0.727-0.774) in the validation set. The sensitivity and specificity were 70.5% and 70.9%, respectively, which could reduce the 68.8% false-positive rate in simulated LDCT screening. There was no substantial difference between smokers' and nonsmokers' prediction models. CONCLUSION: Our models could facilitate the diagnosis of suspected pulmonary nodules, effectively reducing the false-positive rate of LDCT for lung cancer screening.

[Comparison of the short-term outcomes of surgical treatment for non-small cell lung cancer via video assisted thoracoscopic surgery and open thoracotomy].

OBJECTIVE: To compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT). METHODS: Data of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed. RESULTS: In the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications. CONCLUSIONS: To compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

[Diagnosis and surgical treatment of pulmonary sclerosing hemangioma].

OBJECTIVE: As a rare benign lung tumor, pulmonary sclerosing hemangioma (PSH) occurs predominantly in Asian women in their fifth and sixth decades of life. PSH is considered to be evolved from primitive undifferentiated respiratory epithelium. In this study, we summarized our experience in 89 cases of PSH. METHOD: There were a total of 89 patients who received surgical resection and were histopathologically diagnosed as PSH during the period January 2001 to December 2010 in department of thoracic surgery, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences. The clinical data of these patients including symptoms, disease courses, image characteristics and surgical procedures were collected and reviewed retrospectively. RESULTS: The PSHs were most frequently (50.6%) found in the patients aged 41 to 60 years with a median age of 51 years (range: 24 - 71), and the sex ratio (male/female) was approximately 1:7 in this series. In the 89 patients, 53 (59.6%) were asymptomatic while the other 36 (40.4%) had some non-special symptoms such as cough (30.3%), hemoptysis (24.7%). There were only 3 cases (3.4%) with multiple PSHs, 4 cases (4.5%) combined with synchronous primary lung cancer, and 13 cases (14.6%) with lesions located in the hilar region. The median diameter of the 92 lesions was 2.3 cm (range: 0.3 - 6.0 cm), of which 38% located in the right lower lobe and 26.1% in the right middle lobe, and only about 1/3 were assumed as PSHs preoperatively based on CT imaging. One of the five patients who underwent PET-CT scan had been misdiagnosed as malignant. Of the 92 lesions, 47 were resected by enucleation, 29 by wedge resection, 14 by lobectomy, and 2 by pneumonectomy. CONCLUSION: PSH frequently occurs in the middle-aged women. Most individuals with PSH are asymptomatic or have some non-specific symptoms. Their lesions are usually found accidentally by chest imaging. Although PSH often shows typical imaging characteristics of benign neoplasm of the lung, it is difficult to establish a defined pathological diagnosis preoperatively. The significant error or deferred rate of intraoperative frozen-section evaluation for PSH may result in some unnecessarily extensive surgical procedures. The complete surgical resection is considered the only effective treatment for PSH, and the normal pulmonary tissue should be reserved as possible.

External validation of the eighth edition of the TNM classification for lung cancer in small cell lung cancer.

OBJECTIVES: The newly released eighth edition of the American Joint Committee on Cancer TNM staging system for lung cancer seeks to improve prognostic accuracy but lacks external validation for small cell lung cancer (SCLC). Moreover, previous studies posed a few questions concerning survival differences for patients with specific site N3 node involvement or single-site metastasis (SSM) in different distant organs. The aim of this study was to validate the eighth edition of the TNM classification for SCLC in an independent multi-institutional cohort from China and answer the questions raised by the previous research. METHODS: Patients with SCLC from four Chinese cancer centers between 2009 and 2019 were reclassified according to the seventh and eighth edition of the TNM classification. Survival was estimated using the Kaplan-Meier method. Comparisons between adjacent categories and stage groups were performed using Cox proportional hazard regression. R2 statistics were calculated to evaluate the discriminating performance of editions. RESULTS: Of 3384 enrolled cases, 3358 had clinical stage, 537 had pathological stage, and 511 had both. Progressive deterioration of survival was observed with advancing of TNM categories and stages both in the seventh and the eighth edition. The eighth edition stages had a higher R2 statistic than the seventh edition (0.207 versus 0.197). Newly defined categories M1b and M1c and stages IIIC, IVA and IVB in the eighth edition discriminated groups with significantly different prognosis. Patients with N3 contralateral supraclavicular nodes had a significantly worse prognosis than those without (p = 0.032). For patients with single-site metastasis, liver involvement showed a worse prognosis compared to brain involvement (p = 0.030). CONCLUSIONS: Our study provided an external validation of the eighth edition of the TNM classification for lung cancer in Chinese patients with SCLC, and confirmed its improved prognostic accuracy compared with the seventh edition. Patients with N3 and M1b might represent heterogeneous populations that warrant further research.

Recurrence risk stratification based on a competing-risks nomogram to identify patients with esophageal cancer who may benefit from postoperative radiotherapy.

BACKGROUND: A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC). METHODS: The study retrospectively reviewed 3652 TESCC patients in stage IB-IVA after radical esophagectomy, with or without PORT. In one institution as the training cohort (n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing-risks regression, were used to establish a predicting nomogram, which was validated in an external cohort (n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram. After balancing the baseline of characteristics between treatment groups by inverse probability of treatment weighting, the effect of PORT was evaluated in each risk group. RESULTS: Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 10.2% and 9.4%, respectively (p < 0.05). Although PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved. CONCLUSION: The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.

A highly connected porous coordination polymer with unusual channel structure and sorption properties.

Making connections: A hydroxy-centered trinuclear nickel cluster has been employed to construct a highly connected, highly symmetric framework with a uninodal nine-connected topology. An array of triakis tetrahedra leads to a biporous intersecting-channel system (see picture).

Predictors of lymph node metastasis and possible selective lymph node dissection in clinical stage IA non-small cell lung cancer.

BACKGROUND: The pathologic stages of lymph nodes usually differ from preoperatively predicted in lung cancers and it is difficult to predict the metastasis of lymph nodes for the patients diagnosed as clinical stage IA non-small cell lung cancers (NSCLC). This study aimed to investigate the patterns of lymph node metastasis and the risk factors predicting lymph node metastasis in the patients with clinical stage IA NSCLCs. METHODS: All patients diagnosed as clinical stage IA NSCLC from July 2013 to June 2017 in our center were retrospectively reviewed, and a total number of 1,543 patients who underwent anatomical lobectomy with systematic lymph node dissection were enrolled in this study. Multivariate logistic regression analysis was performed to identify the risk factors predicting lymph node metastasis, and Fisher's exact test was used to confirm the lymph node spread mode according to the locations of primary tumors. RESULTS: Totally, lymph node metastases presented in 131 patients (8.5%) in this series. Sixty-three patients presented N1 diseases, 17 patients showed only skipped N2 diseases, and 51 patients had simultaneous N1 and N2 positive lymph nodes. No lymph node metastasis was found in the patients with pure ground grass opacity (GGO). When patients were arbitrarily divided into six groups by the longest tumor diameter of ≤0.5, 0.6-1, 1.1-1.5, 1.6-2.0, 2.1-2.5, 2.6-3 cm, the lymph node metastasis rates of each group were 0% (0/20), 1.5% (4/264), 4.7% (20/429), 8.6% (29/336), 13.1% (38/290), 19.6% (40/204), respectively. When the patients with pure GGO were excluded, the lymph node metastasis rates in the patients with partial or total solid tumors were 0% (0/10), 2.4% (4/164), 6.6% (20/303), 11.7% (29/249), 16.0% (38/238) and 23.1% (40/173). The cut off value showed by receiver operating characteristic (ROC) curve for tumor size was 1.95 cm, and the area under the curve (AUC) was measured as 0.681 (P<0.001, 95% CI: 0.630-0.726). Multivariate logistic regression analysis indicated that male patients [odds ratio (OR) =3.34, P=0.012], smoking history (OR =14.12, P<0.001), solid components (OR =3.34, P=0.01), large tumor size (OR =1.9, P<0.001), poor differentiation (OR =2.25, P=0.013), lymphovascular invasion (OR =58.45, P<0.001), visceral pleural invasion (OR =48.37, P<0.001) were significantly associated with lymph node metastasis in clinical stage IA NSCLC. The rate of non-lobe specific lymph node metastasis was 15.8-40.0% when any of the lobe specific lymph nodes was positive, while it was only 0-2.2% when all lobe specific lymph nodes were negative. CONCLUSIONS: Tumor size, solid components, poor differentiation, lymphovascular invasion, visceral pleural invasion and smoking history were significant factors predicting lymph node metastasis of clinical stage IA NSCLC. Patients with negative lobe-specific lymph node have very low risk of metastasis to the non-lobe specific lymph nodes. Lobe-specific lymph node dissection may become an alternative lymph node dissection mode for clinical stage IA NSCLC, especially for tumors ≤2 cm.

Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by increasing its cognate gene PHB expression.

Natural antisense transcripts (NATs) as one of the most diverse classes of long noncoding RNAs (lncRNAs), have been demonstrated involved in fundamental biological processes in human. Here, we reported that human prohibitin gene pseudogene 1 (PHBP1) was upregulated in ESCC, and increased PHBP1 expression in ESCC was associated with clinical advanced stage. Functional experiments showed that PHBP1 knockdown inhibited ESCC cells proliferation, colony formation and xenograft tumor growth in vitro and in vivo by causing cell-cycle arrest at the G1-G0 phase. Mechanisms analysis revealed that PHBP1 transcript as an antisense transcript of PHB is partially complementary to PHB mRNA and formed an RNA-RNA hybrid with PHB, consequently inducing an increase of PHB expression at both the mRNA and protein levels. Furthermore, PHBP1 expression is strongly correlated with PHB expression in ESCC tissues. Collectively, this study elucidates an important role of PHBP1 in promoting ESCC partly via increasing PHB expression.

[Comparison of clinical and surgico-pathological TNM stage of 2007 lung cancer patients].

OBJECTIVE: An accurate clinical TNM staging of lung cancer is essential for the precise determination of the extent of the disease in order that an optimal therapeutic strategy can be planned. This is especially true in patients with marginally resectable tumors. Clinical over-staging of the disease may deny a patient the benefit of surgery, whereas under-staging may oblige a patient to accept a fruitless or even harmful surgery. We aimed to analyze preoperative clinical (c-TNM) and postoperative surgico-pathologic staging (p-TNM) of lung cancer patients in order to evaluate the accuracy of our clinical staging and its implications on the surgical strategy for lung cancer. METHODS: We did a retrospective comparison of c-TNM and p-TNM staging of 2007 patients with lung cancer surgically treated from January 1999 to May 2003. Preoperative evaluation and c-TNM staging of all patients were based on physical examination, laboratory studies, routine chest X-ray and CT scan of the chest and upper abdomen. Other examinations included sputum cytology, bronchoscopy, abdominal ultrasonography, bone scintiscan, brain CT/MRI, and mediastinoscopy whenever indicated. RESULTS: In the present study the comparison of c-TNM and p-TNM staging of 2007 patients with lung cancer revealed an overall concurrence rate of only 39.0%. In the entire series the extent of disease was clinically underestimated in 45.2% and overestimated in 15.8% of the patients. Among all c-TNM stages the c-IA/B stage of 1105 patients gave the highest rate (55.2%) of underestimating the extent of disease. Clinical staging of T subsets was relatively easy with an overall accuracy rate of 72.9%, while that of N subsets was relatively more difficult with an overall accuracy rate of 53.5%. Analysis also showed that c-IV stage may not be an absolute contraindication to surgery, because in half of the patients, c-M1 turned out to be p-M0, providing the possibility of resectional surgery depending on the status of T and N. CONCLUSION: For reasons to be further determined, the present preoperative clinical TNM staging of lung cancer remains a crude evaluation. Further efforts to improve its accuracy are needed.

[Diagnosis and surgical treatment of metachronous second primary lung cancer].

OBJECTIVE: To review the experience of the diagnosis, surgical treatment and prognosis of metachronous second primary lung cancers. METHODS: Between January 1983 and April 2004, 32 patients with metachronous second primary lung cancers were operated in our department. Clinical data of all these patients were reviewed retrospectively. RESULTS: The initial procedures for their first primary lung cancers were lobectomy or pneumonectomy. Lobectomy or completion pneumonectomy for the second primary lung cancers were performed in 17 cases, limited pulmonary resection was done in 14 cases and exploration was in 1 case. The postoperative morbidity and mortality were 12% (4/32) and 3% (1/32), respectively. The 1-, 3-, and 5-year survival rate after second operation were 66% (19/29), 32% (9/28) and 19% (4/21), respectively. CONCLUSIONS: The incidence of metachronous second primary lung cancers has been increasing gradually during recent years. The closely follow-up for patients undergoing resection for their first primary lung cancers is most important factor for improvement of the diagnosis of metachronous second primary lung cancers. Limited resection and incomplete lymph node dissection might be the factors contributing to the poor prognosis.

Partial esophagogastrostomy with esophagogastric anastomosis below the aortic arch in cardiac carcinoma: characteristics and treatment of postoperative anastomotic leakage.

BACKGROUND: Anastomotic leakage is a severe and common complication for surgeries of cardiac cancer. Here we explore the clinical features, diagnosis, and treatment strategies of anastomotic leakage in cardiac carcinoma patients after esophagogastric anastomosis. METHODS: From January 2009 to December 2013, 1,196 patients with cardiac carcinoma underwent esophagectomy and esophagogastric anastomosis in Cancer Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences. Of them, 25 patients developed symptomatic anastomotic leakage. Their clinical data were retrospectively reviewed. RESULTS: Among these 25 patients with anastomotic leakage, three died after active treatment and fifteen healed with thoracic drainage time 18-115 days. The left seven patients who did not heal until discharge developed chronic infection sinus of anastomotic leakage. Without infection symptoms, they were discharged 30-100 days after surgery with nasoenteral tube and thoracic drainage. CONCLUSIONS: Anastomotic leakage in cardiac carcinoma patients after esophagogastric anastomosis can be classified into five subtypes: occult type, left thoracic type, right thoracic type, mediastinal type, and mixd type. Subtyping of anastomotic leakage is useful and convenient for diagnosis and treatment.

Comparative study of minimally invasive versus open esophagectomy for esophageal cancer in a single cancer center.

BACKGROUND: In order to minimize the injury reaction during the surgery and reduce the morbidity rate, hence reducing the mortality rate of esophagectomy, minimally invasive esophagectomy (MIE) was introduced. The aim of this study was to compare the postoperative outcomes in patients with esophageal squamous cell carcinoma undergoing minimally invasive or open esophagectomy (OE). METHODS: The medical records of 176 consecutive patients, who underwent minimally invasive esophagectomy (MIE) between January 2009 and August 2013 in Cancer Institute & Hospital, Chinese Academy of Medical Sciences, were retrospectively reviewed. In the same period, 142 patients who underwent OE, either Ivor Lewis or McKeown approach, were selected randomly as controls. The clinical variables of paired groups were compared, including age, sex, Charlson score, tumor location, duration of surgery, number of harvested lymph nodes, morbidity rate, the rate of leak, pulmonary morbidity rate, mortality rate, and hospital length of stay (LOS). RESULTS: The number of harvested lymph nodes was not significantly different between MIE group and OE group (median 20 vs. 16, P = 0.740). However, patients who underwent MIE had longer operation time than the OE group (375 vs. 300 minutes, P < 0.001). Overall morbidity, pulmonary morbidity, the rate of leak, in-hospital death, and hospital LOS were not significantly different between MIE and OE groups. Morbidities including anastomotic leak and pulmonary morbidity, inhospital death, hospital LOS, and hospital expenses were not significantly different between MIE and OE groups as well. CONCLUSIONS: MIE and OE appear equivalent with regard to early oncological outcomes. There is a trend that hospital LOS and hospital expenses are reduced in the MIE group than the OE group.

Application of video-assisted thoracic surgery in the standard operation for thoracic tumors.

OBJECTIVE: To evaluate the short-term outcomes of video-assisted thoracic surgery (VATS) for thoracic tumors. METHODS: The data of 1,790 consecutive patients were retrospectively reviewed. These patients underwent VATS pulmonary resections, VATS esophagectomies, and VATS resections of mediastinal tumors or biopsies at the Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and January 2012. RESULTS: There were 33 patients converted to open thoracotomy (OT, 1.84%). The overall morbidity and mortality rate was 2.79% (50/1790) and 0.28% (5/1790), respectively. The overall hospitalization and chest tube duration were shorter in the VATS lobectomy group (n=949) than in the open thoracotomy (OT) lobectomy group (n=753). There were no significant differences in morbidity rate, mortality rate and operation time between the two groups. In the esophageal cancer patients, no significant difference was found in the number of nodal dissection, chest tube duration, morbidity rate, mortality rate, and hospital length of stay between the VATS esophagectomy group (n=81) and open esophagectomy group (n=81). However, the operation time was longer in the VATS esophagectomy group. In the thymoma patients, there was no significant difference in the chest tube duration, morbidity rate, mortality rate, and hospital length of stay between the VATS thymectomy group (n=41) and open thymectomy group (n=41). However, the operation time was longer in the VATS group. The median tumor size in the VATS thymectomy group was comparable with that in the OT group. CONCLUSIONS: In early-stage (I/II) non-small cell lung cancer patients who underwent lobectomies, VATS is comparable with the OT approach with similar short-term outcomes. In patients with resectable esophageal cancer, VATS esophagectomy is comparable with OT esophagectomy with similar morbidity and mortality. VATS thymectomy for Masaoka stage I and II thymoma is feasible and safe, and tumor size is not contraindicated. Longer follow-ups are needed to determine the oncologic equivalency of VATS lobectomy, esophagectomy, and thymectomy for thymoma vs. OT.