Computer tomography-guided negative pressure drainage treatment of intrathoracic esophagojejunal anastomotic leakage: A case report.

BACKGROUND: Esophagojejunal anastomotic leakage (EJAL) is a serious and potentially crucial complication of total gastrectomy and represents the major cause of postoperative death, with a mortality rate of up to 50%. However, treatment remains challenging and controversial. We report here the case of a patient whose intrathoracic EJAL was successfully treated with computer tomography (CT)-guided negative pressure drainage treatment. CASE SUMMARY: A 69-year-old male patient complained of difficulty swallowing within the last six months. He was diagnosed with esophagogastric junction carcinoma, Siewert II, cT3N0M0 stage II. Total gastrectomy and Roux-en-Y esophagojejunostomy were performed. High fever, left chest pain and dyspnea appeared on postoperative day 5, and EJAL was confirmed by CT, gastroscopy and oral blue-dimethylene tests. Conservative treatment measures were applied immediately, including antibiotics, nasojejunal tubes, and repeated thoracic puncture and drainage under ultrasound guidance. However, without sufficient and effective drainage, the thoracic infection and systemic condition continued to deteriorate. With the cooperation of multiple departments, percutaneous CT-guided drainage (24 Fr 7 mm) in the thoracic cavity was successfully placed near the anastomotic leakage. Because of continuous negative pressure suction, the infection symptoms were effectively controlled and the general situation gradually recovered. Subsequent follow-up examination showed that the patient was in good condition. CONCLUSION: Negative pressure drainage via CT may represent an effective minimally invasive approach to treating intrathoracic EJAL.

Albumin-Based LL37 Peptide Nanoparticles as a Sustained Release System against Pseudomonas aeruginosa Lung Infection.

Pseudomonas aeruginosa (PA) has emerged as a pressing challenge to pulmonary infection and lung damage. The LL37 peptide is an efficient antimicrobial agent against PA strains, but its application is limited because of fast clearance in vivo, biosafety concerns, and low bioavailability. Thus, an albumin-based nanodrug delivery system with reduction sensitivity was developed by forming intermolecular disulfide bonds to increase in vivo LL37 performance against PA. Cationic LL37 can be efficiently encapsulated via electrostatic interactions to exert improved antimicrobial effects. The LL37 peptide exhibits greater than 48 h of sustained released from LL37 peptide nanoparticles (LL37 PNP), and prolonged antimicrobial effects were noted as the incubation time increased. Levels of inflammatory cytokines secreted by peritoneal macrophages, including TNF-α and IL-6, were reduced significantly after LL37 PNP treatment following PA stimulation, indicating that LL37 PNP inhibits PA growth and exerts anti-inflammatory effects in vitro. In a murine model of acute PA lung infection, LL37 PNP significantly reduced TNF-α and IL-1ß expression and alleviated lung damage. The accelerated clearance of PA indicates that LL37 PNP could improve PA lung infection and the subsequent inflammation response more efficiently compared with free LL37 peptide. In conclusion, this excellent biocompatible LL37 delivery strategy may serve as an alternative approach for the application of new types of clinical treatment in future.

TGF-ß in pancreatic cancer initiation and progression: two sides of the same coin.

Pancreatic cancer is highly lethal malignant tumor with characterised rapid progression, invasiveness and resistance to radiochemotherapy. Transforming growth factor-ß (TGF-ß) signaling plays a dual role in both pro-tumorigenic and tumor suppressive of pancreatic cancer, depending on tumor stage and microenvironment. TGF-ß signaling components alteration are common in pancreatic cancer, and its leading role in tumor formation and metastases has received increased attention. Many therapies have investigated to target TGF-ß signaling in the preclinical and clinical setting. In this review, we highlight the dual roles of TGF-ß and touch upon the perspectives on therapeutic target of TGF-ß signaling in pancreatic cancer.

Meta-analysis of oxaliplatin-based versus fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer.

A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched for relevant randomized controlled trials (RCTs) until January 31 2017. Review Manager (version 5.3) was used to analyze the data. Dichotomous data were calculated by odds ratio (OR) with 95% confidence intervals (CI). A total of 8 RCTs with 6103 stage II or III rectal cancer patients were analyzed, including 2887 patients with oxaliplatin+fluorouracil regimen and 3216 patients with fluorouracil alone regimen. Compared with fluorouracil-based regimen group, oxaliplatin-based regimen group attained higher pathologic complete response (OR = 1.29, 95% CI: 1.12-1.49, P = 0.0005) and 3-year disease-free survival (OR = 1.15, 95% CI: 0.93-1.42, P = 0.21), but suffered greater toxicity (OR = 2.07, 95% CI: 1.52-2.83, P < 0.00001). Also, there were no significant differences between two regimens in sphincter-sparing surgery rates (OR = 0.94, 95% CI: 0.83-1.06, P = 0.33), 5-year disease-free survival (OR = 1.15, 95% CI: 0.93-1.42, P = 0.21) and overall survival (3-year, OR = 1.14, 95% CI: 0.98-1.34, P = 0.09; 5-year, OR = 1.06, 95% CI: 0.78-1.44, P = 0.70). In conclusion, the benefits of adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer remains controversial, and cannot be considered a standard approach.

Meta-analysis of transcatheter arterial chemoembolization plus radiofrequency ablation versus transcatheter arterial chemoembolization alone for hepatocellular carcinoma.

This meta-analysis was conducted to compare transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with TACE alone for hepatocellular carcinoma. We searched MEDLINE, EMBASE and CENTRAL for all relative randomized controlled trials (RCTs) and retrospective studies until October 31 2016. Tumor response, recurrence-free survival, overall survival and postoperative complications were the major evaluation indices. Review Manager (version 5.3) was used to analyze the data. Dichotomous data was calculated by odds ratio (OR) with 95% confidence intervals (CI). There were 1 RCT and 10 retrospective studies with 928 patients in this meta-analysis: 412 patients with TACE plus RFA and 516 patients with TACE alone. Compared with TACE alone group, TACE plus RFA group attained higher tumor response rates (OR = 6.08, 95% CI = 4.00 to 9.26, P < 0.00001), achieved longer recurrence-free survival rates (ORRFS = 3.78, 95% CI: 2.38 to 6.02, P < 0.00001) and overall survival rates (OR1-year = 3.92, 95% CI = 2.41-6.39, P < 0.00001; OR3-year = 2.56; 95% CI = 1.81-3.60; P < 0.00001; OR5-year = 2.78; 95% CI = 1.77-4.38; P < 0.0001). Serious postoperative complications were not observed, although complications were higher in TACE plus RFA group than that in TACE alone group (OR = 2.74, 95% CI = 1.07 to 7.07, P = 0.04). In conclusion, the use of TACE plus RFA for intermediate stage hepatocellular carcinoma can attain higher tumor response rates and improve survival rates than TACE alone.

SRPK2 promotes the growth and migration of the colon cancer cells.

Colon cancer is one of the major causes of cancer-related death in the world. Understanding the molecular mechanism underlying this malignancy will facilitate the diagnosis and treatment. Serine-arginine protein kinase 2 (SRPK2) has been reported to be upregulated in several cancer types. However, its expression and functions in colon cancer remains unknown. In this study, it was found that the expression of SRPK2 was up-regulated in the clinical colon cancer samples. Overexpression of SRPK2 promoted the growth and migration of colon cancer cells, while knocking down the expression of SRPK2 inhibited the growth, migration and tumorigenecity of colon cancer cells. Molecular mechanism studies revealed that SRPK2 activated ERK signaling in colon cancer cells. Taken together, our study demonstrated the tumor promoting roles of SRPK2 in colon cancer cells and SRPK2 might be a promising therapeutic target for colon cancer.

Violet/blue chrysanthemums--metabolic engineering of the anthocyanin biosynthetic pathway results in novel petal colors.

Chrysanthemums (Chrysanthemum×morifolium Ramat.) are an important cut-flower and potted plant crop in the horticultural industry world wide. Chrysanthemums express the flavonoid 3'-hydroxylase (F3'H) gene and thus accumulate anthocyanins derived from cyanidin in their inflorescences which appear pink/red. Delphinidin-based anthocyanins are lacking due to the deficiency of a flavonoid 3', 5'-hydroxylase (F3'5'H), and so violet/blue chrysanthemum flower colors are not found. In this study, together with optimization of transgene expression and selection of the host cultivars and gene source, F3'5'H genes have been successfully utilized to produce transgenic bluish chrysanthemums that accumulate delphinidin-based anthocyanins. HPLC analysis and feeding experiments with a delphinidin precursor identified 16 cultivars of chrysanthemums out of 75 that were predicted to turn bluish upon delphinidin accumulation. A selection of eight cultivars were successfully transformed with F3'5'H genes under the control of different promoters. A pansy F3'5'H gene under the control of a chalcone synthase promoter fragment from rose resulted in the effective diversion of the anthocyanin pathway to produce delphinidin in transgenic chrysanthemum flower petals. The resultant petal color was bluish, with 40% of total anthocyanidins attributed to delphinidin. Increased delphinidin levels (up to 80%) were further achieved by hairpin RNA interference-mediated silencing of the endogenous F3'H gene. The resulting petal colors were novel bluish hues, not possible by hybridization breeding. This is the first report of the production of anthocyanins derived from delphinidin in chrysanthemum petals leading to novel flower color.

The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis.

Many epidemiological studies have found that leptin correlates to body fat extent and breast cancer. Leptin exerts its physiological action through the leptin receptor (LEPR). However, published data on the association between LEPR alleles and breast cancer occurrence have led to in contradictory results. A total of 10 studies were identified to the meta-analysis, including 4,644 cases and 5,485 controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464 controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and rs8051542 polymorphisms. The pooled odds ratios (OR) with 95 % confidence intervals (CI) for breast cancer risk associated with LEPR genotypes were estimated. Elevated breast cancer risk was associated with LEPR rs1137101 polymorphism when all studies were pooled in the meta-analysis (allele contrast model: OR = 0.71, 95 % CI = 0.551-0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95 % CI 0.312-0.550) and dominant model (OR 0.537, 95 % CI 0.370-0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95 % CI 0.595-0.861), homozygote codominant (OR 0.537, 95 % CI 0.370-0.781) and dominant model (OR 1.595, 95 % CI 1.207-2.108). And significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR = 0.666, 95 % CI = 0.603-0.720) and homozygote codominant models (OR = 0.344, 95 % CI = 0.282-0.421). For LEPR rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations were detected in all comparison models. This pooled analysis suggested that rs1137101 and rs1137100 polymorphisms were significantly correlated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant were low-penetrant risk factors for developing breast cancer. Further, no significant associations existed between LEPR rs8179183, rs4655537, and rs3762274 polymorphisms and risk of breast cancer.

Perifosine sensitizes curcumin-induced anti-colorectal cancer effects by targeting multiple signaling pathways both in vivo and in vitro.

Our study shows that coadministration of curcumin and an orally bioactive alkylphospholipid perifosine results in a significant increase in colorectal cancer cell apoptosis and a marked inhibition of cell growth both in vitro and in vivo. This novel combinatorial regimen leads to changes of multiple cell signaling pathways including inactivation of Akt and nuclear factor-κB as well as activation of c-Jun N-terminal kinases and endoplasmic reticulum stress. Further, perifosine and curcumin synergistically increase intracellular level of reactive oxygen species and ceramide, and downregulate the expression of cyclin D1 and Bcl-2 in colorectal cancer cells. These changes at molecular level together account for the cancer cell apoptosis and growth inhibition. We conclude that perifosine sensitizes colorectal cancer cells to curcumin by modulating multiple signaling pathways. Adding perifosine with curcumin may represent an effective therapy regimen against colorectal cancers, and possible other aggressive tumors.

Current treatment of rectovaginal fistula in Crohn's disease.

Rectovaginal fistula (RVF) continues to be the most difficult perianal manifestation of Crohn's disease to treat. This devastating and disabling complication has a significant impact on patients' quality of life and presents unique management challenges. Current therapeutic approaches include many medical therapeutics and surgical treatments with a wide range of success rates reported. However, current evidence is lacking to support any recommendation. The choice of repair depends on various patient and disease factors and basic surgical tenets. In this article, we review the current options to consider in the treatment of Crohn's-related RVF, and try to evaluate their effects on fistulae closure and quality of life.

Association between mitogen-activated protein kinase kinase kinase 1 rs889312 polymorphism and breast cancer risk: evidence from 59,977 subjects.

Published data on the association between mitogen-activated protein kinase kinase kinase 1 (MAP3K1) gene rs889312 polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of seven eligible articles including 26,015 cases and 33,962 controls based on the search criteria were involved in this meta-analysis. We observed that the MAP3K1 rs889312 polymorphism was significantly correlated with breast cancer risk from the fixed effects model when all studies were pooled into the meta-analysis (the allele contrast model: OR 1.09, 95% CI 1.07-1.12; the homozygote codominant: OR 1.22, 95% CI 1.15-1.29; the heterozygote codominant: OR 1.07, 95% CI 1.04-1.11; the dominant model: OR 1.10, 95% CI 1.06-1.13; the recessive model: OR 1.18, 95% CI 1.12-1.25). No significant association was found in the BRCA1 mutation carriers in all genetic models. When stratified by BRCA2 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (C vs. A: OR 1.12, 95% CI 1.01-1.23; CC vs. AA: OR 1.35, 95% CI 1.06-1.71; the recessive model: OR 1.31, 95% CI 1.05-1.65). There was no evidence for significant association between MAP3K1 rs889312 polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort for all comparison models. In conclusion, this meta-analysis suggests that the MAP3K1 rs889312 C allele is a low-penetrant risk factor for developing breast cancer, and there is limited evidence to indicate that MAP3K1 rs889312 polymorphism is associated with increased risk of breast cancer in BRCA1 mutation carriers.

Association between polymorphisms of trinucleotide repeat containing 9 gene and breast cancer risk: evidence from 62,005 subjects.

Trinucleotide repeat containing 9 (TNRC9) is a gene located at chromosome 16q12. Although of an uncertain function, it is a newly described risk factor for breast cancer. It contains a putative high-mobility group box motif, suggesting its possible role as transcription factor; it has been implicated in breast cancer metastasis. Published studies on the association between TNRC9 polymorphisms and breast cancer risk remain inconclusive, and a meta-analysis is required to verify the association. This pioneering research performed a meta-analysis of eight studies comprising a total of 25,828 cases and 36,177 controls. Significantly elevated breast cancer risk was associated with TNRC9 rs3803662 polymorphism when all studies were pooled in the meta-analysis (T vs. C allele contrast model: OR 1.18, 95% CI 1.09-1.28; TT vs. CC homozygote codominant model: OR 1.26, 95% CI 1.02-1.55; TT vs. CC+CT recessive model: OR 1.23, 95% CI 1.06-1.42). For TNRC9 rs12443621 polymorphism, no significant association was detected in all genetic models. For TNRC9 rs12443621 polymorphism, meanwhile, no significant association was observed in all comparison models. Conclusively, this meta-analysis suggests that TNRC9 rs3803662 polymorphism was significantly correlated with breast cancer risk and the variant T allele of TNRC9 rs3803662 polymorphism is a low-penetrant risk factor for developing breast cancer. There is no significant association between TNRC9 rs12443621 and rs8051542 polymorphisms and risk of breast cancer in current literature.

Association between two polymorphisms of ABCB1 and breast cancer risk in the current studies: a meta-analysis.

Previous epidemiological studies have evaluated the association between the ABCB1 polymorphism and the risk of breast cancer with conflicting results. Hence, we conducted a meta-analysis of the ABCB1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase, and Web of Science databases were searched. A total of eight studies including 3,829 cases and 6,193 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of associations between the ABCB1 C3435T and rs2214102 G>A polymorphisms and risk of breast cancer. Of these studies, only one deviated from Hardy-Weinberg equilibrium. Summary estimates indicated that the ABCB1 C3435T polymorphism was not associated with increased risk of breast cancer in the allele contrast model (T vs. C, pooled OR = 1.15; 95% CI = 0.89-1.48); the co-dominant model (CT vs. CC, OR = 1.12 [0.86-1.46] and TT vs. CC, OR = 1.30 [0.79-2.15]); the dominant model (OR = 0.80 [0.63-1.02]; and the recessive model (OR = 0.83 [0.57-1.22]). In the sensitivity analysis by ethnicity, no statistically significant associations were detected in Asians. However, in Caucasian women the T allele contrast model and the TT genotype were each associated with increased risk: T vs. C, pooled OR (95% CI) = 1.26 (1.04-1.52) and TT vs. CC, OR = 1.48 (1.04-2.11). Accordingly, the dominant model yielded statistically significant results (pooled OR = 0.71, 95% CI: 0.52-0.96) but not with the allele contrast model or the co-dominant model. There was evidence of publication bias (P = 0.02 for recessive model). In conclusion, there is limited evidence to indicate that the ABCB1 C3435T and rs2214102 G>A polymorphisms are associated with increased risk of breast cancer.

Association between polymorphisms of the ataxia telangiectasia mutated gene and breast cancer risk: evidence from the current studies.

Epidemiological studies have evaluated the association between ataxia telangiectasia mutated (ATM) gene polymorphisms and breast cancer risk. However, published data are still inconclusive. We performed a meta-analysis for the first time, based on currently available evidence, by searching PubMed, ISI Web of Knowledge, and Embase databases to derive a more precise assessment of the relationship. Following the inclusion and exclusion criteria, nine publications were included in this meta-analysis. Of these studies, one had a deviation from the Hardy-Weinberg equilibrium (HWE) at a statistical significance level of 0.01 in controls, and another two had no available data for HWE. We observed that the ATM 5557G>A polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (recessive model: odds ratio, OR = 0.67; 95% confidence interval (CI) 0.51-0.89). For the ATM IVS38-8T>C polymorphism, no significant association was found in the allele contrast, heterozygote codominant, and dominant models. There were no available data to perform this meta-analysis in the homozygote codominant and recessive models. For the ATM IVS1+19A>T polymorphism, a significant association with breast cancer risk was found in the allele contrast model (C vs. T: OR = 1.60; 95% CI 1.02-2.52). For the IVS34+60G>A polymorphism, no significant association was found in the allele contrast, codominant, dominant, and recessive models. Egger's test did not suggest any evidence of publication bias (P = 0.47 for the recessive model). In conclusion, there is limited evidence to indicate that ATM polymorphisms are associated with increased risk of breast cancer.