Gastrointestinal

High Ran level is correlated with poor prognosis in patients with colorectal cancer.

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Abstract

Background

The Ras-like nuclear protein (Ran) is involved in the regulation of nuclear transport, microtubule nucleation and dynamics, and spindle assembly. Its fundamental function is nucleocytoplasmic transport of RNA and proteins. The expression and potential role of Ran in colorectal cancer (CRC) remain unclear. The aim of this study was to investigate the relationship between Ran expression and CRC characteristics. The potential role of Ran as a prognostic indicator was also evaluated.

Methods

We used immunohistochemistry and western blotting to detect Ran expression in 287 CRC tissues. The relationships between Ran expression and clinicopathological characteristics and overall survival rate were statistically analyzed.

Results

CRC tissues had significantly higher Ran expression than normal colorectal epithelial cells. Ran was positively correlated with depth of invasion, lymph node metastases, distant metastases, tumor differentiation, and tumor–node–metastasis stage. However, no correlation was found between Ran expression and patient age or sex. The overall survival rate was consistently and significantly lower in patients with Ran-positive tumors than in those with Ran-negative tumors.

Conclusion

Our findings emphasize the important role of Ran in differentiation, disease stage, and metastasis in human CRC. Ran may play an important role in the development of CRC and may serve as a novel prognostic indicator of CRC.

Source: International Journal of Clinical Oncology

Endoscopic evaluation of primary tumor response in patients with metastatic colorectal cancer treated by systemic chemotherapy.

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Abstract

Background

The number of cases of metastatic colorectal cancer treated by chemotherapy without primary tumor resection has recently increased. However, evaluation of primary tumor response by computed tomography is difficult in such cases. In this study, the usefulness of evaluation of primary tumor response to chemotherapy by endoscopy was investigated.

Methods

This retrospective analysis was performed at the Shizuoka Cancer Center and included 31 patients (88 evaluations) with metastatic colorectal cancer. Computed tomography and endoscopy were performed concomitantly between September 2002 and June 2006. Patients were treated by systemic chemotherapy without prophylactic primary tumor resection. Definitions of primary tumor response were as follows: (1) complete response, confirmed by colorectal biopsy; (2) progressive disease, enlargement of at least one of five tumor parameters; and (3) neither (1) nor (2). Computed tomography was performed to evaluate primary tumor response according to the Response Evaluation Criteria in Solid Tumors and to identify colorectal stenosis secondary to primary tumors.

Results

The rate of concordance between endoscopy and computed tomography for evaluation of primary tumor response was 75 %. Colorectal stenosis was detected 14 times by endoscopy (9 cases) and 3 times by computed tomography (3 cases). Of the 7 patients in whom surgery was required, 6 exhibited stenotic symptoms before endoscopic detection.

 

Conclusions

With regard to primary tumor response evaluation, a high concordance rate was observed between endoscopy and computed tomography, although endoscopic evaluation appeared more sensitive in detecting colorectal stenosis requiring surgical treatment.

Source: International Journal of Clinical Oncology

Metabolic syndrome: A novel high-risk state for colorectal cancer

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Metabolic syndrome (MS) and related disorders, including cancer, are steadily increasing in most countries of the world. However, mechanisms underlying the link between MS and colon carcinogenesis have yet to be fully elucidated. In this review article we focus on the relationships between various individual associated conditions (obesity, dyslipidemia, diabetes mellitus type 2 and hypertension) and colon cancer development, and demonstrate probable related factors revealed by in vivo and in vitrostudies. Furthermore, molecules suggested to be involved in cancer promotion are addressed, and the potential for cancer prevention by targeting these molecules is discussed.

 

Source: cancer letters

 

 

 

 

Current status on the diagnosis and evaluation of pancreatic tumour in Asia with particular emphasis on the role of endoscopic ultrasound.

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In Asia, the incidence of pancreatic cancer in some countries has been increasing. Owing to most cases being diagnosed late, prognosis for pancreatic cancer remains dismal. It is clear the future for pancreatic cancer is early detection. While the possible presence of pancreatic masses is often first raised by non-invasive abdominal imaging such as computerized tomography (CT) and magnetic resonance imaging (MRI), smaller lesions and locoregional lymph node metastases are often not detectable by these means. Endoscopic ultrasonography (EUS) offers a higher sensitivity (93-100%) for the detection of small potentially curable pancreatic masses than other existing imaging modalities. It is also recommended to evaluate portal vein confluence, portal vein, celiac axis and SMA origin, and exclude respectability. Due to the closer proximity of EUS to the target structure, and lower rate of needle tract seeding, EUS-guided fine needle aspiration (FNA) of pancreatic mass is considered the most suitable tissue acquisition technique. Lastly, EUS also enables the performance of endoscopic interventions. Its performance can be further enhanced with newer techniques, including contrast enhanced ultrasound and elastrography. It is anticipated that in the near future, molecular technologies may make it possible to detect microscopic amounts of cancer in tissue or blood, predict relapse and survival after therapy, as well as determine optimal therapy.

 

 

 

 

Hepatocellular Carcinoma after the Fontan Procedure.

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Long-term hepatic dysfunction is an increasingly recognized complication of corrective surgery for complex cyanotic congenital heart disease.1 We report four cases of hepatocellular carcinoma in patients with congenital heart disease with univentricular physiology that was palliated by means of the Fontan procedure (

Patient 1, a 32-year-old woman with a cirrhotic liver, was shown to have a 4-cm hepatocellular carcinoma on biopsy. She underwent transarterial chemoembolization and was put on the waiting list for combined heart and liver transplantation.

Patient 2, a 24-year-old man with portal-vein thrombosis, ascites, and innumerable bilobar hepatic nodules, was shown to have neither cirrhosis nor hepatocellular carcinoma on targeted biopsies. A third biopsy revealed well-differentiated hepatocellular carcinoma. He died from metastatic hepatocellular carcinoma.

Patient 3, a 33-year-old man with a dominant liver nodule, had findings on imaging that were characteristic of hepatocellular carcinoma. He was put on the waiting list for combined heart and liver transplantation and underwent radioembolization at another institution. He had massive gastrointestinal bleeding from a hepatic-artery pseudoaneurysm and subsequently died.

Patient 4, a 42-year-old woman with hepatitis C virus infection, advanced liver fibrosis, and two lesions characteristic of hepatocellular carcinoma, underwent successful chemoembolization after being put on the waiting list for combined heart and liver transplantation.

Patients with congenital heart disease who undergo the Fontan procedure may represent a novel group for screening for liver disease. Surveillance for hepatocellular carcinoma may be needed in such patients, especially if the alpha-fetoprotein level is elevated.2 Cirrhosis may develop in persons under the age of 25 years approximately 11 to 15 years after a Fontan procedure; an incidence of cancer of 1.5 to 5.0% per year is estimated on the basis of previous studies. Cirrhosis, a potential prerequisite for hepatocellular carcinoma, may develop because of repetitive mechanical stretch and compression (passive congestion) and tissue hypoxia (low cardiac output) related either to the circulation created by the Fontan procedure or to chronically elevated right atrial pressure.3 The interval for screening for liver disease is unknown.2

Diagnosing hepatocellular carcinoma in patients with congenital heart disease is difficult because hyperenhancing nodules are often present in such patients.4 In patients with cardiac failure and intrahepatic vascular shunts, the typical arterial enhancing pattern of hepatocellular carcinoma may not be obvious. Surgical resection of the carcinoma may be limited by portal hypertension. Local–regional therapy may be limited by the presence of cardiac pacemakers (radiofrequency ablation), extrahepatic shunts (radioembolization), and abnormal vasculature (chemoembolization). Liver transplantation is limited by cardiac function (hypoxemia, pulmonary hypertension, and elevated right atrial pressure). Combined heart and liver transplantation may be feasible, but experience in such cases is limited.5Since corrective surgery for patients with univentricular physiology has substantially reduced childhood mortality associated with complex cyanotic congenital heart disease, urgent attention and vigilance are needed to avoid a similar premature fate in early adulthood.

Source: NEJM