Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

cfTrack: A Method of Exome-Wide Mutation Analysis of Cell-free DNA to Simultaneously Monitor the Full Spectrum of Cancer Treatment Outcomes Including MRD, Recurrence, and Evolution.

PURPOSE: Cell-free DNA (cfDNA) offers a noninvasive approach to monitor cancer. Here we develop a method using whole-exome sequencing (WES) of cfDNA for simultaneously monitoring the full spectrum of cancer treatment outcomes, including minimal residual disease (MRD), recurrence, evolution, and second primary cancers. EXPERIMENTAL DESIGN: Three simulation datasets were generated from 26 patients with cancer to benchmark the detection performance of MRD/recurrence and second primary cancers. For further validation, cfDNA samples (n = 76) from patients with cancer (n = 35) with six different cancer types were used for performance validation during various treatments. RESULTS: We present a cfDNA-based cancer monitoring method, named cfTrack. Taking advantage of the broad genome coverage of WES data, cfTrack can sensitively detect MRD and cancer recurrence by integrating signals across known clonal tumor mutations of a patient. In addition, cfTrack detects tumor evolution and second primary cancers by de novo identifying emerging tumor mutations. A series of machine learning and statistical denoising techniques are applied to enhance the detection power. On the simulation data, cfTrack achieved an average AUC of 99% on the validation dataset and 100% on the independent dataset in detecting recurrence in samples with tumor fractions ≥0.05%. In addition, cfTrack yielded an average AUC of 88% in detecting second primary cancers in samples with tumor fractions ≥0.2%. On real data, cfTrack accurately monitors tumor evolution during treatment, which cannot be accomplished by previous methods. CONCLUSIONS: Our results demonstrated that cfTrack can sensitively and specifically monitor the full spectrum of cancer treatment outcomes using exome-wide mutation analysis of cfDNA.

Multi-region sequencing reveals genetic correlation between esophageal squamous cell carcinoma and matched cell-free DNA.

PURPOSE: This study aimed to determine if both ubiquitous and heterogeneous somatic mutations could be detected in circulating cell-free DNA (cfDNA) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Paired multi-regional tumor tissues, cfDNA, and white blood cells (WBCs) were collected from five ESCC patients before treatment, as part of an ongoing prospective study (NCT02395705). Samples from Cohort 1 were sequenced by whole-exome sequencing and samples from Cohort 2 were sequenced by targeted capture sequencing. Somatic single-nucleotide variations (SNVs) were detected by comparing solid tumor or cfDNA with matched WBCs, with a minimum variant allele frequency (VAF) of 0.1% and P value <0.05. RESULTS: Genomic DNA (gDNA) and plasma-derived cfDNA from 26 samples were sequenced successfully. In Cohort 1, a significant linear relationship between the tumor and cfDNA VAFs (R2= 0.78, P < 0.0001) was found. In Cohort 2, cfDNA could recover an average of 60.7% (31/51; range, 35.7-76.2%) of somatic mutations present in matched solid tumors. There was a significant positive correlation in VAFs between cfDNA and matched solid tumor tissues (R2= 0.92, P < 0.0001). CONCLUSIONS: Both sequencing approaches revealed high intratumoral heterogeneity in ESCC, and enabled the detection of both ubiquitous and heterogeneous mutations in cfDNA.

Sensitive detection of tumor mutations from blood and its application to immunotherapy prognosis.

Cell-free DNA (cfDNA) is attractive for many applications, including detecting cancer, identifying the tissue of origin, and monitoring. A fundamental task underlying these applications is SNV calling from cfDNA, which is hindered by the very low tumor content. Thus sensitive and accurate detection of low-frequency mutations (<5%) remains challenging for existing SNV callers. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this challenge. Furthermore, by leveraging cfDNA's comprehensive coverage of tumor clonal landscape, cfSNV can profile mutations in subclones. In both simulated and real patient data, cfSNV outperforms existing tools in sensitivity while maintaining high precision. cfSNV enhances the clinical utilities of cfDNA by improving mutation detection performance in medium-depth sequencing data, therefore making Whole-Exome Sequencing a viable option. As an example, we demonstrate that the tumor mutation profile from cfDNA WES data can provide an effective biomarker to predict immunotherapy outcomes.

Liquid biopsy for esophageal cancer: Is detection of circulating cell-free DNA as a biomarker feasible?

Esophageal cancer (EC) is a common cancer and is histopathologically classified into esophageal squamous cell carcinoma and esophageal adenocarcinoma. EC is a worldwide public health issue because of late diagnosis and lack of effective therapy. In contrast to standard tumor biopsies, liquid biopsies are emerging as a tool which is minimally invasive that can complement or even substitute more classical approaches. Specifically, cell-free DNA (cfDNA) has shown promise in cancer-related clinical applications. Indeed, cfDNA has been shown to be an effective circulating biomarker for non-invasive cancer diagnosis and monitoring of cancer patients. Although the clinical application of cfDNA has been reported on other cancers, few studies have evaluated its use in EC. Here, we review this relevant literature and discuss limitations and advantages of its application in the diagnosis and monitoring of EC.

Utility of isocitrate dehydrogenase 1 as a serum protein biomarker for the early detection of non-small-cell lung cancer: A multicenter in vitro diagnostic clinical trial.

We aimed to verify the expression status and diagnostic significance of isocitrate dehydrogenase 1 (IDH1) in non-small-cell lung cancer (NSCLC), especially during early stages. Serum IDH1 levels were measured by ELISA. A total of 1223 participants (660 patients with NSCLC, 276 healthy controls [HCs], 95 patients with benign pulmonary conditions [BPCs], 135 patients with other cancers [OCs], and 57 samples with interfering factors) were divided into a training cohort and a validation cohort according to 3 testing centers. The IDH1 concentrations in the NSCLC group were obviously higher than those in the control groups (P < .001). Area under the receiver operating characteristic curves (AUCs) for discriminating NSCLC patients from controls (HC, BPC, and OC) were 0.870 and 0.745 (sensitivity, 63.3% and 55.0%; specificity, 86.8% and 86.3%) in the training cohort and validation cohort, respectively. The AUCs for discriminating stage 0-IA lung cancer patients from HCs were 0.907 and 0.788 (sensitivity, 58.6% and 59.1%; specificity, 92.9% and 89.3%) in 2 cohorts, respectively. Isocitrate dehydrogenase 1 showed specificity for NSCLC and had no diagnostic value for other common cancers. Furthermore, IDH1 was significantly reduced in postoperative serum. Isocitrate dehydrogenase 1 shows clinical utility as a serum protein biomarker for the early diagnosis of NSCLC.

Acetyl-macrocalin B suppresses tumor growth in esophageal squamous cell carcinoma and exhibits synergistic anti-cancer effects with the Chk1/2 inhibitor AZD7762.

Natural products derived from herbal medicines have become a major focus of anti-cancer drug discovery studies. Acetyl-macrocalin B (A-macB) is an ent-diterpenoid isolated from Isodon silvatica. This study aimed to examine the effect and molecular action of A-macB in esophageal squamous cell carcinoma (ESCC) and explore possible drug synergistic modalities. A-macB induced cellular reactive oxygen species (ROS) generation, initiated the p38 mitogen-activated protein kinase (MAPK) signaling pathway, and triggered the caspase-9-dependent apoptosis cascade in ESCC cells. The ROS scavenger N-acetylcysteine (NAC) and the specific p38 inhibitor SB203580 reversed the effects of A-macB on the p38 network and thus rescued ESCC cells from apoptosis. The cellular ROS increase was at least partially due to the suppression of glutathione-S-transferase P1 (GSTP1) by A-macB. A-macB also upregulated the Chk1/Chk2-Cdc25C/Cdc2/Cyclin B1 axis to induce G2/M phase arrest. The cell growth inhibition induced by A-macB was further enhanced by AZD7762, a specific Chk1/Chk2 inhibitor, with a combination index (CI) of <1. Moreover, A-macB efficiently suppressed xenograft growth without inducing significant toxicity, and AZD7762 potentiated the effects of A-macB in the suppression of tumor growth in vivo. Taken together, A-macB is a promising lead compound for ESCC and exerts synergistic anti-cancer effects with AZD7762.

Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and novel effective drugs against NSCLC are urgently needed. Isodon species are rich in ent-kaurane diterpenoids that have been reported to have antitumor bioactivity. Acetyl-macrocalin B (A-macB) is a novel ent-kaurane diterpenoid isolated from Isodon silvatica, and its antitumor efficacy against NSCLC and the underlying mechanisms were scrutinized in depth. The viability of cells treated with A-macB was detected by CCK-8 and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. The mechanisms were investigated by detecting ROS and performing western blotting and verification experiments with specific inhibitors. The in vivo effect of A-macB was explored in a nude mouse xenograft model. A-macB effectively inhibited H1299 and A549 cell viability, triggered apoptosis and delayed cells in the G2/M phase. A-macB induced cellular ROS production and then activated the p38 MAPK-mediated, caspase 9-dependent apoptotic pathway. Both the ROS scavenger NAC and the specific p38 inhibitor SB203580 inactivated the function of p38 induced by A-macB, thus preventing cells from apoptosis. A-macB activated the Chk1/2-Cdc25C-Cdc2/cyclin B1 axis to induce G2/M phase arrest. AZD7762 abrogated the function of Chk1/2, abolished the G2/M delay and enhanced the cytotoxicity of A-macB. Moreover, A-macB efficiently suppressed tumor growth in a mouse xenograft model without noticeable toxicity to normal tissues. Having both efficacy and relative safety, A-macB is a potential lead compound that is worthy of further exploration for development as an anticancer agent.

Rabdocoestin B exhibits antitumor activity by inducing G2/M phase arrest and apoptosis in esophageal squamous cell carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is generally resistant to chemotherapy. In the present study, the cytotoxic activity of Rabdocoestin B (Rabd-B) against ESCC and the underlying mechanisms were investigated. METHODS: The inhibitory effect of Rabd-B on KYSE30 and KYSE450 was evaluated by Cell Counting Kit-8 (CCK8) and colony formation assays in vitro. The cell cycle distribution and apoptosis of cells treated with Rabd-B were determined by flow cytometry. The mechanisms underlying the effects of Rabd-B were systematically examined by Western blot. The in vivo anti-tumor ability of Rabd-B was measured in mouse xenograft models and cisplatin (DDP) was used as positive control. RESULTS: Rabd-B efficiently induced G2/M phase arrest in ESCC cells by upregulating the Chk1/Chk2-Cdc25C axis to inhibit the G2→M transition facilitated by Cdc2/Cyclin B1. Furthermore, Rabd-B suppressed ATM/ATR phosphorylation, thereby inhibiting BRCA1-mediated DNA repair, which resulted in mitotic catastrophe and induced cell apoptosis. Rabd-B also decreased the activity of the Akt and NF-κB survival signaling pathways and ultimately initiated the caspase-9-dependent intrinsic apoptotic pathway in ESCC cells. The apoptosis induced by Rabd-B could be partially reversed by a caspase-9-specific inhibitor (Z-LEHD-FMK) and a pan-caspase inhibitor (Z-VAD-FMK). Moreover, Rabd-B effectively suppressed tumor growth in mouse xenografts which was comparable to that of DDP without significant injuries to the mice. CONCLUSION: Taken together, these findings indicate that Rabd-B is a promising precursor compound that may be useful as a treatment for ESCC and thus warrants further investigation.

The therapeutic effects of Longikaurin A, a natural ent-kauranoid, in esophageal squamous cell carcinoma depend on ROS accumulation and JNK/p38 MAPK activation.

Effective treatments for esophageal squamous cell carcinoma (ESCC), one of the most common cancers in China, are lacking. Longikaurin A (LK-A), an ent-kauranoid diterpenoid isolated from Isodon ternifolius, has been shown to have potent cytotoxic effects on ESCC cells both in vivo and in vitro, mainly by inducing apoptosis. In this study, LK-A inhibited ESCC cells viability and induced G2/M cell cycle arrest. Moreover, LK-A was also highly effective in a KYSE-30 xenograft nude mouse model. Treatment with Z-VAD(OMe)-FMK partially attenuated LK-A-induced apoptosis. LK-A significantly induced reactive oxygen species (ROS) production in ESCC cells, and LK-A-induced apoptosis was attenuated by the ROS scavenger N-acetyl cysteine (NAC). Furthermore, we found that treatment with LK-A activated both the JNK and p38 MAPK signaling pathways, resulting in increases in ROS levels and apoptosis induction. Taken together, these findings indicate that LK-A exerts novel anti-tumor effects in ESCC cells by activating the JNK and p38 MAPK pathways and inducing increases in ROS production, which suggest that the compound may have potential as a clinical therapeutic agent.

Long-term outcomes of 307 patients after complete thymoma resection.

BACKGROUND: Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection. METHODS: We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan-Meier survival analyses. RESULTS: During follow-up (median, 86 months; range, 24-160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resection had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017). CONCLUSIONS: Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

Prognostic value of preoperative serum lactate dehydrogenase in thymic carcinoma.

BACKGROUND: The prognostic value of serum lactate dehydrogenase (LDH) has been demonstrated in various solid tumors. We attempted to determine whether serum LDH was predictive of survival in thymic carcinoma after surgical resection. METHODS: Ninety-five patients with thymic carcinoma treated in our hospital between January 2005 and December 2015 were retrospectively enrolled. Serum LDH was measured before surgery and categorized as low or high relative to the upper limit of normal (ULN) (225 U/L). The relationships of serum LDH level and other clinical variables with survival were estimated by Cox regression and Kaplan-Meier survival analysis. RESULTS: Serum LDH levels were found to be significantly associated with overall survival (OS) and progression-free survival (PFS) of these patients. The 1-, 3-, and 5-year PFS were 76%, 51%, and 38%, and the 1-, 3- and 5-year OS were 97%, 75%, and 46%, respectively. Univariate analysis found that high serum LDH (>225 U/L) was associated with both lower OS [hazard ratio (HR) =2.710; 95% confidence interval (CI): 1.363-1.5.391; P=0.004] and PFS (HR =3.365; 95% CI: 1.776-6.374; P<0.001). Multivariate analysis found that high serum LDH was associated with lower PFS (HR =2.122; 95% CI: 1.056-4.267; P=0.035). Moreover, high LDH was significantly associated with advanced Masaoka stage (P=0.001). CONCLUSIONS: High serum LDH (>225 U/L) was an independent predictor of decreased PFS in thymic carcinoma patients. It was also significantly associated with reduced OS, but was not an independent predictor of death in those patients.

Prognostic value of preoperative neutrophil-lymphocyte ratio is superior to platelet-lymphocyte ratio for survival in patients who underwent complete resection of thymic carcinoma.

BACKGROUND: Preoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have prognostic value in patients with various operable tumors. The aim of our study was to determine whether NLR and PLR are predictive of survival in thymic carcinoma patients after complete resection. METHODS: A total of seventy-nine patients who underwent complete resection of thymic carcinoma at our hospital between January 2005 and December 2015 were retrospectively enrolled. Differential leukocyte counts were collected before surgery, and the relationships of NLR, PLR, and other patient clinical variables with survival were estimated by Cox regression analysis and Kaplan-Meier survival analysis. RESULTS: Univariate analysis found that a high level of NLR was associated with lower disease-free survival (DFS) (HR: 3.385, 95% CI: 1.073-10.678, P=0.037) and lower overall survival (OS) (HR: 12.836, 95% CI: 1.615-101.990, P=0.016). The optimal NLR threshold of 4.1 could stratify the patients with high risk of recurrence or metastasis (P=0.026) and death (P=0.006). Meanwhile, the NLR value of >4.1 in those patients was associated with bigger tumor size (P=0.035) and more advanced Masaoka stages (P=0.040) compared with NLR ≤4.1. However, the PLR and other variables were not significantly associated with survival in thymic carcinoma patients. CONCLUSIONS: The preoperative NLR of >4.1 was significantly associated with larger tumor size, more advanced Masaoka stages and reduced DFS and OS, but was not an independent predictor of survival in thymic carcinoma patients after complete resection.

Open three-stage transthoracic oesophagectomy versus minimally invasive thoraco-laparoscopic oesophagectomy for oesophageal cancer: protocol for a multicentre prospective, open and parallel, randomised controlled trial.

INTRODUCTION: Oesophageal cancer is the eighth most common cause of cancer worldwide. In 2009 in China, the incidence and death rate of oesophageal cancer was 22.14 per 100 000 person-years and 16.77 per 100 000 person-years, respectively, the highest in the world. Minimally invasive oesophagectomy (MIO) was introduced into clinical practice with the aim of reducing the morbidity rate. The mechanisms of MIO may lie in minimising the reaction to surgical injury and inflammation. There are some randomised trials regarding minimally invasive versus open oesophagectomy, with 100-850 subjects enrolled. To date, no large randomised controlled trial comparing minimally invasive versus open oesophagectomy has been reported in China, where squamous cell carcinoma predominated over adenocarcinoma of the oesophagus. METHODS AND ANALYSIS: This is a 3 year multicentre, prospective, randomised, open and parallel controlled trial, which aims to compare the effectiveness of minimally invasive thoraco-laparoscopic oesophagectomy to open three-stage transthoracic oesophagectomy for resectable oesophageal cancer. Group A patients receive MIO which involves thoracoscopic oesophagectomy and laparoscopic gastric mobilisation with cervical anastomosis. Group B patients receive the open three-stage transthoracic oesophagectomy which involves a right thoracotomy and laparotomy with cervical anastomosis. Primary endpoints include respiratory complications within 30 days after operation. The secondary endpoints include other postoperative complications, influences on pulmonary function, intraoperative data including blood loss, operative time, the number and location of lymph nodes dissected, and mortality in hospital, the length of hospital stay, total expenses in hospital, mortality within 30 days, survival rate after 2 years, postoperative pain, and health-related quality of life (HRQoL). Three hundred and twenty-four patients in each group will be needed and a total of 648 patients will finally be enrolled into the study. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Ethics Committees of all participating institutions. The findings of this trial will be disseminated to patients and through peer-reviewed publications and international presentations. TRIAL REGISTRATION NUMBER: NCT02355249.

Over-expression of small ubiquitin-like modifier proteases 1 predicts chemo-sensitivity and poor survival in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. Despite the advances in therapy over the years, its mortality remains high. The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression. We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients. METHODS: A SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells. VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR). Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed. RESULTS: VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues. Inhibition of SENP1 by siRNA was associated with decreased VEGF expression. SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%, 38.2%, and 58.2% in high, moderate and low differentiated tumors, respectively, P = 0.046), higher T stage (10.9% in T1, and 89.1% in T2 and T3 tumor samples, P < 0.001) and TNM stage (10.9% in stage I, and 89.1% in stages II and III tumor samples, P < 0.001). The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%, P < 0.001). Sixty three patients received postoperative chemotherapy, including 34 with SENP1 over-expression and 29 with SENP1 low expression. Among the 34 patients with SENP1 over-expression, 22 (64.7%) patients developed recurrence or metastasis, significantly higher than those in the low expression group 27.6% (8/29) (P = 0.005). Multivariate Cox regression analysis showed that lymph node metastasis (P = 0.015), TNM stage (P = 0.001), and SENP1 expression level (P = 0.002) were independent prognostic factors for the survival of NSCLC patients. CONCLUSIONS: SENP1 may be a promising predictor of survival, a predictive factor of chemo-sensitivity for NSCLC patients, and potentially a desirable drug target for lung carcinoma target therapy.

Comparative study of video-assisted thoracic surgery versus open thymectomy for thymoma in one single center.

BACKGROUND: Due to the popularity of video-assisted thoracic surgery (VATS) techniques in clinical, thymoma patients via VATS thymectomy are increasing rapidly. However, compared with open thymectomy, the potential superiorities and defects of VATS thymectomy remain controversial. METHODS: A number of 129 patients who underwent thymectomy of early stage thymoma (Masaoka stage I and stage II) in one single center from January 2007 to September 2013 were selected in this retrospective study. Of those patients, 38 thymoma patients underwent VATS thymectomy (VATS group) and 91 underwent open thymectomy (open group) via either transsternal [44] or transthoracic approach [47] in the same period. The postoperative variables, which included postoperative hospital length of stay (LOS), the intensive care unit (ICU) LOS, the entire resection ratio, the number of thoracic drainage tubes, the quantity of output and duration of drainage, were analyzed. Meanwhile, the operation time and blood loss were considered as intraoperative variables. RESULTS: All thymoma patients in the analysis included 19 thymoma patients with myasthenia gravis, among which five patients via VATS thymectomy and 14 patients via open thymectomy respectively. There was no death or morbidity due to the surgical procedures perioperatively. The ICU LOS, operation time, entire resection ratio, and the number of chest tubes were not significantly different in two groups. The postoperative hospital LOS of VATS thymectomy was shorter than that of open thymectomy (5.26 versus 8.32 days, P<0.001). The blood loss of VATS thymectomy was less than open thymectomy (114.74 versus 194.51 mL, P=0.002). Postoperatively, the quantity of chest tubes output in VATS group was less than that in open thymectomy group (617.86 versus 850.08 mL, P=0.007) and duration of drainage in VATS group was shorter than that in open thymectomy group (3.87 versus 5.22 days, P<0.001). CONCLUSIONS: VATS thymectomy is a safe and practicable treatment for early-stage thymoma patients. Thymoma according with Masaoka staging I-II without evident invading seems to be performed through VATS approach appropriately, which has shorter postoperative hospital LOS, less blood loss and less restrictions to activities, hence patients will recover sooner.

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.