Beyond colonoscopy: Physical activity as a viable adjunct to prevent colorectal cancer.

Colorectal cancer (CRC) is a common cancer with an increasing incidence worldwide. The implementation of a mass screening program has been proven effective in reducing the global burden of CRC, but its effectiveness is not ideal and some metabolic derangements and lifestyle factors were reported to be attributable for such a deficit. Implementing positive lifestyle intervention as primary prevention therefore becomes critical because colorectal carcinogenesis can be promoted by several lifestyle factors, such as a lack of physical activity. Herein, we review the current evidence on the association and possible mechanisms between physical activity and CRC carcinogenesis. In addition, since CRC prevention heavily relies on resection of precancerous polyps and subsequent surveillance by colonoscopy, this review will also explore the impact of physical activity on populations with different colorectal polyp risks and its potential adjunct role in altering surveillance outcomes.

Can image-enhanced endoscopy improve adenoma detection rate?

An accumulating body of evidence has shown that detection and resection of pre-cancerous adenoma by colonoscopy could effectively prevent colorectal cancer (CRC) and its related mortality. Among various colonoscopy quality indicators, such as cecal intubation rate, withdrawal time, and adenoma detection rate (ADR); ADR is the most important and most closely associated with the subsequent risk of CRC. Image-enhanced endoscopy (IEE), including digital and dye-based IEE, was originally developed to discriminate neoplastic from non-neoplastic lesions but later studies have demonstrated that it can also enhance lesion detection by enhancing the contrast between the lesion and background colonic mucosa. Nevertheless, using IEE in colonoscopy for lesion detection is still not the standard way of practice in the real world. For a better understanding of current IEE modalities, this review introduces and compares the currently available IEE modalities and their efficacy in detecting adenoma from the results of randomized controlled trials or meta-analyses.

Active exercise after polypectomy reduces the risk of metachronous advanced colorectal neoplasm.

BACKGROUND AND STUDY AIMS: Exercise is associated with a lower risk of colorectal neoplasm but its association with metachronous advanced colorectal neoplasm development after polypectomy remains unclear. We aimed to investigate associations between subjects' exercise habits and the risk of metachronous advanced colorectal neoplasm. PATIENTS AND METHODS: This study analyzed subjects older than 40 years who received screening colonoscopy with polypectomy and surveillance colonoscopy between January 2009 and December 2016. All participants completed a standard questionnaire containing exercise habits before surveillance colonoscopy. Subjects' exercise habits were quantified as weekly exercise amounts (metabolic equivalents of task-day/week) and dichotomized (active/sedentary exercise habit) using averages as the cut-off point. The associations between incidence of metachronous advanced colorectal neoplasm and exercise habits were evaluated using Kaplan-Meier analysis and Cox regression models. RESULTS: A total of 1820 subjects comprised the study cohort and 86 (4.73%) of them developed metachronous advanced colorectal neoplasm during the surveillance period. An active exercise habit after polypectomy was associated with a lower risk of metachronous advanced colorectal neoplasm (adjusted hazard ratio [aHR] 0.57, 95% confidence interval [CI] 0.35-0.91). Furthermore, this protective effect from exercise was specific for subjects having advanced neoplasm at screening colonoscopy (aHR 0.32, 95% CI 0.11-0.94). CONCLUSIONS: An active exercise habit after polypectomy, a surrogate for a more active lifestyle, is associated with a lower risk for developing metachronous advanced colorectal neoplasm. A positive lifestyle modification, such as maintaining/establishing an active exercise habit, should be advised after polypectomy, especially for those with advanced colorectal neoplasm during screening.

High Risk of Clinical Relapse in Patients With Chronic Hepatitis B Virus Infection After Cessation of Prophylactic Antiviral Therapy for Rituximab-Containing Chemotherapy.

BACKGROUND: Prophylaxis with nucleos(t)ide analogue (NA) is recommended to prevent hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients receiving rituximab-based B-cell depletion therapy. However, little is known about the risk of clinical relapse after withdrawal of NA. METHODS: We retrospectively analyzed 77 noncirrhotic HBsAg carriers with hematological cancer who received rituximab-containing chemotherapy. All of them received either prophylactic entecavir or tenofovir therapy. The risk of clinical relapse and hepatic decompensation after cessation of NA was explored. RESULTS: Clinical relapse and hepatic decompensation developed in 25 (32.5 %) and 11 (14.3 %) of the patients, respectively, and 2 patients died of hepatic decompensation. Most of the hepatic events occurred within 1 year (20 of 25; 80.0%) after stopping NA. A higher pretreatment viral load (≥2000 vs <2000 IU/mL) was associated with increased risks of clinical relapse (hazard ratio, 3.47; 95% confidence interval, 1.56-7.73) and hepatic decompensation (9.91; 2.14-45.92). Of 51 patients with pretreatment viral load <2000 IU/mL, clinical relapse occurred in 10 (19.6 %) and hepatic decompensation in 2 (3.9%). CONCLUSIONS: Pretreatment HBV DNA ≥2000 IU/mL is associated with increased risk of liver-related disease after cessation of prophylactic NA therapy in patients who received rituximab-containing chemotherapy.

Stacked SiGe nanosheets p-FET for Sub-3 nm logic applications.

The fabrication of vertically stacked SiGe nanosheet (NS) field-effect transistors (FETs) was demonstrated in this study. The key process technologies involved in this device fabrication are low pressure chemical vapor deposition SiGe/Si multilayer epitaxy, selective etching of Si layers over SiGe layers using tetramethyl-ammonium-hydroxide wet solution, and atomic layer deposition of Y2O3 gate dielectric. For the fabricated stacked SiGe NS p-GAAFETs with a gate length of 90 nm, ION/IOFF ratio of around 5.0 × 105 and subthreshold swing of 75 mV/dec were confirmed via electrical measurements. Moreover, owing to its high quality of Y2O3 gate dielectric, the device showed a very small drain-induced barrier-lowering phenomenon. These designs can improve the gate controllability of channel and device characteristics.

Extracellular Vesicle miR-200c Enhances Gefitinib Sensitivity in Heterogeneous EGFR-Mutant NSCLC.

Intratumoral heterogeneity in epidermal growth factor receptor (EGFR)-mutant mutant non-small-cell lung cancer (NSCLC) explains the mixed responses to EGFR-tyrosine kinase inhibitors (TKIs). However, some studies showed tumors with low abundances of EGFR mutation still respond to EGFR-TKI, and the mechanism remained undetermined. Extracellular vesicles (EVs) can transmit antiapoptotic signals between drug-resistant and drug-sensitive cells. Herein, we profiled EVs from EGFR-mutant cells to identify a novel mechanism explaining why heterogenous EGFR-mutant NSCLC patients still respond to EGFR-TKIs. We first demonstrated that the EVs from EGFR-mutant changes the wild-type cells' sensitivity to gefitinib by adding EV directly or coculturing EGFR wild-type (CL1-5) cells and EGFR-mutant (PC9) cells. In animal studies, only the combined treatment of PC9 EV and gefitinib delayed the tumor growth of CL1-5 cells. MicroRNA analysis comparing EV miRNAs from PC9 cells to those from CL1-5 cells showed that mir200 family members are most abundant in PC9 EVs. Furthermore, mir200a and mir200c were found upregulated in plasma EVs from good responders to EGFR-TKIs. Finally, the transfection of CL1-5 cells with miR200c inactivates downstream signaling pathways of EGFR, the EMT pathway, and enhances gefitinib sensitivity. Overall, our results suggest that in heterogeneous EGFR-mutant NSCLC, tumor cells transmit EV miRNAs that may affect sensitivity to EGFR-TKIs and provide potential prognostic biomarkers for EGFR-mutant NSCLC.

Real-world outcomes of NSCLC patients receiving tissue or circulating tumor DNA-guided osimertinib treatment.

BACKGROUND: Osimertinib yields significant tumor responses and durations of progression-free survival (PFS) in patients with acquired T790M mutations. However, the evidence supporting liquid biopsy-guided treatment is still limited. This study examined the real-world benefits of osimertinib in patients with tissue or plasma T790M mutations. METHODS: From January 2016 to June 2018, a total of 183 non-small-cell lung cancer patients were enrolled. The presence of the T790M mutation was assessed by either tissue or plasma. The PFS, overall survival, and tumor response rates of the patients were calculated and compared with those of previous clinical trials. RESULTS: T790M mutations were detected in 51.5% of the patients, including 64 of 140 (45.7%) who underwent liquid biopsies and 23 of 29 (79.3%) who underwent tumor biopsies. After excluding those in clinical trials, 46 patients received osimertinib, including 33 with positive plasma and 13 with positive tissue results for T790M mutations. The median PFS was 11.3 months (interquartile range: 5.2-NR) in all the T790M-positive patients and 10.1 months (interquartile range: 5.9-NR) in the plasma T790M-positive patients. The overall survival, meanwhile, was not reached, whereas the one-year survival rate was 66.1% in all the patients and 61.4% in those who were plasma T790M-positive. The objective response rate and disease control rate were 37.8% and 91.9% in all the patients and 34.6% and 92.3% in the plasma T790M-positive group, respectively. Using a Cox proportional hazards regression, we determined that male gender was a poor prognostic factor for PFS. CONCLUSIONS: In this retrospective real-world analysis, it was determined that both tissue and plasma T790M mutations can be used to guide treatment with osimertinib. Similar disease control rates and survival durations were observed in comparison to those of phase 3 clinical trials.

The impact of EGFR mutations on the incidence and survival of stages I to III NSCLC patients with subsequent brain metastasis.

Previous studies have demonstrated the association between EGFR mutations and distant metastasis. However, the association for subsequent brain metastasis (BM) in stages I-III non-small cell lung cancer (NSCLC) patients remains inconclusive. We conducted a retrospective analysis to clarify the impact of EGFR mutations on the incidence of BM and associated survival in patients with stage I-III NSCLC. A total of 491 patients screened for EGFR mutations were retrospectively enrolled. Brain MRI or CT was used to detect the BM. Cumulative incidence of subsequent BM and overall survival (OS) after diagnosis of BM were estimated by the Kaplan-Meier method and compared using log-rank test. We performed Cox proportional hazard regression for predictors of subsequent BM and determinants of OS after BM. The cumulative incidence of BM seemed higher in patients harboring EGFR mutations than those without EGFR mutations although it did not reach statistical significance (hazard ratio [HR] = 1.75, 95% confidence interval [CI] = 0.73~1.81). After adjusting possible confounders, including age, smoking, stage, and tumor size, EGFR mutation became one of the predictors for subsequent BM (HR = 1.89, 95% CI = 1.12~3.17, p = 0.017). Though there was no statistical difference in survival after BM between patients with EGFR mutations and wild-type EGFR (median survival: 17.8 vs. 12.2 months, HR = 0.79, 95% CI = 0.45-1.40), patients with EGFR 19 deletion (Del) tended to have a longer survival after BM than the non-EGFR 19 Del group (median survival: 29.4 vs. 14.3 months, HR 0.58, 95% CI = 0.32-1.09, p = 0.089). In conclusion, our data suggested EGFR mutation to be one of the predictors for subsequent BM in stage I-III patients. Given the small sample size, more studies are warranted to corroborate our results.

Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer.

INTRODUCTION: Brain metastases (BM) are common in advanced non-small cell lung cancer (NSCLC), and the prognosis is poor with few therapeutic options. This study evaluated the efficacy of three epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in preventing and treating BM in patients with EGFR mutation-positive advanced NSCLC. METHODS: Patients with EGFR mutation-positive advanced NSCLC who visited a tertiary referral center from 1 December 2013 to 30 November 2017 were analyzed retrospectively. They received gefitinib, erlotinib, or afatinib until disease progression, death, or intolerable adverse events. The cumulative incidence of subsequent BM of initial non-BM patients, progression-free survival (PFS), and overall survival (OS) of the BM and non-BM patients were estimated and compared using the Kaplan-Meier and log-rank tests. RESULTS: 306 NSCLC patients were enrolled, with 116, 75, and 115 receiving first-line gefitinib, erlotinib, and afatinib, respectively. The afatinib group had a better PFS [12.7 versus 9.8 months; hazard ratio (HR) 0.59, p = 0.001] and OS (39.1 versus 22.0 months; HR 0.64, p = 0.035) than the gefitinib group. Afatinib tended to provide better BM prevention than gefitinib (BM cumulative incidence, HR 0.49; 95% confidence interval 0.34-0.71, p < 0.001) according to a Cox model adjusted for possible confounders. Patients with initial BM had a shorter PFS (p < 0.001) and OS (p = 0.015) than those without initial BM. Among the former, there were no differences in median PFS (p = 0.34) and median OS (p = 0.46) in the three EGFR-TKI groups. CONCLUSIONS: Our data suggested that, compared with gefitinib, afatinib provided better benefits significantly in terms of PFS and OS. Both had the same effectiveness in preventing subsequent BM.