Objective Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and inhibit T-cell-mediated immune responses against colorectal tumours. Thus, we hypothesized that the amount of Fusobacterium nucleatum in colorectal carcinoma might be associated with worse clinical outcome. Design We utilised molecular pathological epidemiology database of 1,069 rectal and colon cancer cases in the Nurses’ Health Study and the Health Professionals Follow-up Study, and measured Fusobacterium nucleatum DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level methylation). Results Compared to Fusobacterium nucleatum-negative cases, multivariable HRs (95% confidence interval) for colorectal cancer-specific mortality in Fusobacterium nucleatum-low cases and Fusobacterium nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively (p for trend = 0.020). The amount of Fusobacterium nucleatum was associated with MSI-high (multivariable odds ratio, 5.22; 95% CI, 2.86 to 9.55) independent of CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated with Fusobacterium nucleatum only in univariate analyses (p < 0.001) but not in multivariate analysis that adjusted for MSI status. Conclusions The amount of Fusobacterium nucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting gastrointestinal microflora by diet, probiotics, and antibiotics.

The epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2010; 101: 293-299) D evelopment of distant metastases is the final stage of solid cancer progression and is responsible for the majority of cancer-related deaths.(1) Distant metastasis alone or with concurrent locoregional recurrence accounts for nearly 80% of all first relapses in women with breast cancer.(2) While clinically of great importance, the biology of metastasis remains unsolved. The process of tumor metastasis consists of multiple steps, all of which are required to achieve tumor spreading.(3,4) First, cancer cells escape from the primary tumor site. Next, cancer cells invade the tumor stroma and enter the blood circulation directly or the lymphatic system via intravasation. Most circulating cancer cells undergo apoptosis due to anoikis conditions.(5) If cancer cells survive in circulation they may reach more suitable sites by attaching to endothelial cells and extravasating from the circulation into the surrounding tissues. Finally, distal colonization requires that cancer cells invade and grow in the new environment.Recently, the concept of the epithelial-mesenchymal transition (EMT), as developed in the field of embryology, has been extended to cancer progression and metastasis.(6,7) In vitro and experimental animal model data now support the role of EMT in metastasis, concepts supported by analyses of clinical samples. Indeed, the biology of EMT has been clarified in tumor samples through use of EMT-associated markers, such as mesenchymalspecific markers (i.e. vimentin and fibronectin), (8,9) epithelial specific markers (i.e. E-cadherin and cytokeratin), (10,11) and transcription factors (i.e. SNAIL and SLUG). (12) Most recently, several intriguing studies have described the novel mechanism underlying EMT activation. In the current study, we will discuss the role of small non-coding RNA (micro-RNA) in regulating EMT-r...

The aims of this study were to investigate sarcopenia as a novel predictor of mortality and sepsis after living donor liver transplantation (LDLT) and to evaluate the effects of early enteral nutrition on patients with sarcopenia. Two hundred four patients undergoing preoperative computed tomography within the month before LDLT were retrospectively evaluated. The lengths of the major and minor axes of the psoas muscle were simply measured at the caudal end of the third lumbar vertebra, and the area of the psoas muscle was calculated. A psoas muscle area lower than the 5th percentile for healthy donors of each sex was defined as sarcopenia. Ninety-six of the 204 patients (47.1%), including 58.3% (60/103) of the male patients and 35.6% (36/101) of the female patients, were diagnosed with sarcopenia. Sarcopenia was independently and significantly associated with overall survival: there was an approximately 2-fold higher risk of death for patients with sarcopenia versus patients without sarcopenia (hazard ratio 5 2.06, P 5 0.047). Sarcopenia was an independent predictor of postoperative sepsis (hazard ratio 5 5.31, P 5 0.009). Other independent predictors were a younger recipient age (P < 0.001) and a higher body mass index (P 5 0.02). Early enteral nutrition within the first 48 hours after LDLT was performed for 24.2%

Sarcopenia negatively impacts survival in patients undergoing curative resection for stage I-III CRC.

The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).