Nanog: A Potential Biomarker for Liver Metastasis of Colorectal Cancer

Background

At present, the relationship between Nanog expression and the biological behavior and prognosis of colorectal cancer is still unclear.

Aim

The purpose of this study was to evaluate the expression and regulatory effects of Nanog in colorectal cancer and the correlation between Nanog protein expression and the prognosis of patients with colorectal cancer.

Materials and Methods

The differential expression of genes between CD133+ tumor cells and CD133? tumor cells were detected using RT² Profiler? PCR Array. The Nanog mRNA expression level was detected by RT-PCR and the protein level was detected using immunohistochemistry staining. The relationship between Nanog expression and clinicopathological parameters of colorectal cancer was determined.

Results

Nanog were expressed significantly higher in CD133+ tumor cells compared to CD133? tumor cells. It was observed that 72 (20.00?%) of the 360 cases positively expressed Nanog. Univariate analyses indicated that Nanog expression was related to histological grade, lymph node metastasis, TNM stage, and liver metastasis (P?=?0.005, 0.001, 0.001 and 0.012, respectively). Spearman correlation analysis showed that Nanog expression has a linear correlation to liver metastasis (P?=?0.001). After conducting multivariate analysis, histological grade, TNM stage, and Nanog were found to be related to liver metastasis (P?=?0.020, 0.01 and 0.001, respectively). In the Cox regression test, the histological grade, Lymph node metastasis, TNM stage, liver metastasis, and Nanog were detected as the independent prognostic factors (P?=?0.02, 0.045, 0.01, 0.001 and 0.001, respectively).

Conclusions

Nanog protein may be a potential biomarker for postoperative liver metastasis of colorectal cancer.     

MDM2 mRNA Expression in the p53 Pathway May Predict the Potential of Invasion and Liver Metastasis in Colorectal Cancer

Purpose  The p53/MDM2/p14ARF pathway is one of the major signaling cascades involved in the regulation of apoptosis. Although many tumors have been reported to show disruption of the p53/MDM2/p14ARF pathway, few studies have examined p53, MDM2, and p14ARF simultaneously in colorectal carcinoma. The present study was undertaken to clarify whether correlations exist among MDM2, p53, and p14ARF in colorectal cancer. Methods  We determined the presence of mutations in the p53 gene, MDM2 expression, and methylation status of the p14ARF in 97 primary colorectal carcinoma specimens. Associations with survival and clinicopathologic factors were investigated. Results  At least one abnormality of these three molecules was found in 82 (84 percent) tumors. We observed a significant inverse association between MDM2 expression and tumor invasion (P = 0.01). Furthermore, the presence of liver metastasis was also significantly associated with low MDM2 expression (P = 0.02). Conclusions  The results suggest that disruption of the p53/MDM2/p14ARF pathway may frequently participate in colonic carcinogenesis and that MDM2 expression status may be a factor in the prediction of potential invasion and liver metastasis of colorectal carcinomas. Reprints are not available.     

Minor-but-Complex Liver Resection: An Alternative to Major Resections for Colorectal Liver Metastases Involving the Hepato-Caval Confluence

Major hepatectomy (MH) is often considered the only possible approach for colorectal liver metastasis (CRLM) at the hepato-caval confluence (CC), but it is associated with high morbidity and mortality. With the aim to reduce MH, we developed the “minor-but-complex” (MbC) technique, which consists in the resection of less than 3 adjacent liver segments with exposure of the CC and preservation of hepatic outflow until spontaneous maturation of peripheral intrahepatic shunts between main hepatic veins. We have evaluated applicability and outcome of MbC resections for the treatment of CRLM involving the CC.In this retrospective cohort study, all consecutive liver resections (LR) performed for CRLM located in segments 1, 7, 8, or 4a were classified as MINOR – removal of <3 adjacent segments; MbC – removal of <3 adjacent segments with CC exposure; and MH – removal of ≥3 adjacent segments. The rate of avoided MH was obtained by the difference between the rate of potentially MH (PMH) plus potentially inoperable cases and the rate of the MH performed. Taking into account that postoperative mortality is mainly related to the amount of resected liver, MbC was compared with minor resections for safety, complexity, and outcome.Of the 59 LR analyzed, 29 (49.1%) were deemed PMH and 4 (6.8%) potentially inoperable. Eventually, MH was performed only in 8 (13.5%) with a decrease rate of 42.4%. Minor LR was performed in 23 (39.0%) and MbC LR in 28 (47.5%) patients. Among MbC cases, 32.1% had previous liver treatments, 39.3% required vascular reconstruction (no reconstructed vessel thrombosis occurred before maturation of peripheral intrahepatic shunts between main hepatic veins), and 7.1% had grade IIIb–IV complications, their median hospital stay was 9 days and 90-day mortality was 0%. After a median follow-up of 22.2 months, oncological results were comparable with those of minor resections.MbC hepatectomy lowers the need for MH and allows for the resection of potentially inoperable patients without negative impact on safety and survival.     

Clinical and Microbiological Features of Liver Abscess after Transarterial Embolization for Hepatocellular Carcinoma

Objectives: To present the clinical and microbiological features of liver abscess after transarterial embolization (TAE) for hepatocellular carcinoma (HCC). Methods : We retrospectively reviewed records of 452 TAE procedures in 289 patients with HCC over a 2-yr period. Results : Four men and one woman with a mean age of 68.4 yr were diagnosed with liver abscess 1–8 wk (mean 4.6 wk) after the embolization. The incidence was 1.1% (5/452). Common symptoms included fever, chills, and right upper quadrant pain. Serum aminotransferase, alkaline phosphatase, and γ-glutamyltransferase levels and leukocyte count were frequently elevated. All the abscesses appeared as areas of hypodensity on CT scan and hypoechogenicity on ultrasonogram. The areas contained gas in the embolized tumor, which led to the suspicion and finally the diagnosis of abscess. In contrast to predominance of Gram-negative aerobes in sporadic pyogenic liver abscesses, the causative microorganism was predominantly Gram positive (60%). All patients were treated with parenteral antibiotics plus percutaneous aspiration, drainage, or operation, but one patient died from the abscess. Conclusions : For patients receiving TAE for HCC, few specific clinical or radiological features could readily differentiate patients complicated with liver abscess from those without. This may delay a timely diagnosis and lead to significant morbidity. Hence, in patients with risk factors, including old age, previous biliary tract disease, large tumor size (>5 cm), and gas forming in the embolized tumor, aspiration of the suspected focal hepatic lesion should be performed as soon as possible.     

Association of primary tumor laterality with surgical outcomes for colorectal liver metastases: results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC)

BackgroundPrimary laterality of colorectal cancer is thought to be associated with differences in outcomes. Liver metastasis is the most common site of solitary colorectal cancer spread. However, how primary colorectal cancer laterality affects outcomes in colorectal liver metastasis remains unclear.MethodsThe Colorectal Liver Operative Metastasis International Collaborative (COLOMIC) of operative hepatectomy cases for colorectal liver metastasis was compiled from five participating institutions. This included consecutive cases from 2000 to 2018 at all sites. A total of 884 patients were included in this study. Univariate, multivariate, and Kaplan–Meier analyses were performed.ResultsPatients with left-sided versus right-sided cancers had significantly better overall survival: 49.4 vs. 41.8 months (p < 0.05). Patients with KRAS mutations had significantly worse median overall survival compared to KRAS wild-type (43.6 vs 56.1 months; p < 0.001). In left-sided cancers, KRAS mutations were associated with significantly worse median overall survival compared to KRAS wild-type cancers (43.6 vs 56.6 months; p < 0.01). This association was absent in patients with right-sided primary tumors. Multivariate Cox regression analysis revealed different variable sets (non-overlapping) were associated with overall survival, when comparing left-sided and right-sided cancers.ConclusionUnderstanding how primary tumor laterality and related biological aspects affect long-term outcomes can potentially inform treatment decisions for patients with colorectal liver metastases.     

Access to Liver Transplantation in the MELD Era: Role of Ethnicity and Insurance

Factors contributing to inequitable access to liver transplantation include socioeconomic status, geographic location, and delayed referral. The aim of this study is to identify the factors associated with a high MELD at the time of listing. Using the UNOS database, we identified all adults listed from 2002 to 2006. Data collected included demographics, insurance payor (private and government, i.e., Medicaid and non-Medicaid), diagnosis, and MELD score categorized as low (<20) and high (≥20). The results obtained show that a high MELD was associated with age, ethnicity, and insurance (P < 0.001). By multivariate analysis, insurance (OR = 1.21, 95% CI = 1.13–1.30, P < 0.001) and ethnicity (OR = 1.55, 95% CI = 1.28–1.88, P < 0.001) were independently associated with high MELD. In conclusion, ethnic minorities and liver transplant candidates with Medicaid are more likely to have a high MELD score at initial listing. The above results suggest that the type of insurance and ethnicity are independently associated with a high MELD (i.e., sicker patients).     

Molecular Features of the Serrated Pathway to Colorectal Cancer: Current Knowledge and Future Directions

Serrated lesions are the precursor lesions of a new model of colorectal carcinogenesis. From a molecular standpoint, the serrated pathway is thought to be responsible for up to 30% of all colorectal cancer cases. The three major processes of this molecular mechanism are alterations in the mitogen-activated protein kinase pathway, production of the CpG island methylation phenotype, and generation of microsatellite instability. Other contributing processes are activation of WNT, alterations in the regulation of tumor suppressor genes, and alterations in microRNAs or in MUC5AC hypomethylation. Although alterations in the serrated pathway also contribute, their precise roles remain obscure because of the various methodologies and definitions used by different research groups. This knowledge gap affects clinical assessment of precursor lesions for their carcinogenic risk. The present review describes the current literature reporting the molecular mechanisms underlying each type of serrated lesion and each phenotype of serrated pathway colorectal cancer, identifying those areas that merit additional research. We also propose a unified serrated carcinogenesis pathway combining molecular alterations and types of serrated lesions, which ends in different serrated pathway colorectal cancer phenotypes depending on the route followed. Finally, we describe some key issues that need to be addressed in order to incorporate the newest technologies in serrated pathway research and to improve overall knowledge for developing specific prevention strategies and new therapeutic targets.     

Risk Stratification of T1 Colorectal Cancer Metastasis to Lymph Nodes: Current Status and Perspective

With the widely spreading population-based screening programs for colorectal cancer and recent improvements in endoscopic diagnosis, the number of endoscopic resections in subjects with T1 colorectal cancer has been increasing. Some reports suggest that endoscopic resection prior to surgical resection of T1 colorectal cancer has no adverse effect on prognosis and contributes to this tendency. The decision on the need for surgical resection as an additional treatment after endoscopic resection of T1 colorectal cancer should be made according to the metastasis risk to lymph nodes based on histopathological findings. Because lymph node metastasis occurs in approximately 10% of patients with T1 colorectal cancer according to current international guidelines, the remaining 90% of patients may be at an increased risk of surgical resection and associated postoperative mortality, with no clinical benefit derived from unnecessary surgical resection. Although a more accurate prediction system for lymph node metastasis is needed to solve this problem, risk stratification for lymph node metastasis remains controversial. In this review, we focus on the current status of risk stratification of T1 colorectal cancer metastasis to lymph nodes and outline future perspectives.     

Metastasis to the Pancreas: Characterization by Morphology and Contrast Enhancement Features on CT and MRI

Aims: To investigate the characteristics of metastasis to the pancreas using computed tomography (CT) and magnetic resonance imaging (MRI). Methods: Twenty-two patients with métastases to the pancreas were examined preoperatively by MRI (7/22) and/or multidetector CT (15/22). Pre- and post-contrast images were acquired and morphology, size, and contrast enhancement of the tumor analyzed. Subsequently, all patients underwent surgery, and the histopathologic findings were compared with the imaging results, Results: In 22 patients, a total of 29 metastases were found on CT and MRI. These metastases originated from renal cell carcinomas (RCC; 22/29), colorectal carcinoma (3/29), and other malignancies (4/29). The métastases differed not in size or location, but in their contrast enhancement characteristics. RCC métastases had either intense homogeneous enhancement (in small lesions) or rim enhancement (in large lesions). Outer regions of colorectal metastases showed no difference from normal pancreatic tissue, whereas the inner area showed hypo-enhancement due to central necrosis. Conclusion: Imaging features of métastases from RCC point to their primary origin. While they can be distinguished from primary adenocarcinoma of the pancreas, differentiation from endocrine carcinoma might be difficult. Differentiation of colorectal carcinoma remains to be investigated on larger numbers of Cases.