Treatment for liver metastases from breast cancer: Results and prognostic factors

AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients may benefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE). We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACE or systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%, respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the patients with metastatic breast cancer.

Hepatocellular carcinoma: Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.

Prognostic factors in patients with node-negative gastric carcinoma:A comparison with node-positive gastric carcinoma

AIM： To identify the clinicopathological characteristics of lymph node-negative gastric carcinoma, and also to evaluate outcome indicators in the lymph node-negative patients.METHODS： Of 2848 gastric carcinoma patients, 1524 （53.5%） were lymph nede-negative. A statistical analysis was performed using the Cox model to estimate outcome indicators. RESULTS： There was a significant difference in the recurrence rate between lymph nede-negative and lymph node-positive patients （14.4% vs 41.0%, P〈0.001）. The 5-year survival rate was significantly lower in lymph node-positive than in lymph node-negative patients （31.1% vs 77.4%, P〈0.001）. Univariate analysis revealed that the following factors influenced the 5-year survival rate： patient age, tumor size, depth of invasion, tumor location, operative type, and tumor stage at initial diagnosis. The Cox proportional hazard regression model revealed that tumor size, serosal invasion, and curability were independent, statistically significant, prognostic indicators of lymph node-negative gastric carcinoma. CONCLUSION： Lymph node-negative patients have a favorable outcome attributable to high curability, but the patients with relatively large tumors and serosal invasion have a poor prognosis. Curability is one of the most reliable predictors of long-term survival for lymph nodenegative gastric carcinoma patients.

siRNA, miRNA and HIV: promises and challenges

Small interfering RNA (siRNA) and microRNA (miRNA) are small RNAs of 18-25 nucleotides (nt) in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex (RISC) and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 (HIV-1) which is able to evade RNA silencing by either mutating the siRNA- targeted sequence or by encoding for a partial suppressor of RNAi (RNA interference). On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNA- specified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells’ antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs (vmiRNAs).

Early bile duct cancer

Bile duct cancers are frequently diagnosed as advanced diseases. Over half of patients with advanced bile duct cancer present with unresectable malignancies and their prognosis has been very poor even after curative resections. Although there has been a need to diagnose bile duct cancer at its eady stage, it has been a difficult goal to achieve due to our lack of knowledge regarding this disease entity. Early bile duct cancer may be defined as a carcinoma whose invasion is confined within the fibromuscular layer of the extrahepatic bile duct or intrahepatic large bile duct without distant metastasis irrespective of lymph node involvement. Approximately 3%-10% of resected bile duct cancers have been reported to be early cancers in the literature. The clinicopathological features of patients with early bile duct cancer differ from those of patients with advanced bile duct cancer, with more frequent asymptomatic presentation, characteristic histopathological findings, and excellent prognosis. This manuscript is organized to emphasize the need for convening an international consensus to develop the concept of early bile duct cancer.

Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers

AIM： To examine the expression of beta-catenin in colorectal cancer and look for association with other dinico-pathological parameters. METHODS;： Tumor samples from 163 cases of colorectal cancer （CRC） who had undergone primary colectomy between May, 1998 and November, 2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density （OSD） and percentage of cells having nuclear localization was counted as nuclear staining density （NSD）. Univariate exploration used log-rank test and multivariate survival analysis used Cox＇s hazard regression model. RESULTS： Beta-catenin immunoreactivity was detected in 161 samples （98.8%）, of which 131 cases had nuclear staining. High OSD （≥ 75%）, detected in 123 cases （75.5%）, was significantly associated with earlier clinical staging （P 〈 0.01）, lower nodal status （P = 0.02）, non-metastatic status （P 〈 0.01） and better differentiation （P = 0.02）. Multivariate analysis found that high OSD was independently associated with better survival [Cox＇s hazard ratio 0.51, 95% confidence interval （CI） 0.31-0.83]. Although high NSD （≥ 75%） was correlated with high pre-operative serum CEA （P = 0.03）, well differentiation （P 〈 0.01）, and increased staining intensity（P 〈 0.01）, the parameter was not significantly associated with survival. CONCLI3SIOM： Unlike previous reports, the study did not find a predictive value of nuclear beta-catenin in CRC. Instead, the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover, the parameter also independently predicted superior survival.

Long-term prognosis in patients with severe late radiation enteropathy:A prospective cohort study

AIM: To assess persistent symptoms and mortality in a cohort of patients with severe (grade 3-4) radiation enteropathy,59 patients were followed up after 15-18 years. METHODS: Fifty-nine patients were prospectively enrolled by twelve surgical departments. Primary malignant disease,radiation therapy and surgical management were recorded at inclusion. The cause of death or persistence of symptoms was examined in public death records or by interview of survivors. RESULTS: Thirty-nine patients had received radiation therapy for gynaecological cancers,twelve for urological cancers,four for gastrointestinal cancers and four for other malignancies. Forty-five patients (76%) required surgical intervention. Complications occurred in 11 (25%) operated patients. Forty-seven patients had died at the time of follow-up,seven (12%) died as a direct result of radiation enteropathy,while radiation enteropathy contributed to death in an additional seven patients. Four of the twelve surviving patients suffered from chronic debilitating symptoms of radiation enteropathy,while three had moderate symptoms. CONCLUSION: Patients with severe delayed radiation enteropathy have a high risk of persistence of symptoms after surgery. At least one in ten patients dies from radiation-induced bowel injury.

Mechanisms of action of leptin in preventing gastric ulcer

To investigate the effects of leptin （1-20μg/kg） on acidified ethanol （AE）- and indomethacin （Indo）-induced gastric lesions in rats and compare it with ranitidine, lansoprazole, and omeprazole and to determine its mechanisms of actions.METHODS： Gastric ulcers, which were approximately 1 mm in width, formed in the glandular portion of the gastric mucosa produced by oral administration of either AE or Indo were taken as ulcer index. The inhibitory effect of subcutaneous administration of leptin, two proton pump inhibitors （PPIs） lansoprazole and omeprazole, or H2-receptor antagonist ranitidine 30 min before AE or Indo was evaluated.A radioimmunoassay was used to determine the PGE2 concentration in the homogenate of the glandular portion of the stomach. We performed histological study of the glandular stomach for the evaluation of total, acidic, and sulfated mucus content.RESULTS： Subcutaneous administration of leptin, two PPI slansoprazole and omeprazole or H2-receptor antagonist ranitidine 30 min before AE or Indo produced a dosedependent and reproducible inhibition of gastric ulcers （GUs）. This inhibition was found to be more potent than other antagonists used. In N^G-nitro L-arginine methyl ester （L-NAME）-pretreated animals, the ulcer prevention ability of leptin in AE-induced ulcer was significantly reduced,compared to rats without L-NAME pretreatment. However,the ulcer prevention ability of leptin was not altered by L-NAME treatment in Indo-induced ulcers. Leptin produced a dose-dependent increase in PGE2 level in the gastric glandular tissues. Leptin also increased mucus secretion.CONCLUSION： The results of the present study show that leptin inhibits GU formation by AE or Indo in a dosedependent and reproducible manner in rats. The results also suggest that leptin prevents ulcer formation by increasing the activities of the cyclo-oxygenase and/or nitric oxide pathways and by increasing mucus secretion.

Circulating DNA level is negatively associated with the long-term survival of hepatocellular carcinoma patients

AIM： To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma （HCC） and to evaluate its prognostic value. METHODS： Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated. RESULTS： Compared with the healthy volunteers （17.6 ± 9.5 ng/mL）, a significant higher circulating DNA level was found in the patients with HCC （47.1 ± 43.7 ng/ mL, P = 0.000） or with liver cirrhosis （30.0 ± 13.3 ng/ mL, P = 0.002）. The circulating DNA level was closely associated with tumor size （P = 0.008） and TNM stage （P = 0.040）, negatively associated with the 3-year diseasefree survival （DFS） （P = 0.017） and overall survival （OS） （P = 0.001）. CONCLUSION： Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.

Gastroenterology in developing countries:Issues and advances

Developing countries shoulder a considerable burden of gastroenterological disease. Infectious diseases in particular cause enormous morbidity and mortality. Diseases which afflict both western and developing countries are often seen in more florid forms in poorer countries. Innovative techniques continuously improve and update gastroenterological practice. However, advances in diagnosis and treatment which are commonplace in the West, have yet to reach many developing countries. Clinical guidelines, based on these advances and collated in resource-rich environments, lose their relevance outside these settings. In this two-part review, we first highlight the global burden of gastroenterological disease in three major areas： diarrhoeal diseases, hepatitis B, and Helicobacter pylori. Recent progress in their management is explored, with consideration of future solutions. The second part of the review focuses on the delivery of clinical services in developing countries. Inadequate numbers of healthcare workers hamper efforts to combat gastroenterological disease. Reasons for this shortage are examined, along with possibilities for increased specialist training. Endoscopy services, the mainstay of gastroenterology in the West, are in their infancy in many developing countries. The challenges faced by those se^ing up a service are illustrated by the example of a Nigerian endoscopy unit. Finally, we highlight the limited scope of many clinical guidelines produced in western countries. Guidelines which take account of resource limitations in the form of ＂cascades＂ are advocated in order to make these guidelines truly global. Recognition of the different working conditions facing practitioners worldwide is an important step towards narrowing the gap between gastroenterology in rich and poor countries.

Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease

AIM： The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding （UGIB） with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. METHODS： A total of 991 patients with coronary artery disease （CAD） on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. RESULTS： UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension （OR = 4.6, 95%CI 1.5 - 14.7, P = 0.009）, history of peptic ulceration （OR = 3.1, 95%CI 1.1 - 9.0, P = 0.039）, tertiary education （OR = 3.08, 95%CI 1.1 - 9.0, P = 0.039） and higher lean body mass （P = 0.016） were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. CONCLUSION： The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy.

Overview of the South African mine health and safety standardization and regulation systems

Outlined the South African mine health and safety regulatory framework,in- cluding the roles of government,tripartite council,service agencies,mine enterprises, rescue stations and workers unions,analyzed the institutional structures of South African mine health and safety standardization,including the South African standard and specifi- cation systems and standard development processes,and characterized the South African mine health and safety standardization and regulation systems.Intended to provide some suggestions for the transformation and improvement of mine health and safety standardi- zation and regulation systems in China or in similar situations.

The 5-year incidence of male breast cancer in Southwest of China from 2007 to 2011

Objective: Male breast cancer is a rare disease with an incidence of about 1% of breast cancers in USA, but relatively lack of the information of male breast cancer in China, especially in Southwest of China, led us to study its incidence trends. Methods: Chongqing is one of the biggest and the most important areas that is located in Southwest of China. There are around 31.4 million people who live in approximate 82 402.95 km2area of Chongqing. Data about breast cancer patients registered in the Center for Disease Prevention and Control of Chongqing(China) were statistically collected from 187 hospitals, about 58 hospitals in city and 129 hospitals in country, and over 6.2 million people were studied every year. It was tried to represent all the people in villages and cities in Chongqing, China. Results: The incidence of male breast cancer in Southwest of China ranged from 0.34/100 000 to 1.45/100 000 between 2007 and 2011, while the incidence of female breast cancer ranged from 15.40/100000 to 21.66/100000 at the same time. The rate of male breast cancer to female breast cancer ranged from 0.02:1 to 0.07:1, male breast cancer accounted for 1.96% to 6.5%(with the mean value of 2.9%) of breast cancers in Southwest of China from 2007 to 2010. Conclusion: In Southwest of China male breast cancer accounts for about 2.9% of breast cancers which is higher than that in United States. It is important for policy makers and health manager to seriously consider breast cancer in future plan in Southwest of China.

Technique for Controlling Spread of Limnotic Oncomelania

Schistosomiasis is a parasitic disease mostly found in areas along the Changjiang River of China. The disease is spread solely through an intermediary named oncomelania, so its spread of schistosomiasis can be controlled by properly designing water intakes which prevent oncomelania from entering farming land or residential areas. This paper reports a successful design process and a new oncomelania free intake device. The design of the new intake is based on a sound research program in which extensive experimental studies were carried out to gain knowledge of oncomelania eco hydraulic behavior and detailed flow field information through CFD simulation.

Snapshot of HIV pathogenesis in China

Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV- 1 subtypes, consequent emergence of recombinant and novel forms of HIV- 1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naive patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.

Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients

AIM： To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin＇s gastric lymphoma. METHODS： We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results. RESULTS： HLA-DR antigen expression was detected in 33 gastric lymphoma patients （91.7%） and 6 nonmalignant patients （54.5%）. PECAM-1 stained tumor cells of 10 patients （27.8%）, endothelial cells of 9 patients （25%） and inflammatory infiltrate of 4 patients （40%） with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients （47.2%）, while 5 non-malignant patients （50%） were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively （P= 0.009 and P= 0.003）. In the univariate analysis, PECAM-1（＋）/ICAM-3（-） and HLA-DR（-）/ICAM-3（-） patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns （P=0.0041 and P= 0.0091, respectively）. Those patients who were HLA-DR（＋ ）/ICAM-3（＋ ）/PECAM-I（-） （n = 8） had a significantly higher survival rate compared to the rest of the group （n = 24） （P= 0.0289）. CONCLUSION： PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

A prophylactic approach for bone marrow transplantation from a hepatitis B surface antigen-positive donor

It has been accepted that bone marrow transplantation （BMT） is the only curative therapeutic option for certain hematologic malignancies. The southeast Asia region is an endemic area of hepatitis B virus （HBV） infection; thus, BMT using a hepatitis B surface antigen （HBsAg）- positive donor is occasionally unavoidable. Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation. In this report, a four-level approach was designed for a patient with chronic myeloid leukemia, beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor. Prior to BMT, the HBV viral load of the donor was reduced to an undetectable level by anUviral therapy. After BMT, hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug, lamivudine. One year after discontinuation of lamivudine, the patient is still free of HBV infection.

International non-governmental actors in HIV/AIDS prevention in China

International non-governmental organizations were among the first international actors that responded to the emer- gence of AIDS crisis in China. Since 1994, the number of international non-governmental organizations and charitable foundations working in AIDS related issue areas in China has grown steadily and substantially. Despite their organiza- tional differences, most of these non-governmental actors present the characteristics of independent mission, localized practice and diverse working focus. Even though they are constrained by financial and other factors compared with multilateral and bilateral official assistance agencies, they have still played a unique role in fighting against AIDS in China as technical experts, public educators, and civil society supporters.

Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota

The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.

Preservation of Disease-free Shoot Tips of Potato Germplasm through in vitro System

The present investigation was undertaken to find out the best medium composition for medium-term preservation of disease free potato shoot tips in in vitro system.Thirteen potato genotypes and fourteen treatments were taken under consideration for the present experiment.Among fourteen treatments,mannitol and sorbitol containing media proved to be the best for medium-term preservation of potato shoot tips.High concentration of mannitol delayed root formation.