Survival Comparison Between Open and Thoracoscopic Upfront Esophagectomy in Patients With Esophageal Squamous Cell Carcinoma.

BACKGROUND: The survival outcomes of patients with esophageal squamous cell carcinoma (ESCC) after open or thoracoscopic upfront esophagectomy remained unclear. OBJECTIVE: The aim of this retrospective study was to compare overall survival between open and thoracoscopic esophagectomy for ESCC patients without neoadjuvant chemodatiotherapy (CRT). METHODS: The Taiwan Cancer Registry was investigated for ESCC cases from 2008 to 2016. We enrolled 2053 ESCC patients receiving open (n = 645) or thoracoscopic (n = 1408) upfront esophagectomy. One-to-two propensity score matching between the two groups was performed. Stage-specific survival was compared before and after propensity score matching. Univariate analysis and multivariate analysis were used to identify risk factors. RESULTS: After one-to-two propensity score matching, a total of 1299 ESCC patients with comparable clinic-pathologic features were identified. There were 433 patients in the open group and 866 patients in the thoracoscopic group. The 3-year overall survival of matched patients in the thoracoscopic group was better than that of matched patients in the open group (58.58% vs 47.62%, P = 0.0002). Stage-specific comparisons showed thoracoscopic esophagectomy is associated with better survival than open esophagectomy in patients with pathologic I/II ESCC. In multivariate analysis, surgical approach was still an independent prognostic factor before and after one-to-two propensity score matching. CONCLUSION: This propensity-matched study revealed that thoracoscopic esophagectomy could provide better survival than open esophagectomy in ESCC patients without neoadjuvant CRT.

Survival Comparison Among Neoadjuvant Chemoradiotherapy Followed by Esophagectomy, Definitive Chemoradiotherapy, and Esophagectomy Alone for Esophageal Squamous Cell Carcinoma.

BACKGROUND: For patients with locoregional esophageal squamous cell carcinoma (ESCC), survival outcomes among neoadjuvant chemoradiotherapy followed by operation (nCRT-OP), definitive chemoradiotherapy (dCRT), and esophagectomy alone remain controversial. PATIENTS AND METHODS: Information from the 2008-2016 Taiwan Cancer Registry was used. A total of 7637 cT1b-4, N0/+, M0 ESCC patients receiving nCRT-OP (n = 1955), dCRT (n = 4122), or esophagectomy alone (n = 1560) were included. Propensity score matching was performed to balance clinical variables among the three groups. Stage-specific overall survival was compared before and after propensity score matching. Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Propensity score matching resulted in 1407 cases for comparison. The 5-year overall survival rates for matched patients treated via dCRT, nCRT-OP, and esophagectomy alone were 19.77%, 31.23%, and 30.52%, respectively (p < 0.001). On multivariable analysis, treatment modality was still an independent prognostic factor both before and after propensity score matching. nCRT-OP and esophagectomy alone were associated with significantly better overall survival than dCRT for locoregional ESCC patients. CONCLUSIONS: This propensity-matched study revealed that nCRT-OP and esophagectomy provided better survival than dCRT in cT1b-4, N0/+, M0 ESCC patients.

Preoperative biopsy and tumor recurrence of stage I adenocarcinoma of the lung.

PURPOSE: To evaluate whether preoperative biopsy affects the outcomes of patients undergoing at least lobectomy for stage I lung adenocarcinoma. METHODS: We reviewed the medical records of patients who underwent surgery for stage I lung adenocarcinoma between 2006 and 2013. Tumor recurrence and survival were compared between patients who underwent preoperative biopsy, including computed tomographic-guided needle biopsy and transbronchial biopsy, and those who underwent intraoperative frozen section. RESULTS: Among 509 patients, 229 patients (44.9%) underwent preoperative biopsy and 280 patients had lung adenocarcinoma diagnosed by intraoperative frozen section (reference group). Recurrence developed in 65 (12.8%) patients within a median follow-up period of 54.4 months. Multivariate analysis demonstrated that preoperative biopsy (OR 1.97, p = 0.045), radiological solid appearance (OR 5.43, p < 0.001), and angiolymphatic invasion (OR 2.48, p = 0.010) were independent predictors of recurrence. In the overall cohort, preoperative biopsy appeared to worsen 5-year disease-free and overall survival significantly (76.6% vs. 93.0%, p < 0.001; and 83.8% vs. 94.5%, p = 0.002, respectively) compared with the reference group. After propensity matching, multivariable logistic regression still identified preoperative biopsy as an independent predictor of overall recurrence (OR 2.21, p = 0.048) after adjusting for tumor characteristics. CONCLUSION: Preoperative biopsy might be considered a prognosticator of recurrence of stage I adenocarcinoma of the lungs in patients who undergo at least anatomic lobectomy without postoperative adjuvant chemotherapy.

Neoadjuvant Chemoradiation Versus Upfront Esophagectomy in Clinical Stage II and III Esophageal Squamous Cell Carcinoma.

BACKGROUND: The benefits of neoadjuvant chemoradiation (NCRT) compared to upfront esophagectomy (UE) in esophageal squamous cell carcinoma (ESCC) is controversial. Our purpose was to determine whether clinical stages based on the 8th edition American Joint Committee on Cancer Tumor-Node-Metastasis staging system could guide treatment decision. METHODS: Data from 2503 patients with clinical stages II and III ESCC diagnosed between 2008 and 2014 were obtained from a nationwide database. Propensity score matching was used to identify well-balanced pairs of patients. Cox proportional hazards regression and log-rank test were used in the survival analysis. The outcomes of patients receiving "NCRT followed by surgery" or "UE" strategies were compared. RESULTS: The treatment modality (UE or NCRT) was not a prognostic factor in clinical stage II ESCC (HR: 0.97; p = 0.778). In contrast, the UE group demonstrated a significantly worse outcome compared with the NCRT group in clinical stage III ESCC (HR: 1.39; p < 0.001). After matching, patients who underwent UE for clinical stage II ESCC had median survival/3-year overall survival (OS) rates of 27.8 months/39.2% compared with 32.7 months/49.8% in the NCRT group (p = 0.508). The patients who underwent UE for clinical stage III ESCC had median survival/3-year OS rates of 17.9 months/28.2% in the UE group compared with 24.0 months/41.8% in the NCRT group (p < 0.001). CONCLUSIONS: Our data suggest that NCRT strategy improved survival compared with UE in clinical stage III ESCC but not in clinical stage II tumors.

Survival Impact of Total Resected Lymph Nodes in Esophageal Cancer Patients With and Without Neoadjuvant Chemoradiation.

BACKGROUND: Current esophageal treatment guidelines suggest that, when more than 15 lymph nodes are detected, dissection should be done as the minimum requirement for staging in esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy without induction chemoradiotherapy (CRT). However, for neoadjuvant CRT, there is limited information. We sought to clarify the role of lymphadenectomy in ESCC patients with and without neoadjuvant CRT. PATIENTS AND METHODS: Data on 3156 ESCC patients receiving esophagectomy with (group 1, n = 1399) and without (group 2, n = 1757) neoadjuvant CRT between 2008 and 2014 were collected from a national cancer registry in Taiwan. The impact of the resected lymph nodes on overall survival was assessed according to pathologic stages. A Cox regression model was used to identify prognostic factors for overall survival. RESULTS: Five-year overall survival rates were 35.6% for the entire group, 30.32% for group 1, and 39.55% for group 2 (p < 0.0001 for group 1 vs group 2). The best cutoff value was 21 lymph nodes in both group 1 and group 2. In group 1, the independent prognostic factors included age ≥ 54 years, clinical N status, y-pathologic T, y-pathologic N, y-pathologic stage, grade, location, margin status, esophagectomy (thoracoscopic vs open), and number of total resected lymph nodes (≤ 21 vs > 21). For group 2, the independent prognostic factors were gender, clinical stage, pathologic T, pathologic N, tumor length, grade, and margin status. CONCLUSIONS: Extent of lymphadenectomy was associated with survival in patients with neoadjuvant CRT followed by esophagectomy. The optimum lymphadenectomy should be modulated by pathologic stage.

A Propensity-matched Analysis Comparing Survival After Esophagectomy Followed by Adjuvant Chemoradiation to Surgery Alone for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The role of adjuvant chemoradiation in esophageal cancer has been underestimated in the literature. This study was undertaken to determine whether adjuvant chemoradiation improves survival compared with surgery alone. METHODS: Data of 1095 esophageal squamous cell carcinoma (ESCC) patients, including 679 in surgery alone group (group 1) and 416 in surgery followed adjuvant chemoradaition group (group 2), were obtained from the Taiwan Cancer Registry database. Propensity score matching (PSM) analysis was used to identify 147 well-balanced patients in each group for overall survival comparison. RESULTS: After PSM, the 3-year survival rates and median survival were 44.9% and 27.2 (95% confidence interval [CI]: 17.6-40.3) months in group 2, which is significantly higher than that in group 1 (28.1% and 18.2 [95% CI: 14.3-24.5] months, P = 0.0043). In the multivariate survival analysis, pT3/4 stage (Hazard Ratio [HR]: 2.03, 95% CI: 1.38-2.97, P < 0.001), pN+ stage (HR: 1.83, 95% CI: 1.31-2.57, P = 0.0004), tumor length more than 32 mm (HR: 1.93, 95% CI: 1.33-2.79, P < 0.001), R1/2 resection (HR: 1.75, 95% CI: 1.15-2.66, P = 0.009), and adjuvant chemoradiation (HR: 0.57, 95% CI: 0.42-0.78, P < 0.0001) were independent prognostic factors. Subgroup analysis suggested patients with pT3/4 stage, pN+ stage tumors, larger tumor size, poorly differentiated tumors, and R1/2 resections were more likely to demonstrate survival benefit from adjuvant chemoradiation. CONCLUSIONS: Compared with surgery alone, adjuvant chemoradiation provides a survival benefit to ESCC patients, especially those with pT3/4 stage, N+ tumors, larger tumor size, poorly differentiated tumors, and R1/2 resections.

Hypothalamic NUCKS regulates peripheral glucose homoeostasis.

Nuclear ubiquitous casein and cyclin-dependent kinase substrate (NUCKS) is highly expressed in the brain and peripheral metabolic organs, and regulates transcription of a number of genes involved in insulin signalling. Whole-body depletion of NUCKS (NKO) in mice leads to obesity, glucose intolerance and insulin resistance. However, a tissue-specific contribution of NUCKS to the observed phenotypes remains unknown. Considering the pivotal roles of insulin signalling in the brain, especially in the hypothalamus, we examined the functions of hypothalamic NUCKS in the regulation of peripheral glucose metabolism. Insulin signalling in the hypothalamus was impaired in the NKO mice when insulin was delivered through intracerebroventricular injection. To validate the hypothalamic specificity, we crossed transgenic mice expressing Cre-recombinase under the Nkx2.1 promoter with floxed NUCKS mice to generate mice with hypothalamus-specific deletion of NUCKS (HNKO). We fed the HNKO and littermate control mice with a normal chow diet (NCD) and a high-fat diet (HFD), and assessed glucose tolerance, insulin tolerance and metabolic parameters. HNKO mice showed mild glucose intolerance under an NCD, but exacerbated obesity and insulin resistance phenotypes under an HFD. In addition, NUCKS regulated levels of insulin receptor in the brain. Unlike HNKO mice, mice with immune-cell-specific deletion of NUCKS (VNKO) did not develop obesity or insulin-resistant phenotypes under an HFD. These studies indicate that hypothalamic NUCKS plays an essential role in regulating glucose homoeostasis and insulin signalling in vivo.

The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma.

Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase) may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA)-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.

Comparison of pathologic stage in patients receiving esophagectomy with and without preoperative chemoradiation therapy for esophageal SCC.

The prognostic value for the post-chemoradiation therapy (CRT) pathologic stage is uncertain. The purpose of this study was to compare the pathologic stage in patients undergoing esophagectomy with and without preoperative CRT for esophageal squamous cell carcinoma (ESCC). This study retrospectively reviewed the data from 2151 patients with ESCC who underwent esophagectomy with or without preoperative CRT between 2008 and 2011 in Taiwan. Patients were divided into 2 groups. Group A consisted of patients treated with primary surgery without prior treatments (n=1301), and group B consisted of patients receiving preoperative CRT followed by esophagectomy (n=850). In group A, 679 patients received surgery alone, 92 received postoperative chemotherapy, 416 received postoperative chemoradiation therapy, and 114 received postoperative radiation therapy. In group A, the 3-year survival rates by pathologic stage were 82.2% for stage 0, 67.6% for stage I, 50.7% for stage II, 21.5% for stage III, and 14.8% for stage IV (P<.001). In group B, the 3-year survival rates of post-CRT pathologic stages 0, I, II, III, and IV were 59.4%, 46.0%, 40.3%, 19.1%, and 8.2%, respectively (P<.001). In multivariate analysis, the pathologic T, N, and M were all independent prognostic factors in both group A (esophagectomy alone) and B (CRT plus esophagectomy). The current, 7th edition of the esophageal TNM staging system could adequately stratify prognostic groups in patients with squamous cell carcinoma who were treated with preoperative CRT and esophagectomy.

Surgery or Surveillance for Esophageal Squamous Cell Carcinoma With Clinical Complete Response After Neoadjuvant Chemoradiotherapy.

We aimed to evaluate the role of esophagectomy in patients with esophageal squamous cell carcinoma with clinically complete response (cCR) after neoadjuvant chemoradiotherapy. Data of patients with locally advanced esophageal squamous cell carcinoma who achieved cCR after neoadjuvant chemoradiotherapy between October 2008 and September 2018 were retrospectively reviewed. The criteria for cCR include: (1) tumor resolution on computed tomography, (2) maximum standardized uptake value decrement >35% on positron-emission tomography-computed tomography scan, and (3) a negative endoscopic biopsy result. Overall survival (OS) and disease-free survival (DFS) were compared between patients who received surveillance only (surveillance) and those who underwent surgery. A total of 154 patients with cCR, including 54 in the surveillance group and 100 in the surgery group, were included. The 5-year OS rates in the surveillance and surgery groups were 47.9% and 36.9 %, respectively (P= 0.210). The 5-year DFS rates were 38.1% and 28.2%, respectively (P = 0.203). Surgery was not a prognostic factor in the multivariable analysis (OS: HR: 1.26, 95% CI: 0.69-2.33, P = 0.453; DFS: HR: 1.08, 95% CI: 0.60-1.96, P = 0.795). In the surgery group, ypT0N0, ypT+Nany, and ypT0N+ were noted in 54%, 37%, and 9% of patients, respectively. The 5-year OS rates were 55.8%, 22.2%, and 12.4%, respectively (P = 0.001). No survival differences were noted between the surveillance and surgery groups. However, 46% of cCR patients in the surgery group did not have pathological complete response, and their outcomes were poor. Esophagectomy may be the only way to identify patients with residual disease.

Comparing survival between neoadjuvant chemoradiotherapy followed by open or thoracoscopic oesophagectomy in patients with oesophageal squamous cell carcinoma.

OBJECTIVES: The goal of this study was to investigate the overall survival between open and thoracoscopic oesophagectomy in patients with oesophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (NCRT). METHODS: The Taiwan Cancer Registry was queried for ESCC from 2008 to 2016. We enrolled 2250 patients with ESCC receiving NCRT plus open (n = 487) or thoracoscopic (n = 1763) oesophagectomy. One-to-two propensity score matching between open and thoracoscopic oesophagectomy was performed. Overall survival was compared between the 2 groups before and after propensity score matching. Univariable analysis and multivariable analysis were performed to identify prognostic factors. RESULTS: After one-to-two propensity score matching, 353 patients were in the open group and 706 patients were in the thoracoscopic group. The 3-year overall survival rates for matched patients treated with open or thoracoscopic oesophagectomy were similar (39.18% vs 44.33%, p = 0.11). Better overall survival was associated with thoracoscopic oesophagectomy for the patients in the y-pathological complete response stage (pCR) (57.26% vs 65.19%, p = 0.045), y-pathological III stage (12.78% vs 22.31%, p = 0.028) and y-pathological T0N+ stage (15.79% vs 41.01%, p = 0.010). In multivariable analysis, surgical approach was an independent prognostic factor only before propensity score matching. After matching, surgical approach was not an independent prognostic factor. CONCLUSIONS: This propensity-matched study demonstrated that open and thoracoscopic oesophagectomies are associated with similar long-term survival in patients with ESCC undergoing NCRT. Stage-specific comparisons showed that thoracoscopic oesophagectomy is associated with better survival than open oesophagectomy in patients with the pathological complete response, y-pathological III and y-pathological T0N+ stages and with similar survival in y-pathological I/II patients.

Outcomes of patients with different lepidic percentage and tumor size of stage I lung adenocarcinoma.

BACKGROUND: To evaluate the long-term outcomes after surgical resection for stage I lung adenocarcinoma based on the percentage of lepidic component (LC) and invasive tumor size (IS). METHODS: The clinicopathological characteristics of 1049 patients with stage I lung adenocarcinoma who underwent surgery between 2006 and 2016 were retrospectively reviewed. Tumors were categorized into groups: A (LC ≥ 50%) and B (LC < 50%). Groups A0 and A1 consisted of minimally invasive adenocarcinomas (MIA) and other lepidic-predominant invasive adenocarcinomas, respectively. Group B was categorized into B1 (IS ≤ 1 cm), B2 (1 < IS≤2 cm), and B3 (2 < IS≤3 cm) by invasive tumor size and divided into subgroups (B1[lep+]/[lep-], B2[lep+]/[lep-], and B3[lep+]/[lep-]) according to the presence[lep+] or absence[lep-] of LCs. Cumulative incidence of recurrence (CIR) and cancer-specific survival (CSS) were examined. RESULTS: LC decreased with increasing IS. Only 24 (8.5%) tumors in group A had an IS >1 cm. 10-year CIR and CSS were 15.2% and 86.0%. LC and IS were found to be independent predictors of CSS. Patients in group A had 1.4% 10-year CIR and 100% 10-year CSS. In group B, a significantly higher CIR and worse CSS were observed as IS increased (p < 0.001), but LC was not a predictor for CSS (p = 0.593). No significant differences in CIR or CSS were found in presence of LC or not when LC < 50% (B1[lep+]/[lep-], B2[lep+]/[lep-], and B3[lep+]/[lep-]: p = 0.36/0.48, p = 0.82/0.94, and p = 0.90/0.37, respectively). CONCLUSIONS: LC≥50% tumors demonstrated excellent prognosis regardless of IS. The outcomes of LC < 50% tumors were well predicted by IS, corresponding to the T-staging system. The predictive value of LC for prognosis became insignificant.

Sequence for Surgical Resection of Primary Lung Tumor for Oligometastatic Non-small Cell Lung Cancer.

BACKGROUND: Differing surgical series for the treatment of primary lung tumor with synchronous oligometastatic stage IV non-small cell lung cancer (NSCLC) have been published; however, outcomes remain ambiguous. METHODS: Patients with synchronous oligometastatic stage IV NSCLC treated from 2005 to 2017 were enrolled to identify the impact of treatment sequence (primary lung resection vs systemic treatment) on progression-free survival (PFS) and overall survival (OS). RESULTS: Tumor resection occurred in 51 patients (84% adenocarcinoma, 55% nonsmokers, and 65% driver gene mutation) before or after systemic treatment in 33 (64.7%) and 18 (35.3%) patients, respectively. Patients who received resection first were older (62.1 vs 54 years) and at a less advanced intrathoracic stage (18% vs 44%). No significant differences were noted regarding perioperative complications (30% vs 28%), hospital length of stay (9.0 vs 10.5 days), percentage of disease progression (91% vs 94%), overall death (70% vs 78%), median PFS (14.0 vs 22.8 months), and OS (44.6 vs 53.2 months). Patients with single-organ metastasis had significantly longer PFS and OS than those with oligometastases (17.5 vs 12.8 months, P = .040; and 55.6 vs 39.8 months, P = .035), respectively. Multivariable Cox analysis identified nonsolitary metastasis as the only independent predictor of PFS (hazard ratio, 2.27; 95% confidence interval, 1.07-4.81; P = .033). CONCLUSIONS: Primary lung resection before or after induction systemic therapy may benefit patients with oligometastatic NSCLC. Future randomized clinical trials examining the effect of treatment sequence is recommended.

Propensity score analysis comparing survival between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

INTRODUCTION: The purpose of the current study is to compare definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with cT1-3/N0-3 esophageal squamous cell carcinoma in survival. METHODS: Records from 2008 to 2014 of 4931 patients with clinical T1-3/N0-3 esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or esophagectomy with adjuvant chemoradiotherapy were obtained from the Taiwan Cancer Registry. Univariable and multivariable analyses were performed and propensity score matching was used to minimize the bias. Overall survival was compared between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy, and also in the three different clinical stages. RESULTS: Definitive chemoradiotherapy was performed on 4381 patients, and 550 patients received esophagectomy adjuvant chemoradiotherapy. Each group produced 456 patients for comparison after propensity score matching. The 1-year, 2-year, and 3-year overall survival rates for matched patients in with definitive chemoradiotherapy group were 57.18%, 31.92%, and 23.8%. The 1-year, 2-year, and 3-year overall survival rates for matched patients treated in the esophagectomy with adjuvant chemoradiotherapy group were 72.35%, 45.74%, and 34.04%(p<0.0001). In multivariable analysis, treatment modality was an independent prognostic factor. Esophagectomy with adjuvant chemoradiotherapy provided better survival outcome than definitive chemoradiotherapy for patients with clinical stage II/III disease. As for patients with clinical stage I disease, there was no significant survival difference between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy. CONCLUSIONS: Esophagectomy with adjuvant chemoradiotherapy provided better survival than definitive chemoradiotherapy in clinical II/III esophageal squamous cell carcinoma. However, more data are needed to conduct a convincing conclusion in clinical stage I patients.

Significance of preoperative biopsy in radiological solid-dominant clinical stage I non-small-cell lung cancer.

OBJECTIVES: The present study aimed to clarify the association between preoperative biopsy and surgical outcomes in clinical stage I non-small-cell lung cancer (NSCLC) with different proportions of ground-glass opacity (GGO). METHODS: Data on patients who underwent pulmonary resection for NSCLC from 2006 to 2016 were drawn from a prospective registered database and analysed retrospectively. Patient characteristics collected included tumour size, location and staging, surgical approach, consolidation-tumour ratio, histopathology and the presence or absence of preoperative biopsy to identify the independent prognostic factors of disease-free survival (DFS) and cancer-specific survival. A 1:1 propensity score matching was conducted between the preoperative biopsy and reference groups based on their baseline characteristics measured before the decision for preoperative biopsy. RESULTS: A total of 1427 patients were collected to achieve an overall 5-year DFS as 84.5% (median follow-up: 67.3 months), stratified to be 99.5% in the GGO-dominant group (n = 430) and 78.2% in the solid-dominant group (n = 997). Only 2 patients (0.5%) in the GGO-dominant group experienced tumour recurrence. For solid-dominant tumours matched with propensity scores (279 in preoperative biopsy vs 279 in reference group), the independent predictors of DFS included preoperative biopsy, sublobar resection, pathological staging and angiolymphatic invasion. Preoperative biopsy was a predictor of cancer-specific survival in univariable analysis but was not in multivariable analysis. Significant differences were also found between matched groups in those with late-delay surgery, but not in patients receiving preoperative biopsy with early-delay surgery (≤21 days). CONCLUSION: Preoperative biopsy may worsen surgical outcomes in patients with clinical stage I, solid-dominant NSCLC.

Prognostic histologic subtyping of dominant tumor in resected synchronous multiple adenocarcinomas of lung.

The prognostic role of histological patterns of dominant tumor (DT) and second dominant tumor (sDT) in synchronous multiple adenocarcinoma (SMADC) of lung remains unclear. SMADC patients diagnosed between 2003 and 2015 were retrospectively reviewed. DT and sDT were defined as two maximum diameters of consolidation among multiple tumors. Histological pattern was determined using IASLC/ATS/ERS classification system. DTs were divided into low- (lepidic), intermediate- (acinar, papillary) and high-grade (micropapillary, solid) subtypes, and sDTs into non-invasive predominant (lepidic) and invasive predominant (acinar, papillary, micropapillary, solid) subtypes. During mean 74-month follow-up among 149 nodal-negative patients having SMADC resected, recurrence was noted in 44 (29.5%), with significantly higher percentage in high-grade DT (p < 0.001). Five-year overall (OS) and disease-free (DFS) survivals in low-, intermediate- and high-grade DT were 96.9%, 94.3%, 63.3% (p < 0.001) and 100%, 87.2%, 30.0%, respectively (p < 0.001). Cox-regression multivariate analysis demonstrated high-grade DT as a significant predictor for DFS (Hazard ratio [HR] 5.324; 95% CI 2.570-11.462, p < 0.001) and OS (HR 3.287; 95% CI 1.323-8.168, p = 0.010). Analyzing DT and sDT together, we found no significant differences in DFS, either in intermediate- or high-grade DT plus invasive or non-invasive sDT. DT was histologically an independent risk factor of DFS and OS in completely resected nodal-negative SMADCs.

Locally Targeting the IL-17/IL-17RA Axis Reduced Tumor Growth in a Murine B16F10 Melanoma Model.

Interleukin (IL)-17 and the cells that produce it within the tumor microenvironment appear to promote tumor development and are associated with survival in cancer patients. Here we investigated the role of the IL-17/IL-17 receptor A (IL-17RA) axis in regulating melanoma progression and evaluated the therapeutic potential of blocking the IL-17/IL-17RA pathway. First, recombinant mouse IL-17 (γmIL-17) treatment significantly increased proliferation of mouse B16F10 cells and human A375 and A2058 cells. Silencing IL-17RA by small hairpin RNA (shRNA) in B16F10 cells reduced the γmIL-17-elicited cell proliferation, migration, and invasion, and significantly reduced vascular endothelial growth factor and matrix metalloproteinase production. Remarkably, knockdown of IL-17RA led to a significantly decreased capability of B16F10 cells to form tumors in vivo, similar to that in IL-17-deficient mice. Finally, local application of an adenovirus delivering a shRNA against IL-17RA mRNA not only significantly suppressed tumor development, but also enhanced antitumor immunity by increasing the interferon γ-expressing T cells and not T regulatory cells. Our results highlight the critical role of the IL-17/IL-17RA pathway in tumor progression and imply that targeting IL-17RA represents a promising therapeutic strategy.

Comparison Between Esophagectomy and Definitive Chemoradiotherapy in Patients With Esophageal Cancer.

BACKGROUND: This study compared survival between definitive chemoradiotherapy (CRT) and esophagectomy alone among patients with locoregional esophageal squamous cell carcinoma (SCC). METHODS: Data were obtained from the Taiwan Cancer Registry between 2008 and 2014. Included were 5,487 patients with clinical I, II, or III esophageal SCC who received definitive CRT or esophagectomy alone. Patients were stratified according to clinical stage. Overall survival was compared between patients treated with definitive CRT versus esophagectomy alone, and between patients in the three different clinical stages. Propensity-matched analysis along with univariate and multivariate analysis were performed. RESULTS: Treatment was with definitive CRT in 4,251 patients (77.50%) and esophagectomy alone in 1,236 (22.50%). Propensity score matching produced 1,020 patients for comparison. The overall survival rates at 1, 2, and 3 years were 60.92%, 34.96%, and 26.14%, respectively, for propensity-matched patients treated with definitive CRT and were 71.15%, 56.50%, and 46.17%, respectively, for propensity-matched patients treated with esophagectomy alone (p < 0.001). Multivariate analysis showed treatment strategy was an independent prognostic factor. Esophagectomy alone was associated with significantly better overall survival than definitive CRT for patients with clinical stage I/II disease. There was no survival risk difference between definitive CRT and esophagectomy only for patients with clinical stage III disease. CONCLUSIONS: Esophagectomy alone could provide better survival than definitive CRT for patients with clinical stage I/II esophageal SCC. However, definitive CRT and esophagectomy yield similar overall survival rates in clinical stage III patients.

Monitoring of pesticide chlorpyrifos residue in farmed fish: investigation of possible sources.

Chlorpyrifos, a widely used organophosphorus insecticide having many urban and agricultural pest control uses, is one of the major pesticides detected in Taiwan fishery products. Whereas previous studies examined, this study explored possible sources of chlorpyrifos residue, particularly in farmed fish. Eight hundred fourteen samples of marketable fish were analyzed for chlorpyrifos residues. One hundred thirty-seven samples contained detectable residues, and farmed fish showed higher detection rates (23%) than wild fish. Based on the findings of all media of the eleven aquiculture farms, the existence of chlorpyrifos in the farmed fish were positively related to existence in fish feed. A study of indoor carp confirmed dietary accumulation of chlorpyrifos.

Upfront surgery and pathological stage-based adjuvant chemoradiation strategy in locally advanced esophageal squamous cell carcinoma.

Adjuvant chemoradiation is reported to have a survival benefit for esophageal squamous cell carcinoma (ESCC). We evaluated the "upfront surgery and pathological stage-based adjuvant chemoradiation" strategy, in which adjuvant therapy is guided by pathological stage, in locally advanced ESCC. Data from 2976 clinical stage II/III ESCC patients, including 1735 in neoadjuvant chemoradiation and 1241 in upfront surgery groups, were obtained from a nationwide database. Patients in the upfront surgery group were further categorized into the "upfront surgery and pathological stage-based adjuvant chemoradiation" and "upfront surgery only" groups. The 3-year overall survival (OS) rates in the "neoadjuvant chemoradiation", "upfront surgery and pathological stage-based adjuvant chemoradiation", and "upfront surgery only" groups were 41.5%, 45.8%, and 28.5%, respectively. In propensity score matched patients, the 3-year OS rate was 41.7% in the neoadjuvant chemoradiation group, compared to 35.6% in the "upfront surgery and pathological stage-based adjuvant chemoradiation" group (p = 0.147), and 20.3% in the "upfront surgery only" group (p < 0.001). No survival difference was observed between the "neoadjuvant chemoradiation followed by surgery" protocol and the "upfront surgery and pathological stage-based adjuvant chemoradiation" strategy.