Search

BACKGROUND To analysed the short- and long-term outcomes of patients who underwent surgical resection for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) to gain insights into treatment approaches for this rare and heterogeneous entity. METHODS All patients who underwent surgical resection for NF-PNETs at The Second Affiliated Hospital of Guangzhou Medical University, and West China Hospital, Sichuan University, from 2009 to 2019 were retrospectively reviewed. The data of patients was including perioperative management, pathologic analysis and follow-up. RESULTS A total of 119 cases with histologically or cytologically confirmed NF-PNETs, The mean age of the patients was 52, and 56.3% were female. Twenty-three patients received post-operative adjuvant therapy, and five of nine (55.6%) patients with distant metastasis showed recurrence 14(60.9%) G2/G3 patients without distant metastasis received post-operative therapy with octreotide. Of these 14 patients, 3 (21.4%) revealed recurrence. Univariate analysis indicated that symptoms (P = 0.03), tumour size >4 cm (P = 0.029), ENETS stages III-IV (P

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

Background: The case–control study aimed to investigate the association between the −31G>C polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in a Southern Chinese population. Materials and Methods: The study was carried out on 711 healthy controls and 702 CRC cases of a Southern Chinese population. Survivin gene −31G>C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between CRC risk and −31G>C genetic polymorphism was estimated using an unconditional logistic regression model. Results: The number of CC genotype carried in CRC patients was much higher than those of controls (P < 0.001). Compared with CC genotypes, GC, GG genotypes and −31G wild-type genotypes (i.e., GC + GG) had a significantly decreased risk of CRC (P < 0.001). In addition, survivin −31G wild-type genotypes were not associated with decreased risk of sporadic CRC patients with body mass index (BMI) ≥28.0 kg/m2, family cancer history, and premenopausal. Conclusion: Survivin −31G>C polymorphism is associated with sporadic CRC risk in the Southern Chinese population. The −31G wild-type genotypes and GC, GG genotypes are the independent protective factors against sporadic CRC excluding those with a BMI ≥28.0 kg/m2, family cancer history, and premenopausal.

Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termedA total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression ofWe found that the expression of

Purpose Total mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a standard treatment of locally advanced rectal cancer. This study investigated the addition of oxaliplatin with and without preoperative radiotherapy. Methods In this multicenter, open-label, phase III trial, we randomly assigned (1:1:1) Chinese adults (age 18 to 75 years) with locally advanced stage II/III rectal cancer to three treatments: five 2-week cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 h) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (modified FOLFOX6 [mFOLFOX6]), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. Random assignment was performed by using computer-generated block randomization codes. The primary end point was 3-year disease-free survival. Secondary end points of histopathologic response and toxicity are reported. Results A total of 495 patients were enrolled from June 2010 to February 2015; 475 were evaluable (fluorouracil-radiotherapy, n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163). In the fluorouracil-radiotherapy, mFOLFOX6-radiotherapy, and mFOLFOX6 groups, the rate of pathologic complete response (pCR) was 14.0%, 27.5%, and 6.6%, and downstaging (ypStage 0 to 1) was achieved by 37.1%, 56.4%, and 35.5% of patients, respectively. Higher toxicity and more postoperative complications were observed in patients who received radiotherapy. Conclusion mFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate than fluorouracil-based treatment. Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy, with less toxicity and fewer postoperative complications.

Down-regulated expression of the putative tumor suppressor gene spleen tyrosine kinase (SYK) is strongly associated with the development of various cancers, including colorectal cancer (CRC). SYK gene promoter polymorphisms have been shown to be involved in the pathogenesis of multiple malignant tumors. In this study, we investigated associations of SYK gene promoter polymorphisms with the susceptibility to colorectal cancer development in a Southern Han Chinese population. SNPs in the promoter region of the human SYK gene were identified using in silico analysis tools, linkage disequilibrium analysis, and a search for likely transcription factor binding sites via TFSEARCH in the NCBI SNP database (gene ID: 6850). Based on this information, −803A > T and −534T > C were selected as candidates for further analysis. TaqMan-MGB probe analyses were performed in 567 CRC patients and 569 age- and gender-matched healthy controls for SYK gene promoter genotyping. Associations between CRC risk and SNPs were estimated using an unconditional logistic regression model, and environmental risk factors were included in a multivariate logistic regression model for correction. The frequencies of the TA and TT genotypes and the T allele of the –803A > T SNP were found to be significantly higher in the CRC patients compared to the healthy individuals of the control group (P = 0.020, 0.023, and 0.013, respectively). Synergistic effects between –803A > T genotypes (i.e., TA + TT) and age (≤60 years; P = 0.039), male gender (P = 0.011), smoking (P = 0.005), drinking alcohol (P = 0.002), and high BMI (≥24.0 kg/m2; P = 0.009) were found to increase the risk to develop CRC by stratified analyses. The SYK −803 A > T genotypes TA and TT are independent risk factors for CRC development in Han Chinese in Southern China, and an association with TA + TT genotypes appears predominant among younger patients, male patients, patients with a high BMI, and patients who smoke or drink alcohol.

AIM The effects of circulating eosinophils and basophils on cancer survival are unclear. Here, we aimed to explore the impacts of eosinophils and basophils on prognosis of stage I-III colorectal cancer (CRC) patients. METHODS From February 2003 to March 2013, 569 stage I-III CRC patients were enrolled in this retrospective study. The associations between pretreatment circulating eosinophils, basophils and CRC overall survival (OS), disease-free survival (DFS) were investigated. Moreover, the prognostic value of combined eosinophils/basophils and neutrophil to lymphocyte ratio (NLR)/platelet to lymphocyte ratio (PLR) was investigated. RESULTS Kaplan-Meier methods showed the associations of eosinophils

C-Jun plays important roles in the development of multiple cancers, but no well-designed association studies have been conducted to assess the roles of its genetic polymorphisms in cancer risk. In a cohort of 1016 pairs of colorectal cancer (CRC) patients and matched cancer-free controls, we investigated two genetic polymorphisms in the promoter regions of the c-Jun (rs4646999, -673CT and rs2760501, -1318TG) via the Taqman assay and evaluated the association between two polymorphisms and risk of CRC. We found that both the -1318G and -673C variant genotypes were associated with an increased risk of CRC [-1318TG: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.04-1.54; -1318GG: OR = 1.63, 95% CI = 1.03-2.60; -673CT: OR = 1.60, 95% CI = 1.23-2.07; -673CC: OR = 1.80, 95% CI = 1.36-2.37]. Haplotype association analysis showed that compared with the carriers of -1318T-673T haplotype, carriers of the -1318T-673C, -1318G-673T, and -1318G-673C haplotypes all had a significantly increased risk of CRC (P0.05 for all). The combined genotypes incorporating both polymorphisms obtained a more significantly additive risk of CRC (one variant genotype: OR = 1.81, 95% CI = 1.30-2.51; two variant genotype: OR = 2.42, 95% CI = 1.70-3.44). Moreover, we found that the change of the -1318T to G allele interact with the -673T to C allele elevated the transcription activity of the c-Jun, and we confirmed the same trends by analyzing c-Jun protein expression in the CRC tissues from patients carrying different number of variant genotypes. This study suggests that -673CT and -1318TG genetic variants in c-Jun promoter regions contribute to an increased risk of CRC, possibly by elevating the transcription activity and protein expression levels that appeared to upregulate activity of c-Jun thus tumorigenesis.

MKK4 (mitogen-activated protein kinase kinase 4, NM_003010.2), which belongs to the mitogen-activated protein kinase pathways, possesses functions in tumorigenesis. We hypothesized the genetic variants in MKK4 gene may alter its functions and thus cancer risk. In current hospital-based case-control study of 706 patients with sporadic colorectal cancer (CRC) and 723 sex-age–frequency-matched control subjects in a southern Chinese population, we genotyped two polymorphisms of MKK4 promoter (i.e., −1304T>G, rs3826392 and −1044A>T, rs3809728) and assessed their associations with the risk of sporadic CRC. Compared with −1304TT genotypes, −1304TG had a significantly decreased risk of CRC (adjusted odds ratios [OR] = 0.56; 95% CI = 0.44–0.72; p = 3.53 × 10−6), the −1304GG carriers had a further decreased risk of CRC (OR = 0.40; 95% CI = 0.23–0.70; p = 1.32 × 10−3), and there was a significant trend for an allele dose effect on risk of CRC (ptrend = 2.64 × 10−7). The decreased risk associated with −1304G variant genotypes (i.e., TG+GG) was more pronounced in the subjects older than 60 years (adjusted OR = 0.41; 95% CI = 0.29–0.57; p = 2.25 × 10−7), in ever drinkers (adjusted OR = 0.41; 95% CI = 0.28–0.59; p = 2.42 × 10−6). The age and alcohol drinking status interacted with −1304G variant genotypes on reducing cancer risk (p values for interaction were 0.015 and 0.043, respectively). Western blotting analysis showed that the levels of Mkk4 protein in sporadic CRC neoplastic tissues were significantly higher in the carriers of −1304G variant genotypes than that in those with −1304TT genotypes. However, no significant association was observed between −1044A>T polymorphism and risk of CRC. To the best of our knowledge, this is the first study of genetic variants in MKK4 and cancer susceptibility. Larger studies are needed to validate our findings. © 2009 UICC

Evaluate the prognostic value of lymph node ratio (LNR) in patients undergoing resection of stage III colorectal cancer.The clinicopathological and follow-up data were collected from 174 surgical patients with stage III colorectal cancer. The 5-year disease-free survival (DFS) and overall survival (OS) were evaluated using Kaplan-Meier method. The impact of LNR and clinicopathological factors on DFS and OS were evaluated using univariate and multivariate analysis.After a median follow-up of 62.5 months, the 5-year DFS and OS of the patients were 51.8% and 56.3%, respectively. The median number of lymph nodes harvested and the median number of positive lymph nodes examined were 10 and 3, respectively. The patients were stratified into 4 groups according to LNR quartiles (LNR1, LNR≤0.125; LNR2, 0.125LNR≤0.260; LNR3, 0.260LNR≤0.500; LNR4, LNR0.500), whose 5-year DFS and OS were 64.2%, 53.5%, 41.8%, and 25.7% (P0.05) and 68.1%, 60.8%, 49.2%, and 32.7% (P0.05), respectively. Multivariate analysis identified age, T stage and LNR as the independent predictors of both DFS and OS. Subgroup analysis showed that LNR had an independent prognostic value on DFS and OS irrespective of the number of lymph nodes harvested.LNR is an independent prognostic factor for survival in patients with stage III colorectal cancer and is superior to the pN category in TNM staging.

Background Nuclear factor κB (NFκB) plays a key role in the regulation of apoptosis. The function of NFκB is inhibited by binding to NFκB inhibitor (IκB), and disruption of the balance of NFκB and IκB is related to the development of many diseases, including tumors. Therefore, we hypothesized that the NFκB1 (-94del/insATTG) and NFκBIA (2758 A>G) polymorphisms were associated with colorectal cancer (CRC) susceptibility. Methods In a hospital-based case–control study of 1001 CRC patients and 1005 cancer-free controls frequency matched by age and sex, we genotyped polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and performed luciferase assays and Western blotting analysis to identify whether genetic variants in NFκBIA alter its gene expressions and functions and thus cancer risk. Results We found that both NFκB1-94 ins/delATTG and NFκBIA 2758 A>G polymorphisms were correlated with CRC risk (OR = 1.47; 95%CI = 1.14–1.86, and OR = 1.38; 95% CI = 1.14–1.66, respectively). Furthermore, when evaluated these two polymorphisms together, the combined genotypes with 2 variant (risk) alleles (2758GG and -94ins/ins+del/ins) were associated with an increased risk of CRC (OR = 1.71; 95% CI = 1.23–2.38) compared to 0 variant, and the significant trend for 2 variant (risk) alleles were more pronounced among subgroups of aged

Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its expression and thus cancer risk. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we genotyped two common polymorphisms in the MKK4 promoter region (-1304T>G and -1044A>T) with the Taqman assay, and we found that compared with the most common —1304TT genotype, carriers of —1304G variant genotypes had a decreased risk of lung cancer [odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.61-0.90 for TG, and OR = 0.62; 95% CI = 0.41-0.94 for GG] in an allele dose-response manner (adjusted P trend = 0.0005). Further stratification analysis showed that the protective role of the -1304G variant allele was more evident in low or normal body mass index (BMI) but restrained in the overweighters and that the —1304G variant genotypes interacted with BMI in reducing cancer risk (adjusted P interaction = 0.003). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 protein expression levels of the G variant carriers was significantly higher in tumor tissues than those of the —1304TT genotype. However, no significant association was observed between the —1044A>T polymorphism and risk of lung cancer. Our data suggest that the functional —1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to lung cancer.

Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5), which belongs to a network of mitogen-activated protein kinase pathways, play a pivotal role in carcinogenesis. The purpose of this study was to investigate whether variants in the MEK5 gene promoter were involved in susceptivity of individuals to sporadic colorectal cancer (CRC). In the present hospital-based case–control study of 737 patients with sporadic CRC and 703 healthy control subjects in a southern Chinese population, the two polymorphisms of MEK5 promoter (i.e., rs7172582C>T and rs3743354T>C) were genotyped by TaqMan assay. There were significant differences between cases and controls in the genotype and allele distribution of the MEK5 gene rs3743354T>C polymorphism. The rs3743354 CC genotype was associated with a significantly decreased risk of CRC when compared with the TT genotype (adjusted odds ratios [ORs]=0.43; 95% confidence interval [CI], 0.24–0.77). Compared to the T allele, a significant correlation was detected between the presence of the C allele and decreased risk of CRC (adjusted OR=0.79; 95% CI, 0.61–0.94). The decreased risk of CRC associated with rs3743354 variant genotypes (i.e., CT+CC) was found in the smoker subgroup (adjusted OR=0.63; 95% CI=0.45–0.88). Further, environmental factors, including smoking and drinking, interacted with rs3743354C variant genotypes to reduce CRC risk. Western blot analysis showed that the levels of MEK5 protein in sporadic CRC neoplastic tissues and adjacent normal colorectal epithelium tissues were lower in the carriers of rs3743354 CC genotypes than that in those with rs3743354 TT genotypes or those with rs3743354 TC genotypes. However, no significant association was found between the rs7172582C>T polymorphism and risk of CRC. These data indicate that the rs3743354 polymorphism in the MEK5 promoter may affect the risk of developing CRC.