Dynamic Analysis of the Impact of Micropapillary Component on Different Recurrence Patterns of Pathological Stage IA3 Lung Adenocarcinoma: A Multicenter, Retrospective Study.

BACKGROUND: This study aimed to evaluate the dynamic impact of the micropapillary (MIP) component on local recurrence (LR), distant metastasis (DM), and multiple recurrence (MR) of pathological stage IA3 lung adenocarcinoma. METHODS: Between July 2012 and July 2020, a total of 351 patients at two medical institutions were enrolled in this study. Cumulative incidence of curves, dynamic risk curves, and time-dependent multivariate analysis was performed to evaluate the effect of the MIP component on patients. RESULTS: The 5-year cumulative incidence of total recurrence with or without an MIP component was 34.2% and 12.3%, respectively (p = 0.001). In three recurrence patterns, our findings revealed that the 5-year cumulative incidence of LR (p = 0.048) and DM (p = 0.005) was higher in the 'MIP-present' group than in the 'MIP-absent' group. In the dynamic recurrence curve, the risk of the three recurrence patterns was different and varied over time between the two groups, especially in DM. Moreover, the dynamic cumulative event curve showed that after 1, 2, and 3 years of survival, the cumulative incidence of DM in the group with MIP continued to be higher than that in the group without MIP (all p < 0.05). Time-dependent Cox regression analysis indicated that the MIP component continued to be an independent risk factor for the cumulative incidence of DM in patients with 3-year survival. CONCLUSIONS: Of the three recurrence patterns, the MIP component mainly aggravated the risk of DM in patients with pathological stage IA3 lung adenocarcinoma, which persisted for 3 years.

Impact of minimally invasive total mesoesophageal excision and minimally invasive esophagectomy on failure patterns of locally advanced esophageal squamous cell carcinoma: a matched cohort study with long-term follow-up.

BACKGROUND: The effects of minimally invasive total mesoesophageal excision (MITME) on the long-term prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remain unknown. The objective of this study was to compare the static and dynamic failure patterns of MITME and minimally invasive esophagectomy (MIE) for locally advanced ESCC. METHODS: We use propensity score matching (PSM) method to analyze the postoperative failure patterns of the two groups. Cumulative event curves were analyzed for cumulative incidence of failure between different groups, and independent prognostic factors were assessed using time-dependent multivariate analyses. The risk of dynamic failure calculated at 12-month intervals was compared between the two groups using the lifetime table. RESULTS: A total of 366 ESCC patients were studied by 1:1 PSM for T stage and TNM stage (MITME group, n = 183; MIE group, n = 183). In the matched cohort, there was significant differences between the MITME and MIE groups in the failure pattern of regional lymph node recurrence (0.5 vs 3.8%, P = 0.032) and non-tumor death (10.9 vs 31.7%, P < 0.001). The cumulative event curve found that the 5-year cumulative failure rate was lower in the MITME group than in the MIE group (3.3 vs 17.1%, P = 0.026) after 5 years of survival. In addition, multivariate Cox regression analysis showed that MIE was an independent poor prognostic factor for a high cumulative failure rate in locally advanced ESCC patients at 5 years after surgery (HR:4.110; 95% CI 1.047-16.135; P = 0.043). The dynamic risk curve showed that the MITME group had a lower risk of failure within 5 years after surgery than the MIE group. CONCLUSION: Considering that MITME can significantly improve the postoperative failure pattern and the benefit lasts for at least 5 years, it is feasible to use MITME as a treatment for locally advanced ESCC.

Effects of a ground-glass opacity component on the recurrence and survival of pathological stage IA3 lung adenocarcinoma: a multi-institutional retrospective study.

Background: This study aimed to evaluate the effect of the presence of a radiographically manifested ground-glass opacity (GGO) component on the prognosis of patients with pathological stage IA3 lung adenocarcinoma. Methods: Patients diagnosed with pathological stage IA3 lung adenocarcinoma who underwent radical surgery at two medical institutions in China between July 2012 and July 2020 were enrolled. The cumulative incidence of recurrence (CIR) and cumulative incidence of death (CID) in patients with and without a GGO component were compared. Risk curves for the recurrence and tumor-related death overtime were analyzed between the two groups according to life table. In order to validate the prognostic value of GGO components, the recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated. Decision curve analysis (DCA) was performed to evaluate the clinical benefit rate of different models. Results: Among the 352 included patients, the presence of a GGO component was radiographically shown in 166 (47.2%) patients, while 186 (52.8%) displayed solid nodules. Patients exhibiting the absence of a GGO component had higher incidences of total recurrence (17.2% vs. 3.0%, P<0.001), local-regional recurrence (LRR) (5.4% vs. 0.6%, P=0.010), distant metastasis (DM) (8.1% vs. 1.8%, P=0.008), and multiple recurrences (4.3% vs. 0.6%, P=0.028) than the presence-GGO component group. The 5-year CIR and CID were 7.5% and 7.4% in the presence-GGO component group, and 24.5% and 17.0% in the absence-GGO component group, respectively, with statistically significant differences between the two groups (P<0.05). The risk of recurrence in patients with the presence of GGO components showed a single peak at 3 years postoperatively, while patients with the absence of GGO components showed a double peak at 1 and 5 years after surgery, respectively. However, the risk of tumor-related death peaked in both groups at 3 and 6 years postoperatively. Multivariate Cox analysis showed that the presence of a GGO component was a favorable independent risk factor for pathological stage IA3 lung adenocarcinoma patients (P<0.05). Conclusions: Pathological stage IA3 lung adenocarcinoma with or without GGO components are two types of tumors with different invasive abilities. In clinical practice, we should develop different treatment and follow-up strategies.

A Multi-institutional Analysis of the Combined Effect of Micropapillary Component and Consolidation-to-Tumor Ratio >0.5 on the Prognosis of Pathological, Stage IA3, Lung Adenocarcinoma.

INTRODUCTION: The study investigated the synergistic effect of the micropapillary (MIP) component and consolidation-to-tumor ratio (CTR) on the recurrence and survival of patients with pathologic stage IA3 lung adenocarcinoma. METHODS: We enrolled 419 patients confirmed pathological stage IA3 adenocarcinoma from four institutions. Kaplan-Meier analysis was performed to examine the value of the MIP component and CTR on relapse-free survival (RFS) and overall survival (OS). The cumulative recurrence between different stages was analyzed by using cumulative event curves. RESULTS: RFS (P < 0.0001) and OS (P = 0.008) in the presence of the MIP group were significantly lower than those in the absence of the MIP group, and CTR > 5 only reduced RFS (P = 0.0004), but not OS (P = 0.063), in the patients. In addition, the prognosis of patients with both the MIP component and CTR > 5 was worse than that of those without the MIP component or CTR ≤ 5. Therefore, we established new subtypes of the stage IA3: IA3a, IA3b, and IA3c. RFS and OS for IA3c staging were significantly lower than those for IA3a and IA3b. For IA3c, the cumulative incidence of local recurrence (P < 0.001) and that of distant metastasis (P = 0.004) were significantly higher than those for IA3a and IA3b. CONCLUSIONS: The MIP component combined with CTR > 0.5 can effectively predict the prognosis of patients with pathological stage IA3 lung adenocarcinoma and may offer more detailed recurrence and survival information according to the established subtype stage of IA3.

Inflammatory and Nutritional Status Influences Outcomes of Minimally Invasive Esophagectomy.

INTRODUCTION: The potential association between severe postoperative complications (SPC) and the oncological outcomes of esophageal squamous cell carcinoma (ESCC) patients according to the different Naples Prognostic Score (NPS) of the inflammatory nutritional status after minimally invasive esophagectomy (MIE) is unclear. METHODS: Kaplan-Meier survival analysis was used to evaluate overall survival (OS) and disease-free survival (DFS) between with or without SPC (Clavien-Dindo grade ≥ III) in low NPS status (NPS = 0 or 1) and high NPS status (NPS = 2 or 3 or 4) patients. Cox multivariable analysis was carried out to analyze the various independent factors of OS and DFS, and a nomogram based on SPC was established. RESULTS: A total of 20.7% (125/604) ESCC patients developed SPC after MIE. Patients with SPC exhibited poor 5-year OS and DFS compared to those without SPC (all P < 0.001). Further analysis revealed that SPC significantly reduced OS and DFS in patients with high NPS status (all P < 0.001) but had little effect on the prognosis of patients with low NPS status (all P > 0.05). Multivariable Cox analysis revealed that SPC could be an independent influence indicator for OS and DFS in patients with high NPS status. Therefore, a novel nomogram combining SPC and tumor-node-metastasis (TNM) staging has been developed, which was found to be relatively more accurate in predicting OS and DFS than TNM staging alone. CONCLUSION: Severe complications can adversely affect the long-term oncological outcome of ESCC patients with high systemic inflammatory response and malnutrition after MIE.

External validation of a risk model for survival prediction in older patients with cancer undergoing elective abdominal surgery: a prospective cohort study.

We previously developed a Chang Gung Memorial Hospital (CGMH) model to predict the 1-year postoperative mortality risk in patients with solid cancer undergoing cancer surgery. This study aimed to externally validate the CGMH score for survival outcome and surgical complication prediction in a prospective patient cohort. A total of 345 consecutive patients aged ≥65 years who underwent elective abdominal surgery for cancer treatment were prospectively enrolled. Patients were categorized into the low, intermediate, high, and very high-risk groups according to the CGMH score for comparison. The postoperative 1-year mortality rate was 12.5% in the entire cohort. The postoperative 1-year mortality rates were 0%, 2.2%, 14.0%, and 31.6% among patients in the low, intermediate, high, and very-high risk groups, respectively. The c-statistic of the CGMH model was 0.82 (95% confidence interval [CI], 0.76-0.88) for predicting the 1-year mortality risk. Hazard ratios for overall survival were 3.73 (95% CI, 2.11-6.57; P<0.001) and 10.1 (95% CI, 5.84-17.6; P<0.001) when comparing the high and very-high risk groups with the low/intermediate risk groups, respectively. Patients in the higher CGMH risk groups had higher risks of adverse surgical outcomes in terms of longer length of hospital stay, major surgical complications, postoperative intensive care unit stay, and in-hospital death. The CGMH model accurately predicted thesurvival probabilityand risk of adverse surgical outcomes in older patients with cancer undergoing elective abdominal surgery. Our study justifies the prospective use of the CGMH model for survival outcome and safety profile predictionfor cancer surgery in older patients.

[The Effect of Exercise Interventions on Alleviating Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review].

BACKGROUND: 85%-95% of patients with cancer experience chemotherapy-induced peripheral neuropathy (CIPN), which may lead to neuropathic pain, emotional distress, functional difficulties, and interpersonal problems. Although exercise interventions have been proposed for improving and preventing CIPN, evidence regarding the efficacy of these interventions has been inconsistent and of inadequate quality. In addition, few domestic systematic reviews have examined the effects of exercise on CIPN. PURPOSE: To examine the effects of exercise interventions in cancer patients with CIPN using a systematic review (SR) method. METHODS: An SR method was used in this paper by applying the concept of PICO using keywords P "cancer", I "rehabilitation", "exercise", C "usual care, standard of care", and O "chemotherapy-Induced peripheral neuropathy" in a search of the Ovid Medline, PubMed, Cochrane Library, EMBASE and Airiti Library databases for articles published from 2002 to 2021. Based on the inclusion and exclusion criteria, a total of 13 research articles were identified for review in this study. RESULTS: The 13 randomized controlled trials reviewed in this SR included 909 cancer patients during or after chemotherapy who were receiving exercise interventions. The results indicate that single or combined exercise protocols have consistent benefits in terms of improving CIPN symptoms. However, because of the relatively small sample sizes (n = 19-355) and the multiple types (n = 9), frequencies (1-7 day/week), and durations (5-60 minutes/time) of exercise protocols used in these studies, future research is necessary to explore differences in the types and subgroup effects of exercise. CONCLUSIONS: The results from this systematic review indicate that the combined exercise model has consistent benefits in terms of helping prevent and alleviate the symptoms of CIPN. In clinical practice, healthcare providers may consider encouraging cancer patients to initiate mild physical activity when their physical conditions are stable and without evident side effects from chemotherapy to minimize the impacts of CIPN on daily functioning and quality of life.

Nomogram for prognosis of patients with esophageal squamous cell cancer after minimally invasive esophagectomy established based on non-textbook outcome.

BACKGROUND: Non-textbook outcome (non-TO) represents a new prognostic evaluation index for surgical oncology. The present study aimed to develop new nomograms based on non-TO to predict the mortality and recurrence rate in patients with esophageal squamous cell cancer (ESCC) after minimally invasive esophagectomy (MIE). METHODS: The study involved a retrospective analysis of 613 ESCC patients, from the prospectively maintained database from January 2011 to December 2018. All the included ESCC patients underwent MIE, and they were randomly (1:1) assigned to the training cohort (307 patients) and the validation cohort (306 patients). Kaplan-Meier survival analysis was used to analyze the differences recorded between overall survival (OS) and disease-free survival (DFS). In the case of the training cohort, the nomograms based on non-TO were developed using Cox regression, and the performance of these nomograms was calibrated and evaluated in the validation cohort. RESULTS: Significant differences were recorded for 5-year OS and DFS between non-TO and TO groups (p < 0.05). Multivariate cox analysis revealed that non-TO, intraoperative bleeding, T stage, and N stage acted as independent risk factors that affected OS and DFS (p < 0.05). The results for multivariate regression were used to build non-TO-based nomograms to predict OS and DFS of patients with ESCC, the t-AUC curve analysis showed that the nomograms predicting OS and DFS were more accurate as compared to TNM staging, during the follow-up period in the training cohort and validation cohort. Further, the nomogram score was used to divide ESCC patients into low-, middle-, and high-risk groups and significant differences were recorded for OS and DFS between these three groups (p < 0.001). CONCLUSIONS: Non-TO was identified as an independent prognostic factor for ESCC patients. The nomograms based on non-TO could availably predict OS and DFS in ESCC patients after MIE.

Textbook outcome after minimally invasive esophagectomy is an important prognostic indicator for predicting long-term oncological outcomes with locally advanced esophageal squamous cell carcinoma.

Background: The textbook outcome (TO) emerges as a novel prognostic factor in surgical oncology. The present study aimed to evaluate the effect of TO on the risk of death and recurrence in patients with esophageal squamous cell carcinoma (ESCC) after minimally invasive esophagectomy (MIE). Methods: The study involved retrospective analysis of 528 patients with ESCC who were subjected to MIE from January 2011 to December 2017. TO included 8 parameters: complete resection; microscopically tumor-negative resection margins (R0); ≥15 lymph nodes removed and examined; no serious postoperative complications; no postoperative intervention; no re-admission to the intensive care unit (ICU); hospital stay ≤21 days; and no readmission ≤30 days. The Cox and logistic regression model were used to analyze the prognostic factors of survival and risk factors for TO. Results: Among the 528 patients with ESCC who were subjected to MIE, 53.2% reached TO. In the case of patients with locally advanced ESCC, 5-year overall survival (OS) was 51.1% (41.2-61.2%) for the TO group but 33.7% (23.7-43.7%) for the non-TO group (HR =0.644, 95% CI: 0.449-0.924, P=0.015). Similarly, 5-year disease-free survival (DFS) was 47.6% (38.0-57.2%) for the TO group but 29.1% (20.1-38.1%) for the non-TO group (HR =0.671, 95% CI: 0.479-0.940, P=0.018). In addition, 5-year recurrence-free survival (RFS) was 62.9% (53.7-72.1%) for the TO group but 39.8% (29.4-50.2%) for the non-TO group (HR =0.606, 95% CI: 0.407-0.902, P=0.012). Multivariate logistic regression analysis further showed that age, American Society of Anesthesiology (ASA) score, intraoperative blood loss, and smoking status acted as independent risk factors for TO. The results of the multivariate analysis assisted in the establishment of a nomogram for the prediction of TO occurrence. This nomogram exhibited satisfactory consistency and prediction ability [area under the receiving operator characteristic (AUROC) =0.717]. Conclusions: The present study showed that achieving of TO after MIE improves survival rate and reduce the recurrence rate in patients with locally advanced ESCC. The study further determined the independent factors associated with TO achievement and established a prediction model.

Attitudes and Intentions of Adult Patients With Cancer Toward Advance Directive: Direct and Indirect Relationships.

BACKGROUND: Advance directives (ADs) are used to respect the will of patients experiencing a terminal illness regarding preferred medical treatment and to protect their rights. However, the AD completion rate is low. OBJECTIVE: The aim of this study was to explore the factors influencing patient intentions toward AD. METHODS: The Theory of Planned Behavior was used as the framework for this study. This study used a cross-sectional design using a face-to-face interview with structured questionnaires. A total of 230 patients with cancer were recruited. Path analysis was used to examine the hypotheses. RESULTS: Demographic variables were not correlated with patients' attitudes toward AD. Patients' knowledge of AD ( ß = .68, t = 16.15, P < .00) and recognition of important others' attitudes toward AD ( ß = .30, t = 10.74, P < .00) were predictors of patients' attitudes toward AD. Patients' attitudes toward AD ( ß = .27, t = 3.74, P < .00) and behavior control over AD ( ß = .09, t = 1.99, P < .04) predicted patients' intentions toward AD. CONCLUSION: Patients' knowledge of AD, the patients' important others' attitudes, and behavior control toward AD are predictively associated with the intention toward AD completion. IMPLICATIONS FOR PRACTICE: Only when patients with cancer are provided an accessible approach for obtaining knowledge regarding AD and are given sufficient time and space can they and their significant others understand the meaning of AD and decide to complete one on their own terms.

Survival outcomes of management in metastatic gastric adenocarcinoma patients.

Chemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan-Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44-0.51), 1.22 (95% CI 1.1-1.36), and 3.23 (95% CI 3.01-3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease.

A prospective nutritional assessment using Mini Nutritional Assessment-short form among patients with head and neck cancer receiving concurrent chemoradiotherapy.

BACKGROUND: No gold standard of nutritional assessment is established among patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the clinical significance of pre-treatment nutritional status using the Mini Nutritional Assessment-short form (MNA-SF) among HNC patients receiving CCRT. METHODS: A total of 461 consecutive patients with newly diagnosed HNC treated with definitive CCRT at three medical institutes were prospectively enrolled. Nutritional status was assessed using MNA-SF within 7 days before CCRT initiation. Patients were classified as having normal nutrition, at risk of malnutrition, and malnourished groups according to MNA-SF for comparison. RESULTS: The 1-year overall survival rates were 89.8%, 76.8%, and 67.7% in the normal nutrition, at risk of malnutrition, and malnourished groups, respectively. Patients with normal nutrition had significantly lower rates of uncompleted radiotherapy and chemotherapy (4.5% and 4.1%, respectively) compared with patients at risk for malnutrition (14.1% and 11.5%, respectively) and those malnourished (11.1% and 11.1%, respectively). Patients with normal nutrition had significantly lower treatment-related complication rates regarding emergency room visits, hospital admission, and need for tubal feeding than those with at risk of malnutrition and malnourished. Patients with normal nutrition had significantly fewer severe hematologic toxicities (p = 0.044) and severe non-hematologic toxicities (p = 0.012) of CCRT than those malnourished. CONCLUSION: Pre-CCRT nutritional status identifies HNC patients vulnerable to treatment interruption and treatment complications. We suggest that nutritional assessment with MNA-SF should be incorporated in pre-CCRT evaluation for all HNC patients.

Expression of AKT and p-AKT protein in lung adenocarcinoma and its correlation with PD-L1 protein and prognosis.

BACKGROUND: The PI3K/AKT/mTOR signaling pathway were significantly associated with EGFR mutation in lung adenocarcinoma (LUAD), but its correlation with PD-L1 protein and prognosis are not clear. The aim of this study was to evaluate the expression of AKT and phosphorylated AKT (p-AKT) in LUAD and its correlation with programmed death ligand-1 (PD-L1); and to analyze the factors affecting LUAD prognosis. METHODS: The expression of AKT, p-AKT, and PD-L1 was examined using immunohistochemistry in LUAD tissues from 110 patients who underwent surgical treatment. RESULTS: AKT protein expression was examined in 64.5% (71/110) of the LUAD samples, and p-AKT protein expression was examined in 44.5% (49/110) of the LUAD samples. The positive rate of PD-L1 at TC1/2/3 was 38.2% (42/110). AKT and p-AKT expression was significantly associated with epidermal growth factor receptor (EGFR) mutation (P=0.016, P=0.014 respectively). Pearson's correlation analysis indicated a negative correlation of p-AKT with PD-L1 protein (P=0.022). Out of the 62 patients with EGFR mutation, the expression of PD-L1 was negatively correlated with that of p-AKT protein (P=0.032). The expressions of AKT and p-AKT were not associated with prognosis. Multivariate analysis showed that tumor-node-metastasis (TNM) stage (P=0.013) and differentiation (P=0.046) were independent prognostic factors for overall survival. CONCLUSIONS: PI3K/AKT/mTOR in the downstream pathway of EGFR may negatively regulate the expression of PD-L1, which may partly explain why patients with EGFR mutation respond poorly to PD-1/PD-L1 inhibitors.

Non-randomized preliminary study of an education and elastic-band resistance exercise program on severity of neuropathy, physical function, muscle strength and endurance & quality of life in colorectal cancer patients experiencing oxaliplatin-induced peripheral neuropathy.

PURPOSE: Many colorectal cancer (CRC) patients report having Oxaliplatin-induced peripheral neuropathy (OXAIPN), compromising their overall quality of life (QoL). Yet, the existing studies on examining the effects of elastic-band resistance exercise yielded inconsistent results and there was a scare study with CRC population employing a longitudinal research design. The purpose of this non-randomized preliminary study was to examine the effects of an educational program providing skills and knowledge about OXAIPN along with home-based lower extremity elastic-band exercise training in a sample (n = 42) of Taiwanese patients with CRC. METHOD: A quasi-experimental study with one-group, pretest-posttest repeated measures and longitudinal design was employed. The 4.5-month interventional protocol included 8 sessions of face-to-face education from the 3rd to the 7th cycles of chemotherapy. Physical exams, muscle strength and endurance, and self-reports regarding adverse impacts of OXAIPN and QoL were obtained at three time points throughout chemotherapy course. RESULTS: The most consistently significant increase was the participants' muscle strength and endurance measured with one-repetition maximum and 6-min walk distance, respectively (both P < .001). The participants' OXAIPN-related QoL showed significant improvements at some time points of the chemotherapy cycles, but not others. CONCLUSION: Study findings indicated that an educational program combined with knowledge about OXAIPN symptom management and skills with lower extremity resistance training had potential benefits over time on muscle strength and endurance and autonomic dimension of CIPN-related QoL. These preliminarily results may assist healthcare providers to incorporate self-management strategies such as lower extremity exercise for patients with OXAIPN to partially mitigate its negative effects.

Inhibition of lncRNA PART1 Chemosensitizes Wild Type but Not KRAS Mutant NSCLC Cells.

BACKGROUND: Lung cancer has the highest incidence among solid tumors in men and is the third most common cancer in women. Despite improved understanding of genomic and mutational landscape in non-small cell lung cancer (NSCLC), the five-year survival in these patients has remained stagnant at a dismal 15%. The first line of treatment commonly adapted for NSCLC patients with somatic mutation in EGFR is tyrosine kinase inhibitor gefitinib or erlotinib. EGFR mutant cells seem to be intrinsically sensitive to tyrosine kinase inhibitors; however, the remaining 20-30% patients are resistant to tyrosine kinase inhibitor. MATERIALS AND METHODS: Here we show, using in vitro normal and NSCLS cell lines, that the lncRNA Prostate androgen-regulated transcript 1 (PART1) is expressed at higher levels in NSCLC cells compared to normal lung epithelial cell line, corroborating two earlier studies. RESULTS: We additionally show that these cells are resistant to erlotinib which is reversed in some, but not all, cell lines following suppression of PART1 expression. The differential response to erlotinib following siRNA-mediated knockdown of PART1 was found to be related to the mutational status of KRAS. Only in cells with wild-type KRAS suppression of PART1 sensitized them to erlotinib. Knockdown of mutant KRAS did not sensitize those cell lines to erlotinib. But knockdown of mutant KRAS along with suppression of PART1 sensitized the cells to treatment with erlotinib. The results from the study reveal a yet undefined and important role of lncRNA PART1 in defining sensitivity to erlotinib. This action is mediated by mutation status of KRAS. CONCLUSION: Even though preliminary, our results indicate PART1 might be a potential candidate for targeted therapy or used as a predictor of chemosensitivity in patients with NSCLC.

Feasibility and strategy of common hepatic artery lymph node dissection in thoracolaparoscopic esophagectomy for thoracic esophageal squamous cell cancer.

Controversy about the adequate extent of lymph node (LN) dissection persists in surgery for thoracic esophageal squamous cell carcinoma (ESCC). The present study estimates the feasibility and strategy of common hepatic artery LN dissection during ESCC surgery.The clinical data of 482 patients with ESCC, who underwent thoracolaparoscopic esophagectomy at Fujian Medical University Union Hospital, were retrospectively selected. Among the 482 ESCC patients, 224 patients underwent thoracolaparoscopic esophagectomy with routine common hepatic artery LN dissection (cohort 1), while 258 patients underwent the same procedure without common hepatic artery LN dissection (cohort 2). The proposed operation method was introduced to safely dissect the common hepatic artery LN. Both univariate and multivariate analyses were performed to analyze the clinicopathological factors correlated to the common hepatic artery LN metastasis.The main postoperative complications were pneumonia, anastomotic leakage, vocal cord palsy and cardiovascular disease. There was no significant difference in the incidence of major postoperative complications between the 2 cohorts (P >.05), and the incidence was similar in a number of reports. The metastatic rate of common hepatic artery LNs was 4.91%, which was relatively lower. Based on the logistic regression analysis of 5 factors, tumor location and T classification were risk factors for common hepatic artery LN metastasis (P <.05).Routine common hepatic artery LN dissection is safe and feasible during a thoracolaparoscopic esophagectomy for ESCC. Although the metastatic rate is lower, common hepatic artery LN dissection should be performed for lower thoracic ESCCs, especially for tumors that invade the outer membrane.

Laparoscopic versus open gastrectomy for early gastric cancer in Asia: a meta-analysis.

OBJECTIVE: To perform a meta-analysis comparing laparoscopic versus open gastrectomy (LG vs. OG) for early gastric cancer (EGC) in Asia. METHODS: PubMed, Embase, CINAHL, AMED, the Cochrane database of Systematic Reviews, the Cochrane Controlled Trials Register, and the China National Knowledge Infrastructure electronic databases were systematically searched for studies published between January 1, 1992 and July 1, 2012. A series of clinical indices, including operative time, incision length, blood loss, harvested lymph nodes, time to flatus postoperatively, time to first oral intake postoperatively, use of analgesics, complications, duration of hospital stay, recurrence, and mortality were compared using weighted mean differences (WMDs) and odds ratios (ORs). RESULTS: Five randomized controlled trials and 11 case controls were included, including 1665 patients with EGC (919 LG, 746 OG). LG was associated with less trauma (incision length: WMD -12.91 cm; P<0.00001), less blood loss (WMD -121.04 mL, P<0.00001), less postoperative pain (number of times to use analgesics: WMD -1.64; P=0.001), faster bowel recovery (time to flatus: WMD -0.62 d; P=0.0001), fewer serious complications (OR 0.57; P=0.01), and shorter postoperative hospital stay (WMD -3.73 d; P=0.0007). However, LG had longer operative times (WMD 44.09 min; P<0.00001). LG also had fewer harvested lymph nodes, although this difference was not statistically significant (WMD -3.43 lymph nodes; P=0.04). There was no difference in recurrence rates (OR 0.58; P=0.33) and mortality between LG and OG. CONCLUSIONS: For the treatment of EGC in Asia, LG has several advantages, including safety, less trauma, and faster recovery. Our results should be validated in western studies.

Role of ARABIDOPSIS A-FIFTEEN in regulating leaf senescence involves response to reactive oxygen species and is dependent on ETHYLENE INSENSITIVE2.

Leaf senescence is a highly regulated developmental process that is coordinated by several factors. Many senescence-associated genes (SAGs) have been identified, but their roles during senescence remain unclear. A sweet potato (Ipomoea batatas) SAG, named SPA15, whose function was unknown, was identified previously. To understand the role of SPA15 in leaf senescence further, the orthologue of SPA15 in Arabidopsis thaliana was identified and characterized, and it was named ARABIDOPSIS A-FIFTEEN (AAF). AAF was expressed in early senescent leaves and in tissues with highly proliferative activities. AAF was localized to the chloroplasts by transient expression in Arabidopsis mesophyll protoplasts. Overexpression of AAF (AAF-OX) in Arabidopsis promoted, but the T-DNA insertion mutant (aaf-KO), delayed age-dependent leaf senescence. Furthermore, stress-induced leaf senescence caused by continuous darkness was enhanced in AAF-OX but suppressed in aaf-KO. Transcriptome analysis of expression profiles revealed up-regulated genes related to pathogen defence, senescence, and oxidative stress in 3-week-old AAF-OX plants. Indeed, elevated levels of reactive oxygen species (ROS) and enhanced sensitivity to oxidative and dark stress were apparent in AAF-OX but reduced in aaf-KO. ETHYLENE INSENSITIVE2 (EIN2) was required for the dark- and ROS-induced senescence phenotypes in AAF-OX and the induction of AAF expression by treatment with the immediate precursor of ethylene, 1-aminocyclopropane-1-carboxylic acid. The results indicate the functional role of AAF is an involvement in redox homeostasis to regulate leaf senescence mediated by age and stress factors during Arabidopsis development.