Predictors of adherence, contamination and dropout in home-based walking by lung and oesophageal cancer patients from two randomised control trials: An exploratory study.

OBJECTIVES: In this study, we examined predictors of exercise adherence, contamination and dropout in lung and oesophageal cancer patients who participated in two randomised controlled trials. METHODS: We used data on 188 lung and oesophageal cancer patients from two previous studies (intervention: moderate-intensity walking for 12 weeks). Baseline measurements included demographic variables, disease characteristics, Hospital Anxiety and Depression Scale and Bouchard 3-day physical activity (PA) record. We used multiple linear and logistic regressions to analyse predictors of exercise adherence in the walking group, contamination in the control group and dropout in both groups. RESULTS: Pre-intervention exercise habits and baseline depression scores predicted adherence, with an explanatory power of 16.7% (p < 0.0001). Pre-intervention exercise habits (odds ratio [OR] 19.65, 95% confidence interval [CI] 2.76-139.97), baseline moderate PA (min/day) (OR 1.03, 95% CI 1.01-1.05) and baseline vigorous PA (min/day) (OR 1.09, 95% CI 1.01-1.18) predicted contamination. Baseline mild PA (10 min/day) (OR 0.94, 95% CI 0.89-0.99) predicted dropout. CONCLUSIONS: Pre-intervention exercise habits and baseline depression levels predicted exercise adherence in the walking group. In the control group, pre-intervention exercise habits and baseline moderate and vigorous PA predicted contamination. Baseline mild PA predicted dropout rates in both groups.

Taiwan Society of Colon and Rectal Surgeons (TSCRS) Consensus for Cytoreduction Selection in Metastatic Colorectal Cancer.

BACKGROUND: Taiwan has witnessed a surge in the incidence of colorectal cancer (CRC), of which 40-60% metastasize. Continuous updating of cytoreductive strategies in metastatic CRC (mCRC) has contributed to median overall survival reaching 40 months. In this changing scenario, to standardize the approaches across Taiwan, a group of experts from the Taiwan Society of Colon and Rectal Surgeons (TSCRS) convened to establish evidence- and opinion-based recommendations for defining the criteria of "resectability" in mCRC. METHODS: Over the course of one-on-one consultations, lasting 30-40 min each, with 30 medical specialists (19 colorectal surgeons, 4 general surgeons, and 7 medical oncologists) from 16 hospitals in Taiwan followed by a 2-h meeting with 8 physician experts (3 general surgeons, 4 colorectal surgeons, and 1 thoracic surgeon), 12 key questions on cytoreduction were addressed. This was further contextualized based on published literature. RESULTS: The final consensus includes eight recommendations regarding the criteria for metastasis resection, role of local control treatment in liver potentially resectable patients, management of synchronous liver metastases, approach for peritoneal metastasis, place for resection in multiple-organ metastasis, and general criteria for resectability. CONCLUSIONS: mCRC patients undergoing R0 resection have the greatest survival advantage following surgery. Our role as a multidisciplinary team (MDT) should be to treat potentially resectable mCRC patients as rapidly and safely as possible, and achieve R0 resection as far as possible and for as long as possible (continuum of care). This TSCRS consensus statement aims to help build clinical capacity within the MDTs, while making better use of existing healthcare resources.

Gene Expression Profile in Primary Tumor Is Associated with Brain-Tropism of Metastasis from Lung Adenocarcinoma.

Lung adenocarcinoma has a strong propensity to metastasize to the brain. The brain metastases are difficult to treat and can cause significant morbidity and mortality. Identifying patients with increased risk of developing brain metastasis can assist medical decision-making, facilitating a closer surveillance or justifying a preventive treatment. We analyzed 27 lung adenocarcinoma patients who received a primary lung tumor resection and developed metastases within 5 years after the surgery. Among these patients, 16 developed brain metastases and 11 developed non-brain metastases only. We performed targeted DNA sequencing, RNA sequencing and immunohistochemistry to characterize the difference between the primary tumors. We also compared our findings to the published data of brain-tropic and non-brain-tropic lung adenocarcinoma cell lines. The results demonstrated that the targeted tumor DNA sequencing did not reveal a significant difference between the groups, but the RNA sequencing identified 390 differentially expressed genes. A gene expression signature including CDKN2A could identify 100% of brain-metastasizing tumors with a 91% specificity. However, when compared to the differentially expressed genes between brain-tropic and non-brain-tropic lung cancer cell lines, a different set of genes was shared between the patient data and the cell line data, which include many genes implicated in the cancer-glia/neuron interaction. Our findings indicate that it is possible to identify lung adenocarcinoma patients at the highest risk for brain metastasis by analyzing the primary tumor. Further investigation is required to elucidate the mechanism behind these associations and to identify potential treatment targets.

AKT1 internal tandem duplications and point mutations are the genetic hallmarks of sclerosing pneumocytoma.

Sclerosing pneumocytoma is a unique benign neoplasm of the lungs. The molecular alterations in sclerosing pneumocytoma are not well understood. In a previous whole-exome sequencing study, recurrent AKT1 point mutation was observed in about half of the cases of sclerosing pneumocytoma. However, in the remaining half, cancer-related mutations have still not been identified. In this study, we first analyzed the raw sequence data from the previous whole-exome sequencing study (PRJNA297066 cohort). Using Genomon-ITDetector, a special software for detection of internal tandem duplications, we identified recurrent internal tandem duplications in the AKT1 gene in 22 of the 44 tumor samples (50%). All the cases positive for AKT1 internal tandem duplications lacked AKT1 point mutations. Next, we performed targeted next-generation sequencing in an independent cohort of sclerosing pneumocytoma from our hospital (VGH-TPE cohort), and again identified recurrent AKT1 internal tandem duplications in 20 of the 40 (50%) tumor samples analyzed. The internal tandem duplications resulted in duplications of 7 to 16 amino acids in a narrow region of the Pleckstrin homology domain of the AKT1 protein. This region contains the interaction interface between the Pleckstrin homology and kinase domains, which is known to play a critical role in the activation of the AKT1 protein. Moreover, we found that AKT1 internal tandem duplications were mutually exclusive of other forms of AKT1 mutations, including point mutations and short indels. Taking all forms of AKT1 mutations together, we detected AKT1 mutations in almost all the sclerosing pneumocytomas in our study (PRJNA297066 cohort: 41 out of 44 cases, 93%; VGH-TPE cohort: 40 out of 40 cases, 100%). Our results suggest that AKT1 mutation is the genetic hallmark of sclerosing pneumocytoma. These results would help in better understanding of the pathogenesis of sclerosing pneumocytoma.

CT-Guided Core Biopsy for Peripheral Sub-solid Pulmonary Nodules to Predict Predominant Histological and Aggressive Subtypes of Lung Adenocarcinoma.

BACKGROUND: Adenocarcinoma is the most common type of lung cancer, and pre-operative biopsy plays an important role to determine its major subtypes. As proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) in 2011, the predominant histological subtype of adenocarcinoma is an indicator of outcomes and recurrence rate. However, the value of CT-guided core biopsy in predicting the predominant subtype and detecting the presence of an aggressive subtype of adenocarcinoma, peripheral sub-solid nodule, has less been discussed. METHODS: We retrospectively reviewed 318 consecutive peripheral sub-solid nodules that underwent percutaneous CT-guided lung biopsy and surgical resection, between October 2015 and December 2018 and were diagnosed as adenocarcinoma with histological subtype. The subtyping results from biopsy and surgical pathology were compared to evaluate the concordance rate. RESULTS: The overall concordance rate between biopsy and surgical pathology in determining the predominant histological subtype was 64%. Better concordance was found in small tumors (≤ 2 cm), in predicting either predominant histology (χ2 = 7.091, P = 0.008) or high grade adenocarcinoma, micropapillary and/or solid subtype, MIP-SOL (χ2 = 22.301, P < 0.001). The analysis of ground glass opacity (GGO) component (C/T ratio) obtained significantly higher accuracy in the pure GGO group than in the other two groups in predicting predominant histology or high grade adenocarcinoma (χ2 = 17.560, P < 0.001 and χ2 = 61.938, P < 0.001, respectively). CONCLUSIONS: CT-guided core biopsies provide additional value in predicting the histological subtype of lung adenocarcinoma after surgical resection, especially in small tumors (≤ 2 cm) or an initially pure GGO group.

The Prognostic Impact of Extracapsular Lymph Node Involvement in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The role of extracapsular lymph node involvement (ELNI) in esophageal cancer has not been fully investigated. We aim to assess its incidence and prognostic significance in patients with esophageal squamous cell carcinoma (ESCC) treated with and without neoadjuvant treatments. METHODS: Data of patients who underwent esophagectomy for ESCC in a single medical center was retrospectively reviewed. Patients with positive lymph node involvement were classified as either with ELNI or without ELNI (intracapsular lymph node involvement, ILNI). The impact of ELNI on overall survival (OS), disease-free survival (DFS), and disease recurrence was analyzed. RESULTS: A total of 336 patients, including 179 without (NCRT -) and 157 with (NCRT +) neoadjuvant chemoradiotherapy, were included. Seventy-two of 179 (40.2%) patients in NCRT - group were with positive lymph node, of whom 19 (26.4%) had ELNI, whereas 49 (31.2%) patients in NCRT + group had positive lymph node, of whom 25 (51.0%) had ELNI. In NCRT + group, patients with ELNI had worse outcome compared to those with ILNI in 5-year OS (10.4 vs. 13.8%, p = 0.008), and DFS (5.3 vs. 17.5%, p = 0.008). The presence of ELNI was also associated with more distant recurrence (p = 0.03). In contrast, there was no survival difference between patients with ELNI and ILNI in NCRT - group. CONCLUSIONS: Compared with ILNI, ELNI is a significant poor prognostic factor in patients with ESCC treated with neoadjuvant treatments, but not in those with primary surgery.

Relationships of exercise timing with sleep, fatigue and rest-activity rhythms of lung cancer patients in Taiwan: An exploratory study.

OBJECTIVE: To explore the relationship of exercise timing (exercising close to bedtime, exercising in daylight and maintaining fixed exercise schedule) with sleep quality, fatigue and rest-activity rhythms among lung cancer patients in Taiwan. METHODS: Results from 43 lung cancer patients who were assigned and adhered to the exercise intervention in a 12-week randomised controlled trial were analysed. The MD Anderson Symptom Inventory and Pittsburgh Sleep Quality Index (PSQI) were administered. Actigraphs were used to assess rest-activity rhythms (in-bed less than out-of-bed dichotomy index, I < O) and objective sleep parameters, including total sleep time (TST) and sleep onset latency (SOL). RESULTS: Patients who exercised >4 hr before bedtime had significant improvement in fatigue (p < .0001), sleep quality (p = .012 for PSQI; p = .037 for TST; p = .017 for SOL) and rest-activity rhythms (p = .048 for I < O). Furthermore, patients who exercised with daylight exposure had a significant improvement in fatigue (p = .037) and sleep quality (p = .039 for PSQI). CONCLUSIONS: Exercising >4 hr before bedtime with daylight exposure is associated with improvement in rest-activity rhythms, sleep quality and fatigue in lung cancer patients. The causal relationship requires further investigation with experimental design.

Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression.

Nicotine in tobacco smoke is considered carcinogenic in several malignancies including lung cancer. The high incidence of lung adenocarcinoma (LAC) in non-smokers, however, remains unexplained. Although LAC has long been less associated with smoking behavior based on previous epidemiological correlation studies, the effect of environmental smoke contributing to low-dose nicotine exposure in non-smoking population could be underestimated. Here we provide experimental evidence of how low-dose nicotine promotes LAC growth in vitro and in vivo. Screening of nicotinic acetylcholine receptor subunits in lung cancer cell lines demonstrated a particularly high expression level of nicotinic acetylcholine receptor subunit α5 (α 5-nAChR) in LAC cell lines. Clinical specimen analysis revealed up-regulation of α 5-nAChR in LAC tumor tissues compared to non-tumor counterparts. In LAC cell lines α 5-nAChR interacts with epidermal growth factor receptor (EGFR), positively regulates EGFR pathway, enhances the expression of epithelial-mesenchymal transition markers, and is essential for low-dose nicotine-induced EGFR phosphorylation. Functionally, low-dose nicotine requires α 5-nAChR to enhance cell migration, invasion, and proliferation. Knockdown of α 5-nAChR inhibits the xenograft tumor growth of LAC. Clinical analysis indicated that high level of tumor α 5-nAChR is correlated with poor survival rates of LAC patients, particularly in those expressing wild-type EGFR. Our data identified α 5-nAChR as an essential mediator for low-dose nicotine-dependent LAC progression possibly through signaling crosstalk with EGFR, supporting the involvement of environmental smoke in tumor progression in LAC patients.

The role of bile acids in cellular invasiveness of gastric cancer.

BACKGROUND: Bile acids have been implicated in the development of digestive tract malignancy by epidemiological, clinical and animal studies. The growth and transformation signaling by most of the bile acids is thought to be related to the induced cyclooxygenase-2 (COX-2) expression and increased production of prostaglandin E2 (PGE2). The highly hydrophobic bile acids such as chenodeoxycholic acid (CD) and deoxycholic acid can promote carcinogenesis and stimulate the invasion of colon cancer cells. On the contrary, ursodeoxycholic acid (UDCA), a less hydrophobic stereoisomer of CD, inhibits proliferation and induces apoptosis in colon cancer cells. We examined the effects of bile acid on human gastric cancer cells MKN-74. METHODS: Early-passage human gastric cancer MKN-74 cells were used for drug treatment, preparation of whole cell lysates, subcellular extracts and Western blot analysis. The levels of PGE2 released by the cells were measured by enzyme inummoassay to indicate COX-2 enzymatic activity. Cellular invasion assay was performed in Boyden chamber. RESULTS: Exposure of CD led to activation of protein kinase C (PKC) alpha, increased COX-2 expression and increased PGE2 synthesis. The induced COX-2 protein expression could be detected within 4 h exposure of 200 µM CD, and it was dose- and time-dependent. PGE2 is the product of COX-2, and has been reported to cause tumor invasion and angiogenesis in animal study. Safingol (SAF), a PKC inhibitor, suppressed the COX-2 protein expression and PGE2 production by CD in MKN-74. Furthermore, UDCA suppressed PGE2 production by CD but did not affect COX-2 protein expression induced by CD. Using a Boyden chamber invasion assay, both SAF and UDCA impeded CD induced tumor invasiveness of MKN-74 by 30-50%. CONCLUSIONS: Our results indicate that signaling of hydrophobic bile acid such as CD in gastric cancer cells is through PKC activation and COX-2 induction, which leads to increased cellular invasion. By perturbing the bile acid pool, UDCA attenuates CD-induced PGE2 synthesis and tumor invasiveness.

Prognostic histological factors in patients with esophageal squamous cell carcinoma after preoperative chemoradiation followed by surgery.

BACKGROUND: Pathological response is an important marker for tumor aggressiveness in patients with esophageal squamous cell carcinoma (ESCC) who receive preoperative chemoradiation followed by esophagectomy. We aim to evaluate the prognostic value of histological factors after trimodality treatments. METHODS: 91 patients who received preoperative chemoradiation followed by transthoracic esophagectomy between 2009 and 2014 were included. The pathological examination was reviewed. Overall survival and disease free survival were recorded. Survival analysis was performed using the Cox regression model, and the survival curves were compared by the log-rank test. RESULTS: Survival analysis showed lymphovascular invasion (LVI, hazard ratio [HR]: 2.009, p = 0.029), perineural invasion (PNI, HR: 2.226, p = 0.019), ypN stage (HR: 2.041, p = 0.019), extracapsular invasion (ECI, HR: 2.804, p = 0.003), and incomplete resection (HR: 1.897, p = 0.039) as unfavorable prognostic factors affecting overall survival (OS). Moreover, tumor regression grade (TRG, HR: 1.834, p = 0.038), LVI (HR: 1.975, p = 0.038), ECI (HR: 2.836, p = 0.003), and incomplete resection (HR: 2.254, p = 0.007) adversely affected disease-free survival (DFS). Prognostic classification based on poor primary tumor (TRG2/3, LVI(+), and PNI (+)), lymph node (ypN(+) and ECI(+)), and surgical (incomplete resection) factors significantly predicts OS (p = 0.013) and DFS (p = 0.017). However, the use of postoperative adjuvant therapy was not a significant prognostic factor even in medium- and high-risk ESCC patients who underwent trimodality treatments. CONCLUSIONS: Histological factors, including primary tumor, lymph node, and surgical factors has high prognostic value for predicting outcomes in ESCC patients receiving preoperative chemoradiation followed by surgery.

Effect of walking on circadian rhythms and sleep quality of patients with lung cancer: a randomised controlled trial.

BACKGROUND: Sleep disturbances and poor rest-activity rhythms, which can reduce the quality of life, are highly prevalent among patients with lung cancer. METHODS: This trial investigated the effects of a 12-week exercise intervention including home-based walking exercise training and weekly exercise counseling on 111 lung cancer patients. Participants were randomly allocated to receive the intervention or usual-care. Outcomes included objective sleep (total sleep time, TST; sleep efficiency, SE; sleep onset latency, SOL; and wake after sleep onset, WASO), subjective sleep (Pittsburgh Sleep Quality Index, PSQI), and rest-activity rhythms (r24 and I

Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data.

BACKGROUND: Few studies have investigated prognostic biomarkers of distant metastases of lung cancer. One of the central difficulties in identifying biomarkers from microarray data is the availability of only a small number of samples, which results overtraining. Recently obtained evidence reveals that epithelial-mesenchymal transition (EMT) of tumor cells causes metastasis, which is detrimental to patients' survival. RESULTS: This work proposes a novel optimization approach to discovering EMT-related prognostic biomarkers to predict the distant metastasis of lung cancer using both microarray and survival data. This weighted objective function maximizes both the accuracy of prediction of distant metastasis and the area between the disease-free survival curves of the non-distant and distant metastases. Seventy-eight patients with lung cancer and a follow-up time of 120 months are used to identify a set of gene markers and an independent cohort of 26 patients is used to evaluate the identified biomarkers. The medical records of the 78 patients show a significant difference between the disease-free survival times of the 37 non-distant- and the 41 distant-metastasis patients. The experimental results thus obtained are as follows. 1) The use of disease-free survival curves can compensate for the shortcoming of insufficient samples and greatly increase the test accuracy by 11.10%; and 2) the support vector machine with a set of 17 transcripts, such as CCL16 and CDKN2AIP, can yield a leave-one-out cross-validation accuracy of 93.59%, a test accuracy of 76.92%, a large disease-free survival area of 74.81%, and a mean survival prediction error of 3.99 months. The identified putative biomarkers are examined using related studies and signaling pathways to reveal the potential effectiveness of the biomarkers in prospective confirmatory studies. CONCLUSIONS: The proposed new optimization approach to identifying prognostic biomarkers by combining multiple sources of data (microarray and survival) can facilitate the accurate selection of biomarkers that are most relevant to the disease while solving the problem of insufficient samples.

Percutaneous cryoablation for inoperable malignant lung tumors: midterm results.

OBJECTIVE: To retrospectively analyze the efficacy and short- to mid-term survival rate of cryoablation for malignant lung tumors. METHODS: Percutaneous CT-guided cryoablation for 45 malignant lung tumors in 26 patients during 41 sessions from 2009 to 2013 were performed. Follow up CT-scan were used to determine local tumor progression. Survival rate, local tumor control rate and associated risk factors were analyzed. RESULTS: The immediate during and short-term complications with CTCAE grade 2 or upper include pneumothorax (15%), pleural effusion (20%), pulmonary hemorrhage (24%), pneumonitis (15%), hemothorax (15%), hemoptysis (10%), pain (20%), bronchopleural fistula (n=1), and empyema (n=2). Life-threatening bleeding or hemodynamic instability was not observed. There was no procedural-related mortality. Overall survival rate of 1, 2, 3 years are 96%, 88%, 88%. For curative intent, local tumor control (LTC) rate of 1, 2, 3 years are 75%, 72%, 72%. CONCLUSION: Cryoablation for malignant lung tumors is effective and feasible in local control of tumor growth, with good short- to mid-term survival rate, as an alternative option for inoperable patients.

Open versus thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma.

BACKGROUND: The impact of minimally invasive esophagectomy on patient prognosis, particularly disease-free survival (DFS), has not been well addressed. We compared the clinical outcomes of open and thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Sixty-three and 66 patients, nonrandomized, underwent open and thoracoscopic esophagectomies for ESCC between 2008 and 2011 were included. The clinicopathological data were reviewed retrospectively. Perioperative outcome, overall survival (OS), DFS, and the recurrence sites after open and thoracoscopic esophagectomy were compared. RESULTS: The open and thoracoscopic groups were comparable with regard to the total number of harvested lymph nodes and the percentage patients undergoing R0 resection. Fewer patients in the thoracoscopic group had pneumonia and wound complications. Intensive care unit (ICU) stay also was shorter in the thoracoscopic group. The recurrence pattern was similar in the two groups. In the open and thoracoscopic groups, the 3-year OS rates were 47.6 and 70.9 % (p = 0.031), respectively, and the 3-year DFS rates were 35 and 62.4 % (p = 0.007), respectively. However, the trends in better OS and DFS in the thoracoscopic group were not significant after stratification according to pathologic stage. CONCLUSIONS: The perioperative benefit of thoracoscopic esophagectomy included fewer postoperative complications and shorter ICU stays. Mid-term OS and DFS associated with thoracoscopic techniques are at least equivalent to those associated with open procedures.

Chylothorax complicating video-assisted thoracoscopic surgery for non-small cell lung cancer.

BACKGROUND: Chylothorax is an infrequent but well-known complication in lung cancer surgery. Previous published studies on this topic are limited, and thoracotomy has been the main surgical approach for treatment. However, chylothorax after lung cancer surgery performed solely by video-assisted thoracoscopic surgery (VATS) has rarely been investigated. The purpose of this study is to evaluate chylothorax after VATS for lung cancer. METHODS: The records of 776 patients with primary non-small-cell lung cancer (NSCLC) who underwent VATS for pulmonary resection and mediastinal lymph node dissection (MLND) at our hospital from January 2010 to August 2013 were retrospectively reviewed. Twenty patients with chylothorax (2.58 %) were included in the analysis. RESULTS: The 20 patients with chylothorax were all treated conservatively, but five patients (25 %) subsequently required reoperation for chylothorax. In patients with pleural drainage of less than 400 ml the first postoperative day, the chylothorax resolved with conservative treatment. Chylothorax also resolved in patients with pleural drainage of more than 400 ml the first or second postoperative day if drainage was less than 400 ml on postoperative day 4 and thereafter. Reoperations were required in cases with an increasing amount of pleural drainage on postoperative day 4 and thereafter. CONCLUSIONS: Most of the chylothorax following VATS for lung cancer can be treated conservatively. However, the timing of surgical intervention for chylothorax following VATS for lung cancer can be earlier if pleural drainage does not show a trend toward decreasing with conservative treatment.

Learning thoracoscopic lobectomy in resident training.

BACKGROUND: Thoracoscopic lobectomy is a safe and effective procedure; however, the ways by which to incorporate this technically demanding procedure into residency training is still unknown. We reported on the outcomes of thoracoscopic lobectomies performed by a single thoracic resident, who was simultaneously undergoing training for both open and thoracoscopic lobectomies. PATIENTS AND METHODS: Between January 2010, and May 2011, data from 87 consecutive thoracoscopic lobectomies that were performed by a trainee surgeon (B.-Y.W.) were prospectively obtained. Data were grouped into the first 30 and subsequent 57 cases. Patient characteristics, operative data, complications, and surgical pathology were analyzed. RESULTS: The mean operating time in group 2 was significantly lower compared with group 1 (264.0 ± 45.9 min in group 1 vs. 197.5 ± 57.7 min in group 2; p<0.001). There were no mortalities in both the groups and no significant differences in postoperative complications. CONCLUSIONS: Thoracoscopic lobectomy can be taught to a nonexperienced thoracic resident during an open procedure without compromising the safety of patients. It appears that surgical performance reaches a plateau after the completion of 30 cases.

Relationships Among Physical Activity, Daylight Exposure, and Rest-Activity Circadian Rhythm in Patients With Esophageal and Gastric Cancer: An Exploratory Study.

BACKGROUND: Although rest-activity circadian rhythm (RACR) disruption is associated with mortality in patients with cancer, few studies have examined the effect of RACR on patients with esophageal and gastric cancer. OBJECTIVE: The aim of this study was to identify the predictors of RACR. METHODS: This cross-sectional, single-site study included 276 patients with esophageal and gastric cancer recruited from chest-surgery and general-surgery outpatient departments. Actigraphy was used to assess objective physical activity (PA), daylight exposure, and RACR, and 3-day PA was used to indicate the subjective amount of PA. The parameter of objective PA was the up activity mean; the parameter of daylight exposure was >500 lx, and the parameters of RACR were the 24-hour correlation coefficient, in-bed less than out-of-bed dichotomy index, midline estimating statistic of rhythm, and amplitude. The subjective amount of PA was calculated as the sum of mild, moderate, and vigorous PA. RESULTS: The up activity mean predicted 24-hour correlation coefficient. The PA amount and up activity mean predicted in-bed less than out-of-bed dichotomy index. The up activity mean and >500-lx daylight exposure predicted midline estimating statistic of rhythm. Finally, the PA amount and up activity mean predicted the amplitude. CONCLUSIONS: Increased PA and daylight exposure may improve RACR. IMPLICATIONS FOR PRACTICE: Patients with esophageal and gastric cancer should be encouraged to engage in outdoor PA during the daytime as part of their regular lifestyle to maintain a robust circadian rhythm.

Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification on death and recurrence in completely resected stage I lung adenocarcinoma.

OBJECTIVE: This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage I lung adenocarcinoma. METHODS: Histological classification of 283 patients undergoing surgical resection for stage I lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification after comprehensive histological subtyping with recording of the percentage of each histological component (lepidic, acinar, papillary, micropapillary, and solid) in 5% increments. Their impact on overall survival, recurrence, and postrecurrence survival was investigated. RESULTS: The 5-year overall survival and recurrence-free rates were 81.6% and 76.9%, respectively. During follow-up, 57 (20.1%) patients developed recurrence. The 2-year postrecurrence survival rate was 72.3%. The solid predominant group is associated with significant more male sex, higher smoking exposure, larger tumor size, and more poorly differentiated histological grade. Lepidic predominant group had significantly better overall survival (P = 0.002). Micropapillary and solid predominant groups had significantly lower probability of freedom from recurrence (P = 0.004). Older age (P = 0.039), visceral pleural invasion to the surface (PL2) (P = 0.009), and high grade (micropapillary/solid predominant) of the new classification (P = 0.028) were predictors of recurrence in multivariate analysis. The solid predominant group tends to have significantly worse postrecurrence survival (P = 0.074). CONCLUSIONS: The new adenocarcinoma classification has significant impact on death and recurrence in stage I lung adenocarcinoma. Patients with PL2 and micropapillary/solid predominant pattern have significant higher risk for recurrence. This information is important for patient stratification for aggressive adjuvant chemoradiation therapy.

Prognostic factors in resected pathological N1-stage II nonsmall cell lung cancer.

Stage II nonsmall cell lung cancer (NSCLC) has been redefined in the seventh edition of tumour, node, metastasis (TNM) classification for lung cancer. Stages IIa and IIb both contain node-negative (N0) and node-positive (N1) subgroups. The aim of this study was to evaluate the prognostic factors for overall survival in patients with resected N1-stage II NSCLC. Between January 1992 and December 2010, we retrospectively reviewed the clinicopathological characteristics of 163 N1-stage II (T1a-T2bN1M0) NSCLC in patients undergoing curative resection as primary treatment. Median follow-up time was 37.2 months. The 1-, 3- and 5-yr overall survival rates were 85.3%, 62.1% and 43.5%, respectively. Tumour involvement of the hilar/interlobar nodal zone and poorly differentiated histological grade were significant predictors for worse overall survival using multivariate analysis (p = 0.001 and p = 0.015, respectively). There were trends toward worse overall survival in older patients and those with larger tumour size (p = 0.063 and p = 0.075, respectively). In resected N1-stage II NSCLC, hilar/interlobar nodal involvement and poorly differentiated histological grade were significant predictors of worse overall survival. The differences in survival between these subgroups of patients may lead to the use of different adjuvant therapies or post-surgical follow-up strategies.