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Incidence of Venous Thromboembolism Following Surgery in Patients With Colorectal Cancer

ABSTRACT: Venous thromboembolism (VTE) has harmful effects on morbidity and mortality of cancer patients. In Western VTE guidelines, all solid cancer patients receiving abdominal major surgery are strongly recommended to receive pharmacologic prophylactic anticoagulation such as low molecular weight heparin (LMWH) in the perioperative periods. These recommendations are based on the high incidence of postoperative VTE development in Western cancer patients. However, there have been many cumulative data about the effect of different ethnicity on the VTE development and more and more investigators and clinicians admit that Asian ethnicity has lower incidence of VTE than Western ethnicity. Therefore, it may not be advisable to apply Western guidelines as it is to the clinical situation of Asian cancer patients. Although colorectal cancer (CRC) is one of the common cancers and the incidence is rapidly increasing in Asia, there have been few prospective data on the incidence of VTE development during the postoperative period in Asian CRC patients. To our knowledge, there have been a few small-sized prospective studies in Asia and thus clear conclusions could have not been drawn based on those studies. Most Korean colorectal surgeons think that the incidence of postoperative VTE development is very rare based on their own clinical experiences. They also have much concern about the complications such as bleeding that might be caused by routine use of pharmacologic thromboprophylaxis during the perioperative periods. Therefore, in most clinical situation, many Korean colorectal surgeons do not perform perioperative pharmacologic thromboprophylaxis using LMHW. Considering these clinical situations in Asia including Korea, the uncritical acceptance of Western guidelines may be inappropriate. The necessity of pharmacologic thrombo-prophylaxis can be answered only from our own prospective study on the incidence of postoperative VTE development after CRC surgery. Moreover, current surgical trend in cancer patients is minimally invasive approach such as laparoscopic surgery. However, the necessity of pharmacologic thromboprophylaxis in patients receiving laparoscopic cancer surgery has not been evaluated even in Western countries. Western guidelines also cannot exactly answer whether pharmacologic thromboprophylaxis is really necessary in cancer patients receiving laparoscopic cancer surgery. On above backgrounds, this study was designed.

DISEASE(S): Venous Thromboembolism,Asymptomatic Venous Thromboembolism,Colorectal Cancer,Colorectal Neoplasms,Symptomatic Venous Thromboembolism,Thromboembolism

PROVIDER: 2123017 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background Worldwide, gastric cancer is the fourth most common malignancy and the most common cancer in East Asia. Development of targeted therapies for this disease has focused on a few known oncogenes but has had limited effects. Objective To determine oncogenic mechanisms and novel therapeutic targets specific for gastric cancer by identifying commonly dys-regulated genes from the tumors of both Asian-Pacific and Caucasian patients. Design We generated transcriptomic profiles of 22 Caucasian gastric cancer tumors and their matched non-cancerous samples, and performed an integrative analysis across different gastric cancer gene expression datasets. We examined the inhibition of commonly overexpressed oncogenes and their constituent signaling pathways by RNAi and/or pharmacologic inhibition. Results We found that HNF4α upregulation was a key signaling event in gastric tumors from both Caucasian and Asian patients, and HNF4α antagonism was antineoplastic. Perturbation experiments in GC tumor cell lines and xenograft models further demonstrated that HNF4α is downregulated by AMPKα signaling and the AMPK agonist metformin; blockade of HNF4α activity resulted in cyclin downregulation, cell cycle arrest, and tumor growth inhibition. HNF4α also regulated WNT signaling through its target gene WNT5A, a potential prognostic marker of diffuse type gastric tumors. Conclusions Our results indicate that HNF4α is a targetable oncoprotein in gastric cancer, is regulated by AMPK signaling through AMPKα, and resides upstream of WNT signaling. HNF4α may regulate “metabolic switch” characteristic of a general malignant phenotype and its target WNT5A has potential prognostic values. The AMPKα-HNF4α-WNT5A signaling cascade represents a potentially targetable pathway for drug development. Integrative analysis of Caucasian and Asian-Pacific gastric tumor expression datasets (including newly generated transcriptomic profiling of 22 tumors in this study) revealed a relatively small common sets of highly overexpressed genes.

Project description:The 'Thin on the Outside Fat on the Inside' TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow’s milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0 g (water control), 12.5 g (low protein, LP) and 50 g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T0-240mins) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort’s WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models’ discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.

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Incidence of Venous Thromboembolism Following Surgery in Patients With Colorectal Cancer

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