Silencing phospholipid scramblase 1 expression by RNA interference in colorectal cancer and metastatic liver cancer

BACKGROUND:Phospholipid scramblase 1(PLSCR1) not only participates in the transbilayer movement of phospholipids,but also plays a role in the pathogenesis and progression of cancers.The present study aimed to evaluate the effect of silencing PLSCR1 expression by RNA interference in colorectal cancer(CRC) and metastatic liver cancer.METHODS:The expression of PLSCR1 in CRC and metastatic liver cancer samples was assessed by immunohistochemistry.The cultured cells with the highest expression were selected for subsequent experiments.We designed three siRNA oligonucleotide segments targeted at PLSCR1.Successful transfection was confirmed.The biological behavior of the cells in proliferation,adhesion,migration and invasion was determined.RESULTS:PLSCR1 protein expression increased significantly in the majority of CRC and metastatic liver cancer samples compared with normal samples.Lovo cells had the highest expression of PLSCR1.The siRNA-390 oligonucleotide segment had the best silencing effect.After transfection,Lovo cell proliferation was significantly inhibited compared with the controls in the MTT assay.Laminin and fibronectin adhesion assays showed Lovo cell adhesion was also significantly inhibited.In the migration assay,the number of migrating cells in the PLSCR1 siRNA-390 group was 50±12,significantly lower than the number in the siRNA-N group(115±28) and in the control group(118±31).In an invasion test,the number of invading cells in the PLSCR1 siRNA-390 group was 60±18,significantly lower than that in the siRNA-N group(97±26) and the control group(103±24).CONCLUSIONS:PLSCR1 is overexpressed in CRC and metastatic liver cancer.Silencing of PLSCR1 by siRNA inhibits the proliferation,adhesion,migration and invasion of Lovo cells,which suggests that PLSCR1 contributes to the tumorigenesis and tumor progression of CRC.PLSCR1 may be a potential gene therapy target for CRC and associated metastatic liver cancer.

Focal peliosis hepatis in a colon cancer patient resembling metastatic liver tumor

Peliosis hepatis(PH) is a rare benign condition characterized by the presence of multiple,randomly distributed,blood filled cystic areas of variable size within the liver parenchyma.PH is difficult to recognize and may be mistaken for neoplasm,metastases or multiple abscesses.A 75-year-old female with a previous history of colon cancer was admitted when a liver mass in the right liver lobe was found 11 mo after surgery during the follow-up period.Computed tomography and magnetic resonance imaging scan of the abdomen were performed.The initial possible diagnosis was metastatic hepatocellular carcinoma.The patient underwent excision of the hepatic segment where the nodule was located.The pathological diagnosis of the surgical specimen was PH.PH should be considered in the differential diagnosis of new liver lesions in patients whose clinical settings do not clearly favor metastasization.Clinicians and radiologists must recognize these lesions to minimize the probability of misdiagnosis and inappropriate treatment.

Limited influences of chemotherapy on healthy and metastatic liver parenchyma

AIM: To examine the expression of E-cadherin, β-catenin,γ-catenin, VEGF, and p53 in 39 patients with hepatic metastasis from colorectal cancer immunohistochemically.METHODS: The patients were divided into two groups:those (n = 16) who had no chemotherapy for at least 6 mo before the liver resections and those (n = 23)who were treated with chemotherapy before liver resections. A score from 0 to 3 was given for the number of positive cells and from 0 to 3 for the intensity of staining in these cells, in both healthy and metastatic liver parenchyma.RESULTS: No significant differences in the expression of E-cadherin, β- and γ-catenin, VEGF and p53, could be observed between patients who received and did not receive chemotherapy, in both normal and metastatic liver parenchyma.CONCLUSION: Despite the assumption that chemotherapy had an effect on liver metastasis, no influences were noticed immunohistochemically.

Metastatic disease to the liver:Locoregional therapy strategies and outcomes

Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases.While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease,a majority of patients present with bilobar disease not amenable to curative local resection.Furthermore,by the time metastasis to the liver has developed,many tumors demonstrate a degree of resistance to systemic chemotherapy.Fortunately,catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease.These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors,downstaging of large tumors for resection,or locoregional control and palliation of advanced disease.Their use has been associated with increased tumor response,increased disease-free and overall survival,and decreased morbidity and mortality in a broad range of metastatic disease.This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal,neuroendocrine,breast,and lung cancer,as well as uveal melanoma,cholangiocarcinoma,and sarcoma.Therapies discussed include bland transarterial embolization,chemoembolization,radioembolization,and ablative therapies,with a focus on current treatment approaches,outcomes of locoregional therapy,and future directions in each type of metastatic disease.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.

Neoadjuvant chemotherapy for metastatic colorectal cancer to the liver: from chemotherapy to targeting therapy

Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found at the time of diagnosis.[1] Surgical resection is now the standard treatment and also the only potentially curative treatment for resectable lesions.

Major complications after radiofrequency ablation for liver tumors:Analysis of 255 patients

AIM:To investigate the major complications after radiofrequency ablation(RFA) for the treatment of liver tumors and analyze possible risk factors that precipitate these complications.METHODS:From March 2001 to April 2008,255 patients with liver tumors(205 male,50 female;age range,18-89 years;mean age,56.0 years) who received RFA were enrolled in this study.Of these patients,212 had hepatocellular carcinoma,39 had metastatic liver tumors and four had cholangiocellular carcinoma.One hundred and forty eight patients had a single tumor,and 107 had multiple tumors.Maximum diameter of the tumors ranged 1.3-20 cm(mean,5.1 cm).All patients were treated with a cooled-tip perfusion electrode attached to a radiofrequency generator(Radionics,Burlington,MA,USA).RFA was performed via the percutaneous approach(n = 257),laparoscopy(n = 7),or open surgical treatment(n = 86).The major complications related to RFA were recorded.The resultant data were analyzed to determine risk factors associated these complications.RESULTS:Among the 255 patients,425 liver tumors were treated and 350 RFA sessions were performed.Thirty-seven(10%) major complications were observed which included 13 cases of liver failure,10 cases of hydrothorax requiring drainage,three casesof tumor seeding,one case of upper gastrointestinal bleeding,one case ofintrahepatic abscess,one case of bile duct injury,one case of cardiac arrest,and five cases of hyperglycemia.Seven patients had more than two complications.Liver failure was the most severe complication and was associated with the highest mortality.Eleven patients died due to worsening liver decompensation.Child-Pugh classification(P = 0.001) and choice of approach(P = 0.045) were related to post-treatment liver failure,whereas patient age,tumor size and number were not significant factors precipitating this complication.CONCLUSION:RFA can be accepted as a relatively safe procedure for the treatment of liver tumors.However,attention should be paid to possible complications even though the incidences of these complications are rare.Careful patient selection and the best approach choice(percutaneous,laparoscopy,or laparotomy) will help to minimize the incidence and morbidity rate of complications which occur after RFA.

Role of surgical resection for non-colorectal non-neuroendocrine liver metastases

It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases(NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy.

High-frame-rate contrast-enhanced ultrasound findings of liver metastasis of duodenal gastrointestinal stromal tumor:A case report and literature review

BACKGROUND Liver metastasis of duodenal gastrointestinal stromal tumor(GIST)is rare.Most reports mainly focus on its treatment and approaches to surgical resection,while details on its contrast-enhanced ultrasound(CEUS)findings are lacking.The diagnosis and imaging modalities for this condition remain challenging.CASE SUMMARY A 53-year-old Chinese man presented with mild signs and symptoms of the digestive tract.He underwent routine examinations after GIST surgery.Magnetic resonance imaging showed a 2.3 cm hepatic space-occupying lesion.All the laboratory test results were within normal limits.For further diagnostic confirmation,we conducted high frame rate CEUS(H-CEUS)and found a malignant perfusion pattern.Heterogeneous concentric hyper-enhancement,earlier wash-in than the liver parenchyma,and two irregular vessel columns could be observed at the periphery of the lesion during the arterial phase.Ultrasound-guided puncture biopsy was used to confirm the diagnosis of the lesion as liver metastasis of duodenal GIST.Imatinib was prescribed after biopsy,and the patient’s clinical course was monitored.CONCLUSION H-CEUS is useful for detecting microcirculation differences,wash-in patterns,and vascular morphogenesis and diagnosing liver metastasis of duodenal GIST.

A case of primary malignant fibrous histiocytoma of the pancreas with liver metastasis

Malignant fibrous histiocytoma(MFH) is one of most common types of soft-tissue sarcoma. However, it accounts for less than 1% of all human cancer types. In addition, primary MFH of the pancreas is very rare. Herein, we report of a 37-year-old man who presented with a pancreatic mass and did not show any specific symptoms. Pre-contrast computed tomography(CT) showed a heterogeneous, liquid-filled necrotic mass in the uncinate lobe of the pancreas. Contrast-enhanced CT showed a mild enhancement of solid components and the pancreaticoduodenal artery across the mass. The patient underwent a pancreaticoduodenectomy, ethanol ablation of the liver lesions, and chemotherapy with 4 cycles of ifosfamide and doxorubicin. The tumor recurred in the liver, but not in the pancreas, after 8 months.

Clinical Significance of a Rise in AFP in Lung Adenocarcinoma Patients with Liver Metastasis:One Case Report and Literatures Review

IntroductionUsually the alpha fetoprotein （AFP） concentration of patients with metastatic liver cancer is slightly raised. Most of the levels are lower than 400 ug/L. Following biopsies of lung and liver neoplasms, one patient with a clinical diagnosis of lung cancer plus liver metastasis was pathologically diagnosed having an adenocarcinoma. His serum AFP value was 100-300 times the normal value. In order to further explore the clinical significance of an elevation of the AFP level in patients with lung adenocarcinoma plus liver metastasis, and to precisely distinguish a simple liver metastasis from lung adenocarcinoma or from lung hepatoid adenocarcinoma （HAC）, a clinical analysis of the patient, and a literature review was conducted.

Percutaneous hepatic perfusion with melphalan for unresectable liver metastasis

Percutaneous hepatic perfusion(PHP)is an investigative technique for treating patients with diffuse unresectable metastatic liver disease.The technique has been clinically evaluated and shows great treatment potential for regional therapy to the liver.The advantage of PHP lies in its minimally invasive approach and ability to be repeated when compared to isolated hepatic perfusion.In a literature search,135 publications were screened and 16 of these publications,including clinical trials and reviews,contributed to this review of PHP with melphalan.Melphalan is an alkylating agent that,when used as the chemotherapeutic agent in PHP,has shown potential for significant control of tumor burden in the liver,especially in metastatic ocular melanoma.In the current landscape of liver directed therapy,PHP is a viable option for those with unresectable metastatic disease to the liver.This article will focus on the technical aspects of PHP and describe the current data available from clinical trials,including outcomes of patients treated with this minimally invasive approach.