Exosomal circ_0000735 contributes to non-small lung cancer malignant progression.

Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism in NSCLC progression need to be further explored. The expression levels of circ_0000735, miR-345-5p and A disintegrin and metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing and transwell assays were utilized to detect cell proliferation and metastasis. The protein levels of metastasis markers, exosome markers and ADAM19 were determined using western blot. Animal experiments were performed to confirm the role of circ_0000735 in NSCLC tumorigenesis. The exosomes from cells and serum were identified using transmission electron microscopy and nanoparticle tracking analysis. We found that circ_0000735 was upregulated in NSCLC, and its knockdown repressed NSCLC cell proliferation and metastasis. In terms of mechanism, circ_0000735 targeted miR-345-5p to regulate ADAM19. MiR-345-5p inhibitor reversed the suppressive effect of circ_0000735 knockdown on NSCLC progression, and ADAM19 overexpression abolished the inhibition effect of miR-345-5p on NSCLC progression. Also, animal experiments showed that silencing of circ_0000735 reduced NSCLC tumorigenesis. In addition, exosomes mediated the intercellular transmission of circ_0000735, and serum exosomal circ_0000735 might be an important indicator for the diagnosis of NSCLC. In conclusion, circ_0000735 facilitated NSCLC progression via miR-345-5p/ADAM19 pathway, and serum exosomal circ_0000735 might be a potential biomarker for NSCLC diagnosis.

Perioperative Chemotherapy Could Not Improve the Prognosis of Gastric Cancer Patients With Mismatch Repair Deficiency: A Multicenter, Real-World Study.

INTRODUCTION: To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer. MATERIALS AND METHODS: Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival. RESULTS: In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively). CONCLUSION: In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.

Concurrent clinical and pathological response predicts favorable prognosis of patients with gastric cancer after neoadjuvant therapy: a real-world study.

BACKGROUND: Response of locally advanced gastric cancer (LAGC) to neoadjuvant therapy (NAT) may be associated with prognosis, but which of the clinical or pathological evaluation can accurately predict a favorable prognosis is still controversial. This study aims to compare the effect of clinical and pathological response on the prognosis of patients with gastric cancer. METHODS: This study retrospectively analyzed LAGC patients who underwent NAT followed by surgery in the China National Cancer Center from January 2004 to January 2021. Clinical and pathological responses after NAT were evaluated using RECIST 1.1 and Mandard tumor regression grade system (TRG) respectively. Complete response (CR) and partial response (PR) assessed by computed tomography were regarded as clinical response. For histopathology regression assessment, response was defined as Mandard 1, 2, 3 and non-response as Mandard 4, 5. Furthermore, we combined clinical and pathological evaluation results into a variable termed "comprehensive assessment" and divided it into four groups based on the presence or absence of response (concurrent response, only clinical response, only pathological response, both non-response). The association between the prognosis and clinicopathological factors was assessed in univariate and multivariate Cox regression analysis. RESULTS: In total, 238 of 1073 patients were included in the study after screening. The postoperative pathological response rate and clinical response rate were 50.84% (121/238) and 39.92% (95/238), respectively. 154 patients got consistent results in clinical and pathological evaluation (66 were concurrent response and 88 were both non-response), while the other 84 patients did not. The kappa value was 0.297(p < 0.001), which showed poor consistency. Multivariate Cox regression analysis revealed that comprehensive assessment (P = 0.03), clinical N stage(P < 0.001), vascular or lymphatic invasion (VOLI) (HR 2.745, P < 0.001), and pre-CA724(HR 1.577, P = 0.047) were independent factors for overall survival in patients with gastric cancer. Among four groups in the comprehensive assessment, concurrent response had significantly better survival (median OS: 103.5 months) than the other groups (P = 0.008). CONCLUSION: Concurrent clinical and pathological response might predict a favorable prognosis of patients with gastric cancer after neoadjuvant therapy, further validation is needed in prospective clinical trials with larger samples.

The minimum number of examined lymph nodes was 24 for optimal survival of pathological T2-4 gastric cancer: a multi-center, hospital-based study covering 20 years of data.

INTRODUCTION: The current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer. METHODS: We used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999-2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5-6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711-0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399-0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659-0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675-0.888, P < 0.001). CONCLUSION: In conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24.

Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing.

BACKGROUND: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. METHODS: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. RESULTS: Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells. CONCLUSIONS: In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs.

Exceeding 30 ELNs is strongly recommended for pT3-4N0 patients with gastric cancer: A multicenter study of survival, recurrence, and prediction model.

The argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan-Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P = .171). However, the ELNs ≥ 30 group had a better disease-free survival (DFS) outcome compared with the others (all P < .05). An increased ELN group (ELNs ≥ 30) showed an improved OS only for pT3 patients (hazard ratio [HR] = 0.397, 95% confidence interval (CI): 0.182-0.866, P = .020), while an improved DFS for pT3 patients (HR = 0.362, 95%CI: 0.152-0.860, P = .021) and pT4 patients (HR = 0.484, 95%CI: 0.277-0.844, P = .011) in the multivariate analysis. A well discriminated and calibrated nomogram was constructed to predict the probability of the OS and DFS, with the C-index for OS and DFS prediction of 0.782 (95%CI: 0.735 to 0.829) and 0.738 (95%CI: 0.685 to 0.791), respectively. This study provides new and useful insights into the impact of ELN count on reducing stage migration and postoperative recurrence of pN0 patients with gastric cancer in 2000-2017. In conclusion, a larger number of ELNs is suggested for surgeons to prolong the prognosis of pN0 gastric cancer, especially for pT3 patients.

Development and validation of a novel competing risk model for predicting survival of esophagogastric junction adenocarcinoma: a SEER population-based study and external validation.

BACKGROUND: Adenocarcinoma in Esophagogastric Junction (AEG) is a severe gastrointestinal malignancy with a unique clinicopathological feature. Hence, we aimed to develop a competing risk nomogram for predicting survival for AEG patients and compared it with new 8th traditional tumor-node-metastasis (TNM) staging system. METHODS: Based on data from the Surveillance, Epidemiology, and End Results (SEER) database of AEG patients between 2004 and 2010, we used univariate and multivariate analysis to filter clinical factors and then built a competing risk nomogram to predict AEG cause-specific survival. We then measured the clinical accuracy by comparing them to the 8th TNM stage with a Receiver Operating Characteristic (ROC) curve, Brier score, and Decision Curve Analysis (DCA). External validation was performed in 273 patients from China National Cancer Center. RESULTS: A total of 1755 patients were included in this study. The nomogram was based on five variables: Number of examined lymph nodes, grade, invasion, metastatic LNs, and age. The results of the nomogram was greater than traditional TNM staging with ROC curve (1-year AUC: 0.747 vs. 0.641, 3-year AUC: 0.761 vs. 0.679, 5-year AUC: 0.759 vs. 0.682, 7-year AUC: 0.749 vs. 0.673, P < 0.001), Brier score (3-year: 0.198 vs. 0.217, P = 0.012; 5-year: 0.198 vs. 0.216, P = 0.008; 7-year: 0.199 vs. 0.215, P = 0.014) and DCA. In external validation, the nomogram also showed better diagnostic value than traditional TNM staging and great prediction accuracy. CONCLUSION: We developed and validated a novel nomogram and risk stratification system integrating clinicopathological characteristics for AEG patients. The model showed superior prediction ability for AEG patients than traditional TNM classification.

Clinical Outcomes of Proximal Gastrectomy versus Total Gastrectomy for Proximal Gastric Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: The extent of optimal gastric resection for proximal gastric cancer (PGC) continues to remain controversial, and a final consensus is yet to be met. The current study aimed to compare the perioperative outcomes, postoperative complications, and overall survival (OS) of proximal gastrectomy (PG) versus total gastrectomy (TG) in the treatment of PGC through a meta-analysis. METHODS: We systematically searched PubMed, Embase, The Cochrane Library, and Web of Science for articles published in English since database establishment to October 2019. Evaluated endpoints were perioperative outcomes, postoperative complications, and long-term survival outcomes. RESULTS: A total of 2,896 patients in 25 full-text articles were included, of which one was a prospective randomized study, one was a clinical phase III trial, and the rest were retrospective comparative studies. The PG group showed a higher incidence of anastomotic stenosis (OR = 2.21 [95% CI: 1.08-4.50]; p = 0.03) and reflux symptoms (OR = 3.33 [95% CI: 1.85-5.99]; p < 0.001) when compared with the TG group, while no difference was found in PG patients with double-tract reconstruction (DTR). The retrieved lymph nodes were clearly more in the TG group (WMD = -10.46 [95% CI: -12.76 to -8.17]; p < 0.001). The PG group was associated with a better 5-year OS relative to TG with 11 included studies (OR = 1.35 [95% CI: 1.03-1.77]; p = 0.03). After stratification for early gastric cancer and PG with DTR groups, however, there was no significant difference between the 2 groups (OR = 1.35 [95% CI: 0.59-2.45]; p = 0.62). CONCLUSION: In conclusion, PG was associated with a visible improved long-term survival outcome for all irrespective of tumor stage, while a similar 5-year OS for only early gastric cancer patients between the 2 groups. Future randomized clinical trials of esophagojejunostomy techniques, such as DTR following PG, are expected to prevent postoperative complications and assist surgeons in the choice of surgical approach for PGC patients.

Association between air pollutants and atrial fibrillation in general population: A systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with several risk factors. Recent studies have suggested that the exposure to air pollutants may increase the prevalence of AF, we evaluated those studies systematically to better elucidate the correlation between exposure to air pollution and AF. METHOD: We conducted a systematic review of publications using PubMed, Embase, the Cochrane library and Web of Science to explore the association between air pollutants and AF within the general population. The chosen studies were published until 7 July 2020. According to different study designs, we divided the outcomes into "short-term-exposure group" and "long-term-exposure group" for each pollutant. We used I2 statistics and Q-test to examine statistical heterogeneity, and sensitivity analysis to exclude the heterogeneous study. Fixed or random-effect model was used to combine the effects. Final result was presented as the OR and 95% CI of AF prevalence for every 10 µg/m3 increase in the concentration of PM2.5 and PM10;10 ppb increase in the concentration of SO2 ,NO2 ,O3; and 1 ppm increase in the CO concentration. RESULTS: Our analysis contain 18 studies. Underlying short-term exposure effect, for each increment of 10 µg/m3 in the PM2.5 concentration, the combined OR of AF prevalence was 1.01(1.00-1.02), for PM10 was 1.03(1.01-1.05). For a 10 ppb increment in the concentration of SO2, NO2, and O3 was 1.05(1.01-1.09), 1.03(1.01-1.04), and 1.01(0.97-1.06), respectively, for a 1 ppm increase of CO concentration was 1.02(0.99-1.06). Underlying long-term-exposure effect for each increment of 10 µg/m3 in the PM2.5 concentration; the combined OR of AF prevalence was 1.07(1.04-1.10) and that for PM10 was 1.03(1.03-1.04) For a 10 ppb increment in the NO2 concentration was 1.02(1.00-1.04). CONCLUSION: Our meta-analysis indicated that all air pollutants exposure had an adverse effect on AF prevalence in general population.

[Prognosis and Related Factors of Patients with Pathological Complete Response after Neoadjuvant Therapy for Gastric Cancer].

Objective To investigate the related factors of pathological complete response(pCR)of patients with gastric cancer treated by neoadjuvant therapy and resection,and to analyze the risk factors of prognosis. Methods The clinical and pathological data of 490 patients with gastric cancer who received neoadjuvant therapy followed by radical gastrectomy from January to December in 2008 were retrospectively analyzed.Univariate and multivariate analyses were performed to identify the risk factors affecting pCR and prognosis. Results Among the 490 patients,41 achieved pCR,and the overall pCR rate was 8.3%(41/490).The pCR rate was 16.0% in the neoadjuvant chemoradiation group and 6.4% in the neoadjuvant chemotherapy group.The results of multivariate analysis showed that neoadjuvant chemoradiation(OR=4.401,95% CI=2.023-9.574,P<0.001)and preoperative therapeutic response as partial response(OR=40.492,95% CI=5.366-305.572,P<0.001)were independent predictors of pCR after neoadjuvant therapy.Multivariate analysis of prognosis showed that poorly differentiated tumor(HR=1.809,95% CI=1.104-2.964,P=0.019),gastric cardia-fundus-body tumor(HR=2.025,95% CI=1.497-2.739,P<0.001),≤15 intraoperative dissected lymph nodes(HR=1.482,95% CI=1.059-2.073,P=0.022),and postoperative complications(HR=1.625,95% CI=1.156-2.285,P=0.005)were independent risk factors for prognosis,while pCR(HR=0.153,95% CI=0.048-0.484,P=0.001)and postoperative adjuvant chemotherapy(HR=0.589,95% CI=0.421-0.823,P<0.001)were independent protective factors of prognosis. Conclusions Patients who achieved pCR after neoadjuvant therapy for locally advanced gastric cancer might have promising long-term survival,and pCR is an independent predictor for overall survival.Compared with chemotherapy alone,preoperative chemoradiotherapy can significantly improve the pCR rate of patients with locally advanced gastric cancer.

Polybrominated Diphenyl Ethers, Polybrominated Biphenyls, and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study.

A nested case-control study was carried out using data from the US Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 histologically confirmed PTC cases (in 341 women and 401 men) and 742 matched controls with prediagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of 8 congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by sex. BDE-28, a polybrominated diphenyl ether congener, was associated with significantly increased risk of classical PTC (for the third tertile vs. below the limit of detection, odds ratio = 2.09, 95% confidence interval: 1.05, 4.15; P for trend = 0.02), adjusting for other congeners, body mass index, and branch of military service. This association was observed mainly for larger classical PTC (tumor size > 10 mm), with a significantly stronger association among women than men (P for interaction = 0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by sex and tumor size.

Is subtotal gastrectomy feasible for the treatment of gastric stump cancer located at the anastomotic site after distal gastrectomy for benign lesions?

BACKGROUND: Total gastrectomy (TG) is a widely accepted procedure for treating gastric stump cancer (GSC). However, subtotal gastrectomy (SG) would benefit elective patients with GSC. The aim of this study was to clarify the safety and long-term prognosis of SG in treating GSC after distal gastrectomy for benign lesions. METHODS: A total of 53 patients with GSC located at the anastomotic site or gastric body between May 1999 and December 2018 at our hospital were included. In total, 21 patients underwent SG, and the remaining 24 patients underwent TG. Clinicopathological data, operative data, and overall survival (OS) were compared. RESULTS: The operative duration, estimated blood loss volume, and length of hospital stay were similar between the SG and TG groups. The postoperative complications were similar between the two groups, but no cases of anastomotic leakage were noted in the SG group. TG was associated with significantly more retrieved lymph nodes than SG (18.5 ± 11.5 vs. 10.7 ± 9.2; p = 0.017), while the number of metastatic lymph nodes did not differ between the groups (2.9 ± 3.5 vs. 1.9 ± 3.6; p = 0.329). The median survival time in the SG group was 81.0 months (95% confidence interval (CI), 68.906 to 93.094 months), which was similar to the 45.0 months (95% CI, 15.920 to 74.080 months) observed in the TG group (p = 0.236). Both univariate and multivariate analyses showed that tumor location and histological type were prognostic factors, while surgery type was not a prognostic factor. Further stratified analyses according to tumor location revealed that OS was not significantly different between the two groups among patients with tumors located at the anastomotic site, while OS in the TG group was significantly better than that in the SG group among patients with tumors located in the gastric body (p = 0.046). CONCLUSIONS: The results of the current study indicate that SG is a suitable alternative surgical procedure for GSC located at the anastomotic site after distal gastrectomy for benign lesions. The short-term outcomes and long-term prognoses of SG are comparable with those of TG.

Clinicopathological Characteristics, Surgical Treatments, and Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumor.

BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are rare and their clinicopathological features have not been completely described. In this retrospective study, we examined the characteristics and long-term outcomes of patients who underwent surgical treatment for duodenal GISTs. METHODS: We examined patients surgically treated for duodenal GISTs from 1999 to 2016 at the China National Cancer Center. We analyzed patient characteristics, treatments, histological examinations, and survival outcomes. RESULTS: The 52 surgeries performed included 14 pancreaticoduodenectomies (26.9%), 37 limited resections (71.2%), and one palliative bypass procedure (1.9%). No surgery-related death occurred. The complication rate in patients who underwent pancreaticoduodenectomy was slightly higher than that in patients who underwent limited resection. The 5-year overall survival and progression-free survival rates for patients with duodenal adenocarcinoma were 89.1 and 72.9%, respectively. The overall survival and progression-free survival rates were not significantly related to surgical methods. Large tumor size and high mitotic rate were associated with poor overall survival outcomes. However, no independent factor was associated with prognosis, which may be due to the small sample size. CONCLUSION: The prognosis of duodenal gastrointestinal stromal tumors was good. Limited resection seems to be oncologically feasible, with outcomes being less worse than those of pancreaticoduodenectomy.

Alcohol Consumption and Risk of Thyroid Cancer: A Population Based Case-Control Study in Connecticut.

BACKGROUND: Studies examining the association between alcohol consumption and thyroid cancer risk have been inconsistent, in part due to varying types and amounts of alcohol consumption, incomplete information on confounders, and variations in genetic susceptibility in study populations. METHODS: The present study analyzed data from a population-based case-control study in Connecticut in 2010-2011 including 462 histologically confirmed incident thyroid cancer cases and 498 population-based controls. Unconditional logistic regression was used to estimate associations between alcohol consumption and risk of thyroid cancer. Potential confounding variables were age, gender, race, education, body mass index, family history of cancer among first-degree relatives, history of benign thyroid disease, smoking status, and physical activity. RESULTS: Ever consumption of alcohol was associated with a reduced risk of thyroid cancer (OR = 0.71, 95% CI: 0.54-0.95). The younger age at initiation and increasing duration of alcohol consumption were also associated with a reduced risk of thyroid cancer in a dose-dependent manner (P for trend = 0.041 and 0.0065, respectively). Compared to people who never drank alcohol, people who drank alcohol for >31 years were 50% less likely to develop thyroid cancer (OR = 0.50, 95% CI: 0.32-0.80). Alcohol consumption was associated with a reduced risk of papillary thyroid cancer (OR = 0.66, 95% CI: 0.49-0.88) and thyroid cancer with lager tumor size (>1 cm), but no significant association was found between alcohol consumption and non-papillary thyroid cancer or thyroid microcarcinoma. Analyses stratified by specific subtypes of alcohol demonstrated an inverse association for beer (OR = 0.69, 95% CI: 0.49-0.96) and wine consumption (OR = 0.71, 95% CI: 0.53-0.96) as compared to participants who never consumed alcohol, but no significant association was found for liquor consumption (OR = 0.75, 95% CI: 0.53-1.04). CONCLUSIONS: The study findings suggest an inverse association between alcohol consumption and risk of thyroid cancer. Future mechanistic study is warranted to elucidate the underlying mechanisms.

Use of Dietary Vitamin Supplements and Risk of Thyroid Cancer: A Population-Based Case-Control Study in Connecticut.

Certain dietary supplements have been reported to increase the risk of some cancers. Over half of the US population regularly uses dietary supplements. Thyroid cancer incidence has increased over the past several decades. However, few studies have investigated the association between dietary supplements and thyroid cancer. Thus, it is essential to clarify any association between dietary supplements and risk of thyroid cancer. MATERIALS AND METHODS: A population-based case-control study in Connecticut was conducted during 2010-2011 among 462 histologically confi rmed incident thyroid cancer cases and 498 population-based controls. Dietary supplement intake was ascertained through in-person interviews and a food frequency questionnaire. Multivariate unconditional logistic regression models were used to estimate the risk of thyroid cancer and dietary supplement use. RESULTS: Overall, no statistically signifi cant associations were observed between dietary supplementation and thyroid cancer risk. Stratifi ed analyses revealed a suggestive protective effect on risk of papillary microcarcinoma among longterm (> 10 years) use of multivitamins (OR = 0.59, 95 % CI: 0.33, 1.04) and calcium supplementation (OR = 0.45, 95 % CI: 0.22, 0.93). An increased risk of large papillary thyroid cancers (tumor size > 1 cm) was observed among short-term (< 5 years) users of calcium supplements (OR = 2.24, 95 % CI: 1.30, 3.88). DISCUSSION: No signifi cant associations were observed between supplementation and overall thyroid cancer risk. The different associations between calcium supplements and risk of papillary thyroid cancer by tumor size warrant further investigation.

The 7th AJCC/UICC TNM staging system may be not suitable in predicting prognosis of synchronous multiple gastric carcinoma patients with D2 gastrectomy.

To assess the suitability of the 7th AJCC/UICC TNM staging system in predicting the prognosis of synchronous multiple gastric carcinomas (SMGCs). A total of 129 SMGC patients who underwent gastrectomy with D2 lymphadenectomy from January 1999 to January 2009 were enrolled in this study. The location, diameter, and depth of invasion of the main tumor were all related to prognosis (P < 0.05). Multivariate analysis revealed depth of invasion as an independent predictive factor for survival (P < 0.05). Interestingly, logistic regression analysis showed that the 7th AJCC/UICC N staging system was unable to significantly predict survival in SMGCS patients (P > 0.05). Cut-point survival analysis identified the most appropriate cut-offs for metastatic lymph nodes (MLNs) as 0, 1, 6, 10, and 19: patients with 0, 1-6, 7-10, and 11-19, and ≥ 20 MLNs had median survival times of 70, 56, 35, 52, and 32 months, respectively. Multivariate analysis suggested this new categorization of MLNs to be a significant predictor of survival (P < 0.05). Preoperative assessment of depth of invasion can help in the prognosis of SMGCs patients. The 7th UICC TNM staging system may be not suitable for SMGC patients and needs improvement for rational grading of SMGCs.

Association of Genetic Polymorphisms in UDP-Glucuronosyltransferases 2B17 with the Risk of Pancreatic Cancer in Chinese Han Population.

BACKGROUND: This study is aimed to investigate the association between polymorphisms in UGT2B17 and the risk of developing pancreatic cancer in Chinese Han population. METHODS: A hospital-based case-control study was conducted, and 1579 healthy controls and 406 pancreatic cancer patients were enrolled. Real-time PCR was applied to identify the genetic polymorphisms in the subjects, and multivariable logistic regression analysis was performed to investigate the association between UGT2B17 polymorphisms and susceptibility to pancreatic cancer. RESULTS: The prevalence of the UGT2B17 del/del, del/ins, and ins/ins in cases were 72.9%, 24.0%, and 3.1%, respectively, and in controls 66.6%, 30.7%, and 2.7%, respectively. Multivariable logistic regression revealed that, compared with the del/del genotype, the del/ins genotype in UGT2B17 is related to a significant reduction in pancreatic cancer risk (OR = 0.77, 95% CI = 0.60 - 0.99; P = 0.04). In the female subjects, compared with the del/del genotype, the del/ins genotype was related to a substantial reduction in pancreatic cancer risk (OR = 0.59, 95% CI = 0.39 - 0.90, P = 0.01). CONCLUSIONS: All these results indicate a higher ratio of UGT2B17 deletion polymorphisms in Asians. UGT2B17 deletion polymorphisms are associated with the risk of developing pancreatic cancer in Chinese Han population, especially in the female population.

[Value of intraoperative fine needle aspiration cytology in the diagnosis of pancreatic cancer].

OBJECTIVE: To evaluate the value of intraoperative fine needle aspiration cytology (IFNAC) examination in the diagnosis of pancreatic lesions. METHODS: The clinicopathological data of 491 patients with pancreatic lesions treated in our hospital from May 1998 to June 2013 were retrospectively analyzed. Their clinical features, IFNAC findings, pathological results after IFNAC examination and related complications were summarized. The factors affecting the aspiration biopsy accuracy were analyzed using logistic regression and multi factor analysis. RESULTS: 491 patients with pancreatic lesions were examined by IFNAC. Among them, cancer cells were found in 434 cases (positive), and were not found in 57 cases (negative). Among the 310 cases who underwent surgical operation, postoperative pathology confirmed 209 cases of pancreatic ductal adenocarcinoma, 8 cases of pancreatic cystadenocarcinoma, 23 cases of solid pseudopapillary tumor of the pancreas, 15 cases of pancreatic neuroendocrine tumor, 14 cases of intraductal papillary mucinous tumor, 2 cases of primary pancreatic gastrointestinal stromal tumor, 17 cases of pancreatic serous cystadenoma, and 22 cases of chronic mass-forming type pancreatitis. The IFNAC test showed a sensitivity of 97.9% (425/434), and specificity of 89.5% (51/57). The IFNAC examination-related complications were pancreatic leakage in a total of 12 patients which were cured after treatment. No bleeding complication was observed. Logistic multivariate analysis showed that tumor size, cystic degeneration, lymph node metastasis and associated chronic pancreatitis are independent factors affecting the IFNAC examination of pancreatic carcinoma. CONCLUSIONS: IFNAC examination has a high sensitivity and specificity, and with a good safety in clinical use. IFNAC can be used as a powerful tool for the diagnosis of pancreatic cancer, with a high clinical value in use. In the cytology-negative cases, cytology alone can not rule out the diagnosis of pancreatic cancer. Through repeated sampling and combined with intraoperative frozen section pathology can improve the diagnostic accuracy.

[Value of PUSSOM and P-POSSUM for the prediction of surgical operative risk in patients undergoing pancreaticoduodenectomy for periampullary tumors].

OBJECTIVE: To investigate the value of Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and a modification of the POSSUM system (P-P0SSUM) scoring system in predicting the surgical operative risk of pancreaticoduodenectomy for periampullary tumors. METHODS: POSSUM and P-POSSUM scoring systems were used to retrospectively evaluate the clinical data of 432 patients with periampullar tumors who underwent pancreaticoduodenectomy in the Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from January 1985 to December 2010. The predictive occurrence of postoperative complications and mortality rate were calculated according to the formula. ROC curve analysis and different group of risk factors were used to determine the discrimination ability of the two score systems, and to determine their predictive efficacy by comparing the actual and predictive complications and mortality rates, using Hosmer-Lemeshow test to determine the goodness of fit of the two scoring systems. RESULTS: The average physiological score of the 432 patients was 16.1 ± 3.5, and the average surgical severity score was 19.6 ± 2.7. ROC curve analysis showed that the area under ROC curve for mortality predicted by POSSUM and P-POSSUM were 0.893 and 0.888, showing a non-significant difference (P > 0.05) between them. The area under ROC curve for operative complications predicted by POSSUM scoring system was 0.575. The POSSUM score system was most accurate for the prediction of complication rates of 20%-40%, showing the O/E value of 0.81. Compared with the POSSUM score system, P-POSSUM had better ability in the prediction of postoperative mortality, when the predicted value of mortality was greater than 15%, the predictive result was more accurate, and the O/E value was 1.00. CONCLUSIONS: POSSUM and P-POSSUM scoring system have good value in predicting the mortality of patients with periampullary tumors undergoing pancreaticoduodenectomy, but a poorer value of POSSUM score system in prediction of complications. We can establish a more suitable scoring system for pancreaticoduodenectomy by modifying the score constant and weight, to better predict surgical risk and reduce the operative complications and mortality.

[Learning curve for middle pancreatectomy].

OBJECTIVE: To explore the learning curve for middle pancreatectomy by comparing the outcomes of middle pancreatectomy operated by a single treatment group at different stages. METHODS: A total of 48 patients received middle pancreatectomy by single treatment group between January 2006 and April 2014 at our hospital. These 48 cases were divided into 10 stages (5 cases in each) according to the operation sequence. The operation time, blood loss, surgical complications, rate of negative margin and postoperative hospital stay were analyzed retrospectively. RESULTS: There was no significant difference among the 10 stages in respect to surgical complications, rate of negative margin and postoperative hospital stay (P>0.05). The median operation time and blood loss in the first stage was 375 min and 530 ml, respectively. The median operation time and blood loss in the second stage was 280 min and 330 ml, respectively. There were significant differences between these two stages and the other later stages in median operation time and blood loss (P<0.01). However, there was no significant difference among the stages 3 to 10 in the median operation time and blood loss (P>0.05 for all). CONCLUSION: After 10-15 cases of middle pancreatectomy, a surgeon can be skilled and experienced in this surgical procedure with few surgical complications.