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Objective. To construct a nomogram-based prediction model for the clinical prognosis of patients with stage II and III colon cancer who underwent Xelox chemotherapy after laparoscopic radical resection based on large data sets. Methods. A total of 7,832 patients with colorectal cancer who received postoperative Xelox-based chemotherapy were screened from the Surveillance, Epidemiology, and End Results database (USA) as the training data set. In addition, 348 domestic patients were screened as the validation data set. Multivariate Cox regression analysis was performed to identify variables for inclusion in the nomogram-based prediction model. The predictive accuracy of the model was assessed using C-index and calibration curve. Results. Age, cell differentiation, nerve invasion, T and N stages of tumours, number of dissected lymph nodes, and carcinoembryonic antigen (CEA) level were found to influence the efficacy of postoperative chemotherapy. The nomogram-based prediction model was successfully constructed. The C-index of both the training set and validation set were higher than those of the 7th edition of TNM staging system published by the American Joint Commission on Cancer ( C − index of training data set = 0.728 , C − index of validation data set = 0.734 ). The prediction results of the model in the calibration curve showed a good fit with the actual situation. Conclusion. We successfully constructed a nomogram-based model to predict the clinical prognosis of patients with colorectal cancer receiving postoperative Xelox-based chemotherapy after laparoscopic radical resection, which showed good clinical application value for predicting the efficacy of postoperative Xelox-based chemotherapy in patients with colorectal cancer.

Main pointOur retrospective analysis of a large number of cases found in patients with primary colorectal cancer (CRC) carrying positive HBsAg inhibited the occurrence of synchronous liver metastases (SLM). However, liver cirrhosis caused by non-HBV factors promoted the occurrence of SLM.ObjectivesThis study aimed to investigate the effect of HBV on the occurrence of synchronous liver metastases (SLM) of colorectal cancer (CRC).MethodsUnivariate and multivariate analyses were used to analyze the influence of clinical parameters on the occurrence of SLM.ResultsA total of 6, 020 patients with primary CRC were included in our study, of which 449 patients carrying HBsAg(+) accounted for 7.46%. 44 cases of SLM occurred in the HBsAg(+) group, accounting for 9.80%, which was much lower than 13.6% (758/5571) in the HBsAg(-) group (X=5.214, P=0.022). Among CRC patients with HBsAg(-), the incidence of SLM was 24.9% and 14.9% in the group with high APRI and FIB-4 levels, respectively, which were significantly higher than that in the compared groups (12.3% and 12.5%, all PConclusionsThe carriage of HBsAg(+) status inhibited the occurrence of SLM from CRC. HBV-causing liver cirrhosis did not further influence the occurrence of SLM, whereas non-HBV-factor cirrhosis promoted the occurrence of SLM. Nevertheless, this still required prospective data validation.

Long non‑coding RNAs (lncRNAs) are common in the human body. Misregulated lncRNA expression can cause a variety of diseases in the human body. The present study aimed to investigate the effect of lncRNA differentiation antagonizing non‑protein‑coding RNA (DANCR) on glioma proliferation and autophagy through the microRNA (miR)‑33b/distal‑less homeobox 6 (DLX6)/autophagy‑related 7 (ATG7) axis. Reverse transcription‑quantitative PCR was used to detect DANCR and miR‑33b expression. Cell Counting Kit‑8 assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transmission electron microscopy was used to determine the autophagy level by observing intracellular autophagosomes. A western blot assay was used to detect protein expression levels and determine the level of autophagy in different cells. The binding sites of miR‑33b and DANCR or DLX6 were detected using a dual‑luciferase reporter assay. A chromatin immunoprecipitation assay confirmed DLX6 as a transcript of ATG7.

Background: Gallbladder lesions have become more common nowadays. But there is limited evidence-based guidance on surveillance of these patients for malignancy. Predicting malignancy could help clinicians better manage this condition and improve the prognosis. We evaluated the independent and joint effects of metabolic syndrome components on the risk of malignancy among patients with gallbladder lesions. Methods: Using a multicenter database, consecutive patients with pathologically confirmed gallbladder lesions between 2012 and 2019 were identified. Univariate and multivariate logistic regression analyses were used to evaluate the effects of metabolic syndrome components (diabetes, hypertension, dyslipidemia and obesity) as additive or combined indicators for the risk of malignancy. Unadjusted and adjusted odds ratios were calculated. Results: Of the 625 patients, 567 patients were identified with benign gallbladder lesions and 58 patients with gallbladder cancer (GBC). GBC group had less obesity but more dyslipidemia. Among all metabolic syndrome components, only dyslipidemia was significantly associated with GBC (odds ratio 2.674, 95% confidence interval 1.173-6.094). Dyslipidemia was an independent risk factor for malignancy (adjusted odds ratio 2.164, 95% confidence interval 1.165-4.021), regardless of whether the other risk factors and metabolic syndrome components were combined. Patients with decreased high-density lipoprotein had 3.035-fold higher risk of malignancy (adjusted odds ratio 3.035, 95% confidence interval 1.645-5.600). Conclusions: Dyslipidemia is associated with a 2.674-fold increase in the risk of malignancy in patients with gallbladder lesions. Dyslipidemia is an independent risk factor for malignancy, regardless of the presence of the other risk factors and metabolic syndrome components.

Objective The global burden of rectal gastrointestinal stromal tumor (GIST) is increasing. However, a limited number of reports hinder our ability to reach a definitive conclusion regarding the current treatment and prognosis. In this study, we outline our experience with open transanal resection of rectal GIST following neoadjuvant therapy with imatinib mesylate (IM). Patients and methods We retrospectively analyzed 11 patients with rectal GISTs treated with neoadjuvant IM therapy and open transanal resection between April 2011 and April 2017 in Shanghai Changzheng Hospital. Results The patients had 400-600 mg/day IM once daily for a median of 7 months (range: 3-9 months). Tumor size, distance from the lower margin of the tumor to the anal verge (AV), mitotic rates and mutation analysis were assessed on pretreatment biopsy. After reassessment, all 11 patients underwent transanal R0 resection. With median follow-up of 28 months (range: 8-80 months), there was no tumor recurrence or metastasis. Conclusion Open transanal resection of rectal GIST after neoadjuvant treatment with IM has good surgical and survival outcomes.

Background: Metabolomics has demonstrated its potential in the early diagnosis, drug safety evaluation and personalized toxicology research of various cancers. Objectives: We aim to screen for potential diagnostic and capecitabine-related adverse effect (CRAE) biomarkers from urinary endogenous metabolites in Chinese colorectal cancer (CRC) patients. Methods: The metabolic profiles of 139 CRC patients and 50 non-neoplastic controls were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. Results: There were 41 metabolites identified between the CRC patients and the non-neoplastic controls, and 19 metabolites were identified between CRC patients with and without CRAE. Based on these identified metabolites, bioinformatic analysis and prediction model construction were completed. Most of these differential metabolites have important roles in cell proliferation and differentiation and the immune system. Based on binary logistic regression, a CRC prediction model, composed of 3-methylhistidine, N-heptanoylglycine, N1,N12-diacetylspermine and hippurate, was established, with an area under curve (AUC) of 0.980 (95% CI: 0.953-1.000; sensitivity: 94.3%; specificity: 92.0%) in the training set, and an AUC of 0.968 (95% CI: 0.933-1.000; sensitivity: 89.9%; specificity: 92.0%) in the testing set. In addition, methionine and 4-pyridoxic acid can be combined to predict hand foot syndrome, with an AUC of 0.884; ubiquinone-1 and 4-pyridoxic acid can be combined to predict anemia, with an AUC of 0.889; and 5-acetamidovalerate and 3,4-methylenesebacic acid can be combined to predict neutropenia, with an AUC of 0.882. Conclusion: The profiling of urine polar metabolites has great potential in the early detection of CRC and the prediction of CRAE.

Formyl peptide receptor 1 (FPR1) belongs to G protein-coupled receptors expressed mainly in phagocytic leukocytes. The gene encoding FPR1 is highly polymorphic and related to inflammation. In this study, we investigated the single nucleotide polymorphisms (SNPs) of Fpr1 in human colorectal cancer (CRC), and analyzed the association of Fpr1 SNPs with clinicopathological parameters and some specific diagnostic markers of CRC. Although the allele and genotype frequencies of Fpr1 SNPs in CRC tissues were not significantly different from that in whole blood cells derived from healthy Chinese subjects. Significant associations were observed between genotypes of c.289C>A and distant metastasis (P=0.001), and between genotypes of c.306T>C and tumor size (P=0.016). Genotypes of c.546C>A was closer to tumor size and lymphatic invasion (P=0.012 and P=0.043, respectively). Meanwhile, genotypes of c.1037C>A was related with tumor location and differentiation (P=0.000 and P=0.005, respectively). Besides, genotypes of c.576T>C>G was related with pathological type (P=0.000). Furthermore, several Fpr1 SNP positions including c.289 (C>A) and c.576 (G>C>T) were related to the expression of P53 (P=0.004 and P=0.008, respectively), and similar results were observed between other Fpr1 SNP positions and CEA, HER2 and Ki-67 (P

Objective Our objective was to explore the impact of tumor sites on lymph node (LN) status and prognosis in non-distant metastasis colon cancer after radical operation. Methods Surveillance, epidemiology, and end results (SEER) database was used to identify 124, 836 early-stage colon cancer patients between 1988 and 2010, treated with radical surgery with a known tumor site. Seven tumor sites were defined as ascending, hepatic, cecum, transverse, descending, splenic, and sigmoid colons by the anatomical location. The associations of tumor site and LN status, including adequate (≥12) LN harvest and LN positivity, were examined with logistic regression, adjusting for multiple covariates. Relative survival was compared in a flexible parametric model. Results The quartile number of LN examined gradually decreased from ascending to sigmoid colon cancer (P

Self-expanding metallic stent placement as a bridge to surgery has been reported as an alternative to emergency surgery for acute malignant colorectal obstruction. However, results from clinical trials and previous meta-analyses are conflicting. We carried out a meta-analysis to compare the surgical and oncological outcomes between emergency surgery and self-expanding metallic stents for malignant large bowel obstruction. Pubmed, Embase, CINAHL, Web of Science and Cochrane were searched for prospective and randomised controlled trials. The outcomes of focus included 3- and 5-year overall and disease-free survival, overall tumour recurrence, overall complication and 30-day mortality rate, length of hospital and ICU stay, overall blood loss, number of patients requiring transfusion, total number of lymph nodes harvested, stoma and primary anastomosis rate. Twenty-seven studies were included with a total of 3894 patients. There was no significant difference in terms of 3-year and 5-year disease-free and overall survival. Stenting resulted in less blood loss (mean difference -234.72, P < 0.00001) and higher primary anastomosis rate (RR 1.25, P < 0.00001). For curative cases, bridge to surgery groups had lower 30-day mortality rate (RR 0.65, P = 0.01), lower overall complication rate (RR 0.65, P < 0.0001), more lymph nodes harvested (mean difference 2.51, P = 0.005), shorter ICU stay (mean difference -2.27, P = 0.02) and hospital stay (mean difference -7.24, 95% P < 0.0001). Compared to emergency surgery, self-expanding metallic stent interventions improve short-term surgical outcomes, especially in the curative setting, but have similar long-term oncological and survival outcomes.

Negative lymph node (NLN) count has been recognized as a prognostic indicator in various cancers. However, the relationship between NLN count and the prognosis of cervical cancer is still unknown. In this study, 10, 500 cervical cancer patients after radical surgery were selected from Epidemiology and End Results Program (SEER) data. Clinicopathological characteristics were collected for analysis, including year of diagnosis, age, race, grade, primary site, FIGO stage and cause specific survival (CSS). Univariate and multivariate Cox proportional hazards model was used to assess risk factors for survival of patients. X-tile plots identified 6 as the optimal cutoff value of NLN count to divide patients into high and low risk subsets in terms of CSS (χ2 = 183.95, P < 0.001). The rate of 5-year CCS of cervical cancer patients was improved with an increase in NLN count from 0 to 23 (all P < 0.001). NLN count was validated as an independently prognostic factor by the multivariate Cox analysis (HR: 1.571, 95% CI: 1.370~1.801, P < 0.001). Subgroup analysis showed that NLN count was a prognosis factor in FIGO stage I (χ2=35.023, P < 0.001), stage II (χ2 = 12.910, P < 0.001), stage III + IV (χ2 = 9.732, P = 0.002) and unknown stage (χ2 = 16.654, P < 0.001). Conclusively, this study demonstrated the NLN count was an independent prognostic factor for cervical cancer patients.

The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects. In addition, knockdown of TROP2 increased the expression of total PTEN, p-PTEN and PDK-1 but reduced p-AKT via PI3K/AKT pathway. TROP2 downregulation also inhibited vimentin and increased E-cadherin expression during epithelial-mesenchymal transition (EMT). Moreover, gallbladder cancer cells with TROP2 knockdown formed smaller xenografted tumors in vivo. In consistent with in vitro results, TROP2 inhibition decreased Akt phosphorylation, increased PTEN expression and postponed EMT of gallbladder cancer cells in vivo. In conclusion, we revealed that TROP2 promoted the proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT. TROP2 could serve as a potential prognostic biomarker and therapeutic target for the clinical management of gallbladder cancer.

// Xinxing Li 1, * , Weigang Zhang 1, * , Xianwen Zhang 1, * , Haolu Wang 2 , Kai Xu 1 , Houshan Yao 1 , Jun Yao 1 , Xiaowen Liang 2 and Zhiqian Hu 1 1 Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China 2 Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia * These authors have contributed equally to this work Correspondence to: Xiaowen Liang, email: x.liang@uq.edu.au Zhiqian Hu, email: huzhiq163@163.com Keywords: gastric cancer, preoperative radiotherapy, negative lymph node, survival Received: October 29, 2016 Accepted: December 27, 2016 Published: February 01, 2017 ABSTRACT Negative lymph node (NLN) count provides accurate prognostic information in patients with gastric cancer. However, it is unclear whether NLN still has prognostic value for patients received preoperative radiotherapy. In this study, Surveillance, Epidemiology, and End Results Program (SEER)-registered gastric cancer patients were used for analysis. Clinicopathological characteristics and survival time were collected. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. NLN count was validated as an independent prognostic factor in both univariate and mulivariate analysis (P < 0.001). X-tile plots identified 12 as the optimal cutoff value to divide the patients into high and low risk subsets in terms of survival rate. Nomogram based on cancer-specific survival was successfully established according to all significant factors. The C-index was 0.630 (95% CI: 0.605–0.655). Subgroup analysis showed that NLN count was a prognosis factor for patients with advanced gastric cancer (stage ypII and ypIII). In conclusion, our results firmly demonstrated that NLN count was an independent prognostic factor for patients with gastric cancer who received preoperative radiotherapy. It provides more accurate prognostic information especially for patients with advanced gastric cancer (stage ypII and ypIII). Nomograms based on cancer-specific survival could be recommended as practical models to evaluate prognosis.

Background There is a lack of well-established biomarkers to predict the efficacy of pemetrexed-based therapy. In this prospective phase II study, we investigated the correlation of folate receptor (FR)-positive circulating tumor cell (CTC) level with pemetrexed efficacy in patients with advanced non-squamous non-small cell lung cancer (nsNSCLC). Methods A total of 98 nsNSCLC patients were enrolled. Peripheral blood was collected from each patient prior to initiation of treatment. FR-positive CTCs were enriched by immunomagnetic leukocyte depletion and quantified using LT-PCR method. Results Patients with relatively low CTC level (11-16 FU/3 mL, n = 32) showed a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to the ‘high CTC level group’ (≥16 FU/3 mL, n = 28; median PFS: 133 versus 320 days, hazard ratio[HR]=4.78, P = 0.0008; median OS: 632 days versus ‘not reached’, HR = 10.89, P = 0.0013). The ‘high CTC level group’ also achieved superior objective response rate (ORR) and disease control rate (DCR) over the ‘low CTC level group’ (ORR: 40.9% versus 9.5%, P = 0.0339; DCR: 100% versus 81.0%, P = 0.0485). The efficacy of pemetrexed in the ‘negative-CTC group’ ( Conclusions Our results implied that FR-positive CTC is an efficacious biomarker to predict the outcome of first-line pemetrexed-based therapy in nsNSCLC patients. Clinical trial identification ChiCTR-ONC-13003475. Legal entity responsible for the study Shanghai Pulmonary Hospital. Funding This study was partially supported by Shanghai Committee of Science and technology (No. 14411970800). The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Disclosure All authors have declared no conflicts of interest.

Astrocytomas are one of the most vascularized types tumor in human cancers. Micro-vascular proliferation is an important factor for the classification of astrocytoma. Vasculogenic mimicry (VM) is a novel tumor vascular model that develops independently of endothelial cells, and serves an important role in astrocytoma. Twist family bHLH transcription factor 1 (Twist1) is able to regulate the formation of VM; thus in the present study, the expression and importance of Twist1 was studied in astrocytoma tissues. The present study confirmed that the expression of Twist1 was associated with the grade of astrocytoma. Twist1 promotes the formation of VM and the development of astrocytomas, and may also regulate the formation of VM via vascular endothelial-cadherin and matrix metalloproteinase-9.

Background: Lymph node (LN) positivity is a prognostic indicator in patients with colon cancer regardless of age, and age is an important parameter that impacts therapeutic recommendations. But little is known about the impact of age on LN positivity in patients with colon cancer.Methods: We analyzed 257,334 patients with colon cancer diagnosed from SEER database. Logistic regression was used to examine the association of age and LN positivity. Poisson regression was used to evaluate whether age was associated with the number of positive LNs.Results: LN positivity was inversely associated with age (P < .001 for each T stage). Age was predictive of LN positivity after adjustment for number of LNs examined and other covariates (P < .001 for each T stage). Adjusted odds ratios (ORs) for LN positivity for age 20 to 39 vs 80+ were 3.06 for stage T1 (95 % CI, 2.09 to 4.48), 2.46 for stage T2 (95 % CI, 2.00 to 3.02), 1.77 for stage T3 (95 % CI, 1.62 to 1.93), and 1.68 for stage T4 (1.51 to 1.86). Young age was a significant predictor of an increased number of positive LNs (P < .005 for each T stage). Conclusion: Young age at diagnosis is associated with an increased risk of LN positivity. LN examination and resection could aid younger patients more with detection and removal of metastasis. Guidelines that define post detection interventions may be needed to limit the over treatment of older patients, who may be vulnerable to unnecessary tests and treatments. Refereed/Peer-reviewed

This article has been corrected: Due to errors in image processing, Figure 2C contains an image from the wrong cell line (GBC-SD cells). The corrected Figure 2C is shown below. The authors declare that these corrections do not change the results or conclusions of this paper.

Background Epidermal growth factor receptor (EGFR) exon 19 deletion (19del) and L858R mutation respond differently to first generation tyrosine kinase inhibitors (TKIs), however, the clinical outcomes of different 19del variants to TKIs and the resistance patterns are not well studied. Methods From April 2016 to August 2017, 194 treatment-naive NSCLC patients detected as EGFR exon 19 deletions using amplification-refractory mutation system were included. DNA sequencing was used to detect the subtypes. Clinicopathological features as well as patients’ outcomes to first-line EGFR TKIs were analyzed. Results Twelve EGFR 19del variants were confirmed in 169 of the 194 samples. Among these, p.E746_A750del was the most frequent variant (147/169, 87.0%). p.E746_A750del was more frequently found in females (p = 0.008) and never smokers (p = 0.004) than other deletions. And deletions starting with E746 was also more frequently found in these patients than L747 (p = 0.014 and p = 0.018, respectively). Interestingly, T790M occurred more frequently in p.E746_A750del than other deletions (64.3% vs 18.2%, p = 0.017) or deletions started with E746 than L747 (63.6% vs 11.1%, p = 0.012). Patients harboringdeletions starting with L747 plus insertions had significantly shorter progression-free survival (PFS) than no insertions (8.3m vs 15.0m, p = 0.008), as well as other subtypes (8.3m vs 12.8m, p = 0.016). Multivariate analysis showed that only L747 deletion plus insertions and age were independent factors influencing PFS (p = 0.015 and 0.046, respectively). Conclusions p.E746_A750del was the most frequent variant of EGFR exon 19del in NSCLC patients. It was more frequently found in female and never smoking patients. T790M mutation had a higher ratio in these patients when they were resistant to first-line TKI treatment. Deletions starting with L747 plus insertions had shorter PFS than other variants. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Tumor mutation burden (TMB) and T cell receptor (TCR) diversity have been suggested as predictive biomarkers in cancer immunotherapy. It is not clear how chemotherapy influences TMB, and how TMB or clinical factors correlate with TCR clonality. The aim of this study is to investigate the relationship between TMB and TCR clonality and to provide suggestions for patient selection and the opportunity to start immunotherapy in East Asian late-stage lung cancer patients with first-line chemotherapy. Methods 43 NSCLC patients and 18 SCLC patients with no TKI-related driver gene (EGFR, ALK, ROS1, RET, BRAF, C-MET) mutations were enrolled in this study. Genomic variations and TMB were determined with lung cancer tissue by whole-exome sequencing (WES). TCR sequencing was also performed with peripheral blood samples. Sequencing data were analyzed with R packages and statistics analysis was performed with SPSS 20 software. P ≤ 0.05 was regarded as statistically significant. Results The mutation spectrums were changed dramatically after chemotherapy in NSCLC patients. Chemotherapy appeared to cause decreases in the positive detection rate of mutated genes. Significant decrease in TMB from mean value of 3.67 to 1.95 were observed after chemotherapy in these NSCLC patients (p = 0.05), and patients can be dichotomized based on TMB decrease extent. The relationship between TCR clonality and TMB or clinical factors were also explored in NSCLC and SCLC patients. The number of TCR clones was not correlated with TMB, gender, age, metastasis, lung cancer subtype or therapeutic response (p > 0.05). However, it was dramatically higher in patients with smoking history than those with no smoking history (p = 0.01). Conclusions This study suggested that chemotherapy could alter the genomic profiles and TMB dramatically. Patients with decreased TMB after the first-line chemotherapy may be less likely to benefit from immunotherapy. Non-smokers with higher TCR diversity than smokers may be more likely to benefit from immunotherapy. Since the number of TCR clones was not correlated with TMB, it is still worth investigating whether TMB or TCR clonality, or both combined is a better predictive biomarker for immunotherapy. Legal entity responsible for the study The authors. Funding This study was supported in part by a grant from National Natural Science Foundation of China (81802255), Shanghai Pujiang Program (17PJD036) and a grant from Shanghai Municipal Commission of Health and Family Planning Program (20174Y0131). National key research & development project (2016YFC0902300). Major disease clinical skills enhancement program of three-year action plan for promoting clinical skills and clinical innovation in municipal hospitals, Shanghai Shen Kang Hospital Development Center Clinical Research Plan of SHDC (16CR1001A). The fundamental research funds for the central universities. Disclosure All authors have declared no conflicts of interest.

Marital status has been found to be a prognostic factor for survival in various cancers, but its role in gallbladder cancer (GBC) has not been fully studied. In this study, we used the Surveillance, Epidemiology, and End Results Program (SEER)-registered database to analyze the survival of GBC patients with different marital status. A total of 6,627 GBC patients were selected from SEER database from 2004 to 2013. The age, race, grade, histologic type, AJCC stage, SEER stage and marital status were identified as independent prognostic factors. Married GBC patients had a higher 5-year cancer-specific survival (CSS) than that of unmarried ones (20.1% v.s. 17.8%, P

The age-specific impact on the survival of gastric cancer patients with distant metastasis is still unclear. In this study, we identified 11, 299 gastric cancer patients with distant metastasis between 2004 and 2013 from Surveillance, Epidemiology, and End Results population-based dataset. Patients were divided into young (≤60) and elderly groups (>60). Kaplan-Meier methods and multivariable Cox regression were used for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in terms of race, primary site, grade, histologic type, surgery, marital status and clinical T stage (P

Gallbladder cancer (GBC) is highly malignant with a low response rate after chemotherapy and platinum drugs are currently prominent in the treatment of biliary tract cancers. Therefore, the development of novel strategies to enhance the sensitivity of GBC to platinum drugs is required. In the present study, we examined the effects of verapamil, a classic chemosensitizer whose reported mechanisms of action include inhibiting the transport function of P-glycoprotein (MDR1) or stimulating glutathione (GSH) transport by multidrug resistance-related protein 1 (MRP1), in combination with cisplatin (CDDP), carboplatin (CBP) or oxaliplatin on the GBC cell lines, SGC996 and GBC-SD. Our results demonstrated that the co-treatment with verapamil markedly enhanced the chemosensitivity of GBC cells in comparison with platinum drug treatment alone. The mechanisms involved included GSH reduction and MRP1 downregulation. Verapamil/CDDP co-treatment inhibited tumor xenograft growth via the downregulation of MRP1 expression. MRP1 was highly expressed in human GBC tissue compared to non-tumorous gallbladder tissue. Our data demonstrate that verapamil may be used as a safe chemosensitizer for platinum drugs in the treatment of GBC. It functions by ROS and ATP-binding cassette transporter-related mechanisms.

Glioblastoma multiforme (GBM) is one of the most common encephalic malignant tumors. Due to a high recurrence rate and a lack of effective treatments, the average survival rate remains low. Temozolomide (TMZ), a class of alkylating agent, is widely used as a first-line therapeutic drug during the adjuvant treatment for GBM patients. However, most patients exhibit a palpable resistance to TMZ treatment. Additionally, the underlying mechanism remains to be clarified. In this study, glutathione (GSH) and reactive oxygen species (ROS) levels were found to be closely associated with the sensitivity of GBM cells to TMZ. We also found that TMZ markedly induced xCT, the subunit of glutamate/cystine transporter system xc- expression, which together with the GSH synthesis was increased while the TMZ-inducible ROS level was decreased in GBM cells. In addition, the cystathionine γ-lyase (CTH) acivity, a key enzyme in the transsulfuration pathway was enhanced by TMZ, which insured a cysteine supply and GSH synthesis in a compensatory manner when xCT was blocked. Thus, the individual inhibition of xCT by siRNA and a pharmacological inhibitor (sulfasalazine) only partially inhibited GSH synthesis and moderately enhanced the GBM cell sensitivity to TMZ. However, the TMZ‑induced cytotoxicity was markedly increased along with a marked decrease in GSH levels as result of co-treatment with erastin, which inhibited cysteine uptake from xCT transporter and suppressed CTH activity, leading to impaired transformation from methionine to cysteine. In conclusion, to GBM therapy with a drug combination of TMZ and erastin may be beneficial.

Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) models are used extensively to predict postoperative morbidity and mortality in general surgery. The aim was to undertake the first meta-analysis of the predictive value of these models in patients undergoing hepato-biliary-pancreatic surgery. Eligible articles were identified by searches of electronic databases from 1991 to 2012. All data were specific to hepato-biliary-pancreatic surgery. Predictive value of morbidity and mortality were assessed by calculating weighted observed to expected (O/E) ratios. Subanalysis was also performed. Sixteen studies were included in final review. The morbidity analysis included nine studies on POSSUM with a weighted O/E ratio of 0.78 [95 % confidence interval (CI) 0.68–0.88]. The mortality analysis included seven studies on POSSUM and nine studies on P-POSSUM (Portsmouth predictor equation for mortality). Weighted O/E ratios for mortality were 0.35 (95 % CI 0.17–0.54) for POSSUM and 0.95 (95 % CI 0.65–1.25) for P-POSSUM. POSSUM had more accuracy to predict morbidity after pancreatic surgery (O/E ratio 0.82; 95 % CI 0.72–0.92) than after hepatobiliary surgery (O/E ratio 0.66; 95 % CI 0.57–0.74), in large sample size studies (O/E ratio 0.90; 95 % CI 0.85–0.96) than in small sample size studies (O/E ratio 0.69; 95 % CI 0.59–0.79). POSSUM overpredicted postoperative morbidity after hepato-biliary-pancreatic surgery. Predictive value of POSSUM to morbidity was affected by the type of surgery and the sample size of studies. Compared with POSSUM, P-POSSUM was more accurate for predicting postoperative mortality. Modifications to POSSUM and P-POSSUM are needed for audit in hepato-biliary-pancreatic surgery.

Gallbladder carcinoma is known to be an aggressive malignancy and non-sensitive to routine chemotherapy; its prognosis is quite poor. In this study, we show that emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component from Chinese medicinal herbs, can enhance apoptosis of gallbladder cancer cells induced by cisplatin (CDDP) in a reactive oxygen species (ROS)-dependent manner. The expression of survivin, which is involved in the inhibition of apoptosis, was measured after drug treatment and it was found that this could be suppressed by CDDP. Co-treatment with emodin additively inhibited survivin expression in a ROS-dependent manner. Further experiments proved that emodin potentiated the antitumor effects of CDDP in vivo by downregulating the expression of survivin without causing detectable toxic effects on normal tissues.

Background Chemoresistance is one of the most leading causes for tumor progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays a key role in the chemosensitivity of cancer cells. In the present study, emodin (1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in combination with cisplatin in T24 and J82 human bladder cancer cells. Methods Cell viability and apoptosis rate of different treatment groups were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM). The expression of transporters was measured at both the transcription and translation levels using PCR and western blotting. In vitro findings were confirmed by in vivo experiments using tumor-bearing mice. The expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue was measured using immunohistochemistry and side effects of the emodin/cisplatin co-treatment were investigated by histological examination. Results Emodin increased the cellular ROS level and effectively enhanced the cisplatin-induced cytotoxicity of T24 and J82 human bladder cancer cells through decreasing glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance of T24 and J82 cells to cisplatin through suppressing the expression of MRP1. This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder epithelial cells. Consistent with in vitro experiments, emodin/cisplatin co-treatment increased the cell apoptosis and repressed the MRP1 expression in xenograft tumors, and without obvious systemic toxicity. Conclusions This study revealed that emodin could increase the cisplatin-induced cytotoxicity against T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1 expression. We suggest that emodin could serve as an effective adjuvant agent for the cisplatin-based chemotherapy of bladder cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2640-3) contains supplementary material, which is available to authorized users.

Background Negative lymph node (NLN) count has been reported to provide more accurate prognostic information than the N stage alone in patients with rectal cancer (RC). Since preoperative radiotherapy (Pre-RT) can significantly affect the LN status, it is unclear whether NLN count still has prognostic value count on survival of patients with RC who received Pre-RT. Methods In this study, clinicopathological characteristics, number of positive LNs and survival time were collected from Surveillance, Epidemiology, and End Results Program (SEER)-registered RC patients. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. Results X-tile plots identified 9 (P