Development and validation of a clinical decision tool for preoperative micropapillary and solid pattern lung adenocarcinoma of CT≤2 cm.

BACKGROUND: Micropapillary (MP) and solid(S) pattern adenocarcinoma are highly malignant subtypes of lung adenocarcinoma. In today's era of increasingly conservative surgery for small lung cancer, effective preoperative identification of these subtypes is greatly important for surgical planning and long term survival of patients. METHODS: For this retrospective study, the presence of MP and/or S was evaluated in 2167 consecutive patients who underwent surgical resection for clinical stage IA1-2 lung adenocarcinoma. MP and/or S pattern-positive patients and negative-pattern patients were matched at a ratio of 1:3. The Lasso regression model was used for data dimension reduction and imaging signature building. Multivariate logistic regression was used to establish the predictive model, presented as an imaging nomogram. The performance of the nomogram was assessed based on calibration, identification, and clinical usefulness, and internal and external validation of the model was conducted. RESULTS: The proportion of solid components (PSC), Sphericity, entropy, Shape, bronchial honeycomb, nodule shape, sex, and smoking were independent factors in the prediction model of MP and/or S lung adenocarcinoma. The model showed good discrimination with an area under the ROC curve of 0.85. DCA demonstrated that the model could achieve good benefits for patients. RCS analysis suggested a significant increase in the proportion of MP and/or S from 11% to 48% when the PSC value was 68%. CONCLUSION: Small MP and/or S adenocarcinoma can be effectively identified preoperatively by their typical 3D and 2D imaging features.

Computed tomography imaging and clinical characteristics of pulmonary ground-glass nodules ≤2 cm with micropapillary pattern.

BACKGROUND: The aim of this study was to investigate the imaging features, lymph node metastasis, and genetic mutations in micropapillary lung adenocarcinoma (imaging with mixed ground-glass nodules) ≤2 cm, to provide a more precise and refined basis for the selection of lung segment resection. METHODS: A retrospective analysis of 162 patients with surgically resected pathologically confirmed cancers ≤2.0 cm in diameter (50 cases of micropapillary mixed ground-glass nodules [mGGNs], 50 cases of nonmicropapillary mGGNs, and 62 cases of micropapillary SNs [solid nodules]) was performed. mGGNs were classified into five categories according to imaging features. The distribution of these five morphologies in micropapillary with mGGN and nonmicropapillary with mGGN was analyzed. The postoperative pathology and prognosis of lymph node metastasis were also compared between micropapillary mGGNs and micropapillary with SNs. After searching the TCGA database, we demonstrated heterogeneity, high malignancy and high risk of microcapillary lung cancer cancers. RESULTS: Different pathological subtypes of mGGN differed in morphological features (p < 0.05). The rate of lymph node metastasis was significantly higher in micropapillary mGGNs than in nonmicropapillary mGGNs. In the TCGA database samples, lactate transmembrane protein activity, collagen transcription score, and fibroblast EMT score were remarkably higher in micropapillary adenocarcinoma. Other pathological subtypes had a better survival prognosis and longer disease-free survival compared with micropapillary adenocarcinoma. CONCLUSION: mGGNs ≤2 cm with a micropapillary pattern have a higher risk of lymph node metastasis compared with SNs, and computed tomography (CT) imaging features can assist in their diagnosis.

Profile analysis of N4-acetylcytidine (ac4C) on mRNA of human lung adenocarcinoma and paired adjacent non-tumor tissues.

BACKGROUND: RNA modification, a major component of post-transcriptional modification, plays an essential role in tumor initiation and progression. N4-acetylcytidine (ac4C) present in different species as a highly conserved RNA modification. ac4C on mRNA increases the stability of mRNA and the efficiency of protein translation. However, the mRNA profiling of ac4C in lung adenocarcinoma (LUAD) is unknown. METHODS: NAT10 expression was tested using immunohistochemistry in tissue microarray (TMA). The ac4C peaks on mRNA were identified through acetylated RNA immunoprecipitation sequencing in both human LUAD tissues and adjacent non-tumor tissues, and differences of acetylation and mRNA between the two groups were analyzed. Furthermore, the function of AC4C-specific acetylated transcripts was analyzed bioinformatically. And a ac-RIP-PCR was used to verify the ac4C acetylation sites of TFAP2A. RESULTS: The expression of acetylated key enzyme NAT10 was obviously increased in LUAD group. Then we found noticeable differences in ac4C mRNA modification between LUAD and adjacent non-tumor tissues. In addition, bioinformatics analysis showed that the distinctive distribution pattern of mRNA ac4C in LUAD affects a variety of cellular functions, such as protein sumoylation and transmembrane transporter activity. Importantly, we verified the ac4C level of TFAP2A was up-regulated in LUAD. CONCLUSIONS: Our study revealed that the degree of ac4C in mRNA in LUAD was significantly higher than in adjacent tissues and was concentrated mainly in the coding sequences with a implications in a wide range of cellular functions. The ac4C may become a new molecular marker and treatment target for lung cancer.

Expression and clinical significance of CD31, CD34, and CD105 in pulmonary ground glass nodules with different vascular manifestations on CT.

Blood vessel passage on CT exerts a vital part in early diagnosis as well as treatment of carcinoma of the lungs. Intratumoral microvascular density (iMVD) has gradually become the focus of research on biological behavior, appearance, and evolution of malignant tumors nowadays. The aim of this paper was to verify whether there is a correlation between the iMVD and the vascular morphology of ground glass nodules (GGNs). A total of 109 patients with pulmonary GGN were classified into three groups (I,II, and III) according to the vascular morphology on CT, and their expression of CD31-, CD34-, and CD105-labeled iMVD was detected by the streptoavidin-biotin method, statistically analyzing the iMVD values of each group. The expression of CD31, CD34, and CD105 in different lung tissues was significantly different, with remarkably higher iMVD in lung cancer tissues than in adjacent normal lung tissues. In the imaging sort of types I, II, and III according to the means of vascular passage, the iMVD expression of CD31, CD34, and CD105 was significantly different between groups. These data suggest that the presence and the abnormal morphology of vessels seen within GGNs indicate the occurrence and progression of lung cancer in pathology. It offers a strong theoretical foundation for early diagnosis of carcinoma of the lungs, thus providing a more precise clinical diagnosis and prognosis of early-stage lung cancer.

Positive attention bias in high socially anxious individuals: Evidence from an ERP study.

The Bivalent Fear of Evaluation (BFEO) model posits that the fear of positive evaluation (FPE) is a core feature of social anxiety. As such, high socially anxious individuals may show attention bias when faced with positive stimuli. However, most of the previous studies focused on the negative attention bias of social anxiety, and less on the attention bias of positive stimuli. Meanwhile, the effect of stimulus presentation time on the attention bias pattern was unclear. In order to investigate this question, we used a dot-probe paradigm with facial expressions (happy, fearful, angry, neutral) presented for 100 ms and 500 ms. The ERP results showed: (1) For high socially anxious group, happy faces elicited a larger N1 for valid than for invalid cued probes, whereas for healthy control group, angry faces elicited a larger N1 for valid than for invalid cued probes. (2) When valid cues following happy faces presented for 500 ms, the N1 amplitude was larger than that of invalid cues. However, when valid cues following angry and fear faces presented for 100 ms, the N1 amplitude was larger than that of invalid cues. The results showed difficulty in attention disengagement of high socially anxious individuals from positive stimuli, as reflected by N1, illustrating the positive attention bias in social anxiety. These results prove that FPE may contribute to maintaining social anxiety.

Correlation between CT imaging characteristics and pathological diagnosis for subcentimeter pulmonary nodules.

BACKGROUND: Advances in chest computed tomography (CT) have resulted in more frequent detection of subcentimeter pulmonary nodules (SCPNs), some of which are non-benign and may represent invasive lung cancer. The present study aimed to explore the correlation between pathological diagnosis and the CT imaging manifestations of SCPNs. METHODS: This retrospective study included patients who underwent pulmonary resection for SCPNs at Shandong Provincial Hospital in China. Lesions were divided into five categories according to their morphological characteristics on CT: cotton ball, solid-filled with spiculation, solid-filled with smooth edges, mixed-density ground-glass, and vacuolar. We further analyzed lesion size, enhancement patterns, vascular aggregation, and SCPN traversing. Chi-square tests, Fisher's exact tests, and Welch's one-way analysis of variance were used to examine the correlation between CT imaging characteristics and pathological type. RESULTS: There were statistically significant differences in the morphological distributions of SCPNs with different pathological types, including benign lesions and malignant lesions at different stages (p < 0.01). The morphological distributions of the four subtypes of invasive lung adenocarcinoma also exhibited significant differences (p < 0.01). In addition, size and enhancement patterns differed significantly among different pathological types of SCPNs. CONCLUSION: Different pathological types of SCPNs exhibit significant differences based on their morphological category, size, and enhancement pattern on CT imaging. These CT characteristics may assist in the qualitative diagnosis of SCPNs.

Triglyceride-Glucose Index Is Not Associated With Lung Cancer Risk: A Prospective Cohort Study in the UK Biobank.

BACKGROUND: The triglyceride-glucose (TyG) index is a practical substitute measure for insulin resistance (IR). The relationship between IR and lung cancer has been examined in previous studies; however, the findings have been controversial. In addition, previous studies had small sample sizes. Thus, we systematically examined the association between IR and lung cancer risk based on the UK Biobank with IR measured by the TyG index and further examined the interactions and joint effects for lung cancer. METHODS: A total of 324,334 individuals free from any type of cancer at recruitment from the UK Biobank prospective cohort were included. The participants were predominantly between 40 and 70 years old. After adjusting for relevant confounders, multivariable Cox regression models were constructed to examine the relationship between the TyG index and the risk of lung cancer. We also checked the interactions and joint effects using a polygenic risk score (PRS) for lung cancer. RESULTS: During a median follow-up of 9 years, 1,593 individuals were diagnosed with lung cancer. No association was found between the TyG index and lung cancer risk after multivariate Cox regression analysis adjusted for risk factors (hazard ratio: 0.91; 95% confidence interval: 0.64-1.18). No interaction or joint effects for genetic risk and the TyG index were observed. CONCLUSION: The TyG index was not associated with the risk of lung cancer. Our results provide limited evidence that IR is not correlated with the risk of lung cancer.

The arterial-ligation-alone method for identifying the intersegmental plane during thoracoscopic anatomic segmentectomy.

BACKGROUND: Currently, methods for identifying the intersegmental plane during anatomical segmentectomy can be classified into 2 categories: the bronchial method and the vascular method. One of the vascular methods, the arterial-ligation-alone method, has not yet been validated or objectively evaluated in a large case series. We thus aimed to confirm that the arterial-ligation-alone method could effectively and accurately identify the intersegmental plane. METHODS: We retrospectively reviewed the records of 104 patients who were scheduled for thoracoscopic anatomic segmentectomy. Preoperative three-dimensional (3D) reconstruction was performed on all the affected lungs to distinguish the targeted segmental arteries, veins and bronchi. The procedure was as follows: first, based on the 3D reconstruction of the lung, the targeted segmental arteries were distinguished and ligated. Second, bilateral pulmonary ventilation was performed with pure oxygen. When the affected lung had completely inflated, contralateral pulmonary ventilation was performed. After waiting for some time, the first intersegmental plane could be obtained, and the time was recorded as T1, with an electric coagulation hook being used for marking. Thirdly, when the targeted segmental veins and bronchi had been ligated, the second intersegmental plane could be obtained by the inflation-deflation method as before, with the waiting time being recorded as T2. The differences between the 2 intersegmental planes were evaluated by 2 experienced chief thoracic surgeons. RESULT: In a total of 99 (95.2%) patients, the intersegmental planes were successfully and accurately identified by the arterial-ligation-alone method. Ultimately, 85 (81.7%) patients underwent thoracoscopic anatomic segmentectomy. The results for evaluating the differences between the 2 planes were as follows: completely consistent (94 cases, 94.9%), basically consistent (5 cases, 5.1%), and discrepant (0 cases, 0%). The mean T1 was 13.6±2.7 minutes (range, 8-25 minutes), and the mean T2 was 13.0±2.6 minutes (range, 8-23 minutes), with P=0.100 (95% CI). For 99 patients, the mean nodule size was 1.1±0.34 cm. In the 85 patients who underwent segmentectomy, the mean margin width was 2.84±0.51 cm, the mean operative duration was 165.6±18.3 minutes, the mean operative hemorrhage was 52.1±20.2 mL, and the mean duration of chest tube drainage was 3.9±1.3 days. Postoperative complications related to operative procedures occurred in 2 cases. CONCLUSIONS: The arterial-ligation-only method can effectively, accurately and inexpensively identify the intersegmental plane, and is especially suitable for the patients whose veins or bronchi are difficult to anatomize. Whether the target bronchus is ligated has no effect on the intersegmental plane.

Prolonged endotracheal intubation: a feasible option for tracheomalacia after retrosternal goitre surgery.

BACKGROUND: Tracheomalacia may be caused by long-standing compression of retrosternal goitre because of destruction of support of tracheal cartilages. Life-threatening airway collapses may occur after surgical removal of goitre. However, available literature on management methods of tracheomalacia is sparse. Our study highlights prolonged endotracheal intubation as a feasible treatment method. METHODS: This retrospective study analysed 106 thyroidectomies for retrosternal goitre performed between 1994 and 2019. We recorded each patient's clinical profile. Severe tracheomalacia was confirmed through the following: soft and floppy trachea on intra-operative palpation and the collapse of cross-sectional tracheal area measured in computed tomography (CT) images by >80%. We assessed the extent of airway stenosis of these cases. All severe cases were treated by prolonged endotracheal intubation. RESULTS: Surgical treatment was successfully performed in all 106 retrosternal goitre patients with no mortality. Seventeen severe tracheomalacia cases were confirmed. The extent of airway stenosis was assessed: the minimal tracheal diameter of compressed trachea was 0.2-0.4 [mean 0.31, standard deviation (SD) 0.06] cm, and the narrow tracheal length was 4-6.7 (mean 5.1, SD 0.6) cm. These patients underwent endotracheal intubation for 17-47 h after surgery. All patients were transferred to the general ward after extubation and successfully discharged. There were no cases of tracheal stenosis on follow-up. CONCLUSIONS: Tracheomalacia is a rare but serious complication of retrosternal goitre surgery. Based on our experience, prolonged endotracheal intubation is a feasible treatment for tracheomalacia after retrosternal goitre surgery.

Correlation between computed tomography imaging and pathological stages and subtypes in early lung adenocarcinoma.

BACKGROUND: Detection of early-stage lung cancers has increased due to computed tomography (CT). The pathological stages and subtypes of early lung cancer determine the treatment strategy. We aimed to investigate the correlation between CT characteristics and pathological status in early lung adenocarcinoma (ADC). SUBJECTS AND METHODS: Between June 2018 and December 2019, 415 consecutive patients who underwent surgery for lung ADC with pathological atypical adenomatous hyperplasia (AAH) and ADC in situ (AIS), T1a (mi) N0M0, and T1a-cN0M0 were analyzed. The relationship between CT imaging and pathological status was investigated using Chi-squared or Kruskal-Wallis test and binary logistic regression. RESULTS: When cases of AAH, AIS, and T1a (mi) N0M0 were used as the control group, the lesion size, solid component ratio (SCR), and spiculation were significantly and independently associated with T1a-cN0M0 (P < 0.01). SCR >50% (P < 0.01) and spiculation (P < 0.05) were significantly and independently associated with T1aN0M0. In cases of pathological T1a-cN0M0, SCR >50% was significantly different between adherent wall growth ADC and mucinous ADC (P < 0.01). CONCLUSIONS: Some CT characteristics are related to the pathological stage and subtypes of early lung ADC. Larger diameter, spiculation, and SCR >50% are associated with invasive ADC. SCR >50% is positively correlated with mucinous ADC and negatively with adherent growth ADC.

Gefitinib Versus Adjuvant Chemotherapy in Patients With Stage II-IIIA Non-Small-Cell Lung Cancer Harboring Positive EGFR Mutations: A Single-Center Retrospective Study.

BACKGROUND: The superior efficacy of first-line treatment with gefitinib over that of standard chemotherapy was demonstrated in patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive mutation of epidermal growth factor receptor (EGFR). However, scarce evidence showing the superiority of gefitinib to chemotherapy exists regarding the postoperative adjuvant therapy of EGFR mutation-positive patients with stage II-IIIA NSCLC. To address this important gap, we undertook a retrospective study to assess the efficacy of adjuvant gefitinib versus adjuvant chemotherapy (AC) in patients with completely resected EGFR-mutant stage II-IIIA NSCLC. PATIENTS AND METHODS: A total of 116 patients with completely resected II-IIIA NSCLC and confirmed positive EGFR mutation (exon 19 deletion or exon 21 Leu858Arg) between January 2013 and March 2017 were included in our study. Disease-free survival (DFS) was analyzed in 55 patients treated with gefitinib and 61 patients treated with a platinum-based 2-drug-combination AC. Propensity score matching allowed the generation of best matched pairs for the 2 categories (1:1 ratio). Factors affecting survival were assessed by the Kaplan-Meier method and Cox regression analysis. RESULTS: The matched cohort consisted of 52 gefitinib and 52 AC patients with a median follow-up of 37.1 and 31.5 months, respectively. DFS was significantly longer in the gefitinib group than that in the AC group (34.9 months [95% confidence interval (CI), 21.1-48.7] versus 19.3 months [95% CI, 13.3-25.3]; hazard ratio = 0.36 [95% CI, 0.19-0.68], log-rank P = .001). In the gefitinib group the most common adverse events (AEs) were rash (76.9%), aminotransferase elevation (53.8%), and diarrhea (46.2%), whereas in the AC group the most common AEs were neutropenia (67.3%), nausea or vomiting (63.5%), and anemia (44.2%). Less frequent grade 3 or higher AEs were observed in the gefitinib group (15.4% vs. 38.5% in the AC group). After receiving gefitinib for 3 months, one patient was diagnosed with interstitial lung disease, which was regarded as the most severe treatment-related AE. No deaths were treatment related. CONCLUSION: In this retrospective study, compared to AC, gefitinib provided a statistically significant DFS benefit, reduced toxicity in EGFR mutation-positive patients with resected II-IIIA NSCLC. These results require further validation by prospective randomized trials.

Surgical treatment is an effective approach for patients with synchronous multiple primary lung cancers.

OBJECTIVE: The detection rate of synchronous multiple primary lung cancers (SMPLC) showed an increasing trend year by year. In an attempt to identify the optimal treatment strategy for SMPLC, we retrospectively analyzed our surgical treatment outcomes of a series of patients with SMPLC. MATERIALS AND METHODS: A total of 43 SMPLC patients who met the modified Martini-Melamed criteria and with clinical data retained between November 2012 and July 2016 underwent complete resection without any preoperative induction therapy at the Department of Thoracic Surgery, Shandong Provincial Hospital. The relationships between gender, age, family history of cancer, the number of tumors, the location of tumors, tumor size, tumor histology, regional lymph node metastasis, type of surgery, pathological stage, epidermal growth factor receptor (EGFR) mutation, mortality, and survival were further analyzed. RESULTS: Among the 43 patients, 29 (67.4%) patients had ipsilateral tumors, whereas 14 (32.6%) patients had contralateral tumors. Nine patients with contralateral tumors underwent one-stage surgical treatment, with mean postoperative hospitalization days of 9.8. EGFR mutations were detected in 5 patients with synchronous multiple primary lung adenocarcinomas (SMPLA) for each lesion independently. The results showed different tumors in the same patient could carry different EGFR mutations. The 1- and 3-year overall survival (OS) rates were 97.0% and 76.7%, respectively. Larger maximal tumor dimension (P = 0.015), advanced pN stage (P = 0.002), advanced pT stage (P = 0.046), advanced TNM stage (P = 0.013), and postoperative adjuvant chemotherapy (P = 0.025) were correlated with poor OS. CONCLUSIONS: SMPLC could be considered to be a local disease rather than the systemic disease. Surgical treatment is an effective approach for patients with SMPLC. Mutational status of EGFR could be used as a diagnostic criterion, especially in patients with SMPLA.

Analysis of giant thoracic neoplasms: Correlations between imaging, pathology and surgical management.

BACKGROUND: A giant thoracic neoplasm is extremely rare and poorly understood. Our systemic study introduced computed tomography angiography (CTA) with three-dimensional (3D) reconstruction imaging and evaluated correlations between imaging, pathology, and surgical management. METHODS: Data from 45 patients undergoing surgery for giant thoracic neoplasm in our institution between May 2007 and November 2015 were collected. The clinical characteristics, imaging manifestations, preoperative biopsy, surgical management, postoperative pathology, and prognosis and their correlation were analyzed. RESULTS: The clinical characteristics, imaging manifestations, and pathological types were complicated. Four patients underwent CTA with 3D reconstruction imaging and feeding vessels were found in three cases. Twenty-four selected patients accepted preoperative biopsy, eight of which were inconsistent with postoperative pathology. Complete resection was performed in 39 cases, 20 of which underwent extended excision. The median survival duration of all patients was 58 months (range 3.0-118.0). The one, three, and five-year survival rates were 86.0%, 64.4%, and 47.0%, respectively. Univariate analyses showed tumor size and resection status were prognostic factors for survival (P = 0.003 and P < 0.001, respectively). CONCLUSIONS: A giant thoracic neoplasm should preferably be treated in experienced centers for precise diagnosis and optimal therapy schemes with comprehensive consideration of clinical characters, imaging manifestations, pathology, surgical management, and prognosis. Innovative CTA with 3D reconstruction imaging together with preoperative biopsy are feasible and effective in therapeutic decision-making and surgical planning. Complete surgical resection remains the mainstay of curative therapy for all resectable tumors.

Secondary aorto-esophageal fistula after esophagectomy treated with endovascular treatment: A case report.

RATIONALE: Aorto-esophageal fistula (AEF), a postoperative complication of esophagectomy, constitutes a very small percentage of all cases presenting with AEF; however, it is associated with a high mortality rate. Acute massive hemorrhage is the single largest cause of death in patients developing AEF. There is a lack of consensus on the optimal treatment of AEF. PATIENT CONCERNS: We present 3 cases secondary to esophagectomy due to lower thoracic esophageal carcinoma. All 3 patients presented with similar acute symptoms including a critical and life-threatening course with dead feeling, thoracic pain, and projectile hematemesis, and also hypovolemic shock. DIAGNOSES: Digital subtraction angiography identified AEF as the diagnosis of these 3 cases. INTERVENTIONS: All patients were treated with emergency thoracic endovascular aortic repair, the aortic fistulas were repaired. OUTCOMES: All patients successfully survived the perioperative period. LESSONS: Thoracic endovascular aortic repair, a minimally invasive technique, is a better method to achieve faster and safer hemodynamic stability in patients with AEF compared with open thoracic aortic repair.

[Surgical Treatment and Prognosis for Patients with 
Synchronous Multiple Primary Lung Adenocarcinomas].

BACKGROUND: With the popularization of high-resolution computed tomography (HRCT), there is a rising trend of the detection of multiple primary lung cancers (MPLC). Adenocarcinomas is the major pathological type of MPLC. At present, reports on MPLC are relatively common, but few study focused on synchronous multiple primary lung adenocarcinomas (SMPLA). We carried out this study in an attempt to enhance our understanding about SMPLA. METHODS: Data from 38 patients undergoing surgery for SMPLA in our institution frrom December 2012 and July 2016 were retrospectively collected. RESULTS: Among the 38 patients, 12 patients were male, 26 patients were female, with a median age of 58 (ranging from 39 to 73). Surgical outcomes verified 29 patients with 2 tumors and 9 patients with more than 2 tumors. There were 26 patients with tumors in ipsilateral lung while 12 patients in contralateral lung. Eight patients underwent one-stage surgical treatment for contralateral tumors with mean postoperative hospitalization of 10 days. The gene detection results of 5 patients showed different epidermal growth factor receptor (EGFR) mutations can be found in one patient's different tumors. The 1-year and 3-year overall survival (OS) rate were 96.6% and 74.2%. Larger maximal tumor dimension (P<0.001), advanced pT stage (P=0.003), lymph nodes metastases positive (P=0.001), advanced TNM stage (P=0.022) and postoperative adjuvant chemoradiotherapy (P=0.009) were correlated with poor OS. CONCLUSIONS: Multiple lung malignant lesions should not be taken as metastasis for granted and the possibility of MPLC also should be considered. Mutational status of EGFR could be used as a clinical reference to diagnose patients with SMPLA.

Small activating ribonucleic acid reverses tyrosine kinase inhibitor resistance in epidermal growth factor receptor-mutant lung cancer by increasing the expression of phosphatase and tensin homolog.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (TKI-EGFRs) present a new prospect for the treatment of lung cancer. However, in clinical application, the majority of patients become TKI resistant within a year. More and more studies have shown that a loss of phosphatase and tensin homolog (PTEN) expression is associated with TKI resistance. An alternative method of upregulating PTEN expression may reverse TKI resistance. METHODS: We designed five candidate small activating ribonucleic acids (saRNAs) to target PTEN, and transfected them into H-157 cells to screen out functional saRNA. We used reverse transcriptase-polymerase chain reaction and Western blot to evaluate the effect of saRNA to PTEN expression. We then analyzed the growth and apoptosis of cells transfected with saRNA under the treatment of TKI to investigate whether saRNAs can reverse TKI resistance by upregulating PTEN expression. RESULTS: The functional saRNA we designed could upregulate PTEN expression. The H-157 cells transfected with saRNA grew slower in the presence of TKI drugs than the cells that were not transfected with saRNA. The apoptosis rate was also obviously higher. CONCLUSIONS: Our study proves that loss of PTEN expression is an important mechanism of TKI resistance. It is possible to control TKI resistance by upregulating PTEN expression using RNA activation technology.

Curative effect comparison between Ivor-Lewis esophagectomy and left transthoracic esophagectomy in treatment of middle thoracic esophagus carcinoma.

BACKGROUND/AIMS: The aim of this study is to compare and evaluate the therapeutic efficacy of Ivor-Lewis esophagectomy and one incision esophagectomy through left thoracic and above aortic arch anastomosis approach (left transthoracic esophagectomy) in order to choose a proper surgical procedure to treat middle esophageal carcinoma. METHODOLOGY: Patients who underwent Ivor-Lewis esophagectomy (n=132) and who underwent left transthoracic esophagectomy (n=52) between January 2003 and June 2005 were included. The survival rate was calculated by Kaplan-Meier method and the prognostic risk factors were assessed by Cox regression analysis. RESULTS: Postoperative complications occurred in 43 patients (23.4%), with 31 patients (23.5%) and 12 patients (23.1%) in the Ivor-Lewis group and in the left transthoracic esophagectomy group, respectively. The overall 5-year survival rate was 36.4%, with 37.1% and 34.6% in the Ivor-Lewis group and in the left transthoracic esophagectomy group, respectively (p>0.05). In Cox regression analysis, T classification (HR=1.43, p=0.025) and N classification (HR=1.76, p=0.004) were the independent prognostic risk factors. CONCLUSIONS: Ivor-Lewis esophagectomy and left transthoracic esophagectomy are both feasible options to treat middle thoracic esophageal squamous cell carcinoma. Patients' individual condition is suggested to be taken into account when choosing the operative approach.