Impact of carbonic anhydrase 9 gene polymorphism on the progression of colorectal cancer.

Colorectal cancer (CRC) is a commonly occurring tumor type worldwide, and its development is governed by a connection between genetic variations and acquired factors. Carbonic anhydrase 9 (CA9) is a cell-surface pH modulator that has been demonstrated to contribute to key steps of cancer progression. Here, we attempted to interrogate the effect of CA9 gene polymorphisms on the development of CRC in 470 cases and 470 gender- and age-matched non-cancer controls. We found that none of three CA9 single-nucleotide polymorphisms (SNPs) tested, including rs2071676, rs3829078, and rs1048638, was significantly associated with the occurrence of CRC. Yet, while evaluating the clinicopathological variables, cases carrying at least one reference allele (G allele) of rs2071676 tended to develop poorly differentiated tumors less frequently than those who are homozygous for the alternative allele (A allele) of rs2071676 (GA+GG vs AA; OR, 0.483; 95% CI, 0.242-0.963; p=0.036). Further stratification revealed that as compared to homozygous carriers of the alternative allele (AA), cases of colon cancer bearing at least one reference allele of rs2071676 (GA+GG) less frequently developed poorly differentiated tumors (OR, 0.449; 95% CI, 0.221-0.911; p=0.024) and lymphovascular invasion (OR, 0.570; 95% CI, 0.361-0.900; p=0.015). Such genetic effect was exclusively observed in colon cancer but not in rectal cancer. Our results indicate an anatomical site-specific impact of CA9 gene polymorphisms on modulating the progression of colorectal malignancies.

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan.

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.

The Impact of Matrix Metalloproteinase-11 Polymorphisms on Colorectal Cancer Progression and Clinicopathological Characteristics.

Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide and the most prevalent cancer in Taiwan. The matrix metalloproteinase (MMP)-11 is a proteolytic enzyme of the MMP family which is involved in extracellular matrix degradation and tissue remodeling. In this study, we focused on the associations of MMP-11 single-nucleotide polymorphisms (SNPs) with CRC susceptibility and clinicopathological characteristics. The MMP-11 SNPs rs131451, rs738791, rs2267029, rs738792, and rs28382575 in 479 controls and 479 patients with CRC were analyzed with real-time polymerase chain reaction. We found that the MMP-11 SNP rs738792 "TC + CC" genotype was significantly associated with perineural invasion in colon cancer patients after controlling for clinical parameters [OR (95% CI) = 1.783 (1.074-2.960); p = 0.025]. The MMP-11 rs131451 "TC + CC" genotypic variants were correlated with greater tumor T status [OR (95% CI):1.254 (1.025-1.534); p = 0.028] and perineural invasion [OR (95% CI):1.773 (1.027-3.062); p = 0.040) in male CRC patients. Furthermore, analyses of The Cancer Genome Atlas (TCGA) revealed that MMP-11 levels were upregulated in colorectal carcinoma tissue compared with normal tissues and were correlated with advanced stage, larger tumor sizes, and lymph node metastasis. Moreover, the data from the Genotype-Tissue Expression (GTEx) database exhibited that the MMP-11 rs738792 "CC" and "CT" genotypic variants have higher MMP-11 expression than the "TT" genotype. In conclusion, our results have demonstrated that the MMP-11 SNPs rs738792 and rs131451 may have potential to provide biomarkers to evaluate CRC disease progression, and the MMP-11 rs131451 polymorphism may shed light on sex discrepancy in CRC development and prognosis.

Primary malignant peritoneal mesothelioma mimicking tuberculous peritonitis: A case report.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignancy arising in mesothelial cells in the peritoneum. It can be mistaken for many other diseases, such as peritoneal carcinomatosis and tuberculous peritonitis (TBP), because its clinical manifestations are often nonspecific. Therefore, the diagnosis of MPM is often challenging and delayed. CASE SUMMARY: A 42-year-old man was referred to our hospital with lower abdominal pain for 1 wk and ascites observed under abdominal sonography. His laboratory findings revealed an isolated elevated tumor marker of carcinoma antigen 125 (167.4 U/mL; normal, < 35 U/mL), and contrast enhanced computed tomography showed peritoneal thickening. Thus, differential diagnoses of TBP, carcinomatosis of an unknown nature, and primary peritoneal malignancy were considered. After both esophagogastroduodenoscopy and colonoscopy produced negative findings, laparoscopic intervention was performed. The histopathological results revealed mesothelioma invasion into soft tissue composed of a papillary, tubular, single-cell arrangement of epithelioid cells. In addition, immunohistochemical staining was positive for mesothelioma markers and negative for adenocarcinoma markers. Based on the above findings, TBP was excluded, and the patient was diagnosed with MPM. CONCLUSION: It is important to distinguish MPM from TBP because they have similar symptoms and blood test findings.

Risk factors and prognoses of invasive Candida infection in surgical critical ill patients with perforated peptic ulcer.

BACKGROUND: The risk of invasive Candida infection (ICI) is high in patients with perforated peptic ulcer (PPU) who received laparotomy or laparoscopic surgery, but the risk factors and predictors of morbidity outcomes remain uncertain. This study aims to identify the risk factors of ICI in surgical critically ill PPU patients and to evaluate the impact on patient's outcomes. METHODS: This is a single-center, retrospective study, with a total of 170 surgical critically ill PPU patients. Thirty-seven patients were ICI present and 133 were ICI absent subjects. The differences in pulmonary complications according to invasive candidiasis were determined by the Mann-Whitney U test. Evaluation of predictors contributing to ICI and 90-day mortality was conducted by using multivariate logistic regression analysis. RESULTS: Candida albicans was the primary pathogen of ICI (74.29%). The infected patients had higher incidence of bacteremia (p < 0.001), longer intensive care unit (p < 0.001) and hospital (p < 0.001) stay, longer ventilator duration (p < 0.001) and increased hospital mortality (p = 0.02). In the multivariate analysis, serum lactate level measured at hospital admission was independently associated with the occurrence of ICI (p = 0.03). Liver cirrhosis (p = 0.03) and Sequential Organ Failure Assessment (SOFA) score (p = 0.007) were independently associated with the 90-day mortality. CONCLUSIONS: Blood lactate level measured at hospital admission could be a predictor of ICI and the surgical critically ill PPU patients with liver cirrhosis and higher SOFA score are associated with poor outcomes.

Risk of Mortality among Patients with Gastrointestinal Bleeding with Early and Late Treatment with Tranexamic Acid: A Population-Based Cohort Study.

Tranexamic acid (TXA) is an antifibrinolytic pharmacological agent, but its use in gastrointestinal bleeding remains contentious. Moreover, studies on the timing of TXA administration are limited. We examined whether early TXA administration reduced the risk of mortality in patients with gastrointestinal bleeding in a Taiwanese population. We used the National Health Insurance Research Database to identify patients diagnosed with gastrointestinal bleeding with early and late TXA treatment. We defined early treatment as initial TXA treatment in an emergency department and late treatment as initial TXA treatment after hospitalization. Mortality within 52 weeks was the primary outcome. A multivariable analysis using a multiple Cox regression model was applied for data analysis. Propensity score matching (PSM) was performed to reduce the potential for bias caused by measured confounding variables. Of the 52,949 selected patients with gastrointestinal bleeding, 5127 were assigned to either an early or late TXA treatment group after PSM. The incidence of mortality was significantly decreased during the first and fourth weeks (adjusted HR (aHR): 0.65, 95% CI: 0.56−0.75). A Kaplan−Meier curve revealed a significant decrease in cumulative incidence of mortality in the early TXA treatment group (log-rank test: p < 0.0001). Multiple Cox regression analysis revealed significantly lower mortality in the early TXA treatment group compared with the late treatment group (aHR: 0.64, 95% CI: 0.57−0.73). Thromboembolic events were not significantly associated with early or late TXA treatment (aHR: 1.03, 95% CI: 0.94−1.12). A Kaplan−Meier curve also revealed no significant difference in either venous or arterial events (log-rank test: p = 0.3654 and 0.0975, respectively). In conclusion, early TXA treatment was associated with a reduced risk of mortality in patients with gastrointestinal bleeding compared with late treatment, without an increase in thromboembolic events. The risk of rebleeding and need for urgent endoscopic intervention require further randomized clinical trials.

Genomic and Metabolomic Landscape of Right-Sided and Left-Sided Colorectal Cancer: Potential Preventive Biomarkers.

Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence and mortality rates of CRC are significantly higher in Taiwan than in other developed countries. Genes involved in CRC tumorigenesis differ depending on whether the tumor occurs on the left or right side of the colon, and genomic analysis is a keystone in the study and treatment of CRC subtypes. However, few studies have focused on the genetic landscape of Taiwanese patients with CRC. This study comprehensively analyzed the genomes of 141 Taiwanese patients with CRC through whole-exome sequencing. Significant genomic differences related to the site of CRC development were observed. Blood metabolomic profiling and polygenic risk score analysis were performed to identify potential biomarkers for the early identification and prevention of CRC in the Taiwanese population. Our findings provide vital clues for establishing population-specific treatments and health policies for CRC prevention in Taiwan.

Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer.

Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of FGFR4 gene polymorphisms on the risk and progression of CRC. Three FGFR4 single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG; AOR, 0.236; p = 0.046) or rs351855 (GA and AA; AOR, 0.191; p = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression.

The Role of Series Cholecystectomy in High Risk Acute Cholecystitis Patients Who Underwent Gallbladder Drainage.

Background: Cholecystectomy (CCY) is the only definitive therapy for acute cholecystitis. We conducted this study to evaluate which patients may not benefit from further CCY after percutaneous transhepatic gallbladder drainage (PTGBD) has been performed in acute cholecystitis patients. Methods: Acute cholecystitis patients with PTGBD treatment were selected from one million random samples from the National Health Insurance Research Database obtained between January 2004 and December 2010. Recurrent biliary events (RBEs), RBE-related medical costs, RBE-related mortality rate and an RBE-free survival curve were compared in patients who accepted CCY within 2 months and patients without CCY within 2 months after the index admission. Results: Three hundred and sixty-five acute cholecystitis patients underwent PTGBD at the index admission. A total of 190 patients underwent further CCY within 2 months after the index admission. The other 175 patients did not accept further CCY within 2 months after the index admission. RBE-free survival was significantly better in the CCY within 2 months group (60 vs. 42%, p < 0.001). The RBE-free survival of the CCY within 2 months group was similar to that of the no CCY within 2 months group in patients ≥ 80 years old and patients with a Charlson Comorbidity Index (CCI) score ≥ 9. Conclusions: We confirmed CCY after PTGBD reduced RBEs, RBE-related medical expenses, and the RBE-related mortality rate in patients with acute cholecystitis. In patients who accepted PTGBD, the RBE and survival benefits of subsequent CCY within 2 months became insignificant in patients ≥ 80 years old or with a CCI score ≥ 9.

Interactive association between dietary fat and sex on CDH13 cg02263260 methylation.

BACKGROUND: DNA methylation of Cadherin 13 (CDH13), a tumor suppressor gene is associated with gene repression and carcinogenesis. We determined the relation of dietary fat and sex with CDH13 cg02263260 methylation in Taiwanese adults. METHODS: Data of 870 eligible participants (430 men and 440 women) between 30 and 70 years were obtained from the Taiwan Biobank (TWB) database. The association of dietary fat and sex with CDH13 cg02263260 methylation was determined using multiple linear regression. RESULTS: The association between sex and cg02263260 methylation was significant: beta-coefficient (ß) = 0.00532; 95% confidence interval (CI) = 0.00195-0.00868. Moreover, the interaction between sex and dietary fat on cg02263260 methylation was significant (P-value = 0.0145). After stratification by sex, the association of dietary fat with cg02263260 methylation was significant only in women. Specifically, high dietary fat was positively associated with cg02263260 methylation in women (ß = 0.00597; 95% CI = 0.00061-0.01133) and the test for trend was significant (P-value = 0.0283). CONCLUSION: High fat intake was significantly associated with higher cg02263260 methylation in women and the test for trend was significant. These findings suggest that the association of fat intake and CDH13 cg02263260 might vary by sex and CDH13 cg02263260 methylation levels in women might increase as fat intake increases.

Enterotype-based Analysis of Gut Microbiota along the Conventional Adenoma-Carcinoma Colorectal Cancer Pathway.

The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides- and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.

Preoperative MRCP to detect choledocholithiasis in acute calculous cholecystitis.

PURPOSE: There are risks of common bile duct (CBD) stones in acute cholecystitis, and there is a move among surgeons to identify choledocholithiasis before surgery. Magnetic resonance cholangiopancreaticography (MRCP) has the potential to accurately detect choledocholithiasis in patients with acute cholecystitis. The aim of this study was to evaluate the predictive values of MRCP and elevated biochemical predictors for choledocholithiasis in patients with acute cholecystitis. METHODS: Between September 2006 and August 2008, of 84 patients with acute cholecystitis based on the diagnosis criteria of the Tokyo guidelines, 57 had MRCP preoperatively. The predictive values of six biochemical predictors for choledocholithiasis were also evaluated. RESULTS: Of the 57 patients, seven (12.28%) had choledocholithiasis, of whom three had CBD stones in nondilated ducts. The smallest stone detected in a dilated CBD and nondilated duct was 3.19 and 4.55 mm in diameter, respectively. None of our patients whose MRCP showed a clear CBD returned with symptomatic choledocholithiasis during the follow-up period. All biochemical predictors and CBD diameter had limited positive predictive values. CONCLUSIONS: Magnetic resonance cholangiopancreaticography is a reliable evaluation technique for the detection of choledocholithiasis. It reduces the misdiagnosis of retained choledocholithiasis with normal biochemical predictors and prevents the risk of overlooking choledocholithiasis. No single predictor or combined markers have been found to be reliable for including/excluding the presence of choledocholithiasis.

Plectin deficiency on cytoskeletal disorganization and transformation of human liver cells in vitro.

Plectin is a versatile cytoplasmic cross-linking protein that connects intermediate filaments to microfilaments, microtubules, and membrane adhesion sites. The cross-linking functions of plectin help organize the cytoskeleton into a stable meshwork important for maintaining uniformity in cell size and shape. As cells of hepatocellular carcinoma are morphologically different from normal human hepatocytes, we hypothesized that altered plectin expression and cytoskeletal organization underlies this pleomorphic transformation. To test this hypothesis, we analyzed expression levels and organization of all cytoskeletal elements, including intermediate filaments, microfilaments, and microtubules, after plectin knockdown in human Chang liver cells. We found that expression of cytokeratin 18, but not actin or tubulin, was downregulated by suppression of plectin protein. Furthermore, cytokeratin networks were partially collapsed and actin-rich stress fibers were increased. The organization of microtubule networks, by contrast, was unaltered. These findings support our hypothesis that, via effects on cytoskeletal organization, plectin deficiency might play an important role in the transformation of human liver cells.